Hemolytic Disease of the Newborn

Etiology of immune conflict

The primary cause of the disease is blood incompatibility based on erythrocyte antigens. Two main scenarios are distinguished:

• Rh incompatibility. Occurs if the mother is Rhesus-negative (Rh-) and the fetus is Rhesus-positive (Rh+).
• AB0 incompatibility. Develops when the woman has blood type 0(I) and the child has type A(II) (about 65% of cases) or type B(III) (35%). This variant is more common than Rh incompatibility, but runs a milder course and often remains undiagnosed.

Interestingly, in dual incompatibility (e.g., mother 0(I) Rh-, and fetus A(II) Rh+), the disease is more commonly manifested by AB0 system antigens rather than the Rh factor.

Sensitization mechanisms

For the pathology to develop, the maternal immune system must recognize foreign antigens.

In Rh incompatibility, prior sensitization (contact with Rh+ blood) is mandatory. During the first pregnancy, fetal erythrocytes enter the maternal circulation (especially during labor), triggering the synthesis of anti-Rh antibodies. Therefore, this form affects children from subsequent pregnancies.

In the case of AB0 incompatibility, the disease can start as early as the first pregnancy. This is explained by background everyday sensitization: A and B antigens enter the woman's body with food, vaccination, or infections long before conception.

Clinical variants

The clinical picture depends on the volume of maternal antibodies transferred to the child:

1. Hydrops fetalis (2%). The most severe outcome with intrauterine onset. Massive hemolysis causes severe anemia, hypoxia, and a drop in blood protein. Pronounced tissue edema and ascites develop. Hemoglobin drops below 100 g/L. Mortality in the first days reaches 50%.
2. Icteric form (88%). Manifests with the classical triad: anemia, early jaundice, and hepatosplenomegaly. Jaundice is absent at birth, but rapidly increases in the first 1–3 days due to the influx of antibodies upon the rupture of the placental barrier. The skin changes color from orange to lemon-greenish.
3. Anemic form (10%). Hemolysis is moderate; the liver manages to excrete bilirubin. Pallor, lethargy, and hepatosplenomegaly come to the forefront. An increase in nucleated erythrocyte precursors (normoblastosis) is recorded in the blood.

Complications and toxic injury

An excess of unconjugated bilirubin is toxic to all internal organs, but is most dangerous to the central nervous system. At concentrations above 340 µmol/L in full-term infants (and >200 µmol/L in preterm infants), bilirubin breaches the blood-brain barrier.

Kernicterus (bilirubin encephalopathy) develops. Its signs include:

• Nuchal rigidity and head retraction (opisthotonos);
• Piercing "cerebral" cry;
• Bulging fontanelle and seizures;
• "Sunsetting" sign.

A late complication of the icteric form is bile plug syndrome (by the end of the first week). Due to excess bilirubin, bile becomes overly viscous. Stool becomes clay-colored (acholic), urine darkens, and the conjugated bilirubin fraction increases in the blood.

Class and exam questions

What else to study on this topic

• Features of laboratory diagnostics: analysis of complete blood count and biochemical profile in various forms of HDN.
• Detailed mechanism of competition between bilirubin and fatty acids for binding to albumin.
• Pathophysiology of hypoproteinemia and ascites development in the hydrops form.
• Dynamics of neurological symptoms: from hypotonia to seizure syndrome.

Other topics in «Chapter 2. Neonatology»

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