Membership of the Royal College of Paediatrics and Child Health (MRCPCH) Neonatology and Perinatal Medicine Syllabus

What is the pathophysiology of kernicterus and which bilirubin fraction is responsible?

Unconjugated (lipid-soluble, fat-soluble) bilirubin crosses the blood-brain barrier and deposits in the basal ganglia and brainstem nuclei, causing bilirubin encephalopathy. It presents with lethargy, hypertonia, opisthotonus, and a high-pitched cry; survivors develop choreoathetoid cerebral palsy, sensorineural deafness and upward gaze palsy.

Compare the causes of unconjugated versus conjugated neonatal hyperbilirubinaemia.

Unconjugated: haemolysis (rhesus/ABO, G6PD, spherocytosis), physiological, breast milk jaundice, sepsis, hypothyroidism, Crigler-Najjar. Conjugated (>25 µmol/L or >20% of total): biliary atresia, neonatal hepatitis, TPN, choledochal cyst, metabolic disease — always pathological and needs urgent investigation (biliary atresia is time-critical).

At what age must biliary atresia surgery (Kasai portoenterostomy) ideally be performed, and why?

Ideally before 60 days (8 weeks) of age. Outcomes (bile drainage, native liver survival) deteriorate sharply with later surgery, hence the urgency of investigating prolonged conjugated jaundice with pale stools and dark urine.

Define neonatal hypoglycaemia and list the main at-risk groups.

Operationally a blood glucose persistently below $2.6\ \text{mmol/L}$ (lower transitional thresholds tolerated in first hours if asymptomatic). At-risk groups: preterm, small-for-gestational-age, infants of diabetic mothers, large-for-gestational-age, hypothermic/septic/asphyxiated infants, and those with hyperinsulinism.

What is the immediate management of a symptomatic hypoglycaemic neonate?

Give IV glucose: a bolus of $2\ \text{mL/kg}$ of 10% dextrose followed by an infusion. Calculate the glucose infusion rate (GIR) and titrate; persistent hypoglycaemia requiring a GIR $>8\text{-}10\ \text{mg/kg/min}$ suggests hyperinsulinism. Glucagon may be used if no IV access.

Give the formula for glucose infusion rate (GIR) and a normal starting value.

$$GIR\ (\text{mg/kg/min}) = \frac{\text{dextrose concentration (\%)} \times \text{rate (mL/h)}}{6 \times \text{weight (kg)}}$$ A normal starting/maintenance rate is approximately 4-6 mg/kg/min.

Which nerve roots are injured in Erb's palsy versus Klumpke's palsy, and what is the clinical picture?

Erb's palsy: C5-C6 (upper roots) — the 'waiter's tip' posture (arm adducted, internally rotated, forearm pronated, wrist flexed) with intact grasp. Klumpke's palsy: C8-T1 (lower roots) — claw hand with loss of intrinsic muscle function, and possible Horner syndrome if T1 sympathetic fibres are involved.

Compare caput succedaneum and cephalohaematoma.

Caput succedaneum: diffuse, oedematous scalp swelling that crosses suture lines, present at birth, resolves in days. Cephalohaematoma: subperiosteal bleed that does NOT cross suture lines, appears hours after birth, may cause jaundice, resolves over weeks. A subgaleal haemorrhage crosses sutures and can cause dangerous blood loss.

What is the underlying surfactant deficiency in respiratory distress syndrome (RDS), and which cells produce surfactant?

RDS results from deficiency of pulmonary surfactant produced by type II pneumocytes. Surfactant (mainly dipalmitoylphosphatidylcholine/lecithin) reduces alveolar surface tension; its lack causes diffuse alveolar collapse, reduced compliance and ground-glass appearance with air bronchograms on CXR.

How does antenatal corticosteroid administration reduce RDS, and what is the recommended window?

Antenatal betamethasone or dexamethasone given to the mother (ideally 24 hours to 7 days before delivery, between 24-34 weeks) accelerates type II pneumocyte maturation and surfactant production, reducing RDS, intraventricular haemorrhage, NEC and neonatal mortality.

State the Laplace relationship explaining why surfactant prevents alveolar collapse.

$$P = \frac{2T}{r}$$ where $P$ is collapsing pressure, $T$ surface tension and $r$ alveolar radius. Smaller alveoli (small $r$) generate higher collapsing pressure; surfactant lowers $T$, especially as $r$ falls, stabilising small alveoli and preventing atelectasis.

How is bronchopulmonary dysplasia (BPD) / chronic lung disease of prematurity defined?

BPD is defined as an oxygen requirement at 36 weeks corrected gestational age (or at 28 days of life). It results from lung injury (volutrauma, oxygen toxicity, inflammation, infection) in the immature lung, with impaired alveolarisation.

What is the pathophysiology and first-line drug treatment of apnoea of prematurity?

Immature respiratory drive causes apnoea (cessation >20 s, or shorter with bradycardia/desaturation), often central or mixed. First-line treatment is caffeine citrate (a methylxanthine that stimulates the respiratory centre); CPAP helps obstructive/mixed apnoea.

Why does the ductus arteriosus shunt left-to-right after birth, and what are the signs of a haemodynamically significant PDA?

After birth, systemic pressure exceeds pulmonary pressure, so flow reverses to left-to-right (aorta to pulmonary artery). Signs: a continuous 'machinery' murmur, bounding pulses, wide pulse pressure, an active precordium, worsening ventilatory requirement and pulmonary oedema.

What pharmacological and surgical options exist for closing a symptomatic PDA?

Pharmacological closure uses prostaglandin synthesis inhibitors — indomethacin or ibuprofen (or paracetamol). Contraindications include renal impairment, NEC, bleeding and thrombocytopenia. If these fail and the PDA is significant, surgical ligation (or transcatheter device closure) is performed.

Describe the classic radiological signs and a hallmark feature of necrotising enterocolitis (NEC).

On abdominal X-ray: pneumatosis intestinalis (intramural gas, the pathognomonic sign), dilated bowel loops, portal venous gas, and pneumoperitoneum (free air — Rigler's sign/football sign) indicating perforation. Clinically: feed intolerance, bilious aspirates, abdominal distension and bloody stools.

What is the Bell staging used for, and what does stage III indicate?

Modified Bell staging classifies NEC severity. Stage I is suspected NEC, stage II is definite NEC (with pneumatosis), and stage III is advanced NEC with severe systemic illness, peritonitis and/or perforation requiring surgery. Management: stop feeds, NG decompression, broad-spectrum antibiotics, and surgery for perforation.

Compare germinal matrix/intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL) in preterm infants.

IVH is bleeding from the fragile germinal matrix capillaries, graded I-IV (IV = parenchymal involvement); risk highest in the first 72 hours. PVL is ischaemic white-matter necrosis around the ventricles, presenting later as cystic change on cranial ultrasound; it is the strongest predictor of spastic diplegia/cerebral palsy.

State the Papile grading of intraventricular haemorrhage.

Grade I: confined to the germinal matrix. Grade II: IVH without ventricular dilatation. Grade III: IVH with ventricular dilatation. Grade IV: parenchymal (periventricular venous) haemorrhagic infarction. Higher grades carry worse neurodevelopmental outcomes and risk post-haemorrhagic hydrocephalus.

What is the pathophysiology of retinopathy of prematurity (ROP), and who is screened?

ROP is abnormal retinal neovascularisation driven by hyperoxia-induced vaso-obliteration followed by VEGF-driven proliferation in the immature avascular retina. UK screening targets infants <32 weeks or <1501 g, starting at 4-6 weeks postnatally; treatment is laser photocoagulation or anti-VEGF injection.

What are the Sarnat stages of hypoxic-ischaemic encephalopathy (HIE)?

Sarnat stage 1 (mild): hyperalert, normal tone, no seizures, good prognosis. Stage 2 (moderate): lethargy, hypotonia, seizures common — variable outcome. Stage 3 (severe): comatose, flaccid, suppressed brainstem/autonomic function, seizures, poor prognosis.

State the criteria and therapeutic window for therapeutic hypothermia (cooling) in HIE.

For infants $\geq 36$ weeks with moderate-severe HIE, started within 6 hours of birth. Criteria include evidence of perinatal asphyxia (e.g. Apgar $\leq 5$ at 10 min, pH $<7.0$ or base deficit $\geq 16$, need for resuscitation) plus moderate/severe encephalopathy or abnormal aEEG. Cool to a core temperature of 33-34°C for 72 hours, then rewarm slowly.

Differentiate CPAP, HFNC and conventional/high-frequency ventilation as modes of neonatal respiratory support.

HFNC (high-flow nasal cannula) and CPAP deliver continuous distending pressure to keep alveoli open (non-invasive). Conventional mechanical ventilation delivers tidal breaths via an ETT. High-frequency oscillatory ventilation (HFOV) delivers very small tidal volumes at high rates (~10-15 Hz) and is used as rescue for severe lung disease or air leak.

What is the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), and what investigation confirms a right-to-left shunt?

Failure of the normal postnatal fall in pulmonary vascular resistance keeps pulmonary pressures high, causing right-to-left shunting across the ductus arteriosus and foramen ovale and hypoxaemia. A pre-/post-ductal saturation difference (>3% higher in the right hand than the foot) and echocardiography confirm it.

What is the targeted treatment for PPHN, and what is its mechanism?

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that increases cGMP in pulmonary vascular smooth muscle, reducing pulmonary vascular resistance without systemic hypotension. Supportive measures include optimal oxygenation, ventilation, sedation and avoiding acidosis; severe refractory cases may need ECMO.

Differentiate early-onset and late-onset neonatal sepsis by timing and common organisms.

Early-onset (<72 h, often <48 h): vertically acquired — Group B Streptococcus (commonest), E. coli, Listeria. Late-onset (>72 h): often nosocomial — coagulase-negative staphylococci, Staph aureus, Gram-negatives, Candida. Empirical early-onset cover is typically benzylpenicillin + gentamicin.

What are the common causes and the typical EEG/clinical features of neonatal seizures?

Commonest cause is HIE; others include stroke, intracranial haemorrhage, infection (meningitis), metabolic (hypoglycaemia, hypocalcaemia, hyponatraemia), and inborn errors. Neonatal seizures are often subtle (lip-smacking, cycling, eye deviation, apnoea) with poor clinical-electrical correlation; first-line treatment is usually phenobarbital after correcting metabolic causes.

What clinical and biochemical features suggest an inborn error of metabolism presenting in the neonatal period?

A previously well baby who deteriorates after feeding with poor feeding, vomiting, lethargy, encephalopathy and seizures. Clues: metabolic acidosis with raised anion gap, hyperammonaemia (urea cycle defects/organic acidaemias), hypoglycaemia, ketosis or unusual ketosis pattern, and a family history of neonatal death or consanguinity.

What does a markedly raised plasma ammonia with a normal anion gap and no acidosis suggest in a sick neonate?

A urea cycle defect (e.g. ornithine transcarbamylase deficiency). Organic acidaemias also cause hyperammonaemia but with a high-anion-gap metabolic acidosis and ketosis. Severe hyperammonaemia is a medical emergency requiring stopping protein, high-dose dextrose, ammonia scavengers and possibly dialysis.

Describe the pathophysiology and classic presentation of congenital diaphragmatic hernia (CDH).

A diaphragmatic defect (most often a left posterolateral Bochdalek hernia) allows abdominal viscera into the chest, causing pulmonary hypoplasia and PPHN. Presents with respiratory distress, a scaphoid abdomen, displaced heart sounds and bowel sounds in the chest. Management: intubate (avoid bag-mask ventilation), NG decompression, stabilise PPHN, then delayed surgical repair.

Compare gastroschisis and exomphalos (omphalocele).

Gastroschisis: a paraumbilical full-thickness defect (usually to the right of the cord) with free, uncovered bowel and no covering sac; rarely associated with other anomalies. Exomphalos: a central defect at the umbilicus with herniated viscera covered by a peritoneal/amniotic sac through which the cord inserts; strongly associated with chromosomal and other anomalies (e.g. Beckwith-Wiedemann, cardiac).

What antenatal and postnatal clues suggest oesophageal atresia with tracheo-oesophageal fistula, and what is the commonest type?

Antenatal polyhydramnios and a small/absent stomach bubble; postnatally excessive frothing/secretions, choking and inability to pass a nasogastric tube (it coils in the upper pouch on X-ray). The commonest type (~85%) is proximal oesophageal atresia with a distal tracheo-oesophageal fistula. Look for the VACTERL association.

Differentiate duodenal atresia and jejunal/ileal atresia on X-ray and aetiology.

Duodenal atresia: 'double bubble' sign (gas in stomach and proximal duodenum) with bilious vomiting; associated with Down syndrome and a failure of recanalisation. Jejunoileal atresia: multiple dilated loops/air-fluid levels, thought to result from an intrauterine vascular accident; less syndromic association.

What is the significance of bilious vomiting in a neonate, and which emergency must be excluded?

Bilious (green) vomiting in a neonate is a surgical emergency until proven otherwise. Malrotation with midgut volvulus must be urgently excluded (upper GI contrast showing an abnormally placed duodenojejunal flexure) because volvulus can rapidly cause ischaemic bowel necrosis.

List the cardinal dysmorphic features of trisomy 21 (Down syndrome) detectable in the newborn.

Hypotonia, upslanting palpebral fissures, epicanthic folds, flat nasal bridge and occiput, Brushfield spots, single palmar (simian) crease, sandal gap, short neck with excess nuchal skin, and clinodactyly. Associations: AVSD/cardiac defects, duodenal atresia, Hirschsprung disease and congenital hypothyroidism.

Contrast the dysmorphic features of Edwards syndrome (T18) and Patau syndrome (T13).

Edwards (T18): clenched overlapping fingers, rocker-bottom feet, micrognathia, prominent occiput, low-set ears, cardiac and renal defects. Patau (T13): midline defects — holoprosencephaly, cleft lip/palate, microphthalmia, polydactyly, scalp defects (cutis aplasia), cardiac defects. Both carry a very poor prognosis.

What features characterise Turner syndrome (45,X) and Noonan syndrome in the neonate?

Turner (45,X, female): lymphoedema of hands/feet, webbed neck (cystic hygroma antenatally), widely spaced nipples, coarctation of the aorta/bicuspid aortic valve. Noonan (autosomal dominant, e.g. PTPN11, normal karyotype, both sexes): similar webbed neck and chest but with pulmonary stenosis and hypertrophic cardiomyopathy.