High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal hemolytic disease

Abstract

Intrauterine fetal transfusion is currently the therapy of choice in cases of severe anti-D isoimmunisation. However, its efficacy is reduced in patients with early severe hydrops fetalis due to the technical difficulties in performing this procedure before 20 weeks' gestation. The purpose of this study was to determine whether early onset of high-dose gammaglobulin therapy followed by intrauterine transfusions (IUTs) is more effective than IUTs alone in the treatment of very severe isoimmunised fetuses. The population studied in this retrospective clinical research was assigned to one of the following two groups: 1) Gamma group: 30 patients receiving gammaglobulin therapy before 21 weeks' gestation and IUTs after 20 weeks; or 2) IUT group: 39 patients receiving IUT treatment starting at a gestational age of 20-25 weeks. Both groups were statistically similar regarding history of perinatal deaths and anti-D antibody titers. The number of hydropic fetuses at the first IUT and of fetal deaths were significantly higher in the IUT than in the Gamma group. No significant differences were observed between the groups in fetal hematocrit at first IUT and at birth. However, the percentage of severely anemic fetuses was higher in the IUT group. Fetal mortality rate was 36% less in the Gamma group. Our results suggest that high-dose gammaglobulin therapy followed by IUTs may improve fetal survival in these severe cases. Further randomised clinical trials are needed to confirm these results.

Early intrauterine transfusion in severe red blood cell alloimmunization

“…In order to overcome the difficulty in accessing a small vessel measuring less than 3-5 mm in early gestation, treatment with plasmapheresis and IVIG, aiming to prolong gestation before the need for IUT, has been reported 18,19 . Ruma et al described nine patients with severe RBC alloimmunization, who were treated with combined plasmapheresis and IVIG, which deferred their first IUT to a mean gestational age of 24 weeks, when the procedure is easier to perform, resulting in the survival of all infants 19 .…”

“…Objective To determine perinatal outcome in pregnancies with early severe red blood cell (RBC) IUT was 20.4 (range,[16][17][18][19][20][21][22] weeks, and between one and nine transfusions were needed during pregnancy. Transfusion was via the intrahepatic vein (IHV) (n = 19), umbilical vein (n = 6) or umbilical artery (n = 2), or was intracardiac (n = 2) or intraperitoneal (n = 1).…”

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

“…In most fetal therapy centers applying IVIG, it is started at 400 mg/kg maternal weight/day for 5 consecutive days, repeated every 2-3 weeks [80,82,84,85]. An alternative regime could be 500 mg-1 g/kg maternal body weight weekly [78,86].…”

“…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]. However, in another small series of four cases of severe RhD-immunization, IVIG did not seem to have any effect on transfusion frequency, maternal antibody titers or hydrops [91].…”

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. In the more recent case series, Fox et al [25] described the management of six pregnant women, with a previous pregnancy complicated by severe anemia before 20 weeks ' gestation, with intraperitoneal transfusion at 2-week intervals between 16 and 21 weeks and adjuvant maternal IVIG therapy.…”