Postponing Early intrauterine Transfusion with Intravenous immunoglobulin Treatment; the PETIT study on severe hemolytic disease of the fetus and newborn

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.