Intravenous immunoglobulin in the management of severe early onset red blood cell alloimmunisation

Abstract

Summary Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case–control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti‐D or anti‐K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti‐D in 17 women and anti‐K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8–53.2, p = 0.0013) and improved perinatal survival (eight of eight vs. none of six, p = 0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early‐onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.

Clinical response to therapeutic plasmapheresis and intravenous immunoglobulin in pregnancies complicated by alloimmunization despite persistently high titers: Report of two cases

“…One of the essential findings among our patients was that clinical response was achieved despite the lack of a significant drop in antibody titer. In other studies, antibody titer dropped significantly after plasmapheresis and remained low during IVIG therapy 3–13 …”

“…Plasmapheresis and IVIG have been used as immunomodulatory measures in many conditions. Several case reports, case series, and case–control studies support the effectiveness and safety of their use, separately or in combination, in patients at risk of early HDFN to delay the need for the first IUBT 3,4,6–14 . A Cochrane review search for randomized clinical trials evaluating the effect of IVIG in pregnancies affected by HDFN failed to identify any trials, 15 and we could not identify any such trials in our literature search.…”

“…Several case reports, case series, and case-control studies support the effectiveness and safety of their use, separately or in combination, in patients at risk of early HDFN to delay the need for the first IUBT. 3,4,[6][7][8][9][10][11][12][13][14] A Cochrane review search for randomized clinical trials evaluating the effect of IVIG in pregnancies affected by HDFN failed to identify any trials, 15 and we could not identify any such trials in our literature search. Such a trial is eagerly awaited, given the risk of publication bias and the various regimens described.…”

“…In other studies, antibody titer dropped significantly after plasmapheresis and remained low during IVIG therapy. [3][4][5][6][7][8][9][10][11][12][13] Although anti-D and anti-K are both IgG antibodies recognized to have the potential for causing severe HDFN, anti-K has a unique suppressive effect on fetal erythroid progenitors, in addition to antibody-mediated hemolysis. Despite the difference in characteristics between anti-D and anti-K and the differences between our patients' past obstetric history and antibody titers, successful obstetric outcomes were achieved using our current protocol in both patients.…”

Immunomodulation for early‐onset haemolytic disease of the fetus/newborn: Can we delay the need for intrauterine transfusions?

“…In their paper, Vlachodimitropollou and coauthors 9 report their experience with intravenous immune globulin in 22 cases of severe red‐cell alloimmunization. Patients with a previous history of second‐trimester fetal loss or a loss later in gestation associated with a high anti‐red‐cell titre were treated with 2 g/kg weekly IVIG every three weeks starting between 11 and 14 weeks of gestation.…”