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

Fetal Diagn Ther. 2015;38(2):147-53. doi: 10.1159/000380907. Epub 2015 Apr 17.

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 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Female
  • Fetal Diseases / diagnosis
  • Fetal Diseases / drug therapy*
  • Fetal Diseases / epidemiology
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage*
  • Immunoglobulins, Intravenous / adverse effects
  • Infant, Newborn
  • Internationality
  • Intracranial Hemorrhages / diagnosis
  • Intracranial Hemorrhages / epidemiology
  • Intracranial Hemorrhages / prevention & control*
  • Pregnancy
  • Thrombocytopenia, Neonatal Alloimmune / diagnosis
  • Thrombocytopenia, Neonatal Alloimmune / drug therapy*
  • Thrombocytopenia, Neonatal Alloimmune / epidemiology
  • Young Adult

Substances

  • Immunoglobulins, Intravenous