Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial

Abstract

Objective: Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e. 0.5 g/kg. Methods: This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. Results: A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10⁹/l (range 8-269) in the 0.5 g/kg group versus 110 × 10⁹/l (range 11-279) in the 1 g/kg group (p = 0.644). Conclusion: The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review

“…IVIG only treatment had a 98.7% success rate for preventing ICH (4 ICHs occurred in 315 pregnancies). 16,17,[19][20][21][22][23][24][26][27][28][29][30][31][32]34,35 This is consistent with the rate of 97.3% found in the Cochrane analysis reported by Rayment et al, 16 which included 37 pregnancies treated with IVIG only. However, none of the studies were powered to detect a significant difference in bleeding outcomes.…”

“…Whether the commonly used dose of 1 g/kg per week is the best treatment for all FNAIT pregnancies, or whether this could be reduced or increased in certain subgroups remains unclear. Data from the previously described randomized controlled trial 30 and retrospective data provided by Van Der Lugt et al 31 showed that the lower dose of 0.5 g/kg per week appeared not to be inferior to the 1 g/kg per week IVIG in standard risk (ie, a previous sibling that did not have an ICH) populations. Given the dose-related side effects and costs, a dose of 0.5 g/kg per week could be regarded as suitable for these women.…”

“…21,22,[27][28][29] FBS was performed in all but 3 studies. [30][31][32] The earliest that fetal blood was sampled was in gestational week 16,33 but most commonly, sampling began in weeks 20 or 22. Of the 16 studies performing IUPT, 8 reported a fetal PLT count threshold to infuse PLTs.…”

“…Of the 26 studies, 17 had a treatment arm with IVIG alone, 19,20,[22][23][24]26,27,[29][30][31][32][33][34][35][36][37][38] 3 studies had a treatment arm with corticosteroids alone, 29,35 and 11 had a study arm that combined IVIG and corticosteroid treatment. 19,20,22,24,32,[35][36][37][39][40][41] There were 2 studies that compared all 3 arms.…”

Fetal and Neonatal Alloimmune Thrombocytopenia: Management and Outcome of a Large International Retrospective Cohort

“…This study was prematurely ended in 2008 due to lack of inclusion [8] . The registry was kept open for fetal treatment centres worldwide to enter data on pregnancies complicated by FNAIT.…”