A two-center study on the pharmacokinetics of intravenous immunoglobulin before and during pregnancy in healthy women with poor obstetrical histories.

BACKGROUND: Despite the increasing use of intravenous immunoglobulin (IVIG) in obstetrics, information on its pharmacokinetics and optimal dosing during each trimester pregnancy is lacking. The aim of this study was to characterize IVIG pharmacokinetics in pregnant women with a history of idiopathic secondary recurrent miscarriage or obstetrical antiphospholipid syndrome and to make dosing recommendations by comparing serum immunoglobulin G (IgG) concentrations in women receiving IVIG to placebo controls, before and during pregnancy.
METHODS: Women enrolled in an IVIG trial for idiopathic secondary recurrent miscarriage (n = 25) or an IVIG study for obstetrical antiphospholipid syndrome (n = 10); 22 received IVIG 0.5-1.0 g/kg and 13 received the equivalent volume of saline, every 4 weeks from pre-pregnancy until 18-20 weeks of gestation, with dosing adjusted for her weight prior to each infusion. Serum IgG concentrations were measured by rate nephelometry before and 0.5 h, and 1, 2, 3 and 4 weeks following an infusion. Sampling was performed pre-pregnancy and in the first and second trimesters.
RESULTS: Area under the curve (AUC) did not differ significantly within the IVIG group between the three sampling periods. Estimated contributions of IVIG [calculated as mean AUC (IVIG group) minus mean AUC (control group)] were 4890.8 g h/l pre-pregnancy, 5591.4 g h/l first trimester and 4755.1 g h/l second trimester (P> 0.05, non-significant). For the IVIG 0.5 and 1.0 g/kg subgroups, the overall estimated contribution of exogenous IVIG was ~4000 and ~6400 g h/l, respectively.
CONCLUSIONS: With a weight-adjusted dosage of IVIG, drug exposure, based on AUC calculations, was maintained at the pre-pregnancy level. Therefore, we recommend a weight-adjusted dosage of IVIG during the first and second trimesters.

RCT Entities:   Population Interventions Outcomes