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. In order to further evaluate the response to IVIG therapy, the 13 cases in our population with a history of fetal/neonatal death in the previous pregnancy were analyzed separately. The results obtained in this particular group of patients demonstrated again the effectiveness of IVIG treatment. Conclusions: There were no adverse effects on the mother or fetus, and there was no need for neonatal intensive care. Results were more favorable if treatment was started before 28 weeks’ gestation in nonhydropic fetuses.

Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn – review on current management and outcome

“…IVIG treatment caused a significant decline in anti-D titers and hemolysis rate and even averted invasive IUT in this severely affected group if started before 28 weeks' gestation. Nevertheless, they concluded that for hydropic fetuses and for fetuses with advanced fetal anemia, IUT is inevitable [90]. In a retrospective study of the same group, patients receiving IVIG before 20 weeks had significantly less hydropic fetuses and a lower fetal mortality rate compared to patients treated with IUT alone [84].…”

“…A truly evidence-based noninvasive approach to further reduce fetal loss rates is however not yet available. Nevertheless, the use of intravenous immunoglobulins to postpone these hazardous early IUTs, potentially combined with TPE, shows promising results in case series and single center case-control studies [84,90]. Therapeutic plasma exchange alone seems unable to create similar results.…”

Therapeutic management of fetal anemia: review of standard practice and alternative treatment options

“…Margulies et al [43] conducted the largest prospective series to date in which 24 severely Rh-sensitized pregnant women were treated with IVIG alone until delivery and demonstrated that IVIG use should be initiated before 28 weeks or before the appearence of hydrops. In addition, Voto et al [85] demonstrated the predominance of the combined treatment with IVIG and IUT over IUT alone, as in the fi rst group, severe fetal anemia was less common and fetal mortality was reduced by 36 % compared with the second group.…”

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“…Unfortunately, the dosage of IVIg administered to the fetus in this study was too low to expect macrophage blocking. The largest case study comprising 24 severely Rh-sensitized pregnant women found a reduction of in utero hemolysis and fetal death when maternal IVIg treatment was started before the 28th week in non-hydropic fetuses (97). In 3 randomized trials (98-100) administration of IVIg after delivery to neonates with rhesus hemolytic disease significantly reduced the need for exchange transfusions.…”

“…** Non-randomized prospective series in which at least 2 patients were described. ll In the study of Margulies (97). it is not possible to exactly identify the responders to IVlg.…”