A 2-day-old preterm neonate (32 weeks gestation) born to an O Rh-negative mother (previously sensitized) presents with jaundice and hepatosplenomegaly. Serum bilirubin is 10 mg/dL. What is the most common cause of hemolytic disease of the newborn in India?

Question

Accepted Answer

A. ABO incompatibility. ## Hemolytic Disease of the Newborn: Most Common Cause in India

**Key Point:** **ABO incompatibility** is the most common cause of hemolytic disease of the newborn (HDN) in India (and worldwide). Rh incompatibility, while more severe, is less frequent overall.

### Why ABO Incompatibility Is the Most Common Cause of HDN

1. **High prevalence of blood group O mothers** — Group O mothers naturally carry anti-A and anti-B antibodies (including IgG subclass), which can cross the placenta
2. **No prior sensitization required** — Unlike Rh incompatibility, ABO HDN can occur in the **first pregnancy**
3. **Frequency** — ABO incompatibility accounts for approximately **20–25% of all pregnancies** with maternal-fetal blood group mismatch, making it far more prevalent than Rh incompatibility
4. **Rh-negative prevalence in India is low** — Only ~5–8% of Indians are Rh-negative, limiting the pool at risk for Rh HDN

### Comparison: ABO vs. Rh Incompatibility

| Feature | ABO Incompatibility | Rh Incompatibility |
|---------|--------------------|--------------------|
| **Frequency (most common)** | ✅ Yes — most common overall | Less common (Rh-negative rare in India) |
| **First pregnancy affected** | Yes | Rarely (requires prior sensitization) |
| **Severity** | Usually mild | Often severe |
| **Hepatosplenomegaly** | Minimal | Marked |
| **Anemia** | Mild | Severe |
| **Hydrops fetalis** | Rare | Possible |
| **Antibody type** | IgM + IgG | IgG (crosses placenta) |
| **Prevention** | None | Anti-D (RhIG) prophylaxis |

### Understanding the Clinical Vignette

The stem describes a **sensitized Rh-negative mother** with a preterm neonate showing classic features of **Rh incompatibility** (early jaundice, hepatosplenomegaly, severe disease). However, the question asks for the **most common cause of HDN in India** — which is a separate epidemiological fact.

**ABO incompatibility** is the most common cause of HDN in India per standard pediatric references (Ghai's Essential Pediatrics, Nelson Textbook of Pediatrics). Rh incompatibility is the most common cause of **severe** HDN requiring exchange transfusion, but not the most common cause overall.

**High-Yield (Ghai's Essential Pediatrics / Nelson):** ABO incompatibility is the most common cause of HDN globally and in India. It typically presents in group A or B babies born to group O mothers. Disease is usually mild and self-limiting, but can occasionally require phototherapy.

**Clinical Pearl:** When a question asks "most common cause of HDN," the answer is **ABO incompatibility**. When it asks "most common cause of severe HDN" or "most common cause requiring exchange transfusion," the answer shifts toward **Rh incompatibility** in resource-limited settings with poor anti-D prophylaxis coverage.

Answer

B. G6PD deficiency

Answer

C. Rh incompatibility

Answer

D. Hereditary spherocytosis

A 2-day-old preterm neonate (32 weeks gestation) born to an O Rh-negative mother (previously sensitized) presents with jaundice and hepatosplenomegaly. Serum bilirubin is 10 mg/dL. What is the most common cause of hemolytic disease of the newborn in India?

Explanation

Hemolytic Disease of the Newborn: Most Common Cause in India

Why ABO Incompatibility Is the Most Common Cause of HDN

Comparison: ABO vs. Rh Incompatibility

Understanding the Clinical Vignette

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Feature	ABO Incompatibility	Rh Incompatibility
Frequency (most common)	✅ Yes — most common overall	Less common (Rh-negative rare in India)
First pregnancy affected	Yes	Rarely (requires prior sensitization)
Severity	Usually mild	Often severe
Hepatosplenomegaly	Minimal	Marked
Anemia	Mild	Severe
Hydrops fetalis	Rare	Possible
Antibody type	IgM + IgG	IgG (crosses placenta)
Prevention	None	Anti-D (RhIG) prophylaxis