VALENCIA, Spain—Preventing kernicterus should be the main aim of neonatal management of hemolytic disease of the fetus and newborn (HDFN), according to Enrico Lopriore, MD, PhD, a professor of neonatology and fetal medicine and the head of the Neonatal Intensive Care Unit at the Leiden University Medical Center in the Netherlands.

The early phase or the first week of neonatal management should consist of optimizing intensive phototherapy, which should start directly after birth, according to Dr. Lopriore. Exchange transfusion should be considered if needed but with caution due to the fact that it is a complex, invasive, and long procedure. 

Intravenous immunoglobulin (IVIG) should not routinely be used as it does not offer any additional benefit, according to systematic reviews.

Finally, the optimal gestational age at birth should be discussed between the gynecologist and neonatologist, Dr. Lopriore said.

In the late phase (up to 3 months from birth), erythropoietin infusion, hemoglobin levels, and retic count should be measured once a week, top-up transfusion should be performed if necessary, and erythropoietin infusion should be considered, he said.

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This final recommendation is based on results from the phase 2/3 EPO-4-Rhesus study, the aim of which was to determine whether erythropoietin treatment could reduce the need for top-up transfusions in neonates. The results of the study showed that the use of erythropoietin reduced the need for postnatal transfusion by 50%. 

Enrico Lopriore, MD, PhD, speaks at the 20th World Congress in Fetal Medicine. (Photo by Larry Luxner)

In the long term, “outcome is good,” Dr. Lopriore said, except in the case of hydrops, based on the findings of the so-called LOTUS study in which 291 children receiving intrauterine transfusion were followed up for 20 years. The risk of developmental defects in these children was around 4%-5%.

“Do all you can to prevent kernicterus,” Dr. Lopriore stressed once again.

The lecture was presented at the 20th World Congress in Fetal Medicine held in Valencia Spain, on June 25-29, 2023.

HDFN is a blood disorder in a fetus or newborn that develops as a result of a woman’s antibodies passing through the placenta during pregnancy and attacking the baby’s red blood cells, causing hemolysis and anemia.

HDFN can also cause kernicterus in the newborn, a type of brain damage that can occur as a result of high levels of bilirubin in the baby’s blood caused by the breakdown of red blood cells.


Lopriore E. Neonatal management and long-term outcome of hemolytic disease of the fetus and newborn. Oral presentation at: 20th World Congress in Fetal Medicine; June 26, 2023; Valencia, Spain.