Diagnosis and Treatment of Hemolytic Disease of the Newborn

Antenatal monitoring and intrauterine therapy

Management of pregnant patients in high-risk groups is based on monitoring anti-Rh antibody titers. Until the 30th week, blood tests are performed monthly; from the 31st to the 36th week, twice a month; and weekly thereafter. The greatest danger is posed not simply by a steadily high titer, but by its fluctuating (unstable) values.

If the antibody titer reaches critical levels (1:16, 1:32 or higher) at 26–28 weeks of gestation, transabdominal amniocentesis is indicated. The physician evaluates the bilirubin concentration in the amniotic fluid to decide on intrauterine treatment.

The key method for detecting the hydrops fetalis form of HDN is ultrasound. If a severe course is suspected, umbilical cord puncture (cordocentesis) is performed to accurately determine fetal hemoglobin. The primary method for saving the fetus in such cases is intrauterine transfusion, in which washed donor erythrocytes along with a 20% albumin solution are transfused under ultrasound guidance.

Postnatal diagnostics: how not to miss hemolysis

Mandatory screening is initiated immediately after birth: cord blood from all infants born to Rh-negative mothers is tested for blood group, Rh factor, and baseline bilirubin levels.

Early clinical markers of HDN:

• Appearance of jaundice in the first hours or days of life.
• Lethargy and muscular hypotonia.
• Hepatosplenomegaly (pathological enlargement of the liver and spleen).

Mandatory laboratory minimum:

1. Hematological analysis: reveals normochromic anemia and compensatory reticulocytosis (massive release of immature erythrocytes).
2. Biochemical analysis: registers hyperbilirubinemia caused by an increase in the toxic (unconjugated) fraction.
3. Immunological test: direct Coombs test (antiglobulin test), confirming the presence of fixed maternal antibodies on the infant's erythrocytes.

Exchange blood transfusion (EBT)

In severe forms of HDN, there is a risk of developing bilirubin encephalopathy. In such cases, extracorporeal detoxification methods are used: plasmapheresis, hemosorption, and, most frequently, exchange blood transfusion (EBT). Its main goal is the elimination (removal) of toxic free bilirubin from the bloodstream.

Absolute indications for EBT in full-term infants on the 1st day of life:

• Unconjugated bilirubin level in cord blood exceeds 60 µmol/L.
• Hourly rate of bilirubin increase exceeds 6–10 µmol/L per hour.
• Critical bilirubin level in peripheral blood reaches > 340 µmol/L.
• Severe anemia (hemoglobin level drops below 100 g/L).

Selection of transfusion media strictly depends on the type of incompatibility. In Rh incompatibility, Rh-negative packed red blood cells (compatible with the infant's blood group) and fresh frozen plasma are transfused. In ABO incompatibility, group 0(I) erythrocytes and AB(IV) plasma or group-compatible plasma are used.

Conservative management and feeding tactics

In mild and moderate cases, as well as during the convalescence stage after EBT, the baseline therapeutic method is phototherapy.

Under the influence of the blue light spectrum, photo-oxidation of the unconjugated bilirubin molecule occurs: it changes its structure, turning into water-soluble isomers (specifically, biliverdin). These isomers are easily excreted from the body via feces and urine, bypassing the hepatic conjugation system. The procedure is performed using fluorescent lamps or fiber-optic systems (illuminated blankets). The total duration of irradiation is 72–96 hours (in cycles of 6–12 hours or continuously).

Medical support:

• Infusions: dextrose solutions (for energy) and albumin (to bind free bilirubin in the blood).
• Immunotherapy: early administration of normal human immunoglobulin blocks macrophage Fc receptors, halting erythrocyte destruction.
• Symptomatic correction: for bile plug syndrome, antispasmodics and ursodeoxycholic acid (UDCA) preparations are prescribed; to improve metabolism, B-group vitamins, ascorbic acid, and cocarboxylase are used.

Feeding issue. It was traditionally believed that in HDN, breastfeeding should be postponed until the end of the first week so that antibodies would disappear from the milk. However, modern data indicate that putting the baby to the breast is safe: maternal isoantibodies are completely inactivated by digestive enzymes and hydrochloric acid in the infant's stomach, without provoking further hemolysis.

Prevention and prognosis

The prognosis of the disease entirely depends on the degree of toxic damage to the central nervous system. Severe consequences include the development of cerebral palsy (CP) and severe psychomotor retardation. Mild and moderate forms can lead to sensorineural hearing loss, strabismus, and learning difficulties.

HDN can be prevented through specific prophylaxis. It consists of administering human anti-Rh Rho[D] immunoglobulin to an unsensitized Rh-negative woman strictly within 24 hours after giving birth to an Rh-positive child (or after an abortion). Exogenous antibodies bind fetal erythrocytes that have entered the maternal bloodstream and accelerate their elimination. This prevents the maternal immune system from recognizing the antigen and blocks the production of its own lethal antibodies. Nonspecific prophylaxis includes strict monitoring of the Rh factor during any blood transfusions and the minimization of abortions.

Class and exam questions

What else to study on this topic

• Pathogenesis of bilirubin encephalopathy and kernicterus
• Differential diagnosis of jaundice in newborns
• Procedure and interpretation of the direct Coombs test
• Treatment of bile plug syndrome in neonatal hemolysis
• Technique for performing intrauterine fetal transfusion

Other topics in «Chapter 2. Neonatology»

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