notes/DC Dutta Obstetrics 10th Edition_8.txt

Labor duration is curtailed by low rupture  of the membranes in the first stage; and forceps or ventouse in second stage. Injection oxytocin 10 IU IM following the delivery of the baby is given to the mother.
POSTPARTUM MANAGEMENT: •  The  patient is to  be watched closely for at least 48 hours, the period during which convulsions usually occur. • Antihypertensive drug treatment should be continued if the BP is high (systolic >150 mm Hg or diastolic >100 mm Hg).• Oral nifedipine 10 mg at every 6 hours is given until BP remains below the hypertensive levels for at least 48 hours. • Oral frusemide 20 mg a day for 5 days is also found to improve recovery and to reduce the need of antihypertensive drugs in severe pre-eclampsia. • Magnesium sulfate (for at least 24 hours) and antihypertensive drugs to be continued in women with severe hypertension. These patients are at increased risks  of  eclampsia,  pulmonary  edema  and  stroke. The patient is to be kept in the hospital, till the blood pressure is brought down to a safe level. In breastfeeding women, labetalol, nifedipine or enalapril may be used on discharge. Methyldopa is avoided due to the risks of
postpartum depression.

GESTATIONAL HYPERTENSION (GH)

A sustained rise of blood pressure to 140/90 mm Hg or more (without proteinuria) on at least two occasions 4  or  more  hours   apart   beyond   the  20th  week  of pregnancy or within the first 48 hours of delivery in a previously normotensive woman is called gestational hypertension.  It  is  associated  with  a  much  higher incidence  of  essential hypertension  in  later  life  than pre-eclampsia. Both  (PE and GH)  thus  appear to be two phases of the same disorder. It should fulfill the following criteria:

1. Absence of any evidences for the underlying cause of hypertension.
2.  Generally  unassociated  with  other  evidences  of preeclampsia (edema or proteinuria).
3. Majority of cases are  37 weeks of pregnancy.
4.  Generally  not  associated  with  hemoconcentration or thrombocytopenia, raised serum uric acid level or hepatic dysfunction.
5.  The  blood pressure should  come down to normal within 12 weeks following delivery.
6. However, in  25% of women with gestational HTN
may go to proteinuric phase and may evolve to pre­ eclampsia. It is a retrospective diagnosis.
The hypertensive effect may be a stress response. There are no longer any real differences in management between  PE  and  gestational  HTN,  in  terms  of  BP management and in the decision to deliver. A case of severe HTN, with appearance of symptoms or abnormal laboratory values, suggests delivery.
Severe GH is defined as systolic BP  160 mm Hg or diastolic BP  110 mm Hg on at least two occasions at least 4 hours apart or once if acute antihypertensive drugs are used prior to 4 hours.
Gestational proteinuria is the presence of protein of more than 0.3 g in the 24 hours urine during or under the influence of pregnancy in the absence of hypertension, edema  or   renal  infection.  It   may   be   orthostatic proteinuria. Patient may be evaluated with blood tests and frequent BP monitoring to exclude pre-eclampsia.

ACUTE FULMINANT PRE-ECLAMPSIA (Synonym: Pre-eclamptic State)
It is a clinical entity where the onset of the pre-eclamptic manifestations is acute, occurring de nova or there is rapid deterioration in an established case of pre-eclampsia with severe hypertension over a short period of time. There is a constant threat of convulsion, cerebral hemorrhage, cardiac failure, pulmonary edema or placental abruption. All the features of severe pre­ eclampsia are intensified.

TREATMENT: Detected at home, or at a primary health care facility, the patient should be adequately sedated by  midazolam  1-2  mg IV,  may  be  repeated  in  5-10 minutes time or diazepam 10 mg IV (slow). Prophylactic magnesium sulfate should be given before transfer.
She should be shifted with an attendant doctor or a midwife, during the journey to the hospital.
In the hospital, the patient is to be kept in eclampsia
room    under    close    supervision.   Prophylactic anticonvulsant therapy is to be continued  (Magpie Trial-2002). Administration of magnesium sulfate IM or IV regimen in a dose schedule as mentioned in the treatment of eclampsia is recommended. The blood pressure is to be stabilized by antihypertensive drugs given parenterally. First-line antihypertensives are: (a) Labetalol (IV) or
Chapter 18: Hypertensive Disorders in Pregnancy     ml'

{b)  Hydralazine (IV) need to be started. Response to treatment should be watched carefully noting frequently the  blood  pressure,  urinary  output,  proteinuria  and hematological parameters (Table 18.2).
Obstetric  management:  As  there  is  a  constant threat of eclampsia, maternal interest should always be considered.  In  cases  with  pregnancy  beyond  37 completed weeks or where the condition fails to improve within a reasonable period  (say  6-8 hours),  delivery should be seriously considered irrespective of period of gestation (Box  18.5). Termination (delivery) is done either by low rupture of the membranes aided by oxytocin infusion or  by  cesarean  section  depending  upon  the
severity of the condition and state of the cervix. PGE2  gel may help in cervical ripening. Corticosteroid is given if
pregnancy is <34 weeks (Boxes 18.3 and 18.4).
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• Pulse, blood pressure, respiratory     Every 10-30 minutes. rate, SaO2_

superimposed  on  essential  hypertension  or  chronic nephritis.
INCIDENCE: The incidence varies widely  from country to country and even  between  different  zones  of  the same  country.  Eclampsia contributes significantly  to the maternal  deaths. The hospital incidence in India ranges from 1 in 500 to 1 in 30. It is more common in primigravidae (75%),  five times more common in twins than in singleton pregnancies and occurs between the 36th week and term in more than 50% cases.
PATHOPHYSIOLOGY: Since eclampsia is a severe form of pre-eclampsia, the histopathological and biochemical changes are similar; although, intensified than those of pre-eclampsia as already described.
CAUSE OF CONVULSION: The cause of cerebral irritation leading to convulsion is not clear. The irritation may be provoked by:
1. Anoxia-spasm of the cerebral vessels ➔ increased cerebral vascular resistance ➔ fall in cerebral oxygen consumption ➔ anoxia.
2.  Cerebral edema-may contribute to irritation.



■   Temperature, lung sounds.
■   Deep tendon reflexes, level of


Every 2 hours.
Every 4 hours.

3.  Cerebral dysrhythmia-increases following anoxia or edema.



consciousness, assessment of headache, visual disturbances, epigastric pain.
■   Intake and output record.	 Intake IV crystalloids (normal saline),  colloids  (albumin, blood), total sl 25 ml/h.
II     Fetal monitoring (antenatal and	Continuous EFM. intrapartum).
According to gestational age, pre-eclampsia may be: (A) Early: <34 weeks and (BJ Late >34 weeks



■   Persistent symptoms of severe pre-eclampsia.
■   Pulmonary edema/hypoxia (PaO2  <95%).
11      Hepatocellular injury: Increased AST, ALT (x twice the normal).
■   Oliguria <500 ml/24 hours. 11  Persistent cerebral symptoms. ■   Abnormal coagulation profile.
11      FGR with non reassuring fetal status.
11   Eclampsia. 11  Serum creatinine >1.1 mg/dl. ■   UA-Doppler: REDF.

ECLAMPSIA

The  term  eclampsia  is  derived  from  a  Greek  word, meaning 'like a flash of lightening'. It may occur quite abruptly, without any warning manifestations. In majority (over 80%), however, the disease is preceded by features of severe pre-eclampsia.
Pre-eclampsia when complicated with grand mal seizures (generalized tonic-clonic convulsions) and/or coma is called eclampsia. Thus, it may occur in patients with pre-eclampsia or in patients who have pre-eclampsia


4.  Excessive release of excitatory neurotransmitters (glutamate).
5.  Loss of cerebrovascular autoregulation with forced dilatation and vasospasm.
ONSET  OF FITS: Fits occur more commonly in the third trimester  (>50%).  On rare occasions,  convulsion may occur in early months as in hydatidiform mole.
11    Antepartum (50%):  Fits  occur  before  the onset of labor. More often, labor starts soon after and at times, it is impossible to differentiate it from intrapartum ones.
ll    Intrapartum (30%): Fits occur for the first time during labor.
fJ    Postpartum  (20%):  Fits occur for  the  first  time in puerperium, usually within 48-72 hours of delivery. Fits occurring beyond 48 hours but less than 4 weeks after delivery is accepted as late postpartum eclampsia.
a  Intercurrent (antenatal): When the patient becomes conscious after  recovery from convulsions and the pregnancy continues beyond 48 hours. The time limit is arbitrary as a period of 7-10 days has  also been mentioned.
Cerebral pathology includes cortical or subcortical edema, infarction and hemorrhage. The neurological abnormalities are often due to hypoxia, ischemia or edema. Several neurodiagnostic tests, e.g., EEG, CT, cerebral Doppler velocimetry, MRI, MRI angiography reveal presence of edema and infarction. Findings are similar to those as seen in hypertensive encephalopathy. Cerebral imaging (MRI) indicated when there is focal n eurologic deficits, prolonged coma or atypical presentation for eclampsia (Fig. 18.1). The important findings are: Patchy and diffuse areas of low density, white matter edema (occipital lobe) and areas of cerebral hemorrhage and infarctions.
-- ---fm Chapter 18: Hypertensive Disorders in Pregnancy I CLINICAL FEATURES
Except on rare occasions, an eclamptic patient always shows manifestations of acute fulminating preeclamp­ sia-called premonitory symptoms.
Eclamptic convulsion or fit: The fits are epileptiform and consist of four stages.
1.  Premonitory stage: The patient becomes unconscious. There is twitching of the muscles of the face, tongue and limbs. Eyeballs roll or are turned to one side and become fixed. This stage lasts for about 30 seconds.
2.  Tonic stage: The whole body goes into a tonic spasm-the trunk-opisthotonus, limbs are flexed and hands clenched. Respiration ceases and the tongue protrudes between the teeth. Cyanosis appears. Eyeballs become fixed. This stage lasts for about 30 seconds.
3.  Clonic stage: All the voluntary muscles undergo alternate contraction and relaxation. The twitchings start in the face then involve one side of the extremities and ultimately the whole body is involved in the convulsion. Biting of the tongue occurs (Fig. 18.4). Breathing is stertorous and blood stained frothy secretions fill the mouth; cyanosis gradually disappears. This stage lasts for 1-4 minutes.
4.  Stage of coma: Following the fit, the patient passes on to the stage of coma. It may last for a brief period or in others deep coma persists till another convulsion. On occasion, the patient appears to be in a confused state following the fit and fails to remember the happenings. Rarely, the coma occurs without prior convulsion.
The  fits  are usually multiple,  recurring at varying intervals.  When it occurs in quick succession, it is called status eclampticus. Following the convulsions, temperature usually rises;  pulse and respiration rates are  increased  and  so  also  the  blood  pressure.  The urinary output is markedly diminished;  proteinuria is pronounced, and the blood uric acid is raised.
DIFFERENTIAL DIAGNOSIS:  The  diseases,  which  are associated with convulsions and/or coma are to be borne in mind while arriving at the diagnosis of eclampsia. Such diseases are:
















Fig. 18.4: Extensive tongue bite injury following an eclamptic convulsion. It usually occurs in clonic stage.




1.  Epilepsy (seizure	6. Cerebral venous thrombosis. disorders).	7. Hypertensive
2.  Hypoglycemia.	encephalopathy.
3.  Encephalitis.	8. Cerebral malaria in tropics. 4.  Meningitis.	9. Intracranial tumors.
5.  PRES.	10. HIE.
Absence  of  previous  history  of  convulsion  with presence of edema, hypertension and proteinuria along with fits or coma during pregnancy or soon after, points to the diagnosis of eclampsia. In doubtful cases,  it is desirable to place the patient in the obstetric unit for observation until the final diagnosis is made.
I PROGNOSIS
MATERNAL: Immediate: Once the convulsion occurs, the prognosis becomes uncertain. Prognosis depends on several factors: (1) Long interval between the onset of fit and commencement of treatment (late referral). (2) Antepartum eclampsia especially with early onset ( <28 weeks). (3) Number of fits more than ten. (4)  Coma in between fits. (5) Temperature over 102°F with pulse rate above  120/minute. (6) Pulmonary edema.  (7) Oliguria (<400 mL/24 hours) with proteinuria >5 g/24 hours. (8) Nonresponse to treatment. (9) Jaundice.
Mortality: Maternal mortality in eclampsia has been reduced significantly in India (2-20%). Prevention and treatment of pre-eclampsia with severe features and early treatment for eclampsia are the important measures.
Causes  of  maternal  deaths:  (1)  Cardiac  failure. (2)  Pulmonary edema.  (3) Aspiration and/or septic pneumonia. (4) Cerebral hemorrhage.  (5) Acute renal failure. (6) Cardiopulmonary arrest. (7) Adult Respiratory Distress  Syndrome  (ARDS).  (8)  Pulmonary embolism. (9) Postpartum shock.  (10) HELLP syndrome (Tables 18.6 and  18.7).  Maternal complications are  higher in antepartum eclampsia.
Remote: If the patient recovers from acute illness, she is likely to recover rapidly within 2-3 weeks. Recurrence of eclampsia in subsequent pregnancies is uncommon; although, chance of pre-eclampsia is about 30%.
FETAL: The perinatal mortality is high to the extent of about 10-20%. The causes are:
1.  Prematurity-spontaneous or induced.
2.  Intrauterine asphyxia due to placental insufficiency arising out of infarction, retroplacental hemorrhage.
3.  Effects of the drugs used to control convulsions.

I MANAGEMENT
PREDICTION AND PREVENTION: In majority of cases, eclampsia is preceded by severe pre-eclampsia. Thus the prevention of eclampsia rests on early detection and effective institutional treatment with judicious termination of pregnancy during pre-eclampsia. However, eclampsia
Chapter 18: Hypertensive Disorders in Pregnancy



■  Injuries: Tongue bite, injuries due to fall from bed, bed sore.
■  Pulmonary complications:
•  Edema-due to leaky blood capillaries. •  Pneumonia-due to aspiration,
hypostatic or infective.
• Adult  respiratory  distress  syndrome. •  Embolism.
■  Hyperpyrexia.


•  Cardiac-acute left ventricular failure.
•  Cardiomyopathy. ■  Renal failure.
11      Hepatic-necrosis, subcapsular hematoma.
■  Cerebral-edema (vasogenic) hemorrhage.
■   Neurological deficits

■  Disturbed vision-due to retinal detachment or occipital lobe ischemia (Fig.18.1).
11      Hematological:
•  Thrombocytopenia.
• Disseminated intravascular  coagulopathy. ■  Postpartum:
• Shock. • Sepsis.
• Psychosis.


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Intravenous (Zuspan or Sibai)
Low dose (Chowdhury-Dhaka)

4 g (20% solution) IV over 3-5 minute followed by 10 g (50%), deep IM (5 g in each buttock).
4-6 g IV slow over 15-20 minute.
4 g (20%) IV slow over 15 min, followed by 3 g (50%) IM in each buttock.


5 g (50%) IM 4 hourly in alternate buttock.
1-2 g/h IV infusion.
2.5 g IM 4 hourly in alternate buttock.




can occur bypassing the pre-eclamptic state (20-40%) and as such, it is not always a preventable condition. Eclampsia may present in atypical ways; hence, it is at times difficult to predict. Use of antihypertensive drugs, prophylactic anticonvulsant therapy and timely delivery are important steps. Close monitoring during labor and 24 hours' postpartum is also important in prevention of eclampsia. Magpie trial (2002) showed prophylactic use of magnesium sulfate lowers the risk of eclampsia.
FIRST AID TREATMENT  OUTSIDE  THE HOSPITAL:  The patient, either at home or in the peripheral health centers should be shifted urgently to the referral care hospitals. There is no place of continuing  the treatment in  a primary care hospital. Transport of an eclamptic patient to a tertiaiy care center is important. The medical team at the tertiary care hospital should be informed beforehand.
Such a patient needs neonatal and obstetric intensive care management. Important steps in transport are:
11    All maternal records and a detailed summary should be sent with the patient.
11    BP  should be stabilized and convulsions should be arrested.
11    Magnesium sulfate  ( 4 g IV  loading dose with  10 g IM) is given. Labetalol 20 mg IV is given to control hypertension. Diuretic is given if there is pulmonary edema.
11     One medical personnel or a trained midwife should accompany the patient in the ambulance equipped to prevent injury, recurrent fits and to clear air passage (Box 18.5).
GENERAL MANAGEMENT  {MEDICAL  AND  NURSING) (Box 18.5)
♦  Supportive care: (i} To prevent serious maternal injury from  fall,  {ii}  prevent aspiration,  (iii}  to  maintain airway and (iv) to ensure oxygenation.


 • {,  18.5: Medical managementof eclam sJ ;-l!l'.i  la  !le   reJ.' C
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♦   Call for extra help (communication).
♦   Control of seizures: MgS04, (IV/IM regimens).
♦  To put patient in left lateral recumbent position. ♦   Maintain oral airway.
♦  02 inhalation-nonbreather mask; 10 Uminute.
♦  Commence IV lines; 1 or 2 wide bore cannulas. ♦   Foley catheter with urometer.
♦  To monitor 02 saturation; Pulse 0ximeter (SP02 >95%).
+  To monitor vitals; fetal status and magnesium toxicity.
♦   Control of hypertension-labetalol, hydralazine (Table 18.3).
♦   Fluids-crystalloids (saline) or colloids (albumin/blood) ,;125 mUh. ♦   Suction-oropharyngeal.
♦   Diuretics-pulmonary edema.
♦   Investigations to organize: Blood-CBC, AST, ALT, LDH, creatinine, uric acid, urine analysis-protein.
♦   For obstetrical management.
♦  To prevent injury (tongue bite/fall). ♦  To prevent complications.
♦  To deliver by 6-8 hours. ♦   Postpartum care.

Patient is kept in an intensive care facilities with a railed cot and a tongue blade is inserted between the teeth. She is kept in the lateral decubitus position to avoid aspiration. Vomitus and oral secretions are removed by  frequent  suctioning,  oxygenation  is  maintained through  a  face  mask  (8-10  L/minute)  to  prevent respiratory acidosis. Oxygenation is monitored using a  transcutaneous pulse oximeter. Arterial blood gas
analysis is needed when 02 saturation falls below 92%.
The patient should have a doctor or at least a trained midwife for constant supervision.
♦    Detailed history is to be taken from  the relatives, relevant to the diagnosis  of eclampsia,  duration of pregnancy, number of fits and nature of medication administered outside.
-  ··•·ml Chapter 18: Hypertensive Disorders in Pregnancy

♦   Examination:  Once  the  patient  is  stabilized,  a thorough but quick general, abdominal and vaginal examinations are made. A self-retaining catheter is introduced and the urine is tested for protein. The continuous drainage facilitates measurement of the urinary output and periodic urine analysis.
♦    Monitoring: Half hourly pulse, respiration rate and blood pressure are recorded. Hourly urinary output is to be noted.  If undelivered, the uterus should be palpated at regular intervals to detect the progress of labor and the fetal heart rate is to be monitored. Immediately after a convulsion, fetal bradycardia is common.
♦    Fluid balance: Crystalloid solution (Ringer's solution) is started as a first choice.  Total  fluids  should not exceed the previous 24 hours urinary output plus 1000 mL (insensible loss through lungs and skin). Normally,  it should not  exceed 2  liters in 24 hours. Infusion of balanced salt solution should be at the rate of 1 mL/kg/h.  In pre-eclampsia-eclampsia although there is hypovolemia, the tissues are overloaded. An excess of dextrose or crystalline solutions should not be used as it will aggravate the tissue overload leading to pulmonary  edema  and  adult respiratory distress syndrome. Colloids (albumin or hemaccel) remain in the vascular  tree and they withdraw fluids from the interstitial space. Unless used carefully,  they can lead to circulatory overload. CVP monitoring is needed for a patient with severe hypertension and reduced urine output.  In pre-eclampsia,  eclampsia,  both the PCWP and  CVP  appear  to  be  in  the  low  to  normal  range.
Invasive hemodynamic monitoring is rarely indicated. +  Antibiotic: To prevent infection, ceftriaxone 1 g IV
twice daily is given.


For IV administration, concentration of Mg504  should not exceed
20%. One part of 50% Mg504 injection is diluted with 1.5 parts of
water for injection to make it 20%. It is then given   IV slowly.

Repeat injections are given only if the knee jerks are present, urine output exceeds 30 mL/h and the respiration rate is more than 12/minute. The therapeutic level of serum magnesium is 4-7 mEq/L. Serum magnesium levels  may  be  monitored  in  selected  cases  (renal insufficiency, absent deep tendon reflexes).
Prevention/management of complications:
•   Calcium gluconate is administered as an antidote to severe cardiac toxicity related to hypermagnesemia.
•   Magnesium toxicity: This is uncommon in women with adequate renal function. Toxicity correlates with level of serum magnesium concentration (Box 18.6).
Contraindications  of  MgS04:  Myasthenia,  gravis,
moderate to severe renal failure, cardiac ischemia, heart block, myocarditis.
Seizure prophylaxis of MgS04: Therapeutic range is
4-8 mEq/L (5-9 mg/dL; 2-3.5 mmol/L). Patients with high BMI need high dose.
To control fits, optimum serum magnesium level 4.8-8.4 mg/ dL ( 4-7 mEq/L) is to be maintained. Serum magnesium levels to be measured when serum creatinine is ,_l mg/dL.
Calcium gluconate is the antidote to cardiac toxicity due to hypermagnesemia.
Magnesium sulfate is continued for 24 hours after the last seizure or delivery whichever is later. For recurrence of fits, further 2 g IV bolus is given over 5 minute in the above regimens. If the patient seizes, despite magnesium therapy,  midazolam 1-2 mg IV  is  given  (and  may  be repeated in 5-10 minutes time) (Boxes 18.7 and 18.8).



SPECIFIC MANAGEMENT: Anticonvuisant regime: The aim is to control the fits and to prevent its recurrence. In areas where eclampsia is frequently encountered, it is obvious that the obstetric care is inadequate. In such circumstances any complicated regime is unlikely to give good result.


Loss of deep tendon reflexes.
Respiratory depression.
Altered cardiac conduction.


?.7 mEq/L

.?.10 mEq/L
?.15 mEq/L


>9 mg/dl

>12 mg/dl
>17 mg/dl


>3.5 mmol/L

>5 mmol/L
>7 mmol/L



•   Magnesium sulfate is  the  drug of  choice  (Table 18. 7).  It  acts  as  a  membrane  stabilizer  and neuroprotector. It reduces motor endplate sensitivity to  acetylcholine.  Magnesium  also  blocks  neuronal calcium influx. The other mechanism of actions are: ( a) decreased presynaptic release of neurotransmitter glutamate  {b) receptor  blockage  for  glutamatergic
N-Methyl-D-Aspartate  (NMDA),  (c) activation  of adenosine action. It induces cerebral vasodilatation, dilates uterine arteries,  increases  production  of endothelial  prostacyclin   and   inhibits  platelet activation. It has no detrimental effects on the neonate within therapeutic level. It has got excellent result with maternal mortality of 3%. However, it does not control hypertension.


Cardiac arrest.	?.25 mEq/L    >30 mg/dl     > 12.5 mmol/L



+   Loss of deep tendon reflexes.
+   Decreased respiration rate (<16 per minute). +   Urine output (<30 ml/h).
+   Chest pain, heart block, pulmonary edema. +   02 saturation monitoring (Pa02  <95%).

· Box 18.8: Man gement for magnesium t0><icity.
+  To stop magnesium therapy.
+   Estimation of serum magnesium and creatinine levels.
+   Injection calcium gluconate 10 ml (10% solution), IV slowly.
+   Fluid loading and forced diuresis.
Chapter 18: Hypertensive Disorders in Pregnancy    ED

Other regimens are: (1) Lytic cocktail (Menon 1961) using  chlorpromazine,  promethazine  and  pethidine. (2) Diazepam (Lean) and (3) Phenytoin. Compared to other regimes, magnesium sulfate has got the following benefits:   (i)   It  controls  fits  effectively  without  any depression effect to the mother or the infant, (ii) reduced risk  of  recurrent  convulsions  (9%),  (iii)  significantly reduced  maternal  death  rate  (3%)  and  (iv)  reduced perinatal mortality rate.
Antihypertensives   and   diuretics:   In   spite   of anticonvulsant regime, if the blood pressure remains more than 160/110 mm Hg, antihypertensive drugs should be administered. First-line of antihypertensive drugs are: labetalol  and hydralazine  (ACOG-2011).  Target level of BP is SBP: 140-160 mm Hg and DBP: 90-100 mm Hg. Labetalol 20 mg IV is given. Repeat doses may be needed after an interval of 10 minutes. Alternatively hydralazine 5 or 10 mg IV is given. Repeat dose may be needed if no response occurs after 20 minutes time.
Presence  of pulmonary  edema  requires diuretics. In such cases,  the potent one (furosemide) should be administered in doses of 20-40 mg intravenously and to be repeated at intervals.
Management during fit: (a) In the premonitory stage, a mouth gag is placed in between the teeth to prevent tongue bite and should be removed after the clonic phase is over. (b) The air passage is to be cleared off the mucus with a mucus sucker. The patient's head is to be turned to one side and the pillow is taken off. (c) Oxygen is given until cyanosis disappears.
Status  eclampticus:  Thiopentone  sodium  0.5  g dissolved in 20 mL of 5% dextrose is given intravenously very slowly. The procedure should be supervised by an expert anesthetist. If the procedure fails, use of complete anesthesia, muscle relaxant and assisted ventilation may be employed. In unresponsive cases, cesarean section in ideal surroundings may be a lifesaving attempt.

INDICATIONS OF INTUBATION
■   Patient remains unconscious in    ■   Signs of aspiration. post-seizure period.                        ■   Persistent hypoxia.
11      Seizures not controlled.

Prevention and treatment of complications  (Tables 18.4 and 18.5): Patient needs intensive care management. Prophylactic  use  of  antibiotics  markedly  reduce  the complications like pulmonary and puerperal infection.
Pulmonary edema: Furosemide 40 mg IV followed by 20 g of mannitol IV reduces pulmonary edema and also  prevents  adult  respiratory  distress  syndrome. Pulse oximeter is very useful to monitor such a patient. Aspiration of the mucus from the tracheobronchial tree by a suction apparatus is done.
Heart failure: Oxygen inhalation, parenteral lasix and digitalis are used.

Anuria: The treatment should be in the line as formu­ lated in Ch. 39. Dopamine infusion (1 mg/kg) is given with oliguria when CVP is above 8 mm Hg. It is often surprising that urine output returns to normal following delivery.
Hyperpyrexia:  It  is  difficult  to  bring  down  the temperature  as it is central in origin.  However,  cold sponging and antipyretics may be tried.
Intensive care monitoring: Patient with multiple organ dysfunction needs to be admitted in an intensive care unit. Multidisciplinary approach: Obstetrician, obstetric nurse, anesthesiologist, neonatologist, intensive care unit team should be involved. Cardiac, renal or pulmonary complications are managed effectively. Neuroradiologic imaging is strongly advised in the postpartum period for cases with neurologic symptoms and focal deficit.
OBSTETRIC MANAGEMENT (Flowchart 18.3): During preg­ nancy: In majority of cases with antepartum eclampsia, labor starts soon after convulsions. But when labor fails to start, the management depends on-(i) whether the fits are controlled or not and (ii) the maturity of the fetus. The decision to deliver is made once the woman is stable. Epidural anesthesia can be used during labor and delivery. 11    Fits controlled:
- Pregnancy ( 34 weeks): Delivery should be done.
a.   Cervix is favorable and there is no contraindication of vaginal delivery,  surgical induction by low rupture of the membranes is done. Oxytocin drip may be added, if needed.
b.  When the cervix is unfavorable, cervical ripening with PGE  gel or pessary could be achieved before ARM.
2
c.   Cesarean delivery is done for obstetric indications (malpresentation).
- Pregnancy (s34 weeks): Delivery is recommended in a set up with Neonatal Intensive Care Unit (NICU). Recurrent convulsions may  cause  IUFD.  Steroid therapy is given when pregnancy is less than 34 weeks.  Conservative management  at  an  early pregnancy may improve perinatal outcome but this must be carefully balanced with maternal wellbeing (RCOG-2006).
- Baby dead: The pre-eclamptic  process gradually subsides and eventually expulsion of the fetus occurs. Othe1wise medical method of induction is started.
11    Fits not controlled: If the fits are not controlled with anticonvulsant within a reasonable period (6-8 hours), termination of pregnancy should be done. Low rupture of the membranes is done. Oxytocin infusion may be added. The uterus responds well to oxytocin in such cases.  In presence of unfavorable factors,  cesarean delivery is done.
Following delivery: 10 units of oxytocin IM or IV slowly given.  One should remain vigilant about postpartum hemorrhage.
Indications of cesarean section: (i) Eclampsia before 30 weeks gestation with unfavorable cervix. (ii) Uncontrolled
BI Chapter 18: Hypertensive Disorders in Pregnancy
Flowchart 18.3: Scheme of obstetric management of eclampsia.

Initial control of seizures, Patient stable (cardiovascular and pulmonary) to continue medical management (see p. 223)

OBSTETRIC MANAGEMENT
i

Clinical assessment of patient and the fetal status


Not in labor	Epidural labor analgesia	In labor (majority)
i







Term
t


Delivery


Fits controlled

Baby
t
l
Preterm
t

Steroid therapy

Delivery

• Fits not controlled and/or
• Non-reassuring fetal status

Delivery


Dead	CS
I


I Introduction
of labor

ARM ±     ytocin r

Forceps/ventouse
+

Delivery

CS obstetric indication




Induction
• PGE  gel
2
•ARM
• Oxytocin (±)
i

cs	Delivery Obstetric
indication
l


Postpartum care (see p. 220) I	j Postpartum care (see p. 220)


+ Neonatal resuscitation. + MgSO4 to be continued for another 24 hours following delivery or after the last seizure whichever
is later. +  Neuroradiologic imaging (CT/MRI) to be done in the postpartum period for cases with signs of neurologic injury or focal deficit or prolonged coma. + Multidisciplinary team approach involving obstetricians, anesthetists and critical care unit



fits  in  spite  of  therapy.  (iii)  Obstetric  indications (malpresentation).
Postpartum management: MgSO 4  is continued for 24
hours after the last seizure or delivery whichever is later. Follow-up and prognosis: Patient should be followed
up in the postnatal clinic by 6 weeks of time.
Recurrence risk varies between 2 and 25%. The risk of pre-eclampsia and eclampsia to the daughter of an eclampsia patient is about 25% and 3%, respectively.
11    Atypical   pre-eclampsia   is   defined   as   the development of pre-eclampsia (even eclampsia) without
fulfilling the standard definition or criteria (hypertension or proteinuria). The common presentations are:
Early onset pre-eclampsia/eclampsia less than 20 weeks,  u  Late postpartum pre-eclampsia,  eclampsia more  than  48  hours  postpartum,  ■  Women  with gestational  hypertension  or  gestational  proteinuria presenting  with  symptoms  of  (a)  Pre-eclampsia,  (b) Thrombocytopenia and (c) Elevated liver enzymes.
11   Women with atypical pre-eclampsia and who have other diagnostic criteria of severe pre-eclampsia should be treated as if they have severe pre-eclampsia. Such patients are also treated with parenteral MgSO4.


CHRONIC HYPERTENSION IN PREGNANCY
Chronic Hypertensive Disease (CHD) is defined as the presence of hypertension of any cause antedating or before the 20th week of pregnancy and its presence beyond the  12 weeks after delivery.  The  condition poses a dificult problem as regards the diagnosis and management when seen for the first time, beyond the 20th week of pregnancy. Overall incidence is 2-4% of which 90% are due to essential hypertension.
The high-risk factors for CHD are: (i) Age (>40 years), (ii) Duration of hypertension (>15 years), (iii) Level of BP  (>160/110  mm  Hg),  (iv)  Presence  of  any  medical disorder (renovascular or collagen vascular disease) and (v) Presence of thrombophilias. Majority of women with CHD are  low-risk  and have satisfactory maternal  and fetal outcome without any antihypertensive therapy. The overall risk of superimposed PE is 25%.

ESSENTIAL HYPERTENSION IN PREGNANCY
Apart from the specific hypertensive disorder in pregnancy (PIH), essential hypertension is the common hypertensive state in pregnancy. Its incidence varies from 1 to 3%.
Chapter 18: Hypertensive Disorders in Pregnancy     ma Table 18.8: Differential features of pre-eclampsia with gestational and essential hypertension.

Parameters Age
Parity
Past history Family history
Onset of hypertension
Follow-up BP following delivery
Proteinuria Eye changes

Cerebral Symptoms Specific blood values


Pre-eclampsia Mostly young.
Primigravidae-common.
Pre-eclampsia in previous pregnancy. May be present.
After 20th week of pregnancy. Subsides completely.

Present.
Usually none. Extreme cases-retinal edema, constriction of arterioles, nicking of the veins.
Cerebral symptoms+  Hemoconcentration + Thrombocytopenia + Serum uric acid >5 mg/dl. Raised liver enzymes.


Gestational hypertension Young.
Primigravidae. May be present. Unrelated.
Usually in third trimester. Subsides completely.

Absent. None.

Absent.

Essential hypertension Usually elderly. Multipara-common.
Prepregnant hypertension present. Often present.
Before 20th week of pregnancy. Persists even after 3 months

Usually absent.
Silver wiring of the arterioles. Hypertensive retinopathy.
May be present.



DIAGNOSIS: The diagnostic criteria are: (1) Rise of blood pressure to the extent of 140/90 mm Hg or more during pregnancy  prior to the  20th week  (molar pregnancy excluded), (2) Cardiac enlargement on chest radiograph and ECG,  (3) Presence of medical disorders,  and  (4) Prospective  follow-up  shows  persistent  rise  of blood pressure even after 42 days following delivery. Differential diagnosis with pre-eclampsia, gestational hypertension and essential hypertension are discussed (Table 18.8).
EFFECTS OF PREGNANCY ON THE DISEASE: (1) There may be a midpregnancy fall of blood pressure in about 50%. However, the blood pressure tends to rise in the last trimester which may or may not reach its previous level,  (2)  In 50%,  the  blood  pressure  tends  to  rise progressively as pregnancy advances, (3) In about 20%, it is superimposed by pre-eclampsia,  (4)  Rarely,  new onset of proteinuria (>300 mg/24 hours) or P/C ratio >0.3 and (5) In 30%, there is permanent deterioration of the hypertension following delivery.
EFFECT  OF THE DISEASE ON PREGNANCY:  Maternal risk:  In the  milder  form,  the  maternal  risk  remains unaltered but in the severe form or when superimposed by preeclampsia (14-28%) the maternal and perinatal risk is much increased. Other complications are: Placental abruption and FGR.
Fetal risk: Due to chronic placental insufficiency, the babies are likely to be growth restricted. Preterm birth is high. In the milder form, with the blood pressure less than 160/100 mm Hg, the perinatal loss is about 10%. When  blood  pressure  exceeds  160/100 mm  Hg,  the perinatal loss increases by three to four times and when complicated by pre-eclampsia, it increases further. Risk of placental abruption is high (0.5-10%).
MANAGEMENT: The principles of management are: (1) To stabilize the blood pressure to below 160/100 mm Hg,  (2)  To prevent superimposition of pre-eclampsia, (3) To monitor the maternal and fetal wellbeing, (4) To terminate the pregnancy at the optimal time.


Preconceptional  evaluation  and  counseling  is essential to assess the etiology, severity of hypertension and possible outcome of pregnancy.
Antihypertensive drugs: Routine use of antihyperten­ sive drug is not favored. It may lower the blood pressure and thereby  benefit  the  mother  but the diminished pressure may reduce the placental  perfusion which may be detrimental to the fetus. Thus, antihypertensive drugs (labetalol, nifedipine or hydralazine) should be used only when the pressure is raised beyond 160/100 mm Hg, to prevent target organ damage (stroke, renal or cardiac failure). In cases, where these drugs have been used before pregnancy, care should be taken to adjust the dose during pregnancy, especially, during midpregnancy when the blood pressure tends to fall.
OBSTETRIC MANAGEMENT: In mild cases, spontaneous labor is awaited. In severe or complicated cases, the aim is to try to continue the pregnancy to at least 34 weeks otherwise up to the 37th week to attain fetal maturity and then to terminate the pregnancy. These women need BP control for the first 24 hours postpartum.

CHRONIC RENAL DISEASES IN PREGNANCY
The overall incidence of chronic renal disease in pregnancy is rare (0.2%).
Features suggestive of chronic renal disease in pregnancy are: A. Urine on microscopic examination:
(i)  RBCs more than 1-2/HPF or RBC casts. (ii) Increased number ofWBCs or casts.
B. Serum levels of uric acid and creatinine raised.
MILDLY  COMPROMISED  RENAL  FUNCTION:  (Serum creatinine <125 mmol/L) is generally not associated with any adverse maternal or fetal outcome. Effect of pregnancy on long-term renal function and development of end-stage renal failure (serum creatinine >500 mmol/L) or the need of dialysis is very low (5%).
Moderately or severely compromised renal function (high serum creatinine >125 mmol/L) is associated with adverse pregnancy outcome (50%) as the renal function deteriorates.
!I Chapter 18: Hypertensive Disorders in Pregnancy
Effects of renal disease on pregnancy: Pregnancy outcome depends on the level of: (i) hypertension, (ii) proteinuria, and (iii) serum creatinine. Miscarriage, preterm labor, JUGR and IUFD are the known fetal risks. However, with improved pregnancy surveillance and neonatal care, outcome has improved. Superimposed pre-eclampsia adversely affects the course and perinatal loss may go as high as up to 40-60%. Women with stage I CKD (creatinine  <1.4 mg/dL)  will have a healthy newborn. Those with moderate to severe CKD (creatinine  1.4 mg/dL) the live birth rate is 92-93%.
Effects of pregnancy on renal disease: It depends on the severity of renal disease. When the renal function is mildly compromised (serum creatinine <125 mmol/L) the risk of end stage renal failure is low (5%).
On the contrary renal failure may be as high as 10% when renal function is compromised moderately (serum creatinine 125-250 mmol/L) or severely (serum creatinine >250 p mol/L). Superimposed pre-eclampsia worsens the prognosis. The prognosis of membranoproliferative Glomerulonephritis (GN), focal glomerulosclerosis or immunonephropathy (IgA) is poor when compared to primary glomerulonephritis.

MANAGEMENT: Persistent or  severe BP elevation causes deterioration of renal function. Prepregnancy counseling­ women with severely compromised renal function should be discouraged to become pregnant as the risks of develop­ ing end stage renal failure is high.
Antenatal care is done with periodic assessment of renal function. A 24-hour urine collection is done for creatinine clearance (P/C ratio ,:0.3 mg/dL), and total protein excretion. Antihypertensive therapy is started early (nifedipine, hydralazine, clonidine or beta blockers) to preserve renal function. Diuretics may be used in cases with massive edema. Regular hemodialysis during pregnancy in a patient with moderate renal compromise may improve the outcome. Sudden volume shift and hypotension should be avoided.
Women planning pregnancy following renal transplant should maintain the following: (a) Plasma creatinine <1.5 mg/dL (<130 pmol/L); (b) Controlled hypertension; (c) No or minimal proteinuria; (d) On maintenance level of immunosuppression; (e) No evidence of graft rejection.
Anemia from chronic renal insuficiency may be treated with recombinant erythropoietin.
Fetal surveillance is maintained more closely. Timing of delivery is decided on individual basis depending upon the control



of hypertension, fetal viability and the level of renal function. Preterm delivery is common (50%).

PREGNANCY AFTER RENAL TRANSPLANT

PREPREGNANCY COUNSELING FOR THE  RENAL TRANSPLANT RECIPIENT: As maternal mortality and morbidity is increased, effective  contraception  is  recommended  until  prepregnancy counseling has been done. Conception is not advised within the first year following renal transplantation. The risk of acute rejection  in  the first year is  10-15%.  Teratogenic  medications need to be discontinued. This includes mycophenolate mofetil, Angiotensin   Converting   Enzyme   Inhibitors   (ACEi)   and angiotensin receptor antagonists.
Effect of renal transplantation on pregnancy: The impact of renal transplantation on pregnancy is dependent upon the level of renal function and the coexistence of hypertension and proteinuria. Hypertension predates the pregnancy and persists in more than 50% of pregnant women with renal transplants. All renal transplant recipients have an increased risk of pre-eclampsia. There is risk of Gestational Diabetes Mellitus (GDM) in renal transplant recipients. Calcineurin inhibitors (tacrolimus and ciclosporin) and prednisolone have dose-dependent, diabetogenic effects. Cesarean delivery rates are higher due to pre-eclampsia or fetal growth restriction leading to iatrogenic preterm delivery. However, renal transplantation is not a contraindication to vaginal delivery. Effect of pregnancy on the renal transplant: An acute graft rejection rate during pregnancy is around 5%. Creatinine rise more than 20% during pregnancy is most commonly due to pre-eclampsia. Transplant  rejection can be treated with corticosteroids and tacrolimus/ciclosporin. The majority of these drugs are actively transported across the placenta. Babies exposed to biologic drugs in utero should avoid Jive vaccines during the first 6 months of life as the levels of these immunomodulators tend to remain. Proteinuria adds to the hypercoagulable state
of pregnancy and risk of venous thromboembolism. Heparin prophylaxis should be given and other risk factors for venous thromboembolism should be assessed.
Antenatal management: It is same as in cases of high-risk pregnancies. Multidisciplinary approach is recommended. Pre­ eclampsia, eclampsia are managed as per routine drugs. Extra monitoring is required.
Postpartum management: Prior to discharge from hospital, blood pressure should be stable and lower than 140/90 mm Hg. Women with an indication for an ACEi can be prescribed like, enalapril, which is safe during breastfeeding. Advice on contraception is mandatory.





>  Hypertension in pregnancy is the most common medical complication.
>  Pre-eclampsia and eclampsia are the leading causes of maternal mortality and morbidity in India and worldwide.
>  Pre-eclampsia is a syndrome of multiple organ dysfunction. It is peculiar to the pregnant state. It usually manifests for the first time beyond the 20th week and is characterized by the appearance of hypertension to the extent of 140/90 mm Hg or more and proteinuria
with or without pathological edema.
>  Presence of proteinuria is no longer required for the diagnosis of pre-eclampsia (ACOG, 2013).
>  The etiology remains obscure but the basic pathology is endothelial dysfunction and vasospasm.
>  Etiopathological basis of pre-eclampsia is thought to be an imbalance of vasodilatory factors (PGl , PGE , VEGF, nitric oxide) with that of vasoconstrictors (TXA2, ROS, superoxide radicals, lipid peroxides, sFlt-1 and endothelin-1) resulting in endothelial dysfunction and vasospasm. The exact etiology is unknown.
2	2
Contd...
Chapter 18: Hypertensive Disorders in Pregnancy     mJ, Contd...

►   Endothelial dysfunction leads to increased capillary permeability (leak). This is manifested as: ascites, pulmonary edema, proteinuria, pleural effusion and activation of coagulation system (thrombocytopenia, DIC, HELLP syndrome). Others are: visual disturbances, retinal hemorrhage.
►   Pregnancy-Induced Hypertension (PIH) includes: (i) Gestational hypertension, (ii) Pre-eclampsia and (iii) Eclampsia.
►  According to gestational age, pre-eclampsia may be: (Al Early <34 weeks and (B) Late >34 weeks. Late-onset pre-eclampsia often has favorable outcome.
►   The pathological organ changes due to vasospasm are more evident in uteroplacental bed ➔ IUGR, placental abruption; Kidney➔ proteinuria, oliguria, renal failure; Liver➔ necrosis, subcapsular hematoma, raised level of AST and ALT; CNS➔ seizures. Posterior reversible encephalopathy syndrome (PRES), involving the parietal and occipital lobes, cortical blindness.
►   The clinical manifestations are based on the pathological changes, e.g., vasoconstriction➔ hypertension, diminished organ perfusion➔ oliguria, IUGR;     vascular permeability➔ edema and proteinuria; endothelial damage➔ thrombocytopenia and HELLP syndrome.
t
►   Pre-eclampsia may be with severe or non-severe features and the complications involve both the mother and the fetus if left untreated. ►  Prediction and prevention-no screening test is helpful but presence of high-risk factors may help to identify an individual. Interventions to prevent preeclampsia are: high protein and low salt diet, anti-thrombotic agents, low dose aspirin, calcium, magnesium, zinc and vitamin
E and C.
►   Management of eclampsia and severe pre-eclampsia includes: (A) Control of fits and (Bl Control of hypertension. Drug used for control of fits is magnesium sulfate {IM/IV regimens). First-line antihypertensives are: (a) Labetalol, (b) Hydralazine or (c) Nifedipine. Target levels of BP to control is SBP = 140-160 mm Hg and DBP = 90-100 mm Hg.
►   Termination of pregnancy (delivery) is the only definitive treatment for pre-eclampsia.
►   Acute fulminant pre-eclampsia runs the high-risk of eclampsia. Prophylactic anticonvulsant therapy (Mg5O4) is recommended (Magpie Trial-2002).
►   Eclampsia a complication of pre-eclampsia is characterized by grand mal seizures. Eclampsia is a significant cause of maternal death. ►   Convulsions in eclampsia has got four stages: Premonitory stage, tonic stage, clonic stage and stage of coma.
►  Complications of eclampsia are many. Prevention of eclampsia depends on early detection and management of preeclampsia. Prophylactic
Mg5O4 therapy and timely delivery are the important steps of management.
►   Eclampsia should be managed in a tertiary care hospital. Principles of management involves general care of the patient, to arrest
convulsions, control of hypertension and to expedite delivery.
►   Women with eclampsia should be delivered within a period of 6-8 hours even if the fits are not controlled.
►   Gestational hypertension is not associated with edema, proteinuria or other hematological changes. Blood pressure usually subsides within 12 weeks following delivery.
►   Pre-eclampsia needs to be differentiated from essential hypertension and chronic renal diseases. Prognostically each has got different pregnancy outcome.
►   Patients with non severe pre-eclampsia  37 weeks or severe pre-eclampsia  34 weeks should be delivered.
►   Patients with severe pre-eclampsia of <34 weeks should be delivered if criteria mentioned in Box 18.4 are met.
►   Control of BP should be to a level between 140 and 160 mm Hg systolic and between 90 and 105 mm Hg diastolic.
►   MgSO4 should be used in patients with eclampsia, HELLP syndrome, pre-eclampsia with severe features and in patients with unstable mild pre-eclampsia. HELLP syndrome may develop in the absence of maternal severe hypertension and proteinuria.
►   MgSO4 is the drug of choice in the management of eclampsia to control convulsions. It is continued for 24 hours after the last seizure or delivery whichever is later.
►   Repeat doses of MgSO4 are given only if the knee jerks are present, urine output exceeds>30 ml/hour, and the respiration rate is> 12/ min. ►   Therapeutic level of MgSO4 is 4-7 mEq/L. For IV administration, concentration of Mg5O4 should not exceed 20%. One part of 50% Mg5O4
injection is diluted with 1.5 parts of water for injection to make it 20%. It is then given IV slowly.
►   Corticosteroids should be used for cases with preterm delivery and in cases with HELLP syndrome.
►   Patients with gestational hypertension/atypical pre-eclampsia and who have other diagnostic criteria of severe pre-eclampsia should be treated as if they have severe pre-eclampsia.
►   There are no longer any real differences in management between PE and gestational hypertension, in terms of BP management and in the decision to deliver. Gestational hypertension may go to protein uric phase and may evolve to pre-eclampsia.
►   Antihypertensive medications is recommended for severe hypertension during pregnancy. ►   Daily low dose aspirin in the management of pre-eclampsia is given in high-risk women.
►   The decision to deliver a women should not be based on the severity of proteinuria (ACOG-2013).
►   Magnesium sulfate is recommended in the management of severe pre-eclampsia, eclampsia or HELLP syndrome.
►   The progression of pathology for Gestational Hypertension (GH)-pre-eclampsia (GH-PE) to severe PE, HELLP syndrome or eclampsia may be very rapid and unpredictable.
►  Classification of pre-eclampsia can be misleading as an apparently mild disease may rapidly progress to a severe one.
►   Low dose aspirin is used for PE prophylaxis at 16 weeks and continuing until delivery. There is no proven method to prevent PE. ►  Women with GH, PE without severe features at >37 weeks should be delivered.
►   MgSO4 should be used for prevention and treatment of seizures for women with GH and PE with severe features or eclampsia. ►   Women with GH presenting with severe BP should be managed with the same manners as for a woman with severe PE.
►   A clear cause for pre-eclampsia has yet to be elucidated.
►   It is thought that pre-eclampsia may be due to placental and maternal vascular dysfunction. Although incompletely understood, it is thought that impaired remodeling of uterine spiral arteries leads to reduce placental perfusion.
►   In PE, there is increased inflammation, increased production of antiangiogenic factors, and resultant maternal endothelial cell
damage that manifest in the signs and symptoms of preeclampsia.
►   Rare cases of eclampsia can develop <20 weeks and >48 hours postpartum.


Antepartum Hemorrhage



CHAPTER  


 

❖ Placenta Previa ►  Etiology
► Clinical Features
►  Differential Diagnosis ►  Complications
►  Prognosis
►  Management



❖ Practical Guide for Cesarean Delivery ❖ Practical Approach to Lower Segment
CD for Placenta Previa
❖ Practical Guide to Lower Segment Approach for Placenta Previa Accreta
❖ Abruptio Placentae ► Clinical Features



► Complications ►  Diagnosis
►  Management
►  Treatment in the Hospital ►  Indeterminate Bleeding




DEFINITION: It is defined as bleeding from or into the genital tract after the 20th week of pregnancy but before the birth of the baby ( the first and second stage of labor are thus included). The 28th week is taken arbitrarily as the lower limit of fetal viability. The incidence is about 3% amongst hospital deliveries.
CAUSES  (Flowchart  19.1 ):  The  causes of antepartum hemorrhage  fall  into  the  following  categories.  The hospital figures do not give a true picture of the incidence of the  different  varieties.  However,  on an average,  the incidence of placenta previa, abruptio placentae and the indeterminate group is almost the same.

PLACENTA PREVIA
DEFINITION: When the placenta is implanted partially or completely over the lower uterine segment ( over and adjacent to the internal os) is called placenta previa. The term previa (Latin: in front of) denotes the position of the placenta in relation to the presenting part.
INCIDENCE:  About  one-third  cases  of  antepartum hemorrhage belong to  placenta previa. The incidence of placenta previa ranges from 0.5 to 1 % amongst hospital

deliveries.  In  80%  cases,  it  is  found  in  multiparous women.  The incidence is increased beyond the  age of 35 years, smokers and in multiple pregnancy. Increased family planning acceptance with limitation and spacing of birth lowers the incidence of placenta previa.
I ETIOLOGY
The exact cause of implantation of the placenta in the lower segment is not known. The following theories are postulated.
ll   Dropping down theory: The fertilized ovum drops down and is implanted in the lower segment.  Poor decidual reaction in the upper uterine segment may be the cause. Failure of zona pellucida to disappear in time can be a hypothetical possibility. This explains the formation of central placenta previa.
■   Persistence of chorlonic activity in the decidua capsularis and its subsequent development into capsular placenta which comes in contact with decidua vera of the lower segment can explain the formation of lesser degrees of placenta previa.
ii  Defective decidua, results in spreading of the chorionic villi over a wide area in the uterine wall to get nourishment. During this process, not only the placenta becomes membranous but encroaches onto the lower segment. Such a placenta previa


Flowchart 19.1:  Causes of Antepartum Hemorrhage (APH).
I




l
Placental bleeding (70%)
l



Placenta previa	Abruptio placentae
(35%)	(35%)

APH



Unexplained (25%) or
Indeterminate (excluding placental bleeding and local
lesions)
■ Vasa previa
■ Succenturiate lobe





Extra placental causes (5%)
Local cervicovaginal lesions:
■ Cervical polyp
■ Carcinoma cervix
■ Varicose vein
■ Local trauma
■ Cervical ectopy
I
L
Chapter 19: Antepartum Hemorrhage    ii



11   Multiparity.
■   Maternal age: >35 years-4-fold increase.
11   Prior Cesarean Delivery (CD) or uterine surgery. 11   Race: Asian women.
11   Maternal factors: Infertility treatment.
11    Presence  of   uterine   scar:  Cesarean  section,  myomectomy, hysterotomy.
■    Prior curettage.
11    Prior placenta previa. 11    Multiple pregnancy.
■    Pregnancy following ART.
11   Placenta size and abnormality: Succenturiate lobes, big placenta. ■   Smoking:  Causes  placental  hypertrophy  to  compensate  CO­
induced hypoxemia.

may invade the underlying decidua or myometrium to cause placenta accreta, increta or percreta.
ll    Big surface area of the placenta (hyperplacentosis) as in twins may encroach onto the lower segment.
The rise of PP increases with the number of prior Cesarean Delivery (CD). Placenta previa occurs in 0.9% of women with one prior to 3% with prior ?.3 CD.
The high-risk factors for placenta previa are shown  in Box 19.1.
ATHOLOGICAL ANATOMY
Placenta: The placenta may be large and thin. There is
often a tongue-shaped extension from the main placental mass.  Extensive areas of  degeneration  with infarction and calcification may be evident. The placenta may be morbidly adherent due to poor decidua formation in the lower segment.
Umbilical cord: The cord may be attached to the margin (battledore) or into the membranes (velamentous). The insertion of the cord may be close to the internal os or the fetal vessels may run across the internal os in velamentous insertion giving rise to vasa previa,  which may rupture along with rupture of the membranes.
Lower uterine segment: Due to increased vascularity, the lower uterine segment and the cervix becomes soft and more friable.

TYPES OR DEGREES (Figs. 19.1 A to D): There are two types of placenta previa depending upon the degree of extension of placenta to the lower uterine segment.
Currently with ultrasound precision,  more accurate placental  location is made in relation to the cervical internal os.
Revised classification  (ACOG, ACR, 2014):  (A) True placenta previa: Placenta covers the internal os (B) Low­ lying placenta: Placenta lies within 2 cm of internal os but does not cover it.
Dangerous placenta previa is the name given to the type II posterior placenta previa (Figs. 19. IC and D). Because of the curved birth canal, major thickness of the placenta (about 2.5 cm) overlies the sacral promontory, thereby diminishing the anteroposterior diameter of the inlet and prevents engagement of the presenting part. This hinders effective compression of the separated placenta to stop bleeding. The patient suffers profuse bleeding.

CAUSE OF BLEEDING: As the placental growth slows down in  later  months and the  lower  segment progressively enlarges, the inelastic placenta is sheared off the wall of  the  lower  segment.  This  leads  to  opening  up  of uteroplacental vessels and leads to an episode of bleeding. As it is a physiological phenomenon which leads to the separation of the placenta, the bleeding is said to be inevitable. However, the separation of the placenta may be provoked by trauma including vaginal examination, coital act, external version or during high rupture of the membranes.  The  blood  is almost  always  maternal, although  fetal  blood  may  escape  from  the  torn  villi especially when the placenta is separated during trauma.
The mechanisms of spontaneous control of bleeding are: (1) Thrombosis of the open sinuses. (2) Mechanical pressure by the presenting part. (3) Placental infarction.
Placental migration: Ultrasonography at  1 7 weeks of gestation reveals placenta covering the internal os in about 15% of cases. Repeat ultrasonography at 34 weeks showed no placenta in the lower uterine segment in more than 90% of cases. Lower uterine segment expands from 0.5 cm at 20 weeks to more than 5 cm (10-fold) at term. The term placental migration (though misnomer)











0


Normally implanted placenta	Low lying placenta	Placenta previa -  -   -Figs. 19.1A to D: Degree  of  placenta  previa with  findings on  ultrasound  examination.
-    Chapter 19: Antepartum Hemorrhage


could be explained in two ways: (i) With the progressive increase in the length of lower uterine segment,  the lower placental edge relocates away from the cervical os and (ii) due to trophotropism (growth of trophoblastic tissue towards the fundus as it is more vascular), there is resolution of placenta previa.
I CLINICAL FEATURES
SYMPTOMS: The only symptom of placenta previa is vaginal bleeding. The classical features of bleeding in placenta previa are sudden onset, painless, apparently causeless and recurrent. In about 5% cases, it occurs for the first time in the second and third trimester or during labor, especially in primigravidae. In about one-third of cases, there is a history of 'warning hemorrhage' which is usually slight.
The bleeding is unrelated to activity and often occurs during sleep and the  patient  becomes  frightened  on awakening  to  find  herself  in  a  pool  of  blood.  The bleeding is unassociated with pain unless labor starts simultaneously.  Obvious  causes  for  the  placental separation such as trauma or hypertension are usually absent. The first bout of bleeding is usually not alarming but subsequent bouts may be heavier than the previous one due to separation of fresh areas of placenta. Usually one-third women will present  before  30 weeks,  one­ third between 30 and 36 weeks and the rest third after 36 weeks. Earlier bleeding is more likely to occur in major degrees.  However,  there may  not be any bleeding in central placenta previa until labor starts. Asymptomatic cases may be detected by sonography or at the time of
cesarean section.
SIGNS: General condition and anemia are proportionate to the visible blood loss. But in the tropics, the picture is often confusing due to pre-existing anemia.
Abdominal examination:
♦    The size of the uterus is proportionate to the period of gestation.
♦    The uterus feels relaxed, soft and elastic without any localized area of tenderness.
♦    Persistence  of  malpresentation  like  breech  or transverse or unstable lie is more frequent. There is also increased frequency of twin pregnancy.
♦    The head is floating in contrast to  the period of gestation. Persistent displacement of the fetal head is very suggestive. The head cannot be pushed down into the pelvis.

♦    Fetal heart sound is usually present, unless there is major separation of the placenta with the patient in exsanguinated condition.  Slowing of the  fetal heart rate on pressing the head down into the pelvis which soon  recovers  promptly  as  the  pressure  is  released is suggestive of the presence of low-lying placenta especially of posterior type (Stallworthy's sign). But this sign is not always significant because it may be due to fetal head compression even in an otherwise normal case.
Vulval inspection:  Only inspection is to  be done to note whether the bleeding is still occurring or has ceased, character of the blood-bright red or dark colored and  the amount of blood loss-to be assessed from the blood-stained clothing. In placenta previa,  the blood is bright  red as the bleeding occurs from the separated uteroplacental sinuses close to the cervical opening and escapes out immediately.
Vaginal  examination  should  not  be  done  in  a diagnosed or suggested case of placenta previa. It may be done prior to termination of pregnancy in the operation theater under anesthesia, keeping everything ready for cesarean section.
I CONFIRMATION OF DIAGNOSIS
DIAGNOSIS: Painless and recurrent vaginal bleeding in the second half of pregnancy should be taken as placenta previa unless proved otherwise.  Ultrasonography is the initial procedure either to confirm or to rule out the diagnosis (Table 19.1).
I PLACENTOGRAPHY
■  Sonography: It is the diagnostic technique of choice (RCOG-2001). It provides the simplest, most precise and safest method of placentallocalization (Figs. 19.2A to D). In addition, it is helpful for assessing the fetal size
and status. It also provides information pertaining to maturity and wellbeing of the fetus for guiding the management.
■  Transabdominal (TAS): The accuracy after 30th week of gestation is about 100%. False-positive result may be due to full  bladder or myometrial contractions. Poor imaging could be due to maternal obesity and posteriorly situated placenta. The reasons for poor imaging in a posteriorly situated  placenta are­ (a) acoustic shadow from the fetal presenting part may obscure the placental view, (b) there is no anatomical landmark posteriorly ( anteriorly uterovesical angle)



Table 19.1: Localization of placenta (placentography). I. Imaging studies
•  Sonography
• Transabdominal Ultrasound (TAS).
• Transvaginal Ultrasound (TVS) (Figs. 7.2A to C, p. 63). • Transperineal ultrasound (Ch. 24).
• Color Doppler flow study. • 3D power Doppler study.



•  Magnetic resonance imaging (MRI) For better diagnosis of:
• Placenta previa.
• Placenta previa accreta (details in Ch. 41 and 42).


II. Clinical
♦  Direct visualization during cesarean section.
♦  Examination of the placenta following vaginal delivery.
♦  By internal examination (double set up examination).
Chapter 19: Antepartum Hemorrhage    mJ










Figs. 19.2A to D: Ultrasonography and MRI showing central placenta previa: (A) USG: Gray-scale imaging; (Bl USG: Color Doppler imaging; (C) MRI coronal view; (D} MRI (T2 images) sagittal view (PL: Placenta; H: Fetal Head) (read more in Ch. 42, p. 627).


below which placenta is defined as previa ( an arbitrary distance of 5 cm from the internal os is considered as lower segment). As such, a positive case should be subjected to repeat scan after emptying the bladder. Cases of placenta previa detected in earlier weeks should be  subjected  to repeat scan at 36 weeks or earlier for detection of placental migration (see above).
■    Transvaginal (TVS): Transducer is inserted within the vagina without touching the cervix. The probe is very close to the target area and higher frequencies could be used to get a superior resolution. It is safe, obviates the discomfort of full bladder and is more accurate (virtually 100%) than TAS. Complete placenta previa diagnosed  in  the  second  trimester  will  persist  into the third trimester in 26% of cases, whereas marginal placenta previa with persist in only 2.5% cases.
■  Transperineal (TPS): This is well accepted by patients. Internal os is visualized in 97-100% of cases.
■   Color Doppler: Diffuse vascular lakes with turbulent flow  in  the  hypoechoic  areas  near  the  cervix  is consistent  with  the  diagnosis  of  placenta  previa. Three-Dimensional (3-D) power Doppler is the best. Hypervascularity at the uterine serosa-bladder junction is diagnostic.
■   Magnetic Resonance Imaging (MRI): It is a noninva­ sive method without any risk of ionizing radiation. Dark intraplacental bands are seen on T2-weighted images. MRI is better than ultrasonography to diagnose pos­ terior placenta previa and placenta previa accreta or percreta with bladder invasion. Limitations of MRI are more time consuming, lack of portability and the cost.
■   Advantages of ultrasonography and MRI:  (1) Need of vaginal examination with the risk of hemorrhage is avoided. (2) The need of prolonged and unnecessary hospital stay in patients with clinical diagnosis of APH can be reduced. (3) Diagnosis of placenta previa can be made even before the bleeding starts. ( 4) Diagnosis of morbid adherent placenta (especially in a woman with  placenta  previa  and  prior  cesarean  delivery) can be made.  (5)  Plan of delivery can be organized accordingly.

■ CLINICAL CONFIRMATION
Double set-up examination (vaginal examination): It is not done  these  days.  The  indications are:  (i)  Inconclusive USG report, (ii) USG revealed placenta away from the OS or (iii) USG facilities not available  that  time.  It is  done  in the  operation theater under anesthesia keeping everything ready for cesarean section. Palpation of the placenta on the lower segment not only confirms the clinical diagnosis but also identifies its degree.
Visualization of the placental implantation on the lower segment can be confirmed during cesarean section.
Examination of the placenta following vaginal delivery reveals: (a) A tongue-shaped comparatively thin segment of placental tissue projecting beyond the main placental mass with evidences of degeneration. (b) Rent on the membranes is situated on the margin of the placenta. (c) Abnormal attachment of the cord (marginal or membranous) is more common.

I DIFFERENTIAL  DIAGNOSIS

Placenta previa is at times confused with other causes of bleeding occurring in later months of pregnancy. The most common one from which it has to be differentiated is bleeding from premature separation of a normally situated placenta (abruptio placentae). The differentiating features are described in a tabulated form (Table 19.2).
The local cervical lesions (polyps, carcinoma) can easily be differentiated by a speculum examination. However, both the conditions can co-exist. In circumvallate placenta, the bleeding is slight and the diagnosis is only made after examining the placenta following delivery.

■ COMPLICATIONS
Maternal  and  fetal  morbidity  and  mortality  from placenta previa are significantly high.

Maternal: During pregnancy and the others.
Antepartum hemorrhage with varying degrees of shock is an inevitable complication. The first bout of hemorrhage is seldom severe but subsequent hemorrhage may be torrential. Co-existent placental abruption is about 10%.
•  Malpresentation: There is increased incidence of breech pre­ sentation (Fig. 19.3) and transverse lie. The lie often becomes unstable.
♦  Premature labor either spontaneous or induced is common.
ml Chapter 19: Antepartum Hemorrhage
Table 19.2: Distinguishing features  f placenta previa and abruptio placentae.

Parameters
■  Clinical features:
• Nature of bleeding


• Character of blood
• General condition and anemia
• Features of pre-eclampsia 11     Abdominal examination:
• Height of uterus
• Feel of uterus


Placenta previa

a. Painless, apparently causeless and recurrent. b. Bleeding is always revealed.

Bright red.
Proportionate to visible blood loss.

Not relevant.

Proportionate height to gestational age.
Soft and relaxed.


Abruptio placentae

a. Painful, often attributed to pre-eclampsia or trauma and continuous.
b. Revealed, concealed or usually mixed.
Dark colored.
Out of proportion to the visible blood loss in concealed or mixed variety.
Present in one-third cases.

May be disproportionately enlarged in concealed type.
May be tense, tender and rigid.

• Malpresentation	Malpresentation is common. The head is high floating.   Unrelated, the head may be engaged.

• FHS
II    Placentography (USG, MRI)


Usually present.
Placenta in lower segment.


Usually absent especially in concealed type.
Placenta in upper segment.

■  Vaginal examination	 Placenta is felt on the lower segment (not to be done   Placenta is not felt on lower segment. Blood clots in a suspected case).	should not be confused with placenta.




•  Early rupture of the membranes.
♦  Cord prolapse due to abnormal attachment of the cord (Fig. 19.31, ♦  Slow dilatation of the cervix due to the attachment of placenta
on the lower segment.
♦  lntrapartum hemorrhage due to further separation of placenta with dilatation of the cervix.
♦  Increased incidence of operative interference (cesarean delivery, hysterectomy).
♦  Postpartum hemorrhage is due to:
o Imperfect retraction  of the  lower  uterine segment upon which the placenta is implanted.
• Large surface area  of placenta  with  atonic uterus with pre-existing anemia.
• Association (1 S/o) morbidly adherent placenta (placenta accreta, increta, percreta) on the lower segment.
• Placenta previa accreta is a serious complication that may cause maternal death. Often the placenta previa and accreta are managed by hysterectomy.
• Trauma to the cervix and lower segment because of extreme softness and vascularity.
• Death is due to massive hemorrhage during the antepartum, intrapartum or postpartum period. Operative hazards, infection or embolism are also the cause of death.
o It should be remembered that because of antepartum anemic state, the patient may become shocked with relatively small amount of blood loss.
♦  Retained placenta and increased incidence of manual removal add further hazard to the postpartum shock. Increased incidence of retained placenta is due to: (1) Increased surface area and (21 Morbid adhesion. The risk of placenta previa being accreta in a woman with previous one cesarean section is 10-1 S/oand it rises to about 60% with three or more prior cesarean section.


♦  Sepsis is increased due to: (a) Increased operative interference, (bl placental site near to the vagina, (cl anemia, and (d) devitalized state of the patient.
♦  Subinvolution. +  Embolism.


♦  Low birth weight babies are quite common  (15%) which may be the effect of preterm labor either spontaneous or induced.
♦  Fetal growth restriction: Repeated small bouts of hemorrhage while carrying on the expectant treatment can cause chronic placental insufficiency.
♦  Asphyxia is common and it may be the effect of-(al early separation of placenta, (bl compression of the placenta or (cl compression of the cord.
♦  Intrauterine death is more related to severe degree of separation of placenta, with maternal hypovolemia and shock. Deaths are also due to cord accidents (Fig. 19.31.
♦  Birth injuries are more common due to increased operative interference.
♦  Congenital malformation is three times more common in placenta previa.
♦  Maternal and fetal morbidity and mortality from placenta previa are significantly high.

















Fig. 19.3: Labor in a  woman  with placenta previa complicated with prolapse of umbilical cord and footling.
Courtesy: Dr S Bhattacharya, Silchar.


I PROGNOSIS
MATERNAL:  There  has  been  a substantial reduction of  maternal deaths in placenta previa throughout the Globe. The contributing factors are:
a.  Early diagnosis ( diagnosis can even be made prior to bleeding).
b.  Omission of internal examination.
c.  Free availability of blood transfusion facilities. d. Potent antibiotics.
e.  Wider use of cesarean section with expert anesthetist. f.   Skill and judgment with which the cases are managed.
All these factors have led to reduction of maternal deaths from placenta previa to less than 1% or even to zero in some centers. Risk of recurrence of placenta previa in subsequent pregnancy is about 8 times.
FETAL: The reduction in perinatal deaths is principally due  to  judicious  extension  of  expectant  treatment thereby reducing the loss from prematurity, liberal use of cesarean section which greatly lessens the loss from hypoxia and improvement in the neonatal care unit. But still the perinatal mortality ranges from 10 to 25%. The causes of death are-(a) prematurity, (b) asphyxia and (c) congenital malformation.

I MANAGEMENT
PREVENTION:  Placenta previa is one of the inherent obstetric hazards and in majority the cause is unknown. Thus to minimize the risks, the following guidelines are useful.
a  Regular antenatal care to improve the health status of women and correction of anemia.
■  Antenatal diagnosis of low lying placenta at 20 weeks with  routine  ultrasound  needs  repeat  ultrasound examination at 34 weeks to confirm the diagnosis. Significance of 'warning hemorrhage' should not be ignored.
■
11    The  woman is advised to avoid sexual intercourse or digital vaginal examination that could disrupt the placenta.
■
Color flow Doppler USG in placenta previa is indicated to detect any placenta accreta. Colorflow Doppler (CD) in cases with asymptomatic placenta previa is done preferably between 36 and 37 weeks. In cases of placenta previa with complications (hemorrhage), delivery is done immediately regardless of gestational age.
■
MRI is superior to USG. MRI can diagnose posterior placenta previa, placenta accreta, increta and percreta with bladder invasion. Findings are: dark intraplacental bands, tenting of bladder and uterine bulging.

MANAGEMENT: AT HOME
1.  The patient is immediately put to bed.

Chapter 19: Antepartum Hemorrhage    ll 2. To assess the blood loss:
a.  Inspection of the clothing soaked with blood.
b. To note the pulse, blood pressure and degree of anemia. 3.  Quick but gentle abdominal examination to mark the
height of the uterus, to auscultate the fetal heart sound and to note any tenderness on the uterus.
4. Vaginal  examination  must  not   be  done.   Only inspection is done to see whether the bleeding is present or absent and to put a sterile vulval pad.
TRANSFER TO HOSPITAL: Arrangement is made to shift the patient to an equipped hospital having facilities of blood  transfusion,  emergency  cesarean  section  and Neonatal Intensive Care Unit (NICU).  'Flying Squad' service is ideal for transfer of such type of patients. An intravenous Ringer's  solution  drip  should  be  started and is kept running during transport. Patient should be accompanied by two or three persons fit for donation of blood, if necessary.
ADMISSION IN HOSPITAL: All cases of APH, even if the bleeding is slight or absent by  the  time-the patient reaches the hospital, should be admitted. The reasons are:  (1)  All the cases of APH  should be  regarded  as due to placenta previa unless proved otherwise. (2) The bleeding may recur sooner or later and none can predict when it recurs and how much she will bleed. ■TREATMENT ON ADMISSION
n  Immediate attention
Formulation of the line of treatment
IMMEDIATE ATTENTION: Overall assessment of the case is quickly made as regards:
1.  Amount of the  blood loss-by noting the general
condition,  pallor,  pulse  rate  and  blood  pressure (hemodynamic assessment).
2.  Blood samples are taken for group, cross-matching, hemoglobin, hematocrit and coagulation parameter.
3.  A large-bore IV cannula is sited and an infusion of normal saline is started and compatible cross-matched blood transfusion should be arranged.
4.  Gentle abdominal palpation to ascertain any uterine tenderness and auscultation to note the fetal heart rate.
5.  Inspection of the vulva to note the presence of any active bleeding.
Confirmation  of   diagnosis   is   made  from  the history,  physical examination and with sonographic examination.
FORMULATION  OF  THE  LINE  OF  TREATMENT:  The definitive  treatment  depends  upon  the  duration  of pregnancy, fetal and maternal status and extent of the hemorrhage (Flowchart 19.2).
■  Expectant management
a  Active (definite) management
II Chapter 19: Antepartum Hemorrhage
Flowchart 19.2: Scheme of management of placenta previa.


All APH patients are to be admitted

• General and abdominal examination. • Clinical assessment of blood loss.
• Hb/o, hematocrit, ABO and Rh group.



• Resuscitation, if necessary. (IV infusion/transfusion using wide bore cannula).
• Localization of placenta (USG).



Expectant treatment

■ No active bleeding.
■ Pregnancy less than 37 weeks.
■  Patient-stable hemodynamically. ■ FHR-reassuring.
■ CTG-reassuring FHR*.

37 weeks


Active interference   I

■  Bleeding continues.
■ Pregnancy more than 37 weeks. ■ Patient in labor.
■ Exsanguinated.
■ FHR-nonreassuring/absent. ■ Gross fetal malformation.
■  Steroid therapy if duration. of pregnancy <34 weeks.



Ultrasonographic examination



Placental edge is >2-3 cm
away from the internal cervical os.
i When trial of
labor is decided.
l

Internal examination in OT (double set-up
examination-rarely done).


Most women with low-lying placenta are also delivered by cesarean section.


Placental edge within 2 cm.





Cesarean Delivery (CD).


ARM± Oxytocin.



Satisfactory progress of labor.

Vaginal delivery.

• Bleeding continues. • No labor initiation.
* CTG = Cardiotocography Cesarean delivery.
i




♦   Expectant treatment: The policy had been advocated by  McAfee  and Johnson  (1945),  in  an attempt  to improve the fetal salvage without increasing undue maternal hazards. The aim is to continue pregnancy for fetal maturity without compromising the maternal health.
Vital  prerequisites:  (1)  Availability  of  blood  for transfusion  whenever  required.   (2)   Facilities  for cesarean section should be available throughout 24 hours, should it prove necessary.
Selection  of cases:  Suitable  cases  for  expectant management are: (1) Mother is hemodynamically stable (hemoglobin  10 g%; hematocrit >30%). (2) Duration of pregnancy is less than 37 weeks.  (3) Active vaginal bleeding is absent. ( 4) Fetal wellbeing is assured ( CTG and USG).
Conduct of expectant treatment:  0 Bedrest (pelvic rest)  with washroom privileges. @  Investigations-like hemoglobin  estimation,  blood  grouping  and  urine


for   protein   are   done.   @   Periodic   inspection   of the   vulva!   pads   and   fetal   surveillance  with  USG at interval of 2-3 weeks. 8 Supplementary hematinics (oral/IV)  should be given and the blood loss is replaced by adequate cross-matched  blood   transfusion,   if  the patient  is  anemic. 0 When the patient is allowed out of the bed (2-3 days after the bleeding stops), a gentle speculum  (Cusco's)  examination is made to exclude local cervical and vaginal lesions for  bleeding.  However, their   presence   does   not  negate  placenta  previa. 0 Use of tocolysis (magnesium sulfate) can be done if vaginal  bleeding  is  associated with uterine contractions. fJ Use of cervical cerclage to reduce  bleeding  and  to prolong pregnancy  is  not  helpful  (RCOG-2005).  0 Rh immunoglobulin should be  given  to  all  Rh-negative (unsensitized) women.
Expectant management at hospital  or  at  home? Hospital setting is ideal.  But considering the cost of prolonged hospitalization and psychological morbidity, home care may be allowed in some. Selected cases are-


(a) patient's compliance, (b) patient lives close to hospital, (c) 24-hour transportation to hospital is available,  {d) activity restrictions and rest assured, and (e) patient is well-motivated to understand the risks.
Termination  of  the  expectant  treatment:  The expectant  treatment  is  carried  up  to  37  weeks  of pregnancy. By this time, the baby becomes sufficiently mature.
a   Preterm delivery may have to be done in conditions, such as: (I) Recurrence of brisk hemorrhage and which is continuing. (2) Nonreassuring fetal status. (3) The fetus is dead. Repeated small bouts of hemorrhage are not an indication for termination of expectant treatment. Replacement of the blood loss can be made by blood transfusion. However, there is the risk of IUGR.
•  Steroid therapy is indicated when the duration of pregnancy  is  less  than  34  weeks.  Betamethasone reduces the risk of respiratory distress of the newborn when preterm delive1y is considered.
Active (definite) management (delivery):
The indications of definitive management (delivery) are: (I) Bleeding occurs at or after 37 weeks of pregnancy. (2) Patient is in labor. (3) Patient is in exsanguinated state on admission. (4) Bleeding is continuing and of moderate degree.  (5)  Baby  with  nonreassuring  cardiac  status. (Flowchart 19.2).
A. Cesarean  delivery  is  done  for  all  women  with sonographic  evidence  of  placenta  previa  where placental  edge  is within  2  cm from the internal os. It is especially indicated if it is posterior or thick (RCOG-2005). Most women with low-lying placenta are also delivered by cesarean section.
During the recent years, there has been wider use of cesarean section, in an attempt not only to reduce the maternal risk but also to improve the fetal salvage. Cesarean  delivery  in  cases  with  asymptomatic placenta previa is done preferable between 36 and 37 weeks. In cases of placenta previa with complications (hemorrhage), delivery is done immediately regardless of gestational age.
B. Vaginal delivery may be considered where placenta edge is clearly 2-3 cm away from the internal cervical os (based on sonography).
VAGINAL EXAMINATION: Not done these days. It is only done with a double set up arrangement in the operation theater keeping everything ready for cesarean section (see above).
Contraindications of vaginal examination:
(I) Patient in exsanguinated state.  (2)  Diagnosed cases of placenta previa confirmed by ultrasonography.  (3) Associated complicating factors such as malpresentation, pregnancy with history of previous cesarean section.

Chapter 19: Antepartum Hemorrhage     il PLACENTA ACCRETA-SPECTRUM (PAS)
(ADHERENT PLACENTA)
Placenta accreta (adherent placenta) is the invasion of placenta directly to the myometrium without any intervening decidua basalis (Fig.19.4). Fibrinoid layer is either incomplete or absent. Types of morbid adherent placentas are: (a) Plcenta accreta, (b) placenta increta and (c) placenta percreta. Overall incidence adherent placenta is 3 per 1000 deliveries. Important risk factors for placenta accreta are: placenta previa and prior cesarean delivery. It increases from 3% with prior no CD to 40% with prior two CD and as much as 61 % with prior 3 CD. Presentation: Profuse bleeding following attempted manual separation of placenta. Hematuria may be present when bladder is involved. Diagnosis is made by 3-D power Doppler and MRI (Figs. 19.2A to D).
Diagnosis: Radiologic imaging can make the diagnosis. Early diagnosis prevents maternal complications (hemorrhage, blood transfusion) and improves maternal outcome.
USG: Absence of normal hypoechoic placental and myometrial zone. Thinning out and disruption of the uterine and bladder interface and presence of lacunae and presence of many intraplacental vascular lacunae. USG has a sensitivity of 90% and a specificity of97%. MRI is useful when sonography is equivocal, for posterior placenta and determination of placental invasion with parametrium and bladder. MRI has the diagnostic
sensitivity of94% and specificity of 84%.
Management: Placenta accreta is ideally managed by a multidisciplinary team approach involving obstetrician, neonatologist, anesthetist, pelvic surgeon and urologist. It is often associated with massive hemorrhage leading peripartum hysterectomy and at times maternal death. Delivery is planned with prior arrangement of surgical team members and availability of resources (blood, uterine artery embolization) placement of ureteral stents before operation.





















Fig. 19.4: Placenta  increta  (arrows).  Hysterectomy  done due to uncontrolled PPH in a case with prior cesarean delivery.
Courtesy: Dr Manas Saha, Assistant Professor, CNMCH, Kolkata.
II Chapter 19: Antepartum Hemorrhage

PRACTICAL GUIDELINES FOR CESAREAN DELIVERY

(1) The operation should be performed by a senior obstetrician with the help of an experienced senior anesthetist. (2) Choice of anesthesia is to be made by the anesthetist. General anesthesia is preferred. (3) If the patient is in hypovolemic state and the bleeding continues, the operation has to be performed immediately along with restorative measures.  (4) Blood and blood products should be made available. (5) Counseling and consent for possible other interventions (hysterectomy) should be taken. (6) Multidisciplinary involvement should be made ( urologist, transfusion specialist). (7) Availability of a bed in a critical care unit to be ensured.  (8) Interventional radiology service is of help, especially in a case with placenta previa and accreta.
Type of incision-lower segment or classical? Ideally, surgeon should make the incision away from the placenta when placenta previa accreta is diagnosed or suspected (RCOG).
I. Classical cesarean section: (A) Advantages: (1) The operation can be done more quickly. (2) Baby is delivered without disturbing the placenta. ( 3) There is no risk of fetal exsanguination. (4) Placenta may be left in situ (in case of placenta accreta) if no bleeding, (5) Uterus may be preserved and (6) Reduction of morbidity in terms of hemorrhage, blood transfusion, ITU admission and urological injury.
(B) Disadvantages: (1) The lower segment over which the placenta is implanted cannot be visualized and as such, it is dificult to control bleeding when it is present. (2) All the hazards (immediate and remote) of classical cesarean.
2. Lower segment cesarean section: (A) Advantages: (1) Conversant technique. (2) The bleeding sinuses at the placental site can be better dealt with under direct vision and as such the decision to preserve or to remove the uterus can easily be made. (3) Placenta accreta, if accidentally met, can also be tackled effectively.
(B) Disadvantages:
1.  Engorged vessels on the anterior lower segment (anterior placenta previa) bleed profusely when they are cut.
2.  In  anteriorly situated  placenta,  the  placenta has  to  be cut or separated to deliver the baby. This causes massive hemorrhage.
3.  Risks of fetal exsanguination with such delivery is a real threat to the baby.
4.  Delivery is to be expedited to avoid fetal exsanguination.
5.  Umbilical cord should be clamped immediately to prevent neonatal hypovolemia and anemia.
6.  Risks of cesarean hysterectomy is high in such a case.
■
!]
7.  The edges of uterine cut margins become so vascular and friable, that the tissues may cut through during suturing.

PRACTICAL APPROACH TO LOWER SEGMENT CESAREAN SECTION FOR PLACENTA PREVIA
■   To  make  an  infraumbilical  longitudinal   !]	!]
abdominal incision.	·	,:-,·
a   To tackle the engorged vessels on the anterior	:i uterine wall. A vertical uterine incision is often
preferred.  Otherwise,  to put two ligatures and to cut in

between the running vessel,  while making the transverse incision. Some, however, ignore the vessels.
11  To tackle the placenta lying underneath the incision­ incision  should  be made away  from  the  placental  site. Alternatively, the placenta may have to be cut promptly to enter into the amniotic sac to deliver the baby expeditiously. The  cord  is to be clamped  quickly to prevent further fetal  exsanguination.  In  fact,  fetal blood  loss  starts  from the moment the placenta is separated or cut. In either case maternal and fetal outcomes are rarely affected.
II   Once the placenta is separated and delivered, the lower segment should be inspected for any oozing point which is over sewed, if needed. Aggressive use of oxytocics can control bleeding.
11  If hemostasis by sutures fails, the uterus could be preserved using Cho suture. Hemostasis at placental site can be achieved with Bakri or Foley balloon temponade. Other options are bilateral interailiac artery ligation (uterine devascularization), embolization or hysterectomy. Tight intrauterine packing is done to give firm pressure on the oozing area. The plug end is brought out through the vagina and suturing the uterine incision is done over the plug. The procedure most often pays good dividend. The plug is removed vaginally after 48 hours.
■   Isthmic-cervical apposition suture-helps  to control bleeding from the lower segment,  especially in a case with  placenta  previa or  morbid  adherent  placenta.  A suture is passed through the lower flap of  the  uterine incision  (2  cm  medial  to  its  lateral  border)  to  the posterior aspect. The same suture is then brought back through (1 cm medial to the first) posterior to the anterior uterine wall and then tied anteriorly. The same procedure is repeated on the other side. The cervical canal is kept patent while tightening the apposition suture. Injury to the bladder and uterus are avoided.
■   Baby's blood hemoglobin level is to be checked at birth and if necessary, arrangement is made for blood transfusion.

PRACTICAL GUIDE TO LOWER SEGMENT APPROACH FOR PLACENTA PREVIA ACCRETA
■  Women   with   anterior   placenta   previa,    !]d.!]
implanted at the site of prior hysterotomy or
i1   · .
cesarean incision,  there is an increased risk   -of placenta accreta  (Fig.  19.4).  The risk of   .I placenta previa increases with the number of
prior cesarean delivery. This may need hysterectomy. The risk of placenta previa accreta increases from 3% with no prior to 61 % with three prior cesarean deliveries. MRI is useful to confirm the diagnosis.
■   A multidisciplinary team  approach  (urologists,  pelvic surgeons, transfusion specialists) should be made.
Management: Tertiary care center with availability of resources: ♦    Interventional radiologist.
♦    Delivery   $34°17    weeks   of   gestation   with   antenatal corticosteroid administration.
♦   Anesthesia-general.
♦    Central line or arterial vascular access. ♦   Placement of retrograde ureteral stent.
♦  Uterine artery catheter for embolization and/or balloon occlusion.


♦   Blood bank facilities for availability of PRBC, FFP; Platelets.
-"  Incision is made away from  the placenta.  Incising  the placenta for delivery causes massive hemorrhage and may end in hysterectomy (Fig. 19.4).
"  Delivering the baby without placental separation may allow conservative management of placenta, if there is no bleeding.
"  In a case with morbid adherent placenta without bleeding, placenta may be left in situ. The uterus is then closed when preservation of the uterus is desired.
"  Any attempt of placental separation in a case with morbid adherent placenta (placenta accreta) should be avoided as it excites massive hemorrhage and risks hysterectomy.
"  In presence  of bleeding,  hysterectomy could be  done after closing the uterus without any attempt to separate the placenta. This reduces blood loss.

ABRUPTIO PLACENTAE (Syn: Accidental Hemorrhage, Premature Separation of Placenta)

DEFINITION: It is one form of antepartum hemorrhage where   the   bleeding   occurs   due   to   premature separation of normally situated placenta. Out of the various nomenclatures, abruptio placentae seems to be appropriate one.
VARIETIES (Figs. 19.SA to D)
(I) Revealed: Following separation of the placenta, the blood insinuates downwards between the membranes and the decidua. Ultimately, the blood comes out of the cervical canal to be visible externally. This is the most common type.
(2)  Concealed:  The  blood  collects  behind  the separated   placenta   or   collected   in   between   the membranes  and  decidua.   The  collected  blood  is prevented from coming out of the cervix by the presenting part which presses on the lower segment. At times, the blood may percolate into the amniotic sac after rupturing the membranes. In any of the circumstances blood is not visible outside. This type is rare (10-20%).
(3) Mixed: In this type, some part of the blood collects inside (concealed) and a part is expelled out (revealed). Usually one variety predominates over the other. This is quite common.

Chapter 19: Antepartum Hemorrhage

Bleeding is almost always maternal. But placental tear may cause fetal bleeding.
Incidence and significance: The overall incidence is about 1 in 100 deliveries.  Depending on the extent (partial or complete) and intensity of placental separation, it is a significant cause of perinatal mortality (10-15%) and maternal mortality  (2-5%). Abruptio placentae contributes nearly 30% of allAPH cases and majority (60%} occur in the third trimester ofpregnancy.
PATHOGENESIS:  Depending  upon  the  etiological factors, premature placental separation is initiated by hemorrhage into the decidua basalis. The collected blood (decidual hematoma) at the early phase, hardly produces any morbid pathological changes in the uterine wall or on the placenta. However, depending upon the severity (acute or chronic abruption), changes in the spiral arteries lead to degeneration, infarction and necrosis of the decidua basalis as well as the placenta adjacent to it.  Histologic  features  of  chronic  deciduitis,  decidual vasculopathy, villitis are present.
Rupture  of  the  basal  plate  may  also  occur,  thus communicating the hematoma with the  intervillous space. The decidual hematoma may be small and self­ limited; the entity is evident only after the expulsion of the placenta (retroplacental hematoma). It has to be remembered that absence of rhythmic uterine contractions plays a  significant  role for the  blood to  remain concealed  (Table  19.3).  The features of retroplacental hematoma are: (a) Depression found on  the  maternal  surface  of the  placenta  with a  clot which may be found firmly attached to the area, and (b)  Areas  of  infarction  with  varying  degrees  of organization (Fig. 19.6).
When a major spiral artery ruptures, a big hematoma is formed. Thrombin generated following decidual hemor­ rhage, triggers the action of matrix metalloproteinases, inflammatory cytokines and the coagulation cascade.
COUVELAIRE UTERUS (uteroplacental apoplexy) (Fig. 19.7): It is a pathological entity first described by Couvelaire and is met with in association with severe form of concealed













Figs. 19.SA to D: Varieties of abruptio placentae: (Al Concealed; (BJ Revealed; (CJ Marginal (subchorionic); (D) Preplacental (subamniotic).
ED Chapter 19: Antepartum Hemorrhage



Clinical manifestations of hemorrhage
■   Blood may accumulate behind the placenta when it is totally separated from the uterine wall except at the margin (Fig. 19.SA)-concealed type.
■   Blood may dissect downwards in between the membranes and the uterine wall and ultimately escapes out through the cervix or may be kept concealed by the pressure of the fetal head on the lower uterine segment (Fig. 19.SB)-revealed type.
■  Blood may gain access to the amniotic cavity after rupturing the membranes (Fig.19.5D).
■   Blood may percolate through the layers of myometrium up to the serous coat, known as Couvelaire uterus (Fig.19.7).

















Fig. 19.6: Appearance of a placenta following delivery. Placenta shows adherent clots and depression.

Ultrasonographic localization of hemorrhage
■   Retroplacental: Between the placenta and the myometrium (Figs.19.SA and B) (fetal mortality-SO%).
■   Subchorionic:  Between  the  placenta  and  the  membranes (Fig. 19.SC) (fetal mortality< 10%).
■   Pre-placental: Between the placenta and the amniotic fluid, within amnion and chorion (subamniotic) (Fig.19.5D).

■   Fetal prognosis depends upon: (i) size and (ii) the type of the hematoma. Retroplacental hematoma (based on USG) has got worst prognosis with high fetal mortality (50%). Subchorionic smaller-sized hemorrhages have less (10%) fetal mortality. Subamniotic is clinically less significant.

















Fig. 19.7: Couvelaire uterus. Uterus was preserved.



abruptio placentae. There is massive intravasation of blood into the uterine musculature up to the serous coat. The condition can only be diagnosed on laparotomy.
Naked eye features: The uterus is of dark port wine color which may be patchy or diffuse. It tends to occur initially on the cornu before spreading to other areas, more specially over the placental site. Subperitoneal petechial hemorrhages are found under the uterine peritoneum and may extend into the broad ligament. There may be free blood in the peritoneal cavity or broad ligament hematoma.
Microscopic appearance: The uterine muscles over the affected area are necrosed and there is infiltration of blood and fluid in between the muscle bundles. Most of the muscular dissociation occurs in the middle and outer muscle layers. The serosa may split on occasions, to allow the blood to enter the peritoneal cavity. The blood vessels show acute degenerative changes with thrombosis.
The myometrial hematoma rarely interferes with uterine contractions following delivery. Thus, the presence ofCouvelaire uterus as observed during cesarean section is not an indication per se for hysterectomy.
CHANGES IN OTHER ORGANS: In the liver, apart from the changes found in pre-eclampsia, presence of fibrin knots in the hepatic sinusoids is an important finding.


Kidneys may show acute cortical necrosis or  acute tubular necrosis. The precise mechanism is not clear but may be due to intrarenal vasospasm as a consequence of massive hemorrhage. Shock proteinuria is probably due to renal anoxia which usually disappears 2 days after delivery, whereas proteinuria due to pre-eclampsia tends to last longer.

Etiology of placental abruption.
The exact etiology of separation of a normally situated placenta remains obscure in majority of cases.
Risk factors are:
+   Prior abruption: Risk of recurrence varies from 5-17%.
+   General factors: (a) High parity (,,5) pregnancies, three times more common than in first  birth,  (b) advancing age of the mother, (c) poor socioeconomic condition, (d) low nutritional state, and (e) smoking (vasospasm).
+   Hypertension in pregnancy is most important. Pre-eclampsia, gestational hypertension and essential  hypertension all are associated (10-50%). The mechanism is: Spasm of the vessels in the  uteroplacental  bed (decidual spiral  artery)  ➔  anoxic endothelial damage ➔ rupture of vessels and extravasation of
blood in the decidua basalis (retroplacental hematoma).

Contd...


Contd...
♦  Trauma: Traumatic separation of the placenta usually leads to its marginal separation with escape of blood outside. The trauma may be: (i) External cephalic version, especially under anesthesia using great force, (ii) Road traffic accidents, blunt trauma or blow on the abdomen, and (iii) Needle puncture at amniocentesis.
♦  Sudden uterine decompression of the uterus leads to diminished surface area of the uterus adjacent to the placental attachment and results in shearing of the placenta. Clinical situations are: (a) following delivery of the first baby of twins, (bl sudden escape of liquor amnii in polyhydramnios, and (cl Premature Rupture of Membranes (PROM).
♦  Short cord, either relative or absolute, can bring about placental separation during labor by mechanical pull.
•  Supine hypotension syndrome: There is passive engorgement of the uterine and placental vessels resulting in rupture and extravasation of the blood.
♦  Placental anomaly: Circumvallate placenta.
♦  Sick placenta: Poor placentation, as evidenced by abnormal uterine artery Doppler waveforms. (lschemic placenta).
•  Folicacid deficiency even without evidence of overt megaloblastic erythropoiesis.
•  Uterine factor: Placenta implanted over a septum (septate uterus) or a submucous fibroid.
♦  Torsion of the uterus leads to increased venous pressure and rupture of the veins with separation of the placenta.
•  Cocaine abuse is associated with increased risk of transient hypertension, vasospasm and placental abruption.
•  Thrombophilias: Both the inherited or acquired are associated. •  Hyperhomocysteinemia is associated with recurrent abruption.

BLOOD COAGULOPATHY: It is due to excess consump­ tion  of  plasma   fibrinogen   due   to   disseminated intravascular  coagulation  and  retroplacental  blee­ ding. There is overt hypofibrinogenemia ( <150 mg/ dL) and elevated levels of fibrin degradation products and D-dimer (Table 41.9).
CLINICAL CLASSIFICATION: Depending upon the degree of placental abruption and its clinical effects, the cases are graded as follows:
•   Grade 0: Clinical features may be absent. The diag­ nosis is made after inspection of placenta following delivery.
•   Grade 1  (40%):  (i) vaginal bleeding is slight,  (ii) uterus: irritable, tenderness may be minimal or absent, (iii)  maternal BP and fibrinogen levels unaffected and (iv) FHS is good.
•   Grade 2 ( 45%): (i) vaginal bleeding mild to moderate, (ii)  uterine  tenderness  is  always  present,  (iii) maternal pulse t,  BP is maintained,  (iv) fibrinogen level may be decreased,  (v) shock is absent and (vi) fetal distress or even fetal death occurs.
•   Grade 3 (15%): (i) bleeding is moderate to severe or may be concealed, (ii) uterine tenderness is marked, (iii) shock is pronounced, (iv) fetal death is the rule and (v) associated coagulation defect or anuria may complicate.

Chapter 19: Antepartum Hemorrhage    II fB CLINICAL FEATURES

The clinical features depend on: (i) Degree of separation of placenta, (ii)  Type of abruption-acute or chronic separation  occurs  and  (iii)  Variety-concealed  or revealed.  But it may be very deceptive in posteriorly implanted placenta. Acute abruption (concealed variety) typically presents with abdominal pain, vaginal bleeding, uterine contractions and tenderness. The clinical features of the revealed and mixed variety are given in tabulated form (Table 19.4).
DIAGNOSIS: Mainly clinical. Ultrasonography or MRI may be helpful. MRI is useful when USG is equivocal.
Laboratory findings: Rise in abnormal serum markers in early pregnancy: elevated MSAFP, hCG, reduced levels of PAPP-A or estriol are associated with increased risks ofplacental abruption.
DIFFERENTIAL DIAGNOSIS: (a) Revealed type: There may be occasional diagnostic difficulty with placenta previa. The differentiating points have been given previously in  tabulated  form  (Table  19.2).  Confusion  with  the indeterminate causes of APH  is  difficult  to eliminate and (b) Mixed or concealed type: This variety is often confused  with-(i)  rupture  uterus,  (ii)  rectus  sheath hematoma, (iii) appendicular or intestinal perforation, (iv) acute hydramnios and (v) tonic uterine contraction.
The essential points to arrive at the diagnosis of the
concealed variety are: (i) shock out of proportion to external bleeding, (ii) unexplained extreme pal101; (iii) presence of pre­ eclamptic features, (iv) uterus is tense, tender and woody hard, (v) FHS: irregular (hypoxia), or is absent (dead fetus), (vi) diminished urinary output, (vii) presence of blood coagulation disorders.
PROGNOSIS: The prognosis of the mother and the baby depends on the clinical types (revealed, mixed or purely concealed), degree of placental separation, the interval between the separation of the placenta and delive1y of the baby and the eficacy of treatment. Hypofibrinogenemia and consumptive coagulopathy are often observed with severe abruption. Perinatal morbidity and mortality are increased.  Perinatal death is increased by ten-fold. Bleeding  in  placental  abruption  is  almost  always maternal. Fetal bleeding is observed only with traumatic variety of placental abruption.  Chronic  abruption often presents  with  chronic  placental  inflammation  and dysfunction (IUGR, oligohydramnios).
Maternal morbidity is high. Maternal mortality varies from 2-8%. However, with better understanding in the management of  shock,  coagulation  failure  and renal failure, maternal death has been reduced markedly. Some cases who manage to survive may develop features of ischemic pituitary necrosis. There is failure of lactation ( Sheehan' s syndrome) later on.

I MANAGEMENT

Prevention: The prevention aims at-(1) Elimination of the known factors likely to reduce placental separation.
EI  Chapter 19: Antepartum Hemorrhage

Table 19.4: Clinical features of revealed and mixed variety of abruptio placentae.


..



Parameters Symptoms

Character of bleeding
General condition

Pallor
Features of pre-eclampsia
Uterine height Uterine feel

Fetal parts FHS
Urine output Laboratory tests Blood:Hb%
Coagulation profile




Urine for protein
Confusion in diagnosis


Revealed
Abdominal discomfort or pain followed by vaginal bleeding (usually slight).
Continuous dark color (slight to moderate).

Proportionate to the visible blood loss, shock is usually absent.
Related with the visible blood loss. May be absent.

Proportionate to the period of gestation.
Normal feel with localized tenderness, contractions frequent and local amplitude
Can be identified easily.
Usually present FHR-irregular (hypoxia). Normal.

Low value proportionate to the blood loss. Usually unchanged.





May be absent.
With placenta previa. As such vaginal examination is withheld unless certain in the diagnosis.


Mixed (concealed features predominate)
Abdominal acute intenses pain followed by slight vaginal bleeding. The pain becomes continuous.
Continuous, dark color (usually slight) or blood-stained serous discharge.
* Shock may be pronounced which is out of proportion to the visible blood loss.
Pallor is usually severe and out of proportion to the visible bleeding. Frequent association.

May be disproportionately enlarged and globular. Uterus is tense, tender and rigid.

Difficult to make out.
Usually absent (fetus-dead). Usually diminished.

Markedly lower, out of proportion to the visible blood loss.
Variable changes (consumptive coagulopathy): Clotting time increased (>6 min). Fibrinogen level-low (<150 mg/dl).
•
•
•
•
•
Platelet count-low (consumptive coagulopathy) . t partial thromboplastin time.
t FDP and D-dimer.
Usually present.
With acute obstetrical-gynecological-surgical complications.

* Shock: Shock is often due to blood loss and hypovolemia or due to coagulopathy. Mild hemorrhage (<15% of the blood volume loss) is generally not associated with any change of vital signs. Moderate hemorrhage (15-30% of the blood volume loss) is associated with tachycardia, hypotension,-!-pulse pressure and mean arterial pressure whereas severe hemorrhage (loss >30-40%) is associated with features of shock.


(2) Correction of anemia during antenatal period so that the patient can withstand blood loss. (3) Prompt detection and institution of the therapy to minimize the grave complications namely shock, blood coagulation disorders and renal failure.
Prevention of known  risk factors likely to cause placental separation are:
•   Early  detection  and  effective  therapy  of  pre­ eclampsia  and  other  hypertensive  disorders  of pregnancy.
•  Needle puncture during amniocentesis should  be under ultrasound guidance.
•  Avoidance of trauma-especially forceful external cephalic version under anesthesia.
•  To avoid sudden decompression of  the uterus­ in acute or  chronic  hydramnios,  amniocentesis is preferable to artificial rupture of the membranes.
•  To avoid supine hypotension the patient is advised to lie in the left lateral position in the later months of pregnancy.
•  Routine administration of folic acid from the early pregnancy-of doubtful value.

I TREATMENT IN THE HOSPITAL

The patient is to be treated as outlined in placenta previa and arrangement should be made to shift the patient to an equipped maternity unit as early as possible.

IN THE HOSPITAL: Assessment of the case is to be done as regards: (a) Amount of blood loss, (b) maturity of the fetus, (c) whether the patient is in labor or not (usually labor starts), (d) presence of any complication and (e) type and grade of placental abruption (p. 239).
Emergency   measures:   (i)   Blood   is   sent   for hemoglobin and  hematocrit estimation,  coagulation profile (fibrinogen level, PDP, prothrombin time, activated partial thromboplastin time  and  platelets),  ABO  and Rh grouping  and  urine  for detection  of  protein  and (ii) Ringer's solution drip is started with a wide bore cannula and arrangement for blood transfusion is made for resuscitation. Close monitoring of maternal and fetal condition is done (Flowchart 19.3).
Management options are:  (a) Immediate delivery, (b) management of complications if there is any and (c) expectant management (rare).
Chapter 19: Antepartum Hemorrhage     ea -Flowchart 19,3: Scheme of management of abruptio placentae.
L












!
Patient in labor

ARM± oxytocin

I   Abruptio placentae   I
Emergency measures	■ General and abdominal examination • lnfusion-crystalloids	■ Fetal status clinical
■ USG-fetal status
• Blood transfusion	■ Grade of abruption (see p. 239)
• Periodic coagulation profile	■ Hb%, hematocrit, platelet count, coagulation profile
• Urine output	■ ABO and Rh group • Fetal monitoring (electronic)               Resuscitation
l
I	l
Revealed	Expectant management of	Concealed placental abruption is an
!
1
!
exception, not the rule.	Delivery Patient not in labor
+

Deliyery	ARM ± oxytocin	Cesarean delivery
+






I

Vaginal jdelivery	VAaRgMin±al bdxeylitvoecriyn	Cesarean+ delivery	Vaginal delivery j(selected cases)
OXYTOCICS TO BE CONTINUED TO IMPROVE UTERINE TONE ALONG WITH BLOOD TRANSFUSION	I
!
!



♦   Definitive treatment (immediate delivery):
11   The patient is in labor: Most patients are in labor following a term pregnancy: The labor is accelerated by low rupture of the membranes.  Rupture of the membranes with escape of liquor amnii accelerates labor and increases the uterine tone also. Oxytocin drip may be started to accelerate labor when needed.
Vaginal delivery is favored in cases with: (i) Limited placental abruption,  {ii) FHR tracing is reassuring,  {iii) facilities for continuous (electronic) fetal monitoring is available, {iv) prospect of vaginal delivery is soon or (v) placental abruption with a dead fetus.
The  advantages  of  amniotomy  are:     Initiates myometrial contraction and labor process, G)  expedites delivery, ft better compression of spiral artery to arrest hemorrhage,  r)   reduces  entry of thromboplastin  into maternal circulation and thereby   reduces the risk of renal cortical necrosis and DIC.
■  The patient is not in labor: (i) Bleeding continues and (ii) >Grade I abruption: Delivery either by (A) induction of labor or (B) cesarean section.
(A)  Induction  of  labor  is  done  by  low  rupture of membranes. Oxytocin may be added to  expedite delivery. Labor usually starts soon in majority of cases and delivery is completed quickly ( 4-6 hours). Placenta with varying  amount of retroplacental clot is expelled most often simultaneously with the delivery of the baby. Injection  oxytocin  10 IU IV  (slow) or IM or injection methergine 0.2 mg IV is given with the delivery of the baby  to  minimize  postpartum  blood  loss.  Oxytocics should be used to improve the uterine tone along with blood transfusion.

(B)  Cesarean section: Indications  are:  (a) severe abruption with a live and viable fetus, (b) appearance of adverse features (fetal distress, falling fibrinogen level, oliguria). (c)  amniotomy could not be done (unfavorable cervix), {d) prospect of immediate vaginal delivery despite amniotomy is remote,  (e) amniotomy failed to control bleeding,  (f)  amniotomy failed to arrest the process of abruption (rising fundal height).
Anesthesia  during  cesarean  section:   Regional anesthesia is generally avoided when there is significant hemorrhage.  This is to avoid profound  and persistent hypotension.
Expectant  management  in  a  case  of  placental abruption is an  exception  and not the rule.  Cases of  chronic abruption  (small  size)  where  bleeding  is slight and has stopped (grade I abruption), fetus with reactive CTG and remote from term ( <34 weeks), may be considered.  The goal is to prolong the pregnancy with the hope of improving fetal maturity and survival. Continuous electronic fetal monitoring is maintained. Patient should be observed in the labor ward for 24-48 hours to ensure that  no  further  placental  separation is occurring.  Meanwhile betamethasone is given to accelerate fetal lung maturity in  the  event  preterm
delivery is contemplated. Tocolysis with MgSO4 has been
found to reduce further  separation.  MgS04  may give
added benefits of neuroprotection. Further separation of placenta at any moment may cause fetal death. Currently expectant  management  with  placental  abruption, in selected cases,  showed  prolongation  of pregnancy (>l week) without any adverse maternal and fetal effect.
Management  of complications  (Table  19.5):  The major  complications  of  placental  abruption  are:
mJ Chapter 19: Antepartum Hemorrhage



Maternal
■  In revealed type-maternal risk is proportionate to the visible blood loss and maternal death is rare.
■  In concealed variety-the following complications may occur either singly or in combination. • Hemorrhage which is concealed inside the uterus. It may be intra peritoneal or broad
ligament hematoma.
• Shock may be out of proportion to the blood loss, need of Cesarean Delivery (CD), need  of blood transfusion, amniotic fluid embolism is high.
• Blood coagulation disorders (consumptive coagulopathy). • Pituitary failure (Sheenhan syndrome).
• Organ damage:  Oliguria and renal failure high due to-(a) hypovolemia, (b) serotonin
liberated from the damaged uterine muscle producing renal ischemia and (c) acute tubular necrosis. In a severe case: (d) cortical necrosis and renal failure.
• Postpartum hemorrhage due to-(a) atony of the uterus and (b) increase in serum FDP. • Puerperal sepsis.	• Death
Risk of recurrence in subsequent pregnancy is about 5-20% with high perinatal mortality.

Fetal/Neonatal
■  In revealed type: The fetal death is to the extent of 25-30%.
■  In concealed type: Fetal death is high (50-100%). The deaths are due to prematurity and anoxia due to placental separation.
■  Fetal  mortality: (a)  In cases with retroplacental hematoma-50% and (bl Subchorionic hemorrhage-10%.
■  Fetal hypoxia leads to periventri-cular leukomalacia and sudden infant death syndrome.
■  Neonatal: Prematurity and the complications (Ch. 32).



(a) hemorrhagic shock, (b) DIC, (c) renal failure and (d) uterine atony and postpartum hemorrhage.
Hypovolemia  should  be  corrected  early.  Blood pressure may not be a correct guide to assess shock, as it may be high due to severe degree of vasospasm. Irrespective of the patient's general condition, at least 1 L of blood transfusion should be the minimum when the diagnosis of concealed accidental hemorrhage is made. The best  guide  to monitor  the  patient  is  the  use  of Central Venous Pressure (CVP), which is maintained at
IO cm of water. Hematocrit should be at least 30% and urinary output   30 mL/h.
A.  Hemorrhagic shock-classificationof obstetric hemorrhage is based upon volume deficit. Details of management is discussed.
B.  DIC-release of tissue thromboplastin in placental abruption causes consumptive coagulopathy (defibrination syndrome). Diagnosis is based on the coagulation profile assessment. Treatment is to restore the hematologic deficiency (fibrinogen level >150 mg/dL), 1 unit  (500 mL) of fresh blood raises the  blood volume and the  fibrinogen level approximately by 12.5 mg/100 mL. Platelet count increases by 10,000-15,000/mm3 to replenish the volume deficit and to arrest the pathologic process. Details of management is discussed on p. 584.
Fetomaternal hemorrhage is common with traumatic variety of placental abruption. To combat fetomaternal hemorrhage 300 mg of anti-D immunoglobulin is administered to all Rh-negative women. The amount of fetal to maternal bleed is usually <15 mL.

I INDETERMINATE BLEEDING

The exact cause of vaginal bleeding in late pregnancy is not clearly understood in few cases.  The diagnosis of unclassified bleeding should be made after exclusion of placenta previa,  placental  abruption  and local causes. Rupture  of  vasa  previa,   marginal  sinus  hemorrhage, circumvallate placenta,  marked  decidual reaction  on endocervix or excessive show may be a possible causes of such bleeding.


VASA PREVIA: Overall incidence is 1 in 2500 deliveries. The  unsupported  (without Wharton  Jelly)  umbilical vessels in velamentous placenta, lie below the presenting part and run over the cervical os. These vessels are torn either spontaneously or during rupture of membranes. Diagnosis: USG with color Doppler and pulse Doppler mapping is useful to detect umbilical vessels over the cervical os.  Fetal  mortality  is  high  (50%)  due  to fetal exsanguination. Detection of nucleated red blood cells (Singer's alkali denaturation test) or fetal hemoglobin (Apt  test)   is  diagnostic.  Vaginal  bleeding  is  often associated with fetal distress  ( tachycardia,  sinusoidal FHR tracing).
MANAGEMENT:   Management   depends   on   fetal gestational  age,  severity  of  bleeding,  persistence  or recurrence of bleeding. Center must be equipped with appropriate neonatal care facilities in view of preterm delivery.
A.  Considering  the risks  of  bleeding,  patient  with confirmed vasa previa, needs antenatal admission at 28-32 weeks of gestation. Management is similar to placenta previa.  Antenatal  monitoring with  NST twice  a  week is done to assess cord compression.  Cesarean delivery between 34°17  to 36°17 is to be done. Expectant management can be done in selected cases for fetal lung maturity similar to placenta previa. Antenatal corticosteroids should be given.
B. Any case with bleeding vasa previa, delive1y should be done  by category-I  emergency cesarean section. Intrapartum diagnosis of vasa previa, needs expeditious delive1y.
C. A case of confirmed vasa previa at term ( 37 weeks) should be delivered by elective cesarean section prior to onset of labor.
D.  Delivery  at 35  weeks  may  be  needed  to  avoid catastopic hemorrhage.
E. Neonatal blood transfusion may be needed.
Chapter 19: Antepartum Hemorrhage    1D
fi-mH-i
>  Hemorrhage is a major cause of maternal morbidity and mortality throughout the world and it is also the important cause for Obstetric Intensive Care admission.
>  Antepartum hemorrhage is defined as the bleeding from or within the genital tract after 28th week of pregnancy but before the birth of the baby. Causes may be placental, extraplacental or unexplained.
>  Major causes of APH are two-placenta previa and abruptio placentae.
>  Placenta previa is classified into two types. Placentography (USG} confirms the. Abruptio placentae should be differentiated from placenta previa. Revised classification (ACOG, ACR, 2014): (a} True placenta previa: Placenta covers the internal os, (b} Low-lying placenta: Placenta lies within 2 cm of internal os but does not cover it.
>  Placenta previa can be diagnosed by-(i} ultrasonography (preferred}, (ii} clinically, transvaginal ultrasound classify placenta previa:
>  (a} within 2 cm or (b} >2 cm from the undilated internal cervical os. Vaginal examination for the diagnosis of placenta previa should not be done as it provokes severe hemorrhage.
>  Imaging modalities (Doppler USG, MRI} have reduced the need of double set up examination and the risk of bleeding thereof as they can make improved diagnosis of placenta previa, accreta and abruption.
>  MRI is superior to USG. MRI can diagnose posterior placenta previa, placenta accreta, increta and percreta with bladder invasion.
>  Management of placenta previa-(a) Expectant: Pregnancy is preterm (<37 weeks}, no active bleeding and the fetus is reactive (CTG}, patient is admitted and managed expectantly, (b} Active intervention: Presence of active bleeding, term pregnancy, patient in labor or with non-reassuring fetal status-delivery.
>  Maternal complications of placenta previa are-hemorrhage (antepartum, intrapartum, postpartum}, retained placenta (placenta accreta}, increased operative delivery and maternal morbidity and mortality.
>  Fetal complications of placenta previa are-prematurity, asphyxia, IUFD and increased perinatal mortality.
>  Delivery is planned based on the sonographic location of placenta. Women with placenta previa with placental edge within 2 cm of internal os are delivered by cesarean section. Otherwise vaginal delivery may be allowed. Most women with low-lying placenta are also delivered by cesarean section.
>  Risk of placenta accreta is high in a woman with placenta previa when she has got uterine scar (myomectomy, hysterotomy}.
>  Risk of placenta previa accreta is high in a woman with prior cesarean delivery. The risk increases from 3% with no prior to 61% with three prior cesarean deliveries.
>  Antenatal diagnosis of placenta accreta should be made with radiographic studies (Doppler USG, MRI}.
> Placenta accreta should be managed with a multidisciplinary team approach (hematologists, anesthetists, urologists, obstetrician and pelvic surgeons}.
>  Risk factors for placental abruption are-previous abruption, increased maternal age, increased parity, hypertension, thrombophilia, rapid uterine decompression (polyhydramnios}, trauma or smoking.
>  Placental abruption is diagnosed mainly clinically and supported by laboratory, USG or MRI.
>  Management of placental abruption depends on severity of placental abruption, gestational age and condition of the mother and the fetus.
>  Delivery is done in most cases of placental abruption. Betamethasone is given to accelerate fetal lung maturation. Tocolysis with Magnesium Sulfate (MgSO } has been found helpful to stop further abruption. MgSO  is a neuroprotector also. Expectant management of placental abruption is rarely done.
4
4
>  Maternal complications of placental abruption are-hemorrhage, shock, coagulation failure, oliguria, anuria, PPH and even maternal death.
>  Perinatal morbidity and mortality are high mainly due to prematurity and hypoxia. >  The important risk factors for placenta previa accreta is prior CD.
>  Imaging with USG is superior to MRI for routine evaluation.
>  Superitory of MRI over USG is to assess the degree of invasion to adjacent pelvic organs/tissues.
>  Delivery should be done at or around 34 weeks with prior corticosteroid therapy. Incision is made above the placental site. >  No attempt is made to disturb the placenta.
>  Delivery is done at a teritary care center and managed by multidisciplinary team. The place of interventional radiology should judge in terms of benefits and the risks involved in the procedure.

Medical and Surgical Illnesses
Complicating Pregnancy






,   CHAPTER OUTLINE  ,
❖ Hematological Disorders in Pregnancy
► Anemia in Pregnancy
►  Iron Deficiency Anemia ► Megaloblastic Anemia ► Dimorphic Anemia
► Aplastic Anemia
► Hemoglobinopathies
► Sickle Cell Hemoglobinopathies ► Thalassemia Syndromes
►  Platelet Disorders
❖ Heart Disease in Pregnancy ► General Management
► Management during Labor


► Specific Heart Disease during Pregnancy and the Management
❖ Diabetes Mellitus and Pregnancy ► Gestational Diabetes Mellitus
(GDM)
► Overt Diabetes
❖ Thyroid Dysfunction and Pregnancy ❖ Jaundice in Pregnancy
❖ Viral Hepatitis
❖ Epilepsy in Pregnancy ❖ Asthma in Pregnancy
❖ Systemic Lupus Erythematosus (SLE) ❖ Tuberculosis in Pregnancy
❖ Syphilis in Pregnancy


❖ Parasitic and Protozoa! Infestations in Pregnancy
❖ Pyelonephritis in Pregnancy
► Asymptomatic Bacteriuria (ASB) ❖ Viral Infections in Pregnancy
❖ Human Immunodeficiency Virus (HIV) Infection and Acquired Immunodeficiency Syndrome (AIDS)
❖ COVID-19 in Pregnancy
❖ Surgical Illness during Pregnancy ❖ Acute Pain in Abdomen during
Pregnancy
❖ Headache in Pregnancy
❖ Acute Fatty Liver in Pregnancy





HEMATOLOGICAL DISORDERS IN PREGNANCY

■ ANEMIA IN PREGNANCY

Anemia is the most common hematological disorder that may occur in  pregnancy,  the others  being rhesus isoimmunization  and blood coagulation disorders.
INCIDENCE: According to the standard laid down by WHO, anemia in pregnancy is present when the hemoglobin (Hb} concentration in the peripheral blood is 11 g/100 mL or less (or the hematocrit <33%). With this criteria 50%  of pregnant women are anemic. The centers for disease control and prevention (CDC} defines anemia as the hemoglobin concentration of <11 g/dL (hematocrit <33%} in the first or third trimester or a hemoglobin concentration of <10.5 g/dL (hematocrit <32%} in the second  trimester.  During  pregnancy  plasma volume expands (maximum around 32 weeks} resulting in Hb dilution. For this reason, Hb level below 10 g/dL at any time during pregnancy is  considered  anemia  (WHO, CDC}. Hb level at or below  9  g/dL requires detailed investigations and appropriate treatment. Adopting this lower level, the incidence of anemia in pregnancy ranges widely from 40 to 50% in the tropics compared to 3-38% in the high income countries. Anemia is responsible for 20% of maternal deaths in the low and middle income
countries.

I CLASSIFICATION
The anemia may be classified in various ways. For all practical purposes, a simplified classification is given which is helpful in the management of the cases. Not uncommonly, an atypical form of anemia may be met with and in such cases, the opinion of a hematologist should be sought for:
■   Physiological anemia of pregnancy. ■   Pathological:
♦    Deficiency anemia (isolated or combined}: •    Iron deficiency (95%}.
•    Folic acid deficiency.
•   Vitamin B12 deficiency. •    Protein deficiency.
♦    Hemorrhagic:
•   Acute: Following bleeding in early months or APH. •    Chronic: Hookworm infestation, bleeding piles.
♦    Hereditary-hemoglobinopathies: •   Thalassemias.
•    Sickle cell hemoglobinopathies. •    Other hemoglobinopathies.
•   Hereditary hemolytic anemias (RBC membrane defects, spherocytosis ).
♦    Bone marrow insufficiency-hypoplasia or aplasia due to radiation, drugs (aspirin, indomethacin}.
♦    Anemia ofinfection (malaria, tuberculosis, kala-azar).
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy


♦    Chronic disease (renal) or neoplasm.
♦    Hematologic malignancy (leukemias, lymphomas).
♦   Hemolytic:  SLE,  HELLP syndrome, autoimmune hemolysis, drug induced G6PD deficiency.


Table 20.1: Normal blood values in nonpregnant and pregnant state.
Second-of-half Blood values	Nonpregnant	pregnancy
Hemoglobin (Hb)	14.8 g/100 ml	11-14 g/100 ml



However, the obstetricians are more concerned with two common types of anemia-the deficiency anemia and hemorrhagic anemia. For detailed description of other types, any standard book ofhematology may be consulted.


Red Blood Cells (RBC)

Packed Cell Volume (PCV) (hematocrit)


5 million/mm3

39-42%


4-4.5 million/ mm3
32-36%



I CONCEPT OF PHYSIOLOGICAL ANEMIA
Maternal  plasma  volume  increases  by about 40-50%. RBC volume increases by 20%. There is relative fall in the level of hemoglobin and hematocrit during pregnancy. All these values return to normal by 6 weeks postpartum. In addition, there is marked demand of extra iron during pregnancy especially in the second half. Even an adequate diet cannot provide the extra demand of iron. Thus, there always  remains a physiological iron deficiency state during pregnancy. As a result, there is not only a fall in hemoglobin concentration and hematocrit value in the second half of pregnancy but there is also associated low serum iron, increased iron binding capacity and increased rate of iron absorption as found in iron deficiency anemia.
Thus,  the  fall  in  the  hemoglobin  concentration during pregnancy is due to combined effect of hemo­ dilution and negative iron  balance. The anemia is normocytic and normochromic in type. Normal blood values in nonpregnant and pregnant state are given in Table20.l.
CRITERIA OF PHYSIOLOGICAL ANEMIA: The lower limit of physiological  anemia during the  second  half of pregnancy should fulfil the following hematological values: (I) Hb-10 g%, (2) RBC-3.2 million/mm3,  (3) PCV-32%  and  (4)  Peripheral  smear  showing normal morphology of the RBC with central pallor.
ERYTHROPOIESIS: In adults,  erythropoiesis is confined to the bone marrow.  Red blood cells are formed through stages of pronormoblasts ➔ normoblasts ➔ reticulocytes ➔ to mature non-nucleated etythrocytes. The average lifespan of red blood cells is about 120 days after which the RBC degenerate and the hemoglobin is broken down into hemosiderin and bile pigment. For proper erythropoiesis, adequate nutrients are needed. These are minerals, vitamins, proteins and hormones.
(A) Minerals: (i)  Iron is essential element in the synthesis of hemoglobin and (ii) Traces of copper and cobalt are also required  in  the  synthesis.  Non-heme  iron  from  cereal  and vegetables contains ferric forms  of iron.  The ferrous form is better absorbed from the gut. The ferric iron is reduced to ferrous form by the stomach acid, ascorbic acid and enzymes.
(B) Vitamins: The specific vitamins required are-vitamin B folic acid and vitamin C. Folic acid and vitamin B   are essential in the synthesis of nucleoprotein, particularly of erythropoietic cells. Vitamin B    acts at an early stage in the synthesis of RNA but folic acid acts at a later stage in the synthesis of DNA. Thus, deficiency of vitamin B12 results in defective synthesis of both
12,
12
12

Mean Corpuscular	75-100µ3	75-95µ3 Volume (MCV)
Mean Corpuscular	27-32	26-31 pg Hemoglobin (MCH)	micromicron
(picogram-pg)
Mean Corpuscular	32-36%	30-35% Hemoglobin
Concentration (MCHC)
Serum iron	60-120 µg/100 ml    Slightly lowered (65-75µg/100 ml)
Total Iron Binding              300-350 µg/100        Increased (300-Capacity (TIBC)                   ml                            400 µg/100 ml)
Saturation percentage	30%	Less than 16% (ratio-serum iron:
TIBC)
Serum ferritin	20-30  tg/L (mean)   15 mg/L (mean)

RNA and DNA, while the deficiency of the folic acid results in defective synthesis of DNA only. Vitamin C is essential for conversion of folic acid to folinic acid. ( C) Proteins: Hepcidin is a peptide hormone that regulates iron uptake and its release from stores. Hepcidine prevents entry of iron from the enterocytes to the circulation, if it is not required. It reduces the expression of ferroprotein. Ferroprotein is a transmembrane protein that transports iron from the enterocytes to the circulation. The proteins supply the amino acid for the synthesis of glob in moiety. Transferrin is a iron binding protein mostly produced by the liver. It is an intercellular transporter of iron. About 3 mg of total body iron is bound to transferrin at any time. (D) Erythropoietin: The hormone is responsible for increase in red cells mass, by stimulating the stem cells in the bone marrow. Increased secretion of erythropoietin is brought about mostly by placental lactogen and also by progesterone. Erythropoietin is produced by the kidneys (90%) and the liver (10%).

CAUSES OF INCREASED PREVALENCE OF ANEMIA IN TROPICS

Iron deficiency anemia is very much prevalent in the tropics  particularly  amongst  women  of  childbearing age (75%), especially in the underprivileged sector.  In a healthy individual,  a daily intake of dietary iron of 15 mg can replenish the daily loss of about 1.5 mg of iron  assuming an absorption  rate of  10%.  Normally the average daily need of iron for a pregnant women is 3.5 mg. But in the tropical countries especially with low socioeconomic group, the daily requirement is likely to be more because of the following.
II Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

BEFORE PREGNANCY
■   Faulty dietetic habit: Presence of high phosphate and phytic acid in carbohydrate rich diet, causes formation of insoluble iron phosphate and phytates in the gut. This reduces the absorption of iron.
■    Faulty   absorption    mechanism:   Prevalence    of intestinal infestation and intestinal hurry reduces the iron absorption. Hypochlorhydria when present also hinders absorption.
■   Iron loss: (i) More iron is lost through sweat to the extent of 15 mg per month. (ii) Repeated pregnancies at short intervals along with a prolonged period of lactation puts a serious strain on the iron reserve. It has been estimated that a normal healthy woman with adequate diet takes about 2 years to replenish about 1,000 mg of iron lost during childbirth and lactation.
(iii) Excessive blood loss during menstruation which is left  untreated  and uncared for.  (iv)  Hookworm infestation with consequent blood depletion to the extent of 0.5-2 mg of iron daily ( each worm extracts up to 0.05 mL of blood per day). (v) Blood loss due to malaria or bleeding piles and dysentery also causes iron deficiency anemia.
DURING PREGNANCY: The factors responsible are:
■    Increased demands of iron: Demand of iron during pregnancy  is  markedly  increased.  An  adequate balanced diet contains not more than 18-20 mg of iron and assuming that the absorption rate is increased by two-fold (20%), the demand is not fulfilled.
■   Diminished intake of iron: Vegetarian diet, iron-poor diet, loss of appetite and vomiting in pregnancy are responsible factors.
■   Diminished absorption: Acid  environment in the duodenum helps iron absorption. Intake of antacids,
H2  blockers and proton pump inhibitors inhibit iron
absorption. Others: Helicobacter pylori colonization, IBS, celiac disease, gastritis.
■    Infection: Presence of infection (asymptomatic bacteri­ uria) markedly interferes with the erythropoiesis.
■   Prepregnant health status: Majority of the women start pregnancy on a pre-existing anemic state with reduced iron reserve.
■   Excess demand: (i) Multiple pregnancy increases the iron demand by two-fold.  (ii)  Women with rapidly recurring pregnancy, within 2 years following the last delivery, need more iron to replenish deficient iron reserve. (iii) Women with Heavy Menstrual Bleeding (HMB).   Worldwide,   fibroid  uterus  is  the  most common cause ofHMB. (iv) Blood donation.
I IRON DEFICIENCY ANEMIA
CLINICAL FEATURES: The clinical features depend more on the degree of anemia. In majority, the patients have
got no symptom and the entity is detected accidentally


during examination. However, the following features may develop slowly.
Symptoms:  (1)  Easy  fatigue  or  weakness  may  be the earliest manifestations.  (2) The other features are anorexia and indigestion; palpitation caused by ectopic beats, dyspnea, giddiness and swelling of the legs.
On  examination:  (1)  There  is  pallor  of  varying degrees; evidences of glossitis and stomatitis and angular cheilitis, (2) Nails become brittle, fragile with ridges, (3) Koilonychias (spoon-shaped nails) due to impaired nail
bed epithelial tissue growth, (4) Edema of the legs may be due to hypoproteinemia or associated pre-eclampsia, (5) A soft systolic murmur may be heard in the mitral area. There may be tachycardia, and cardiac enlargement, (6) Crepitations may be heard at the base of the lungs due to congestion, (7) Plummer Vinson syndrome: Triad of dysphasia, stomatitis and iron deficiency anemia.

INVESTIGATIONS: The patient having a hemoglobin level 9 g% or less should be subjected to a full hematological inves­ tigation. The objectives of investigation are to ascertain:
♦   Degree of anemia ♦   Type of anemia
♦   Cause of anemia
To note the degree of anemia: This requires hematological examination which includes estimation of: (1) Hemoglobin, (2) total red cell count and (3) packed cell volume. All these help to note the degree of pathological anemia. Arbitrary grading of pathological anemia (WHO 2011) is done according to the level of hemoglobin (Box 20.1).
To ascertain the type of anemia:
■    Peripheral  blood  smear:  Examination  of  a  well­ prepared  peripheral  blood   smear   stained  with Leishman stain to study the morphology of the red cells gives a better idea, about the type of anemia. Abundant presence of small pale staining cells with variation in size (anisocytosis) and shape (poikilocytosis) suggest microcytic hypochromic anemia. This is typical in iron deficiency anemia. Reticulocyte count may be slightly raised (Fig. 20.1).
■    Hematological indices: Calculation of MCHC, MCV and  MCH  is  based  on  the  values  of  hemoglobin estimation, total red cells count and PCV. MCV and MCH values are not much dependable.  MCHC is the most  sensitive  index  of  iron  deficiency  anemia.
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■  Normal level in pregnancy 11 g/dl
WHO	ICMR
Mild	10.0-10.9g/dl	10.0-10.9g/dl Moderate	7-9.9g/dl	7-l0g/dL Severe                                <7 g/dl                         <7 g/dl
Very severe	<4 g/dl
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy    JD














Fig. 20.1: Hypochromic microcytic anemia.

It should be remembered that these hematological indices  should supplement and not substitute the blood smear examination for correct typing of anemia. A typical iron deficiency anemia shows the following blood values: Hemoglobin-less than 10 g%, red blood cells-less than 4 million/mm3,  PCV-less than 30%, MCHC-less  than  30%,  MCV-less  than  75  µ3   and MCH-less than 25 pg (Box 20.2).
To find out the cause of anemia: Appropriate investi­ gations should be undertaken as per the history and clinical examination to find out the cause of anemia. But the following should be done as a routine.
11    Examination of stool: This should be done as a routine especially in tropics, to detect helminthic (particularly hookworm) infestation.
•  The urine is examined for the presence of protein, sugar and pus.cells. A 'clean catch' midstream specimen of urine is subjected to culture and colony count. If the counts are over 105 /mL, it indicates infection.
Other  investigations  are:  (I)  X-ray  of  chest  in suspected pulmonary tuberculosis. (2) Osmotic fragility in hereditary spherocytosis or hemoglobinopathic disorders.
Place of bone marrow study: This is not done as a routine  but  indicated in:  (1)  Cases  not responding


■  Serum iron is <30 µg/100 ml.
11     Total iron binding capacity is raised (>400 µg/dl). 11      Percentage saturation is 10% or less.
11     Serum ferritin below 30 µg/L (confirms iron-deficiency anemia). ■  Serum bilirubin is not raised.
■  Serum ferritin is the most reliable indicator of iron deficiency in
the absence of inflammation and chronic disease. Serum ferritin
is the main storage protein for iron. It is found in all cells but heighest in the hepatocytes.
■  Hematocrit <33%.
■  Mean corpuscular volume <79 fl. •  Transferring saturation <16%.
■  Bone marrow biopsy-lack of stained iron in macrophages and
in erythroid precursors.
■  Iron refractory anemia in most cases are due to genetic mutation
(TM PRSS6).

to therapy according to hematological typing.  (2) To diagnose hypoplastic anemia. (3) To diagnose kala-azar by detecting LD bodies.  In iron  deficiency  anemia, the bone marrow is normoblastic in character. There is absence of hemosiderin granules when stained with Prussian blue.
DIFFERENTIAL DIAGNOSIS: All the causes of hypochromic anemia  are  to  be  differentiated.  Anemia   due  to thalassemia is differentiated from iron deficiency anemia by: (a) Normal serum iron; {b) Normal serum ferritin; (c) Presence of stainable iron in the narrow and {d) Elevated
levels of hemoglobin A2• Apart from iron deficiency, other
causes of hypochromic anemia are:  (1) Infection,  (2) nephritis and pre-eclampsia, (3) hemoglobinopathies.

■ COMPLICATIONS OF ANEMIA IN PREGNANCY
DURING  PREGNANCY:  The  following  complications are  increased:  (I)  Pre-eclampsia  may  be  related  to hypoproteinemia. (2) Intercurrent infection. Presence of any pre-existing disease, may flare up. It should be noted that the infection itself impairs  erythropoiesis  by bone marrow depression. (3) Angina pectoris. (4) Sideropenic dysphagia  (Plummer  Vinson  syndrome).   (5)  Atrophic glossitis.  (6) Heart failure  at 30-32 weeks of pregnancy. (7) Preterm labor and prematurity.

DURING LABOR: (1) Uterine inertia is not a common associate, on the contrary the labor is short because of a small baby and multiparity. (2) Postpartum hemorrhage is a real threat even with a minimal amount of blood loss. (3) Congestive cardiac failure occurs mostly during labor or  immediately following delivery. As the blood in the uterine circulation is squeezed in the general circulation, it  puts  additional strain  on  the myocardium already compromised  by  hypoxia.  ( 4)  Shock-even  a  small amount of hemorrhage may produce shock or hypoxia which may be lethal.

PUERPERIUM: There is increased risks of: (I) Puerperal sepsis, (2) Subinvolution, (3) Poor lactation, (4) Puerperal venous thrombosis, (5) Pulmonary embolism, (6) Poor wound healing and (7) Postpartum depression.
Risk  periods:  The  risk  periods  when  the  patient may even die suddenly are: (I) At about 30-32 weeks of pregnancy, (2) During labor, (3) Immediately following delivery  and  (4)  Anytime  in  puerperium  especially 7-10 days following delivery due to cardiac failure or pulmonary embolism.

EFFECTS ON BABY: Amount of iron transferred to the fetus is unaffected unless the mother suffers from severe iron deficiency anemia. (I) There is increased incidence of IUGR (Ch. 32). (2) Preterm delivery. (3) In severe anemia: low fetal, oxygenation, reduced amniotic fluid volume and IUD. The sum effect is increased in perinatal loss and (4) Anemia in infancy due to reduced iron store.
&I Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy
I PROGNOSIS	Hospitalization:  (l)   Ideally  all  patients  having MATERNAL: If detected  early and proper  treatment is     hemoglobin level 8 g/100 mL or less should be admitted instituted, anemia improves promptly. At times, there is     prevalence of anemia with an arbitrary hemoglobin level In fact, anemia either directly or indirectly contributes     be  hospitalized.  (2)  Associatedeobstetrical-medical
for  investigation  and  treatment.   But  due  to  high
a tendency for anemia to recur in subsequent pregnancy.
of7.5 g/dL may be considered, wh  n the patient should
to about 20% of maternal deaths in the low and middle
income countries.
complication even with moderate degree of anemia.
General treatment:
FETAL: Baby born at term, to an anemic mother may not
be anemic at birth, but as there is little or no reserve iron,	♦    Diet: A realistic balanced diet rich in proteins, iron and anemia develops in neonatal periods. Mean cord blood
vitamins and which is easily assimilable is prescribed.
To eradicate even a minimal septic focus by approp­
riate antibiotic therapy.
levels of serum iron, ferritin, B12 and folate are higher than	♦
that of mother. However, total iron binding capacity and
serum level of vitamin E are lower than that of mother.	♦   Effective therapy to cure the disease contributing to the cause of anemia.
I
TREATMENT	Specfic therapy:

Prophylactic
In majority of the cases the iron deficiency anemia are either pre-existing or aggravated during pregnancy.
♦    Spacing   of   birth-a   minimum   interval   between pregnancies, should be at least 2 years, if not three, to replenish the lost iron during childbirth process and lactation.
♦    Supplementary iron therapy: Only 20% of pregnant women  have  iron  stores  of  500  mg  which  is  the minimum essential  for  pregnancy  and  about  40% women have virtually no iron stores.
Therefore, most women should be given iron supple­ mentation during pregnancy. Even with a well-balanced diet, supplementary iron should be a routine. Daily administration of 200 mg of ferrous sulfate ( containing 60 mg of elemental iron) along with 1 mg folic acid is a quite effective prophylactic procedure. Tea should be avoided within 1 hour of taking iron tablet.
♦   Dietary prescription: A realistic balanced diet, rich in iron and protein, should be prescribed. The foods rich in iron are liver, meat, egg, green vegetables, green peas,  figs,  beans,  whole wheat and green plantains, onion  stalks,  jaggery,   etc.   Iron  utensils  should preferably be used for cooking and the water used in rice and vegetable cooking should not be discarded.
♦    Treatment should be instituted to eradicate hookworm infestation,  dysentery,  malaria,  bleeding  piles  and urinary tract infection.
♦    Early detection of falling hemoglobin level is to be made. Hemoglobin level should be estimated at the first antenatal visit, at the 30th week and finally at 36th week.
Curative
Anemia  is not a disease but a  sign  of an underlying disorder. Treatment must be preceded by an accurate diagnosis of the cause of anemia and type of anemia (Flowchart 20.1).


The principle is to raise the hemoglobin level as near to normal as possible. Thereafter, an attempt is made to restore the iron reserve at least in part, if possible, before the patient goes in labor.
Choice of therapy depends on: (l) Severity of anemia, (2) duration of pregnancy ( time available before delivery) and (3) associated complicating factors.

IRON THERAPY: ♦ Oral therapy ♦ Parenteral therapy
Oral therapy
Iron is best absorbed in the ferrous form and as such any of the ferrous preparations available either in tablets or capsules.
The  preparations  available  are  ferrous  gluconate, ferrous fumarate or ferrous succinate (Table 20.2). In spite of claims about the superiority of one preparation over the other, ferrous sulfate is widely used. Fersolate tablet contains 325 mg ferrous sulfate which contains 60 mg of elemental iron, trace of copper and manganese. The initial dose is one tablet to be given thrice daily 30 minutes before meals. If larger dose is necessary (maximum six tablets a day), it should be stepped up gradually in 3-4 days.  The treatment should be continued till the blood picture  becomes  normal;  thereafter  a  maintenance dose of one tablet daily is to be continued for at least 100 days following delivery to replenish the iron stores. Hemoglobin  should rise by 2.0 g/ dL  every  3-4 weeks with start of oral iron therapy.
■   Iron poloymaltose (ferric iron with maltol) soluble in neutral pH. Each tablet contains 100 mg elemental iron in ferric form.  It has fewer gastrointestinal problems and improved absorption when taken with food.
■   Side effects of oral iron therapy: (a) Gastric irritation, (b)  Constipation,   (c)  Diarrhea,   (d)  Nausea,   (e) Vomiting, (f) Epigastric pain and (g) Metallic taste.
(l)  Intolerance: The intolerance is evidenced by­ epigastric  pain.  Metallic  taste  may  be  related  to increased dose of iron or to some preparation. To avoid
Chapter 20: Medical and Surgical Illnesses Complicating Pregnancy

Flowchart 20.1: Scheme of investigations and specific therapy for anemia in pregnancy (Hb  9 g/dl and Hct <30%).

Anemia in pregnancy

• Hb :,9 g/dl	• Hct <30%

• MCV (µ3)
• Peripheral Blood Film (PBF) • Reticulocyte count




MCV (<80) (microcytic)


Serum iron studies
l


• Serum iron • Serum iron
binding capacity • Serum ferritin


MCV-normal (80-94) (normocytic)
l



Reticulocyte-normal	Reticulocyte >2-3%.
or low.     l	l
• Drugs.	• Hemolysis
• Chronic disease.	• Hemoglobinopathies
• Bone marrow	• Autoimmune diseases pathology.	• Drugs
• G6PD deficiency • Bleeding
j
l

Therapy specific
to cause	Therapy as appropriate.

MCV >94 (macrocytic)
• Hypersegmented neutrophil
l
'f


• Red cell folate <3 ng/ml.
• Sec,m	io B,, <80 pg/ml.



Folate and B12  deficiency.