Intrauterine Growth Restriction (IUGR) - Long Question (Paediatrics)

Definition

• Medical Physiology, p. 1678; Robbins & Kumar Basic Pathology, p. 136

Classification

1. Symmetrical IUGR (20-30% of cases)

• All parameters affected uniformly: weight, length, head circumference all <10th percentile
• Results from a long-standing insult in early gestation (4-20 weeks) during the hyperplastic phase (when cell numbers increase)
• Fewer total cells in the fetus ("decreased cell number")
• Causes: Chromosomal disorders (trisomies), congenital infections (TORCH: Rubella, CMV, Toxoplasmosis), congenital malformations, maternal alcohol/drug/tobacco use, severe maternal malnutrition
• ~25% of severely affected early-onset cases have aneuploidy

2. Asymmetrical IUGR (70-80% of cases)

• Weight is most affected; length less so; head circumference is relatively spared ("brain-sparing effect")
• Results from an insult in later gestation (after 28 weeks) during the hypertrophic phase (cell enlargement and fat/muscle accretion)
• Due to redistribution of fetal blood to the brain, heart, and adrenals at the expense of the liver, adipose tissue, and abdominal organs
• Causes: Uteroplacental insufficiency (most common), pre-eclampsia, chronic maternal hypertension, renal disease, severe diabetes with vascular disease, multiple gestation

3. Intermediate / Combined IUGR (5-10% of cases)

• Occurs during the middle phase of fetal growth (20-28 weeks)
• Caused by conditions like chronic hypertension or lupus nephritis starting early in the second trimester
• Shows symmetric growth pattern but without significant brain-sparing

Etiology / Causes

A. Fetal Causes

• Chromosomal abnormalities: Trisomy 13, 18, 21 (birth weights lowest in T13/T18)
• Congenital structural anomalies (22.3% of anomalous infants have IUGR)
• Congenital infections: TORCH (Rubella, CMV most established); Varicella, Toxoplasmosis, HIV, Malaria, Zika
• Metabolic disorders

B. Maternal Causes (most common category)

• Vascular disease: Pre-eclampsia, chronic hypertension
• Hypercoagulable states (acquired or inherited thrombophilia)
• Renal disease, Systemic Lupus Erythematosus
• Severe diabetes mellitus with vascular insufficiency
• Malnutrition (particularly third-trimester caloric restriction <1500 kcal/day)
• Teratogenic drugs: Phenytoin, warfarin, methotrexate, alcohol, narcotics
• Heavy smoking: Associated with small placentas and low birth weight
• High altitude (reduced oxygen availability)
• Multiple gestation

C. Placental Causes

• Placenta previa (low implantation)
• Placental abruption (retroplacental haematoma)
• Placental infarction
• Umbilical cord anomalies (single umbilical artery)
• Twin-twin transfusion syndrome (monochorionic twins)
• Histologic chorioamnionitis

Pathophysiology

1. Fetal haemodynamic redistribution: Doppler studies show increased resistance in the umbilical artery and decreased resistance in the middle cerebral artery ("brain-sparing"). In severe cases, absent or reversed end-diastolic flow in the umbilical artery indicates critical compromise.
2. Hormonal changes: Reduced IGF-1 (major intrauterine growth factor under nutritional control), reduced insulin levels; conversely, cortisol may be elevated.
3. Metabolic adaptation: Decreased fat, glycogen, and protein deposition. The liver (a major glycogen store) is disproportionately small, explaining hypoglycaemia after birth.
4. Haematopoietic response: Chronic hypoxia stimulates erythropoietin → polycythaemia.

Clinical Features / Recognition at Birth

Physical Appearance

• Low birth weight for gestational age
• Loose, dry, wrinkled skin with decreased subcutaneous fat (depleted fat stores)
• Thin, wasted limbs; prominent ribs
• Relatively large-appearing head (in asymmetric IUGR)
• Reduced abdominal circumference (small liver)
• Alert, wide-eyed appearance ("old man" facies)
• Meconium-stained skin, nails, and cord (chronic hypoxia causes meconium passage in utero)

Ponderal Index (PI)

• PI = Birth weight (g) × 100 / Crown-heel length (cm)³
• In asymmetric IUGR: PI is low (wasted)
• In symmetric IUGR: PI may be normal

Neonatal Complications

Antenatal Diagnosis

Ultrasonography (key tool)

• Biometric parameters: Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) - plotted serially on growth charts
• AC is the most sensitive single parameter (reflects liver size and fat stores)
• HC/AC ratio: Elevated in asymmetric IUGR (head spared relative to abdomen)
• Estimated fetal weight (EFW) <10th percentile for gestational age
• Serial ultrasounds every 2-4 weeks to assess growth velocity

Doppler Studies

• Umbilical artery: Increased systolic/diastolic ratio, absent end-diastolic flow (AEDF), or reversed end-diastolic flow (REDF) - each indicates progressively worsening placental resistance
• Middle cerebral artery (MCA): Decreased resistance (compensatory vasodilation) - "brain sparing"
• Cerebroplacental ratio (CPR): MCA PI / UA PI - reduced CPR is an adverse sign
• Ductus venosus / umbilical venous pulsations: Absent or reversed 'a' wave in DV indicates imminent cardiac decompensation

Biophysical Profile (BPP)

• Assesses fetal breathing movements, body movements, tone, amniotic fluid volume, NST
• Score ≤4/10 is an indication for delivery

Other Investigations

• Chromosomal analysis (karyotype ± microarray) when structural anomaly or early-onset severe IUGR
• TORCH serology (maternal and sometimes fetal blood)
• Maternal blood pressure, urine protein, renal function, antiphospholipid antibodies, CBC

Management

Antenatal

1. Identify and treat underlying cause (control hypertension, manage diabetes, stop smoking/alcohol)
2. Serial fetal surveillance: Growth ultrasound every 2-4 weeks; Doppler weekly or more frequently if abnormal
3. Corticosteroids (Betamethasone 12 mg IM × 2 doses 24h apart): if delivery anticipated before 34 weeks - accelerates lung maturity
4. Aspirin (low-dose, 150 mg nocte) started before 16 weeks - reduces placental dysfunction in high-risk women
5. Timing of delivery: Balance fetal compromise against prematurity:
   • Absent/reversed end-diastolic flow: consider delivery at 34 weeks
   • Abnormal ductus venosus: deliver regardless of gestation
   • Continuous CTG abnormality: emergency delivery

Neonatal Management (Paediatrics focus)

• Anticipate birth asphyxia; have full resuscitation team available
• Clamp cord early only if baby compromised (delayed cord clamping preferred otherwise)

1. Prevent hypothermia: Warm environment, pre-warmed towels, incubator for preterm IUGR babies
2. Blood glucose monitoring: Start within 30 minutes of birth; feed early (within 1 hour)
   • Target glucose >2.6 mmol/L (>47 mg/dL); IV dextrose if hypoglycaemia persists
3. Manage polycythaemia: If symptomatic (plethora, respiratory distress, jitteriness, convulsions) with haematocrit >65%: partial exchange transfusion with normal saline
4. Calcium supplementation if hypocalcaemic
5. Watch for NEC: Avoid aggressive enteral feeds in asphyxiated IUGR neonates; start minimal enteral nutrition and build up slowly
6. Respiratory support: If meconium aspiration or PPHN - oxygen, CPAP, mechanical ventilation, inhaled NO for PPHN

Long-term Consequences

1. Neurodevelopmental: Cerebral dysfunction, learning disabilities, attention deficit, sensory impairment (visual and hearing), lower IQ - particularly in symmetric IUGR
2. Growth: Approximately 10-15% of IUGR children fail to show "catch-up growth" and remain short; growth hormone therapy may be indicated in SGA children with persistent short stature after age 4 years
3. Barker Hypothesis / Developmental Origins of Health and Disease (DOHaD): Fetal undernutrition programs permanent metabolic changes:
   • Type 2 diabetes mellitus
   • Insulin resistance / metabolic syndrome
   • Hypertension
   • Cardiovascular disease (coronary artery disease)
   • Chronic kidney disease (reduced nephron number from impaired nephrogenesis)
4. Reproductive: Girls who were IUGR have increased risks in their own pregnancies

Summary Table: Symmetric vs Asymmetric IUGR

Important Exam Points (High-Yield)

• IUGR definition: birth weight <10th percentile for gestational age
• Most common type: Asymmetric (70-80%), due to uteroplacental insufficiency
• Most common neonatal complication: Hypoglycaemia (depleted glycogen stores)
• Brain-sparing = relatively preserved head circumference in asymmetric IUGR
• "TORCH" infections = symmetric IUGR
• Absent/reversed umbilical artery end-diastolic flow = severe fetal compromise
• Long-term: Barker hypothesis - increased risk of adult-onset T2DM, hypertension, CAD
• IUGR children not showing catch-up by age 4 → consider recombinant GH therapy