A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy

OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survi val among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may redu ce the rates of these obstetric complications, but the efficacy of this tre atment remains unproven. This pilot study was undertaken to determine the f easibility of a multicenter trial of intravenous immune globulin and to ass ess the impact on obstetric and neonatal outcomes among women with antiphos pholipid syndrome of the addition of intravenous immune globulin to a hepar in and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compar ed treatment with heparin and low-dose aspirin plus intravenous immune glob ulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin an tibodies, or both. Patients with a single live intrauterine fetus at less t han or equal to 12 weeks' gestation were randomly assigned to receive eithe r intravenous immune globulin (1 g/kg body weight) or an identical-appearin g placebo for 2 consecutive days each month until 36 weeks' gestation in ad dition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Stud ent t test and the Fisher exact test as appropriate. RESULTS: Sixteen women were enrolled during a 2-year period; 7 received int ravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and ge stational age at the initiation of treatment. Obstetric outcomes were excel lent in both groups, with all women being delivered of live-born infants af ter 32 weeks' gestation. The rates of antepartum complications such as pree clampsia, fetal growth restriction, and placental insufficiency (as manifes ted by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 +/- 1.1 weeks; placebo group, 36.7 +/- 2.1 weeks) and birth weights (i ntravenous immune globulin group, 2249.7 +/- 186.1 g; placebo group; 2604.4 +/- 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo gr oup, 33%) and neonatal intensive care unit admission (intravenous immune gl obulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differenc es were not significant. CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low -dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care uni t admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.