In infants with hemolytic disease of the fetus and newborn (HDFN), the management of cases of severe neutropenia entails careful monitoring, supportive care and early medical intervention, and publications and data on neutropenia occurring along with HDFN are limited.
Realizing this, researchers involved in a retrospective cohort study published recently in the International Journal of Pediatrics and Adolescent Medicine sought to estimate the incidence of neutropenia and to identify those factors associated with the disorder among a group of infants at the King Faisal Specialist Hospital and Research Hospital. The study was conducted from March 2008 through September 2023 at a tertiary care center in Riyadh, Saudi Arabia.
In the current analysis, neutropenia was defined as “an absolute neutrophil count of less than 1.5 µL.” Functioning as a type of white blood cell that helps the body fight infection caused by microorganisms, including viruses and bacteria, neutrophils are a key component of the body’s immune system.
A lesser known cause of neonatal neutropenia is alloimmune HDFN. Infants who are hospitalized in neonatal intensive care units (NICUs) frequently develop neutropenia, with incidence rates of up to 8% reported.
Read more about HDFN testing and diagnosis
Risk factors and occurrence of neutropenia
Risk factors that increase the probability of an infant with HDFN developing neutropenia include male gender, low gestational age (GA), low birth weight and the need to undergo an exchange transfusion. Clinical presentations of HDFN can vary from anemiaAnemia A condition that occurs when the body doesn’t have enough healthy red blood cells to carry oxygen to its tissues. In HDFN, anemia occurs when maternal antibodies destroy fetal red blood cells. that is asymptomatic, to jaundiceJaundice A common symptom of HDFN, jaundice is caused by excess bilirubin and is characterized by a yellow tint to the skin or eyes., and even to hydrops fetalisHydrops fetalis A serious, sometimes fatal condition in which fluid builds up in a baby’s tissues and organs due to severe anemia from HDFN..
For the purposes of the present study, HDFN severity was classified into one of three possible levels:
- Severe: hydrops fetalis was reported
- Moderate: transfusions were needed but hydrops fetalis was not reported
- Mild: transfusions were not required
The study included a total of 339 neonates with HDFN, with 170 males and 169 females evaluated. At birth, the median GA was 36 weeks + 0 days (range in GA, 34 weeks + 4 days to 37 weeks + 3 days). Low birth weight was reported among 154 of the participants; 185 neonates had a normal birth weight.
Overall, 212 of the participants had mild HDFN, 113 had moderate HDFN and 14 had severe HDFN.
Rhesus (RhRh factor A protein or antigen found on red blood cells. When an Rh-negative mother carries an Rh-positive fetus, her immune system may make antibodies that attack the fetus' red blood cells.) isoimmunization was the most frequently reported antibodyAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. type (in 199 neonates), which was followed by ABO incompatibility (in 140 neonates) and Rh isoimmunization due to minor blood groups (in 7 neonates).
The incidence of neutropenia in the study cohort was 4.1 per 1000 person-days. In fact, 25 of the 339 infants exhibited neutropenia at birth. Among these 25 neonates, symptoms resolved within 2 days in 17 of them.
“Neutropenia in infants with HD[F]N, irrespective of antibody type, is generally a benign, self-limiting condition,” the authors noted. “This condition predominantly affects male neonates with moderate-to-severe HD[F]N and prematurity and can be managed conservatively.”