Congenital malformations

Hemolytic disease of the newborn (HDN)

HDN (erythroblastosis) develops due to blood incompatibility between the mother and fetus regarding erythrocyte antigens, leading to an immunological conflict.

Causes of the conflict:

• Rh incompatibility: The most frequent cause. Mainly associated with the D-antigen. If the fetus inherits the paternal Rh factor absent in the mother, sensitization of the maternal immune system occurs. The first pregnancy often proceeds without complications. Active antibody production is triggered by massive entry of fetal blood into the maternal bloodstream (most often during labor). An important role is played by IgG class antibodies, which easily cross the placenta and destroy fetal erythrocytes.
• ABO incompatibility: The second most frequent cause. Usually occurs in mothers with blood type I (0). It is milder because anti-A and anti-B antibodies are predominantly IgM (do not cross the placenta), and the expression of A and B antigens on fetal erythrocytes is weak.

Mechanism of development: Destruction of erythrocytes (hemolysis) triggers two main processes:

1. Anemia. Leads to compensatory extramedullary hematopoiesis (enlargement of the liver and spleen). Tissue hypoxia causes damage to the myocardium (heart failure, edema) and liver (decreased protein synthesis, which increases edema).
2. Jaundice. Erythrocyte breakdown is accompanied by the release of unconjugated bilirubin. Due to the immaturity of the newborn's liver, it is conjugated slowly. Unconjugated bilirubin is toxic, lipid-soluble, and crosses the blood-brain barrier, causing damage to the subcortical nuclei — kernicterus.

Forms and morphology of HDN

Clinically, three forms of HDN are distinguished:

• Hydrops fetalis — the most severe form. Characterized by anasarca (generalized edema), fluid in body cavities, and marked hepatosplenomegaly. Often ends in intrauterine or early neonatal death.
• Icteric form — the most frequent. Manifests on days 1–2, dangerous due to the development of kernicterus.
• Anemic form — proceeds with prevailing anemia; jaundice is poorly expressed.

Pathological anatomy:

• Enlargement of the liver and spleen due to extramedullary hematopoiesis.
• Accumulation of hemosiderin in internal organs due to intravascular hemolysis.
• In kernicterus, the brain is edematous, the basal ganglia are stained yellow (pigmentation disappears rapidly even upon fixation).
• In the bone marrow, erythropoiesis is hyperactive. In the blood, there is an abundance of reticulocytes and normoblasts.
• The placenta is enlarged, pale, with edematous villi.

Hemorrhagic Disease of the Newborn

True hemorrhagic disease is associated exclusively with vitamin K deficiency. It occurs in 0.25–0.5% of newborns.

Normally, vitamin K is necessary for the activation of clotting factors (II, VII, IX, X) in the liver. In the fetus, vitamin K crosses the placenta poorly. Upon its deficiency, inactive acarboxy factors are formed, incapable of binding calcium and participating in coagulation.

Risk factors:

• Maternal intake of anticoagulants, anticonvulsants, or antibiotics.
• Gestosis, maternal liver and kidney pathologies.
• Prematurity.

Manifestations: Melena (tarry stools), bloody vomiting, skin hemorrhages (especially in the presenting part), cephalhematomas. May be triggered by hypoxia and birth trauma.

Other pathologies: Persistent fetal circulation and Necrotizing enterocolitis

Persistent fetal circulation (persistent pulmonary hypertension): Characterized by the persistence of blood flow through the foramen ovale or ductus arteriosus, leading to hypoxemia and cyanosis refractory to oxygen therapy. Causes:

1. Perinatal stress (meconium aspiration, hypoxia) — causes pulmonary vessel spasm.
2. Delayed vascular maturation (hypertrophy of the arteriolar muscular layer).
3. Congenital diaphragmatic hernia (underdevelopment of the lungs).

Morphologically: muscularization of small branches of the pulmonary artery and right ventricular hypertrophy.

Necrotizing enterocolitis: Ulcerative-necrotic intestinal lesion characteristic of extremely premature infants. Predisposing factors include hypoxia, respiratory distress syndrome, and umbilical vein catheterization. All parts of the intestine are affected, except the duodenum.

Class and exam questions

What else to study on this topic

• Pathogenesis of umbilical sepsis (omphalitis, umbilical vessel phlebitis)
• Morphological changes of the placenta in hemolytic disease
• Histological picture of kernicterus in the basal ganglia
• Role of maternal history (gestosis, medication intake) in the development of vitamin K deficiency in the fetus

Other topics in «Chapter 24. Childhood Diseases»

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.