What is the prognosis of hemolytic disease of the newborn (HDN)?

Updated: Dec 28, 2017
  • Author: Sameer Wagle, MBBS, MD; Chief Editor: Muhammad Aslam, MD  more...
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Overall survival is 85-90% but reduced for hydropic fetuses by 15%. Most survivors of alloimmunized gestation are intact neurologically. Fetal hydrops does not seem to affect long-term outcome. [16] However, neurologic abnormality has been reported to be closely associated with severity of anemia and perinatal asphyxia. Sensorineural hearing loss may be slightly increased.


Almost 50 different red cell surface antigens have been found to be responsible for hemolytic disease of fetus and newborn. Only 3 antibodies are associated with severe fetal disease: anti-RhD, anti-Rhc, and anti-Kell(K1). Nearly 50% of the affected newborns do not require treatment, have mild anemia and hyperbilirubinemia at birth, and survive and develop normally. Approximately 25% are born near term but become extremely jaundiced without treatment and either die (90%) or become severely affected by kernicterus (10%). The remaining 25% of affected newborns are severely affected in utero and become hydropic; about half of newborns are affected before 34 weeks' gestation, and the other half are affected between 34 weeks' gestation and term. [1]

Before any interventions were available, the perinatal mortality rate was 50%. Wallerstein introduced exchange transfusion in 1945 and reduced the perinatal mortality rate to 25%. Later, Chown suggested the early delivery of those severely affected nonhydropic fetuses by 34 weeks' gestation followed by prompt exchange transfusion helped improve survival. The introduction of intraperitoneal transfusion by William Liley in 1963 and intravascular transfusion (IVT) by Rodeck in 1981 reduced the perinatal morbidity and the mortality rate was further reduced to the current rate of 16%.

Mortality rises to 30% with any degree of fetal hydrops. Most fetuses who are able to reverse fetal hydrops after IVT survive, compared with 25% of those in whom fetal hydrops was severe and persisted despite treatment. The overall rate of neurodevelopmental impairment is 10%, which is comparable to that found in the general population, but hearing loss is increased 5-10 fold over the general population in those infants who require in utero therapy for hemolytic disease of the newborn. The LOTUS study in a Dutch population reported neurodevelopmental outcomes in 281 children with hemolytic disease of the fetus treated with IVT at 8 years, showing normal outcome in 94%, cerebral palsy in 2.1%, severe developmental delay in 3.1%, and bilateral deafness in 1%. [17]  Severe hydrops fetalis was the only independent risk factor identified for poor outcome.

No relationship was noted between global developmental scores and the severity of hemolytic disease of the newborn (as evidenced by such factors as the number of intrauterine transfusions [IUTs], the lowest hematocrit [Hct] level, or the presence of hydrops). Normal neurological outcome is noted in more than 90% of infants even if fetal hydrops noted at the time of the first IUT. [18]

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