M. Selinger

Serial fetal blood sampling for the management of pregnancies complicated by severe rhesus (D) isoimmunization

Summary. Fifty‐one pregnancies complicated by rhesus (D) isoimmunization have been managed by serial fetal blood sampling between 17 and 36 weeks gestation as an alternative to amniocentesis for ΔOD453 measurements. In 36 pregnancies where the fetus was shown to be rhesus (D) positive and both measurements were made before any intrauterine fetal transfusions, the ΔOD453 value gave misleading predictions on 13 of 63 occasions (21%). Fetal haematocrit estimations provided a direct assessment of the haemopoietic compensation occurring, but fetal bilirubin and albumin concentrations did not correlate directly with disease severity. It is proposed that pregnancies complicated by severe isoimmunization can be more precisely managed by serial fetal blood sampling for haematocrit estimation than amniocentesis for ΔOD453 measurement thus avoiding unnecessary intervention or delayed treatment.

The placental transfer of mifepristone (RU 486) during the second trimester and its influence upon maternal and fetal steroid concentrations

Summary. A double‐blind, placebo‐controlled study has assessed the maternal and fetal endocrine effects of the maternal administration of the anti‐progestin mifepristone in mid‐pregnancy. There were six women in each group. Four hours after oral administration of 600 mg mifepristone, the drug was detected in both maternal and fetal circulations and in the amniotic fluid. No significant changes in progesterone, cortisol, oestradiol, or aldosterone concentrations were detected in the maternal circulation after treatment with mifepristone or placebo. In women treated with mifepristone, the mean fetal aldosterone level was 1699 (SD 217) pmol/1 which was significantly higher than the mean level of 999 (SD 84) pmol/1 in the control group but no significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour.

Progesterone inhibition in mid-trimester termination of pregnancy: physiological and clinical effects.

Summary. A double‐blind, placebo controlled clinical trial was conducted to assess the clinical and physiological effects of‘epostane’, a progesterone synthesis inhibitor, in mid‐trimester prostaglandin termination of pregnancy. Mean peripheral progesterone levels had fallen by 74% after 72 h in the patients treated wtih epostane. The mean induction abortion interval in the treatment group was 490 (SD 271) min, compared with 1432 (SD 640) min in the control group. Intrauterine pressure recording demonstrated increased sensitivity to prostaglandin E2 after epostane treatment but no change in oxytocin sensitivity. The clinical implications of facilitated induction of abortion are discussed.

Immunoprophylaxis for rhesus disease—expensive but worth it?

In little over half a century obstetricians have progressed from being perplexed by a disease of unknown aetiology to a useful understanding of rhesus(D) alloimmunization. Screening, investigation and management have been refined but anti-D prophylaxis remains the major effector in prevention. Post-natal and ‘sensitizing event’ prophylaxis should be an aim of health care systems in developing countries where rhesus disease is perceived as a significant problem. Haemolytic disease of the newborn (HDN) is caused by antibodies resulting from maternal sensitization following two feto-maternal haemorrhages (F-MH) when the fetus is rhesus positive and the mother rhesus negative. Antibody production following initial sensitization is usually slow and modest whereas a second sensitizing stimulus can lead to very high anti-D levels. The volume of F-MH required to provoke the sensitization is much smaller than that causing initial sensibilization and secondary sensitization occurs most frequently at delivery (MacKenzie et al. 1991). Fortunately, immunoprophylaxis is possible by providing the mother with enough exogenous anti-D to remove all the Rh negative cells resulting from an ‘average’

Antenatal fetal blood sampling for the management of alloimmunized pregnancies: effect upon maternal anti-D potency levels

Summary. Increase in maternal anti‐D concentrations after intrauterine investigation has been studied retrospectively in 95 rhesus (D) alloimmunized pregnancies; 48 were managed by fetal blood sampling (FBS) procedures (using fetoscopy or ultrasound‐guided needle sampling) and 47 using amniocentesis. In those pregnancies where the fetus was rhesus (D) positive, the frequency of procedure‐related increases (>50%) in maternal anti‐D potency was estimated following single procedures and found to be similar for the two methods of FBS employed (28%) and for amniocentesis (31%). The proportion of pregnancies showing an increase in anti‐D potency was higher after ultrasound‐guided needle sampling (75%) than after fetoscopic FBS (40%) and after amniocen tesis (44%).

Mid-trimester termination of pregnancy with 16,16-dimethyl-trans-Δ2 PGE1 vaginal pessaries: A comparison with intra- and extra-amniotic prostaglandin E2 administration

PGE1 analogue (gemeprost) vaginal pessaries administered three hourly for three doses has been compared with a single extra‐ or intra‐amniotic injection of PGE2 for mid‐trimester termination of pregnancy in 450 women between 13 and 20 weeks gestation. The mean (SD) induction‐abortion interval (IAI) in the vaginal pessary group of 19.5 (8.4) h was significantly longer than the respective intervals of 14.4 (9.3) and 16.1 (6.8) h in the patients treated extra‐ or intra‐amniotically (P < 0.001). Seventy‐three percent treated with gemeprost aborted within 24 h of initial treatment compared with 84% and 87%, respectively in the extra‐ and intra‐amniotic groups (P < 0.05). Patients treated with gemeprost were more likely to need further prostaglandin treatment and had an increased incidence of gastrointestinal side effects. Despite these differences vaginal gemeprost pessaries provide a safe, effective, easy to administer method for midtrimester termination of pregnancy.

Management of intra-uterine fetal death with vaginal administration of gemeprost or prostaglandin E2: A random allocation controlled trial

SummarySixty-nine patients with a confirmed intra-uterine fetal death in the second or third trimester of pregnancy were allocated at random to receive the prostaglandin E, analogue gemeprost, 1 mg vaginally three hourly for three doses, or a single vaginal insertion of prostaglandin E2, 25 mg as a pessary or as a gel. Intravenous oxytocin was given 15–20 h later if necessary. All pregnancies were successfully expelled using each of the three regimens employed. There were no differences between the induction-expulsion intervals between the three groups: the median interval for all the patients was 14–4 ± 9–6 h (s.d.). Delivery within 24 h of prostaglandin treatment occurred in 16/20 of the gemeprost patients and 20/27 and 19/22 respectively in the prostaglandin E2 pessary and gel groups. There were no differences in the incidences of gastrointestinal side effects or analgesic requirements between the three groups. Overall 17/69 patients required surgical evacuation of the uterus for immediate incomplete a...

Anti‐D concentrations in fetal and maternal serum and amniotic fluid in rhesus allo‐immunised pregnancies

Objective To investigate the relation between anti‐D concentrations in maternal serum, fetal serum and amniotic fluid, and the development of fetal anaemia.

The effect of epostane, a 3-beta hydroxy steroid dehydrogenase inhibitor, on maternal and fetal steroid levels during mid-gestation

Summary. A double‐blind, placebo‐controlled trial was conducted to assess the maternal and fetal endocrine effects of epostane, an inhibitor of progesterone synthesis, in mid‐pregnancy. Although present in the maternal circulation, epostane was not detected in cord blood or amniotic fluid. Maternal and fetal progesterone levels fell by 80% and 95% respectively with maintenance of the fetal arterio‐venous difference while oestradiol and aldosterone levels were affected to a lesser extent. The mechanism of 3‐beta hydroxy steroid dehydrogenase suppression and the relation between fetal and maternal progesterone levels are discussed.

The Placental Transfer of Mifepristone (RU 486) during the Second Trimester and Its Influence upon Maternal and Fetal Steroid Concentrations

A double-blind, placebo-controlled study has assessed the maternal and fetal endocrine effects of the maternal administration of the anti-progestin mifepristone in mid-pregnancy. There were six women in each group. Four hours after oral administration of 600 mg mifepristone, the drug was detected in both maternal and fetal circulations and in the amniotic fluid. No significant changes in progesterone, cortisol, oestradiol, or aldosterone concentrations were detected in the maternal circulation after treatment with mifepristone or placebo. In women treated with mifepristone, the mean fetal aldosterone level was 1699 (SD 217) pmol/l which was significantly higher than the mean level of 999 (SD 84) pmol/l in the control group but no significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour.