The near disappearance of fetal hydrops in relation to current state‐of‐the‐art management of red cell alloimmunization

Abstract

ObjectiveIn this study, we aim to evaluate trends in the condition of fetuses and neonates with hemolytic disease at the time of first intrauterine transfusion (IUT) and at birth, in relation to routine first‐trimester antibody screening, referral guidelines, and centralization of fetal therapy.MethodWe conducted a 30‐year cohort study including all women and fetuses treated with IUT for red cell alloimmunization at the Dutch national referral center for fetal therapy.ResultsSix hundred forty‐five fetuses received 1852 transfusions between 1 January 1987 and 31 December 2016. After the introduction of routine first‐trimester antibody screening, the hydrops rate declined from 39% to 15% (OR 0.284, 95% CI, 0.19‐0.42, P < 0.001). In the last time cohort, only one fetus presented with severe hydrops (OR 0.482, 95% CI, 0.38‐0.62, P < 0.001). Infants are born less often <32 weeks (OR 0.572, 95% CI, 0.39‐0.83, P = 0.004) and with higher neonatal hemoglobin (P < 0.001). Neonatal hemoglobin was positively independently associated with gestational age at birth, fetal hemoglobin, and additional intraperitoneal transfusion at last IUT.ConclusionSevere alloimmune hydrops, a formerly often lethal condition, has practically disappeared, most likely as a result of the introduction of routine early alloantibody screening, use of national guidelines, and pooling of expertise in national reference laboratories and a referral center for fetal therapy.

It is time to reconsider the risks of transfusing RhD negative females of childbearing potential with RhD positive red blood cells in bleeding emergencies

“…Ultrasound also allowed for easier and safer access to the fetal intravascular compartment through cordocentesis, which in turn allowed for accurate assessment of fetal anemia, and for IUT. The combination of the early detection of severe fetal anemia before hydrops fetalis develops, and safe IUT have virtually eliminated the progression of RBC alloimmunization to severe HDFN‐mediated erythroblastosis fetalis in developed countries . Intrauterine transfusions themselves coupled with more effective intensive phototherapy and the use of intravenous immune globulin (IVIG) in affected neonates have reduced the need for exchange transfusion postnatally .…”

“…Thus, accurate follow up of pregnancies that are affected by HDFN can be obtained. In a recent study of 645 fetuses that received at least one IUT because of maternal alloimmunization primarily to the D antigen in the Netherlands between 1987‐2016, the overall survival was 93% . Overall fetal survival increased from 79% in 1987‐1992 to 96% in 2011‐2016 largely due to improvements in diagnosis and management, and a reduction in the number of fetuses with severe hydrops.…”

Three non-classical mechanisms for anemic disease of the fetus and newborn, based on maternal anti-Kell, anti-Ge3, anti-M, and anti-Jra cases

“…HDFN mortality dramatically declined during a 30-year-period in the Netherlands, as nationwide screening and intervention were systematically introduced. In a predominantly Caucasian population, incidence of maternal alloimmunization against D was followed by Kell, but hydrops from anti-Kell was still 3.5 times higher than from anti-D, and intrauterine transfusions begin about 3 weeks earlier in this well-organized Dutch health care system [7].…”

Red cell alloimmunization: A 2020 update

“…Alloantibody glycosylation pattern has been proposed as a better marker of adverse fetal outcome than titer . In the Netherlands, antibody‐dependent cell‐mediated cytotoxicity is measured in addition to antibody titers to assess risk of severe hemolysis …”