■ EFW or AC <10th percentile, a. EFW or AC <10th combined with one or more of percentile. the following: b. EFW or AC crossing a. UA Pl >95th percentile percentiles; > 2 quartiles b. UtA Pl >95th percentile on growth percentiles. c. CPR <5th percentile or (EFW: estimated fetal weight) UA Pl >95th percentile. FIG0-2021 (AERDV: Absent End Diastolic Velocity; UA: Umbilical Artery; UtA: Uterine Artery) Ponderal index, normal subcutaneous fat and usually have uneventful neonatal course. 2. Fetuses whose growth is restricted by pathological process (true FGR). Depending upon the time of onset, relative size of their head, abdomen and femur, the fetuses are subdivided into: (a) Early onset or symmet­ rical, or (b) Late onset or asymmetrical (Fig. 32.3 and Table 32.3). Early onset (symmetrical) 20%: The fetus is affected from the noxious effect very early in the phase of cellular hyperplasia. The total cell number is less. This form of growth restriction is Fig. 32.3: Pregnancy complicated with chronic hypertension, delivered by CS at 38 weeks. The baby weighed 1.9 kg with features of asymmetrical FGR. Physical features (wrinkled skin, scaphoid abdomen, head circumference > abdominal circumference) give the baby an "old-man look''. Chapter 32: Low Birth Weight Baby lmL -- most often caused by structural or chromosomal abnormalities or congenital infection (TORCH) or early onset severe hypertension. The pathological process is intrinsic to the fetus and involves all the organs including the head (Table 32.3). Late onset (asymmetrical) 80%: The fetus is affected in later months during the phase of cellular hypertrophy. The total cell number remains the same but size is smaller than normal. The pathological processes that too often result in asymmetric growth retardation, are maternal diseases extrinsic to the fetus. These diseases alter the fetal size by reducing uteroplacental blood flow or by restricting the oxygen and nutrient transfer or by reducing the placental size. ETIOLOGY: The causes of fetal growth restriction can be divided into four groups: ■ Maternal ■ Fetal 11 Placental ■ Unknown ■ Maternal factors: • Constitutional: Small women, slim, maternal genetic and racial background. ■ Others: • Age >40 years; • Maternal BMI ( <20 or >35}; • IVF singleton pregnancy; • Nullipar­ ity; • Poor weight gain during pregnancy; • Anemia, malnutrition; • Hypoxemia (lung disease}; • Smok­ ing, alcohol, drugs; • Previous pre-eclampsia, SGA, stillbirth; • Pregnancy interval <6 or 60 months. ■ Placental factors: • Poor uterine blood flow (maternal vascular malperfusion; • Infarction (5%}, abruption, mosaicism; • Diabetes with vascular disease; • Antiphospholipid syndrome; • Placental inflammation ( villitis). 11 Umbilical cord factors: • Increased cord length; • Single umbilical artery; • Velamentous cord inser­ tion; • Cord knot (true). 11 Fetal factors: • Genetic (chromosomal, aneuploidy, microdeletion duplications, single site mutations. • Structural anomalies • Congenital infection (CMY, TORCH} • Terato gen exposure (drugs) • Multiple pregnancy ■ Toxins: Alcohol, smoking, cocaine, heroin, drugs. 11 Unknown ( 40%) Predictivefactorsfor FGR: A. Maternal: • Elderly (>35 years) • Underweight • Severe anemia, hemoglobinopathies. B. Medical: Hypertension, SLE, IBS, APLS, DM (long standing), CKD. C. Obstetric: Previous pregnancy affected by FGR, pre-eclampsia D. Biochemical markers: • Low PLGF; • Low PAPPA; • High APP E. USG based markers: • UtA: PI >95 percentile; • UtA notching (bilateral); • Single umbilical arte1y; • Velamentous cord insertion; • Abnormal placental morphology. F. Summary of risk factors at booking assessment (first trimester): Minor riskfactors: Maternal age 35 years; IVF singleton pregnancy; Nulliparity; BMI <20 or >35; Previous pre-eclampsia; Pregnancy interval <6 or >60 months. Major riskfactors: Maternal age >40 years; Paternal SGA; Previous SGA baby; Previous stillbirth; Maternal SGA; Chronic hypertension; Diabetes with vascular disease; Renal impairment; Antiphospholipid syndrome; Heavy bleeding similar to menses and PAPP-A <0.4 MoM. Pathophysiology: Basic pathology in small for gestational age is due to reduced availability of nutrients in the mother or its reduced transfer by the placenta to the fetus. It may also be due to reduced utilization by the fetus. Brain cell size as well as cell numbers are reduced. Liver glycogen content is reduced. There is oligohydramnios as the renal and pulmona1y contribution to amniotic fluid is diminished due to reduction in blood flow to these organs. The SGAfetus is at risk of intrauterine hypoxia and acidosis, which, if severe, may lead to intrauterine fetal death. PREDICTION AND DIAGNOSIS: Significant improvements have been made by clinical and biophysical methods in prediction (see above) and diagnosis of a growth restricted fetus. CLINICAL: Detailed history for the risk factors: ■ Clinical palpation of the uterus for the fundal height, liquor volume and fetal mass may be used for screening. It is simple, safe and inexpensive. But it is less sensitive. 11 Symphysis Fundal Height (SFH} measurement in centimeters closely correlates with gestational age after 24 weeks. A lag of 3 cm or more suggests growth restriction. It is a fairly sensitive parameter (30-85%). Serial measurement is important. ■ Maternal weight gain remains stationary or, at times, falling during the second-half of pregnancy. ■ Measurement of the abdominal girth showing statio­ nary or falling values. Biophysical: 11 USG examination is done to confirm the clinical evaluation of gestational age. USG is extremely useful for structural anomalies, soft markers and related infections (CMV, rubella, toxoplasma). Sonographic predictive values that are commonly used are: ♦ Head Circumference (HC) and Abdominal Circumference (AC) ratios: In a normally growing fetus the HC/ AC ratio exceeds 1.0 before 32 weeks. It is approximately 1.0 at 32 to 34 weeks. After 34 weeks, it falls below 1.0. If the fetus is affected by asymmetric FGR, the HC remains larger. The HC/ AC is then elevated. In symmetric FGR, both the HC and AC are reduced. The HC/ AC ratio remains normal. Using HC/ AC ratio, 85% of FGR fetuses are detected. Transcerebellar diameter correlates well with the gestational age. ♦ AC is the single most sensitive parameter to detect FGR (Fig. 42.51A). Serial measurements of AC and estimation of fetal weight are more diagnostic to fetal growth restriction. Im Chapter 32: Low Birth Weight Baby ♦ Femur Length (FL) is not affected in asymmetric FGR. The FL/AC ratio is 22 at all gestational ages from 21 weeks to term. FL/AC ratio greater than 23.5 suggests FGR. ♦ Amniotic fluid volume: Amniotic fluid pocket 32 weeks). Decision for early delive1y may increase the risk of neonatal deaths due to complications, on the other hand, delay in delivery may increase the risk of IUFD. General: At present, there is no proven therapy for preventing growth restriction once it is established. However, the following may be tried with some success: 1. Rest, especially in left lateral position; 2. Improve nutritional status by balanced diet: 300 extra calories per day are to be taken; 3. To institute appropriate therapy for the associated complicating factors likely to produce growth restriction; 4. Avoidance of smoking, tobacco and alcohol; 5. Maternal hyperoxygenation at the rate of 2.5 L/min by nasal prong, for short-term prolongation of pregnancy; 6. Low-dose aspirin (75-150 mg daily) since 12 weeks may be helpful in very selected cases with history of thrombotic disease, hypertension, pre-eclampsia, or recurrent FGR; 7. Maternal hyperalimentation by amino acids can improve fetal growth if it was due to maternal malnutri­ tion. Maternal hyperalimentation is only helpful when IUGR is due maternal malnutrition. It is not helpful when placental function is deficient; 8. Maternal circulatory volume expansion may be helpful in improving placental perfusion. Antepartum evaluation: Serial evaluations of fetal growth and assessment of wellbeing should be done once the diagnosis is made (Flowchart 32.1). ■ Ultrasound examination should be done at an interval of 1-2 weeks for the assessment of BPD, HC/AC, fetal weight and AFI for high risk fetus (based on history, biochemistry, UtA Doppler or single SFH measurement <10th centile or serial measurements indicative of FGR). ■ Fetal wellbeing is assessed by • Kick count, • NST, • Biophysical profile, • Amniotic fluid volume • Monitoring • CTG • Monitoring frequency: CTG/ NST twice weekly. 11 Doppler ultrasound parameters are to be studied. At present, there is no effective treatment to improve FGR. There is no proven treatment for FGR. Phosphodiesterase type-5 inhibitors (sildenafil citrate) was used to release NO for vasodilatation. It did not improve the result. Vascular Endothelial Growth Factor, gene therapy is underway for improving local vasodilatation and angiogenesis. Timing of delivery is a critical issue. This is to balance the risk of prematurity against the risk of continued pregnancy. Unless carefully judged, continued pregnancy may end in IUFD or organ damage due to hypoxia. TIMING OF DELIVERY: The factors to be considered are: (1) Presence of fetal abnormality; (2) Duration of pregnancy; (3) Onset ofFGR; (4) Associated complicating factor; (5) Underlying pathology (if known); (6) Results of antenatal fetal surveillance; and (7) Availability of neonatal intensive care unit (NICU). Optimum time of delivery for a growth-restricted fetus may be between 34 weeks and 37 weeks depending upon the presence of any additional risk factor(s) (e.g., oligohydramnios, pre-eclampsia, abnormal Doppler study). ■ Pregnancy near to 37 weeks-uncomplicated mild FGR: Fortunately, the majority fall in this group. Usual treatment as outlined above to improve the placental function may be employed. Pregnancy is continued at least 37 weeks. Thereafter delivery is done. ■ Cases with mild SGA (estimated fetal weight: 3rd to 9th percentile) with normal Doppler studies: ➔ Delivery by ·Im Chapter 32: Low Birth Weight Baby Flowchart 32.1: Management protocol for fetal growth restriction (FGR). >­ J: 0. <( :: !) 0 z 0 J) I CLINICAL EVALUATION I • Antenatal assessment of risk factors (age >35 years, oligohydramnios, hypertension, renal disease) • SFH: Measurement at each antenatal visit after 24 weeks • A discrepancy of >3 cm (in the absence of obesity, multiple pregnancy, fibroid uterus) or single SFH <10th centile i USG diagnosis -A Fetal biometry(• BPD • HC • AC • FL). -A Single OR EFW, AC <10th centile. -A Serial measurements indicative of FGR. Medical management + Increased rest. + Folic acid. ■ To exclude congenital anomalies, genetic + Increased fluid intake. syndromes and infections + Low-dose aspirin (selective). ■ To treat underlying pathology (if known) + To treat underlying pathology(if any). ! Fetal surveillance Management summary of FGR based on Doppler study: + ·Early onset FGR cases are more difficult in management compared to late oriset FGR. + UA Doppler is the only parameter that provides both diagnostic and prognostic information in the management. -♦ Once FGR (estimated fetal weight <10th centile) is identified, UA.PI, MCA ■ DFMCR, • CTG, NST Pl, CPR should be measured. Stages(severity) of hypoxia can be determined ■ BPP • Amniotic fluid liy ch_anges with the UA and. DV Doppler . volume(DVP) • Uterine Artery Doppler Pl (UtA Pl) when abnormal, one can predict poor outcome in a growth restricted fetus. • Progression of UA Doppler patterns from reduced to absent and further to reversed end-diastolic flow, correlates with worsening severity of fetal hypoxia and acidosis, ending with fetal death (Box 32.1). · .♦ Growth-restricted fetuses with EFW <3rd centile, have much higher risk of adverse perinatal outcome compared to fetuses with EFW <10th centile. • Ductus Venosus (DV) Doppler is strongest single parameter to predict fetal acidemia when there is absent or reversed flow velocities. With this, Timing of delivery · delivery is recommended at any gestational age after completion of corticosteroid therapy. <37 weeks 37 weeks➔ delivery ♦ All Doppler signs should be confirmed at least twice at 12 hours apart. -- ------------------ ------ -- ! if Umbilical Artery (UA), u Doppler Study ­ c i Repeat study at (Pl/RI > +2 SD) :, i . interval of 10-14 days End -dIastolIc ve oc1ty (EDV) . I . :: * • USG (AC, EFW) (10-14 days] Present EDV Absent or reversed EDV Absent or reversed o. • Doppler (UA, MCA, CPR, DV) (AREDV) (AREDV) ! Normal l c Repeat study + abnormal • USG (AC, EFW) weekly Doppler study DV Doppler • Doppler study: Twice weekly • UA • MCA • CPR • DV (Daily) (DV A-wave: l (UA, MCA, CPR, DV) Absent/reversed) Delivery by 37-39 weeks I Persistent Persistent lPresent Delivery by 34 /7 weeks Delivery by 30°" weeks 26-30 weeks Delivery by 1 1 ! • TO ADMINISTER CORTICOSTEROID BEFORE • Mgso. WHEN <32 WEEKS • AVAILABILITY OF NICU FACILITIES PRETERM (<34 WEEKS) DELIV ERY (SEFW: Sonographic Estimated Fetal Weight) ?:37 weeks. Until then monitoring to be continued with CTG, NST, BPP (fortnightly) or by Doppler, ■ Cases with FGR with early Doppler changes/or with oligohydramnios, P ➔ delivery by 34-37 weeks: until this continued monitoring with CTG, NST, BPP (weekly) and UA Doppler (twice weekly). E ■ FGR with UA, AEDV with abnormal CTG, NST, EPP (Box 32.1) delivery➔ by 32 weeks. 11 Cases of FGR with UA REDV; ➔ Delivery by 30 weeks. ■ Cases of FGR with abnormal DV ➔ Doppler: delivery by 26-30 weeks (Box 32.1). ■ Administration of antenatal corticosteroid in FGR to be used. 11 Absolute indications for delivery: Irrespective of gestational age are: CTG/NST abnormalities: Reduced variability, repetitive late deceleration, severe PE with end-organ damage. 11 When delivery is to be done before 32 weeks, magnesium sulfate should be given (additional) to the mother for fetal and neonatal neuroprotection. Chapter 32: Low Birth Weight Baby - ., Fetal circulation: ■ UA : !-EDV (UA Pl f) (fetal hypoxia) 1, ■ MCA: fDiastolic flow (MCA Pl l-) 1, Hypoxic response: Blood flow redistribution -1, ■ UA : Absent flow (AEDFV) 1, o MCA: fPSV 1, II UA Reverse flow (fetal hypoxia) 1, II DV Absent/Reversed flow (hypoxia/acidemia) 1, ■ UV Pulsatile flow (acidemia) (UA: Umbilical Artery; MCA: Middle Cerebral Artery; DV: Ductus Venosus; UV: Umbilical Vein; AEDFV: Absent End Diastolic Flow Velocity) 11 Fetuses with aneuploidy or congenital infection have poor outcome irrespective of gestational age and timing of delivery. Mode of delivery: FGR alone is not an indication of Cesarean Delivery (CD). 11 Indications for CD are: (a) Early onset FGR, (b) with UA, AEDV, REDV or changes in DVand (c) abnormal CTG, NST, BPE 11 Delivery should be in centers with intensive neonatal care facilities. 11 Low rupture of the membranes followed by oxytocin is employed in cases with pregnancy beyond 34 weeks with favorable cervix and the head is deep in the pelvis. ■ Placenta should be sent histopathological examination for counseling the future pregnancies. IMMEDIATE CARE OF THE BABY AFTER BIRTH ■ A pediatrician should be present at the time of delivery. ■ The same precautions as outlined in the preterm delivery are to be taken to prevent the complications. Intensive care protocols: Special precaution is to be taken to prevent and treat complications (p. 421). POSTPARTUM FOLLOW UP AND COUNSELLING FOR FUTURE PREGNANCIES: To educate women about the preventive strategies to decrease the risk in future pregnancy. Infant follow up, counseling the woman regarding the importance of diet, weight, cessation of smoking, use of aspirin, monitoring of BP and fetal growth during the next pregnancy. ► A low birth weight infant is one whose birth weight is less than 2500 g irrespective of gestational age. It is a major cause of perinatal morbidity and mortality (Table 32.2). ► Fetal Growth Restriction (FGR) is defined when baby's birth weight is below the 10th percentile of the average for gestational age FGR is a major cause of perinatal morbidity and mortality. ► Etiology of FGR is many. Symmetrical (early onset) FGR infants face more complications and have got poor prognosis compared to asymmetrical (late onset) ones. ► Serial measurement of Symphysis Fundal Height (SFH) should be done at each antenatal visit from 24 weeks onwards. It can predict the FGR well. ► When SFH revealed slow or static fetal growth, the woman should have ultrasound evaluation of fetal growth. USG diagnosis of FGR is made from four biometric measures: (1) BPD, (2) HC, (3) AC, and (4) FL. The estimated fetal weight can be derived from these va I ues. ► When sonographic estimated fetal weight is <10th centile (FGR), fetal genetic syndrome (aneuploidy), infections and placental insufficiency are to be ruled out. ► The terms FGR and SGA used interchangeably to define small fetuses whose birth weight is below the 10th centile. FGR indicates a pathologically small fetus whereas SGA indicates a fetus below the specific cut-off value but otherwise normal. ► Further evaluation for FGR is done with UA and MCA Doppler and the CPR. Normal study report with all these parameters, even on repeat examination after 14 days, suggests a SGA (constitutionally small) fetus. Contd... !1 Chapter 32: Low Birth Weight Baby Contd... ·1 ► Amniotic fluid volume assessment should be done measuring the Single Deepest Vertical Pocket. ► With ultrasound evidence of FGR, the woman should be referred to a fetal medicine unit for fetal anatomy survey and uterine artery Doppler study. Serological screening may be done when congenital infection is suspected ► Antiplatelet agent (aspirin) is given in cases with pre-eclampsia or high-risk factors. ► Management of FGR depends on its time of onset, severity and duration of pregnancy. Serial assessment of fetal growth and surveillance is needed. Timing of delivery is based on the fetal surveillance of fetal hypoxia and acidemia. ► In high-risk women, use of Umbilical Artery Doppler Velocity (UADV) study is the primary surveillance tool for a growth restricted fetus (RCOG). It reduces perinatal morbidity and mortality. ► When UADV indices are abnormal (Pl or RI >2 SDs above the mean for gestational age) ➔ Repeat surveillance is done. ► A growth-restricted fetus is previable when delivery is done before 28 weeks of gestation. Interventions need to be undertaken in consideration with maternal health (severe pre-eclampsia). ► Optimum time for delivery for a woman with FGR is between 34 and 37 weeks. ► Presence of recurrent late decelerations in CTG, oligohydramnios, BPP score <6 and reversal of DV Doppler A-wave, suggest maximum risk of fetal acidemia and death. ► Woman with FGR showing AREDV in the umbilical artery-needs to be delivered (cesarean section). Absolute indications of delivery are: CTG/NST abnormalities and abnormal DV Doppler. ► Delivery for FGR should be organized in a center with NICU facilities. ► The neonatal morbidities in FGR are: Birth asphyxia, meconium aspiration, hypothermia and others. ► FGR can cause short-term as well as long-term morbidities (Table 32.2). ► No single parameter is of absolute value to assess the severity of fetal hypoxemia and acidemia. Multiple parameters are involved as below: (a) CTG: Repetitive late decelerations (b) USG: Olighydromnios is studied to make the decision of delivery (c) BPP score <6. (d) DV Doppler >3 SDs with reversal of DV A-wave. (e) Reversed/absent UA Doppler velocity. ► Doppler changes in fetal circulation are directly correlated with progressive fetal hypoxia and acidemia. - C H A P T E R !11:•: '! J Diseases of the Fetus and the Newborn CHAPTER OUTLINE . !] . ": ❖ Perinatal Asphyxia ► Fetal Respiration ► Clinical Features ► Management ❖ Respiratory Distress in the Newborn ► Idiopathic Respiratory Distress Syndrome ❖ Transient Tachypnea of the Newborn (TTN) ❖ Meconium Aspiration Syndrome (MAS) ❖ Jaundice of the Newborn ► Management of Jaundice in the Newborn ❖ Hemolytic Disease of the Newborn ► ABO Group Incompatibility ❖ Bleeding Disorders in the Newborn ❖ Anemia in the Newborn ❖ Seizures in the Newborn ❖ Birth Injuries of the Newborn ► Injuries to the Head ► lntracranial Hemorrhage ► Other Injuries ❖ Perinatal Infections ► Modes of Infection ► Ophthalmia Neonatorum ► Skin Infections ► Necrotizing Enterocolitis ► Mucocutaneous Candidiasis ❖ Congenital Malformations and Prenatal Diagnosis ► Down's Syndrome (Trisomy 21) ❖ Surgical Emergencies ❖ Nonimmune Fetal Hydrops PERINATAL ASPHYXIA DEFINITION: Perinatal asphyxia refers to a condition during pregnancy and labor in which impaired placental gaseous exchange leads to fetal hypoxemia, acidosis and hypercarbia. The essential neonatal features for the diagnosis are: (i) Persistent bradycardia ( 7.20, it is unlikely that intrapartum hypoxia, is the cause of neonatal encephalopathy. (4) Need for positive pressure ventilation. (5) Seizures within 12-24 hours of birth. (6) Suppressed background pattern on EEG. According to the parameters denoted by Apgar (Dr Virginia Apgar-1953), a scoring procedure has been designed for simple understanding of the clinical state. Long-term neurological correlation is obtained at the 5-minute score which is of more value. In cases where the score remains significantly depressed at 5 minutes, it should be evaluated again after 15 minutes. This scoring Chapter 33: Diseases of the Fetus and the Newborn ID L Table 33.1: Apgar scoring. Parameters Score Signs 0 1 Respiratory Absent Slow, irregular effort Heart rate Absent <100 bpm Muscle tone Flaccid Flexion of extremities. Reflex irritability No response Grimace 2 Good, crying >100 bpm Active body movements. Cough or sneeze 3. Delayed cord clamping (until 60-90 sec) to support transfusion (placental to fetal). 4. Intrapartum fetal close clinical monitoring for early detection of fetal distress and delivery. 5. Intrapartum use of electronic fetal monitoring and scalp blood pH assessment when indicated. 6. Judicious use of anesthetic agents and sedatives during labor. 7. Avoidance of dificult or traumatic delivery. 8. Management in the delivery room. Color Blue, pale Body pink, Complete pink extremities blue. • Total score= 1 O; • No depression = 8-1 O; • Mild depression = 5-7; • Moderate depression= 3-4; • Severe depression= 0-2 is done in a newborn baby at 1 minute, 5 minutes and 15 minutes and can be tabulated as follows (Table 33.1). The etiology of ?:90% of cases of Cerebral Palsy (CP) remains unknown. Apgar score alone should not be taken as an evidence of neurological damage. Cord blood pH can assess fetal oxygenation status better. Normal range of arterial blood gas values for a term newborn are: Pa02 50-95 mm Hg; PaC02 35-45 mm Hg; HC03 24-26 mEq/L and pH 7.35-7.45. Clinical sequelae of birth asphyxia: The variable clinical signs of CNS injury with HIE are: hypoxia, seizures, apnea, respiratory failure, hypotension, NEC, thrombocytopenia, metabolic acidosis and hypoglycemia. Initial response is hyperapnea and hypertension ➔ primary apnea ➔ gasping attempt to breathe ➔ (if unresolved) ➔ secondary apnea ➔ bradycardia and shock ➔ diminished cerebral blood flow ➔ cerebral hemorrhage ➔ hypoxic ischemic encephalopathy (HIE) ➔ (if severe)➔ either death or disability (if the baby survives). Neonatal diagnosis: A full array EEG (a EEG) is used to select babies for cooling to detect subclinical seizure activity and as long-term prognostication. CT is used to detect cerebral edema, hemorrhage and the eventual HI brain injury. MRI (Tl and T2 weighted) are the best modality to detect the severity and extent of irreversible HI brain injury. Diffusion weighted imaging (DWI), proton Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance (MR) angio- or venography may be useful for cases with suspected sinus venous thrombosis or vascular anomalies. Cranial Ultrasonography ( CUS)-detect edema, intracranial hemorrhage, but it is insensitive to detect HI brain injury. Common patterns of brain injury seen on MRI are: Infarction, intraventricular and intraparenchymal hemor­ rhage, or metabolic encephalopathies. I MANAGEMENT Management of perinatal asphyxia can be divided into two areas: ■ Preventive II Definitive PREVENTIVE 1. Antenatal detection of high-risk factors. 2. Antenatal administration of corticosteroids to the mother when preterm delivery (<34 weeks) is antici­ pated. DEFINITIVE: • Delayed cord clamping (until 60-90 sec). Apgar rating-classically, the evaluation of the cardiopulmonaiy status in the newborn has been assessed at 1 minute and 5 minutes after birth. But in certain circumstances, it is inappropriate to delay resuscitative efforts until the 1 minute Apgar score is obtained (Flowchart 33.1). However, most infants born with Apgar scores of7-10 are essentially normal (Figs. 33.2A to F). 11 Neonatal heart rate <100/min for >2 min in the first 5 min after birth increases the mortality by 4-5 folds. EFM monitoring in high-risk cases is needed. Pulse oximetry with saturation gradually rising from 60% to 90% over first 10 min is satisfactory when heart rate is within the normal range. Presence of bradycardia (<100/min) and lower SpO2 ( <80%) in the first 5 min is associated with death or intracranial hemorrhage. This is especially in preterm neonates. 11 Spontaneously breathing babies, need to stabilize with CPAP of at least 6 cm H2O via with mask or nasal prongs. 11 Oxygen for resuscitation should be given, using a blended air/oxygen. Initial FiO2 of 0.30 for babies <28 weeks gestation and 0.21 for 32 weeks and above. FiO2 adjustment of up or down should be guided by pulse ornetry. 11 Intubation should be reserved for babies not respond­ ing to positive pressure ventilation via face mask. 11 Babies requiring intubation for stabilization should be given surfactant. 11 Plastic bags or occlusive wrapping under warmers should be used during stabilization in the delivery suite for babies <28 weeks. 11 In preterm babies receiving oxygen the saturation target should be between 90 and 94%. The alarm limits should be set to 89 and 95%. 11 CPAP involves delivering gas ideally heated and humi­ dified with a measurable and controllable pressure. 11 CP AP with early rescue surfactant is considered optimal for babies with RDS. m Babies at risk of RDS ( <30 weeks, who do not need intubation), should be started with CPAP. 11 Heated humidified HFNC are increasingly used as an alternative to CPAP. 11 Short binasal prongs or mask with a starting pressure of about 6-8 cm HzO could be initiated. Im Chapter 33: Diseases of the Fetus and the Newborn Flowchart 33.1: Resuscitation of the newborn in the delivery room. Ventilatory resuscitation: ► Dry the infant, to place under the radiant heater. ► Place the infant with head in midline position neck with slight extension. ► Suction of mouth, oropharynx with a suction bulb. ► Assess the infant's condition: Respira­ tory effort (apnea or regular breathing) and heart rate. ► Infants with regular breathing and heart rate >100 bpm need no further intervention; if cyanotic, provide 02 supplementation. ► Infants HR <100 bpm, apnea or irregular respiration: Bag and mask ventilation (100% 02) to be given. A soft mask that seals around the mouth and nose is to be used. ► Most neonates can be effectively managed with a bag and face mask. If no improvement by another 30-40 seconds-intubation and proceeded. ► Monitoring equipment is pulse oxi­ meter (enhanced) ECG; Medications: Normal saline, epinephrine. Chest compression: The sternum is compressed about one-third the diameter of the chest at a regular rate of 90 compressions/min while ventilating (PPV) the infant at 30 breaths/min (3:1). The HR is checked periodically and chest compression is discontinued when the HR is >60 bpm. The thumbs are placed together over the lower third of the sternum. The palms encircle the torso and support the back. Medications: Epinephrine: 0.1-0.3 ml/ kg in 1:10,000 dilution is given IV or endotracheal, when there is persistent bradycardia [<60 bpm despite adequate ventilation with 100% 02 (30 sec), chest compression (60 sec)] until the HR >60 bpm. It may be repeated at every 3 to 5 minutes. Volume expansion: Indications: Neonates with acute bleeding, pallor, or shock. Immediate infusion of normal saline boluses is needed. 10 ml/kg can be given through an umbilical venous catheter over 5-10 min. Antenatal counseling Team briefing and equipment check Birth Infant stays with mother for routine Term gestation? care: warm and maintain normal Good tone? 1--- temperature, position airway, check Yes Breathing or crying? secretions if needed, dry. Ongoing evaluation No Warm, dry, stimulate, position airway, suction only if required. Apnea or gasping? No Labored breathing or HR below 100/minute? persistent cyanosis? Yes Yes PPV Position and clear airway, SpO,, SpO2 monitor more supplementary O, as Consider ECG mionitor needed consider CPAP. HR below 100/minute? Post-resuscitation care Yes Team debriefing. Check chest movement Ventilation corrective steps if needed Targeted preductal SpO ETT or laryngeal mask if needed. after birth 2 1 minute 60-65% 6 0/ t HR b e low minue? 2 minutes 65-70% Yes 3 minutes 70-75% Intubate if not already done. 4 minutes · 75-80% Chest compressions 80-85% 5 minutes Coordinate with PPV. 100% 02 10 minutes 85-95% ECG monitor Consider emergency UVC. Delivery room resuscitation protocol following American Heart Association, __ t _ - -, No r- - - H R b - _ _ __ - 6 0 - / - i elow m nue? _ American Academy of Pediatrics and National Neonatology Forum YesL J (NNF), India. IV epinephrine if HR persistently below 60/minute Consider hypovolemia. Consider pneumothorax. Airway management Thermoregulations • Bulb suction ♦ Radiant warmer, caps. • Suction catheter ♦ Warm blankets. ♦ Stethoscope • Plastic wrap for covering the baby. ♦ Ventilation ♦ Temperature probe. ♦ Bag and mask • Oral airways Gastric decompression • 0 source ♦ Orogastric tube 2 • Laryngoscope ♦ Suction • Endotracheal Tubes (ETT). ♦ Personal Protection Equipment ♦ Um bilical Vein Catheter (UVC). (PPE). Chapter 33: Diseases of the Fetus and the Newborn l@;J1 . Figs. 33.2A to F: Top: (1) Infant resuscitation bag and mask (Ambu bag), (2) Short binasal prongs. Bottom: Use of face mask: (A) Correct; (B and C) Incorrect; (D) Correct positioning (neck slightly extended); (E) Chest compression (thumb method); (Fl A neonate of 27 weeks under endotracheal tube ventilation, umbilical venous catheter, due to RDS, in a NICU. ■ During weaning HFNC can be used as an alternative to CPAP for some babies. 11 Mechanical Ventilation (MV) may be needed in babies with RDS when other methods of respirat01y support have failed. ■ Targeted tidal volume ventilation is preferred as it reduces lung injmy. ■ Caffeine is often used to facilitate weaning from MV. 11 A short tapering course of low dose dexamethasone could be used to facilitate extubation for babies on MVfor l-2weeks. 11 Inhaled budesonide is considered for infants at very high risk of Bronchopulmonaiy Dysplasia (BPD). Other Supportive Cases 11 Core temperature-to be maintained between 36.5 and37.5C. ° 11 IV fluids 7 0-80mL/kg/day-in a humidified incubator. Fluids need to be tailored for an individual baby. ■ Parenteral nutrition is needed from birth. 11 Early feeding with mother's milk should be started, once the baby is hemodynamically stable. ■ Hemoglobin level should be at normal limit. ■ Antibiotics need to be started as indicated. Drugs used for resuscitation: Drugs are needed for a persistent HR <6 0 bpm even after ventilation and chest compression. Drug of choice is epinephrine. Other drugs are given as needed (Flowchart 33.1). PROGNOSIS: The prognosis is dependent on: (I) Gestational age; (2) Duration and intensity of hypoxia and acidosis as evidenced by Apgar score and blood pH-higher the Apgar score, normal the pH, better is the prognosis; (3) Facilities for immediate and competent management of a compromised baby. Most survivors of perinatal asphyxia do not have any major sequelae. Factors for sequelae are: (i) Apgar score of 0-3 at 20 minutes of age; (ii) Presence of multiorgan failure (oliguria >24 hours of life); (iii) Severity of the neonatal neurological syndrome. Severe HIE carries mortality about80%, and (iv) Presence of neonatal seizure. COMPLICATIONS: Immediate: (a) Cardiovascular­ hypotension, cardiac failure; (b) Renal-acute cortical necrosis, renal failure; (c) Liver function-compromised; (d) Gastrointestinal-ulcers and necrotizing enterocol­ itis; (e) Lungs-persistent pulmonaiy hypertension; (f) Brain-cerebral edema, seizures, irritability, poor tone. Delayed: (a) Retarded mental and physical growth; (b) Epilepsy-up to 30% in severe asphyxia; (c) Minimal brain dysfunction. RESPIRATORY DISTRESS IN THE NEWBORN (Syn: Hyaline Membrane Disease) Increased alveolar fluid content, inadequate clearance of lung fluid, lack or inhibition of surfactant function, or reduced surface area for gas exchange is the basic pathology for respirat01y distress. The important clinical causes are shown in Table 33.2. Respiratory distress syndrome is defined as the persistence of arterial 02 tension (PaO2) <50 mm Hg and central cyanosis in room air. Supplemental oxygen supply is required to maintain PaO2 >50 mm Hg or pulse oximeter saturation >85%. Chapter 33: Diseases of the Fetus and the Newborn Table 33.2: Causes of respiratory distress. Pulmonary. ♦ Hyaline Membrane Disease (HMD) or RDS ♦ Meconium aspiration + Clear fluid aspiration + Pulmonary hypoplasia ♦ Bronchopulmonary dysplasia + Bronchopneumonia ♦ Airway obstruction ♦ Transient tachypnea ♦ Pneumothorax ♦ Pulmonary edema Cardiovascular ♦ Congenital heart disease Aortic stenosis, coarctation of aorta. Cyanotic-transposition of great vessels. - Tetralogy of Fallot. - PDA - VSD + Heart failure ♦ Persistent Pulmonary Hypertension of Newborn (PPHN). Noncardiopulmonary ♦ Metabolic acidosis ♦ Hypo-or hyperthermia ♦ Hypoglycemia + Asphyxia ♦ Drugs (pethidine) ♦ Birth trauma ♦ lntracranial injury INCIDENCE: It ranges from 75% at around 28 weeks to 52% at 30 weeks of gestation. Use of exogenous surfactant has significantly reduced the risk of neonatal death by <10%. PATHOGENESIS: The primary cause is inadequate pulmonary surfactant (Flowchart 33.2). Deficiency of surfactant in the lung alveoli increases alveolar surface tension. It is seen within first 24 hours of birth. Surfactant is a surface active material. It is produced by alveolar epithelial cells called type II pneumocytes at 24-28 weeks gestation. Antenatal corticosteroids enhances but fetal hyperinsulinemia delays surfactant synthesis. Other factors that enhance maturity of type II cells are: chronic stress, PIH, FGR, twins and placental insuficiency. There is poor lung compliance, reduction in ventilation-perfusion ratio and progressive atelectasis. Hyaline Membrane Disease (HMD) is further complicated by the weak respiratory muscles of the newborn. The consequent finding is widespread atelectasis. A homogeneous eosinophilic membrane (Fig. 33.3) (hyaline membrane) plastering the alveolar ducts and terminal bronchioles is found. Factors that affect lung maturation: 1. Maternal diabetes: Uncontrolled maternal diabetes is associated with enhanced increased production of fetal insulin. Insulin inhibits production of surfactant phospholipids. 2. Labor: Causes endogenous production of maternal glucocorticoids. This enhances sodium resorption by the epithelial sodium channels. Preterm babies, delivered by cesarean section have a higher incidence of RDS. 3. Male infants have higher risk of RDS as fetal androgens inhibits surfactant synthesis. Blood biochemical changes: The infant develops both metabolic and respiratory acidosis. Pa02 <50 mm Hg and PC02 may rise to even 80 mm Hg in a severe case. Normal blood gas values are: Arterial 02 tension of 50-70 mm Hg, arterial CO2 tension of 45-60 mm Hg, pH at or above 7.25. Arterial 02 saturation at 88-95%. Hypocalcemia and hypoglycemia can cause respiratory distress and tachypnea. OTHER INVESTIGATIONS: ♦ Sepsis workup: CBC, Absolute Neutrophil Count (ANC), band cell, micro-ESR, CRP, blood culture are done to detect early onset of sepsis (Group B Streptococcus). ♦ Blood glucose, calcium levels. ♦ Serum electrolyte levels. ♦ Echocardiography to exclude PDA, congenital heart disease. CLINICAL FEATURES: RDS is commonly found in preterm infant, <34 weeks of gestation. It develops soon after the birth. (1) Respiratory rate (tachypnea). (2) Rib retractions­ to maximize the negative inspiratory pressure. This results in subcostal, intercostal and suprasternal retractions. (3) Grunting is due to exhalation active exhalation against a partially closed glottis. ( 4) Hypoxia. (5) Tachypnea. (6) Nasal flaring to reduce the resistance of air flow. (7) Silverman-Andersen scoring-higher the score (2:5), more is the work of breathing and higher is the need of respiratory support. (8) Central cyanosis. Chest X-ray shows uniform reticulogranular pattern known as ground-glass mottling (Fig. 33.3) due to Flowchart 33.2: Etiopathological causes of respiratory distress syndrome. Neonates ♦ Preterm (<34 mm). ♦ Diabetic mother. • Cesarean delivery. • Hypothermic. • Hypovolemic. • Genetic factor. • Multiple pregnancy. + Male baby. -.1 Deficient I I I surfactant I Eitopathology Collapse of alveoli ' Atelectasis I I Hypoxemia and acidosis (metabolic and respiratory)➔ Increased pulmonary vascular resistance➔ hypoperfusion. ➔ alveolar epithelial damage. ➔ increased capillary permeability. ➔ leakage of plasma into alveolar spaces. ➔ combines with cellular debris to form characteristic hyaline membrane change. Recovery phase: Regeneration of alveolar cells and type II cells. There is increase in surfactant activity. Chapter 33: Diseases of the Fetus and the Newborn flb . Fig. 33.3: Hyaline membrane atelectasis. extensive atelectatic process. Homogeneus white lung with contrast "black" bronchi is the typical appearance. DIFFERENTIAL DIAGNOSIS: (1) Aspiration pneumonia (liquor amnii or meconium); (2) Transient tachypnea of newborn (TTN); (3) Pneumothorax; (4) Diaphragmatic hernia; (5) Congenital heart disease. PREVENTION: (1) Administration of betamethasone (12 mg) to the mother two doses IM 24 hours apart, especially before 34 weeks. Cortisol acts on type II pneumocytes to stimulate phospholipid synthesis. Benefits are obtained after 24 hours of therapy and continue for 7 days. Fetal hyperinsulinism blocks cortisol action; (2) Assessment of lung maturity before premature induction of labor and to delay the induction as much as possible without any risk to the fetus; (3) Prevent fetal hypoxia in diabetic mothers. Decreased risk factors are: ♦ Vaginal delive1y ♦ Corticosteroid therapy • Thyroid hormones ♦ Prolonged rupture of membranes ♦ Female baby. TREATMENT Pl"inciples of management in HMD are: (i) Prevent hypoxia and acidosis; (ii) Maintain fluid and electrolyte balance; (iii) Prevent atelectasis and pulmonary edema; and (iv) Avoid lung injury (barotrauma) and infection. Management: The key principles are to establish and maintain Functional Residual Capacity (FRC) at the earliest. The role of pulmonaiy surfactant in the alveoli and the bronchioles is to maintain a low surface tension. ■ The baby should be placed in neonatal intensive care unit and nursed in a warm incubator with high humidity (neutral thermal condition). Air passage is cleaned periodically through endotracheal suction. ■ Adequate warmed and humidified oxygen therapy in concentration of 35-40% under positive pressure is to be administered through endotracheal tube to relieve hypoxia and acidosis. If the arterial oxygen tension (PO2) cannot be maintained above 50 mm Hg, application of Continuous Positive Airway Pressure (CPAP) at 5-8 cm of water is indicated. Warm humidified air oxygen mixture is critical for the health of the respirat01y epithelium. ■ Correction of hypovolemia with albumin or other colloid solution. ■ Treatment of anemia, electrolyte imbalance if any and prevention of infection. ■ Frequent monitoring of the arterial PO2, PCO2, pH and base excess are to be determined to diagnose metabolic and respiratory acidosis. Higher than necessary FiO2 may cause lung injury and retinopathy of prematurity. ■ Acidosis should be corrected by adequate ventilation and oxygenation. ■ Continuous Positive Airway Pressure (CPAP) helps the infants with RDS to maintain FRC: Nasal (NCPAP) or nasopharyngeal (NPCPAP) is used early to delay or prevent the need for mechanical ventilation and tracheal intubation. ■ Surfactant replacement therapy has significantly improved the outcome of the infants with RDS. Surfactant is composed chiefly of phospholipids 80% and protein 10%. It is produced and stored in the characteristic lamellar bodies of type II pneumocyte. Reduction of surface tension and stabilization of alveolar air-water interface is its basic function. Surfactants of human, bovine (Survanta), porcine (Curosurf) or Calf (Infasurf) or synthetic preparations (Exosurf) have been used. Prophylactic surfactant replacement has reduced the risk of Bronchopulmonary Dysplasia (BPD), Chronic Lung Disease (CLD) and Deaths. Natural surfactants are the treatment of choice. Mechanical ventilation is less often needed when the technique 'Intubate-Surfactant-Extubate to CPAP' is done. Prophylactic therapy is given (within 15 minutes of birth) in very premature infants. Direct tracheal instillation is done through a feeding tube. Oxygen tension (PaO2) is adequately maintained. With the use of antenatal corticosteroids, early initiation of CPAP and the use of surfactant, the survival outcome even for smallest infant has improved significantly. Early rescue (within 2 hours of age) is preferable rather than delayed treatment. Surfactant reduces the need of intubation and mechanical ventilation (MV). Administration: commonly tracheal intubation and bolus administration is done. Less Invasive Surfactant Administration (LISA), is done using a special catheter either by direct or by video­ laryngoscopy. It reduces the need of MV. Complication: Pulmonary hemorrhage, air leak are rare complications of surfactant therapy. Surfactant Preparation and Dose Schedule ■ Surfactant may be used for RDS complicated with pneumonia or ■ In babies with pulmonary hemorrhage. Surfactant use and preparations Generic name Trader name Source Dose (volume) Beractant Survant Bovine 100 mg/kg/dose (4 ml/kg) Bovactant Aveofact Bovine 50 mg/kg/dose (1.2 ml/kg) Poractant Curosurf Porcine 100-200 mg/kg/dose (1.25-2.5 ml/kg f' -­ l t - Chapter 33: Diseases of the Fetus and the Newborn Table 33.3:The sequelae of perinatal asphyxia. System Manifestations Acute Long-term Cardiac ■ Cardiogenic shock. Papillary muscle dysfunction. • CNS ■ Cerebral edema. ■ Cerebral Palsy (CP). ■ Seizures. Epilepsy. • ■ Hemorrhage. ■ Mental retardation ■ HIE. (most CP, however, is not related to birth asphyxia). Pulmonary ■ Aspiration syndromes. ■ Chronic lung Pulmonary hemorrhage . disease (following • ■ HMO. HMO). Renal ■ Acute tubular necrosis, ■ Retinopathy of oliguria. prematurity. Adrenal • Hemorrhage . GI system ■ Necrotizing enterocolitis. Metabolic ■ Hypoglycemia. Hematologic • DIC, thrombocytopenia . ■ Mechanical ventilation-Indications are: Babies with poor respiratory effort, recurrent apnea with severe RDS (high Fi02 need, high CO2 despite optimal CPAP and surfactant). ■ Antibiotic therapy against common neonatal infections should be started initially. COMPLICATIONS: Acute complications of RDS include­ (i) Infection; (ii) Air leak (pneumothorax); (iii) Pneumo­ mediastinum; (iv) Persistent patent ductus arteriosus. Other complications are: (a) Intraventricular hemorrhage, (b) chronic lung disease (CLD), (c) bronchopulmonary dysplasia (BPD), (d) intracranial hemorrhage, (e) retin­ opathy of prematurity, (f) pulmonary hemorrhage, (g) barotrauma-pneumothorax, (h) retrolental fibroplasia; and (i) neurological abnormalities (Table 33.3). PROGNOSIS: With the widespread use of antenatal corticosteroids, early use of CPAP and exogenous surfactant, presently cases of RDS has been reduced significantly to few hours. RDS infants born 2:32 weeks of gestational and without other complications resolves completely without any long-term pulmonary squealae. TRANSIENT TACHYPNEA OF THE NEWBORN (TTN) Tachypnea of the newborn (TTN) is a self-limiting type of respiratmy distress due to delayed clearance of lung fluid. It is commonly seen in the preterm and less commonly in term newborns. It develops shortly after birth and usually resolves within 3-5 days. TTN-the incidence of TTN is 0.3% of the term and 1 % of the preterm deliveries. Physiology of pregnancy and labor: During preg­ nancy, fetal pulmonary epithelium actively secretes fluid into the alveoli. With the onset of labor and stress, fetal hormones and catecholamines (glucocorticoids, thyroid hormones, adrenaline) are released. This opens up the sodium channel mechanism for active absorption of sodium. During labor, there is rise in intrapulmonaiy pressure with uterine contractions and opening up of sodium channels. This results in shift of alveolar fluids from the alveoli to the interstitium. The fluid in the interstitium is slowly absorbed by the lymphatics and blood vessels. Pathology of TTN A. Absence of catecholamine surge: Infants born by Elective CS are not exposed to the stress of labor. These infants run the high risk ofTTN. B. Uterine contractions during labor increase the intra­ pulmonary pressure. This causes eflux of lung fluid via trachea. This is absent in the neonate born by cesarean delive,y. C. Birth through the vagina increases the transpulmo­ nary and intra-abdominal pressure of the neonate. This increased pressure forces the lung fluid out through the nose and mouth. This squeeze effect is absent in elective cesarean delivery. D. Relative deficiency of phosphatidylglycerol and surfactant at birth in these neonates is also seen. E. Genetic predisposition is also associated. Risk factors for TTN: a. Cesarean delive1y b. Preterm infant c. Male baby d. Breech delive1y e. Multiple gestation f. Infant of a diabetic mother g. Birth asphyxia h. Instrumental delive1y i. Macrosomia. ( forceps/ventouse) Clinical presentation: • Tachypnea (breaths >60 per minute), • grunting, • nasal flaring, • ribs retraction, cyanosis (rarely), chest radiograph may show 'double lung point', due to difference of lung echo between upper and lower lung areas. Management: Prevention: (a) To perform elective CS after 38 completed weeks, (b) antenatal betamethasone use. Actual management: ■ a. Oxygenation: With hood or nasal cannula, b. Nasal Continuous Positive Airway Pressure (NCPAP), when oxygen need is >30%, c. Intubation (rarely) when oxygen need >40%. ■ Neutral thermal condition to maintain. ■ Feeding: Oral when respiratory rate is <60 breaths per minute otherwise with nasogastric tube. ♦ N nutrition when RR is >80 breaths per minute. ■ Prognosis: Excellent, it usually lasts for 2-5 days. II MECONI UM ASPIRATION SYNDROME (MAS) Meconium Aspiration Syndrome (MAS) usually occurs in term or post-term babies who are small for gestational age (IUGR). Chapter 33: Diseases of the Fetus and the Newborn aa· Overall incidence of Meconium-Stained Amniotic Fluid (MSAF) varies between 10% and 15%. Chronic placental insufficiency leads to intrauterine hypoxia with passage of meconium. The meconium-stained liquor may be aspirated by the fetus-in-utero or during first breath. Pathophysiology includes: (a) airway obstruction, lung atelectasis causing hypoxia and increased pulmonary vascular resistance (PVR); (b) chemical pneumonitis; (c) pulmonary inflammation due to release of cytokines. This causes airway edema and hypoxia; (d) surfactant dysfunction; and (e) development of Persistent Pulmonary Hypertension (PPHN). Not all the infants with meconium aspiration will develop MAS. Features of respiratory distress develop immediately after birth in only 5-10% infants. The infant manifests with tachypnea, nasal flaring, intercostal retractions and cyanosis. Diagnosis is mainly based on: (a) Aspiration of meconium from the trachea at birth; (b) Signs of respiratory distress; (c) Radiologically hyperinflated lung fields, flattened diaphragm with coarse and patchy infiltration; and (d) Cyanosis. Management ♦ Careful intrapartum monitoring; ♦ Amnioinfusion in oligohydramnios-may reduce cord compression, grasping and intrapartum aspiration. ♦ Maintenance of: (a) thennoneutral environment; (b) blood; to correct metabolic abnormalities (glucose, calcium); (c) circulatory support (normal saline or whole blood). ♦ Liberal oxygen supply and monitoring of SpO2• ♦ Depending on the severity, infant may need assisted ventila-tion and/or CPAP and often associated with PPHN. ♦ Antibiotic coverage, as meconium invites infection. ♦ In a severe case arterial blood gas analysis should be done. ♦ Surfactant therapy is beneficial; corticosteroid not routinely used. Inhaled Nitric Oxide (iNO) and Extracorporeal Membrane Oxygenation (ECMO) may be needed in cases with refractory respiratory failure. ♦ General management includes correction of hypoxia, acidosis, hypoglycemia and hypocalcemia. Mechanical ventilation is required where PO2 is less than 50 mm Hg and PCO2 is above 50 mm Hg. Complications like air leak (pneumothorax), PPHN, bronchopulmonary dysplasia or chronic lung diseases are common. New modalities of therapy have reduced mortality to <5%. Prognosis: MAS may be associated with neurodevelopmental delay, cerebral palsy and mental retardation. Infants need long-term follow-up. JAUNDICE OF THE NEWBORN Yellow discoloration of the skin and the mucosa is caused by accumulation of excess of bilirubin in the tissue and plasma (serum bilirubin level should be in excess 7 mg/dL). A value >15 mg/dLis considered severe. About 80% of term newborn and most of preterm newborns develop clinical jaundice. Bilirubin source and metabolism: RBC hemoglobin ➔ breakdown in RE system➔ biliverdin, CO2 (excreted by lungs) and iron (reutilized). Biliverdin is reduced to bilirubin by the enzyme biliverdin reductase. I g hemoglobin produces 35 mg of bilirubin. Bilirubin bound to serum albumin is transported to the liver cells➔ carried to the smooth endoplasmic reticulum by cytoplasmic ligandin (Y protein). Unconjugated (indirect) bilirubin is converted to Conjugated (direct) Bilirubin (CB) by Uridine Diphosphoglucoronate Glucoronosyl Transferase (UGTIAI). CB excreted in GI tract, is eliminated by stool. When CB is acted upon by J3 glucuronidase, it is converted to UCB which is reabsorbed back to the liver (enterohepatic circulation) for reconjugation. Sulfonamides, and free fatty acids can displace bilirubin from albumin. Phenobarbitone can induce the enzyme UGPG-GT and catalyze the conjugation process. Conjugated bilirubin is water soluble and nontoxic. Unconjugated bilirubin is toxic and causes neuronal dysfunction and death. I CAUSES OF NEONATAL JAUNDICE ♦ Physiological ♦ Nonphysiological PHYSIOLOGICAL: The jaundice usually appears on 2nd and 3rd day and disappears by 7th-10th day, a little later in premature neonates. In a term infant, the level may be 3-5 mg/dL on 3rd day. A rise of unconjugated serum bilirubin to 12 mg/dL is in the physiological range. In a preterm infant the peak level of 12-15 mg/dL in the 1st week may be without any abnormality. Causes of excessive bilirubin production are: 1. Increased red cell volume per kg and increased red cell destruction due to shorter lifespan (90 days compared to 120 days in adult) in the neonate. 2. Transient decreased conjugation of bilirubin due to decreased UGPG-GT activity. 3. Increased enterohepatic circulation due to decreased gut motility and high level of intestinal p glucuronidase. 4. Decreased hepatic excretion of bilirubin; and 5. Decreased liver cell uptake of bilirubin due to decreased ligandin (transport protein). Labor and Delivery (a) Birth trauma; (b) Oxytocin use; (c) Infants with hypoxic ischemic insult; (d) Delayed cord clamping. Treatment: No specific treatment is required. The baby is given more frequent feeds. In premature babies, careful observation is required and evidences of rising bilirubin near critical level need exchange transfusion. However, use of phenobarbitone or phototherapy is quite useful in such cases. PATHOLOGICAL CAUSES OF SEVERE NEONATAL HYPERBILIRUBINEMIA A. Excessive red cell hemolysis i. Hemolytic disease of the newborn: • Fetomaternal blood group incompatibilities: Rh (most common), ABO (rare), immunization against Kell antigen (rarest). • Increased red cell fragility-congenital sphero­ cytosis. • Deficient red cell enzyme-Glucose-6-Phosphate Dehydrogenase (G6PD deficiency and drugs). ii. Sepsis: Intrauterine (Toxoplasma, Rubella), neonatal (E. coli) omphalitis. Im Chapter 33: Diseases of the Fetus and the Newborn iii. Blood extravasation ( cephalhematoma, intraven­ tricular hemorrhage). B. Defective conjugation of bilirubin and clearance i. Congenital deficiency of glucuronyl transferase • Preterm babies with impaired liver function. • Crigler-Najjar syndrome (Autosomal Recessive), • Gilbert syndrome (Autosomal Dominant), C. Breast milk jaundice: The activity of the enzyme-glucuronyl transferase is inhibited by a specific steroid 3a, 20 ­ pregnanediol and increased fatty acids of breast milk. The bilirubin level rises fom the 7th day after birth to a maximum of 20-30 mgldL by 14th day. Jaundice is usually mild and it takes a time (4-12 weeks) to disappear. It rarely causes kernicterus. It requires no treatment. If the bilirubin level is more, temporary withdrawal of breastfeeding cures jaundice. Breast milk jaundice may recur in 70% offuture pregnancies. Breastfeeding jaundice is due to decreased intake of milk that leads to increased enterohepatic circulation. r D. Metabolic and endocrine disorders: Galactosemia, hypo­ thyroidism (unconjugated hyperbilirubinemia). Galactosemia: There is heredita1y deficiency of an enzyme­ galactose-1-phosphate uridyl transferase which converts galactose derived from the milk into glucose-1-phosphate. As a result there is increased accumulation of galactose that leads to periportal fibrosis and cirrhosis of liver. The biliary canaliculi are blocked by inspissated bile and obstructive jaundice results. Baby develops jaundice, hepatomegaly and feeding intolerance. A reducing substance (lactose) is detected in the urine by clinistix. Breastfeeding is contraindicated because of high lactose content. Lactose-free milk feeding should be recommended. E. Increased enterohepatic circulation of unconjugated bilirubin: Duodenal atresia, pyloric stenosis, less frequent feeding. F. Substances and disorders that affect binding of bilirubin to albumin: Aspirin, sulfonamides, fatty acids and asphyxia, acidosis, sepsis, or hypothermia increases free unconjugated bilirubin level. G. Miscellaneous: • Congenital obstruction (atresia or stricture of biliary canaliculi), • asphyxia, • polycythe­ mia and • thalassemia. I HYPERBILIRUBINEMIA OF THE NEWBORN When the bilirubin (unconjugated) level rises more than the arbitrary cut-off point of 12 mg/dL, in a term infant the condition is called 'hyperbilirubinemia of the newborn'. The face and chest of the infant are usually stained yellow at this level of serum bilirubin (Box 33.2). Conjugated hyper­ bilirubinemia is never normal or physiologic. ■ Unconjugated: Hemolytic disease due to Rh (common) or ABO (rare) incompatibility, increased red cell fragility (spherocytosis), prematurity, glucose-6-phosphate­ dehydrogenase deficiency, sepsis, iatrogenic (drugs), breast milk jaundice, cephalhematoma, hemoglo­ binopathy, infant of diabetic mother, hypothyroidism, idiopathic neonatal hepatitis. ■ Jaundice appearing within 24 hours of birth. ■ Bilirubin level increasing at the rate of >5 mg/dl/day or >0.2 mg/dl/hour. ■ Conjugated bilirubin >2 mg/dl. ■ Clinical jaundice persisting > 1 week in a term infant or >2 weeks in a preterm infant. ■ Jaundice requiring phototherapy. ■ Sick baby. Table 33,4: Dermal icterus zone and serum bilirubin level. Derma/zone Blirubin (mgldL) 1 5 2 10 3 12 Fig. 33.4: Dermal icterus 4 15 zone and serum bilirubin (indirect) level in a term > 15 5 infant (Kramer-1969). ■ Conjugated: Neonatal hepatitis, bacterial infection, intra­ uterine TORCH infection, trisomy 21, 18; galactosemia, cystic fibrosis, biliary atresia, drugs (anticonvulsants), panhypopituitarism, etc. Management of Hyperbilirubinemia in Newborn Infant >35 Weeks of Gestation (AAP) (Box 33.3) ■ Lower gestational age (<37 weeks). ■ Jaundice in the first 24 hour after birth. ■ Pre-discharge Transcutaneous Bilirubin (TcB) or Total Serum Bilirubin (TSB) concentration close to the phototherapy threshold (Fig. 33.5). ■ Hemolysis from any cause (based on a rapid rate of increase in the TSB orTcB of >0.3 mg/dl per hour in the first 24 hour or >0.2 mg/dl per hour thereafter). ■ Phototherapy before discharge. ■ Previous sibling with jaundice. ■ Family history of inherited red blood cell disorders, including (G6PD) deficiency. ■ Scalp hematoma or significant bruising. ■ Macrosomic infant of a diabetic mother. DIAGNOSIS OF NEONATAL HYPERBILIRUBINEMIA A. Clinical: Evaluation of jaundice is done by blanching the skin with digital pressure. Visual inspection is not a reliable indicator of serum TB level. Severe hyperbilirubinemia (TB >25 mg/dL) is associated with the increased risk ofBilirubin Induced Neurologic Dysfunction (BIND). Clinical jaundice in a neonate indicates serum bilirubin of more than 5 mg/dL. Cephalocaudal progression of dermal icterus is a useful clinical tool (Fig. 33.4). Dermal icterus zone and serum bilirubin (indirect) level in a term infant (Kramer-1969) (Table 33.4). Chapter 33: Diseases of the Fetus and the Newborn A thorough physical examination of the infant is done. Abnormal neurologic signs are: lethargy, poor feeding, vomiting, hypotonia and seizures. B. Laboratory studies: Serum bilirubin level > 12 mg/ dL, requires further investigations. 1. Blood group (ABO, Rh) status-mother and infant. Antibody screen of the mother. 2. Direct Coombs' test (infant)-for alloimmunization disorder. Positive➔ Antibody study (Rh, ABO, Kell). 3. Total bilirubin, conjugated bilirubin and unconjugated bilirubin. 4. Complete hemogram including reticulocyte count: • Hemolytic anemia: ,I, Hb%, t reticulocyte count, presence of nucleated red cells. • Sepsis: WBC count (total and differential) I,, neutrophil I,, band cell, micro ESRt, CRPt. ♦ Polycythemia: Hematocrit (>65%) t. • Hereditary spherocytosis: Peripheral blood film t reticulocyte count. 5. Serum albumin to detect total bilirubin binding sites and to assess the need of albumin infusion. 6. Other laboratory tests: ♦ Urine for reducing substance (galactosemia), culture for infection. ♦ Hemoglobin electrophoresis. ♦ Osmotic fragility tests. ♦ Thyroid and liver function tests. ♦ G6PD screening. ♦ LFT (AST, ALT, PT). C. Ultrasonography or MRI to detect intestinal obstruction, intraventricular hemorrhage and tumor. COMPLICATION (unconjugated)-kernicterus is the important complication which is more often fatal, if not promptly detected and adequately treated. II KERNICTERUS Kernicterus is the chronic and permanent squealae of bilirubin toxicity that develop during the first year of the age. The other signs are: ♦ Choreoathetoid cerebral palsy with neuromotor impairment. ♦ Sensory neural hearing loss. ♦ Limitation of upward gaze and ♦ Dental enamel dysplasia Basal ganglia, cerebellum, cranial nerve nuclei, hippocampus, brainstem nuclei and anterior horn cells of the spinal cord are commonly affected. The critical level of bilirubin causing kernicterus in a term infant is more than 20 mg/dL (340 µmol/L). Bilirubin enters the brain in free (unbound) form (Box 33.4). Risk of bilirubin encephalopathy is unlikely, if the total bilirubin level is <20 mg/dL. Hypoxia, acidosis, hypoglycemia, hypothermia, sepsis or prematurity enhance the pathogenesis so affection may occur even at a low level ofbilirubin. Excess rise of conjugated bilirubin cannot produce kernicterus. It is clinically characterized by lethargy, hypotonia, poor feeding and loss of neonatal reflexes, and oculogyric crisis. ■ Gestational age <38 weeks. Risk increases with degree of prematurity. ■ Serum albumin <3.0 g/dl. ■ Hemolytic conditions (Rh-ABO disease, G6PD deficiency, others). ■ Sepsis. MANAGEMENT OF JAUNDICE IN THE NEWBORN I Objective of management is prevention of encephalo­ pathy or severe hyperbilirubinemia of the newborn l9 Chapter 33: Diseases of the Fetus and the Newborn (>25 mg/dL in a term, baby). Three methods of treatment are used to reduce the level of unconjugated bilirubin: (1) Phototherapy; (2) Exchange transfusion. 1. Phototherapy: It is best when used in moderate cases where the bilirubin level rises above 12 mg%. Total Serum Bilirubin (TSB) or Transcutaneus Bilirubin (TcB) to be measured. Phototherapy is discontinued when serum bilirubin level is <13 mg/dL in term and <11 mg/dL in preterm neonates. A rebound increase in serum bilirubin may occur once phototherapy is stopped. Adequate hydration of the neonate has to be maintained. Special blue lamps with an output of 460-490 nm wavelengths are the most effective. Double phototherapy ( overhead light-plus light from below or fiberoptic blanket) is twice as effective as single phototherapy. Bilirubin (indirect) absorbs light maximally at that range and undergoes photoisomerization and is converted to less toxic polar isomer (4Z, 15E) which is excreted into the bile. Phototherapy also converts bilirubin to lumibilirubin by structural isomerization. Lumibilirubin is excreted in the bile and urine without conjugation. Light sources: Blue Light-Emitting Diodes (LEDs) are the optimum in the absorption spectrum of bilirubin. These are available as either overhead or underneath devices and can be placed closer to the infant. Sunlight also lower the TB level effectively. Risks are due to ultraviolet light and skin burn. Monitoring: TB is to be measured to monitor the response to therapy. TB decreases during the first 4-6 hours of exposure. Urine output, weight record are maintained. Breastfeeding is continued. Phototherapy should be started early, exposing the maximum surface area and shielding the eyes. It may be continuous or interrupted for breastfeeding. Phototherapy causes increased insensible fluid loss of the neonate. Oral hydration with frequent breast milk is encouraged. IV fluid therapy or nasogastric feeding may be needed. Fiberoptic blankets protect the infants. Adverse effects ofphototherapy are: Watery diarrhea, skin rashes, dehydration, bronze baby syndrome (dark brown discoloration of the skin), low calcium levels and retinal damage. Treatment decision (phototherapy) depends on the Total Serum Bilirubin levels (TSB). Presence of risk factors (Box 33.4) lower the threshold for phototherapy {Fig. 33.5). All infants should be visually assessed for jaundice at least every 12 hours following delivery. TSB or TcB should be measured as soon as possible especially those with high-risk factors (Box 33.4). There is a good correlation between TcB and TSB concentration for infants >35 weeks. TcB is noninvasive. It measures bilirubin levels by comparing the wavelengths of lights directed into the skin of the neonate and those reflected back. TSB generally remains within 3 mg/dL of the TcB. TSB should be measured if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold or if the TcB is >15 mg/dL. Phototherapy decreases bilirubin concentrations. Intensive phototherapy is recommended at the total serum bilirubin thresholds {Fig. 33.5). Phototherapy treatment thresholds take ■ When there is progressive rise of bilirubin (> 1 mg/dl/hour) in spite of phototherapy. ■ Rate of bilirubin rise >0.5 mg/dl/hour despite phototherapy when Hb is between 11-13 g/dl. ■ To improve anemia and congestive cardiac failure of the neonate. the gestational age and also other high risk factors for neurotoxicity (Fig. 33.5). Infants under phototherapy should have the tests for hemoglobin, hematocrit to detect any anemia. G6PD activity should be measured when TSB increases despite intensive phototherapy. Phototherapy is discontinued when there is fall of TSB by at least 2 mg/dL below the hour specific threshold. Infant should be followed after phototherapy to detect any rebound hyperbilirubinemia. Escalation of care: Exchange transfusion is needed when there is rapid rise of serum bilirubin. The escalation of care threshold is 2 mg/dL below the exchange transfusion threshold. Intravenous Immune Globulin (IVIG-0.5 to 1 g/kg over 2 hours) is given for infants with isoimmune (Rh or ABO incompatibility) hemolytic disease. Urgent exchange transfusion is done when TSB rises despite phototherapy or is within 2-3 mg/dL of the threshold recommended for ET. 2. Exchange Transfusion (ET) is done to remove bilirubin when intensive phototherapy fails to prevent rising bilirubin or neurologic signs suggesting bilirubin toxicity (Box 33.5). Double-volume exchange replaces 85% of circulating red blood cells and reduces bilirubin level by 50%. In nonimmune hyperbilirubinemia blood is typed and cross-matched with the infant. Two-volume exchange is usually done. If the newborn's blood volume is 80 mL/kg, then 160 mL/kg of blood is used for exchange transfusion. Complications of exchange transfusion: • Air embo­ lism, • thrombosis, • hypervolemia, RDS, hypothermia, acidosis, infection, hyperkalemia, hypocalcemia, hypo­ glycemia, cardiac arrhythmias, thrombocytopenia, coagulopathies and necrotizing enterocolitis. HEMOLYTIC DISEASE OF THE NEWBORN Hemolytic Disease of the Newborn (HDN) is due to hemolysis of the fetal red blood cells (RBCs) due to passively acquired maternal antibodies. Hemolysis is manifested by a: • Decreased hematocrit, • Increased reticulocyte count and • Increased bilirubin level. The common causes are shown in Table 33.5. I __ABO GROUP INCOMPATIBILITY___ _ Principle: The mother with blood group O has got naturally occurring anti-A and anti-B agglutinins. These antibodies are mainly IgM and do not cross the placenta. If the fetus happens to be blood group A or B corresponding to that of the father, the Table 33.S: Common causes of HDN. A.Immune B. Inherited RBC C.Acquired hemolysis disorders heriolysis ■ Rh • RBC membrane • Infection: incompatibility defects bacterial, viral, ■ ABO incom- (spherocytosis, parasitic (rubella, patibility elliptocytosis) syphilis) ■ Other blood ■ Metabolic: G6PD ■ DIC group deficiency ■ Acute transfusion incompatibility ■ Systemic diseases hemolysis (C, E, Kell, Dufy) (galactosemia) ■ Vitamin E ■ M<1ternal diseases ■ Hemoglobinopathies deficiency (lupus); drugs (a-and -thalas- ■ Drugs (vitamin K, semia syndrome) nitrofurantoin) Management is to treat this underlying primary disorder, simple transfusion, exchange transfusion and nutritional support (Fe, folate, vitamin E). immune antibodies are formed in response to the entry of A or B antigen bearing fetal red cells, into the maternal circulation. As these are mainly IgG, they can cross across the placenta into the fetal circulation and cause a variable amount of hemolysis due to antigen-antibody reaction. Although 15% of the babies have got ABO blood group incompatibility, only in 34 weeks gestation are 14-20 g/dL with an average value of 17 g/dL. DEFINITION: Central venous hemoglobin level <13 g/dL in an infant of >34 weeks gestation is considered anemia. PATHOPHYSIOLOGY: Anemia in the newborn infant may be due to any one of the three pathologies: a. Physiologic anemia of infancy is due to shorter lifespan of RBCs and less erythropoietin production. b. Loss of RBCs (hemorrhagic anemia). c. Destruction of RBCs (hemolytic anemia); or d. Under-production of RBCs (hypoplastic anemia). CAUSES: (1) Hemorrhagic anemia: A. Obstetric causes: (a) Abruptio placentae; (b) Placenta pre­ via; (c) Traumatic rupture of umbilical cord; (d) Obstetric trauma (dificult delive1y with visceral or intracranial hemor­ rhage); (e) Twin-twin transfusion; (f) Delivery of the baby by cesarean section after cutting through the placenta in anterior ,·­ ! - "' ·L_J__ Chapter 33: Diseases of the Fetus and the Newborn placenta previa; (g) Ruptured vasa previa; (h) Excessive feto­ maternal bleed; {i) Anemia of prematurity; {j) Hereditaty RBC disorders-hemoglobinopathies. B. Neonatal causes: (a) Caput succedaneum; {b) Cephal­ hematoma; (c) Intracranial hemorrhage; ( d) Visceral hemorrhage (spleen, kidneys and adrenals); (e) DIC; (f) Thrombocytopenia; and (g) Hemorrhage due to deficient vitamin K dependent factors (II, VII, IX and X). (2) Hemolytic anemia (p. 452). (3) Under-production of RBCs: (a) Congenital hypoplastic anemia, {b) Leukemia, and (c) Infections (rubella, syphilis). Diagnosis: (1) History: (a) Family history of bleeding and (b) Maternal medications (phenytoin, warfarin); (2) Clinical examination (jaundice, splenomegaly, skin bruises); and (3) Laboratory tests: Complete blood count, RBC indices, blood smeat; reticulocyte count, Kleihauer Betke test, coagulation profile, intrinsic RBC defect, TORCH study and ultrasound of abdomen and head. TREATMENT: Treatment of anemia in neonates, involves treatment of the underlying primaty disorder along with blood transfusion, exchange transfusion and nutritional support. (1) Replacement transfusion in neonates with hemorrhagic anemia (hematocrit <35%); (2) Oral iron in suspension (2-4 mg elemental iron/ kg) and folic acid 50 µg/day vitamin E 25 JU/day have to be continued for a longer period; (3) Recombinant human etythropoietin (rh-EPO) for anemia of prematurity; (4) Exchange transfusion-in neonates with: {i) hemolytic or hemorrhagic anemia with raised CVP, (ii) Rh incompatibility. Treatment of selected disorders (e.g., consumption coagulopathy, immune thrombocytopenia). Prognosis depends on the basic underlying pathology and its severity. SEIZURES IN THE NEWBORN A seizure is a paroxysmal manifestation of neurological dysfunction (i.e., behaviors, motor or autonomic function). Overall incidence ranges from 1 to 5 per 1,000 live births. Pathophysiology: The basic mechanism is excessive depolarization ( excitation) of neurons within the CNS. Three possible reasons for excessive depolarization are proposed: A. Failure of sodium-potassium pump operation; B. Relative excess of excitato1y neurotransmitter compared to the inhibitory ones; C. Relative deficiency of inhibit01y neurotransmitters. Neonatal convulsion is usually a visible manifes­ tation of some underlying pathology (Table 33.6). Rarely, a baby may have convulsion where the cause can­ not be detected. The common causes of convulsion in the newborn are shown in Table 33.6. Risk factors: (a) Prematurity, (b) Birth weight <2.5 kg, (c) Maternal age 2:40 years, (d) Traumatic delivery (forceps). Common clinical seizure patterns are: (a) Focal clonic (b) Focal tonic (c) Myoclonic and (d) Automatic seizures. DIAGNOSIS History: Details of delivery, Apgar score at birth, birth weight, gestational age, breastfeeding or not, maternal drug history, family history of seizures, inborn errors of metabolism, withdrawal of narcotic drugs. INVESTIGATIONS: Laboratory studies • Full blood count • Blood, urine and CSF cultures. • Serum IgM and IgG-specific TORCH titers. • Blood biochemical-estimation for glucose, ammonia, calcium, magnesium, bilirubin and electrolytes, if needed. • Blood gas levels to detect acidosis and hypoxia. Imaging studies: EEG, ultrasonography and CT scan of the head-to detect intraventricular and/or subarachnoid hemorrhage. They are also useful to detect any congenital malformation. MRI-congenital abnormalities (lissencephaly, IVH, HIE). EEG diagnosis: Continuous Electroencephalogram (CEEG): >3 hours of monitoring is considered the gold standard for the diagnosis of neonatal seizures. TREATMENT: The principles of treatment are: (1) To control convulsions; (2) To stabilize the vital functions; (3) To treat the underlying pathology; and (4) To maintain supportive therapy­ nutrition, ventilation, cardiac output, serum electrolytes and pH. Neurologic consultation should be done. To control convulsions: Intravenous administration of phenobarbitone 20 mg/kg body weight slowly over a period of 20 minutes is effective. A maintenance dose of3-4 mg/kg bodyweight per day administered orally or IV for at least a period of2 weeks or even longer. In resistant cases IV phenytoin (dilantin), 15-20 mg/ kg at the rate of 1 mg/kg/min is administered. Maintenance dose of3-4 mg/kg/day is divided 12 hourly. Fosphenytoin is preferred. Many anticonvulsants (phenytoin, valproic acid, vigabatrin) increased the rate of apoptotic neuronal cell death. The drugs topiramate, levetiracetam do not have this effects. Table 33.6: Etiological factors for neonatal seizures. Traumatic ♦ Perinatal asphyxia. ♦ Hypoxic-lschemic Encephalopathy (HIE). ♦ lntracranial hemorrhage (subarachnoid, peri-or intraventricular or subdural). Metabolic ♦ Hypoglycemia ♦ Kernicterus ♦ Hypocalcemia ♦ Hypercalcemia ♦ Hyponatremia ♦ Hypomagnesemia ♦ Pyridoxine dependence Inborn error of metabolism ♦ Pyridoxine-dependent seizure. ♦ Mitochondrial disorders. ♦ Aminoacidopathies ♦ Organic acidurias Infective ♦ High fever ♦ CNS infection due to: • Group B Strepyococcus • E.coli • TORCH infection • Tetanus Iatrogenic ♦ Narcotic withdrawal ♦ Drug toxicity theophylline ♦ Respiratory stimulants Others (congenital) ♦ Cerebral malformation. ♦ Neonatal epileptic syndromes. ♦ Chromosomal syndromes. ♦ Unknown Levetiracetam, loading dose 20-50 mg/kg. IV bolus and maintenance dose: 20-80 mg/kg/day. Twice daily dosing is commonly used. To treat the underlying pathology: Hypoglycemia: Glucose infusion, 2 mL/kg of 10% glucose, through an intravenous line is given over 2-3 minutes. Blood glucose should be maintained at 70-100 mg/dL. Hypomagnesemia: Magnesium sulfate (0.4-0.8 mg/kg) is given 1V every 12 hours until magnesium level is normal. Infection: Appropriate antibiotic therapy following complete septic work-up. Hypocalcemia: Intravenous administration of 2 mL/kg of 10% calcium gluconate taken over 5 minutes. This is to be followed by oral calcium 40-50 mg/kg/day for few days. Pyridoxine deficiency: Intravenous administration of 100 mg pyridoxine is effective. Prognosis varies with the etiology. Convulsions due to transient or metabolic disorders (hypocalcemia) have an excellent prognosis whereas seizures secondary to congenital malformations, HIE, have poor outcome. The overall mortality rate has decreased but neurological sequelae (neurodevelopmental impairment, CP, epilepsy) are still around 30-40%. BIRTH INJURIES OF THE FETUS AND NEWBORN Birth injury is an impairment of the infant's body function or structure due to adverse influences that occurred at birth. Injmy commonly occurs during labor or delive1y. Antenatal injuries may be due to amniocentesis and intrauterine transfusion and intrapartum injury may occur following fetal scalp electrodes and intrapartum monitoring. Birth injuries may be severe enough to cause neonatal deaths, stillbirths or number of morbidities (Box 33.6 and Table 33. 7). Chapter 33: Diseases of the Fetus and the Newborn ■ Prolonged or obstructed labor. ■ Fetal macrosomia. ■ Cephalopelvic disproportion. " Very low birth weight infant 11 Vaginal breech delivery (breech). a Instrumental delivery (forceps or ventouse). 11 Difficult labor. 11 Shoulder dystocia. ■ Inadequate maternal pelvis. 11 Oligohydramnios. 11 Fetal anomalies. ■ Precipitate labor. 11 Manipulative delivery (IPV). Table 33.7: Birth injuries. Types of injury Organ(s) affected Soft tissue Skin: Lacerations, abrasions, fat necrosis, petechiae. Muscle Sternocleidomastoid. Nerve Facial nerve, brachia! plexus, Duchenne Erb (C5, C6), Klumpke (C7, C8, T1), spinal cord, phrenic nerve (C3, C4 or C5), Homer's syndrome, recurrent laryngeal nerve. Eye Hemorrhages: Subconjunctiva, vitreous, retina. Viscera Rupture of liver, adrenal gland, spleen testicular injury. Scalp Laceration, abscess, hemorrhage, caput succedaneum. Dislocation Hip, shoulder, cervical vertebrae. Skull Cephalhematoma, subgaleal hematoma, fractures. lntracranial Hemorrhages: lntraventricular, subdural, subarachnoid. I INJURIES TO THE HEAD Bones Fractures: Mandible, clavicle, humerus, femur, skull and nasal bones. CEPHALHEMATOMA: It is a collection of blood in between the pericranium and the flat bone (subperiosteal) of the skull, usually unilateral and over a parietal bone (Fig. 33.6). It is due to rupture of a small emissary vein from the skull and may be associated with fracture of the skull bone. This may be caused by forceps delivery but may also be met with following a normal labor. Ventouse application does not increase the incidence of cephalhematoma. It is never present at birth but gradually develops after 12-24 hours. The swelling is limited by the suture lines of the skull as the pericranium is fixed to the margins of the bone (Fig. 33.6). It is circumscribed, soft, fluctuant and incompressible. There may be underlying fracture of the skull. It can cause hyperbilirubinemia when extensive, and the infant may need blood transfusion. MRI scan should be done if neurologic symptoms are present. The condition may be confused with caput succedaneum or meningocele. Meningocele always lies over a suture line or fontanel and there is impulse on crying. Management: Observation is done. The blood is absorbed in course Injuries may involve: (i) Soft tissue (most common) and/or (ii) Bones (rare) Faix cerebelli Tentorium cerebelli Fig. 33.5: Excessive molding of the head with marked elongation of the mentovertical diameter resulting in tear of the tentorium cerebelli. El Chapter 33: Diseases of the Fetus and the Newborn of time (6-8 weeks) leaving an entirely normal skull. Prognosis is good. Rarely, suppuration occurs. No active treatment is necessary. Prevention of infection and avoidance of trauma are important. Anemia and hyperbilirubinemia should be treated. Subgaleal hematoma is the hemorrhage under the scalp aponeurosis. It may occur following vacuum or forceps delivery. The hematoma can spread across the entire calvarium over the suture lines unlike cephal-hematoma. It may be progressive and needs frequent reassessment. Clinically, it is noted as a fluctuant swelling with insidious onset. Rarely rapidly progressive to cause shock even. Management: The infant needs to be observed care­ fully for signs of hypokalemia. Blood transfusion may be need.ed. Head circumference monitoring, phototherapy for any hyperbilirubinemia may be needed. Surgical drainage rarely indicated. SCALP INJURIES: Minor in1uries of the scalp such as abrasion in forceps delivery (tip of the blades), incised wound inflicted during cesarean section, scalp-electrode placement or episiotomy may be met with. On occasion, the incised wound may cause brisk hemorrhage and requires stitches. The wound should be dressed with an antiseptic solution like 2% mercurochrome. Fracture skull: Fracture of the vault of the skull (frontal or anterior part of the parietal bone) may be of linear or depressed type. Fractures are due to the effect of a dificult forceps delivery. The fracture may be associated with cephalhematoma, extradural or subdural hemorrhage or a hematoma or brain contusions. Linear fracture if uncomplicated is usually symptomless. Depressed fracture may occasionally cause pressure effect. Neurological manifestations may occur later on due to effect of compression. Treatment is conservative in symptomless cases. Neurosurgical consultation should be obtained in presence of symptoms and X-ray or MRI studies are needed. The depressed bone has to be elevated or subdural hematoma may have to be aspirated or drained surgically. i lNTRACRANIAL HEMORRHAGE ♦ Traumatic ♦ Anoxic ♦ Primary hemorrhagic disease (p. 453) Intracranial Hemorrhage {ICH) may be-(a) external to the brain (epidural, subdural or subarachnoid spaces); {b) in the parenchyma of brain (cerebrum or cerebellum); and (c) into the ventricles from subependymal germinal matrix or choroid plexus. Ve1y common is subdural hemorrhage (70%), then subarachnoid (20%) ➔ intracerebral (20%) ➔ intraventricular and epidural hemorrhage. The most common ICH in preterm infants is bleeding from the germinal matrix and that may result in intraventricular or periventricular hemorrhage. Traumatic ■ In Epidural Hemorrhage (EH) blood collects between inner skull and the dura mater. It is rare in newborn. Usually associated with fracture skull bone following dificult instrumental delivery (described earlier). EH does not always need surgical intervention. It needs monitoring with serial imaging. ■ Subdural Hemorrhage (SDH) is the accumulation of blood between the dura and arachnoid membrane. ♦ Slight hemorrhage may occur following: (i) fracture of skull bone; {ii) rupture of the inferior sagittal sinus; or (iii) ruptme of small veins leaving the c01tex. The hemorrhage, so occurring, produces hematoma which may remain stationa1y or increase in size. Neurological symptoms may appear acutely or may have insidious onset, like vomiting, irritability and failure to gain weight. Hydrocephalus and mental retardation may be a late sequelae. ♦ Massive hemorrhage: Massive subdural hemorrhage usually results from-(1) Tear of the tentorium cerebelli thereby opening up the straight sinus or rupture of the vein of Galen or its tributaries; (2) Injury to the superior sagittal sinus. Clinical presentation: Nuchal rigidity, coma, apnea, bulging fontanel (increased intracranial pressure) nonreactive pupils, seizures may be present. Meehani,m oftento,iol tea, Causes: {i) Excessive moulding in deflexed vertex I.": with gross disproportion; (ii) Rapid compression of • the head during delivery of the aftercoming head of • breech or in precipitate labor; and {iii) Forcible forceps traction following wrong application ofthe blades (other than biparietal diameter). !] .,. Clinical features: The hemorrhage may be fatal and the baby is delivered stillborn or with severe respiratory depression. In lesser affection, the baby recovers from the respiratory depression. Gradually, the features of cerebral irritation appear, such as, frequent high-pitch cry, neck retraction, incoordinate ocular movements, convulsion, vomiting and bulging of the anterior fontanel. Subarachnoid Hemorrhage (SAH) is an accumulation of blood between the arachnoid and the pia mater. It is due to the rupture of small vessels due to birth trauma or birth asphyxia. It may be idiopathic and significant at times. The symptoms may appear late (1 week). Clinical presentations are: seizures, irritability and lethargy with focal neurological signs. Anoxic damage may be: (A) Cerebral intraparenchymal hemorrhage (IPH) or (B) Intraventricular hemorrhage (IVH)/ Germinal Matrix Hemorrhage (GMH). Fu, Hemonhage due to Ano>ia Diagnosis is made invariably by neuroimaging ,- studies: Real time portable Cranial Ultrasonography ., · . !J, · (CUS) is the procedure of choice in the term newborn. IVH is diagnosed by head CT or CUS. MRI is also helpful. Risk factors for GMH/IVH: Extreme prematurity (32 weeks), and birth asphyxia. PVH, IVH and PVL are the most common neurologic complications of prematurity. GMH/IVH originates from the fragile involuting vessels of the subependymal germinal matrix. PREVENTION: Comprehensive antenatal and intranatal care is the key to success in the reduction of intracranial injuries. Antenatal measures to prevent IVH/GMH 1. Tocolysis with indomethacin should be avoided. 2. In utero transfer of preterm labor to a center with NICU. 3. Cesarean delivery before active phase of labor in preterm infants. 4. Antenatal steroids can reduce the risk by threefold. 5. To prevent or to detect at the earliest, intrauterine fetal asphyxia by intensive fetal monitoring. 6. To avoid traumatic vaginal delivery in preference to cesarean section. Difficult forceps should be avoided. 7. Administration of vitamin K I mg intramuscularly soon after birth in susceptible babies. Postnatal prevention: Avoid birth asphyxia, fluctuation of blood pressure and correct acid-base abnormalities. Surfactant therapy is found helpful. INVESTIGATIONS 1. Cranial Ultrasonography (CUS) is used to detect intraventricular hemorrhage; 2. Doppler ultrasonography can detect any change in cerebral circulation; 3. CT scan is useful to detect cortical neuronal injury; 4. Magnetic Resonance Imaging (MRI) is the best for Cerebral Intraparenchymal Hemorrhage (IPH). In addition MR angiography/venography may be useful to demonstrate a vascular anomaly, arterial embolus or sinus venous thrombosis. MRI is superior than CT, CUS to establish the etiology of IPH, to determine the long term prognosis of the newborn (Fig. 33.7); and 5. CSF-elevated RBCs, WBCs and protein. MANAGEMENT: Prnvention: Antenatal glucocorticoids reduce GMH/IVH. Supportive care: To maintain normal circulatory volume, cerebral perfusion, serum electrolytes and blood gases. Packed red blood cells transfusion may be needed where IVH is large. Thrombocytopenia and coagulation parameters should be corrected, seizures should be treated. Fig. 33.7: MRI of brain showing massive areas of hypoxic and ischemic injury (arrows). Chapter 33: Diseases of the Fetus and the Newborn TREATMENT ■ Follow-up with serial neuroimaging Cranial Ultrasound (CUS and MRI) to detect any progressive hydrocephalus. ■ Anticonvulsant: Any of the following may be useful­ (a) Phenobarbitone; (b) Phenytoin; (c) Levetiracetam. ■ Subdural hematoma: (a) Subdural tap-aspiration of the blood through lateral angles of the anterior fontanel may be required which may have to be repeated; (b) Open surgical evacuation-serial CT is indicated before surgical interven­ tion. The infant should be monitored for any hydrocephalus. Surgical removal of the clot including the capsule may have to be done to prevent development of neurological sequelae; and (c) Rarely, subdural-peritoneal shunting may be needed. Neurosurgeon is consulted. PROGNOSIS: Prognosis of GMH/IVH depends on the severity of IVH, brain lesions, birth weight and gestational age of the infant. The surviving infants usually behave normally in later life. There is, however, some correlation with mental retardation and neurological disorders. Epilepsy may develop later in life. Management of IPH: Acute management is similar to SDH and SAH. Any large IPH with severe neurologic compromise, needs prompt neurosurgical intervention. A large IPH when associated with IVH or SAH, should be observed at a regular interval. Long-term prognosis largely relates to the location, size of the IPH and the gestational age of the newborn. Major cerebellar IPH in preterm newborns may result severe cognitive and motor disability. I OTHER INJURIES SKIN AND SUBCUTANEOUS TISSUES: Bruises and lacerations on the face are usually caused by forceps blades. Scalpel cut or laceration injury may occur during cesarean section. They usually occur on the buttocks, scalp or thigh. Small cut heals spontaneously. Laceration injury may need repair by stitches with 7-0 nylon. Healing is usually rapid. MUSCLES ■ Sternocleidomastoid (SCM) injury (congenital torticollis) is characterized by a well-circumscribed immobile mass in the midpoint of the SCM. The head tilts towards the involved side. The patient cannot move the head normally. ■ Sternomastoid hematoma usually appears about 7-10 days after birth and is usually situated at the midposition of the muscle. It is caused by rupture of the muscle fibers and blood vessels, followed by a hematoma and cicatricial contraction. It may be associated with difficult breech delivery or attempted delivery following shoulder dystocia or excessive lateral flexion of the neck even during normal delivery. There is transient torticollis and it is wise not to massage. Treatment is conservative. Stretching of the involved muscle should be done several times a day. Recovery is rapid (3-4 months) in majority of cases. Surgery is needed if it persists after 6 months of physical therapy. NERVE INJURIES: Facial (cervical nerve VII) palsy (peripheral): The facial ne1ve remains unprotected after its exit through the stylomastoid foramen. It is involved by direct pressure of the forceps blades or by hemorrhage and edema around the nerve. It may even be involved in spontaneous delivery when too much pressure is applied on the ramus of the mandible where Im Chapter 33: Diseases of the Fetus and the Newborn the nerve crosses superficially. Diagnosis is made by noting the eye of the affected side which remains open and eyelids are immobile. On c1ying, the angle of the mouth is drawn over to the unaffected side. No nasolabial fold is present. Sucking remains unaffected. Treatment aims at protecting the eye, which remains open even during sleep, with synthetic tears (1 % methyl cellulose drops). The condition usually disappears within 2-3 weeks unless complicated by intracranial damage (Figs. 33.8A and B). ■ Brachial plexus palsy: Either the nerve roots or the trunk of the brachia! plexus are involved. The damage of the nerve is due to stretching (common) or effusion or hemorrhage inside the sheath. Tearing of the fibers is rare. The cause is undue traction on the neck during attempted delivery of the shoulder. The affection is due to hyperextension of neck to one side with forcible digital extension and abduction of the arm in an attempt to deliver the shoulders. The risk factors are: macrosomia, shoulder dystocia, instrumental delivery. Unilateral involvement is common. Two clinical types are met depending upon the nerve root involved. Rarely, both types are present together. Management: Early mobilization and referral to a specialist team if not improved by 1 month. ■ Duchenne-Erb's palsy: This is the most common type when the 5th and 6th and rarely the 7th cervical nerve roots are involved. The resulting paralysis causes the arm to lie on the side (adducted) with extension of the elbow, pronation of the forearm and flexion of the wrist (Waiter's tip). Winging of the scapula is common. Moro reflex is absent. There may be associated ipsilateral phrenic nerve (diaphragmatic) paralysis (C3, 4, 5). ■ Iaumpke's palsy: This type of palsy is due to the affection of the lower cords of the plexus involving 7th and 8th cervical or even the first thoracic nerve roots. There is paralysis of the muscles of the forearm. The arm is flexed at the elbow and the wrist is extended. The forearm is supinated and a claw­ like deformity of the hand is observed. When thefirst thoracic nerve is involved, there may be ipsilateral ptosis with small pupil due to sympathetic nerve involvement (Homer's syndrome). Treatment consists of immobilization and prevention of contractures. Physical therapy and passive movements are advocated. Full recovery takes weeks or even months. Severe injmy may produce permanent disability (Figs. 33.8A and B). Bony injmy should be excluded with radiography. Prognosis is usually good, if it is due to stretching. But if it is due to hemorrhage or avulsion, the deformity may be permanent. ■ Brachial plexus injury: The incidence is about 0.1-0.2% of shoulder dystocia, even in normal delivery, macrosomia, ., Figs. 33.SA and B: (A) Facial palsy; (Bl Erb's palsy. malpresentation and instrumental deliveries. The entire arm is flaccid. All reflexes are absent. ■ Phrenic nerve injury (C3, 4 or 5) causes paralysis of the ipsilateral diaphragm. This is due to excessive stretching of the neck at birth. Risk factors are: Breech or dficult forceps delivery. Infants present with respiratory distress, cyanosis and tachypnea. Diagnosis is made by USG showing paradoxical movement of the diaphragm. Treatment is supportive. Continuous Positive Airway Pressure (CPAP) or mechanical ventilation may be needed. Recovery is usually completed in 1-3 months of time. FRACTURES ♦ Skull bone-(p. 455) ♦ Spines-fracture of the odontoid process or fracture dislocation of the fifth-sixth cervical vertebrae may occur due to acute bending of the spine while delivering the aftercoming head or in shoulder dystocia. The result is instantaneous death of the baby due to compression on the medulla. ♦ Long bones-bones commonly involved in fractures are-the humerus, the clavicle and the femu,: These occur in breech delivery. Fractures are usually of greenstick type but may be complete. Rapid union occurs with callus formation. Deformity is a rarity even where the bone ends are not in good alignment. n·eatment: Fracture femur and humerus are treated by immobilization (splinting). X-ray studies are done. Closed reduction and casting are needed when bones are displaced. Limb motion is restricted. Healing with callus formation occurs over 2-4 weeks. Usually there is complete recovery. DISLOCATIONS: The common sites of dislocations of joints are shoulder, hip, jaw and fifth-sixth cervical vertebrae. Confirmation is done by radiology or ultrasonography and the help of an orthopedic surgeon should be sought. VISCERAL INJURIES: Liver, kidneys, adrenals or lungs are commonly injured mainly during breech delive,y. The most common result of the injury is intraperitoneal hemorrhage. Severe hemorrhage is fatal. In minor hemorrhage, the baby presents features of blood loss in addition to the disturbed function of the organ involved. Treatment is directed: (1) To correct hypovolemia, anemia and coagulation disorders; (2) Specific management-surgical or otherwise, to tackle the injured viscera. PERINATAL INFECTIONS Perinatal infection is still one of the leading causes of neonatal death. The neonates are more susceptible to infection as they are deficient in natural immunity and acquired immunity. Preterm infants are at high-risk for perinatal infections (Box 33.7). Neonates who survive from sepsis often suffer from severe neurological as well as severe parenchymal lung diseases. Early Onset Sepsis (EOS) occurs within first 3 days oflife. I MODE OF INFECTION ♦ Antenatal ♦ Intranatal ♦ Postnatal ANTENATAL: Transplacental: Maternal infection that can affect the fetus through transplacental route are predominantly Chapter 33: Diseases of the Fetus and the Newborn ID ♦ Rupture of membranes> 18 hours. ♦ Maternal intrapartum fever> 100.4°F. ♦ Low birth weight infant (<2,500 g). ♦ Early preterm infant (<34 weeks). ♦ Chorioamnionitis. + Male infants. ♦ Mother with Group B f3-hemolytic streptococcal (GBS) colonization. ♦ Repeated vaginal examination in labor. ♦ Invasive procedures of monitoring. the viruses. They are rubella, cytomegalovirus, herpes virus, HIV, chickenpox and hepatitis-B and C, COVID virus. Other infections are syphilis, toxoplasmosis and tuberculosis. Amnionitis: Amnionitis following premature rupture of the membranes can affect the baby following aspiration or ingestion of infected amniotic fluid. INTRANATAL ■ Aspiration of infected liquor or meconium following early rupture of the membranes or repeated internal examination. ■ While the fetus is passing through the infected birth passage-(a) eyes are infected-ophthalmia neonatorum, or (b) oral thrush with Candida albicans. ■ Improper asepsis while caring the umbilical cord. POSTNATAL: Nosocomial infections-(i) Transmission due to human contact-infected mother, relatives or staff of the nurse1y; (ii) Cross-infection from an infected baby in the nurse1y; (iii) Infection through feeding, bathing, clothing or airborne; and (iv) Infection in the environment of neonatal intensive care unit (NICU) or invasive monitoring. Clinical presentation of early-onset neonatal sepsis (EOS): It is abrupt and 90% infants become symptomatic by 24 hours of age. Tachypnea, grunting, lethargy, hypotension, cyanosis, jaundice, vomiting, diarrhea and RDS are the common symptoms. Other less common presentations are: DIC, meningitis and Persistent Pulmonary Hypertension of the Newborn (PPHN). Infections with A. baumannii can cause: septicemia, pneumonia, meningitis, UTI and soft tissue infection. Poor perfusion, irritability and DIC with petechiae can occur in more severe sepsis. There may be hypothermia (preterm), or hyperthermia (term) infants. Common pathogens are: Acenetobacter species, gram-negative: A. Baumannii (multidrug resistant). ESKAPE organisms are: Enterococcus faeciam, S. aureus, K. pneumoniae, A. baumannii, Pseudonona aeruginosa. These organism efficiently evade the effects of antibiotics. Others are: Group B Streptococcus (GBS), Staphylo­ coccus aureus, E. coli, Klebsiella, Haemophilus, Enterobacter, B. fragilis and Citrobacter, Pseudomonas, fungus ( Candida) and anaerobes. The infection is acquired during intrapartum period from the genital tract. The infant is colonized with pathogen in the perinatal period. The prima,y sites of colonization are: skin, nasophaiynx, orophaiynx, conjunctiva and the umbilical cord. DIAGNOSIS: Laboratory evaluation includes: Complete Blood Count (CBC), platelet count, blood and urine culture and acute phase reactants. An elevated WBC (>40,000) count with polymorphonuclear cells or a depressed total WBC ( <5,000) and absolute neutropenia ( <1,500) are commonly found. Coagulation profile (PT, PTT, INR), LP for CSF cell count, protein, glucose are to be done. C-Reactive Protein (CRP) remains elevated with inflammation and decline rapidly with resolution. Serial tests are needed. Imaging studies: Chest X-ray and renal ultrasound are needed depending upon the presentation. PREVENTION OF NEONATAL INFECTION: GBS prophylaxis can reduce EOS significantly. Empiric antibiotic therapy with broad coverage (P lactam and Aminoglycoside) are started. Emergence of Multidrug-Resistant (MDR) Organisms (MDROs) need therapy with Piperacillin­ Tazobactum and gentamicin. TREATMENT: Antibiotic therapy (Table 33.8)-Aceneto­ bacter sepsis is treated with carbapenem (imipenem or meropenem). Resistant cases are treated with polymyxin antibiotics. Other antibiotics are: Colistin, Tigecycline and Rifampicin. Broad spectra are given to cover the gram-positive and gram-negative organisms as well as the anaerobes. Immunotherapy with IV Immunoglobulin (IVIG), monoclonal antibodies, Granulocyte Colony Stimulating Factor (GM-CSF) are used as an adjuvant to the antibiotics. Till date the benefits are limited. SUPPORTIVE TREATMENT FOR SEPSIS: Mechanical venti-lation, surfactant therapy for pneumonia and RDS, pressor drugs for hypotension and anticonvulsants for seizures are to be maintained. Echocardiography may be helpful in selected cases ( cyanotic infant, pulmonary hypertension). COMMON SITES OF INFECTION n·ivial but may be serious: (i) Eyes-ophthalmia neonatorum; (ii) Skin; (iii) Umbilicus; (iv) Oral thrush. Severe systemic: (i) Respiratory tract; (ii) Septicemia; (iii) Meningitis; (iv) Intra-abdominal infection. OPHTHALMIA NEONATORUM (CONJUNCTIVITIS) Ophthalmia neonatorum is defined as inflammation of conjunctiva during first month of life. CAUSES: The common causative agents are: (i) Chlamydia trachomatis (oculogenitalis); (ii) Other bacterial causes: (a) Gonococcus (rare), Staphylococcus, Pseudomonas, (b) Chemical­ silver nitrate, (c) Viral-herpes simplex (type II). MODE OF INFECTION: Infection occurs mostly during delive1y by contaminated vaginal discharge. It is more likely in face or breech delive,y. During neonatal period, there may be direct contamination from other sites of infection or by chemical. Im Chapter 33: Diseases of the Fetus and the Newborn Table 33.8: Antibiotics used to treat neonatal sepsis. Drug Ampicillin Amikacin Gentamicin Cefotaxime Nature Bactericidal Bactericidal Bactericidal Bactericidal Bacterial coverage Both gram +ve and gram -ve Primarily gram -ve Primarily gram -ve Mainly gram -ve Daily dose Route 150 mg/kg/q 12 h IV/IM 15 mg/kg/q 24 h -do-3-4 mg/kg/q 24 h -do- 50 mg/kg/q 12 h -do- Side effects Diarrhea, skin rash, nausea, vomiting. Nephrotoxicity, ototoxicity. Ototoxicity, nephrotoxicity. Hypersensitivity, thrombophlebitis, diarrhea. Organism GBS Escherichia coli CONS Klebsiella, Serratia Cefuroxime Ceftriaxone Bactericidal Bactericidal Both gram +ve and gram -ve -do- 50 mg/kg/q 12 h -do- 50 mg/kg/q 12 h -do- Generally free from toxicity, hypersensitivity (rarely). Diarrhea, eosinophilia, skin rash, neutropenia. Enterobacter Listeria Meropenem Bactericidal A+vereoabnicd agnrdaman-aveerobic gram 20 mg/kg/q 12 h -do- tDhiarorrmhbeao,clyetuokpoepneina,iaa,naphylaxis. Enterobacter Piperacillin/ tazobactam Bactericidal Mainly gram +ve gram -ve 2 g + 250 mg (Tazo) q 12 IV hourly (see infusion guide) Allergic rash, anemia, candidiasis, fever, Pseudomonas diarrhea. Vaneomycin Bactericidal eMnotsetrogcraomcci+avneearonbdics 15 mg/kg/day IV or 12 Allergy hours Allergy, ototoxicity, nephrotoxicity, thrombophlebitis. MRSA (IM: Intramuscular; IV: Intravenous; q 12 h: every 12 hours; q 24th: every 24 hours; CONS: Coagulase Negative Staphylococci; MRSA: Methicillin-Resistant Staphylococcus aureus; ESBL: Extended-Spectrum j3 Lactamase) The clinical picture varies and the discharge may be watery, mucopurulent to frank purulent in one or both eyes. The eyelids may be sticky or markedly swollen. Cornea may be involved in severe cases. Prognosis is favorable to most cases. PREVENTION: Any suspicious vaginal discharge during the antenatal period should be treated and the most meticulous obstetric asepsis is maintained at birth. The newborn baby's closed lids should be thoroughly cleansed and dried. INVESTIGATIONS: The discharge is taken for-(a) Gram stain smear; (b) Culture and sensitivity; (c) Scraping material from lower conjunctiva for Giemsa staining and also culture in suspected chlamydial infection; and (d) Culture in special viral media for suspected herpes simplex infection. TREATMENT: Prophylaxis: Erythromycin or gentamicin ophthal­ mic drops, ointment is effective without any complication. (a) Gonococcal: Infant is isolated during the first 24 hours of treatment. Eyes are irrigated with sterile isotonic saline eve1y 1-2 hours until clear. In severe and culture positive cases, systemic ceftriaxone 25-50 mg/kg/IV/IM or cefotaxime 100 mg/ kg is given IM/IV. Single dose in infant without dissemination or for 7 days when there is dissemination, is usually given. (b) Chlamydia: Elythromycin suspension 40 mg/kg daily orally divided into 4 doses for 14 days is given to prevent systemic infection. Topical treatment alone is ineffective. (c) Herpes simplex: The infant is isolated. Systemic therapy with acyclovir 20 mg/kg eve1y 8 hours for 2 weeks is given IV. Topical use of 3% vidarabine or 0.1% iododeoxyuridine ointment 5 times a day for 10 days is used. Ophthalmologist should be consulted for any severe infection. I SKIN INFECTIONS Newborn's skin infections may manifest as skin rashes, pustulosis or cellulitis. The causative organisms are: Gram-positive, Gram­ negative and anaerobic organisms. Staphylococcus aureus is the predominant one. Common sites of infections are: face, axilla, groin, scalp and periumbilical area. Colonization of the newborn skin occurs during birth from vaginal flora as well as from the environment (nosocomial, cross-infection from the carriers). Localized infections are often due to traumatized skin. The common sites are: venipuncture or scalp electrode. PUSTULOSIS-is usually caused by S. aureus. Rarely, it may be epidemic, and results in septicemia or pyemia. Some skin lesions may be bullous or scalded. Treatment of S. aureus pustulosis depends on the severity of infections and condition of the infant. Mild infections may be treated with topical mupirocin and oral therapy with amoxycillin/ or cephalexin. More extensive lesions require therapy with nafcillin or oxacillin MRSA infection need to be treated by Vancomycin. v. Cellulitis-usually occurs at a traumatic skin site (see above). It is usually treated with local antibiotic ointment (bacitracin). In severe infections or in a premature infant, Complete Blood Count (CBC) and, blood culture are to be obtained. Systemic antibiotic (oxacillin or nafcillin and gentamicin) IV is given. Epidemic outbreaks due to nosocomial acquisition of S. aureus in newborn nurseries or NICU need intensive surveillance of the staff members and the newborns with culture. UMBILICAL SEPSIS (OMPHALITIS) It is not uncommon for mild umbilical sepsis to occur. The causative organisms include both gram-positive and gram­ negative organisms. The infection is manifested by serous or seropurulent umbilical discharge which may be offensive. The base of the cord stump looks moist and the periumbilical skin becomes red and swollen. There is delay in falling off of the cord. Systemic manifestations include pyrexia and features of toxemia or jaundice in severe infection. SPREAD OF INFECTION: (1) Periumbilical cellulitis with suppuration; (2) Thrombophlebitis of the umbilical vein with extension of the infection to the liver producing hepatitis or pyemic liver abscess; (3) Peritonitis; and (4) Necrotizing fasciitis. PREVENTION: Antiseptic and aseptic precaution should be taken right from the time of cutting the cord to the time of complete Chapter 33: Diseases of the Fetus and the Newborn ID epithelialization of the area after falling of the cord. The care of the umbilical cord as mentioned in Ch. 31 should be followed. CURATIVE: Treatment: Complete septic work up (CBC, blood and umbilical swab culture) is done. Antibiotic therapy with Nafcillin and Gentamicin or Oxacillin or Piperacillin/ Tazobactam may be used depending upon the severity of infection. The wound is dressed like any surgical wound with spirit and antiseptic powder. TETANUS NEONATORUM: It is rare nowadays. The infection is caused by the neurotoxin of Clostridium tetani and the portal of entty is through the umbilical cord. The features are evident within 5-15 days after birth. The striking features are: Inability to suck associated with marked trismus followed by rigidity of the body with opisthotonus, pyrexia and convulsions. Prevention includes immunization of the mother during pregnancy with tetanus toxoid. Babies born in safe conditions without previous immunization of the mother, should be given 1,500 IU of antitetanus serum intramuscularly soon after birth. Curative treatment includes: (l) The baby should be isolated in the infectious disease hospital; (2) Tetanus immune globulin (human) 500 IU is given intramuscularly; (3) Antibiotics, particularly Penicillin G should be given (100,000 units/kg/day divided every 4-6 hours for 7-10 days); (4) Sedation and muscle relaxants to be given; (5) Endotracheal intubation and mechanical ventilation may be needed; (6) Nutrition is to be maintained by intragastric feeding. (7) MG to be given ifTIG is not available. The infant after recovety should be given standard tetanus immunization. Prognosis: Mortality is up to 60-80%. I NECROTIZING ENTEROCOLITIS NEC is an acute ischemic and inflammatory injury of the distal small and often proximal large intestine. Surgical pathology revealed segmental coagulative necrosis of mucosa, intramural gas (pneumatosis) and sloughing of mucosa. Incidence: An estimated 0.3 per 1000 live births. Risk factors: (a) Premature infants; (b) Perinatal asphyxia; (c) Hypotension; (d) Polycythemia; (e) Umbilical cord catheter­ related thromboembolism; (f) Septicemia due to E.coli, Klebsiella, Pseudomonas; (g) Exchange transfusion; and (h) Congenital heart disease; (i) Bacterial dysbiosis. Pathophysiology: There is ischemic and/ or toxic damage to the mucous membrane of the gut commonly in the ileocecal region. It is associated with bacterial proliferation and gas formation. There is excessive and inappropriate intestinal inflammatory response. Inflammatory mediators (platelet activating factors, endotoxins, TNF, inflammatory mediators, interleukins) are present. Gradually, there is ischemic necrosis of the muscular wall of the gut, gangrene ultimately leads to perforation and peritonitis. Diagnosis: Systemic signs: Respiratory distress, bradycardia, hypotension, acidosis, oliguria are present. Abdominal signs: dystonia, vomiting, hematochezia or ascites, feeding intolerance, acidosis, oliguria, bleeding diathesis, abdominal distension and tenderness. Laboratory findings are of less value, Imaging studies: X -ray abdomen reveals abdominal gas pattern with dilated loops. Pneumatosis intestinalis is the hallmark of diagnosis. Ultrasonography, including Doppler, can detect gas bubbles in liver parenchyma, portal venous system, bowel necrosis and perforation. Grossly bloody stool is common in NEC. Thrombocytopenia, metabolic acidosis and hyponatremia are the triad of signs to confirm the diagnosis. Prevention: Human (mother's) milk can prevent NEC. Probiotics and nutrients enhance the growth of beneficial microbes. Prolonged use of antibiotics should be avoided. TREATMENT: (i) Respiratory system: Supplemental 02 and mechanical ventilation may be needed; (ii) Support to the cardiovascular system: Circulatory volume, blood pressure, arterial blood gas, tissue perfusion. Nutrition-(i) Discontinuation of oral feeding and to start nasogastric suction; (ii) Total parenteral nutrition; (iii) Laboratory monitoring for arterial blood gas, serum electrolytes, blood glucose,. platelet count, acid-base balance and septic work up are done; (iv) Antibiotics-Vancomycin, Piperacillin/ Tazobactam, Gentamycin and Metronidazole; (v) Bowel resection in the case of perforation. Prognosis: Mortality is up to 40% when associated with pe1foration. Overall mortality is about 10-12%. Prevention of NEC: Prevention of preterm birth is the key factor. Others are: (i) Antenatal Corticosteroid for GI maturation (ii) Exclusive feeding with human milk. (iii) Enterally fed probiotics to normalize intestinal microflora colonization (Lactobacillus GG) and (iv) Nutritional supplements: (a) Poly unsaturated fatty acids (PUPA), (b) growth factors: Transforming Growth Factor Beta (TGFB). I MUCOCUTANEOUS CANDIDIASIS ORAL THRUSH: Infection of the buccal mucous membranes and the tongue by the fungus Candida albicans is not uncommon, especially in bottle-fed babies. Contamination by the organisms occurs from the feeding bottle, pacifiers, nurse's hand, mother's nipple and infected vagina. The fungus grows on the mucous membrane and produces milky white elevated patches resembling milk curd, which cannot be easily wiped off. Rarely, the fungal infection may spread down to involve the gastrointestinal or respiratoty tract. It usually appears in the late first week or during the 2nd week. The infant refuses to take feeds. Constitutional upset is unusual but becomes evident in extraoral spread to the respiratory tract. The typical patches are visible on the mouth and an attempt to remove the patch leaves behind a raw oozing surface. Spots on the edges of the tongue are diagnostic, as suckling would remove the milk curd from that region. PROGNOSIS: If effectively treated, cure is vety prompt; but, in neglected cases, especially with alimentaty or respiratoty tract involvement, rapid deterioration occurs. PREVENTION: Maternal fungal infection in the vagina is to be adequately treated before delivety. Utensils, including feeding bottles and teats, are to be properly cleansed before and after each feed. TREATMENT: Nystatin oral suspension (100,000 U/mL), 1 mL is applied to each side of the mouth 4 times a day for about 2-3 weeks. Fluconazole 6 mg/kg IV or orally once followed by 3 mg/kg IV/PO each day can be used for severe oral candidiasis. Systemic fluconazole is highly effective in treating chronic candidiasis in the immune compromised host. Infants with chronic, severe thus should be evaluated for immune deficiency. ID Chapter 33: Diseases of the Fetus and the Newborn Mother with superficial or ductal candidiasis in the breast, should be treated concurrently. Term infant can continue breast feeding during treatment. Infants with chronic thrush refractory to usual treatment should be investigated for immunodeficiency. Diaper candidal dermatitis is treated with topical 2% nystatin ointment, 2% miconazole ointment or I% clotrimazole cream. Intestinal colonization should be treated with oral nystatin at the same time. TERATOLOGY AND MAJOR MALFORMATIONS The incidence of major congenital malformations is about 2-5% at birth, a lower incidence of 1 in 500, is however, reported from the hospital statistics of India. Developmental defects are mainly from the genetic (25-30%), environmental or unknown causes (65%). Drug exposure accounts for only 2-5% of birth defects. In general population the incidence of major malformations is about 2-5%. Defects in the central nervous system account for about 50% of malformations. ETIOLOGY: The causes are not fully understood and are grouped as follows (Flowchart 33.3). When a fetus is exposed to a teratogenic agent, the resultant effect will depend on the duration of gestation and the genetic susceptibility of the fetus. Calculating from the first day of LMP (D 31 to D 71 is the critical period of organ development). GENETICS: The defect is inherited through the genes in the ovum or sperm. Single gene disorders either Autosomal or X-linked, which may be Dominant or Recessive. ENVIRONMENTAL: The fetal affection due to a given teratogen will depend on the dose administered, the gestational age at exposure and the maternal and fetal immune response to the agent. The fetus is, infact, potentially susceptible to some teratogenic effecteven after the completion of morphogenesis. The net effect may be death, malformation, growth retardation or functional disorder. ■ Advancing maternal age increases the incidence of Down's syndrome to the extent of 1 in 100 births at the age of 40 years. Increasing parity is associated with high incidence of malformations. ■ The adverse effects of drugs (Fig. 33.3) on the preimplantation and postimplantation phase remain unpredictable. However, wa,Jarin, lithium, dilantin, antifolic acid group of drugs have got established risks on the growing conceptus. The malformation effects of the various drugs are mentioned in Ch. 34 (p. 478). ■ Infections-maternal Rubella, Cytomegalovirus, Toxoplasma either latent or overt in the first trimester, produces congeni­ tal malformation of the fetus. The correlation with other maternal infections are described in Ch. 20. ■ Irradiation is a potential danger to the fetus, especially in early emb1yonic phase. Irradiation of gonads of either parent may result in mutation of genes. Maximal ionizing radiation currently thought to be safe for the human emb1yo and fetus at any stage of gestation (as stated by the National Committee on Radiation Protection) is 5 rads. It is safer to limit its use, especially during first trimester. Radiation can cause fetal morbidity (FGR, genetic muta­ tions, neurologic abnormalities, mental retardation, childhood leukemia) and mortality. Radiation risks are high with radiation after the first 2 weeks postconception and within the first trimester (period of organogenesis). Exposure >15 rad during second and third trimester or >5 rad in the first trimester needs patient counseling. ■ Terntogenicity: Diagnostic range of radiation exposure (less than 5 rad) is not associated with any significant congenital malformation either in human or in animal. II Oncogenicity: Dividing cells, particularly in the first trimester are more sensitive to injury from radiation. Diagnostic radiation with fetal exposure is associated with an increased risk of malignancy. ■ Genetic damage: No radiation-induced transmissible gene mutations have been seen in humans. II Intrauterine death: Low-dose radiation (1-5 rad) is not associated with any fetal death. Flowchart 33.3: Causes of congenital abnormalities. CAUSES Chromosomal (6%) Single gene Infections (2%) Maternal Drugs and • Trisomy-21 disorder •Rubella illness (5%) Environmental (Down's (5%) •Cytomegalo- • Diabetes (2-3%) syndrome) virus • Epilepsy ■Warfarin • Trisomy-18 •Varicella ■ Lithium (Edward's • Parvovirus ■ Dilantin syndrome) •Trisomy-13 • Toxoplasma ■ACE inhibitors ■Radiation (Palau's ■Alcohol syndrome) ■Hypoxia Autosomal X-linked disorders ■ Recessive-5% ■ Dominant-rare Dominant (70%) Recessive (20%) •Hemophilia • Achondroplasia • Cystic fibrosis • Duchenne muscular dystrophy • Marfan's syndrome • Galactosemia •Color blindness • Neurofibromatosis • Sickle cell anemia • Fragile X syndrome Multifactorial (20%) ■ Neural lube defects ■Congenital heart defects ■ Cleft palate and cleft lip ■ Teratogenicity ■ Oncogenicity ■ Genetic damage ■ Intrauterine death Idiopathic (60%) To Defer Conception with the following drugs: 1. Deferasirox or Deferiprone: to stop before 3 months. Desferrioxamine may be started after 20 weeks of pregnancy. 2. Methotrexate, Mycophenolate: to stop before 3 months. 3. Rituximab: to stop before 6 months. 4. ACE inhibitors, Angiotensin receptor antagonists and Warfarin: to be changed during pregnancy. Chapter 33: Diseases of the Fetus and the Newborn ml ■ Maternal malnutrition, metabolic and endocrinal disorders like uncontrolled diabetes, and epilepsy are related with increased incidence of fetal malformations. MULTI FACTORIAL: Most of the malformations probably result from delicate and complex interactions between genetic, infections and altered environmental factors, the nature of which remains obscure. The malformation may affect a single organ and a particular sex. I DOWN'S SYNDROME (TRISOMY 21) Trisomy 21 is the most frequent Autosomal (chromosomal) syndrome. The defect is due to: (1) Inclusion of an additional chromosome, trisomy 21 (95%)-47 instead of 46 chromosomes. Triplication may be caused either by the presence of an entire additional chromosome 21 or the addition of only band q 22. (2) Chromosomal translocation defect (14 : 21) (rare)­ especially occurring in young mothers. There is transfer of a segment of one chromosome to a different site of the same chromosome or to a different chromosome. There is 30% chance of recurrence in translocation defect. Incidence: The overall incidence is 1 in 600. The incidence rises with advancing age of the mother, reaching a peak of about 1 in 25 by the age of 45 years. Diagnosis of the affected baby: ■ Exracardiac: Craniofacial abnormalities include small ears (100%), brachycephaly, upwards and outwards slanting of the eyes with epicanthic folds; short upper lip with small mouth and macroglossia (Fig. 33.9). The hands are short and broad with a single palmar crease (30%). There is increased association of omphalocele, cataracts and esophageal atresia, duodenal atresia and imperforate anus. The affected baby is mentally retarded. Cardiac features (40-50% ): Complete Atrioventricular Canal (CAVC), VSD most common, others are: TOF, ASD, PDA. Hypotonia may cause breathing difficulties, poor swallowing and aspiration. Joint hyperextensibility is observed. Expectation of life is reduced. In adult age they often develop leukemia. Male infertility is the rule. In female, puberty may be delayed and may be fertile. ■ Confirmation is established by chromosomal analysis (ka1yo­ type) using bone marrow aspiration or leukocyte culture. Genetic counseling in subsequent pregnancy. The risk of rec-urrence due to trisomy 21 is 1 %. That of translocation is higher. Prenatal diagnosis is possible. CONGENITAL MALFORMATIONS IN NEWBORN AND THE SURGICAL EMERGENCIES ♦ Imperforate anus ♦ Esophageal atresia ♦ Meconium ileus ♦ Exomphalos ♦ Diaphragmatic hernia ♦ Duodenal atresia IMPERFORATE ANUS: It is more prevalent in males than females. Two types are met with: A. High imperforate anus; where rectum ends above the pubo­ rectalis sling (80-90%). There may be associated rectourinary fistula in males or rectovaginal fistula in females (95%). B. Low imperforate anus where rectum has traversed the puborectalis sling. This variant may be associated with or without perinea! fistula. Diagnosis is made by: (1) Absence of meconium passage; (2) Absence of anal opening; (3) Failure to pass a rectal thermometer rubber catheter or lubricated little finger; (4) A cystogram may show a fistula and document the level of distal rectum. This is also defined by ultrasonography. (5) Imaging study (X-ray, USG) of the lumbosacral spine and urinary tract should be done to exclude any other abnormality in this area. Management 1. Cruciate incision (perinea! anoplasty) is made on the membrane in case of the simple membranous obstruction which is evidenced by marked bulging over the anal pit when the baby cries; 2. In high imperforate anus, colostomy is done and pull through operation is done at a later date (Table 33.9). A temporary colostomy may be necessary in neonates without a perinea! fistula. Primary repair without a colostomy is now being performed at many centers. ESOPHAGEAL ATRESIA: The esophagus ends blindly about 12 cm from the nares. Babies born to mothers having hydramnios should be checked carefully at birth to exclude this abnormality. Simultaneous distal Tracheoesophageal Fistula (TEF) too often (85%) coexists. Excessive salivation, increasing respiratmy distress and even a small amount of fluid by mouth causing Table 33.9: Age for elective surgical procedures. tf Fig. 33.9: Baby with Down's syndrome. Malformation Cleft lip Cleft palate Umbilical hernia Inguinal hernia Hydrocele Undescended testicle Patent ductus arteriosus Coarctation of aorta Hypospadias (other than glandular) Optima/age 6 weeks to 6 months. 9-12 months. After 1 year, if required. As early the infant's general condition permits. After 1 year. Between 1 and 2 years of age. At birth. 3-4 years or soon after the infant has been medically stabilized. 6-18 months. r. Chapter 33: Diseases of the Fetus and the Newborn cough and cyanosis point strongly towards the entity. Distal TEF causes reflux of gastric contents into the tracheobronchial tree causing chemical pneumonitis and pneumonia. Diagnosis is made by failure to pass a nasogastric tube down through the esophagus. Confirmation is done by radiography with prior insertion of a radiopaque catheter into the esophagus. Management: (1) Withhold fluids by mouth; (2) Frequent suctioning to prevent aspiration; (3) Place the baby in relatively upright position (45°) to prevent reflux; ( 4) Broad spectrum antibiotic should be administered; (5) Placement of a gastrostomy tube; (6) Ligation of tracheoesophageal fistula and esophageal anastomosis by thoracotomy or thoracoscopy are the principal steps of the operation. MECONIUM ILEUS: It is a manifestation of fibrocystic disease of the pancreas(90%). Deficiency of the pancreatic enzyme makes the meconium in the intestine inspissated which, in turn, obstructs the lumen of the lower ileum. Diagnosis is based on clinical manifestations of small gut obstruction. Sweat test: A patient with cystic fibrosis is found to lose large quantities of sodium in the sweat. Blood sample for DNA analysis to screen for cystic fibrosis is done. Straight radiographic pictures of the abdomen reveal the solid nature of the meconium with a granular appearance. Rectal mucosa! biopsy may have to be done to demonstrate the absence of ganglion cells in Hirschsprung disease. Contrast enema (meglumine diatrizoate) can be both diagnostic and therapeutic. Surgery includes resection and anastomosis of the gut containing the inspissated meconium followed by treatment with pancreatic enzymes and vitamins. Surgical therapy: Surge1y may be done open, laparoscopic and transanal. Different methods are: Staged repair with colostomy, one stage pull through or delayed I-stage repair when the infant has gained (double) weight. Prenatal diagnosis with DNA probes is possible from chorionic villus sampling. EXOMPHALOS (OMPHALOCELE): It is a congenital herniation of the abdominal contents (usually small gut) through the defect in the abdominal wall at the base of the umbilical cord. The anterior abdominal wall is defective in its entire thickness. Associated congenital anomalies occur in about Fig. 33.10: USG: Stomach, liver and small intestine are in the left side of the thoracic cavity, fetal heart is pushed to the right. Mediastinal shift is present. 30-40% of infants (chromosomal abnormalities, CDH, cardiac defects). Omphalocele differs from that of gastroschisis by the following anatomic features: (a) A protective membrane encloses the abdominal contents, {b) Contents of umbilical cord course individually over the sac and come out at the apex. Every effort should be made to protect the membranes from rupture. Cesarean delive1y may prevent rupture of this sac. A moist sterile saline dressing should be applied and arrangement is made for immediate surgical closure, if possible, in one stage ( <5 cm opening) or in two stages. Prenatal diagnosis with ultrasound is possible. CONGENITAL DIAPHRAGMATIC HERNIA (CDH): Incidence is about 1 in 4,000 live births. Congenital diaphragmatic hernia occurs where the abdominal contents herniate through a defect in the diaphragm (patent pleuroperitoneal canal) into the thorax. It usually occurs on the left side through foramen of Bochdalek {95%). CDH following delive1y: infants may develop (A) Pulmonary parenchymal insufficiency due to hypoplastic lungs, and {B) Pulmonaiy hypertension of the newborn. Symptoms include: acute respirato1y distress with marked cyanosis which may be relieved by holding the baby in an upright position. Signs include: unequal movements of the thorax, absent breath sounds on the affected side with scaphoid abdomen. In left-sided CDH, apical impulse is shifted to the right and heart sounds are better heard over the right side of chest. USG chest reveals gas shadow of small bowel in the thorax and mediastinal shift away from the affected side (Figs. 33.10 to 33.12). It may be associated with trisomies (13, 18) and 45XO. Prenatal diagnosis with ultrasound is possible around 16 to 18 weeks. Management-supportive care: Intubation and PPV is to be initiated immediately. Replacement of surfactant is helpful. 1. Cases diagnosed antenatally may be managed with delive1y by EXIT procedure. Multidisciplinary team (obstetricians, anesthesiologist, surgeon, neonatologists) management is started since delivery with intubation and ventilation. 2. Correction of acidosis; blood gas levels should be monitored. 3. Extracorporeal membrane oxygenation is used for neonates with respiratory failure due to pulmonary hypoplasia; Fig. 33.11: USG with Doppler study: Stomach, liver in the left side of the thoracic cavity, fetal heart is pushed to the right. Courtesy: Professor K Ghosh of IOFM. Chapter 33: Diseases of the Fetus and the Newborn - Fig. 33.12: Large left-sided pleural effusion (arrow) in a fetus with extrapulmonary sequestration (nonimmune hydrops). 4. Surgical repair is done either through the abdomen or the chest, with reduction of intestines into the abdominal cavity. Open surgical procedures have better outcomes. ♦ Other congenital abnormalities (5%): Diaphragmatic hernia, renal abnormality, cystic hygroma. ♦ Hematological (10%): Beta-thalassemia, Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, leukemia. ♦ Infections (6-7%}: Parvovirus, rubella, toxoplasma, syphilis, cytomegalovirus, hepatitis. ♦ Placenta and umbilical cord pathology (5%): Twin-to-twin transfusion, chorioangioma, umbilical vein thrombosis, TRAP. ♦ Maternal diseases (5%): Uncontrolled diabetes, severe anemia, thyrotoxicosis. ♦ Urinal tract malformations (2%): Urethral obstruction. Prune belly syndrome. ♦ Lymphatic dysplasia (7%): Lymphatic dysplasia ♦ Miscellaneous (4%): CNS malformations, skeletal abnormali­ ties, lysosomal disorders. ♦ Idiopathic (18%) 5. Intrauterine fetal surgery has been done in few cases to Pathology: Pathology depends on the etiological factor. prevent pulmonary hypoplasia. However, ultimate pathology is development of severe Prognosis is largely related to severity of pulmonary anemia, hypoproteinemia ( decreased colloid osmotic hypoplasia and associated structural malformations ( congenital pressure), asphyxia, increased capilla1y permeability and heart disease). heart failure. DUODENAL ATRESIA: In atresia, the lumen is completely Prenatal diagnosis is made with high Investigations: obstructed s whereas in stenosis, it is narrowed. Duodenal resolution ultrasound scan, Doppler flow study, echocar­ atresia: It i often associated (70%) with other malformations, diography and cordocentesis. Down syndrome (33%), CV and GI anomalies. Prenatally it is diagnosed by ultrasonography. Vomiting is a prominent 1. Maternal blood for complete blood count, ABO feature, the vomitus being copious and bile stained (atresia is and Rh group, red cell antibody titers, hemoglobin usually below the Ampulla of Vater). The upper abdomen may electrophoresis, VDRL, Kleihauer test, glucose be distended and following the passage of meconium ( usually tolerance test, G6PD deficiency and serological tests for white), no further stools are passed. infections. Doppler study for fetal anemia measuring Plain X-ray of the abdomen or USG in upright position MCA peak velocity. shows the typical 'double-bubble appearance' -gas in fundus of stomach and in the vault of the proximal half of duodenum with 2. Ultrasound-detailed scan of the fetus for echocardiog­ raphy, structural lesions (Fig. 33.12), and Doppler flow no air in the small or large bowel. Prenatal diagnosis is made with studies (MCA) is most important for diagnosis and fol­ Management: (1) Withhold fluids by mouth; (2) Parenteral low up. ultrasound. for chromosomal, biochemical and 3. Amniocentesi·s replacement of fluids and electrolytes; (3) Prompt corrective surgery of duodenojejunostomy by open or MIS techniques. enzyme studies. 4. Cordocentesis for study of chromosomal and single NONIMMUNE FETAL HYDROPS gene disorders, enzymes, plasma proteins, blood gases Nonimmune Fetal Hydrops (NIFH) is defined !] !] and antibodies, hemoglobin electrophoresis, PCR, DNA studies. as the accumulation of extracellular fluid :- · =- · n · !l ■ .. 5. Neonatal: Chromosomal study, placental examination, autopsy study if there is stillborn. in tissues and serous cavities in conditions ,.,T:• • other than Rh incompatibility. It is usually 1,ia associated with increased skin thickness (>5 mm), Management: It is directed according to the cause due to generalized subcutaneous edema in the fetus, and severity of the pathology. Termination of pregnancy placental enlargement, pericardial effusion, pleural may be an option when the parents desire, especially in effusion and/or ascites in at least two fetal body presence of chromosomal or structural abnormality. compartments. With complete prevention of Rh problem, Transplacental therapy for fetal dysrhythmias could be more than 75% of the fetal hydrops are related to NIFH. made by administering digoxin orally to the mother. Causes: ♦ Chromosomal abnormality (12%): Trisomies (13, 18, 21), Turner syndrome, triploidy, aneuploidy. ♦ Cardiovascular (20%): Congenital heart block, supraven­ tricular tachycardia, structural major cardiac abnormality (hypoplastic left heart). Direct fetal therapy may be done by intraperitoneal, intramuscular or intravascular ( umbilical vein) routes. Fetal transfusion may be given through umbilical vein or peritoneal cavity to improve anemia. Drainage of pleural fluid, pericardia! fluid or ascitic fluid under ultrasound guidance may be needed. ID Chapter 33: Diseases of the Fetus and the Newborn Obstetric management: 1. Laser photocoagulation for twin-twin transfusion. 2. Intrauterine paracentesis or thoracocentesis prior to delivery is helpful for easy delivery and for neonatal resuscitation. 3. Place of cesarean section depends on obstetric reasons. 4. Antenatal corticosteroid therapy is to be given when delivery is planned preterm. 5. Intensive neonatal care including ventilator support is needed. Prognosis: Perinatal mortality is high (50-100%), especially in presence of a structural and/ or chromo­ somal abnormality. ► Perinatal asphyxia is a significant cause of perinatal death (50%). ► The essential requirements for extrauterine independent survival are the formation of thin air blood barrier and the production of surfactant by the type two alveolar cells. ► Surfactant reduces surface tension and prevents alveolar collapse. ► Several hormones (glucocorticoids, thyroid hormones, TRH) and growth factors are needed for lung maturation and pulmonary phospholipid development. Glucocorticoids are the most essential hormone. ► Resuscitation of the newborn in the delivery room are done following the protocol of AAP and NNF, India. ► Important causes of respiratory distress in the newborn are many. RDS is mainly due to deficient pulmonary surfactant. Antenatal betamethasone accelerates pulmonary surfactant synthesis. ► Antenatal corticosteroid therapy has the following benefits: (a) Acceleration fetal lung maturation, (b) Reduction of RDS in preterm infants, (c) Reduction of ICH and NEC, and (d) Decrease in neonatal mortality. ► Common causes of neonatal hypoglycemia are: preterm and IUGR infants, perinatal hypoxia, RDS, and neonatal hyperinsulinism (infant of a diabetic mother). ► The neonatal hyperbilirubinemia is principally due to: (a) Increased red cell mass with decreased red cell survival, and (2) decreased hepatic intake and conjugation of bilirubin, (3) decreased excretion of bilirubin. ► The major concern with neonatal hyperbilirubinemia is the development of kernicterus. The critical level of bilirubin to cause kernicterus in a term infant is >20 mg/dl (340 tmol/L). ► Causes of seizures in newborn may be traumatic, metabolic, infective, iatrogenic and others. ► Birth injuries of the newborn may involve the soft tissues (skin, nerves) and/or the bones (clavicle). ► Risk factors for neonatal infections are: Rupture of membranes> 18 hours, maternal fever, prematurity, repeated vaginal examinations in labor. ► Mode of infection may be antenatal, intranatal or postnatal. Common pathogens are Group B Streptococcus (GBS), Staphylococcus aureus, E.coli, Klebsiel/a also anaerobes. ► Causes of Nonimmune Fetal Hydrops (NIFH) are many. ► Ultimate pathology of NIFH is development of severe anemia, hypoproteinemia, asphyxia and heart failure. Pharmacotherapeutics in Obstetrics CHAPTER CHAPTER OUTLINE ❖ Oxytocics in Obstetrics ► Oxytocin ► Methods of Administration ► Ergot Derivatives ► Prostaglandins (PGs) ❖ Antihypertensive Therapy ❖ Diuretics ❖ Tocolytic Agents ❖ Anticonvulsants ❖ Anticoagulants ❖ Maternal Drug Intake and Breastfeeding ❖ Fetal Hazards of Maternal Medication during Pregnancy ► Teratology and Prescribing in Pregnancy ❖ Analgesia and Anesthesia in Obstetrics ► Anatomical and Physiological Considerations ► Analgesia during Labor and Delivery ► Inhalation Methods ► Regional (Neuraxial) Anesthesia ► Infiltration Analgesia ► General Anesthesia for Cesarean Section OXYTOCICS IN OBSTETRICS DEFINITION: Oxytocics (ecbolics) are the drugs of varying chemical nature that have the power to excite contractions of the uterine muscles. Amongst the large number of drugs belonging to this group, the following are the important ones and are extensively used in clinical practice. ♦ Oytocin ♦ Ergot derivatives ♦ Prostaglandins I OXYTOCIN PHARMACOLOGY: Oxytocin is a nonapeptide. In 1950, de Vigneaud and coworkers were awarded Nobel Prize for their work on structure of oxytocin. It is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. By nerve axons, it is transported from the hypothalamus to the posterior pituitary where it is stored and eventually released. Oxytocin has a half-life of 3-4 minutes and a duration of action is approximately 20 minutes. It is rapidly metabolized and degraded by oxytocinase. MODE OF ACTION: Myometrial oxytocin receptor concentration increases maximum (100-200 fold) during labor. Oxytocin acts through G-protein coupled receptor and voltage-mediated calcium channels to initiate myometrial contractions. It stimu­ lates amniotic and decidual prostaglandin production. Bound intracellular calcium is eventually mobilized from the sarcoplasmic reticulum to activate the contractile protein. The uterine contractions are physiological, i.e., causing fundal contraction with relaxation of the cervix. Oxytocin and vasopressin have a similar structure, and the oxytocin receptor has equal affinity for oxytocin and ADH. V1 receptors have a higher affinity for ADH but high doses of oxytocin induce similar action. PREPARATIONS USED: (i) Synthetic oxytocin (Syntocinon­ Sandoz or Pitocin-Parke-Davis) is widely used. It has only got oxytocic effect without any vasopressor action. The syntocinon is available in ampoules containing 5 IU/mL: Pitocin 5 IU/mL. (ii) Syntometrine (Sandoz)-a combination of syntocinon 5 units and ergometrine 0.5 mg. (iii) Desamino-oxytocin-it is not inactivated by oxytocinase and is 50-100 times more effective than oxytocin. It is used as buccal tablets containing 50 IU. (iv) Oxytocin nasal solution contains 40 units/mL. EFFECTIVENESS: In the first trimester, the uterus is almost refractory to oxytocin. In the second trimester, relative refractoriness persists, and, as such, oxytocin can only supplement other abortifacient agents in induction of abortion. In later months of pregnancy and during labor in particular, it is highly sensitive to oxytocin even in small doses. Oxytocin loses its effectiveness unless preserved at the correct temperature (between 15°C and 30°C). INDICATIONS: Oxytocin may be conveniently used in preg­ nancy, labor or puerperium. The indications are grouped as follows: ♦ Therapeutic ♦ Diagnostic THERAPEUTIC ■ Pregnancy ■ Labor ■ Puerperium Pregnancy ■ Early: • To accelerate abortion-inevitable or missed. • To expedite expulsion of hydatidiform mole. • To stop bleeding following evacuation of the uterus. • Used as an adjunct to induction of abortion along with other abortifacient agents (PGE1 or PGEz). &J Chapter 34: Pharmacotherapeutics in Obstetrics ■ Late: • To induce labor. • To ripen the cervix before induction. • Augmentation of labor. • Uterine inertia. Labor: ■ Active management of third stage of labor. ■ Following expulsion of placenta as an alternative to ergometrine. Puerperium: To minimize blood loss and to control postpartum hemorrhage. DIAGNOSTIC ■ Contraction Stress Test (CST)-p. 469 ■ Oxytocin Sensitivity Test ( OST)-p. 469 I SIDE EFFECTS AND DANGERS OF OXYTOCIN The dangers are particularly noticed when the drug is administered late in pregnancy or during labor (Table 34.1). ♦ Maternal ♦ Fetal MATERNAL ■ Nausea, vomiting, arrhythmias ■ Uterine hyperstimulation (overactivity)-is a frequently observed side effect. There may be excessive duration of uterine contraction (hypertonia) or increased frequency (>6 in 10 min time) of contractions (tachysystole). It is often associated with abnormal FHRpattern (p. 342, Fig. 25.2). ■ Uterine rupture-may be seen with violent uterine contractions. High-risk cases are: Grand multipara, malpresentation, contracted pelvis, prior uterine scar (cesarean) and excessive oxytocin use. ■ Water intoxication is due to its antidiuretic function when used in high dose (30-40 mIU/min). Water intoxication is manifested by hyponatremia, confusion, coma, convulsions and congestive cardiac failure. It is prevented by strict fluid intake and output record, use of crystalloid solution and by avoiding high-dose oxytocin for a long time. ■ Hypotension: Bolus IV injections of oxytocin cause hypotension, especially when patient is hypovolemic or with a heart disease. Occasionally, it may produce angina! pain. Table 34.1: Contraindications of Oxytocin. Pregnancy Labor Anytime Grand multipara All the contraindi- Hypovolemic cations in pregnancy. state. Contracted pelvis Obstructed labor. Cardiac disease History of cesarean lncoordinate uterine section or hysterotomy contraction. Malpresentation Fetal distress. ■ Antidiuresis: Antidiuretic effect is observed when oxytocin infusion rate is high ( 40-50 mIU/min) and continued for a long time. (Rare: Anaphylactoid reactions, amniotic fluid embo­ lism). FETAL: Fetal distress, fetal hypoxia or even fetal death may occur due to uterine hyperstimulation. Uterine hypertonia or tachysystole causes reduced placental blood flow. ROUTES OF ADMINISTRATION ■ Controlled intravenous infusion is the widely used method. ■ 5-10 units IV or IM after the birth of the baby as an alternative to ergometrine. ■ Intramuscular-the preparation used is syntometrine. ■ Buccal tablets or nasal spray-limited use on trial basis. I METHODS OF ADMINISTRATION OF OXYTOCIN ♦ Controlled intravenous infusion ♦ Intramuscular CONTROLLED INTRAVENOUS INFUSION: Oxytocin infu­ sion should be ideally by infusion pump. Fluid load should be minimum. It is started at low dose rates (1-2 mIU/min) and increased gradually. ♦ For induction of labor ♦ For augmentation of labor For induction of labor Principles: (1) Because of safety, the oxytocin should be started with a low dose and is escalated at an interval of 20-30 minutes where there is no response. When the optimal response is achieved (uterine contraction sustained for about 45 seconds and numbering 3 contractions in 10 minutes), the administration of the particular concentration in mIU/minute is to be continued. This is called oxytocin titration technique; (2) The objective of oxytocin administration is not only to initiate effective uterine contractions but also to maintain the normal pattern of uterine activity till delive1y and at least 30-60 minutes beyond that. Calculation of the infused dose: Nowadays the infusion is expressed in terms of milliunits per minute. This can give an accurate idea about the exact amount administered per minute irrespective of the concentration of the solution. Regulation of the drip: The drip is regulated by­ (1) Manually, counting the drops per minute commonly practiced; (2) Oxytocin infusion pump which automati­ cally controls the amount offluid to be infused. Convenient regime: Because of wide variation in response, it is a sound practice to start with a low dose (1-2 mIU/min) and to escalate by 1-2 mIU/min at every 20 min intervals up to 8 mIU/min. The patient should preferably lie on one side or in semi-Fowler's position to minimize vena caval compression. ' - • , M Table 34.2: Calculation of the dose delivered in milliunits (mlU) and its correlation with drop rate per minute. Units ofoxytocin mixed in Drops per minute 500 ml Ringer solution (15 drops= 1 ml) 15 30 60 (1 unit= 1000 milliunits) (m/UJ In terms of mlU/minute Chapter 34: Pharmacotherapeutics in Obstetrics -