High‐Dose Intravenous IgG for the Treatment of Severe Rhesus Alloimmunization

Abstract

The value of intravenous immunoglobulin (IVIG) in the treatment of 24 severely Rh-sensitized pregnant women was studied. IVIG was infused at a daily dose of 0.4 g/kg maternal body weight for 4-5 consecutive days, and was administered again 15-21 days later until delivery, depending on the evolution of the hemolytic disease. Our population was divided into 3 groups according to the time of onset of therapy: group 1 (n = 8), before 20 weeks' gestation; group 2 (n = 7), 20-28 weeks, and group 3 (n = 9), after 28 weeks. Initial mean anti-D level was significantly higher in group 1 (25.9 +/- 12.9 IU/ml) than in the other 2 groups, whose mean values were, however, higher than 10 IU/ml. Amniotic-fluid total bilirubin levels before the onset of therapy were pathologic, and in 55% of the cases they coincided with zone 3 of Liley's chart. Hydrops fetalis at the onset of treatment accounted for the only 3 fetal deaths in groups 1 and 2. None of the fetuses developed hydrops during treatment. Six of the 9 neonates in group 3 were depressed at birth (1-min Apgar below 7). However, at 5 min only 1 newborn showed an Apgar below 7. Mean birth weight was over 2,500 g in all the cases. Neonatal hematological condition in group 2 (50% of the babies required only phototherapy) was better than in the other 2 groups (transfusional therapy). There was a significant fall in maternal anti-D titers and intrauterine hemolysis after IVIG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Transfer of Anti‐d Antibodies Across the Isolated Perfused Human Placental Lobule and Inhibition by High‐dose Intravenous Immunoglobulin: A Possible Mechanism of Action

“…4 g/kg) prevents severe RhD-HD, although this finding was complicated by the additional use of maternal plasma exchange (Berlin et al, 1985;Besalduch et al, 1991). In contrast, two studies have shown the effectiveness of high-dose IVIgG alone when administered consecutively for 4-5 d, every 2 weeks (de la Camera et al, 1988) and particularly when initiated before 28 weeks gestation to severely affected neonates in the absence of hydrops fetalis (Margulies et al, 1991). A total of 100 g IVIgG given over 5-6 consecutive days, starting at 22 weeks gestation and repeated after 6 weeks, was also successful in maintaining higher fetal haemoglobin levels when compared to a control group (Gottvall & Selbing, 1995).…”

“…Although the mode of action of IVIgG in HD is not fully understood, it may significantly reduce the levels of maternal anti-D IgG (Bowman, 1990;Margulies et al, 1991). This may occur by direct inhibition of maternal immunoglobulin synthesis (de la Camera et al, 1988) possibly by enhancing T suppresser cell functions (Delfraissy et al, 1985) or from the high plasma IgG levels increasing the fractional catabolic rate of IgG and eliminating alloimmune antibody (Masson, 1993).…”

“…Although controversial, the use of intravenous immunoglobulin (IVIgG) may provide a relatively safe and non-invasive form of treatment for the fetus at a time before intrauterine transfusion can be given safely. Highdose IVIgG administered early in pregnancy may reduce the severity of HDN (Rewald, 1985;Berlin et al, 1985;de la Camera et al, 1988;Scott et al, 1988;Besalduch et al, 1991;Margulies et al, 1991). On the other hand, a maternal dose of 1 g/kg once per week was reported as ineffective in preventing RhD hydrops fetalis, but may have had an effect in reducing fetal morbidity from anti-Kell (Chitkara et al, 1990).…”

Efficacy of Antenatal Intravenous Immunoglobulin Treatment in Pregnancies at High Risk due to Alloimmunization to Red Blood Cells

“…Several case series and case reports indicate a beneficial role of IVIG, at least in delaying the development of significant anemia [36]. Admittedly, focusing on the reported cases in the literature, the administration of IVIG varied considerably and was inadequate due to low doses, delayed administration (after fetal anemia was already present), and/or inconsequent administration in a number of cases (table 2) [30,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57]. Only one study has shown that the administration of 1 g/kg/week in four women with anti-D did not appear to improve outcomes of affected fetuses [58].…”

Intravenous Immunoglobulin: Striving for Appropriate Use

“…Although case reports, case series, an uncontrolled prospective trial, and a retrospective trial appear to reveal benefits from IVIG, prospective controlled trials are needed before this therapy can be recommended routinely[ 61, 62]. …”