Perinatal Pathology and Congenital Disorders

Hemolytic Disease of the Newborn (HDN)

HDN (erythroblastosis fetalis) develops due to maternal-fetal blood incompatibility regarding erythrocyte antigens, leading to an immunological conflict.

Causes of the Conflict:

• Rh Incompatibility: The most frequent cause, primarily 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 when a large amount of fetal blood enters the maternal circulation (usually during delivery). IgG class antibodies play a critical role because they easily cross the placenta and destroy fetal erythrocytes.
• AB0 Incompatibility: The second most common cause, typically occurring in mothers with blood type O (I). It is milder because anti-A and anti-B antibodies are predominantly IgM (which do not cross the placenta), and the expression of A and B antigens on fetal erythrocytes is weak.

Pathogenesis: Erythrocyte destruction (hemolysis) triggers two main processes:

1. Anemia: Leads to compensatory extramedullary hematopoiesis (hepatosplenomegaly). Tissue hypoxia causes myocardial damage (heart failure, edema) and liver damage (reduced protein synthesis, which worsens edema).
2. Jaundice: Erythrocyte breakdown is accompanied by the release of unconjugated (indirect) bilirubin. Due to the immaturity of the newborn's liver, its conjugation is slow. Unconjugated bilirubin is toxic, lipid-soluble, and crosses the blood-brain barrier, damaging subcortical nuclei — leading to 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 results in intrauterine or early neonatal death.
• Icteric form — the most frequent. Manifests on days 1–2; poses a high risk for kernicterus.
• Anemic form — presents with predominant anemia, while jaundice is mild.

Pathologic 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, and the basal ganglia are yellow-pigmented (the pigmentation fades rapidly even upon fixation).
• In the bone marrow — hyperactivity of erythropoiesis. In the blood — numerous reticulocytes and normoblasts.
• The placenta is enlarged, pale, with edematous chorionic villi.

Hemorrhagic Disease of the Newborn

Classic hemorrhagic disease of the newborn is strictly related to vitamin K deficiency. It occurs in 0.25–0.5% of newborns.

Normally, vitamin K is required for the hepatic activation of clotting factors (II, VII, IX, X). In the fetus, vitamin K crosses the placenta poorly. Its deficiency leads to the production of inactive acarboxy factors that cannot bind calcium and participate in coagulation.

Risk Factors:

• Maternal intake of anticoagulants, anticonvulsants, or antibiotics.
• Gestational hypertension, maternal liver and renal pathology.
• Prematurity.

Manifestations: Melena (tarry stools), hematemesis, cutaneous hemorrhages (especially on the presenting part), and cephalhematomas. It can be triggered by hypoxia and birth trauma.

Other Pathologies: Persistent Fetal Circulation and Necrotizing Enterocolitis

Persistent Fetal Circulation (Persistent Pulmonary Hypertension of the Newborn): Characterized by the persistence of blood flow through the foramen ovale or ductus arteriosus, leading to hypoxemia and cyanosis that do not respond to oxygen therapy. Causes:

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

Morphology: Muscularization of small pulmonary artery branches and right ventricular hypertrophy.

Necrotizing Enterocolitis (NEC): An ulcerative and necrotic intestinal lesion characteristic of extremely premature infants. Predisposing factors include hypoxia, respiratory distress syndrome, and umbilical vein catheterization. All segments of the intestine can be affected, sparing the duodenum.