The rate of severe prenatal and perinatal outcomes associated with hemolytic disease of the fetus and newborn (HDFN) over a 24-year period have been reported as part of a retrospective cohort study based on an Israeli Maccabi database and recently published in Research Square.
When HDFN occurs during pregnancy, maternal alloantibodies from the immunoglobulin G class cross the placenta and then bind to fetal red blood cells (RBCs) with the corresponding antigen. This, in turn, leads to the destruction of RBCs and the subsequent development of anemia in the fetus or newborn. Among patients with HDFN, the clinical presentation of the disease can vary from mild anemia to severe anemia that can be associated with hydrops fetalis, preterm labor induction, the need for intrauterine transfusion or fetal death.
Study method and objectives
Researchers of the current study sought to better understand the clinical effect of non-ABO HDFN on pregnant women, fetuses and newborns. Secondary study objectives included the assessment of incidence and trends of HDFN in Israel; frequency and outcomes of severe HDFN and and treatment patterns in pregnant women, fetuses and newborns.
Data between January 1998 and December 2021 were extracted from the Maccabi Healthcare Services (MHS) database. Recognized as a nationwide payer-provider health care plan, MHS represents more than one-quarter of the Israeli population. In fact, the MHS database includes longitudinal data on a stable population of more than 2.6 million individuals since 1993.
Read more about HDFN testing and diagnosis
In MHS, data are automatically obtained and comprise comprehensive information from a single central laboratory, complete pharmacy data and extensive demographic data for every enrolled patient. Typically, HDFN is diagnosed via identification of the presence of maternal RBC antibodies. Because alloantibody data were available in the MHS database from 2005 onward, any individual with a diagnosis of HDFN recorded in the MHS database was included in the study, regardless of alloantibody test result.
The cohorts included both women and newborns with an HDFN diagnosis between 1998 and 2021. Women with an HDFN diagnosis during their pregnancy comprised the pregnancy cohort. Those women with multiple pregnancies were able to be included repeatedly in the pregnancy cohort—one time for each HDFN-associated pregnancy. The newborn cohort included offspring from these pregnancies, along with children with a diagnosis of HDFN in their first year of life. Late-onset HDFN was defined as an HDFN diagnosis rendered at 24 weeks’ gestational age or later.
HDFN incidence rate experiences slight decline
Results of the study revealed that the incidence of HDFN was stable in Israel, ranging from 0.4 to one case per 10,000 pregnancies throughout most of the study period. In fact, the incidence of HDFN that was diagnosed among newborns was higher compared with the incidence of HDFN diagnosed during pregnancy. The rates have decreased significantly from 1.8 (95% CI, 0.9-3.4) per 10,000 newborns in 1998 to 1.1 (95% CI, 0.4-2.5) per 10,000 newborns in 2021 (P <.001).
Overall, 76 pregnancies with an HDFN diagnosis were identified; 96% of them had medical information available on their pregnancy course and outcome. The presence of alloantibodies was verified in 27 women during or prior to 28 pregnancies, which represented 38.4% of all the HDFN pregnancies.
Postnatally, 395 additional newborns were diagnosed with HDFN. Of 57 newborns born to HDFN-diagnosed mothers, 55 were located in the MHS database and thus added to the HDFN newborn cohort. Thus, a total of 450 HDFN newborns were identified and verified as having HDFN in their first year of life.
Over the 24-year study period, the incidence rate of HDFN among pregnant women remained stable, whereas the incidence rate among newborns actually declined. In all, severe HDFN was diagnosed in 28.8% of HDFN-affected pregnancies. Of the 450 HDFN newborns, one-third received a diagnosis of jaundice or anemia. There were five cases of kernicterus reported.
“Further studies are needed to understand and evaluate current treatment regimens for HDFN and assess the association between perinatal management and short- to long-term outcomes,” the authors concluded.
