Postponing Early intrauterine Transfusion with Intravenous immunoglobulin Treatment; the PETIT study on severe hemolytic disease of the fetus and newborn.
Zwiers C1, van der Bom JG2, van Kamp IL3, Geloven NV4, Lopriore E5, Smoleniec J6, Devlieger R7, Sim PE8, Ledingham MA8, Tiblad E9, Moise KJ Jr10, Gloning KP11, Kilby MD12, Overton TG13, Jørgensen DS14, Schou KV14, Paek B15, Walker M15, Parry E16, Oepkes D3, de Haas M.
Abstract
BACKGROUND:
Intrauterine transfusion for severe alloimmunization in pregnancy performed before 20 weeks' gestation is associated with a higher fetal death rate. Intravenous immunoglobulins may prevent hemolysis and could therefore be a non-invasive alternative for early transfusions.
OBJECTIVE(S):
We evaluated whether maternal treatment with intravenous immunoglobulins defers the development of severe fetal anemia and its consequences in a retrospective cohort to which 12 fetal therapy centers contributed.
STUDY DESIGN:
We included consecutive pregnancies of alloimmunized women with a history of severe hemolytic disease and by propensity analysis compared index pregnancies treated with intravenous immunoglobulins (n=24) with pregnancies managed without intravenous immunoglobulins (n=28),.
RESULTS:
In index pregnancies with intravenous immunoglobulin treatment, fetal anemia developed on average 15 days later compared to previous pregnancies (8% less often before 20 weeks' gestation). In pregnancies without intravenous immunoglobulin treatment anemia developed 9 days earlier compared to previous pregnancies (10% more before 20 weeks), an adjusted 4-day between-group difference in favor of the immunoglobulin group (95%CI -10 to 18, P=.564). In the subcohort in which immunoglobulin treatment was started before 13 weeks, anemia developed 25 days later and 31% less before 20 weeks' gestation (54% compared to 23%) than in the previous pregnancy. Fetal hydrops occurred in 4% of immunoglobulin-treated pregnancies and in 24% of those without intravenous immunoglobulin treatment (OR 0.03, 95%CI 0 to 0.5, P=.011). Exchange transfusions were given to 9% of neonates born from pregnancies with and in 37% without immunoglobulin treatment (OR 0.1, 95%CI 0 to 0.5, P=.009).
CONCLUSION(S):
Intravenous immunoglobulin treatment in mothers pregnant with a fetus at risk for hemolytic disease seems to have a potential clinically relevant, beneficial effect on the course and severity of the disease. Confirmation in a multicenter randomized trial is needed.
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