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Therapy
• Vitamin B12.
• Felic acid.

Serum iron I, TIBC Ferritin I,

Iron deficiency
t
l

Iron studies-normal or high
l
Hb electrophoresis (HPLC)

(HbA2 level) 1
Hemoglobinopathies

Therapy as appropriate

Pregnancy <30 weeks

Oral iron
■ Intolerance
l ■ Contraindication

Parenteral iron
■ IV ■ IM ■ TOI (see p. 252)

30-36 weeks
l

Parenteral iron
■ IV ■ TOI (see p. 252) ■ IM

>36 weeks

Blood transfusion ■ Packed cell
l
■ Whole blood
■ Partial exchange

)"able 20.2: Preparations and the iron content.
Iron salt Amount(mg) Ferrous iron (mg) Ferrous fumarate 200 65
Ferrous gluconate 300 35 Ferrous sulfate 300 60 Ferrous sulfate (dried) 200 65
intolerance, it is preferable to start the therapy with a smaller dose-one tablet daily and then to increase the dose to a maximum three tablets a day.

(2) Unpredictable absorption rate: Various food content may effect from absorption and its utilization. Antacids, milk, tannins, oxalates, phytates and phosphates will reduce absorption while ascorbic acid, lactate and various amino acids increase its absorption.
(3) With the therapeutic dose, the serum iron may be restored but there is dificulty in replenishing the iron store.
Response of therapy is evidenced by: (1) Sense of wellbeing, (2) Increased appetite, (3) Improved
ma Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy
outlook of the patient and ( 4) Hematological is unsuitable if at least 4 weeks of time is not available, examination: (a) Rise in hemoglobin level, to raise the hemoglobin to a safe level of 10 g/dL before (b) hematocrit value returning to normal, (c) delivery. Thus, it is mostly suitable during 30-36 weeks reticulocytosis within 7-10 days. If no significant of pregnancy where the patient is unwilling or unable improvement is evident clinically and hematologically to complete the course of intramuscular injections and within 3 weeks, diagnostic re-evaluation is needed. (2) Previous history of reaction to parenteral therapy is
11 Rate of improvement: The improvement should be contraindicated for its use.
evident within 3 weeks of the therapy. After a lapse of 11 Iron (ferrous) sucrose (20 mg elemental iron/mL) 100 few days, the hemoglobin concentration is expected to mg/ dose, usually one dose daily for 10 days.
rise at the rate of about 0. 7 g/ 100 mL/week. 11 Sodium ferric gluconate complex 125 mg/dose 11 Causes of failure of improvement: (I) Improper typing usually one dose/day, usually 8 doses needed (12.5 mg
of anemia, (2) Defective absorption due to associated elemental iron/mL).
gastrointestinal disorders, (3) The patient fails to 11 Treatment with iron carboxymaltose, iron isomalt take iron, (4) Concurrent blood loss as in hookworm ose, iron sucrose have similar efficacy. Carboxymaltose infestation or bleeding piles, (5) Inhibition of needs less injection and shorter infusion time. erythropoiesis by infection and (6) Co-existent folate Estimation of the total requirement: Method for
deficiency.
calculations for the total iron dose in general: Total
11 Contraindications of oral therapy: The following are dose of iron required (mg) =body weight (kg) x [target
the contraindications of oral therapy: (I) Intolerance hemoglobin - actual hemoglobin (g/L) x 0.24 plus 500 mg
to oral iron. (2) Severe anemia in advanced pregnancy. (additional to replenish the store)]. The manufacturer's
Considering the unpredictable absorption and utili information is to follow for dose calculation.
zation following oral therapy, parenteral therapy is the Prerequisites: (1) Correct diagnosis of true iron
preferred choice.
deficiency anemia, (2) Adequate supervision and (3) Faci
Parenteral therapy: lities for management of anaphylactic reaction.
■ Intravenous route: (i) Repeated injections and (ii)
total dose infusion (TDI) Preparations and P,rocedures:
■ Intramuscular route Prepara- mgof Maximum Maximum
tion iron/ml single dose frequency Rate of IV infusion
Indications of parenteral therapy: Iron 20 200mg 3times/ 200 mg in 200 ml
■ Contraindications of oral therapy as previously menti hydroxide week 0.9%, salineuver 30
oned. sucrose min.
■ Patient is not cooperative to take oral iron. Ferric 50 1000mg Once/ 1000 mg in 250ml ■ Cases seen for the first time during the last 8-10 weeks carboxy week 0.9%, saline over 15
with severe anemia. maltose min.
The main advantage of parenteral therapy: (a) Iron iso- 100 20mg/ Once/ 11 Total dose in 500
Certainty of iron administration, (b) Avoids the risks maltose kg body week ml 0.9%. Saline: due to intolerance, malabsorption or noncompliance.
weight
over 30 min.
>
1000 mg
Doses
D
The expected rise in hemoglobin concentration after over60min.
parenteral therapy is 0.7-1 g/100 mL/week. (B) Intramuscular therapy: The compounds used ( with
(A) Intravenous route: elemental iron/mL) are:
11 Total Dose Infusion (TDI): The deficit of iron is first ♦ Iron sucrose (20 mg/mL).
calculated and the total amount of iron required to
♦ Iron dextran (imferon) (50 mg/mL).
correct the deficit is administered by a single sitting ♦ Sodium ferric gluconate complex 12.5 mg elemental
intravenous infusion. The compounds used are:
iron (ferrous) sucrose compound, sodium ferric iron/mL.
gluconate, iron carboxymaltose, iron isomaltose and All the above preparations contain different amount of iron dextran. Iron sucrose is safe, effective and has elemental iron in 1 mL. Total dose to be administered is less side effects (ACOG-2008). calculated as that previously mentioned in intravenous
Advantages: (1) It eliminates repeated and painful therapy.
intramuscular injections. (2) The treatment is completed Procedure of injections: After an initial test dose of 1 mL, the
in a day and the patient may be discharged much earlier injections are given daily or on alternate days in doses of 2 mL
intramuscularly.
To prevent dark staining of the skin over the injection sites and to minimize pain, the injections are given with
from the hospital.
(3)
It is less costly compared to the
repeated intramuscular therapy.
a 2 inch needle deep into the upper outer quadrant ofthe buttock
Limitations: (1) As the maximum hemoglobin using a 'Z' technique (pulling the skin and subcutaneous tissues response does not appear before 4-9 weeks, the method to one side before inserting the needle). An additional precaution
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy &IL-

is to inject small quantity of air or saline down the needle before withdrawing it. These procedures prevent even a slight drop of the solution to come beneath the skin surface so as to avoid staining.
Drawbacks: (1) The (IM) injections are painful. (2) Risk of abscess formation and a discoloration of the skin over the injection sites are the problems. (3) Reactions are few: pyrexia, lymphadenopathy, headache, nausea, vomiting and allergic reactions are infrequently met with. Others are: hypotension, arthralgia and abdominal pain.
PLACE OF BLOOD TRANSFUSION: The indication of blood transfusion in anemia during pregnancy is very much limited. The indications are:
11 To correct anemia due to blood loss (APH) and to combat postpartum hemorrhage.
11 Patient with severe anemia seen in later months of pregnancy (beyond 36 weeks)-to improve the anemic state and oxygen carrying capacity of blood before the patient goes into labor.
11 During operative delivery, cases with PPH.
11 Refractory anemia: Anemia is resistant to oral or parenteral iron therapy in spite of correct typing (Box 20.2).
11 Associated infection.
The quality and quantity of blood: The blood to be transfused should be relatively fresh, properly typed, grouped and cross-matched. Only packed red blood cells are transfused. The quantity should be between 80 and 100 mL at a time. To allow time for circulatory readjustment, transfusion should not be repeated within 24 hours.
Advantages of blood transfusion: (1) Increases oxygen canying capacity of the blood, (2) hemoglobin from the hemolyzed red cells may be utilized for the formation of new red cells, (3) stimulates erythropoiesis, ( 4) supplies the natural constituents of blood like proteins, antibodies, etc. and (5) improvement is expected after 3 days.
Precautions: Utmost precautions are to be taken to minimize reaction and overloading of the heart. (1) Antihistaminic (Phenergan 25 mg) is given intramuscularly, (2) Diuretics (Frusemide 20 mg) is given intramuscularly at least 2 hours prior to transfusion to avoid volume overload, (3) The drip rate should be about 10 drops per minute and (4) To observe carefully the pulse, respiration and crepitations in the base oflungs.
Drawbacks: (1) Premature labor may start which is more related to blood reaction. (2) There is increased chance of cardiac failure with pulmonary edema because of overloading of the heart. (3) Features of transfusion reaction, if occur, are often exaggerated.
MANAGEMENT DURING LABOR 11 First stage:
• Patient should be in bed with position comfortable to her. Position may be propped if needed.
• Provision of oxygen inhalation should be there.

• Labor analgesia (epidural) if needed.
• Close monitoring of the women with pulse, BP,
temperature, SPO2 (>95%), chest auscultation for early detection of failure .
• Oral fluid may be allowed. IV fluid when needed, should be restricted to less than 125 mL/hr.
• Minimal pelvic examination as possible. • Strict asepsis to be maintained.
ii Second stage:
• Prophylactic forceps or venture delivery may be done to shorten the duration of second stage.
ll Third stage:
• Active management of third stage of labor-by oxytocin 10 IU IM is given to the mother soon following delivery of the baby.
• Any significant amount of blood loss is compensated by fresh PRBC transfusion. Measures are taken using diuretics (frusemide 20 g IV) to avoid volume overload of the heart.
Puerperium: 0 Prophylactic antibiotics are given to pre vent infection. @ Pre-delivery therapy with hematinic is continued till the woman restores her normal clinical and hematological states. €) Women should be seen in the postpartum clinic for counselling as regard the different measures of contraception.
I MEGALOBLASTIC ANEMIA
In megaloblastic anemia, there is derangement in red cell maturation with the production in the bone marrow of abnormal precursors known as megaloblasts due to impaired DNA synthesis. Thus, it may be regarded as a deficiency disease caused by lack
of either vitamin B12 or folate or both. In pregnancy
folate deficiency is common compared to vitamin
B12• Vitamin B12 is first bound to intrinsic factor which
is secreted by the gastric parietal cells. Thereafter, it is absorbed in the distal ileum ( c.f. iron is absorbed in duodenum and proximal jejunum). Megaloblastic anemia in pregnancy is almost always due to folic acid
deficiency. The daily requirement of vitamin B12 in
nonpregnant condition is 2 µg and during pregnancy is 3 µg. This amount is met with any diet that contains animal products. Only the strict vegetarians, may need supplementation. Folic acid is a water-soluble vitamin. Folate stores are located in the liver. Normal folate store is sufficient for 6 weeks. After 3 weeks of a deficient folate diet, the serum level falls. Two weeks later there is hypersegmentation of neutrophils and after about 17 weeks RBC folate levels drop and then megaloblastic bone marrow develops. The daily folate requirement is about 200 µg during pregnancy. Folate deficiency rarely occurs in the fetus and it is not associated with any significant perinatal morbidity. One mg of folic acid is sufficient to prevent and treat folate deficiency.
· - Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

CAUSES: Common causes of vitamin B12 deficiency are:
(i) Strict vegetarian diet, (ii) Gastritis, (iii) Gastrectomy, (iv) Bariatric surgery, (v) Ilea! bypass, (vi) Crohn's disease, (vii) Drugs-COCs, metformin, proton pump inhibitors, (viii) Helicobacter pylori infection, (ix) Addisonian pernicious anemia-rare in pregnancy and (x) Megaloblastic anemia of malabsorption syndrome.
Addisonian pernicious anemia is caused by lack of absorption
of vitamin B 12 due to lack of intrinsic factor. It is an extremely rare
autoimmune disease in pregnancy because of: (1) Rare occurrence during childbearing period (usually manifests above 40 years). (2) If occurs early, produces infertility.
For cobalamin absorption, the requirements are: (i) Sto mach acid pepsin, (ii) Intrinsic factors secreted by gastric parietal cells, (iii) Pancreatic proteases and (iv) Intact ileum with mucosa!
receptors. Because of abundant vitamin B12 stores in the body
(liver), clinical vitamin B12 deficiency takes several years to occur.
Women following bariatric surgery suffer vitamin B12 deficiency. Similarly women (10-30%) taking metformin.
Women with vitamin B12 deficiency should be given 100 Lg
of vitamin B12 IM or Subcutaneously (SC) monthly.
CAUSES OF FOLIC ACID DEFICIENCY IN PREGNANCY
♦ Inadequate intake due to: (a) Nausea, vomiting and loss of appetite. (b) Dietary insufficiency-the main sources of folic acid are green leafy vegetables, cauliflower, spinach, liver, kidney. Excessive cooking destroys much of the folate in food.
♦ Increased demand due to: (a) Increased maternal tissue including red cell volume, (b) Growing fetus and (c) Multiple pregnancy. Daily requirement of folic acid in a nonpregnant woman is 50-100 µg/day and during pregnancy is increased to 400 µg/ day.
♦ Diminished absorption: Intestinal malabsorption syndrome is responsible for its recurrence in subsequent pregnancies.
♦ Abnormal demand: (a) Infection-infection reduces the lifespan of the red cells and hence increases the demand of folic acid to replenish the red cells; (b) Hemorrhagic states such as peptic ulcer, hookworm infestation, hemorrhoids and the hemolytic states such as chronic malaria, sickle cell anemia or hemoglobinopathy, lead to increased erythropoiesis and exhaustion of the available supply of folic acid resulting in megaloblastic erythropoiesis.
♦ Failure of utilization: This is associated with anti convulsant drugs used in epilepsy or with presence of infection.
♦ Diminished storage: This is associated with hepatic disorders, hyperhomocysteinemia and vitamin C deficiency.
♦ Iron deficiency anemia: Correction of anemia by iron therapy alone may unmask the underlying folic acid deficiency state in the following manner. Anemia ➔ depressed bone marrow➔ iron therapy➔ hyperplastic marrow ➔ increased need for folic acid ➔ if the extra

folic acid is not supplemented, the pre-existing low level of folic acid is further lowered ➔ ineffective erythropoiesis with evidence of megaloblastic features and simultaneous anemic state nonresponsive to simple iron therapy alone. Thus, when the anemia fails to improve with iron therapy, addition of folic acid should be tried before proceeding for a detailed investigation.
An elevated homocysteine level is found when serum folate levels are low. Women with high homocysteine levels are at increased risk of pre-eclampsia, preterm labor and IUGR. Evaluation of methylmalonate and homocysteine levels can be
used to differentiate folate from vitamin B12 deficiency. Increased methylmalonate and folate levels indicate vitamin B12 deficiency whereas increased homocysteine and normal methylmalonate
indicate folate deficiency. Iron deficiency is common with folic acid deficiency. Absence of reticulocytosis following replacement therapy with folic acid, iron deficiency must be excluded. Urinary excretion of formanine glutamic acid (FIG LU) has been used to diagnose foliate deficiency.
INCIDENCE: It is very difficult to estimate the exact incidence, as full hematological or bone marrow study is essential to establish the diagnosis. The incidence varies from 0.5 to 3%. It is more common in multiparae (5 times more than primigravidae) and in multiple pregnancy (eight-fold increase than singleton pregnancy).
CLINICAL FEATURES: (I) The onset is usually insidious and is first revealed in the last trimester or may be acutely manifested in early puerperium, (2) Anorexia or protracted vomiting, (3) Occasional diarrhea and (4) Constitutional symptom like unexplained fever is often associated.
On examination: (1) Pallor of varying degree, (2) Ulceration in the mouth (glossitis) and tongue (one third cases), (3) Hemorrhagic patches under the skin and conjunctiva, (4) Enlarged liver and spleen which may be difficult to palpate due to an enlarged gravid uterus and (5) Features of pre-eclampsia may be present (two and halftimes increased).
Hematological examination and other blood values: (I) Hemoglobin level is usually below 10 g%. (2) Stained blood film: Presence of any two of the following features in the peripheral blood, but more often seen in buffy coat preparations, are diagnostic: (a) Hypersegmentation of the neutrophils (5 or more lobes), (b) macrocytosis and anisocytosis, (c) giant polymorphs, (d) megaloblasts, (e) Howell-Jolly bodies. (3) MCV is more than 100 µ3• MCH is high (more than 33 pg), but MCHC is normal. (4) Associated leukopenia and thrombocytopenia. (5) Serum iron is normal or high and iron binding capacity is low. (6) Red cell folate is below 3 ng/mL (normal nonpregnant
level being 2.8-8 ng/mL). (7) Serum vitamin B12 level is
below 90 pg/mL (normal levels 300 pg/mL). (8) Serum bilirubin-may be raised and (9) Bone marrow-shows megaloblastic erythropoiesis.
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy fa--COMPLICATIONS: The complications of iron deficiency
anemia are mentioned before. The following are the special complications in megaloblastic anemia: (1) Mis carriage, (2) Dysmaturity, (3) Prematurity, (4) Abruptio placentae and (5) Fetal malformation (cleft lip, cleft palate, neural tube defects). There is association between preconceptional folate deficiency and neural tube defects.
PROPHYLACTIC THERAPY: All woman of reproductive age should be given 400 µg of folic acid daily. Additional

amount (5 mg) should be given in situations where the demand is high. Such conditions are: multiple pregnancy, patient having anticonvulsant therapy, hemoglobinopathies, family histo1y of congenital heart disease, or associated chronic infection or disease. Women, who have infants with neural tube defects, should be given 5 mg of folic acid daily beginning 1 month before conception to about 12 weeks of pregnancy.
CURATIVE: Specific therapy includes-daily adminis tration of folic acid 5 mg orally which should be continued for at least 4 weeks following delive1y. Supplementation of 1 mg of folic acid daily along with iron and nutritious diet can improve pregnancy-induced megaloblastic anemia by 7-10 days. Response is evidenced by-(i) sense of wellbeing and increased appetite, (ii) increase in reticulocyte, leukocyte and thrombocyte count and (iii) rise in hemoglobin level. Folic acid should never be given without supplemental iron. Supplementary intramuscular
vitamin B12 100 µg daily or on alternate days may be added when response to folic acid alone is not adequate.
Ascorbic acid 100 mg tablet thrice daily enhances the action of folic acid by converting it into folinic acid.
I DIMORPHIC ANEMIA
This is the most common type of anemia met with in the tropics. It is related to dietary inadequacy or intestinal malabsorption. As such, anemia results from deficiency of both iron and folic
acid or vitamin B12. While there is polydeficiency state, the hematological findings or the bone marrow picture usually
show predominance of one deficiency. The red cells become macrocytic or normocytic and hypochromic or normochromic (Fig. 20.2). Bone marrow picture is predominantly megaloblastic as the folic acid is required for the development of the number of red cell precursors. The treatment consists of prescribing both the iron and folic acid in therapeutic doses.

I APLASTIC ANEMIA
It is rarely seen in pregnancy. There is marked decrease in the marrow stem cells. Exact cause is unknown. It may be immunologically mediated or may be an autosomal recessive inheritance. Known marrow toxins are: phenylbutazone, phenytoin or alkylating chemotherapeutic agents. In about 30% of cases, anemia improves once pregnancy is terminated. The significant complications in pregnancy are-Fetal: Miscarriage, prematurity and IUFD; Maternal: Increased infection, hemorrhage and even death.

Fig. 20.2: Dimorphic anemia (Courtesy: Dr SK Dutta).

Diagnosis: Blood values-anemia, leukopenia and throm bocytopenia. Bone marrow-markedly hypocellular.
Management: Treatment-any toxic agent should be avoided. Other possible treatments are-antithymocyte antibody, corticosteroids or immune suppressive agents. Infection must be treated. Repeated blood transfusions are given to maintain hematocrit level above 20. Specific therapy may be needed, e.g., granulocyte transfusion to combat infection and platelet transfusion to control hemorrhage. Glucocorticoid therapy may be helpful in some patients. In a severe case of aplastic anemia, bone marrow or stem cell transplantation is effective. Vaginal delive1y is always preferred.
Anemia due to chronic diseases, infections or neoplasms is of hypochromic microcytic type. Serum iron level is low, serum ferritin level is usually elevated. Anemia of chronic renal disease is due to deficiency of e1ythropoietin. Recombinant erythropoietin therapy is found effective in cases with chronic renal disease, infection or malignancy.
Drug-induced hemolytic anemia: Common drugs are nitrofurantoins, sulphonamides, some analgesics and some antimalarials. The most common congenital erythrocyte enzymetic defect to cause the condition is glucose-6-phosphate dehydrogenase (G6PD) deficiency (X-linked disorder). Peripheral smear shows spherocytes, helmet cells (fragmented red cells) LDH level is also elevated. Complications: Fetal hemolysis, hydrops, fetalis and fetal death. Management: To stop such medications, supportive care and blood transfusion.
I HEMOGLOBINOPATHIES
Hemoglobin is a conjugated protein which contains a globin fraction bound to 4 heme moieties. There are 4 polypeptide chains within the globin fraction namely alpha, beta, gamma and delta. Composition
of a normal adult hemoglobin is: HbA (a2 2) =
96.98%, HbF (a2 y2) = 0.5-0.8% and HbA2 (a2 I\)= 1.5-3.7%. In normal fetal hemoglobin, the beta chains are replaced by two
gamma chains (a2 y2). The last two varieties constitute not more than 5% in normal human adults.
Hemoglobinopathies are inherited specific biochemical disorders (quantity or quality) within the polypeptide chains of globin fraction. Two common varieties are met. Sickle cell disease is inherited structural abnormality involving primarily the chain of HbA. Thalassemia is inherited defect in the synthesis and production of globin in othe1wise normal HbA. Homozygous and heterozygous forms occur. In homozygous, the abnormal globin chain is inherited from each parent and in
Bl Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

heterozygous, the abnormal globin chain is only inherited from one parent. The latter groups are not anemic but are carriers of the defect.

I SICKLE CELL HEMOGLOBINOPATHIES
Sickle cell hemoglobinopathies are hereditary lil
disorders. It is caused by a point mutation in the
,.
_
:
.
P-globin gene on chromosome 11. This results in
o
substitution ofvaline f r glutamic acid at position :J 6 of the P-chain of normal hemoglobin. Gene
mutation-when homozygous the individual has sickle cell anemia (Hb-SS). She has a small quantity of Fetal Hemoglobin (HbF) but no HbA. Heterozygous individual for sickle cell hemoglobin has sickle cell trait (HbAS). Such an individual has about 55-60% of HbA and 35-40% of HbS. Sickle cells have a life span of 5-10 days compared to normal RBCs of 120 days. The prevalence rate of sickle cell hemoglobinopathies is highest in Africa and ranges from 20-50%.
HbC is produced when there is substitution of lysine for glutamic acid at the sixth position of the globin-chain. HbC is less soluble than HbA and can cause hemolytic anemia. Management of these women with HbC is same as that of with women with HbSS. During crises these patients become profoundly thrombocytopenic and there is fall in hematocrit value.
Sickle cell-P-thalassemia-is observed when one P-chain gene carries the sickle cell mutation and the other gene is deleted. Pregnancy outcome is similar to sickle cell anemia.
Sickle cell trait: Hb-S comprises 30-40% of the total
hemoglobin, the rest being Hb-A, Hb-A2 and Hb-F. If the
husband is a carrier, there is 25% chance that the infant will be homozygous sickle cell disease and 50% sickle cell trait. As such, preconceptional counseling should be done to know whether the husband also carries the trait or not.
There is no special problem so far as reproductive performance is concerned. The patient will require iron supplementation. As the concentration ofHb-S is low, crisis is rare but can occur in extreme hypoxia. Hematuria and urinary infection are quite common.
Sickle cell disease: Homozygous sickle cell disease (Hb-SS) is transmitted equally by males and females. Partner must be tested. Termination of pregnancy is an option if a fetus is diagnosed to have major hemoglobinopathy on prenatal diagnosis by CVS (p. 104).
Pathophysiology: Red cells with HbS in oxygenated state behave normally but in the deoxygenated state it aggregates, polymerizes and distort the red cells to sickle.These sickle-shaped cells block the microcirculation due to their rigid structure. This sickling phenomenon is precipitated by infection, acidosis, dehydration, hypoxia and cooling. The cells have got shorter lifespan and are more fragile. Increased destruction leads to hemolysis, anemia and jaundice.
Diagnosis: (a) Refractory hypochromic anemia, (b) Identi fication by sickling test, (c) Persistent reticulocytosis (10-20%), (d) High fasting serum iron level and (e) Identification of the type of hemoglobinopathies by electrophoresis.
Effects on pregnancy: There is increased incidence of miscarriage (25%), prematurity, IUGR and still birth (8-10%). Perinatal mortality is high. Incidence of pre-eclampsia, postpartum hemorrhage and infection is increased. Increased maternal morbidity is due to infection (UTis), cerebrovascular accident and sickle cell crisis. Maternal death is increased up to

25% due to pulmonary infarction, renal dysfunction acute chest syndrome, congestive heart failure and embolism.
Effects on the disease: There is chance of sickle cell crisis which usually occurs in the last trimester. Two types are met-(1) hemolytic crisis and (2) painful crisis.
Hemolytic crisis: It is due to hemolysis with rapidly developing anemia along with jaundice. There is associated leukocytosis and fever.
Painful (vaso-occlusive) crisis: It is due to vascular occlusion of the various organs by capillary thrombosis resulting in infarction. Organs commonly affected due to vaso-occlusion and infarction are: bones (osteonecrosis), kidney (renal medulla), hepatosplenomegaly, cholelithiasis (30%), lung (infarction) and heart (failure), neurologic (seizures, stroke) and superadded infections (pyelonephritis) are high. Painful crisis occurs in approximately 30 -40% of women. For mild pain: Paracetamol, NSAIDs (between 12 to 28 weeks); for moderate pain: NSAIDs (between 12 to 28 weeks), weak opioids; for severe pain: IV/IM/ SC/oral morphine. Pethidine is avoided due to risk of seizure. Resuscitation with fluid and oxygen is maintained.

MANAGEMENT
Preconceptional counseling: Prenatal identification (CVS) of homozygous state of the disorder is an indication for early termination of the pregnancy, if the parents desire. Management needs multidisciplinary team approach.
During pregnancy: (1) Careful antenatal supervision, (2) Air traveling in unpressurized aircraft is to be avoided, (3) Prophylactically folic acid 5 mg tablet should be given daily, (4) Iron supplementation is reserved only in proven cases of iron deficiency, (5) Prophylactic booster or exchange blood transfusion may be given. The objective of transfusion is to keep the hematocrit value above 25%, HbA >20% and concentration of HbS under 50%, (6) Infection (pneumococcal) or appearance of unusual symptoms necessitates hospitalization. Penicillin prophylaxis is given to all patients with SCD as they are at risk of infection with N. meningitidis, S. pneumoniae and H. influenzae, E. coli, Salmonella and (7) Hydroxy urea is used as a disease modifying drug. It increases HbF, improves red cell hydration and reduces polymerization of HbS and the crises. Hydroxyurea should be stopped at least 3 months before conception as it is teratogenic, (8) Thromboprophylaxis with LMWH is required for both antenatal and postpartum (SCD-VTE score: 3), (9) Vaccine against: (a) H influenza; (b) Meningococcus; (c) Pneumococcus; (d) Hep B.
Aggressive iron chelation before conception should be advised in women who are significantly iron overloaded.
Hemopoietic cell (bone marrow/cord blood stem cell) trans plantation has been used with success. Antenatal fetal imaging (USG) is needed.
Labor and delive,y: Vaginal delivery is preferred. (1) The labor is to be conducted as outlined in anemia, (2) Continuous oxygen
therapy by nasal cannula is done to maintain Pa02 >94%, (3)
Anoxia is to be avoided during anesthesia. Epidural anesthesia is preferred, (4) Adequate fluid infusion to avoid dehydration and acidosis, (5) Cesarean section is performed for obstetric indication only, (6) Routine antibiotic is used in puerperium to prevent infection, (7) Women should be given thromboprophylaxis (LMWH) during pregnancy and up to puerperium and (8) Cord blood is sent for hemoglobinopathy screening.
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy ma

Contraception: (I) Sterilization should be considered even with low parity because of the short life span of the patient, (2) Oral pill is contraindicated as it might aggravate risk of thromboembolism, (3) Intrauterine device is avoided for fear of infection, ( 4) Barrier method of contraceptive is safe and effective, (5) Progesterone containing contraceptives (POP, injectables) and LNG-IUS are safe and (6) Estrogen containing contraceptions should be used as second-line agents.
I THALASSEMIA SYNDROMES
The thalassemia syndromes are the commonly found genetic disorders of the blood. The basic defect is a reduced rate of globin chain synthesis. As a result, the red cells being formed with an inadequate hemoglobin content. There is deficient erythropoiesis, reduced RBCs life span, hemolysis and ultimately anemia. The major syndromes are of two groups-the alpha or P-thalassemia depending on whether the alpha or the beta globin chain synthesis of the adult hemoglobin is depressed. a and p thalassemia exist in both the homozygous (major) and heterozygous (minor) states. Overall incidence during pregnancy is 1 in 300 to 500.
Alpha thalassemia is distributed amongst South-East Asia and China. Alpha thalassemia major is incompatible with life. a-peptide chain production is controlled by four genes, located on chromosome 16 (two on each copy). Depending upon the degree of deficient a-peptide chain synthesis, four clinical types of syndromes have been identified.
A. Mutation of one gene-there is no clinical or laboratory abnormalities. Subject remains as a silent carrier.
B. Mutation in two of the four genes-a-thalassemia minor. It often goes unrecognized and pregnancy is well-tolerated.
C. Mutation in three of the four genes-hemoglobin H disease. The patient has some HbA and large percentage of HbH (four P-chains) and hemoglobin Bart (four y chains). The hemoglobin Bart present at birth, is gradually replaced by hemoglobin H. These women suffer from hemolytic anemia. During pregnancy, anemia deteriorates further.
D. Mutation in all four genes-a-thalassemia major. There is no a-globin chain, hemoglobin Bart (four y chains) and hemoglobin H (four P-chains) are formed. The fetus dies either in utero or soon after birth. This is an important cause of non-immune fetal hydrops and perinatal death.
Parental diagnosis: All forms of a-thalassemia can be diagnosed by CVS or amniocentesis.
Treatment: a-thalassemia minor-the reproductive perfor mance in a-thalassemia minor is usually normal. They require oral iron and folate supplementation during pregnancy. If the hemoglobin is low, blood transfusion is indicated. Parenteral iron therapy should never be given.
Beta thalassemia: This entity (most common form) is predominantly distributed along the Mediterranean coast, South East Asia. Normal adult hemoglobin (HbA) is composed of two a and two p peptide chains (az Pz). p chain production is directed by two genes, one on each copy chromosome I 1. More than 150 point mutations in the p-globin gene have been identified. With P-thalassemia, P-chain production is decreased and excess of a-chains precipitate to cause red cell membrane damage.
Beta thalassemia major (Cooley anemia)-when mutation affect both the genes. There is red cell destruction as there is no

P-chain production. Erythropoiesis is ineffective. Such an infant is transfusion dependent. There is progressive hepatospleno-megaly, impaired growth, anemia, congestive cardiac failure and intercurrent infection. Chance of survival beyond teens is uncommon. They are often sterile. Problem of iron overload is observed beyond the first decade of life. Iron chelation therapy with desferrioxamine and blood transfusion can improve the outcome.
Preconception counseling: Father of the fetus is advised for hemoglobin electrophoresis (if MCV is low). When father has normal hemoglobin-fetus has a 50% chance of P-thalassemia minor and 25% chance of normal hemoglobin. When father is P-thalassemia minor the risk of fetus being P-thalassemia major is 50%. All forms of P-thalassemia can be detected by CVS or amniocentesis (amniocytes). Preimplantation blastomere biopsy and DNA study is possible to select unaffected embryos during in vitro fertilization.
Beta thalassemia minor-when there is mutation of one gene, p peptide chain production is reduced by half. Excess a-chains combine with o-chains producing HbAz ( az oz) or with y chains producing HbF (az y ). Sickle cell trait may coexist with thalassemia minor.
z
Hematological findings in thalassemia: (I) There is low MCV and MCH but normal MCHC (cystic fibrosis-in iron-deficiency anemia where all are low). (2) Serum iron and total iron binding capacity are normal or elevated. (3) Hemoglobin electrophoresis shows raised concentration of HbAz ( az Oz) to more than 3.5% with normal or raised Hb-F (az y ). (4) Serum bilirubin may be raised to about 2-3 mg%. (5) Usually anemia is mild. The diagnosis is often late when the patient fails to respond to oral or parenteral iron therapy to correct anemia. There is thus chance of hepatic and cardiac hemosiderosis from iron overload. ECHO is done regularly to screen for cardiomegaly.
z
Treatment: In thalassemia major oral and IV iron therapy is contraindicated. These women need careful monitoring for cardiac, liver, thyroid and parathyroid functions. These organs are affected due to iron overload. Chelation therapy during pregnancy is safe after 20 weeks with desferrioxamine. It has short halflife. GDM is a common problem. Screening is done with serum fructosamine 3 months before. Frequent evaluation of fetal wellbeing (USG) is needed. Labor and delivery management are usual. Patients with thalassemia major are often small in stature, with small pelvis. Cesarean delivery is often needed. Majority of the women tolerate pregnancy well with good maternal and fetal outcome. Oral folic acid 5 mg supplementation is continued. Oral iron therapy in thalassemia minor is given only when the laboratory diagnosis of iron-deficiency is established. Blood transfusion is rarely indicated.

I PLATELET DISORDERS
Gestational thrombocytopenia is considered when platelet count is less than l,50,000/mm3 (µL). It affects 5% of pregnancies. Platelet count of 50,000 to l,50,000/mm3 during pregnancy is not associated with any increase in maternal or fetal morbidity.
Thrombocytopenia in pregnancy may be due to-(i) defective production (bone marrow pathology), (ii) sequestration ( enlarged spleen) or due to, (iii) accelerated destruction which again may be due to: (a) Non-immunological: pre-eclampsia, HELLP syndrome, abruptio placentae,DIC or (b) Immunological: thrombocytopenic
iJ Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

purpura, lupus anticoagulant, SLE, antiphospholipid antibody. Others: HIY, folic acid deficiency.
Gestational thrombocytopenia: It is mainly the physiologi cal fall resulting from hemodilution of normal pregnancy and increased platelet destruction.
Immune {Idiopathic) Thrombocytopenic Purpura (ITP): It is due to accelerated destruction of antibody-coated platelets in the spleen and other reticuloendothelial systems. Antibodies are of IgG, IgM and IgA types. Patients may present with skin bruising. Generally capillary bleeding or purpura occurs when the platelet count falls below 20,000/mm3. Asymptomatic patient with count more than 50,000/µL with normal bleeding time, generally does not need any treatment.
Fetus and the neonate may be affected due to transplacental carriage of IgG antibodies. Thrombocytopenia in the fetus when severe may cause intracranial hemorrhage especially during labor.
Management: Objective is to maintain platelet count more than 50,000/µL.
During pregnancy: (a) Administer methylprednisolone (1-1.5 mg/kg) or gamma globulin (MG)-only if platelet count is <20,000/mm3. This will increase the platelet count. (b) Platelet transfusion is indicated when there is clinically significant bleeding (platelet count <10,000/mm3). (c) Splenectomy-

as this may be the site of antibody production or red cell sequestration (c) Platelet transfusion-as a temporary measure. (d) In a patient with thrombotic thrombocytopenic purpura plasma exchange should be done. !VIG prevents platelets destruction and may result in long-term remission.
During labor: Vaginal route is the preferred method as severe thrombocytopenia is rarely encountered.
von Willebrand Disease {vWD) is the most common congenital bleeding disorder: Type 1 is an autosomal-dominant disorder. vWD is due to quantitative or qualitative abnormalities of von Willebrand Factor ( vWF). This multimetric glycoprotein is the carrier protein of factor VIII, prolonging its life span in plasma. It also promotes platelet adhesion and aggregation. Abnormalities of vWF are responsible for three types of vWD. Clinical presentation of vWD includes-menorrhagia, bruising, gum bleeding and epistaxis.
Fetal growth is not affected. In pregnancy factor VIII increases along with the vWF multimeric pattern. Bleeding during pregnancy is uncommon as the levels of factor VIII and vWF increase. But the levels drop shortly after delivery. Postpartum hemorrhae may be a problem. Desmopressin (intranasal) is the treatment of choice for type I vWD. Otherwise factor VIII/vWF
concentrate is used.

► Definitions related to iron deficiency anemia: (a) Iron deficiency: A relative or absolute depletion of body iron. Stores are particularly affected and inadequate to maintain the demands for erythropoiesis; (b) Iron-deficiency anemia: Reduced amount of hemoglobin or number of erythrocytes because of insufficient iron for erythropoiesis; (c) Iron-restricted erythropoiesis: Reduced supply of iron for erythropoiesis, irrespective of iron stores; (d) Functional iron deficiency: Erythroid iron not really accessible despite increased requests and apparently adequate body iron stores. Associated with chronic disease, inflammatory conditions and malignancy; (e) Iron-refractory iron-deficiency anemia: In most cases is due to a genetic mutation TMPRS56, regulating in anemia unresponsive to oral iron treatment.
► Anemia in pregnancy is diagnosed when the hemoglobin concentration is less than 11 g/dl or the hematocrit is less than 32%. ► More than 50% of pregnant women are anemic. Anemia accounts for nearly 20% of maternal deaths in the developing countries. ► About 75% of anemia during pregnancy is secondary to iron deficiency. It is the commonest cause.
► Important causes of iron deficiency anemia, are: (a) inadequate dietary intake, (b) faulty absorption mechanism, (c) increased demand during pregnancy, (d) repeated childbirth at short intervals, or (e) due to complications of delivery (PPH).
► Investigations are designed to determine: (a) severity of anemia, (b) type of anemia, and (c) cause of anemia.
► Peripheral blood smear, hematological indices (MCHC, MCV, MCH), serum values (iron, ferritin, total iron-binding capacity) are done.
► Serum ferritin is the single best test to diagnose iron deficiency anemia: (a) It is the main storage protein for iron; (b) Highest concentration is found in the hepatocytes.
► Most serious complications of anemia in pregnancy and labor are: (a) pre-eclampsia, (b) cardiac failure, (c) PPH, and (d) sepsis.
► Any women with a low mean corpuscular volume and without any evidence of iron deficiency need to be screened for thalassemia (hemoglobin electrophoresis).
► When pregnant anemic women do not respond with iron therapy and the reticulocyte count is not increased, she may be screened for concomitant folic acid deficiency.
► Iron deficiency anemia is treated with oral iron supplementation. Few women may need parenteral iron therapy. ► Intravenous iron therapy (TDI) is used as it has the certainty of its administration.
► Parenteral therapy is recommended for women who are either: (a) intolerant or (b) unwilling to daily oral iron or (c) in advanced state of pregnancy (>32 weeks).
► Iron sucrose is safe and has less side effects. However, it needs multiple doses compared to iron dextran that needs single dose.
► Megaloblastic anemia is due to the deficiency of either vitamin B12 (rare) or fol ate (common) or both. Daily requirement of vitamin B12
during pregnancy is 3 µg and that of folic acid is 200 µg.
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

HEART DISEASE IN PREGNANCY
INCIDENCE AND TYPES: The incidence of cardiac lesion is less than 1 % amongst hospital deliveries. The most common cardiac lesion is of rheumatic origin followed by the congenital ones. The ratio
between the two has fallen over the past two decades from 10:1 to about 3:1 or even 1:1 in high income countries. Adequate treatment of rheumatic fever by appropriate antibiotics to cope with the group A -hemolytic streptococcal infection, pari passu with the advancement in cardiac surgery to rectify the congenital heart lesions, are responsible for the change in the profile.
Rheumatic valvular lesion predominantly includes mitral stenosis (80%). Predominant congenital lesions include patent ductus arteriosus, atrial or ventricular septa! defect, pulmonary stenosis, coarctation of aorta and Fallot's tetralogy. Rare causes are: hypertensive, coronary cardiac, thyrotoxic or syphilitic diseases.

I DIAGNOSIS

EFFECT OF CARDIOVASCULAR PHYSIOLOGY ON HEART LESION: Marked hemodynamic changes in pregnancy (Box 20.3) and cardiac output in particular, have profound effects on heart disease. This is specially due to the hemodynamic alteration during labor and the immediate postpartum. Labor is associated with pain, stress and anxiety to cause tachycardia. Each uterine contraction squeezes out 400-500 mL of blood from the uterus to the systemic circulation. In a women with heart disease this increases: (a) Cardiac Output (CO), (b) Pulmonary pressures and (c) Pulmonary congestion. Cardiac failure commonly occurs during pregnancy around 30 weeks, during labor and mostly soon following delivery. Factors responsible for cardiac failure: (1) Advanced age, (2) Cardiac arrhythmias or left ventricular hypertrophy, (3) History of previous heart failure, (4) Presence of 'risk factors' in pregnancy are: infection, anemia, hypertension, excessive weight gain and multiple pregnancy.
EFFECTS OF HEART LESION ON PREGNANCY: There is a tendency of preterm delivery and prematurity. IUGR is quite common in cyanotic heart diseases.

■ Hyperdynamic circulation.
■ Systolic ejection murmur at left sternal border (due to increased blood flow across the aortic and pulmonary valves).
■ Dyspnea, decreased exercise tolerance, fatigue, syncope. ■ Tachycardia, shift of ventricular apex.
■ Continuous murmur at 2nd to 4th intercostal space-mammary souffle.
■ Loud first sound with splitting.
Symptoms must be carefully assessed and investigations are to be done to confirm the diagnosis.

• Symptoms: Dyspnea, nocturnal cough, syncope, chest pain.
♦ Signs: Chest murmurs-pansystolic, late systolic, louder ejection systolic or diastolic associated with a thrill.
♦ Cardiac enlargement, arrhythmia.
♦ Chest radiography (using lead shield): Cardiomegaly, increased pulmonary vascular markings, enlargement of pulmonary veins and CCF.
■ Electrocardiography: T wave inversion, biatrial enlargement, dysrhythmias.
■ Echocardiography (color flow Doppler study): Structural abnor malities (ASD, VSD), valve anatomy, valve area, function, left ventricular ejection fraction, pulmonary artery systolic pressure.
■ Cardiac MRI can delineate complex (anatomy when it is not well evaluated by echocardiography).
■ Cardiac catheterization.

;Table 20.3: Risks or'maternal mortality with heart disease (NYHA,' i ' '
J'j992).' .
Cardiac disease Mortality(%)
Group 1 (minimal risk): ASD, VSD, PDA, Fallot 0-1 tetralogy (corrected), mitral stenosis (NYHA-
Grade I and II), bioprosthetic valve.
Group 2 (moderate risk): MS (NYHA-Grade Ill 5-15 and IV) AS, Marfan syndrome (normal aorta), Fallot tetralogy (uncorrected), MS with atrial fibrillation, artificial valve.
Group 3 (major risk): Pulmonary hypertension, 25-50 Marfan syndrome (aortic involvement), aortic
coarctation with valvular involvement.

Grade-I: Uncompromised and no limitation of physical activity.
Grade-II: Slightly compromised with slight limitation of physical activity. The patients are comfortable at rest but ordinary physical activity causes discomfort.
Grade-Ill: Markedly compromised with marked limitation of activity. The patients are comfortable at rest but discomfort occurs with less than ordinary activity.
Grade-IV: Severely compromised with discomfort even at rest
Limitation: This classification has considered the symptoms only but not the anatomical type and severity of pathology. It does not predict pregnancy outcome.

I PROGNOSIS

♦ Maternal ♦ Fetal
MATERNAL: The prognosis depends on: (1) Nature of lesion, (2) Functional capacity of the heart (Box 20.4), (3) Quality of medical supervision provided during pregnancy, labor and puerperium, (4) Presence of other risk factors mentioned earlier, and (5) Whether patient has undergone corrective surgery or not (Table 20.3 and Boxes 20.5 to 20.7).
Maternal mortality is lowest in rheumatic heart lesions and acyanotic group of heart diseases-less than
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

• · Infections-urinary tract, dental and respiratory tract.
♦ Anemia • Obesity
• Hypertension ♦ Arrhythmias

• Hyperthyroidism
• Drugs-betamimetics • Dietary indiscretion
excess intake of caffeine, alcohol, high calorie diet,
excess salt.

1 %. With elevation of pulmonary vascular resistance especially with cyanotic heart lesions, the mortality may be raised to even 50% (Eisenmenger's syndrome). Most of the deaths occur due to cardiac failure and the maximum deaths occur following birth. The other causes of death are-{a) pulmonary edema, {b) pulmonary embolism, (c) active rheumatic carditis, (d) subacute bacterial endocarditis and (e) rupture of cerebral aneurysm in coarctation of aorta.

Conditions in which pregnancy risk: WHO I • Uncomplicated small or mild:
• Pulmonary stenosis.
• Patent ductus arteriosus. • Mitral valve prolpase.
♦ Successfully repaired simple lesions (atrial or ventricular septal defect, patent ductus arteriosus, and anomalous pulmonary venous drainage).
♦ Atrial or ventricular ectopic beats, isolated.
Conditions in which pregnancy risk: WHO II or Ill WHO II (if otherwise well and uncomplicated)
♦ Unoperated atrial or ventricular septa I defect. ♦ Repaired tetralogy of Fallot.
+ Most arrhythmias.
WHO II or Ill (depending on individual) ♦ Mild left ventricular impairment.
♦ Hypertrophic cardiomyopathy.
• Native or tissue valvular heart disease not considered WHO I or IV. ♦ Marfan syndrome without aortic dilatation.
♦ Aorta <45 mm in aortic disease associated with bicuspid aortic valve.
♦ Repaired coarctation.
WHOIII
♦ Mechanical value.
+ Systemic right ventricle. • Fontan circulation.
+ Cyanotic heart disease (unrepaired).
♦ Other complex congenital heart disease.
• Aortic dilatation 40-45 mm in Marfan syndrome.
• Aortic dilation 45-50 mm in aortic disease associated with bicuspid aortic valve.
Conditions in which pregnancy with high risk: WHOIV (pregnancy contraindicated)
♦ Pulmonary arterial hypertension of any cause.
♦ Severe systemic ventricular dysfunction (LVEF <30%, NYHA Ill to IV).
♦ Previous peripartum cardiomyopathy with any residual impairment of left ventricular function.
• Severe mitral stenosis, severe symptomatic aortic stenosis. ♦ Marfan syndrome with aorta dilated >45 mm.
• Aortic dilation >50 mm in aortic disease associated with bicuspid aortic valve.
• Native severe coarctation.
Guidelines on the management of cardiovascular diseases during pregnancy, of the Task Force on the Management of Cardiovascular DiseasesduringPregnancy of the European Society of Cardiology (ESC). Eur Heart Joural. 2011;32:3147-97.

However, with improved medical care, surgical correction of the congenital lesions and better obstetric care, the maternal mortality has been reduced markedly. Pregnancy however, does not affect the long-term survival of a woman with rheumatic heart lesion provided she survives pregnancy itself. Cardiac disease are the main cause of indirect maternal death. Main causes include: MI, Aortic Dissection, Cadiomyopathy.

FETAL: In rheumatic heart lesions, the fetal outcome is usually good and in no way different from the patients without any heart lesion. However, in cyanotic group of heart lesion, there is increased fetal loss (45%) due to abortion, IUGR and prematurity. Fetal congenital cardiac disease is increased by 3-10% if either of the parents have congenital lesions.
I GENERAL MANAGEMENT

PRINCIPLES
- Early diagnosis and evaluation of anatomical type and functional grade of the case.
- To detect the high risk factors and to prevent cardiac failure.
- Multidisciplinary team approach (obstetrician, cardiologist and neonatologist) and mandatory hospital delivery.
PLACE OF THERAPEUTIC TERMINATION: Considering high maternal deaths, absolute indications are-(a) primary pulmonary hypertension, {b) Eisenmenger's syndrome and {c) pulmonary veno-occlusive disease.
Relative indications are: (a) Parous woman with grade III and IV cardiac lesions and {b) Grade I or II with previous history of cardiac failure in early months or in between pregnancy.
The termination should be done within 12 weeks by suction evacuation (MVA) or by conventional D&E.
Contraindication to pregnancy are (Box 20.7): WHO Categ01y-IV.
ANTENATAL CARE: The patients with heart disease should be supervised in a tertiary care hospital. The initial assessment should be made in consultation with a cardiologist. Injection penidure LA-12 (benzathine penicillin) is given at intervals of 4 weeks throughout pregnancy and puerperium to prevent recurrence of
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy ml
2

rheumatic fever. Counseling is to be done regarding prognosis and risks.
Special care in each antenatal visit is to detect and to prevent cardiac failure in pregnancy.
ROLE OF ANTICOAGULANTS
Recommendation of anticoagulation therapy for pregnant women with mechanical valves (ACC, AHA-2014).
First trimester: Women should be started with LMWH after the first missed period with diagnosis of pregnancy. Warfarin has the risk of teratogenicity (Warfarin embryopathy). Warfarin embryopathy is obser-ved in about 6% of cases when used in the first trimester. It is reduced to 3% when a dose of <5 mg/day is used.
Second and third trimester: Warfarin is started and continued till the onset of labor or induction of labor. Warfarin is superior to heparin therapy. Heparin therapy need to be started with weight-based dose adjustment if it is to be continued in the 2nd and 3rd trimester. Anti factor Xa levels to be monitored for effective therapy. Dose adjusted LMWH or Unfractionated Heparin (UFH) or warfarin can be used in the second and third trimester (ACCS-2012).
Use of anticoagulant in labor and delivery: Prior to labor, warfarin is stopped. Conversion to heparin based (UFH or LMWH) therapy is started after delivery.
Postpartum: Heparin therapy is continued till 7 days postpartum. Conversion to warfarin with overlapping is done thereafter. Dose of warfarin therapy is adjusted to maintain the INR of 2.5 to 3.5. Levels of anti-factor Xa ranging from 1.5 IU/mL (peak) to 1.0 IU/mL (mid) and to 0.6 IU/mL have been recommended. Heparin therapy is monitored with aPTT. A level >2.0 is optimum.
Anticoagulation therapy: LMWH is given twice daily with monitoring anti Xa level. UFH dosed every 12 hours to maintain aPTT twice the control. Protamine sulfate IV is used as an antidote to heparin.
UFH, LMWH and warfarin therapy do not contra indicate breastfeeding.
(a) Prophylactic LMWH: Stop 12 hours before labor/ surgery; (b) Therapeutic LMWH: Stop 24 hours before labor/surgery; (c) After spinal or epidural catheter removal: Start thromboprophylaxis after 4 hours; (d) Prophylactic UFH: Stop 4 hours before labor/surgery; (e) Therapeutic UFH: Stop IV-6 hours before, Stop SC-12 hours before labor/surgery.
Indications for cardiac surgery in pregnancy are:
■ Failure of medical treatment for: (a) Intolerable symptoms and (b) Intractable cardiac failure.

I MANAGEMENT DURING LABOR
PLACE OF INDUCTION: Most patients with cardiac disease go into spontaneous labor and deliver without any dificulty.

However, induction (vaginal PGE ) may be employed in very selected cases for obstetric indications. One should guard against infection and pulmona1y edema due to fluid overload.

LABOR: First stage:
- Position: The patient should be in lateral recumbent position to minimize aortocaval compression.
- Oxygen is to be administered (5-6 L/min) if required. - Analgesia in the majority, is best given by epidural.
- Prophylactic antibiotics against bacterial endocarditis.
- Fluids should not be infused more than 75 mL/hour to prevent pulmonary edema.
- Careful watch of the pulse and respiration rate. If the pulse rate exceeds llO per minute in between uterine contractions, rapid digitalization is done by intravenous digoxin 0.5 mg.
- Cardiac monitoring and pulse oximetry can detect arrhythmias and hypoxemia early.
- Central venous pressure monitoring may be needed in selected cases.
Prophylactic antibiotics for bacterial endocarditis: Amoxicillin 2 g (IV) or ceftriaxone 1 g (IV). For women allergic to penicillin clindamycin 600 mg (IV) is given. Antibiotic prophylaxis during labor and up to 48 hours after delive1y is considered appropriate. This is to prevent bacterial endocarditis.
High-risk patients are: (a) Structural heart disease, (b) Rheumatic heart disease, (c) Cyanotic congenital heart disease, (d) Presence of dental and respiratory tract infections, ( e) Hypertrophic cardiac myopathy, (f) Prosthetic heart valves, (g) Prior history of infective endocarditis and (h) Cardiac transplant.
Second stage: No maternal pushing and the tendency to delay in the second stage of labor is to be curtailed by forceps or ventouse under pudenda! and/ or perinea! block anesthesia. Ventouse is preferable to forceps as it can be applied without putting the patient in lithotomy position (raising the legs increases the cardiac load). Intravenous ergometrine with the delivery of the anterior shoulder should be withheld to prevent sudden overloading of the heart by the additional blood squeezed out from the uterus.
Third stage: Conventional management is to be followed. Slight blood loss is not detrimental but if it is in excess, oxytocin can be given IM or by infusion. This may be accompanied by aggressive diuresis by IV frusemide. It is better to administer oxytocin in preference to ergometrine in all cases of heart disease in third stage.
PLACE OF CESAREAN SECTION: Vaginal delivery is always preferred. Cesarean delivery is for obstetric indications.
CARDIAC INDICATIONS OF CESAREAN DELIVERY (CD) ♦ Coarctation of aorta.
♦ Aortic dissection or anemysm. ♦ Dilated aortic root >4 cm.
♦ Warfarin treatment within two weeks.
♦ Severe symptomatic aortic stenosis.
ED Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

• Recent myocardial infarction.
♦ Need for emergency valve replacement.
In coarctation of aorta, elective cesarean section is indicated to prevent rupture of the aorta or mycotic cerebral anemysm. The anesthesia should be given by expert anesthetist using either epidural (preferred) or general anesthesia.
Cardiac surgery during pregnancy: Cardiac surge1y is indicated in patients who are refractory to medical therapy. Surgery has high risk of maternal and fetal morbidity and mortality. Different types of surgery done are: cardiopulmonary bypass, prosthetic valves, valve replacements. Surgery should be a planned one and preferably during the second trimester of pregnancy (16-18 weeks). Pregnancy after heart transplantation: Women can have pregnancy following 1 year post transplant. The transplanted heart adjust pregnancy well. Complications are: Hypertension, rejection episode and miscarriage.
PUERPERIUM
- The patient is to be observed closely for the first 24 hours. Oxygen is administered. Hourly pulse, BP and respiration are recorded. Diuretic may be used if there is volume overload.
- Breastfeeding is not contraindicated unless there is failure. Anticoagulant therapy is not a contraindication of breastfeeding.
CONTRACEPTION
• Steroidal contraception is avoided as it may cause thromboembolic phenomenon.
• Intrauterine device (copper IUCD or LNG-IUS) is an option. WHO permits its use.
• Progestin only pills or parenteral progestins are safe and effective. They may cause irregular bleeding especially if the patient is anticoagulated.
• Barrier method of contraceptives ( condom) is the best. • Sterilization should be considered with the completion of the family at the end of first week in the puerperium under local anesthesia through abdominal route by minilaparotomy technique. If the heart is not well
compensated, the husband is advised for vasectomy.
MANAGEMENT OF CARDIAC FAILURE IN PREGNANCY: The principles of management are the same as in nonpregnant state. A cardiologist should be involved. Underlying pathophysiology and the cause of failure must be understood. Risk factors for cardiac failure has been discussed in Box 20.6.
To improve forward flow, Systemic Vascular Resistance (SVR) need to be reduced. Pulmonary congestion is reduced with diuresis. Labor and delivery should be managed with standard care. Excess preload results in pulmonary congestion. Poor preload will result in insufficient forward flow.

Management-outlines are: ♦ Propped up position.
♦ 02 administration.
♦ Monitoring with ECG and pulse oximetry.
♦ Diuresis: Frusemide (Loop) (40-80 mg) IV (preload reduction to avoid pulmonary congestion).
♦ Mechanical ventilation.
♦ Digoxin 0.5 mg IM followed by tab digoxin 0.25 mg PO (Digoxin crosses the placenta and is excreted in breast milk).
♦ Dysrhythmias-quinidine or electrical cardioversion. ♦ Tachyarrhythmias-adenosine (3-12 mg) IV or DC
conversion.
♦ Preload reduction-fusemide for diuresis.
♦ Hydralazine-to reduce after load. Heparin therapy to prevent thromboembolism.
♦ Extracorporeal Membrane Oxygenation (ECMO) for women with PPCM and women with pulmonary hyper tension.
PREDICTORS OF ADVERSE MATERNAL OUTCOMES
♦ Prior cardiac failure, arrhythmia or transient ischemic attack.
♦ Baseline NYHA class >2 or associated cyanosis.
♦ Left heart obstruction: Mitra! valve area <2 cm2, aortic valve area <1.5 cm2, or peak ventricular outflow gradient >30 mm Hg by echocardiography.
♦ Left ventricular ejection fraction <40%.

SPECIFIC HEART DISEASE DURING PREGNANCY AND THE MANAGEMENT

VALVULAR (RHEUMATIC) HEART DISEASE
MITRAL STENOSIS: Mitra! Stenosis (MS) is the most common rheumatic and also the acquired valvular lesion met during pregnancy. Death is due to pulmonary edema, right sided heart failure and embolism. Symptoms at rest occur when the valve area <1.5 cm2. Clinical diagnosis is made with mid diastolic rumbling murmur with pre-systolic accentuation. Echocardiography can diagnose steno tic calcified valve, measurement of the valve area, left atrial enlargement, atrial fibrillation, thrombus formation and the risk of embolization. Pulmonary Hypertension (PH) is a complication.
Normal mitral valve area ranges between 4 and 6 cm2• Symptoms usually appear when stenosis narrows this to less than 2.5 cm2• Women with mitral valve area ::1 cm2, have the high rate of pulmonary edema (55%) and arrhythmia (33%). In asymptomatic cases, the mortality is <l % but once it is significantly symptomatic, mortality ranges between 5 and 15%. During labor continuous epidural analgesia is ideal and
intravenous fluid overload is to be avoided.
Goal of management is to increase the CO. Management includes: (a) diuresis to reduce pulmonary congestion and to improve oxygen saturation, (b) P-blocker to reduce heart rate, (c) antibiotic (monthly benzathine penicillin), (d) digoxin, P-blocker can control atrial fibrillation, (e) electrical cardioversion may be necessary, (f) heparin to prevent systemic embolization.
■ Labor pain can be controlled with epidural analgesia. Women with symptomatic stenosis with valve area <l cm2 may
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy mJ

be managed with pulmonary artery catheter. Mode and route of delivery depends on obstetric indication. ■ Second stage need to be curtailed with prophylactic forceps/ventouse delivery. ■ Common complications are: (a) pulmonary edema, (b) arrhythmia. This is specially for women with valve area <l cm2.
Surgical management: Indications: Women with-(i) severe disease and (ii) refractory to medical management. Mitra! vulvoplasty is successful in more than 95% of cases. Maternal mortality (0.5%) and fetal loss (<2%) are low. Most common surgery during pregnancy is balloon vulvotomy.
PLACE OF VALVOTOMY: Surgery should be considered in cases with unresponsive failure with pregnancy beyond 12 weeks. Best time of surgery is between 14 and 18 weeks. Balloon valvotomy can be carried out in early second trimester. Atrial fibrillation is a complication. Digmdn, -blockers and anticoagulation (heparin) should be used.
AORTIC STENOSIS: Most cases of aortic steno sis are congenital, some are rheumatic in origin. Normal aortic valve area is 3-4 cm2• When it is reduced to less than or equal to 1 cm2, stenosis is significant. Cardiac output is reduced. Maternal mortality of significant aortic stenosis is about 15-20% with perinatal loss of about 30%. Epidural anesthesia is contraindicated. During labor, fluid therapy (125-150 mL/h) should not be restricted. Left ventricular after load is high and the pregnant patient is sensitive to hemorrhage.
Diagnosis is often made by harsh systolic murmur with radiation into the carotid arteries. Diagnosis confirmed by echocardiography. Doppler can assess the pressure gradient cross the valve and the valve area can be measured also. In AS there is increased LV afterload, ventricular hypertrophy, increased cardiac oxygen need and impaired coronary perfusion. There is myocardial ischemia. In a patient with AS, excess fluid may lead to pulmonary edema, on the other hand less fluid leads to hypotension. Management of hypotension is difficult compared to pulmonary edema due to fluid overload.
Obstetric management: Adequate antenatal care. Fetal echocardiography is indicated to rule out CHD. Patient may need PAWP monitoring during labor. When PAWP falls, volume can be administered. Second stage labor need to be cut short with forceps or ventouse. Diuretics are given carefully to treat pulmonary edema. Surgical management of valve replacement or vulvotomy in pregnancy is done in patients who remain refractory to medical treatment. Balloon vulvotomy in cases without calcification may be helpful. Narcotic epidural analgesia is safe.
CONGENITAL HEART DISEASE (CHO): CHD is observed in nearly 1 % of all live births. Inheritance of CHD is ranges from 9% to 14%. The rate of CHD with an affected mother is 2 to 3.5 times compared to observed with an affected father. The defect in the child may not be the same as in the parents. All women with CHD should undergo fetal echocardiography during antenatal checking at 18 to 22 weeks gestation. The main pathologies are: (1) Cyanosis, (2) Left ventricular (LV) dysfunction, (3) Pulmonary hypertension, (4) Right ventricular (RV) dysfunction and (5) Severe left outflow tract (systemic) obstruction. Women with cyanotic heart disease often need medical termination of pregnancy (42%).
Common maternal complications are: (i) Congestive cardiac failure, (ii) Pulmonaty edema, (iii) Arrhythmia, (iv) Hypertension, (v) Maternal mortality (Eisenmenger syndrome).

Poor perinatal outcomes are due to: (i) Low birth weight, (ii) Prematurity, (iii) Congenital heart disease, (iv) Miscarriage and (v) Still birth.
fm Acyanotic (L to R shunt)
♦ Atrial Septal Defect (ASD): ASD (ostium secundum type) is the most common congenital heart lesion during pregn ancy. Left to right shunt causes right atrial and ventricular enlargement. Atrial arrhythmias are common with atrial enlargement. Even uncorrected ASD tolerates pregnancy and labor well. Congestive cardiac failure unresponsive to medical therapy requires surgical correction. Shunt reversal is the major risk which may develop in hypovolemia. Such cases may occur in hemorrhagic conditions and following injudicious administration of epidural anesthesia. In the absence of arrhythmias, and pulmonaty hypertension, ASD
does not usually complicate pregnancy.
♦ Ventricular Septa) Defect (VSD): Diagnosis-clinically a harsh systolic murmur, the left sternal border (not to the carotids) suggests VSD. Diagnosis is confirmed with 2-D echocardiography with color-flow Doppler study to show shunting across the ventricular septum. In general, if the defect is less than 1.25 cm2, pulmonary hypertension and heart failure do not develop. Pregnancy is well-tolerated with small to moderate left to right shunt or with moderate pulmonary hypertension. The major risk is shunt reversal leading to circulatory collapse and cyanosis. Hypotension is to be avoided. Fetal loss may be up to 20%.
♦ Patent Ductus Arteriosus (PDA): Presence of continuous murmur at the upper left sternal border is suggestive of diagnosis. In the absence of Eisenmenger syndrome pregnancy is well tolerated. The ductus connects the proximal left pulmonary artery to the descending aorta just distal to the left subclavian artery. Functional closure occurs shortly after birth. Uncorrected PDA cases, have high mortality. Complications are: Pulmonary hypertension, cardiac failure. Cyanosis occur due to shunt reversal from PA to the aorta. The incidence of inheritance is about 4%. Surgical correction during pregnancy can be performed provided there is no pulmonary hypertension. Epidural analgesia is better avoided to minimize shunt reversal due to systemic hypotension. Fetal loss may be up to 7% and there is 4% chance that the child of this parent will suffer from the same abnormality. Endocarditis prophylaxis should be given.
♦ Mitral Valve Prolapse (MVP): It is the most common congenital valvular lesion. Most of them are asymptomatic. Women tolerate pregnancy and labor well. Endocarditis prophylaxis is essential.

I] Cyanotic (R to L shunt)
♦ Fallot's tetralogy: It is the most common form of cyanotic heart lesion. It is a combination of-(a) ventricular septa! defect, (b) pulmona1y valve stenosis (RVOT obstruction), (c) right ventricular hypertrophy and (d) an overriding aorta. Surgical repair includes closure of the VSD and relief of the RV OT obstruction. After surgical correction, patients tolerate pregnancy well. Surgically uncorrected patients are at increased risk. Complications like bacterial endocarditis, brain abscess and cerebral embolism are more common.
mJ Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy
Maternal mortality is 5-10% and the perinatal mortality pregnancy. Beta blocking drugs should be used to maintain is 30-40%. IUGR is common. Systemic hypotension may resting heart rate around 70 bpm. Hypertension should lead even to death. Epidural or spinal anesthesia is avoided. be avoided to prevent aortic dissection. Vaginal delivery is Pregnancy is discouraged in women with uncorrected desirable with shortening of second stage. When the aortic root tetralogy. diameter measures more than 4 cm, mortality increases to
♦ Eisenmenger's syndrome: Patients with Eisenmenger's 50%. Women with aortic diameter more than 5.5 cm should
graft
mostly due to aortic dissection or rupture.
syndrome have pulmonary hypertension with shunt (right have and valve replacement before pregnancy. Death is to left). Initially there is shunting of systemic circulation to
the pulmonary circulation. Systemic pressure and excessive Prosthetic valves: Women with major vulvar disease requires flow lead to microvascular injury, fibrosis and obliteration of surgical repair or valve replacement. Commonly two types of
pulmonary arterioles and capillaries. Consequently there is valves are used (Table 20.4): rise in Pulmonary Vascular Resistance (PVR). VSD, ASD and
ii
Cardiomyopathies
PDA are responsible for 89% cases of Eisenmenger syndrome
Cardiomyopathies-are a heterogeneous group of myocardial diseases affecting women with ventricular dysfunction. Primary is due to dysfunction of cardiac muscles only (hypertrophic dilated or peripartum cardiomyopathy). Secondary-due to systemic
in pregnancy.
Maternal mortality is about
50%
and so also
the perinatal loss
(75%).
Termination of pregnancy should
be seriously considered.
confirmed by echocardiography to reveal
Diagnosis
high pulmonary pressure and the intracrdiac shunt. Cardiac disorders like diabetes, SLE, thyroid dysfunction.
MRI is helpful to make the diagnosis. Complications are-(a) Peripartum Cardiomyopathy (PPCM): Etiology is unknown.
congestive cardiac failure, (b) hemoptysis due to pulmonary Prolactin may have a role as an etiological factor. Proposed
viral myocarditis, abnormal immune response,
factors are:
hemorrhage, (c) sudden death due to arrhythmia and malnutrition and others. Dilated CM is characterized by onset of yp pulmonary edema due to LV dysfunction and dilatation. Women
cerebrovascular accident and h
ervisocity.
Treatment
is with supportive care. Heparin should be used
throughout pregnancy as there is risk of systemic and pulmona1y presents with the symptoms of dyspnea, cough, tachycardia.
The incidence PPCM is 1 in 1300 to 1 in 1500. Cause is
unknown. Half of the patients demonstrate features of the LV
dilatation. Women with moderate to severe LV dysfunction
thromboembolism. Epidural anesthesia is contraindicated. Inhaled nitric oxide or IV prostacyclin is used as a pulmonary
vasodilator. Definitive therapy can be achieved only with have worse outcomes. Women with history of PPCM in previous pregnancy having the high risk of heart failure. Significantly dilated and hypokinetic cardiac chambers are the risk factors for
heart-lung or lung transplantation. Despite management
improvement, prognosis is poor.
II
Other congenital heart lesions thromboembolism. Anticoagulation therapy is needed.
Peripartum cardiomyopathy
is a diagnosis of exclusion. The
♦ the level of ductus arteriosus or tleft subclaviantartery. There patients aref usually multiparous and young (20-35 years). They dyspnea and palpitation. Examination reveals-tachycardia, arrhythmia, peripheral edema and pulmonary rales. Pregnancy
Constric ion of the aor a is at about
Coarctation of aorta:
complain o weakness, shortness of breath, cough, nocturnal
is difference in BP between the right arm and the lower
extremity.
Maternal mortality is high
9%.
Fetal loss is also
increased to
25%.
Surgical correction should be done prior
to pregnancy. Termination of pregnancy should be seriously is poorly tolerated in women with dilated cardiomyopathy.
Important diagnostic criteria are:
Cardiac failure within
considered. Elective cesarean section is preferred to minimize (i)
last month of pregnancy or within 5 months postpartum. (ii) No determinable cause for failure. (iii) Absence of previous heart
dissection associated with labor. blockers are the drug to
control hypertension.
Complications
are-aortic dissection
at the site of coarctation, rupture of berry aneurysms, heart disease. (iv) Left ventricular systolic dysfunction as evidenced on
echocardiography-(a) Ejection fraction less than 45% and (b) CVAs or endocarditis. Left ventricular end diastolic dimension more than 2.7 cm/m2.
are due to: CCF,
failure, cardiac ischemia.
Maternal deaths
Postpartum period is a special risk due to the load of eased thickening of muscular layer of pulmonary arterioles. excess blood volume from uterine contraction, mobilization The cause remains unkno postpartum. The tfetal outlook Table 20.4: Prosthetic valves in pregnancy.
is characterized by incr
Primary pulmonary hypertension
♦
wn.
(75%)
Maternal mor ality is about
majority die
50%,
is also gloomy. Termination of pregnancy is indicated. Bioprosthetic valves Mechanical valves
Bed rest should be imposed from 20 weeks of pregnancy. ■ Less durable (10-15 years). ■ More durable.
(heparin is administered.
i used
Anticoagulant
Sildenafil
as a potent vasodilator )as it increases endogenous snitric ■ When used in young women, ■ Higher rate of lism.
needs replacement in later life.
thromboembo
oxide.
or IV prostacyclin helps pulmonary
Oral nifedipine
vasodilatation. Epidural morphine gives effective analgesia ■ Undergoes accelerated ■ Needs anticoagulation without any hemodynamic change. Women with pulmonary
deterioration with each
pregnancy.
therapy.
h ertension and right ventricular dysfunction are strongly
yp
discouraged to become pregnant. ■ Other complications are less. ■ Other complications
(hemorrhage, valve
Marfan's syndrome:
It is an
autosomal dominant
condition.
♦
There is 50% chance of transmission to the offspring. thrombosis) are more. Dilatation of aorta more than 40 mm as evidenced from • Mitral position valves have higher risks ofthromboembolism
compared to aortic position.
echocardiography (normal 20 mm) is a contraindication of
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy lD!

of extracellular fluid and rise in SVR. There is high risk for LV decompensation. Control of tachycardia, preload and afterload reduction should be done promptly.
Treatment: Nearly half of the women with PPCM recover within 6 months of delivery.
The treatment is bed rest, digoxin, diuretics (preload reduction), hydralazine or ACE inhibitors (postpartum) (afterload reduction), p blocker and anticoagulant therapy. Vaginal delivery is preferred. Epidural anesthesia is ideal. There is no contraindication of breastfeeding. Mortality is high (25-50%)-due to CCF (50%), arrhythmia or thromboembolism. It may recur in subsequent pregnancies (30%).
Myocardial infarction is rare in pregnancy (5 per 100,000 deliveries). Risk factors for MI in pregnancy are: age >40 years, hypertension, diabetes, smoking or postpartum infection; drugs: bromocriptine, ergot alkaloids. Coronary dissection and normal coronary arteries are observed in 50% cases. Diagnosis of MI is often delayed. Chest pain, dyspnea are common. ST segment elevation in ECG in a women with chest pain raises the suspicion.
Management is mostly as in nonpregnant state. Coronary angioplasty, stenting and thrombolytic therapy have been done in pregnancy when indicated. Supine position and hypotension should be avoided.
Labor._managed as with standard cardiac care. Elective delivery within two weeks of infarction should be avoided. Regional analgesia for pain in labor and p blockers for tachy cardia may be used. Maternal pushing is avoided and second stage is shortened by forceps or vacuum. Thrombolytic therapy should be avoided specially with coronary dissection. Medications
like morphine, p blockers, organic nitrates, MgSO 4, calcium
antagonists may be used. Clopidogrel is avoided during cesarean delivery due to the risk of bleeding. Syntocinon could be used in the third stage management. Diuretics to be used postpartum. Percutaneous transluminal coronary angioplasty can be done successfully around 36 weeks of pregnancy if needed.

DIABETES MELLITUS AND PREGNANCY
Diabetes mellitus is a chronic metabolic disorder due to either insulin deficiency (relative or absolute) or due to peripheral tissue resistance (decreased sensitivity) to the action of insulin. The pathophysiology involved are: (i) decreased sensitivity of skeletal muscles and liver to insulin (insulin resistance) and (ii) inadequate secretion of insulin W cell dysfunction). Pregnancy is a state of chronic low grade inflammation. This is associated with increased circulating levels of C-Reactive Protein (CRP) and interleukin-6 (IL-6). Both these factors enhance insulin resistance. The defect lies both in insulin secretion and action. The ultimate effect is the hyperglycemia. Two types are generally described.
A. Type-1 is characterized by young age onset (juvenile) and absolute insulinopenia (P cell destruction). They have genetic predisposition with presence of autoantibodies.
B. Type-2 is characterized by late age onset, overweight woman and peripheral tissue (skeletal muscle, liver) insulin resistance (hyperinsulinemia). Genetic predis position is also observed.

Type l and type 2 may be: (a) without vascular complications or (b) with vascular complications.
Other types: Genetic (mutation, defects), drugs (P agonists), MODY.
Maturity onset diabetes of the youth (MODY) is due to P cell genetic mutation (glucokinase gene). It has an autosomal dominant mode of inheritance. It usually manifests in adulthood.
Placental glucose transport (facilitated diffusion) depends on a family of Glucose Transporters (GLUT). The principal glucose transporter GLUT-1 is located in the placental syncytio trophoblasts. Oral hypoglycemic drugs increase placental GLUT-1 transporter.
Type-I diabetes mellitus: Abrupt onset, at a young age. It is mostly due to mutations in the glucokinase gene. Patients suffer absolute insulinopenia and need life-long insulin replacement. There may be genetic predisposition of autoantibodies against the pancreatic cells. Type-1 diabetes are at increased risk of Diabetic Ketoacidosis (DKA). Sensitivity of insulin in these women is decreased in late gestation by about 50%.
Alternation in lipid metabolism in diabetes: Decrease in HDL cholesterol is observed especially with type-1 diabetes. HDL acts as a plasma antioxidant. Fall in HDL may be a cause for congenital malformations as oxidative stress is a potential factor. Increased free fatty acids have been associated with fetal overgrowth (adiposity). Insulin inhibits lipolysis and decrease FFAlevels.
TNF a is inversely correlated with insulin sensitivity. It is an important predictor to cause decrease insulin sensitivity in pregnancy.
About 1-14% of all pregnancies are complicated by diabetes mellitus and 90% of them are Gestational Diabetes Mellitus (GDM). Nearly 50% of women with GDM will become overt diabetes (type-2) over a period of 5 to 20 years.
GLYCOSURIA IN PREGNANCY: During pregnancy, renal threshold is diminished due to the combined effect of increased glomerular filtration and impaired tubular reabsorption of glucose. It is present most commonly in midpregnancy. If glucose tolerance test is done, glucose leaks out in the urine even though the blood sugar level is well below 180 mg/100 mL (normal renal threshold). No treatment is required and the condition disappears after delivery.
SIGNIFICANCE: Glycosuria is specifically detected by testing a second fasting morning specimen of urine, collected a little later, after discarding the overnight urine. Fasting glycosuria if present, is ominous. Glycosuria on one occasion before 20th week and on two or more occasions, thereafter, is an indication for glucose tolerance test.
I GESTATIONAL DIABETES MELLITUS (GDM)
-ri·,:
!JI:·
NOMENCLATURE: GDM is defined as !] !]
carbohydrate intolerance of variable
severity with onset or first recognition :i . during the present pregnancy (ACOG-2017).
The entity usually presents late in the second or during the third trimester. The definition is used irrespective of the fact that the condition persists after pregnancy or
'Bl Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

not on insulin is used or not for the treatment. However, it includes some women with previously unrecognized overt diabetes. Majority of these women (>50%) with GDM ultimately develop overt diabetes by next 15 to 20 years.
Risk Factors for GDM
a. Positive family history of diabetes (parents or sibling). Family history should include uncles, aunts and grandparents.
b. Having a previous birth of an overweight baby of 4 kg or more.
c. Previous GDM or stillbirth with pancreatic islet hyperplasia revealed on autopsy.
d. Unexplained perinatal loss.
e. Presence of polyhydramnios or recurrent vaginal candidiasis in present pregnancy.
• Women with PCOS
• Hypertension (140/90 mm Hg) f. Persistent glycosuria.
g. Age over 30 years. h. Obesity.
i. Ethnic group (East Asian, Pacific island ancestry).
Screening Strategy for GDM
All pregnant women should be screened for GDM irrespective of risk-factors (ACOG). Screening is done at 24-28 weeks of gestation. Early screening is recommended (ACOG, ADA) for women with high risk factors. Value of
HbA1c is estimated for such women. HbA1c 6.5% suggests
overt diabetes. For these women with diabetes during embyogenesis, a comprehensive ultrasound is done to detect any fetal malformation.
The method is employed by using 50 g oral glucose challenge test without regard to time of day or last meal, between 24 and 28 weeks of pregnancy. A plasma glucose value of 140 mg% or that of whole blood of 130 mg% at 1 hour is considered as cut off point for consideration of a 100 g (WHO, IADPSG-75 g) 2 hour Oral Glucose Tolerance Test (OGTT) (Table 20.5).

Diagnosis of GDM:
• FBS 5.6 mmol/L (100 mg/dl).
• 2 hours plasma glucose 7.8 mmol/L (140 mg/dl).
Advice against pregnancy:
• Women with diabetes whose HbA level is above 10% are strongly advised not to get pregnant because of the associated risks of complications.
1c

DIPSI (Diabetes in Pregnancy Study Group in India) recommends 1-step procedure with 75 g oral glucose without regard to the time of the last meal. A venous plasma glucose value at 2-hour more than 140 mg/dL is diagnosed GDM. DIPSI criteria for the diagnosis of GDM awaits reconsiderations.
MANAGEMENT: Frequency of GDM is rising world wide and overall it is 14%. Diet: Medical Nutrition Therapy (MNT) with 2,000-2,500 kcal/day for normal weight woman and restriction to 1,200-1,800 kcal/day

Table 20.5: Various diagnostic criteria for gestational diabetes
mellitus.
O'Sullivan/
Mahan Carpenter (venous and
whole NDDG Coustan IADPSG Glucose (mg/ blood) (plasma) (plasma) (plasma) dL) (100g) (100 g) (100g) (75g)
Fasting 90 105 95 92 1 hour 165 190 180 180 2 hours 145 165 155 153 3 hours 125 145 140 N/A
(IADPSG: International Association of Diabetes in Pregnancy Study Groups; N/A = Not Available; NADG: National Diabetes Data Group; GTT: Glucose Tolerance Test; IADPSG: diagnosis of GDM is made when one or
more thresholds are met or exceeded)

for overweight woman is recommended. Carbohydrate should be 40-50% of total calories. Complex carbohy drates are preferred because simple carbohydrates produce significant postprandial hyperglycemia. Women should perform self-blood glucose monitoring using reflectance meter. The treatment of GDM has clear ben efits for the mother, fetus and the neonate: There is a less: (a) pre-eclampsia, (b) fetal macrosomia, (c) IUFD, (d) need for Cesarean Delivery (CD), (e) shoulder dysto cia and (f) birth injuries. The patient needs more frequent antenatal supervision with periodic checkup of fasting plasma glucose level which should be less than 95 mg%. The control of high blood glucose is done by restriction of diet, exercise with or without insulin. Nearly 25% women with GDM need insulin therapy. Exercise for 30 minutes daily for 5 days a week (aerobic, brisk walking) programs are safe in pregnancy and may obviate the need of insulin therapy.
One hour PP glucose <140 mg/dL and 2 hour PP glucose <120 mg/dL with diet, is optimum (ACOG, ADA). Pharmacotherapy is recommended when these cut-off values are exceeded following prescribed diet. Insulin or metformin is recommended as first line treatment for GDM (SMFM) though insulin is preferred by others (ACOG, ADA). Insulin does not cross the placenta. Metformin is not teratogenic though it crosses the placenta. However, 46% of women may need supplemental insulin for glycemic control.
Exercise: Walking for 10-15 minutes after each meal helps in controlling PP glucose levels.
Obstetric management: Well-controlled GDM on diet, should be planned for delivery at 39°17 to 40617 weeks gestation. Women on insulin and/or oral medication are planned for delivery at 39°17 to 39617 weeks of gestation. GDM with suboptimal control, delivery is planned at 37°17 to 38°17 weeks of gestation. Individual case may need delivery at late preterm also. Induction of labor may be done with standard approach.
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy - f b, 20:6f( PTiS !iO n; /GDM - J :-:·, l·t r\:,- ': -:: i \}· , i r:: ·t:,il; : }: !:·:;:.t f;-: ':\: : 't:} · '!; ·/ / ; _ ' ,, ' ,.,:c,•,,,\,
y
l
- "' :? 7
'
u
A. Maternal: 8. Fetal/Neonatal C. Long-term effects (maternal}
• Shoulder dystocia. • Increased perinatal loss is with fasting • Hypertension. Polyhydramnios . hyperglycemia. Fetal anomalies are not ■ Obesity.
•
•
•
•
■ Birth injuries. increased. This is due to the absence Insulin resistance.
■ Pre-eclampsia. of metabolic disturbance during Hyperlipidemia.
■ Increased CD due to LGA infant (adiposity). organogenesis. Inflammation. Infection. Increased incidence of macrosomia. ■ Vasoculopathy.
•
•
•
•
Recurrence of GDM in subsequent Birth injuries ■ IUFD ■ Onset of overt diabetes.
pregnancies (50%). ■ Shoulder dystocia ■ RDS ■ Coronary artery disease. (CD: Cesarean Delivery)

Postpartum follow up: Life style changes and phar macotherapy can prevent or delay the onset of type 2 diabetes from GDM. Fasting plasma glucose or a 75 g, 2 hour oral GTT is advised after 4-12 weeks, postpartum. Repeat testing at least every 3 years is suggested (ACOG, ADA).
Long-term effects (Table 20.6); Contraception (Ch. 36). Follow-up: Nearly 50% of women with GDM would
develop overt diabetes over a follow-up period of 5-10 years. Women with fasting hyperglycemia have got worse prognosis to develop type-2 diabetes and cardiovascular complications. Recurrence risk in subsequent pregnancy is more than 48%.
Risks of being overweight for the infants of mother with GDM is two-fold and the risk for metabolic syndrome is about four-fold.

Normal Impaired glucose
Time tolerance tolerance Diabetes

Fasting <100 2100 and<126 2126

2-hour post-glucose <140 2140 and <200 2200

HbAlC <5.6 5.7-6.4 <!6.5
+ Venous whole blood values are 15% less than the plasma. + mmol/L = mg% x 0.0555

Management Summary of GDM: Joint review in ANC with diabetologist ➔ advise self-monitoring blood glucose➔ low glycemic index food, + walking 30 min/day after meal + dietitian advice. Optimum Fasting Plasma Glucose (FPG) level is <126 mg/dL. If glucose target not met➔ start metformin (if not contraindicated), otherwise start insulin. Women with FPG 126 mg/dL ➔ insulin ± metformin. Women with FPG 108-125 mg/dL with macrosomic baby or hydramnios ➔ insulin ± metformin (NICE-2020).

I OVERT DIABETES

A patient with symptoms of diabetes mellitus (polyuria, polydipsia, weight loss) and random plasma glucose level of 200 mg/dL or more is considered overt diabetic. The condition
may be pre-existing or detected for the first time during present pregnancy. According to American Diabetic Association diagnosis is positive if: (a) The fasting plasma glucose exceeds 126 mg/dL, (b) the 2 hours post glucose (75 g) value exceeds 200 mg/dL and (c) HbAlC 6.5% (Table 20.7).
Classification of pregnant diabetic women: Fetal and maternal outcome of diabetic pregnancy depends on severity of the disease and its duration. Priscilla White's classification (Table 20.8) was originally used to assess the perinatal outcome and to formulate

Class
A: Gestational diabetes

Class
Pregastational diabetes
B C D F H R
T

Onset Any age

Age of onset

>20 years
10-19 years
<10 years
Any
Any
Any
Any

Fasting plasma glucose
Al: Glucose <105 mg/dl A2: >105 mg/dl
Duration (years)

<1 O years
10-19 years
>20 years
Any
Any
Any
Any

2-hour postprandial <120 mg/dl >120 mg/dl

Vascular disease

None
None
Benign retinopathy
Nephropathy
Coronary artery disease
Proliferative retinopathy
Renal transplant

Treatment
Diet Insulin
Treatment

Insulin
Insulin
Insulin
Insulin
Insulin
Insulin
Insulin
'mJ Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

the obstetric management. But it is now mainly used for statistical correlation of different types of pregnant diabetics. Vasculopathy is given more importance to predict the outcome. Patients with poor glycemic control and vasculopathy are at increased risk of complication like IUD, IUGR, pre-eclampsia and ketoacidosis.
I EFFECTS OF PREGNANCY ON DIABETES
It is difficult to stabilize the blood glucose during pregnancy due to altered carbohydrate metabolism and an impaired insulin action. The insulin antagonism is due to the combined effect of human placental lactogen, estrogen, progesterone, free cortisol and degradation of the insulin by the placenta. The insulin requirement during pregnancy increases as pregnancy advances. Hence repeated blood glucose estimation becomes mandatory. With the 'accelerated starvation' concept, there is rapid activation of lipolysis with short period of fasting. Ketoacidosis can be precipitated during hyperemesis in early pregnancy, infection and fasting of labor. Insulin requirement falls significantly in puerperium. Vascular changes, especially retinopathy, nephropathy, coronary artery disease and neuropathy may be worsened during pregnancy.
I EFFECTS OF DIABETES ON PREGNANCY
Complications of diabetes (hyperglycemia and adverse pregnancy outcome):
■ Maternal ■ Fetal and neonatal

MATERNAL COMPLICATIONS During pregnancy:
• Abortion: Recurrent spontaneous abortion may be associated with uncontrolled diabetes.
• Preterm labor (26%) may be due to infection or polyhydramnios.
• Infection: Urinary tract infection and vulvovaginitis. ♦ Increased incidence of pre-eclampsia (25%).
• Polyhydramnios (25-50%) is a common association.
Large baby, large placenta, fetal hyperglycemia leading to polyuria, increased glucose concentration of liquor irritating the amniotic epithelium or increased osmosis, are some of the probabilities.
♦ Maternal distress may be due to the combined effects of an oversized fetus and polyhydramnios.
♦ Diabetic retinopathy (Class R) is characterized by the proliferative retinopathy having neovascularization and microaneurysms. These vessels may rupture and may cause vitreous hemorrhage, scarring, retinal detachment and loss of vision. Severity of retinal pathology depends on-(a) age (time) of onset, (b) duration of the disease, (c) degree of
rise in blood Hb AIC and (d) association of hypertension.
Laser photocoagulation is the preferred treatment. Diabetic retinopathy is not a contraindication of vaginal birth.

Termination of pregnancy may be needed for women with severe florid disc neovascularization and not responding to laser therapy.
♦ Diabetic nephropathy (Class F) is diagnosed (2.5%) when creatinine clearance is reduced or there is persistent proteinuria (500 mg/24 hours) during the first 20 weeks of gestation. Predictive factors for perinatal outcome (e.g., low birth weight, preterm delivery or pre-eclampsia) are: (a) Proteinuria >3 g/24 hours, (b) serum creatinine >1.5 mg/dL
Most women (90%) develop pre-eclampsia. Control of hypertension is important to prevent further deterioration of kidney function. Calcium channel blocker is commonly used.
These women have significantly reduced life expectancy. The disease progression is characterized by hypertension, falling glomerular filtration rate and creatinine clearance. The end stage disease needs dialysis or renal transplantation. Renal transplantation improves survival of women with diabetic nephropathy.
♦ Coronary artery disease (Class H): These women run the high risk for ischemic heart disease (infarction) especially when the disease is longstanding.
♦ Ketoacidosis-P. 271.
During labor: There is increased incidence of: 0 Prolongation of labor due to big baby; @ Shoulder dystocia. Shoulder dystocia is due to disproportionate growth with increased shoulder/head ratio; @ Perinea! injuries; 0 Postpartum hemorrhage; 0 Operative interference (CD).
Puerperium: (1) Puerperal sepsis. (2) Lactation failure.

FETAL AND NEONATAL COMPLICATIONS
♦ Fetal macrosomia (40-50%) with birth weight >4 kg (Fig. 20.3) (>90th percentile for population) probably results from: (a) Maternal hyperglycemia ➔ hypertrophy and hyperplasia of the fetal islets of Langerhans ➔ increased secretion of fetal insulin ➔ stimulates carbohydrate utilization and accumulation of fat. Insulin like growth factors (IGF-I and II) are also involved in fetal growth and adiposity. With good diabetic control, incidence of macrosomia is markedly reduced. (b) Elevation of maternal free fatty acid (FFA) in diabetes leads to its increased transfer to the fetus ➔ acceleration of triglyceride synthesis ➔ adiposity.
♦ Congenital malformation (6-10%) is related to the severity of diabetes affecting organogenesis, in the first trimester (both in type 1 and type 2 diabetes). The factors associated with teratogenesis are multifactorial: (a) Genetic susceptibility, (b) Hyperglycemia, (c) Arachidonic acid deficiency, (d) Ketone body excess, (e) Somatomedin inhibition, (f) Free oxygen radical excess (superoxide dismutase, an oxygen radical scavenging enzyme can protect excess malformation) and (g) Lipid peroxidation, thomboxane excess. Risks of fetal chromosomal abnormalities are not increased (Table 20.9).
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

Fig. 20.3: Macrosomic baby, weighing 5.3 kg, of a diabetic mother, looked plethoric (due to polycythemia), with plumpy face, buried eyes and excessive buccal fat.

"''" a\- '• c "" =,.,.: .._U,)tfifl<>l,,u,-..Cs- ,; ..t>>'>l;l>W•:,='>!'"t "' ,,,i,1 Mi:'Sl'._;$t;if!"'', 'l orn rs (6, 1g,>). . . ., " I ..
" "''. - " "
Major birth'defects iit infants of diabetic m
-
T ble 20.9
.
Cardiovascular
(most common} CNS and skeletal Renal Gastrointestinal Others HbA,c

■ VSD, ASD

■ Coarctation of aorta ,
■ Transposition of great vessels
■ Situs inversus

■ Fallot's tetralogy

■ Neural tube defects

■ Anencephaly

■ Microcephaly
■ Holoprosencephaly
■ Caudal regression syndrome

• Sacral agenesis

■ Renal agenesis

■ Hydronephrosis

11 Double ureter

■ Polycystic kidneys

■ Duodenal atresia
■ Anorectal atresia
■ Omphalocele

■ Tracheoeso-phageal fistula

■ Single umbilical artery

■ Rule of 8:
• HbA c of 8% equals to 180 mg/dl, and each percentage of point up and down changes the mean glucose value by 30 mg/dl.
1
• That is an HbA c value of 6 would mean a glucose level of 120 mg/dl.
1

Good glycemic control with preconceptional counseling can reduce the incidence to 0.8-2%

Early detection of fetal anomalies:
♦ Estimation ofglycosylatedhemoglobinA (HbAlc) before 14 weeks reflect the quality of diabetic control over the previous 3 months. Overall risk of fetal malformations are increased when the level of HbAlc is high (normal <6%). Chance of major congenital malformation is about 8% and 23% when the values are 9.5 and 10 respectively.
Good glycemic control with preconceptional counseling can reduce the incidence to 0.8-2%.
♦ Maternal serum a.-fetoprotein level at 16 weeks and a detailed high resolution ultrasonography of the fetus including fetal echocardiography at 20-22 weeks are advocated.
♦ A comprehensive ultrasound examination-including fetal echocardiography is done at 20-22 weeks to detect any cardiac anomaly along with other structural malformation.
• Birth injuries (brachia! plexus) are associated with prolonged labor and shoulder dystocia due to macrosomic baby.
• Growth restriction is less commonly observed and is associated with maternal vasculopathy. Placental amino

acid transporters are involved in fetal macrosomia or lUGR in women with diabetes.
• Fetal death has got multifactorial pathogenesis but the final event being hypoxia and lactic acidemia. It is observed more in patients with poor glycemic control, vasculopathy, pre-eclampsia, ketoacidosis and fetal macrosomia. Fetal hyperglycemia and hyperinsulinemia increase fetal oxygen demand. Glycosylated hemoglobin
carries less oxygen molecule. It binds 02 more avidly and
releases 02 less. Other factors involved are: placental villus edema, fetal polycythemia and hyperviscosity.
• Neonatal complications include-8 Hypoglycemia (50%) is due to hyperinsulinemia following cell hyperplasia. It is due to rapid fall in plasma glucose following umbilical cord clamping. Neonates have got elevated cord blood C peptide and free insulin levels. It is common in macrosomic infants. 1' Respiratory distress syndrome is due to fetal hyperglycemia and hyperinsulinemia that blocks the action of cortisol. Cortisol activates type II pneumocytes for the synthesis of phospholipids (surfactant). Risk of RDS is no higher
!J Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

when diabetes is well-controlled and delivery is done after 38 weeks of gestation, G Hyperbilirubinemia is high (25-50%) due to increased red cell production (polycythemia) and break down of red cells, G, Polycythemia is due to the effects of hypoxia and raised erythropoietin levels. G Hypocalcemia ($7 mg/dL), 0 Hypomagnesemia (<7 mg/dL), it Cardiomyopathy is more common when diabetes is poorly controlled. Hypertrophic cardiomyopathy involving the interventricular septum is mainly due to insulin excess. Obstructive cardiac failure, right ventricular hypertrophy may be present. This may resolve after delivery.
• Long-term effects-hypertension, obesity insulin resis tance, hyperlipidemia, inflammation and vasculopathy.

Classification of diabetes mellitus
Type 1: p cell destruction absolute insulin deficiency. Type 2: Insulin resistance and/or insulin secretory defect.

PERINATAL MORTALITY: The overall perinatal mortality is increased 2-3 times. The neonatal deaths are principally due to hypoglycemia, respiratory distress syndrome, polycythemia and jaundice.
Inheritance of diabetes (Type 1) of an infant when either parent is affected is 3-5%. The risk is higher 40% when both parents are diabetes (type 2). Breastfeeding reduces the risk.
I MANAGEMENT
Preconceptional counseling: Goal is to achieve tight control of diabetes before the onset of pregnancy. Ideally a diabetic woman should be seen jointly by the diabetologist, obstetrician and dietician. Fetal congenital malformations are significantly low (0.8-2%) in women who receive preconceptional counseling. Patients' glycemic control and vascular status are assessed. Folic acid supplementation (5 mg/day) should be started.
HbA1c level should be measured to plan pregnancy. Women are taught for self-glucose monitoring.
Appropriate advice about diet and insulin is given.
Women with preexisting diabetes should be advised to
achieve a HbA1c :;6.5% prior to conception. This reduces the rise of major fetal malformation and other pregnancy
complications.
Antenatal care: For routine care Special care: First trimester • Combined test (P-hCG + PAPPA + NT) is done at 11-14 weeks. NIPT for IDNA may also be done. • USG is repeated along with echocardiography at 20-22 of gestation and USG is repeated at intervals of 2-3 weeks for fetal growth profile (macrosomia or IUGR) and others. Fetal wellbeing assessment is done from 28 weeks onwards (Ch. 11). BPP and NST are preferred besides clinical assessment. Doppler umbilical arte1y velocimet1y is useful in cases with vasculopathy. Due to the higher risk of preeclampsia low dose aspirin 150 mg daily is started since 12 weeks gestation.

Most patients are seen at an interval of 2-3 weeks. Diet-30 kcal/kg for normal weight women, 24 kcal/ kg for overweight women and 12 kcal/kg for morbidly obese women. On average three meals, three snacks a day are followed.
Diet should contain carbohydrate 40-50%, protein 20%, fat 30-40% and saturated fat <10%. Fat may be curtailed, if the patient is obese. Fiber containing diet (complex carbohydrates) is increased. Usually three meal regimen, with breakfast 25% of the total calorie intake, lunch 30%, dinner 30% and three snacks are quite suitable for most of the patients. Diet therapy need to be advised by a nutritionist. Frequent blood sugar estimation is required. Self-monitoring of capillary blood glucose by glucose meter (5-7 times a day) can give an accurate idea about the control. In addition, glycosylated hemoglobin should be determined at the end of first trimester and
trimonthly thereafter. HbA1c level of $6% is desirable.
Presence of vasculopathy is assessed in early pregnancy. Ophthalmoscopic examination is done for diabetic retinopathy. It is repeated in each trimester.
Insulin therapy: A fasting plasma glucose >95 mg/dL postprandial (2 hours) plasma glucose level of more than
120 mg% even with use of oral hypoglycemic drugs is an indication of insulin therapy.
Oral hypoglycemic drugs have been found to be effective and safe. Commonly used drugs are glibenclamide and metformin. Both the drugs cross the placenta. However, no teratogenic effect has been observed as yet.
Ideal levels (mg/dL) for capillary blood glucose should be: Fasting $95; Pre-meal $100; 1 hr PP $140, 2 hr PP $120, between 2 am and 6 am e:60; mean average 100; HbA1c $6%.

The use of Continuous Glucose Monitoring ( CGM) for patients with Type-I diabetes using insulin pump is preferred.
Insulin therapy is the primary medication to achieve optimal glycemic control. Many women who enter pregnancy with metformin therapy, eventually most of them need addition of insulin. Metformin unlike insulin crosses the placenta. It is not teratogenic. Intensive insulin therapy simulates physiologic insulin supply. The treatment regimen includes: twice daily injections of basal insulin (NPH) and injections of rapid acting insulin with each meal or the use of Continuous Subcutaneous Insulin Infusion ( CSII). Semisynthetic human insulin preparations and insulin analogues are preferred in pregnancy (insulin lispro and insulin aspart). Glargine and determir are long-acting insulin analogues. Determir is used as a single bed time dose (Table 20.10).

OBSTETRIC MANAGEMENT: Women with well-controlled diabetes without vascular disease should be delivered by 2:39 weeks. Induction is planned by 39 weeks in such patients. Women with vascular disease is delivered by 2:37 weeks. Delivery may have to be done early in the presence of risk factors like hypertension, FGR or with fetal compromise. In majority of cases (>50%) Cesarean Delivery (CD) is done to avoid the complications of shoulder dystocia and birth injuries.
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy JI
3-4

Table 20.10: Commonly used insulin in pregnancy.

Type Source Onset Peak(hr)
Short acting (SC)
•
Regular Human 30-60 min 2-3
Rapid acting
•
Lispro Analogue <15 min 0.5-1.5
■ Aspart Analogue <15min 0.5-1.5

Duration (hr)

4-8

3-4

in antepartum fetal monitoring, ( 4) Worsening hypertension, (5) Previous still birth, (6) Presence of vasculopathy (proliferative retinopathy) and (7) Obstetric complications like pre-eclampsia, IUGR. As such 50% of diabetic mothers are delivered by cesarean section.
Procedure: For CD: The procedure is scheduled in early morning. See details above.
Epidural or spinal anesthesia is better than general anesthesia as oral feeding could be started soon following the operation.

Intermediate acting
NPH Human 1-2 hours
•
Long acting
•
Determir Analogue 1-4

■ Glargin Analogue 1-4

(NPH: Neutral Protamine Hagedorn)

6-12 12-20

Minimal Upto 24 hours
Minimal Up to 24 hours

To control blood glucose: On the day of operation, breakfast and the insulin dose are omitted. Capillary blood glucose level is checked with a glucose meter. A normal saline infusion is started . Insulin dose is adjusted accordingly. The insulin requirement suddenly falls following delive1y and after the omission of the drip. Hourly estimation of blood glucose levels is done with a glucose meter and the insulin dose is adjusted accordingly. The blood glucose level should be maintained between 80 and 100 mg per 100 mL.

ADMISSION: In uncomplicated cases, the patient is admitted around 36 weeks. Early hospitalization may be needed for: (1) Stabilization of diabetes, (2) To control complications like pre-eclampsia, polyhydramnios and preterm labor and (3) To plan the appropriate time and method of delivery.
I PROCEDURE OF INDUCTION OF LABOR Procedure of glycemic control during labor and delivery:
■
■
■
Usual dose of intermediate acting insulin is given at bed time. No morning dose of insulin.
Procedure is scheduled in the early morning. II IV infusion of normal saline is begun.
■
Once active labor begins or glucose level falls to <70 mg/ dL, the infusion is changed from saline to 5% dextrose and given at a dose of 100 mL/hour to achieve a glucose level of approximate 100 mg/dL.
■ Glucose levels are checked hourly with a reflectance meter for adjustment of the infusion rate.
II Regular (short acting) insulin is given by IV infusion if glucose levels exceed llO mg/dL.
■ Women using continuous insulin infusion pump may continue the pump during labor.
Induction of labor: The indications are-diabetic women controlled on insulin (GDM or class B diabetes) are considered for induction of labor after 38 completed weeks. Blood glucose levels are estimated hourly with a glucometer and the soluble insulin dose is adjusted accordingly.
Epidural analgesia is ideal for pain relief. If the labor fails to start within 6-8 hours or if the labor progresses unsatisfactorily, cesarean section should be performed.
Cesarean section: The indications are-(1) Fetal macrosomia (>4 kg), (2) Diabetes with complications or difficult to control, (3) Fetal compromise as observed

PLACE OF WAITING SPONTANEOUS ONSET OF LABOR AT TERM: The following are the conditions where the pregnancy may be continued awaiting spontaneous onset of labor and vaginal delivery. (1) Young primigravidae or multiparae with good obstetric history and (2) Diabetes well-controlled either by diet or insulin and without any obstetric complication.
Fetal monitoring: Continued fetal monitoring is done preferably with continuous electronic fetal monitoring. CTG using a scalp electrode is maintained (Fig. 39.1). Fetal scalp blood pH sampling is done whenever indicated. The combination of fetal hyperglycemia and anoxia contribute to fetal distress and RDS. However, labor should not be allowed for more than an arbitrary 12 hours and should be augmented by low rupture of the membranes and oxytocin or delivered by cesarean section. The problem of shoulder dystocia should be kept in mind.
Examination of the placenta and cord: Placenta is large, the cord is thick and there is increased incidence of a single umbilical artery. Microscopically, villi show edema and excessive syncytial knots, numerous cytotrophoblasts and thickened basement membrane.
Diabetic ketoacidosis: Precipitating factors: Protracted vomiting; hyperemesis gravidarum; infections; insulin non compliance; medications. Pathology: is insulin resistance ➔ lipolysis ➔ enhanced ketogenesis ➔ fall in plasma HCO -and pH ( <7.30). It may be precipitated with the use of -mimetic agents (isoxsuprine), corticosteroids, infection or persistent vomiting.
3
Diagnosis: Levels of serum bicarbonate <15 mEq/L Anion gap >12 mEq/L, Elevated serum ketones Blood pH value <7.3.
■
■
■
Investigations: Positive serum/urine ketones; hyperglycemia ('.11.0 mmol); low serum bicarbonate ( <15 mEq/L); arterial pH :S7.30; anion gap >12; elevated base deficit '.4 mEq/L; potassium level may be falsely normal/elevated.
m Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy
Management is done in an acute care unit where both neonatal CARE OF THE BABY: A neonatologist should be present at care is also available. Parameters to assess are: Degree of acidosis, the time of delivery. The baby should preferably be kept
alterations in the level of arterial blood gas, blood glucose, ketones in an intensive neonatal care unit and to remain vigilant
and electrolytes. for at least 48 hours, to detect and to treat effectively any
♦ Fluids: NaCl total: 4-51 in first 12 hours. Once plasma glucose complication likely to arise.
level is 200 mg/dL, it is changed to 5% dextrose with 0.45%
is anticipated and be treated effectively.
■
Asphyxia
NaCl at 150 mL/hr. After 8 hours, use half-normal saline at
125 mL/hour. ■ To look for any congenital malformation.

♦ IV insulin: Use regular insulin IV. Loading dose of 0.1-0.2 unit/kg➔ 0.1 unit/kg/hr (to adjust with frequent capillary glucose estimation)➔ to keep plasma glucose levels between 100 and 150 mg/dL.
♦ IV Potassium: If reduced ( <3.3 mEq/L)-to hold insulin and give infusion 15-20 mEq/hr until serum K• >3.3 but <5.3 mEq/L.
♦ Bicarbonate: If PH <7.0: NaHC03 (50 mmoL) in 200 mL water with 10 mEq KCl-infuse over 1 hr. Repeat NaHC03 infusion every 2 hours until pH is 7.0➔ repeat serum NaCH03 levels. Monitor blood pressure, urine output; continue insulin;
metabolic targets: (a) Decrease of blood ketone by 0.5 mmol/L/hom (b) Improvement of venous bicarbonate by 3 mmol/L/hour (3 mEq/1/hour), (c) Decrease of capilla1y glucose by 3 mmol/L/hour (54 mg/dL/hour); DKA resolution criteria: (a) Blood ketone level <0.6 mmol/L, (b) pH >7.3 units, (c) Bicarbonate >15 mmol/L, (d) Anion gap .,12.
PUERPERIUM: Antibiotics should be given prophy lactically to minimize infection. Insulin requirement falls dramatically following delivery. She is to revert to the insulin regime as was prior to pregnancy. A fresh blood glucose level after 24 hours will help to adjust the dose of insulin. Breastfeeding is encouraged. Women who breastfeed should have additional 500 kcal daily in diet. In lactating women insulin dose is lower.

■ All babies should have blood glucose to be checked within 2 hours of birth to avoid problems of hypogly cemia (blood glucose <35 mg/dL).
■ All babies should receive 1 mg vitamin K intramus cularly.
11 Early breastfeeding within half to 1 hour is advocated and to be repeated at three to four hourly intervals there after to minimize hypoglycemia and hyperbilirubinemia.
Improvement in the care of diabetes in pregnancy has reduced perinatal mortality significantly ( <5%).
CONTRACEPTION
• Barrier method of contraceptive is ideal for spacing of births. These do not affect carbohydrate metabolism.
• Low-dose combined oral pills containing third generation progestins, are effective and have got minimal effect on carbohydrate metabolism. Main worry is their effect on vascular disease (thromboembolism and myocardial infarction).
• Progestin-only pill may be an alternative. Long-acting progestins are not used as a first-line method.
• IUCD (both copper and LNG-IUD) may be used. Both are highly effective and safe. Women with vasculopathy can have their option.
• Sterilization is considered when family is completed. Women with vasculopathy may have this option.

r:fi.MH
► Pregnancy is a diabetogenic state. Insulin sensitivity to tissues (muscles, liver) are reduced.
► Maternal hyperglycemia results in fetal hyperglycemia and hyperinsulinemia and the complications.
► Gestational Diabetes Mellitus (GDM) is defined as carbohydrate intolerance of variable severity with onset or fist recognition during the present pregnancy.
► Potential risk factors for GDM are: (a) Positive family history, (b) Previous birth of an overweight baby (>4 kg), (c) Obesity, (d) Others. ► Complications of GDM are: Increased incidence of: (a) Macrosomia, (b) Polyhydramnios, (c) Birth trauma, (d) Increased perinatal loss,
(e) Others.
► Treatment of GDM reduces the risk of fetal macrosomia, shoulder dystocia, pre-eclampsia and cesarean delivery (NICHD, ACHOIS). Pregnancy is a diabetogenic state due to several contrainsulin factors (hPL, cortisol, prolactin, TNF A and others) causing decreased sensitivity of the peripheral tissues to insulin (insulin resistance).
► Metabolic events for a woman with diabetes in pregnancy is Maternal hyperglycemia➔ Fetal hyperglycemia➔ Fetal pancreatic islet cells hyperplasia and hypertrophy➔ Increased fetal insulin secretion➔ Excessive fetal growth➔ Fetal macrosomia➔ Increased birth injury (Pedersen hypothesis).
► Fetal congenital malformations are high (2 to 6-fold increase) in diabetic woman (pregestational diabetes); most common is cardiovascular.
► Complications of diabetes in pregnancy are increased both for the mother, fetus and the neonate. ► Screening for GDM is done between 24 and 28 weeks of pregnancy.
Contd...
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy mJ Contd...
► Treatment of women with diabetes in pregnancy: Dietary therapy. Insulin is given when glycemic control is not achieved with dietary therapy. Oral hypoglycemic agents (glibenclamide, metformin) are also being used to maintain glycemic control. Frequent self monitoring of blood glucose is needed.
► Close antenatal fetal assessment for women with both GDM and pregestational diabetes is maintained. It depends on degree of glycemic control, presence of vascular disease (nephropathy, retinopathy) or hypertension.
► Self-monitoring of capillary blood glucose is encouraged for optimum glycemic control. The 'target' of capillary blood glucose levels (mg/dl) are: fasting 595; 2 hr postprandial 5120; 2-6 am 60; mean 100 and HbA 1 C 56 (ACOG-2005).
► Timing of delivery should be with fetal maturation provided diabetes is well-controlled and fetal surveillance is normal. Delivery is generally delayed in patients with well-controlled diabetes until 39 weeks.
► Mode of delivery depends on level of glycemic control, fetal size, associated complication if any (pre-eclampsia) and pelvic adequacy. As such 50% of diabetic mothers are delivered by cesarean section. However, selected women may be considered for induction of labor or spontaneous onset of labor and vaginal delivery.
► Prepregnancy counseling for a woman with existing DM is essential to improve glycemic control before pregnancy. This can reduce fetal congenital malformation significantly.
► Diabetic women need multidisciplinary team care (obstetrician, endocrinologist, nutritionist).

THYROID DYSFUNCTION AND PREGNANCY
HYPERTHYROIDISM: Physiological changes !] !)
00
·
during pregnancy such as increase in cardiac ;:
output, oxygen consumption and heat produc-tion may mimic mild thyrotoxicosis (Ch. 5).
Hyperthyroidism occurs in about 2 per 1,000 pregnancies.
Causes of hyperthyroidism are:
u Immunological: Graves' disease, chronic thyroiditis
11 Non-immunological: Nodular thyroid disease, subacute thyroiditis
• Gestational: Hyperomesis gravidaum, multiple preg nancy, trophoblastic disease (H. mole, choriocarcinoma).
■ Iatrogenic: Overtreatment with excessive levothyroxine.
Gestational Hyperthyroidism (GH) is due to the high titer of hCG in the first trimester that stimulates the TSH receptors of the thyroid cells. Serum levels of FT4 and TT4 are elevated. Serum TSH levels are often suppressed. Despite the biochemical hyperthyroidism, patient may not have any symptoms or signs. Most cases resolve spontaneously between 14 and 20 weeks. Antithyroid medications are not needed. 1-3% of pregnancies are affected.
COMPLICATIONS IN UNTREATED HYPERTHYROIDISM
MATERNAL: Miscarriage, preterm delivery, pre-eclampsia, congestive cardiac failure, placental abruption, thyroid storm and infection.
FETAL/NEONATAL: LBW, FGR, prematurity, stillbirth, hyperthyroidism, hypothyroidism, increased perinatal morbidity and mortality.
Thyroid-stimulating antibodies cross the placenta and produce neonatal thyrotoxicosis with increased neonatal death. The risk is increased if the antithyroid drug is stopped in late pregnancy or following surgery.

Graves' disease: An undetected or very much
suppressed TSH value in the presence of a high FT 4, or FT 41
or TT4 adjusted for pregnancy confirms hyperthyroidism.
Elevated levels of thyroid peroxides antibodies (TPO Abs) are the marker for Graves' disease.

Clinical diagnosis of hyperthyroidism should always
be confirmed by measuring free T4 (FT4-high), free T4 index (FT4 1- high), FT3 (high) and TSH (suppressed) levels. Ultrasonography of the fetal thyroid gland is done
when the mother is taking antithyroid drugs. Thyroid Peroxidase Antibodies (TPOAb), (antimicrosomal antibodies) and thyroid stimulating immunoglobulin should be measured. Radioactive iodine (1311) uptake and scans should not be done during pregnancy as it will cross the placenta and damage the fetal thyroid gland permanently.
The mainstay of treatment is use of antithyroid drugs [propylthiouracil (PTU) or methimazole (MM)]. Both the drugs are effective. Methimazole is preferably avoided in the first trimester of pregnancy if PTU is available. Methimazole has the risk of embryopathy. Carbimazole is given orally with a daily dose of 10-40 mg and maintained at this dose until the patient becomes euthyroid. Then it is progressively reduced to a maintenance of between 5 and 15 mg daily. Propylthiouracil is given at a daily dose of 300-450 mg and continued till the patient becomes euthyroid-the maintenance dose being 50-150 mg daily. Both the drugs may cause fetal goiter and hypothyroidism. Methimazole embryopathy includes, choanal atresia, tracheoesophageal fistula, esophageal atresia, omphalocele, hypothelia and athelia and minor dysmorphic features.
Fetal hyperthyroidism is diagnosed when there is persistent fetal tachycardia (>160 bpm) FGR, oligohydramnios or fetal goiter on USG. Treatment is to give antithyroid drug to the mother. Normalization of
TSH and FT4 is an indicator to reduce the dose of drugs. Patients having marked tachycardia or arrhythmias
should also have propranolol (P blocking agent).
Fetal surveillance is maintained with serial USG, NST and BPP. The drugs are not contraindicated during breastfeeding provided the dose is kept relatively low. Close monitoring of the neonatal thyroid functions
ml Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

is carried out. Cord blood should be taken for TSH
and free T4 at the time of delivery to detect neonatal hyperthyroidism.
Thyroidectomy, may be required to relieve the pressure symptoms or for women with drug resistance. It can be done safely in the second trimester with prior biochemical control.
Subclinical Hyperthyroidism: It is characterized by abnormally low serum TSH and normal thyroxin hormone levels. Long-term adverse effects are: Osteoporosis and cardiovascular morbidity. In the long run some progress to clinically overt thyrotoxicosis. Subclinical hyperthyroidism is usually not associated with any adverse pregnancy outcomes. These women need periodic follow up.
Preconceptional counseling: Considering the hazards during pregnancy, preconceptional counseling is important. Adequate treatment should be instituted to bring down the thyroid function profile to normal. Radioactive iodine (1311) therapy should not be given to patients wanting pregnancy within one year. Oral pill is to be withheld because of accelerated metabolism and disturbed liver function.
HYPOTHYROIDISM: Overall prevalence is 1-2 per 100 pregnant women. May be subclinical(elevated TSH and normal FT4) or overt(elevated TSH and low FT4).
Importance causes are:
(i) Autoimmune(Hashimoto thyroiditis) (ii) Following thyroidectomy (iii)Treatment with 131 I
(iv) Drug induced(lithium, amiodarone, iodine excess
andATDs).

Indication of thyroid hormone testing in pregnancy ■ Age >30 years.
■ Residing in an area of iodine deficiency. ■ Symptoms of thyroid dysfunction.
11 Family history of thyroid dysfunction. ■ Obesity(BMI 230).
■ Unexplained miscarriage/infertility. ■ Presence of goiter.
■ Presence of autoimmune disorders(Type-I DM).
It is important that patient should be euthyroid at the time of conception.
Complications: Pre-eclampsia (PE), placental abruption, cardiac dysfunction, anemia, LBW, still birth, miscarriage and deficient intellectual development of the child. It is reasonable to estimate the serum TSH levels in the first antenatal clinic in these women with higher risk of thyroid dysfunction though universal testing is also recommended. Chronic autoimmune thyroid disease is more common in women with other autoimmune diseases(Type-I diabetes).
Serum TSH should be repeated at an interval of 6-8 weeks as there is increased demand of thyroid hormone in the second half of pregnancy. If the patient is having substitution therapy in prepregnant state, the dose of levothyroxine need to be increased in pregnancy.
Treatment is started with levothyroxine 2-2.4 µg/kg/ day. The maintenance dose for most patients is between 75 and 150 µg of L-thyroxin per day. The serum TSH should be repeated every 4-6 weeks. In order to keep
serum TSH, serum FT4 or FT41 values within the normal
range, the dose need to be increased in the second trimester of pregnancy. After delivery, dose is reduced. In India, routine screening for thyroid dysfunction is recommended(FOGSI, ITS, ESI).

Primary hypothyroidism met in pregnancy is mostly related to thyroid autoimmunity(Hashimoto thyroiditis). Myxedema rarely presents in pregnancy because they tend to be infertile.
Subclinical Hypothyroidism (SCH) is defined as the state with elevated serum TSH in the presence of normal (trimester specific) FT4 values. TPO Abs are raised in 70%-
80% of women of child bearing age.
The recommended upper limit of serum TSH (gestation specific) is 2.5 mlU/L in the first trimester and up to 3 mIU/L into second and third trimesters. Over clinical hypothyroidism is defined as elevated levels of
serum TSH with low serum T4 or with serum TSH >10 mIU/L irrespective serum thyroxin level. The common
complications of SCH are similar to that of overt clinical situation.
Serum TPO Abs (antimicrosomal antibodies) are elevated in almost 95% of cases with autoimmune hypothyroidism.

Postpartum thyroiditis: It is an autoimmunothyroid disease observed in the first year postpartum due to antimicrosomal antibodies (Hashimoto thyroiditis). Most women present with transient hyperthyroid state of which nearly two-thirds become euthyroid and the remaining one-third become hypothyroid. High-risk factors are infection, traumatic delivery, dehydration and stress. Treatment is symptomatic( blockers and/or levothyroxine).
Thyroid storm is a life-threatening condition. It is diagnosed by features of severe thyrotoxicosis with hyperpyrexia (>103°F), tachycardia (>140 beats/min), CCF, neuropsychiatric symptoms, nausea and vomiting. Laborato1y tests show hyperthyroid changes.
Management includes: Aggressive approach:
(i) Supportive therapy in an intensive care unit: • Fluids
and electrolytes balance, 02 therapy • Acetaminophen
for hyperpyrexia; (ii) Management of CCF: • blockers (propranolol) therapy to control hyperdynamic symptoms, • Antithyroid drug (PTU or MM) to block thyroid
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy aa,

hormone synthesis, • Lugol's iodine solution and • Glucocorticoids (hydrocortisone) to block peripheral conversion of serum T4 to T3•
Thyroid storm is a life-threatening condition with a mortality rate of about 25%.

JAUNDICE IN PREGNANCY
When the serum bilirubin level exceeds 2 mg% !] !] (nmmal being 0.2-0.8 mg%), ,isible yellow

staining of the tissue appear. Overall incidence r.-:i ·. • ·
in India is 1-4 per 1,000 deliveries. The causes !l
of jaundice during pregnancy may be grouped as follows (Table 20.11).
INTRAHEPATIC CHOLESTASIS IN PREGNANCY (Obstetric Cholestasis)
Intrahepatic Cholestasis in Pregnancy (ICP) is the second most common cause of jaundice in pregnancy (in India), the first one being viral hepatitis. Overall incidence is 0.2-2% of pregnant women worldwide. The stasis of bile in the bile canaliculi with rise in conjugated bilirubin is probably due to excess circulating estrogen. Similar manifestation is also observed in women taking contraceptive pills. Genetic, familial and abnormal progesterone metabolism have been observed.
ICP typically presents after 28 weeks with pruritus most commonly of the palms of the hands and the soles mostly at night. Other causes of cholestasis (drug induced liver injury, viral hepatitis and autoimmune liver disease) need to be excluded. Neonatal jaundice is not a feature. OC patients are frequently diagnosed with DM. So screening for GDM is done.
There may be weakness, nausea or even vomiting. Jaundice is slight. Bilirubin level rarely exceeds 5 mg%. Liver biopsy shows the features of intrahepatic cholestasis without any evidence of necrosis.
Investigations: Liver function tests, including serum bile acid levels are evaluated (Table 41.12). Bile acids are the specific measure of the diagnosis and monitoring of ICP. Liver USG is to be done to exclude cholelithiasis. ICP is associated with all adverse perinatal outcomes: preterm birth, low birth weight, RDS, fetal distress, meconium-stained liquor, meconium ileus and stillbirth. Depending upon the levels of bile acids, ICP is grouped

into-(a) Mild (19-39 µmol/L), (b) Moderate ( 40-99 µmol/L) and (c) Severe (>100 µmol/L). Raised levels of serum bile acids (>40 µmol/L) and raised serum levels of AST/ALT suggest delivery of the woman at 37 weeks (ALT more specific). Prothrombin time should be monitored to guide vitamin K therapy. The features subside within two weeks postpartum. The complications are higher in women with high levels of total bile acids, conjugated bile acids and specially cholic acid. Maternal: increased rates of labor induction and cesarean delivery (1 in 3). Fetal: Increased meconium passage (25%); increased premature delivery; increased fetal distress; increased postpartum hemorrhage (1 in 4).
Treatment of ICP with medications, are not supported by any evidence. Cholestyramine is effective for itching. All women with OC should be given vitamin K to reduce postpartum hemorrhage and neonatal bleeding. The neonate should be given vitamin K as a routine. Combined oral contraceptives should be avoided in women with history of obstetric cholestasis. Prothrombin time should be monitored. Ursodeoxycholic Acid (UDCA) is found helpful. It increases bile acid excretion and improves pruritus.
Woman needs to be followed up 6 weeks postpartum with liver function tests, including bile acids to ensure resolution. Women with ICP on long-term follow-up run the higher risk of hepatobiliary diseases, including hepatitis, hepatic fibrosis, gallstones, cardiovascular disease, and hepatic biliary cancer. Recurrence rate is high (50-60%).

VIRAL HEPATITIS
Viral hepatitis is the most common cause !] !]

·
of jaundice in pregnancy in the tropics. At · · .-present with wide spread active immunization m1 .
in childhood, incidence in India is reduced. !lf.£, There are six distinct types of highly contagious hepatitis virus have been identified. Each type (mentioned below) has different clinical effect to the pregnant women and her fetus.
♦ Hepatitis - A (RNA) ♦ Hepatitis - B (DNA)
♦ Hepatitis - C (RNA) ♦ Hepatitis - D (RNA) ♦ Hepatitis - E (RNA) ♦ Hepatitis - G (RNA)

,Table20.11:Causesofjaundiceduring'pregnancy.''., j · '.· ,, ' ·,.',:,, ,"" ,, '-"·, •"·\'' , '.
.W l' g - "'r-'lh!f !..' )'0/Y*>,' • '<'l\:,. '<'ll U ,,, )j'J-
}t
1 -r, r, r :i•~ J.,;i v,,<:,ii-1"' 1 --- " •½'
• • ' ;(c " , ' , " , , , , 1 , 0 a ' '

Jaundice peculiar to the pregnant state
•
lntrahepatic cholestasis (obstetric hepatosis)-
may be recurrent
■ Severe pre-eclampsia, eclampsia, HELLP syndrome. ■ Acute fatty liver (acute yellow atrophy of the liver) ■ Severe hyperemesis gravidarum.
•
Endotoxic shock-Disseminated lntravascular
Coagulation (DIC).

Jaundice unrelated to pregnant state
■ Viral hepatitis-virus A-E, G.
■ Gallstone-obstructive jaundice.
•
•
Drug induced-isoniazid,
phenothiazines.
Hemolytic jaundice-mismatched blood transfusion, malaria, Clostridium
welchii infection, etc

Jaundice when pregnancy is superim-posed on chronic liver disease
• Chronic hepatitis Cirrhosis, tumors
•
ZI Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

Hepatitis A (HAV): Infection is spread by fecal-oral route. Incubation period is 28-30 days. Diagnosis is confirmed by detection of IgM antibody to hepatitis A. Disease is usually self-limited and fulminant hepatitis is rare. Perinatal transmission is rare, chronic carrier state does not exist. The virus is not teratogenic. Pregnant woman exposed to HAV infection should receive immunoglobulin 0.02 mL/kg within 2 weeks of exposure. She should also have hepatitis A vaccine single dose 0.06 mL IM. It is safe in pregnancy. Household contacts should be given immune prophylaxis with HAV (immunoglobulin and HAV vaccine).
Management: Balanced diet and physical rest. HA V is not teratogenic. Preterm birth may be increased. Breast feeding is not in contraindicated.
Hepatitis B Virus (HBV): It is a global public health problem. It is endemic in central and South East Asia, China and many other parts of the world. The virus is transmitted by parenteral route, sexual contact, vertical transmission and rarely through breast milk. The risk of transmission to fetus ranges from 10% in first trimester to as high as 90% in third trimester and it is specially high (90%) from those mothers who are seropositive to Hepatitis B Surface Antigen (HBsAg) and 'e' -Antigen (HBeAg).
Neonatal transmission mainly occurs at or around the time of delive1y through mixing of maternal blood and genital secretions. Transplacental transfer is uncommon. Approximately 25% of the carrier neonate will die from cirrhosis or hepatic carcinoma, between late childhood to early adulthood. HBV is not teratogenic. CS is not a routine.
Maternal infection: The acute infection is manifested by flu-like illness as malaise, anorexia, nausea and vomiting. There may be arthralgia and skin rash. In majority, it remains asymptomatic. Jaundice is rare and fever is uncommon.
Clinical course (HBV): Nearly 90-95% of patients clear the infection and have full recove1y. About 1 % develop fulminant hepatitis resulting in massive hepatic necrosis. 10-15% become chronic and 10% of these chronic cases suffer from chronic active hepatitis, cirrhosis and hepatocellular carcinoma.
Diagnosis is confirmed by serological detection of HBsAg, HBeAg (denote high infectivity) and antibody (IgM) to hepatitis B core antigen (HBc) and HBV DNA titer. Chronic carriers are diagnosed by presence of HBsAg or HBeAg and anti-HBc antibody and HBV-DNA titer (107 to 1011) 6 months after the initial infection. Liver enzymes (ALT) are elevated during the initial phase. Presence of HBe antigen is associated with about 90% vertical transmission ofHBV to the fetus (Table 20.12). Transition from HBe antigen positivity to anti-HBe positivity usually heralds decreased viral replication.
Screening: All pregnant women should be screened for HBV infection at first antenatal visit and it should be repeated

during the third trimester for 'high risk' groups (intravenous drug abusers, sexual promiscuity, hemophiliacs, patients on hemodialysis or having multiple sex partrlers ).
Management HBV infection: Recombinant vacci nation is safely used in pregnancy for prevention.
Hepatitis C (HCV): It is responsible for chronic active hepatitis and hepatic failure. Perinatal transmission (3-10%) is high when viral load is high. Detection is by antibody to HCV by EIA, which develops usually late in the infection. Chronic carrier state is present. No effective vaccine against HCV is available. Women should be immunized against hepatitis A and B if not immune. Obstetric complications are: Preterm birth, low birth weight and cholestosis. Transmission is mainly by parenteral and vertical. 50% of HCV infection become chronic. HCV transmission risk is high with invasive monitoring, rupture of membranes (>6 hours). Cesarean delivery does not reduce perinatal HCV transmission. Drugs using ledipasvir and sofosbuvir are the first line therapy. Breastfeeding is not contraindicated.
Hepatitis D (HDV): It is seen in patients infected with HBV either as a co-infection or super infection. Perinatal transmission is known. Chronic carrier state is seen. Neonatal immunoprophylaxis for HBV is almost effective against HDV. Acute infection with fulminant course results in high maternal mortality (2-20%) due to hepatic failure.
Hepatitis E (HEV): It behaves similar to hepatitis A virus infection. It is observed in Asia and South America. It may lead to fulminant hepatitis. ELISA can detect HEV specific IgG and IgM antibodies or by PCR. Chronic carrier state is present. Perinatal transmission is uncommon. But perinatal morbidity and mortality are high when transmission occurs. Maternal mortality following acute infection is high (15-20%). Preterm delivery is high (60%).
Hepatitis G (HGV): It is related to hepatitis C virus. It is more prevalent but less virulent than HCV. Co-infection with hepatitis A, B, C and HIV is common. Chronic carrier state is known and perinatal transmission is documented.
Prognosis: Fulminant hepatitis is more common in hepatitis E, less common in hepatitis C and rare in hepatitis A. Mortality is very high in fulminant type.
Maternal: There is increased incidence of postpartum hemorrhage, hepatic coma, renal failure, coagulopathy, infection and hepatorenal syndrome. All these lead to increased maternal morbidity and mortality. Medical termination of pregnancy does not alter the prognosis of the patient.
Fetal: There is increased incidence of abortion, preterm birth and intrauterine death leading to increased

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Immunity Immunity
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Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

fetal wastage. Congenital malformation of the fetus following viral hepatitis in early pregnancy is inconclusive. Perinatal mortality is about 20-70%.

MANAGEMENT
PROPHYLAXIS: Improvement in sanitation, supply of safe drinking water and adequate care of personal hygiene are the essential prerequisites. Use of disposable syringe or boiling of syringe prior to use are the positive steps in prevention. Screening of blood donors for HBsAg should be routinely done.
Management of HBV during pregnancy: HBV infection can be prevented by vaccination and the recombinant vaccine is safe in pregnancy.
Pregnant woman who is seronegative, should have HB immunoglobulin (HBIG), 0.06 mL/kg IM, soon following exposure and a second dose after 1 month. Then she should be given recombinant DNA vaccine intramuscularly 1 mL, 3 doses at 0, 1 and 6 months. All infants born to HBsAg positive mothers should have HBIG 0.5 mL IM within 12 hours of birth. Active immunization with HB vaccine (0.5 mL) is also given IM at a separate site at the same time schedule. This is very effective (85-95%) to protect the infant from HBV infection. Breastfeeding is not contraindicated. Similar to HIV, perinatal transmission of HBV depends on maternal viral load. Tenofovir and HBIG are effective to reduce the transplacental transmission of HBV to the fetus. Tenofovir is given 300 mg/day from 34 weeks.
Hepatitis A: Both passive immunization (HAIG) and active immunization with killed virus vaccine are available for the mother. Household contacts should be given immunoprophylaxis with HAV.
Healthcare workers should receive hepatitis B vaccine and they should avoid needlestick injury and blood-to blood contact.
TREATMENT: There is no specific treatment. It is generally supportive. Consultation with a hepatologist is ideal.
♦ Rest: The patient should be put to bed rest, if necessaty by hospitalization.
♦ Isolation: The patient should be kept in isolation. Blood samples are to be collected with gloved hand. Disposable syringes should be used. The excreta is to be disposed carefully.
♦ Nutrition: Diet rich in carbohydrate and adequate protein is to be prescribed. Initially, glucose drink, fruit juice may be given. Dietary fat restriction is not necessary. If the patient cannot tolerate oral feeding, 10% glucose may be given intravenously.
♦ Drugs: To prevent formation of the toxic nitrogenous com pound from the bacterial flora of the gut, oral neomycin (1 g to be given 6 hourly) is helpful. Lactulose (15-30 mL three times daily), reduces colonic ammonia absorption and it acts as an osmotic laxative. Hepatotoxic drugs should not be used. There is no place for termination of pregnancy.

♦ Prevention of complications: Hypokalemia, hypoglycemia and hypocalcemia are corrected by regular blood checkup. Hemorrhagic complications are managed by giving blood or fresh frozen plasma.
♦ During labor: (a) Hepatotoxic drugs should be avoided. (b) To administer vitamin K, 5 mg intramuscularly to raise the prothrombin level and (c) Prophylactic oxytocin is to be given.
♦ Hepatologists to be involved. Patient may need ICU management depending on liver function tests.
EPILEPSY IN PREGNANCY
It is a major neurologic complication in pregnancy. Risk of maternal death is high. Antiepileptic Drugs (AED) and epilepsy have increased risk for fetal congenital malformations. Management with Multidisciplinary Team Approach (MDTA). Obstetrician and the neurologist can improve the pregnancy outcome.
The effect of pregnancy on epilepsy is uncertain. The frequency of convulsions is unchanged in majority (60%), increased in 30% and decreased in about 10% of women. Serum concentration of anticonvulsant falls in pregnancy. All anticonvulsants interfere with folic acid metabolism. Folic acid deficiency has been associated with neural tube defects and other congenital malformations.
Effects of epilepsy on pregnancy-incidence of Major Congenital Malformations (MCM). Birth defects are increased by two-fold. This could be related to the sever ity of the disease with its genetic predilection and also due to the anticonvulsants uses and their dosages. Risks of MCM is related to the type of anticonvulsant drugs va1y (Table 20.13).
The malformations are: Oral clefts, hypospadius, cardiac abnormalities, limb defects mental retardation and hypoplasia of the terminal phalanges. Sodium valproate is associated with neural tube defects. There is chance of neonatal hemorrhage and is related to anticonvulsant induced reduction of coagulation factors (vitamin K dependent).
Prenatal diagnosis with serum a-FP at 16 weeks and detailed fetal anatomy scan by 20-22 weeks with real time ultrasonography (level II) including fetal echocardiography is done.
The lowest effective dose of the most appropriate AED should be used. The fetal anomaly scan at 18-21 weeks of gestation can identify major cardiac defects in addition to neural tube defects. Serial growth scans are required for detection of small-for-gestational-age babies and to plan further management.
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Valproate Carbama- Phenytoin Topiramate Gabapentin zepine (3.0%) (2.9%) (4.2%) (0.7%)
(9.3%)
Lamo- Levetira- Phenob- Controls trigine cetam (2.4%) arbital (1.1%) (2.0%)
(5.5%)
lJ Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

Obstetric complications are increased:
• Pre-eclampsia, • Miscarriages, • Preterm labor, • IUGR, • SGA, • PPH,
• Postpartum depression.
Preconception counseling includes: (1) Family history and genetic counseling. (2) To initiate monotherapy (if possible) replacing polytherapy. (3) To administer folic acid 5 mg daily. (4) Importance of prenatal diagnosis is to be discussed (Ch. 12). (5)
Supplementation with vitamin D3 is to be done as
deficiency is common.
Management: The dose of the chosen drug should be kept as low as possible. Polytherapy to be avoided. Valproate and phenytoin are found to be most teratogenic. Benzodiazepines are the drug of choice. The commonly used drugs are: Lamotrigine 300-500 mg/day is given and it is not an enzyme inducer. Newer drugs used with safety are: levetiracetam 1-3 g/day (not an enzyme inducer). Carbamazepine 0.8-1.2 mg daily in divided doses, phenytoin 150-300 mg daily in two divided doses. Serum levels may be measured in patients with frequent seizures to assess therapeutic levels and compliance.
Fits are controlled by IV phenytoin with a slow loading dose of 15-20 mg/kg. It is highly effective, has a long duration of action and side effects are less. Otherwise benzodiazepine 10-20 mg slow IV may be given. Folic acid 4 mg daily is to be started before pregnancy and to be continued throughout.
There is decrease in free level of most of the anticonvulsants in pregnancy. Patients taking Lamotrigine

monotherapy should be carefully monitored as levels of this drug falls due to E effect in pregnancy. The reasons are: delayed gastric emptying, reduced absorption, increased protein binding, nausea, vomiting, increase in plasma volume, increased hepatic metabolism and renal clearance. Vitamin K 10 mg a day orally is to be given to mother in the last two weeks.
Labor and delivery: Continuous fetal monitoring is done. Seizure in labor are terminated as soon as possible to avoid fetal hypoxia and acidosis. Most women have successful vaginal delivery. Pain relief is prioritized with Entonx and RA. Pethidine is avoided. Diamorphine is preferred. Induction of labor and cesarean delivery are done on obstetric indications only.
There is no contraindication for breastfeeding. Sleep deprivation, stress and missed medication and anxiety are avoided. Infant is given injection vitamin K 1 mg IM at birth to prevent neonatal hemorrhage due to decreased vitamin K dependent clotting factors. The infant may be drowsy. Readjustment of the anticonvulsant dosage is necessary and to bring down the dose to the prepregnant level by 3-4 weeks postpartum.
Steroidal contraceptives are better to be avoided due to hepatic microsomal enzyme induction.
• Most reliable and reversible contraception is IUCD. Both the copper and LNG-IUS are accepted. DMPA can also be advised.
Risk of inheritance; on average the risk of the child inheriting epilepsy is 2-8%.

.:6-mna
► Prepregnancy counseling is essential for a patient with epilepsy.
► The overall risks of teratogenic effects for commonly used AEDs are: Valproate: 4.7-13.8%; Carbamazepine: 2.6-5%; Phenytoin: 2.4-6.7%; Lamotrigine: 2-4.6%; Levetiracetam: 0-2.4%.
► Valproic acid has the increased risk of major fetal congenital malformations. ► Prepregnancy counseling is essential for a patient with epilepsy.
► Considering the risk of teratogenicity of all AEDs: lamotrigine, levetiracetam or carbamazepine is drug of first-line choice. ► Women with AEDs should be given folic acid supplementation 4 mg/day. Vitamin D supplementation is also needed.
► Breastfeeding is not contraindicated.
► Contraception: IUCD (both copper and LNG-IUD) can be used as the method of choice for most women with epilepsy (Ch. 36). ► The risk of developing epilepsy to the offspring of an epileptic mother is 5-8%.

ASTHMA IN PREGNANCY

During pregnancy some amount of breathlessness is common due to the effect of progesterone and fall in
arterial CO2 tension. It is considered physiological where oxygen saturation is more than 95% (Table 41.11).
Asthma is a chronic airway inflammation and its hyper responsiveness to a number of inflammatory mediators and allergens.

The inflammatory mediators are: Histamine, leukotrienes, PGs, cytokines and IgE. The incidence of asthma is about 5-8% of all pregnant women.
Clinical course: There is mild wheezing. With progressive bronchoconstriction there is fall in FFV/FVC ratio. The work of breathing is increased and ultimately leads to ventilation-perfusion mismatching. There is
hyperventilation to maintain normal PO2• PO2 becomes low (respiratory alkalosis). With severe obstruction (FEV1
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy JI

<35%, Po2J,, PC02 tt) acidosis develops and respirato1y failure sets in and mechanical ventilation may be needed.

EFFECTS OF PREGNANCY ON THE ASTHMA: The course of the disease is very much unpredictable. In about 20%, the condition improves, in 30%, it deteriorates and in 50%, it remains unchanged. Bronchodilator influences are due to progesterone and cortisol and bronchoconstrictor influences are due to reduced residual volume and
increased PGF2 and thromboxane. Asthma increases maternal morbidity.
EFFECTS OF ASTHMA ON PREGNANCY: There is increased incidence of preterm labor, PROM, pre-eclampsia, placental abruption, FGR or LBW and neonatal hypoxia. Maternal risk increases with status asthmaticus. Life threatening complications include pneumothorax, cor pulmonale, cardiac arrhythmias and respiratory failure. Actively managed asthma in pregnancy generally have excellent perinatal outcome. Patients on steroids have high incidence of GDM. Hence, screening of GDM is done.
Pulmonary functions tests for patients with asthma in pregnancy
■ Goal of management is to maintain FEVI >80% of normal
■ A mean FEV 1 <80% predicts the risk of preterm delivery and
LBW.
■ PEFR correlates well with the FEV 1• PEFR can predict early
signs of deterioration so that therapy can be started timely. ■ PEFR is measured reliably with peak flow meter.
■ Inhaled corticosteroids are preferred for the management.
FEV 1 = Forced expiratory volume in 1 second; FVC = Forced vital capacity; PEFR = Peak expiratory flow rate.

MANAGEMENT: Preconception counseling: The overall risk of any child having asthma is about 4%. If one parent has asthma, the risk that the child will have asthma increases to 8-16%. If both the parents have asthma and also atopic (allergic), the risk may be as high as 30%.
Pregnancy: Step therapy of asthma is currently recommended (Table 20.14):

MANAGEMENT OF ACUTE ATTACKS OF ASTHMA (ASTHMA EXACERBATION) IN PREGNANCY
- Pregnant women who are not well-controlled should have more antenatal fetal tests with USG and BPP.
- Avoidance of asthma triggers (allergens, irritant) to minimize ailway inflammation and hyper-responsiveness.
- Oxygen inhalation with mask to maintain 02 saturation >95% (pulse oximeter).
- High dose albuterol by nebulization every 20 minutes and inhaled ipratropium bromide and systemic corticosteroid.
Repeat assessment of symptom, physical examination and 02
saturation to be done.
- Corticosteroids: Intravenous hydrocortisone 200 mg stat and to be repeated after 4 hours. Because of long onset of action, corticosteroids should be given along with 2-agonists.

Table 20.14: Step therapy of asthma in pregnancy. Asthma severity Step therapy
Mild intermittent Inhaled agonist (albuterol) as needed.
Mild persistent Low dose inhaled corticosteroid (budesonide) (ICS) or LTRA.
Moderate Low dose or medium dose inhaled persistent corticosteroids and LABA (salmeterol, LTRA).
Severe persistent High dose inhaled corticosteroid and LABA±
ocs.

Very severe High dose inhaled. Corticosteroid and LABA persistent and OCS.
[LTRA: Leukotriene Receptor Antagonist; LABA: Long-Acting Beta Agonist; OCS: Oral Corticosteroids (Prednisone)]

- Forced Expiratory Volume (FEV1) in one second or peak expiratory flow rate (PEFR) <50% and PC02 >42 mm Hg
necessitates intubation and mechanical ventilation with 100% 02 inICU.
- Mechanical ventilation is needed for status asthmaticus to avoid hypoxemia and carbon dioxide retention.
LABOR
- Clinical evaluation of the patient in labor may be inaccurate to predict the severity. PEFR or FEV 1 should be determined.
- Asthma medications to be continued. FEV 1 2:70%, and reassuring fetal status on EFM indicates good response to
therapy.
- Opiate analgesics should be avoided as they are bron choconstrictor and respiratory depressant. Maternal oxygenation should be adequately maintained. Labetalol should be avoided as it may precipitate asthma.
- Hydrocortisone 100 mg IV 8 hourly during labor and 24 hours postpartum is to be given if the patient had steroids within the previous 4 weeks. Inhaled corticosteroid (fluticasone, budesonide) prevents bronchial hyper-responsiveness to allergens.
- Indomethocin, aspirin may precipitate asthma and to be avoided.
- Butrophanol, Fantanyl are safer than morphine, or meperidine,
- Syntocinon is better than ergometrine because of bron choconstrictor effect of the latter. PGF2a should not be used,
as it precipitates bronchospasm. PGE1 and PGE2 compounds
can be used locally for induction of labor or abortion.
- Epidural anesthesia is preferable to general anesthesia because of risk of atelectasis and subsequent chest infection following the latter. Halothane is better in general anesthesia. However, it produces uterine atony.
- Ketamine is used for induction of general anesthesia as it prevents bronchospasm.
- 02 saturation is assessed with pulse oximeter or arterial blood gases.
- Postnatal physiotherapy is maintained and drugs are continued.
Breastfeeding should be encouraged, as it delays the
onset of allergic problems in the child. Drugs used in
lD Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

asthma: Prednisolone, corticosteroids, LABA, LTRA do not contraindicate breastfeeding. Baby may have vomiting, feeding difficulties, jitteriness or cardiac arrhythmia when mother is on theophylline.
Contraception: Barrier method is the best. For terminal contraception, husband is to be motivated for vasectomy.

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
SLE is a serious autoimmune disease with autoantibodies causing specific multisystem (skin, joints, kidneys, lungs, liver, nervous system and other organs) affection. It is 10 times more common in adult women than the adult men. It is first diagnosed during pregnancy in 10-30% cases.
Clinical features: Common presenting features are-fatigue, photosensitivity, skin rash, fever, weight loss, polyarthralgias, arthritis and myalgias. Joint pains, serositis are often migratory in nature. Chronic inflammatory and "Butterfly" malar skin rash is common.
Effects of pregnancy on SLE: Long-term prognosis remains unaffected. There is chance of flare ups (50-80%) especially during first half and maximum in puerperium. Majority of maternal deaths occur in puerperium, the cause being pulmonary hemorrhage and lupus pneumonitis and exacerbation of lupus nephritis.
Effects of SLE on pregnancy: Risks of lupus rash, anemia, leukopenia, thrombocytopenia and renal failure are increased. There are increased risks of first trimester miscarriage, lupus nephritis (30%), recurrent deep vein thrombosis, PIH (30%), preterm birth, IUGR and stillbirths. Neonatal lupus syndrome is due to crossing of maternal lupus antibodies (anti-Ro/SSA or anti-La/SSB) to the fetus causing hemolytic anemia, leukopenia and thrombocytopenia, hepotosplenomegaly. Isolated congenital complete heart block is present in about one-third of cases. It is diagnosed when a fixed rate with fetal bradycardia (50-80 bpm/ min) is detected. The antibodies bind to antigens of fetal cardiac tissues. Subsequently there is damage to cardiac conduction system. Complete CHB is irreversible and is associated with an overall neonatal mortality of 20%. Survivors need space maker. An apparently healthy woman delivering a baby with congenital heart block should be observed for the development of SLE.
Investigation: Diagnostic criteria includes at least four of the 17 clinical and laboratory criteria with a minimum of one clinical and one immunologic criterion (ACR). Antinuclear antibodies are the standard screening test for the disease. Presence of autoantibodies to double-stranded DNA (dsDNA) is highly specific to the diagnosis. Antibodies to Sm antigen (RNA protein) found in 30-40% of SLE patients are highly specific and are correlated with renal involvement. Other antibodies for diagnosis are: Lupus anticoagulant, antiphospholipid antibodies, anti-Ro SSA and anti-La SSB. Baseline laboratory tests are done to assess anemia, thrombocytopenia, renal function tests and serum antibodies (LA, ACL, anti-RO/SSA and anti-La/SSB).
Management: Preconception planning is extremely important since conception during a period of quiescence is most likely to result in a live birth. Lupus can flare any time in pregnancy and postpartum period ( 15-60%). The predictive factors for success ful pregnancy outcome are: (a) Phase of sustained remission

in the past 6 months; (b) Continued use of Hydroxychloroquine (HCQ) through pregnancy. Thromboprophylaxis (Score 3)-is required both antenatally and postpartum.
Corticosteroids (prednisolone) are the commonly used drugs during flare. As an analgesic, paracetamol is the best agent. Non-steroidal anti-inflammatory agents can be used during puerperium. Low dose aspirin 75-150 mg daily is prescribed with advantages (minimizes PIH and IUGR). It should be stopped at least two weeks before delivety. Prednisolone 1-2 mg/kg/day is started initially and the dose is gradually tapered.
Hydroxychloroquine is safe in pregnancy and found to be the best for maintenance. It reduces the risks of prolonged corticosteroid therapy and its risks like preeclampsia, bone dem ineralization, GDM and FGR.
Immunosuppressive drugs (azathioprine) may be needed to control severe cases of SLE. Mode of delivery is guided by the obstetric behavior. Fetus with congenital heart block should be delivered by cesarean section. Patients should receive stress dose of steroids intrapartum and continued postpartum. • Risk of Congenital Heart Block (CHB): 2-3%; • Risk of cutaneous lupus in neonate: 5%; • Risk of recurrent CHB: 16%; • Risk of recurrence if previous child affected: 16-18%; • Risk if recurrence if previous 2 child affected: 50%; • Chance of APLA Ab along with SLE: 30%.
Oral contraceptives may affect SLE and IUCD may predispose to infection in an immunocompromised patient, as such, barrier method of contraceptives are recommended. Progestins do not flare lupus.

TUBERCULOSIS IN PREGNANCY
INCIDENCE: Pregnant women with tuberculosis is confined predominantly to the underprivileged sectors of society. Incidence of tuberculosis is rising worldwide with the rising prevalence of HIV infected patients. In 2000, WHO showed the emergence of Multidrug Resistant Tuberculosis (MDR-TB) all over the world. It is a 'global health emergency'.

RISK FACTORS: ♦ Positive family history or past history♦ Low socioeconomic status ♦ Immunocompromised persons ♦ HIV infection ♦ Alcohol addiction ♦ Intravenous drug abuse ♦ Diabetes, jejunoileal bypass, underweight by 2:15% ♦ Chronic renal failure♦ ExtrapulmonaryTB is less common.
DIAGNOSIS: (i) Tuberculin skin test (TST) with Purified Protein Derivative (PPD) induration 2:5 mm is considered positive especially in presence of risk factors (HIV), (ii) Women with induration are considered positive as follows: <5 mm with HIV infection; 2:5 mm with HIV, close contact and abnormal chest radiograph; 2:10 mm with comorbidities (diabetes); 2:15 mm healthy, (iii) X-ray chest (after 12 weeks), (iv) Early morning sputum (three samples) for acid-fast bacilli (direct amplification test-NAAT), (v) Gastric washings, (vi) Diagnostic bronchoscopy, (vii) Extrapulmonary sites-lymph nodes, bones (rare in pregnancy) and (viii) Direct amplification tests for 16 S ribosomal DNA and gene probe can detect M. tuberculosis with greater sensitivity and specificity. Interferon Gamma Release Assay (IGRA) is superior to TST. It is done with whole blood sample. It is a single visit test with faster results and is not affected by prior BCG vaccination.
Congenital tuberculosis is diagnosed by-(1) Lesion noted in the first week of life, (2) Infection of the maternal genital tract
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy 11

or placenta, (3) Cavitating hepatic granuloma diagnosed by percutaneous liver biopsy at birth and (4) No evidence of postnatal transmission. Congenital tuberculosis is rare but with high mortality (50%) needs the care of a pediatrician. Concomitant HIV infection or when TB is drug resistant, the risk is increased.

PROGNOSIS: Provided the patient remains under medical supervision with adequate treatment, pregnancy has got no deleterious effect on the course of the disease; nor has the disease any adverse effect on the course of pregnancy. In active disease, fetus can be affected by transplacental route or by aspiration of amniotic fluid or by the infected secretions during delivery. Neonatal affection is mainly by postpartum maternal contact. In untreated patients, the incidence of preterm labor, IUGR and perinatal mortality is high. In such a situation maternal morbidity and mortality are also high.
I MANAGEMENT
MEDICAL: Prevention: Women (age <35 years) with positive PPD and no evidence of active disease (asymptomatic)-isoniazid prophylaxis 300 mg/day is started after the first trimester and
continued for 6-9 months. Pyridoxine (vitamin B6) 50 mg/day is added to prevent peripheral neuropathy. No major adverse
fetal or neonatal effects are seen with these antituberculous drugs (Table 20.15).
Treatment: Women with active tuberculosis should receive the following drugs orally daily for a minimum period of 6-9 months (Table 20.15).
Rapid molecular drug sensitivity testing for rifampicin with or without isoniazid to be done.
Latent TB (patient in inactive stage) with risk factor should be treated in pregnancy with isoniozid 300 mg daily for 9 months.

SURGICAL: Major thoracic surge1y should be withheld, if possible, but if deemed necessa1y should be restricted to the first half of pregnancy beyond 12 weeks.
HIV Positive women needs additionally pyrazinamide therapy along with ART.
OBSTETRIC MANAGEMENT
Place of therapeutic termination: Tuberculosis per se is not an indication for termination of pregnancy.
Obstetric management is no different from other pregnant women, once tuberculosis is well managed.
Breastfeeding: Breastfeeding is not contraindicated when a woman is taking antituberculous drugs. Breastfeeding should be avoided if the infant is also taking the drugs (to avoid excess drug level). In active lesion, and when mother is MDR-TB breastfeeding contraindicated and the baby is to be isolated from the mother following delivery. Baby should be given prophylactic isoniazid 1-2 mg/kg/ day for 3 months when the mother is suffering from the active disease. However, if the mother is on effective chemotherapy for at least 2 weeks, there is no need to isolate the baby. BCG should be given to the baby as early as possible.
CONTRACEPTION: Pregnancy is to be avoided until quiescence is assured for about two years. Spacing can be achieved by any methods acceptable to the couple. Oral contraceptives should be avoided when rifampicin is used. Due to accelerated drug metabolism contraceptive failure is high. A barrier method may be used. Puerperal sterilization should be seriously considered, if the family is completed.

Active infection: Four drug regimen with isoniazid, rifampicin, ethambutol and pyrazinamide along with pyridoxine. In the first
SYPHILIS IN PREGNANCY
2 months, all the four drugs are given (bactericidal) phase. This Syphilis is a sexually transmitted disease caused by Treponema is followed by another four months of isoniazid and rifampicin pallidum. Incidence is rising due to upsurge of HIV (continuation phase). Women with MDR-TB need second line infection and the IV drug abuse. Overall frequency of vertical drugs (Table 20.15). transmission (congenital syphilis) is high in primary (50%) and
· Tablei 20.15: Antitubercular drug therapy in'pregna cy ({_"10)r-'!'i';'..'?::•W · · ., , ",•, 0' .. ' . '' '.' "

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First-line drugs
11 lsoniazid (pyridoxine) (H) ■ Rifampicin (R)

■ Ethambutol (E)
■ Pyrazinamide (Z)

Daily dose-PO
5 mg/kg up to 300 mg 10 mg/kg up to 600 mg

15 mg/kg up to 2.5 g
15-30 mg/kg up to 2 g

Major side effects
Hepatitis, peripheral neuropathy, hepatic enzyme elevation, hypersensitivity.
Nausea, vomiting, hepatitis, orange discoloration of urine and secretions, febrile reaction.
Skin rash. Optic neuritis, decreased visual activity.
Hepatotoxicity, skin rash, arthralgias, hyperuricemia, GI upset.

RNTCP recommends: All new cases irrespective of smear positivity: 2 H3 R3 Z3 E3 + 4 H3 R3 and smear positive cases with relapse, failure, default or others: 2 H3 R3 Z3 E3 53 + 1 H3 R3 Z3 E3 + 5 H3 R3 E3.
■ Pyridoxin (vitamin B6) 1-2 mg/kg/day (SO mg/day) to prevent peripheral neuropathy.

Second-line drugs
■ Para-aminosalicylic acid (PO)
■ Cycloserine (PO) ■ Kanamycin (IM) ■ Capreomycin

Daily dose-PO 150 mg/kg up to 1 g
15-20 mg/kg up to 1 g 15-30 mg/kg up to 1 g 20 mg/kg up to 1 g

Major side effects
Gastrointestinal (GI) toxicity, hepatotoxicity
Rash, convulsions
Auditory and renal toxicity, rarely vestibular Auditory, renal, hepatic toxicity
·ED Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

secondary (50%) syphilis. In tertiary syphilis it is about 10%. The risk of transmission following a single unprotected sexual intercourse is 50-60%. Mean incubation period is 21 days, with a range of 10-90 days.
EFFECTS ON PREGNANCY
Mother: Syphilis accelerates the course of HIV infection in pregnant woman.
Baby: Congenital infection results from transplacental migration of spirochete to the fetus (50%). Congenital disease occurs with all stages of maternal infection and at any gestational age. The basic pathology is obliterative endarteritis. There is perivascular infiltration of lymphocytes and plasma cells within the developing fetus. The placenta becomes bulky from increased connective tissue.
Depending upon the intensity and time of occurrence of the infiltration, the fate of the fetus will be as follows: (1) Miscarriage, (2) Preterm birth, (3) Intrauterine deaths leading to either a macerated or a fresh stillbirth, (4) Non-immune fetal hydrops (ascites, hepatomegaly), (5) Delive1y ofa highly infected baby with early neonatal death and (6) Survival with congenital syphilis.

DIAGNOSIS: Mother
■ Obstetric history in multigravidae-with serial pregnancies, there have been gradually improved obstetric performances. A classic history shows-late abortion ➔ macerated stillbirth ➔ fresh stillbirth ➔ congenital syphilitic baby➔ healthy baby.
■ Clinical findings of various stages of syphilis-usually suppressed during pregnancy.
■ Clinical presentations: Primary: Chancre, Inguinal lymph adenopathy. Secondary: Maculopapular rash, myalgia. Latent (early <l year and late >l year). No symptoms, positive serologies. Tertiary: Involvement of CVS (aortic aneurysms, aortic insuficiency, coronary stenosis); CNS (paralysis, tabes dorsalis, dementia); skin-gummas.
■ Investigations: (a) Serological test-this should be done as a routine in the first antenatal visit. VDRL (positive within 4 weeks of infection) is commonly done, {b) A positive VDRL test has to be confirmed by fluorescent treponemal antibody absorption test {FTA-ABS) and Treponema pallidum microhemagglutination (MHA-TP) test which are specific. Husband's blood should also be tested for VDRL, (c) Detection of spirochetes from the cutaneous lesion if any, by dark field microscopic examination and (d) Fetal infection could be diagnosed by Polymerase Chain Reaction (PCR) of T. pallidum in amniotic fluid, fetal serum or spinal fluid. Spirochetes may be detected from fetal liver or spleen.
Clinical features of congenital syphilis:
■ Early (<l year): Maculopapular rash, rhinitis, hepatospleno megaly, jaundice, lymphadenopathy, anemia, chorioretinitis and pneumonia.
■ Late (>1 year): Hutchinson teeth, deafness, saddle nose, saber shins, hydrocephalus, mental retardation, Clutton joint, interstitial keratitis, 8th nerve deafness and optic nerve atrophy.
If the baby is stillborn, spirochetes may be detected from the fetal liver or spleen or from the intimal scraping of umbilical vein.
TREATMENT: Mother: Treatment should be started as soon as the diagnosis is established. The baby may have the chance

of protection even if the treatment is begun late in pregnancy. For primary or secondary or early latent syphilis ( <l year duration: up to 21+6 weeks): benzathine penicillin 2.4 million units intramuscularly single dose. From 28 weeks onwards 2.4 MIU on day 1 and 8 (2 doses). For late syphilis 3 doses is given in all three trimesters. If the patient is allergic to penicillin, oral azithromycin 2 g as a single dose is given. Tertiary disease: Neurosyphilis-aqueous crystalline penicillin G 18-24 million units IV daily for 10-14 days is given. If the treatment is given in early pregnancy, the treatment should be repeated in late pregnancy. Irrespective of the serological report, treatment should be repeated in subsequent pregnancies.
Efficacy of treatment is from 95-100%. Penicillin allergic women need desensitization once confirmed.
Neonate:
■ Positive serological reaction without clinical evidences of the disease: The baby is treated with a single intramuscular dose of penicillin G 50,000 units per kg body weight.
■ Infected baby with positive serological reaction: (1) Isolation with the mother and (2) Intramuscular admi nistration of aqueous procaine penicillin G 50,000 units per kg body weight each day for 10 days.
■ An apparently healthy child of a known syphilitic mother: Serological reaction should be tested weekly for the first month and then, monthly for 6 months.
HANSEN DISEASE (LEPROSY) IN PREGNANCY: Latent infection by M. leprae may become overt for the first time during pregnancy or within few months following delivery. With established leprosy, there is chance of exacerbation of the lesions during pregnancy. Pregnancy may be regarded as a test of cure. Failure of signs of the disease to reappear during or after pregnancy indicates that the leprosy is definitely arrested. Although M. leprae have been found in the placenta and cord, congenital infection of the baby is unlikely. However, the baby should be separated from the infected mother, immediately after delivery. When the disease becomes quiescent and non infectious, the baby may be given to the mother. Dapsone and clofazimine appear safe in pregnancy. Rifampicin may also be used. IUGR is a common problem.
GONORRHEA IN PREGNANCY: The manifestations of the disease are the same as in the nonpregnant state. If the infection takes place during pregnancy, it tends to be more acute. The diagnosis is to be confirmed by bacteriological identification of intracellular Gram-negative diplococci from urethral discharge or NAATs. Serological test is to be done to exclude concurrent syphilitic infection. Infection increases the risk of preterm labor, PROM, intrapartum and postpartum infection. Disseminated infection includes: arthritis, meningitis, endocarditis and perihepatitis (Fitz-Hugh-Curtis syndrome). The baby may be affected during labor while passing through the infected birth canal resulting in ophthalmia neonatorum.
Treatment: Single dose injection of ceftriaxone 250 mg IM or cefixime 400 mg PO single dose or azithromycin 2000 mg orally (single dose) is effective. Both the partners are treated. Ophthalmia neonatorum is treated with either silver nitrate or tetracycline preparation. Infected neonate is treated with single dose of ceftriaxone 50 mg/kg IM.

CHLAMYDIAL INFECTIONS: This bacterial infection is becoming the common sexually transmitted pathogen. The organisms are found in urethra, endocervix and rectum. C. trachomatis
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

isran obligate intPreterm r labor, riPROM, chorioamnionitis, Table 20.16: ffects of malaria on pregnancy. stillbirth, LBW, perihepatitis (Fitz-Hugh-Curtis syndrome).
racellula bacte a.
The adverse effects in
p egnancy are:
Effects on the fetus
Effects on the mother
Puerperal endometritis or acute salpingo-oophoritis may 11 Anemia (megaloblastic) due to hemolysis Pregnancy com-develop. Neonates may develop conjunctivitis or pneumonia and folic acid deficiency. plications are
and even death. ■ Thrombocytopenia. increased:
■ Hypoglycemia: due to increased ♦ Miscarriage now being done. NAATs are superior to culture, antigen detection and the parasites. There is ,I, hepaticost ♦ Preterm labor
DNA/RNA amplification technology
Chlamydia! infection:
glucose consumption both by the h
Prematurity
♦
or DNA probe techniques.
t
gluconeogenesis an
Treatment is highly effective with erythromycin in doses the drugs (quinine).d insulin secretion by ♦ IUGR
Congenital
malaria
IUFD
Fetal anemia
♦
0.5 g 4 times a day for 7-10 days. Azithromycin 1 g in a single ■ Metabolic acidosis (pH <7.3).
dose could also be prescribed. Therapy should be instituted to
Jaundice due to hepatic dysfunction.
■ Renal failure-due to block of renal
microcirculation.
■ Pulmonary edema and respiratory
distress (RDS).
♦
♦
the husband simultaneously. As a prophylaxis to ophthalmia 11 neonatorum, e1ythromycin ointment 1 % is to be applied to the infant's eyes soon following birth. Neonatal infection is treated
with erythromycin 50 mg/kg/day 4 times a day for 14-21 days.
GROUP B STREPTOCOCCAL INFECTION (GBS): Maternal infection 11 Convulsions and coma-cerebral malaria. Increased maternal
and perinatal
mortality
with GBS is an important cause of neonatal infection and high 11 Circulatory collapse.
perinatal mortality. Vaginal and anorectal colonization of ■ Abnormal bleeding (DIC). GBS is the main source of infection. Main risk factors: for
neonatal infection are: • Previous baby affected, • Maternal Effects of pregnancy on malaria: GBS carriage during pregnancy, • PTB, • Pyrexia, • Prolonged
• Risk and severity of infection are high due to immuno
compromised state
rupture of membranes(> 18 hours), pre term labor, • Prolonged
labor and low birth weight. Neonatal infections include: • RDS,
• Pneumonia, • Jaundice, • Hypotension, • Septicemia and • Complications are high (Table 20.16).
• Meningitis. Neonatal mortality is about 30-40%. Management: Prevention from mosquito bites is done Maternal complications include: Endometritis, UTI, PROM using permethrin and pyrethroids spray kill mosquitoes.
and preterm labor and wound infection. Diagnosis is made by Electrically heated mats will kill mosquitoes in the room.
culture of specimens obtained from vagina, perineum using a Chemoprophylaxis: Chloroquine is given unless proved
cotton swab. PCR can also be used.
resistant. It is taken 300 mg base weekly, 2 weeks before
Currently universal cultures for all patients is recommended
travel and covering the period of exposure and 4 weeks
(ACOG-2019) for prevention of GBS infection. Culture should be after leaving the endemic zone. Mefloquine 5 mg/kg/week should receive intrapartum antibiotic prophylaxis. Ampicillin is the alternative drug in second and third trimesters when
performed at 36-37 weeks of gestation.
All test positive women
chloroquine is found resistant.
2 g IV, then 1 g every 4 hours until delivery is given. Penicillin
G, also recommended. Women scheduled for CD do not need Treatment: Risks of malaria is life-threatening in prophylaxis. Intrapartum therapy with ampicillin 2 g initially, pregnancy. So benefits of treatment outweigh the then 1 g 4 hourly is given till delivery. potential risk of antimalarial drugs. Chloroquine-600
mg base PO followed by 300 mg 12 hours later. Then
!]•;•
PARASITIC AND PROTOZOAL INFESTATIONS 300 mg daily for next 2 days. To prevent relapse during IN PREGNANCY pregnancy, 300 mg is to be taken weekly until delivery.
MALARIA: Malaria is predominantly a tropical For radical cure, primaquine should be postponed until disease. In India and other South-East Asian ';',: -.· pregnancy is over. Parasites resistant to chloroquine
countries there is resurgence of malaria. The - • : should be given quinine (10 mg salt/kg PO > every 8 hours diagnosis is confirmed by the detection of malarial for 7 days) under supervision. Patients with severe anemia parasites in peripheral thick blood smear. may need blood transfusion. The antimalarial drugs when
!J • ·
Pathology: The infected erythrocytes become rigid, given in therapeutic doses, have got no effect on uterine irregular and sticky. There is blockage of microcirculation contraction unless the uterus is irritable. Folic acid 10 mg due to the sequestrated red cells. The infected red cells are should be given daily to prevent megaloblastic anemia.
broken down (hemolysis). Maternal HIV or tuberculosis Complicated malaria: Artesunate IV 2.4 mg/kg at 0, causes intense parasitization of the placenta. 12 and 24 hours, then daily thereafter. Oral therapy (2
The fetal effects are due to high fever or due to mg/kg) is started when the patient is stable. Alternatively placental parasitization. The intervillous spaces become Quinine IV followed by oral therapy is given. Artesunate blocked with macrophages and parasites and there is act very fast and resistance is rare. It is as effective as IV diminished placental blood flow. This is mostly seen with Quinine. Use is limited in the second or third trimesters of P. falciparum infection and in the second half of pregnancy only when other drugs are found resistant. pregnancy. Congenital malaria is rare (<5%) unless the Patient with severe malaria needs intensive care unit
placenta is damaged (Table 20.16). management. Supportive care is essential in cases with
ml Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

hyperpyrexia, pulmonary edema, renal failure or DIC. Multidisciplinary team approach is needed.
TOXOPLASMOSIS: Toxoplasmosis is a protozoan infestation caused by Toxoplasma gondii. Infection is transmitted through encysted organism by eating infected raw or uncooked meat or through contact with infected cat feces. It can also be acquired ac1'oss the placenta.
The fetal risk of infection increases with duration of preg nancy and is approximately 15%, 30% and 60% in the first, second and third trimesters respectively. The fetus is only at risk if the mother is seronegative. Risk of fetal damage decreases from 60% in first trimester to almost 0% at the end of pregnancy. There is increased rate of miscarriage, IUGR and stillbirth. During parasitemia, transplacental infection to the fetus occurs. The affected fetus may develop hydrocephalus, ventriculomegaly, ascites, hepatosplenomegaly and IUGR. Antenatal diagnosis of congenital toxoplasmosis could be made by ultrasonography and amniocentesis. The affected baby may present with chorioretinitis, cerebral calcification, microcephaly, seizures and mental retardation. Presence of IgM antibody in the neonates indicates congenital infection. IgG transmitted from the mother persists for many years.
Maternal infection is mostly asymptomatic when she is immunocompetent. Acute infection is diagnosed by detecting IgM specific antibody, high level of IgG antibody titer and detection of seroconversion for IgG from negative to positive Amniotic fluid testing of gene specific to T. gondii with PCR, has positive productive value of 100%. Neonatal infection is common ( 40%) when mother suffers with acute toxoplasmosis. Routine screening is usually not done. Chronic maternal toxoplasmosis is not considered to be a significant cause of recurrent abortion as parasitemia will not be repeated in subsequent pregnancies.
If current infection is confirmed the following tests are carried out: (1) Amniocentesis and cordocentesis for detection of IgM antibody in the amniotic fluid and fetal blood. PCR for T. gondii gene is also done. (2) Ultrasonography findings suggestive of fetal infection are: ventriculomegaly, intracranial calcification, microcephaly, hepatosplenomegaly, ascites and IUGR at 20-22 weeks. If the fetus is infected and hydrocephalus is present, counseling for termination is to be done.
Treatment: Toxoplasmosis is a self-limited illness in an immunocompetent adult and does not require any treatment. Pyrimethamine 25 mg orally daily and oral sulfadiazine 1 g four times a day is effective. Leucovorin is added to minimize toxicity. Four to six weeks course is usually given. Pyrimethamine is not given in the firsttrimester. Spiramycin (3 g orally daily for 3 weeks) has also been used as an alternative. Acute toxoplasmosis during pregnancy is treated with spiramycin. Extended courses may be needed in an immunocompromised patient to cure infection. Treatment to the mother reduces the risk of congenital infection and the late sequelae.
Prevention: Uncooked meat, unpasteurized milk and contact with stray cat or cat litter are to be avoided.

LISTERIOSIS: Listeria Monocytogenes (LM) is an intracellular gram-positive bacillus. It is readily found in soil and vegetation. It can grow and multiply in temperature as low of 0.5°C. Infection is caused by eating infected food or through contact with infected miscarried products of animals. Maternal symptoms

are 'flu-like' or 'food poisoning'. There is no reliable serological test for it except the blood culture during septicemia. Fetus is primarily affected by transplacental transmission. Obstetric complications: Late miscarriage, preterm labor and delivery and stillbirth. LM infections can cause meningitis, encephalitis, bacteremia pneumonia, fever and gastroenteritis. Neonatal death due to septicemia is also high (10%). Overall perinatal mortality is 10%.
Diagnosis: Gram stain (blood or amniotic fluid specimen) revealing gram-positive pleomorphic rods with rounded ends is highly suggestive.
Treatment: Combined therapy with ampicillin, amoxicillin and gentamicin (IV) preferred. Trimethoprim and sulfamethoxazole can also be used.
Prevention of listeriosis during pregnancy according to FDA includes: Not to drink or take-unpasteurized milk, soft cheese, refrigerated smoked seafood (salmon, trout, cod).
INTESTINAL WORMS: Hookworms (Ancylostoma) and round worms (Ascaris lumbricoides) are the common intestinal infestations in the tropics and subtropics. The diagnosis is by stool examination. The treatment consists of eradicating the worms along with treatment of anemia by iron therapy. Deworming is not contraindicated during pregnancy excluding the first trimester.

URINARY TRACT INFECTIONS IN PREGNANCY
There is increased chance of Urinary Tract Infection (UTI) in females as compared to males due to: (i) Short urethra (4 cm), (ii) Close proximity of the external urethral meatus to the areas (vulva and lower third of vagina) contaminated heavily with bacteria, (iii) Catheterization and (iv) Sexual intercourse.

INCIDENCE: The overall incidence of pyelonephritis in pregnancy is between 1 and 3%.

ETIOLOGY: (1) It is more common in primigravidae than multiparae, (2) Previous history of urinary tract infection increases the chance by 50%, (3) Presence of asymptomatic bacteriuria increases the chance by 25% and (4) Abnormality in the renal tract is found in about 25%.
Physiologic changes responsible for acute pyelonephritis in pregnancy are: (1) Low ureteral peristalsis due to high progesterone levels. (2) Dextrorotation of gravid uterus causing compression of right ureter. Pyelonephritis occurs more on the right side (70-80%) compared the left (10-15%).

PATHOGENESIS: Predisposingfactors-dilatation of the ureters and renal pelvis and stasis of the urine in the bladder and ureters are the normal physiological changes during pregnancy. The organisms responsible are E.coli (70%), Klebsiella pneumoniae (10%), Enterobacter, Proteus, Pseudomonas and Staphylococcus aureus group. About 10% of women develop bacteremia following acute pyelonephritis. 70-80% of pyelonephritis occurs on the right side, 10-15% on the·left side and only few are bilateral.

CLINICAL TYPES: Depending upon the mode of onset and the presenting features, the cases are grouped into:
♦ Acute or severe type ♦ Chronic type

ACUTE PYELONEPHRITIS: Clinical features-the onset is acute and usually appears beyond the 16th week. The involvement is
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy ED

bilateral but if unilateral, it is more frequent on the right side. Clinical features are mainly due to endotoxemia. The chemical mediators (cytokines) released are: IL-1, TNF and endogenous pyrogen. Important features are: Acute aching pain over the loins, often radiating to the groin and costovertebral angle tenderness, urgency, frequency, dysuria, hematuria. Fever (spiky 40°C) with chills and rigor followed by hypothermia (34°C); anorexia, nausea, vomiting and myalgias; respiratory distress and pulmonary edema (ARDS) due to endotoxin-induced alveolar injmy. Patients go to preterm labor and septic shock.
Investigations: Apart from the routine ones, serum level of creatinine, electrolytes and culture studies of urine and blood should be done.

DIFFERENTIAL DIAGNOSIS: Includes-(!) Acute appendicitis, (2) Abruptio placentae, (3) Red degeneration of fibroid, (4) Acute cholecystitis, (5) Labor and (6) Chorioamnionitis.

COMPLICATIONS: FETAL: There may be increased fetal loss due to miscarriage, preterm labor, intrauterine fetal death caused by hyperpyrexia and low birth weight babies (prematurity and dysmaturity ).
MATERNAL: Anemia, septicemia, septic shock, renal dysfunction and pulmonary insufficiency. ARDS may develop due to endotoxin-induced alveolar capillary membrane damage following septicemia.
MANAGEMENT: The outlines of management are:
■ Intravenous fluid (c1ystalloid) for adequate hydration.
■ Evaluation of complete hemogram, serum electrolytes, creatinine.
■ Acetaminophen is given for the fever.
■ Monitor urine output (2:60 mL/hr), temperature and BP.
■ IV antibiotics-ceftriaxone, aminoglycosides (gentamicin), cefazolin or aztreonam (500 mg every 8 hours) for 48 hours till culture report is available and then changed to oral therapy for another 10-14 days.
11 Repeat urine culture after 2 weeks of antimicrobial therapy and is repeated at each trimester of pregnancy.
■ If the symptoms recur or the dipstick test for nitrate and leukocyte esterase is positive, urine culture is repeated. The woman needs retreatment if the culture is positive.
■ Patient not responding with this therapy needs to be evaluated (sonography, CT scan, radiography) for urinary tract obstruction. Resistant organism needs repel culture and sensitivity.
a Antimicrobial suppression therapy is continued till the end of pregnancy to prevent recurrence (30-40%). Nitrofurantoin 100 mg daily at bed time is effective.
I ASYMPTOMATIC BACTERIURIA {ASB)
The term asymptomatic bacteriuria is used when a bacterial count of the same species over I 05 / mL in midstream clean catch specimen of urine on two occasions is detected without symp toms of urinary infection. This indicates actively multiplying bacteria within the urinary tract. E. coli is the offending organism in over 90% cases. Other pathogens are Klebsiella pneumoniae and Proteus. To exclude pre-existent ASB, all pregnant women should ideally have a urine culture at their first antenatal visit (ACOG). The overall incidence during pregnancy ranges between 5 and 10%.

Considering its high incidence, screening techniques have a definite place. Urine should be screened for nitrites and leukocyte esterase. If either of these tests is positive, urine culture is indicated.
Twenty-five percent of these women are likely to develop acute pyelonephritis, usually in third trimester, ifleft untreated. The incidence of hypertension and anemia is stated to be high. The increased association of premature labor and growth restricted babies is probably related with the underlying chronic renal lesion.
Asymptomatic bacteriuria if recurrent is associated with high incidence of urinary tract abnormality (20%), congenital or acquired. The woman runs a greater risk of developing chronic renal lesion in later life.
Treatment: The antimicrobial agents should be appropriate to the mother and the fetus. Any one of these drugs could be prescribed, nitrofurantoin (100 mg bid), amoxicillin (500 mg tid), cephalexin (500 mg tid). A course of 10-14 days will cure 70-100% of cases. A single dose therapy of nitrofurantoin 0.2 g or amoxicillin 3 g has been found effective. Most strain of E. coli, Klebsiella and Proteus have developed resistance to ampicillin, amoxycillin. These antibiotics alters the normal bowel and vaginal flora to cause diarrhea or monilial vulvovaginitis. Nitrofurantoin is uniformly effective against the common uropathogens. Long-term prophylaxis with nitrofurantoin (50 mg) or amoxicillin (250 mg) at night may have to be continued until delivery when the infection is recurrent. Women with recurrent UTI should undergo imaging of the upper urina1y tract, 3 months postpartum.
ACUTE CYSTITIS: Women presents with dysuria, urgency, suprapubic pain and dribbling. Hematuria may be pre sent. Urine tests with esterase and nitrate are positive. Catheterized urine sample for culture is desired as it reduces the contamination with vaginal flora. Colony count with a catheterized specimen >102/mL indicates infection. Nitrofurantoin is effective for the treatment.
ACUTE URETHRITIS: Patient presents with dysuria, urgency, frequency, dribbling. Mucopurulent urethral discharge is often present. Common organisms are: E. coli, C. tractomatis or N. gonorrhoeae. Culture ofurethral discharge is helpful to the diagnosis. Urine cultures may reveal low colony counts. NAAT is helpful to identify of chlamydia or gonorrhea. Treatment for chlamydia! infection is azithromycin 1000 mg (single dose). For gonorrhea injection ceftriaxone 250 mg IM and 1000 mg azithromycin orally is given.
HEMATURIA IN PREGNANCY: Presence of few red cells under the microscope in routine examination of urine during pregnancy is mostly due to contamination. Examination of the 'clean catch' midstream urine rules out contamination. The causes of hematuria are manifold and are broadly divided into:
I. Those related to the pregnant state II. Those unrelated to pregnancy
♦ Those related to the pregnant state are: 0 Severe cystitis pyelonephritis, 1) Rupture of bladder varicosities, 0 Following rapid evacuation of urine in acute retention with a retroverted gravid uterus, 0 Lower segment scar rupture involving the bladder and 0 Operative delivery following obstructed labor due to congestion. The possibility of traumatic injury should be ruled out.
II Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy
♦ Those unrelated to pregnancy as urinary calculi, respectively. Multisystem abnormalities are seen following renal tuberculosis, renal neoplasm, papilloma bladder. congenital rubella infection within 12 weeks.
Treatment consists of: (a) To increase the urinary output by Congenital Rubella Syndrome (CRS) predominantly (90%) adequate fluid intake and (b) to correct the pathology by medical include cochlear (sensorineural deafness), cardiac (septa!
or surgical treatment. defects, PDA), hematologic (anemia, thrombocytopenia), liver
and spleen (enlargement, jaundice), ophthalmic (cataracts, during pregnancy state. The causes are divided into-(A) retinopathy, cloudy cornea), bone (osteopathy) and chromosomal uterus gand (2) Impacted pelvic tumors. e(B) etroverted gravid extremely teratogenic if contracted within the first trimester.
RETENTION OF URINE:
It is not an uncommon complication
the fetus and is
abnormalities.
The virus predominantly affects
Incarcerat d r
Durin early pregnancy-(!)
During labor
Type-I diabetes mellitus and
Long-term complications are:
panencephalitis.
(1) Associated with abnormal uterine activity commonly with
incoordinate uterine action and (2) Obstructed labor. (C) There is increased risks of miscarriage, stillbirth and congenitally malformed baby. Infants born with congenital rubella
Duri11g puerperium-(1)
diminished bladder tone,
(2)
reflex
pain from vulva! injuries and
(3)
bruising and edema of the
bladder neck. If simple measures fail, catheterization is to be shed the virus for many months and is a source of infectiontto
others.
Rubella specific IgG antibodies are present for life af er
infection or vaccination.
If
the patient is not im
USG may be used
done using a disposable catheter.
Summary of Urogynecological Problems in Pregnancy: of therapeutic termination may be considered. mune, question
(1)
Stress Urinary Incontinence (SUI): SUI affects 70% of to detect fetal affection. Detection of viral RNA by PCR is possible. women. Weakened pelvic floor muscles cause the bladder Prenatal diagnosis of rubella virus infection using PCR can be done and urethra to stretch. This results in weakness of the from chorionic villi, fetal blood and amniotic fluid samples.
urinary sphincter making UI more common. Pelvic floor Active immunity can be conferred in nonimmune subjects muscle training (PFMT) is the first line of management; by giving live attenuated rubella virus vaccine (MMR) preferably
(2) Pelvic Organ Prolapse (POP): This affects up to 20% during 11-13 years. It is not recommended in pregnant women.
of pregnant women. Both pregnancy and vaginal birth are When given during the child-bearing period, pregnancy should
be prevented within four weeks by contraceptive measure. of labor, delivering a macrosomic baby also contribute. However, if pregnancy occurs during the period, termination of
the risk factors. Use of forceps, prolonged second stage
pregnancy is not recommended.
PFMT is the mode of management along with lifestyle
modifications. Surgical intervention is recommended MEASLES: The virus (RNA) is not teratogenic. However,
high fever may lead to miscarriage, FGR, microcephaly and (OAB): OAB affects 30-40% women in pregnancy. oligohydramnios, stillbirth or premature delivery. Non With the enlarging gravid uterus, the bladder capacity protected by intramuscular injection of immune serum globulin
following completion of family;
(3) Overactive Bladder
immunized women coming
contact with measles may be
in
is reduced causing OAB. Lifestyle modifications with
(5 mL) within 6 days of exposure. Mortality is high when
reduced caffeine intake, Anticholinergic medications complications like pneumonia, encephalitis develop. Diagnosis: (Oxybutynin Immediate Release) are offered; (4) Urinary Koplik spots are pathognomonic, virus-specific assay of IgM and Retention: Retroverted uterus is a cause. Risk factors detection of viral RNA (RT-PCR) are done.
for its development include pelvic adhesions, uterine Management is supportive care. Antibiotics are given to malformations. Usually this resolves as the pregnancy prevent secondary bacterial infections. Ribavirin may be given
advances. A urinary catheter may be required to drain for viral pneumonia. Vaccination with trivalent MMR prevent
urine in some; (5) Recurrent UTI's: Around 10% women measles. Active vaccination (live attenuated) should not be
are affected in pregnancy. Asymptomatic Bacteria (ASB) given in pregnancy.
is the commonest cause. The main risk factors for INFLUENZA: Influenza virus (RNA) are enveloped. Hemagg Recurrent UTI are: History of UTI, frequency of sexual lutinin (H) and neuraminidase (N) are present on the surface. intercourse, multiparity, lower socioeconomic status, Influenza strains are named according to their genus, species
hydronephrosis (diagnosed on renal USG), renal stones and H and N subtypes. The course of pregnancy remains (diagnosed on renal USG). The following antibiotic unaffected unless the infection is severe.
prophylaxis can be used: Trimethoprim 100 mg overnight Effects on pregnancy due to HI-NI infection: Miscarriage,
(ON) (avoid in first trimester) or nitrofurantoin 50-100 mg preterm labor (30%), PROM, pneumonia, ARDS, renal failure, DIC
ON (avoid in third trimester) or amoxicillin 250 mg ON.
VIRAL INFECTIONS IN PREGNANCY
!JI!]

· ·
!]• .... ·
and death. Severity of illness are high in pregnancy. There is no evidence of its teratogenic effect even if it is contracted in the first trimester. However, outbreak of Asian influenza showed increased incidence of congenital malformation (anencephaly) when the
RUBELLA: Rubella or German measles (RNA virus) infection occurred in the first trimester. Influenza (inactivated) is transmitted by respiratmy droplet exposure. vaccine is safe in pregnancy and also with breastfeeding. Maternal rubella infection is manifested by rash, • Intranasal vaccine not to be used in pregnancy as it contains malaise, fever, lymphadenopathy and polyarthritis. live virus. Diagnosis: Rapid Influenza Diagnostic Tests (RIDTs) Fetal infection is by transplacental route throughout pregnancy. are immunoassay used for detection of viral RNA by RT-PCR. Risk of major anomalies when this infection occurs in first, Risk factors for severe illness and death are: asthma, obesity, second and third month is approximately 50%, 25% and 10%, hypertension and delay in treatment.
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy il

Management: Treatment is supportive care. Acetaminophen is used for fever. Oseltamivir (neuraminidase inhibitor), an antiviral drug, reduces the severity, secondary complications and death. It is given 75 mg PO, twice daily for 5 days. High dose may be given for longer duration in cases with severe infection. Alternative drug is zanamivir or peramivir. During influenza season, all pregnant women should be given the Inactivated Vaccine (IM).
VARICELLA (CHICKENPOX): Varicella zoster virus (DNA) does cross the placenta and may cause congenital or neonatal chickenpox. Maternal mortality is high (5%) due to varicella pneumonia (20%). Other maternal complications are: encephalitis and bacterial superinfection.
Congenital Varicella Syndrome (CVS) is characterized by: hypoplasia of limb, psychomotor retardation, IUGR, chorioretinal scarring, cataracts, microcephaly and cutaneous scarring. The risk of congenital malformation is nearly absent when maternal infection occurs after 20 weeks.
Prevention: VZV-vaccine (live attenuated) is given to nonimmune women prior to conception. It is contraindicated during gestation. Pregnancy should be delayed 3 months following vaccination. Management: Varicella PCR can identify VZV specific DNA from vesicular fluid. ELISA can detect VZV specific IgG and IgM. Varicella Zoster Immunoglobulin (VZIG) should be given to exposed non-immune patients as it reduces the morbidity. VZIG should also be given to newborn exposed within 5 days before and 2 days after of delivery. Oral acyclovit; or valacyclovir is safe in pregnancy and reduce the duration of illness when given within 24 hours of the rash (Fig. 20.4). Howevet; it cannot prevent congenital infection.
CYTOMEGALOVIRUS (CMV) INFECTION: It is a DNA virus. Transmission may be sexual, respirato1y droplet or transplacental. Virus is also excreted with saliva, urine, cervix and breast milk. Fetus is affected by transplacental route in about 30-40% cases. Unlike rubella, CMV may damage fetal organs throughout gestation. It is highest in third trimester (30-40%). Amongst all infected fetuses only 10% will suffer serious damage.
The consequences of infection (5-18%) include miscarriage, non-immune hydrops, stillbirth, IUGR, microcephaly, intracranial calcification, hepatosplenomegaly, thrombocytopenia, choroidoretinitis, mental retardation and sensorineural deafness

Fig. 20.4: Chickenpox in pregnancy: Eruption of rashes including papules, vesicles and pustules are seen on the face and the chest (trunk)

(common). Congenitally-affected infants may excrete virus (through urine and nasopharynx) for up to 5-7 years. Diagnosis: viral culture DNA PCR of urine and nasopharyngeal secretions. CMV specific IgM is present with 80% infected infants. Prenatal diagnosis by amniocentesis is possible using PCR to detect CMV DNA. A recombinant protein vaccine against CMV glycoprotein has been shown to prevent maternal CMV infection. Maternal CMV infection is best diagnosed by DNA PCR of blood, urine, saliva, amniotic fluid or cervical secretions. Routine screening for CMV in pregnancy is not recommended.
PARVOVIRUSES: Parvovirus B 19 (DNA) is associated with human infection (fifth disease) during pregnancy. Fetal affection is by transplacental route. Fetal infection occurs in 33% cases following maternal infection. Infection is characterized by facial rash (slapped cheek appearance). It mainly affects the etythroid precursor cells resulting in anemia, thrombocytopenia, aplastic crises, congenital heart failure and hydrops.
Fetal loss is more when infection occurs early ( <20 weeks) in pregnancy. Diagnosis is made by detection (ELISA) of virus specific IgM. PCR amplification of viral DNA from fetal and maternal blood is more sensitive than IgM antibody. Maternal infection is usually self-limited. Serial USG should be performed 10 weeks after maternal illness to detect any fetal hydrops. Fetal middle cerebral artery peak Doppler systolic velocity can be studied to detect any significant fetal anemia before hydrops develop. Intrauterine transfusion may improve the fetal outcome. Nearly 33% of fetal hydrops resolve spontaneously. Otherwise fetal mortality rate is about 10%. Fetal death is rare when maternal infection occurs beyond 20 weeks gestation.
MUMPS (RNA): Maternal mumps has got no ill-effects on the course of pregnancy. The virus is not teratogenic. Incidence is expected to be low with the introduction of Measles-Mumps Rubella (MMR) vaccine to childhood vaccination program. MMR vaccine (live-attenuated viruses) is contraindicated in pregnancy.
HERPES SIMPLEX (DNA) VIRUS (HSV): Infection may be primary, nonprimaty, first episode and recurrent. It is transmitted by sexual contact. Primaty infection may occur during pregnancy. Reactivation or recurrent infection occurs resulting in virus shedding with or without symptomatic lesions. HSV-1 infection is usually herpes simplex labialis (cold sores).
HSV-I infection presents as herpes simplex labialis. HSV-2 involves the genitals including vulva, vagina or the cervix. One third of HSV infected persons have no recurrences, one third have about 3 recurrences per year and another one third have more than 3 recurrences per year. Recurrent infections are less severe.
Effect on pregnancy-increased risk of miscarriage is inconclu sive. If the prima1y infection is acquired in the last trimester there is chance of premature labor or IUGR. Transplacental infection is not usual. The fetus becomes affected by virus shed from the cerix
or lower genital tract during vaginal delivery. The baby may be affected in utero from the contaminated liquor following rupture of the membranes. Local infections are: skin, eyes, mouth, lungs, liver and brains. Disseminated disease cause high morbidity and mortality complications may be hemorrhagic pneumonitis and DIC.
Risk of fetal infection is high in primary genital HSV at term due to high virus shedding compared to a recurrent infection. Cesarean delivery is indicated (ACOG) in an active primary
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genital HSV infection where the membranes are intact or recently ruptured. For primary infection: Acyclovir 400 mg TIO for 7 days or valacyclovir 1 g BID for 7 days is given. For primary infection, remote from term, daily suppressive therapy is given with Acyclovir from 36 weeks along with primary therapy. For recurrent infection acyclovir 800 mg BID for 5 days or valacyclovir 500 mg BID for 3 day is given.
Neonatal infection may be disseminated (fatal) or localized or it may be asymptomatic. Diagnosis is made by detection of the viral DNA by PCR. It is manifested as chorioretinitis, microcephaly, mental retardation, seizures and deaths. Neonatal HSV infection is treated with intravenous acyclovir. Neonatal mortality is high. Prophylactic acyclovir (400 mg twice daily) or valacyclovir (1 g twice daily) can reduce HSV shedding, neonatal transmission and cesarean delivery. Breastfeeding is allowed provided the mother avoids any contact between her lesions, her hands and the baby.
DENGUE: Dengue (RNA) virus is transmitted by Aedes aegypti mosquito. Infected pregnant women present with acute febrile illness, headache, myalgia, facial flushing, retro-orbital pain, skin rashes (maculopapular) and rarely with hemorrhage. Laboratory findings are: leukopenia, thrombocytopenia and elevated serum levels of AST or ALT >1000 U/L. Diagnosis is made by elevated levels of IgM (ELISA) or by antigen detection by ELISA or RT-PCR during the acute phase.
Triad of symptoms are: hemorrhagic manifestations, plasma leakage and platelet counts <100000/mm3. Maternal mortality is high, especially when shock syndrome develops (50%). Pregnancy complications are: miscarriage, preterm lab01; IUFD and stillbirths. Vertical transmission may occur but fetal affection is not severe.
Management: Supportive care. Maintenance ofintravascular volume, blood pressure and fluid replacement is to be done. Ribavirin may be useful, paracetamol is administered for control of pyrexia.

ZIKA VIRUS: It is a RNA virus and is a teratogen primarily transmitted by mosquito bite. Sexual transmission is also possible. The virus remains in body fluids for months. Clinical presentations: Skin rash, fever, arthralgia and conjunctivity is rarely with Guillain-Barre syndrome. There is high fetal infection (6%), mortality (7%) and rate of birth defects (5-15%). Congenital zika syndrome includes microcephaly; ventriculomegaly, intracranial calcifications and ocular anomalies. Women should be advised to postpone pregnancy if travelling to affected areas and for 28 days after return.
Management: Diagnosis is made by detection of Zika virus RNA in blood or urine by PCR. No specific treatment or vaccine is available. Prevention with mosquito netting and avoidance of sexual contact with partners recently exposed.

HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION AND ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)
H= ImmunodefideneyVI"" (HIV) rauses an
incurable infection that leads ultimately to a terminal '·, : disease called Acquired Immunodeficiency .. Syndrome (AIDS).

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Global estimate of HIV burden is 37 million and about 50% of them are women (CDC). The number of perinatally acquired HIV cases has decreased significantly. This is mainly due to the

improved care including: antenatal HIV testing, antiretroviral therapy for the mother and the newborn. The seropositivity rate among US pregnant women is 1-2 per 1000. Prevalence in India for women admitted for delivery is 0.1%. In UK it is 2.2/1000 women. In Sub-Saharan Africa it is 2-3%. Indian states with high rates of infection are: Andhra Pradesh, Tamil Nadu, Maharashtra and Karnataka.
The virus: HIV viruses (HIV 1 and HIV 2) are RNA retroviruses having the enzyme reverse transcriptase, which permits genomic RNA to be transcribed into double stranded DNA. Most cases of HIV throughout the world is caused by HIV-1 infection. HIV preferentially targets lymphocytes, monocytes, macrophages,
expressing CD4 molecules whose action in the immune system
is to combat viruses, bacteria and certain malignancies. There
is gradual depletion of CD 4 + cells. There is also failure of B
lymphocytes to produce antibodies to HIV. These events lead to progressive loss of host immune defence and development of AIDS. AIDS is defined by: • CD4 T-cell count <2000 cells/ µL. • CD4 T -cells are <14% of all lymphocytes or• Presence of one of several AIDS defining illness. Primary infection (3-6 weeks)➔ Acute syndrome (1 week-3 months)➔ Immune response to HIV
(1-2 weeks)➔ Clinical latency (about 10 years) ➔ AIDS.
The main modes of transmission of HIV are-{i) sexual contact (homosexual or heterosexual), (ii) transplacental, {iii) exposure to infected blood or tissue fluids and (iv) through breast milk.
Perinatal transmission of HIV: Vertical transmission to the neonates is about 14-25%. Transmission of HIV 2 is less frequent (1-4%) than for HIV 1 {15-40%). Transplacental transmission occurs: 20% before 36 weeks, over 80% of transmissions occur around the time of labor and delivery. Vertical transmission is more in cases with preterm birth and with prolonged membrane rupture. Risks of vertical transmission is directly related to maternal viral load (measured by HIV RNA) and inversely to maternal immune status (CD/ count). Maternal anti-retroviral therapy reduces the risk of vertical transmission by 70%. Breastfeeding doubles the risk of MTCT transmission (14-28%).
Male to female transmission is about double compared to female to male transmission. Rectal intercourse is more dangerous than vaginal. Parenteral transmission is the most potent route.
Immunopathogenesis: HIV mutates readily and produces several genotypes which are capable of immune control. Profound cell mediated immunodeficiency is the basic pathology. The incubation period is about 1-3 weeks. After a peak viral load, there is gradual fall until a steady state of virus concentration is reached. This is known as set point which is a state of balance between the virus's ability to replicate and the host's ability to protect itself by neutralization and removal of virus. When the set point viral
load is high➔ more destruction of host CD4+cells➔ progressive immunosuppression ➔ opportunistic infections and cancers.
Effects: Pregnancy per se has got no effect on the disease progression in HIV positive women. Increased incidence of abortion, prematurity, pre-eclampsia, IUGR and perinatal mortality in HIV seropositive mothers still remains inconclusive. Maternal mortality and morbidity are not increased by pregnancy.
Clinical presentation: Initial presentation of an infected patient may be fever, malaise, headache, sore
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy !D

throat, pharyngitis, arthralgia, lymphadenopathy and maculopapular rash. Primary illness may be followed by an asymptomatic period. Progression of the disease may lead to multiple Opportunistic Infections ( OI) with candida, tuberculosis, pneumocystis and others. Patient may present with neoplasms such as cervical carcinoma, lymphomas (Hodgkin's and non-Hodgkin's) and Kaposi's sarcoma. There may be associated constitutional symptoms like
weight loss, lymphadenopathy or protracted diarrhea. CD4 +
count <200 cells/mm3 is diagnostic of AIDS. The median time from infection to AIDS is about 10 years.
Diagnosis: HIV diagnosis is made by detecting HIV viral RNA in blood by PCR testing (HIV RNA PCR) or by detecting antibodies to HN (HN 1 and 2) and P-24 antigen. The Enzyme Immunoassay (EIA) is used as a screening test for HIV antibodies. It is extremely sensitive (99.5%), inexpensive but less specific. EIA kits are commercially available. An initial positive EIA test must be confirmed with a second, more specific test. This is confirmed by Western blot or, Immunofluorescence Assay (IFA) or HIV RNA PCR. The Western blot detects specific viral antigens P24 (Capsid), GP41 (envelope) and GP 120/160 (envelope). False-positive rate of Western blot is less than 1 in 10,000. Currently, screening with an HN-1/2 antigen/ antibody combination immunoassay or "Combo assay" is done. Confirmation is done with HIV-1/ HIV-2 antibody differentiation immunoassay and HIV-1 nucleic acid test (NAAT).
Laboratory monitoring: ( 1) In women conceiving on cART there should be a minimum of one CD4 cell count at baseline and one at delivery; (2) Who commence cART in pregnancy, a CD4 cell count should be performed as per routine initiation of cART with the addition of a CD4 count at delivery even if starting at CD4 >350 cells/mm3; (3) HIV viral load should be performed 2-4 weeks after commencing cART, at least once every trimester, at 36 weeks and at delivery; ( 4) Liver function tests (LFTs) should be performed as per routine initiation of cART and then with each routine blood test.
I MANAGEMENT
PRENATAL CARE
(i) Voluntary Counseling and Testing Center (VCTC) at the Antenatal Clinic (ANC) to all pregnant women with an 'Opt Out' approach is offered.
(ii) In seropositive cases the following additional tests should be done. (1) Test for other STDs-such as hepatitis B and C viruses, syphilis, Chlamydia, herpes and rubella, (2) Serological testing for cytomegalovirus and toxoplasmosis, (3) Tuberculosis, (4) Fungal opportunistic infections and (5) Husband should be offered serological testing for HIV.
(iii) Counseling with education to the patient is done about the impact of HIV infection on pregnancy; perinatal transmissions, side effects of medications and mode of delivety. Pregnancy does

not affect the progression of HIV disease. Advise for vaccination (pneumococcal, hepatitis, Tdap and influenza) given.
(iv) Progression of the disease is assessed by-CD4 + T
lymphocyte counts and HIV RNA (viral load). Assessment is done at every 3-4 months interval. A patient with low viral load (<3000 copies/mL) and high CD/ count (>750 cells/mm3) has nearly a zero probability of progressing to AIDS within 3 years.
Women with CD 4 + count (:5 350 cells/mm3) or HIV RNA level
?:50,000 copies/mm3 should be initiated with HAART (WHO).
Stages of HIV infection (CDC): Stage-I (HIV infection) CD/ T-lymphocyte ?:500/mm3; Stage-2 (HIV infection): CD/ T-lymphocyte count of 200-499/mm3; Stage-3 (AIDS): CD/ T-lymphocyte count of :5200/mm3•
( v) Principles ofHAART are: ( a) Suppress viral multiplication and reduced the viral load, (b) reduce perinatal transmission and (c) reduce the risk of drug resistance.
(vi) Prophylactic antibiotics should be started when there is opportunistic infection (Pneumocystis carinii pneumonia).
Anti-HIV I drugs are grouped into:
A. Nucleoside reverse transcriptase inhibitors [NRTis: Zidovudine (AZT), Lamivudine (3TC), Emtricitabine (FTC), Tenofovir (TDF)].
B. Non-nucleoside reverse transcriptase inhibitors [NNRTis: Nevirapine (NVP), Rilpivirine, Efavirenz (EFV)].
C. Protease inhibitors (PI: Atazanavir (ATV), Lopinavir, Ritonavir).
D. Integrase inhibitors: Raltegravir, Dolutegravir. Treatment regimens change frequently. However, recommended regimens are: Two from-Group A plus one from either group B or group C.
Cervical cytology screening is done as per guidelines
Recommended and Alternative Agents in Pregnancy: NRTI back bone (BHIVA-2020):
■ Recommended: • Abacavir/Lamivudine and • Tenofovir • Emtricitabane ■ Alternative: Zidovudine/Lamivudine.
■ Third agent: Efavirenz; Atazanavir. Alternative: Rilpivirine, Darunavir, Raltegravir, Dolutegravir ( after 6 weeks of gestation).
■ Integrase inhibitor based regimen are considered as third agent. PI monotherapy is not recommended in pregnancy.

■ HIV care needs a Multidisciplinary Team (MDT). ■ Laboratory monitoring: HIV resistance testing to be done before the start of treatment. ■ Women on Combined Antiretroviral Therapy (cART), viral load should be estimated 2-4 weeks after start of cART, once in each trimester, at 36 weeks and at delivery. Laboratory monitoring: (a) CD/ cell count, (b) Viral load (HIV RNA-PCR), (c) HIV genotype, (d) HIV resistance testing, (e) Complete Blood Count (CBC), platelet count, LFT, serum urea, creatinine, electrolytes, amylase and G6PD.

ANTENATAL CARE
■ First trimester USG and combined screening including the NIPT is done for fetal aneuploidies.
■ Invasive prenatal diagnostic testing is done when HN viral load is optimally suppressed to <50 HIV RNA Copies/mL.
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■ Diagnosed pregnant women should, start cARTsoon in the second trimester when the base line viral load is o;30,000 HIV RNA copies/mL; ■ cARTshould be started within the first trimester if viral load >100,000 RNA copies/mL and or CD4 cell count is less than 200 cells/mm3• ■ Start cART in all women by 24th week. ■ ART after delivery not to be stopped and women need to be counseled.
■ Women taking HAART can have planned vaginal delivery when plasma viral load is <50 HIV RNA copies/mL measured at 36 weeks (RCOG-2019).
■ Such women can have induction or augmentatation of labor when she has SROM. Delivery should be aimed within 24 hours of SROM.
INTRAPARTUM CARE
Management of an untreated women in labor at term: She should be given a start of nevirapine 200 mg, zidovudine 300 mg, lamivudine 150 mg bd and raltegravir 400 mg bd and to administer injection zidovudine IV for the duration of labor.
♦ Elective cesarean delivery reduces the risk of vertical trans mission by about 50%. Avoidance of breastfeeding, HAART therapy and appropriate mode of delivety has reduced MTCT rates from 25-30% to < 1%. Baby may be bathed immediately.
♦ Planned cesarean delivery is recommended (RCOG-2019) at 39 weeks for women taking HAART who have plasma viral load >50 mcopies/mL measured at 36 weeks.
♦ Amniotomy and oxytocin augmentation for vaginal deliv ery should be avoided whenever possible.
♦ Invasive procedures that might result in break in the skin or mucous membrane of the infants (procedures like attachment of scalp electrode and determination of scalp blood pH) are contraindicated. Instrumentation (ventouse) is avoided.
♦ Delayed cord clamping is safe and reduces neonatal anemia. ♦ Intrapartum IV ZDV is not advised for women receiving ART
regiments with HIV RNA copies <50/mL near delivery.
♦ Perioperative or peripartum broad spectrum antibiotics should be given as per hospital protocol.
♦ Caps, masks, gowns and double gloves (PPE kits) should be worn. Protective eyewear (goggles) should be used.
♦ Blunt tipped needles should be used to avoid needle stick injury and washing on any blood contamination from the skin immediately. Appropriate sterilization of instruments and linens should be done.
♦ Risk factors for increased perinatal transmission are:
(a) Maternal high plasma (f) Invasive intrapartum viral load. procedures,
(b) Low CD4 cell count. (g) Preterm delivery,
(c) Co-existing other STDs (h) Vaginal delivery and and opportunistic infec-
tions
(d) Prolonged rupture of (i) Breastfeeding. membranes,
(e) Chorioamnionitis,

♦ Healthcare workers should be protected from contact with potentially infected body fluids. Estimated risk of infection after parenteral or mucous membrane exposure is 0.36%.
♦ Postexposure prophylaxis with triple therapy for 4 weeks, reduces the risk of seroconversion by more than 80% (ZDV 200 mg tid+ Lamivudine 150 mg bid+ Indinavir 800 mg tid).

♦ Disposable syringes and needles are used and they are deposited in the puncture proof containers.
♦ Intravenous Zidovudine: Should be administered to women when HIV RNA is known or suspected to be > 1,000 copies/ mL (or if HIV RNA is unknown➔ mainly untreated woman) near delivery (spontaneous labor/SROM/PLCS).
♦ Side effects of cARTare: Antiretroviral drugs need monitoring. Neuropathy, myopathy, lactic acidosis, pancreatitis, hepatitis and mitochondrial toxicity have been observed.

POSTPARTUM CARE
■ Women should continue HAART with CD4 count. This
reduces morbidity and mortality due to HIV. She should be followed up according to adult guidelines.
■ Neonatal care: Antiretroviral Therapy (ART) should be given to all neonates regardless of breastfeeding within 4 hours of birth. Usually ZDV or lamivudine monotherapy is started. When HIV RNA viral load tests are negative and the baby is not breastfed a confirmatory HIV antibody test is done at 18 months. Once this test is negative, the child is declared to be free of HIV.
■ Infant feeding: 11 Women living with HIV may feed their babies with formula milk (high income settings).
ll Women on cART who choose to breastfeed is allowed to do so. She is informed about the low risk of transmission of HIV through breastfeeding.
ll The women and her infant need monthly review for HIV RNA viral load testing during and for 2 months after stopping breast feeding. Maternal cART helps to minimize HIV transmission through breast milk and also protects the women. WHO recommends exclusive breastfeeding.
11 For very low-risk women: All the 3 criteria met: (1) The woman has been on cART for longer than 10 weeks; (2) 2 documented maternal HIV VL <50 HIV RNA at least 4 weeks apart; (3) Maternal VL <50 HIV RNA at or after 36 weeks: Two weeks ofzidovudine monotherapy.
11 For low-risk women: All the 3 above criteria not met, but maternal HIV viral load is <50 HIV RNA copies/mL at or after 36 weeks. OR if the infant is born prematurely ( <34 weeks) but most recent maternal HIV viral load is <50 HIV RNA copies/ mL: 4 weeks ofzidovudine monotherapy.
11 For high-risk women: Maternal birth VL is >50 on day of birth: Combination PEP given within 4 hours.

CONTRACEPTIVE COUNSELING AND CARE
• Barrier methods of contraception (condom or female condom) is effective in preventing transmission of the virus.
• COCs are avoided as drug interactions with ARV agents affect their eficacy and safety.
• IUCD (Copper IUCD and LNG-IUS) are found safe and effective.
• Implants and injectables can be safely used.
• However, condom use should be continued regardless of the use of other method of contraception. The disease could be prevented predominantly by health education and by practice of safer sex.
COUNSELING: Prepregnancy, pregnancy and postpartum counseling for HIV infected patient is essential. The woman needs ongoing care with a multidisciplinaty team including social workers and counselors. The counselor must provide up to date knowledge which enables the patient to make an informed choice.
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

Strategy to reduce MTCT (NACO): (a) Primary prevention, {b) Preventing unintended pregnancy in HIV infected women, (c) Preventing MTCT during pregnancy and {d) Treatment and care of infected women.
COVID INFECTION IN PREGNANCY