Multicentre trial of antepartum low-dose anti-D immunoglobulin. Efficacy and safety of a new, chromatographically purified rhesus (D) immunoglobulin. [Ante-partum administration of preventive treatment of Rh-D immunization in rhesus-negative women. Parallel evaluation of transplacental passage of fetal blood cells. Results of a multicenter study carried out in the Paris region]. Pharmacokinetics of anti-D IgG in pregnant RhD-negative women. Prevention of rhesus immunization. A controlled clinical trial with a comparatively low dose of anti-D immunoglobulin. Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial. Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture. High-dose intravenous immunoglobulin therapy for rhesus haemolytic disease. Randomised trial comparing expectant with medical management for first trimester miscarriages.
Routine antenatal Rh immunoprophylaxis would substantially increase the use of anti-D Ig in the U.K. As availability of anti-D Ig is one factor influencing a decision to introduce routine antenatal prophylaxis, a trial was undertaken to test the efficacy of a lower dose of anti-D Ig than that used in earlier studies. RhD-negative primigravidae were randomized as controls or recipients of two doses of 250iu of anti-D Ig given at 28 and 34 weeks gestation. Blood samples were tested at delivery and at 6 months postpartum for the presence of immune anti-D, and again later if results were equivocal. Nine (1.5%) out of 595 control patients had immune anti-D at follow-up at 6 months and later; 4 (0.78%) of 513 treated women were immunized. It was concluded that, while two doses of 250iu of anti-D Ig may reduce alloimmunization, they are not as effective as two doses of 500iu in a previous trial. To study the efficacy, safety, and tolerability of the 300 microg dose of a new chromatographically produced rhesus immunoglobulin (Rhophylac 300) for ante- and postnatal rhesus prophylaxis.
                In an open-label multi-centre study, rhesus D (RhD)-negative women were randomly allocated to receive Rhophylac 300 either intravenously or intramuscularly at the 28th week of gestation and within 72 h after delivery of an RhD-positive child. Serum samples were obtained prior to the antenatal dose and 6-11.5 months after delivery of an RhD-positive child and tested by the indirect antiglobulin test and papain test for anti-D. Safety parameters were assessed in all women who were treated with the study drug.
                Four hundred and thirty two women received the study drug antenatally. No differences were detected in efficacy or tolerability between intravenous and intramuscular administration. Of the 261 women who delivered an RhD-positive child and received rhesus prophylaxis according to the protocol, 248 women returned for follow-up investigations. None of them had detectable anti-D at their last visit. There were no serious adverse events, no cases of infectious disease transmission nor clinically relevant changes in laboratory safety values and vital signs attributable to the study drug.
                The results suggest that Rhophylac 300 given intravenously or intramuscularly is safe and efficacious in preventing rhesus (D) immunisation. 1,969 non immunized rhesus negative primiparous women were followed up in 23 maternity units in the geographical region of Paris. 1,882 could be retained to study antepartum protection and 1,884 to study transplacental passage of fetal blood cells. Two groups were defined according to whether they were born in even or uneven years, so that: 955 were the "control" group who delivered 590 rhesus D positive infants, and 927 were the "treated" group who delivered 599 rhesus D positive infants. The "control" group were used as controls at the 28th and 34th weeks of pregnancy, while the "treated" group received two injections of anti-D immunoglobulin given on the same dates after taking the necessary tests. Immunological testing at the time of the delivery and after the delivery showed that 7 women had become Rh D immunized in the "control" group whereas only one in the "treated" group. This difference, which is statistically significant, confirms the results of other authors about the efficiency of antepartum rhesus disease prevention. The incidence of immunisation during or immediately after the first pregnancy in women who had no previous story of blood transfusions or of terminations of pregnancy is 1.11%, which is a figure relatively low as compared with studies of series carried out in North America, but close to those carried out in other European centres. When primipara of all categories are lumped together the frequency rises to 1.5%. A study of the passage of fetal red blood cells into the maternal circulation shows that at the 29th week of pregnancy out of 1,884 cases there were 5.5% positive kleihauer tests, without a large volume of blood being detected and at the 34th week of pregnancy when 957 tests were carried out, 7% were positive with one of them being of a massive transfusion of blood from the fetus to the mother, which was life-threatening for the fetus. It may be that the incidence had been under-estimated and that the positive results in the two groups, control and treated, show that there is a statistically significant difference that demonstrates that antepartum treatment in the trial has eliminated a worthwhile percentage of positive kleihauer tests which arose from the transfusion of small quantities of blood.(ABSTRACT TRUNCATED AT 400 WORDS) To assess the pharmacokinetics of anti-D IgG in pregnant Rhesus D-negative women after intramuscular and intravenous administration of 300 microg of Rhophylac.
                An open, randomised, multicentre study.
                Seven gynaecological practices in Germany.
                Fourteen RhD-negative pregnant women at risk of becoming Rhesus D immunised received study drug at 28th week of pregnancy either by intramuscular or intravenous route.
                Anti-D IgG concentrations of serum samples obtained up to 11 weeks following antenatal Rhesus D prophylaxis were quantified by flow cytometry.
                Mean anti-D IgG concentrations after intravenous and intramuscular administration differed up to seven days post-injection, from two weeks onwards they were comparable to each other. Irrespective of the administration route, anti-D IgG in serum was detectable in all women up to at least nine weeks post-administration.
                The serum concentrations of anti-D IgG measured after administration of Rhophylac were very similar to those obtained with 300 microg of a different anti-D immunoglobulin product. A controlled clinical trial was carried out to test the effectiveness of a comparatively low dose of anti-D immunoglobulin (250 mug) in preventing rhesus immunization.In the control group 17 out of 329 women (5%) formed rhesus antibodies, whereas in the treated group only 3 out of 333 women (0.9%) showed active immunization, all three of whom had an exceptionally large transplacental bleeding. Couples with unexplained recurrent miscarriage may have an alloimmune abnormality that prevents the mother from developing immune responses essential for the survival of the genetically foreign conceptus. Immunisation with paternal mononuclear cells is used as a treatment for such alloimmune-mediated pregnancy losses. However, the published results on this treatment are conflicting. In this study (the Recurrent Miscarriage [REMIS] Study), we investigated whether paternal mononuclear cell immunisation improves the rate of successful pregnancies.
                Women who had had three or more spontaneous abortions of unknown cause were enrolled in a double-blind, multicentre, randomised clinical trial. 91 were assigned immunisation with paternal mononuclear cells (treatment) and 92 immunisation with sterile saline (control). The primary outcomes were the inability to achieve pregnancy within 12 months of randomisation, or a pregnancy which terminated before 28 weeks of gestation (failure); and pregnancy of 28 or more weeks of gestation (success). Two analyses were done: one included all women (intention to treat), and the other included only those who became pregnant.
                Two women in each group received no treatment, and eight (three treatment, five control) were censored after an interim analysis. In the analysis of all randomised women who completed the trial, the success rate was 31/86 (36%) in the treatment group and 41/85 (48%) in the control group (odds ratio 0.60 [95% CI 0.33-1.12], p=0.108). In the analysis of pregnant women only, the corresponding success rates were 31/68 (46%) and 41/63 (65%; odds ratio 0.45 [0.22-0.91], p=0.026). The results were unchanged after adjustment for maternal age, number of previous miscarriages, and whether or not the couple had had a previous viable pregnancy. Similar results were obtained in a subgroup analysis of 133 couples with no previous livebirth.
                Immunisation with paternal mononuclear cells does not improve pregnancy outcome in women with unexplained recurrent miscarriage. This therapy should not be offered as a treatment for pregnancy loss. Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits.
                Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used.
                From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33).
                The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes. Rhesus haemolytic disease is a continuing problem in the newborn especially in countries where the use of anti-D immunoglobulin is not prevalent. The fetuses may need intrauterine transfusions to prevent hydrops faetalis and they also may need exchange transfusions to treat the hyperbilirubinaemia that develops after birth. These interventions expose the baby to several blood donors, hence the risk of infection and exchange transfusions. This study was performed to test whether the use of high-dose intravenous immunoglobulin soon after the birth of these infants reduced the need for exchange transfusions. After randomization, intravenous immunoglobulin was given at a dose of 500 mg/kg to 22 infants in the treatment group. Nothing was given to the 19 controls. The number of exchange transfusions needed decreased significantly in the treatment group. No side-effects of intravenous immunoglobulins were seen. To compare the efficacy of antiprogesterone (mifepristone) in combination with a synthetic prostaglandin E1 analogue (misoprostol) for outpatient treatment of miscarriages.
                One hundred and twenty-two women with first trimester miscarriages.
                The women were randomised to treatment with mifepristone 400 mg orally followed by a single oral dose of 400 microg misoprostol 48 hours later (n = 60) or expectant management (n = 62). Women were re-evaluated five days later. If retained intrauterine products of conception were found with an antero-posterior diameter above 15 mm on transvaginal ultrasound, surgical evacuation was performed.
                Eighty-two percent of the women randomised to pharmacological treatment and 76% of those randomised to expectant management had an empty uterine cavity after five days. Convalescence time was 1.8 days longer for women randomised to pharmacological treatment. Pain, bleeding, complications, and satisfaction with the treatment did not differ between the groups.
                Most cases of spontaneous incomplete miscarriage will become a complete miscarriage without intervention. This study shows that outpatient treatment with a combination of antiprogesterone and a prostaglandin E1 analogue did not increase the rate of complete miscarriage, compared with expectancy alone, by a clinical important degree.
There are insufficient data available to evaluate the practice of anti-D administration in an unsensitised Rh-negative mother after spontaneous miscarriage. Thus, until high-quality evidence becomes available, the practice of anti-D Immunoglobulin prophylaxis after spontaneous miscarriage for preventing Rh alloimmunisation cannot be generalised and should be based on the standard practice guidelines of each country.