M. D. G. Gillmer

Prenatal sex determination from maternal peripheral blood using the polymerase chain reaction

We have investigated the use of a nested polymerase chain reaction assay for the detection of a fetal-specific Y-chromosomal sequence (DYS14) from DNA extracted from unsorted maternal peripheral blood. Serial dilutions of male DNA into female cord blood DNA indicated that the assay could detect an equivalent of a single male cell in 300000 female cells. The assay exhibited absolute specificity for male DNA with no amplification from a DNA panel obtained from 10 female cord blood samples. When used on DNA extracted from unsorted peripheral blood from a series of pregnant women, the predictive values of a positive test for a male fetus were 86%, 67% and 87% in the first, second and third trimesters, respectively. We have also demonstrated that retesting the samples allows the detection of a proportion of male-bearing pregnancies with a high degree of accuracy, in that all 15 women who gave positive signals in two consecutive amplifications had male fetuses. We have also applied the test at 8 weeks post-partum to eight women who had previously delivered male babies; no Y-specific signal could be detected in any of them, suggesting that most women have cleared their circulation of fetal cells by 8 weeks after parturition.

Changes in fetal monitoring practice in the UK: 1977-1984.

A postal survey was undertaken between 1985 and 1987 to assess the changes that have taken place in fetal monitoring practice since 1977. Replies were received from 253 (92%) of 276 consultant obstetric units canvassed. Biophysical methods of assessing fetal well‐being in the antepartum period are almost universally employed and are accepted as the best discriminators of the need to deliver the pregnancy. The number of fetal heart rate monitors on labour wards has increased by 88%. Overall, 63% of units monitor more than 60% of their patients in labour, and 87% permit suitably trained midwives to apply fetal scalp electrodes, which must now be regarded as standard practice. There is still a need for a simplified technique for fetal blood sampling. The perinatal mortality rate correlates with a prematurity factor and probably bears a greater relation to the population served than to the degree of monitoring provided.

Prenatal Determination of Fetal Rhesus D Status by DNA Amplification of Peripheral Blood of Rhesus‐Negative Mothers

We have developed a sensitive PCR-based assay for the RhD gene and used it to detect circulating fetal cells from RhD-positive fetuses from peripheral blood of RhD-negative mothers. With further improvement in diagnostic accuracy, this assay may have implications in the management of RhD-sensitized pregnancies in women whose partners are heterozygous for the RhD gene. Further studies are required to determine the relationship between maternal anti-D levels and circulating fetal cell numbers.

Caesarean Section for Fetal Distress, the Interval From Decision to Delivery, and the Relative Risk of Poor Neonatal Condition

SummarySummaryThere were 9387 deliveries within the study period, of which 104 (1·1 per cent) were caesarean sections for fetal distress in labour, with a singleton cephalic presentation at 37 or more weeks gestational age. Caesarean section for fetal distress was associated with a significant increase in the incidence of poor neonatal condition as defined by low Apgar scores (P<0·-001) or special care baby unit admission for asphyxia (P<0·001): but not with any increased incidence of fetal scalp blood or umbilical arterial or venous acidaemia.There was an association (P<0·05) between the interval between decision to deliver and operative delivery, and admission to the special care unit. The relative risk doubled between a 10 and a 35 minute interval. No correlation was found between the decision delivery interval and 1 or 5 minute Apgar scores, or cord arterial and venous acid-base results.A short interval from decision to delivery may be important if optimal neonatal condition is to be achieved.

Interruption of first trimester human pregnancy following Epostane therapy. Effect of prostaglandin E2 pessaries

Summary. The effect of Epostane, a competitive inhibitor of the 3β hydroxy steroid dehydrogenase enzyme system in combination with prostaglandin E2 (PGE2) for induction of abortion in early first trimester pregnancy has been studied in a group of 20 women awaiting termination of pregnancy. The women were consecutively assigned to four treatment groups. The first group was treated with PGE2 alone, administered vaginally as a lipid based (Witepsol) pessary. The remaining three groups received Epostane at differing doses for 5 days, and were treated with PGE2 on the fourth day. Significant falls in serum progesterone and oestradiol occurred in the Epostane‐treated patients. Abortion was induced in one of the five control patients and in three of 10 patients treated with low doses (300–400 mg) of Epostane. Intra‐utrine pressure monitoring showed an increased reactivity to PGE2 in the treated groups. At the highest dose (600 mig) of Epostane, serum progesterone and oestradiol showed the greatest decline to 8% and 21% of the pretreatment values, a prompt and sustained pressure response occurred to PGE2 and abortion was induced in all five patients. A critical degree of progesterone suppression appears to sensitize the myometrium to exogenous prostaglandin. This combined treatment is an effective method of early pregnancy termination and may have a role in the management of mid‐trimester abortion.

Endometrial hyperplasia and adenocarcinoma during tibolone (Livial) therapy.

duction. Although this would be consistent with the rise in MSAFP that is well described in association with invasive techniques, such as chorion villus sampling, in multifetal pregnancy reduction care was taken to avoid puncture of the placentae of the surviving fetuses. Therefore, the high levels of MSAFP are unlikely to be the consequence of disruption in the feto-maternal barrier and chronic leakage from the live fetuses to the mother across the placenta; the half-life of alpha-fetoprotein in the maternal circulation is only four to five days (Sappala & Ruoslahti 1973). Furthermore, there was a significant association between MSAFP and number of dead fetuses. The most likely explanation for high MSAFP following reduction is increased concentration of alpha-fetoprotein in the amniotic fluid due to tissue breakdown from the dead fetuses; MSAFP returns to the normal range 8 to 12 weeks after the reduction because by this time there is complete resorption of the dead fetuses. Previous studies have reported high levels of alpha-fetoprotein in the amniotic fluid of twin pregnancies after the spontaneous

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.

Inhibition of 3β-hydroxysteroid dehydrogenase (3β-HSD) activity in first- and second-trimester human pregnancy and the luteal phase using Epostane*

The effects of a competitive inhibitor of 3 β -hydroxysteroid dehydrogenase (3 β -HSD) (Epostane, Sterling Winthrop, Guildford, England) on serum progesterone (P), estradiol (E 2 ), and cortisol have been studied in three groups of pregnant women awaiting termination of pregnancy (5 to 8 weeks, 8 to 12 weeks, and 12 to 18 weeks of pregnancy) and 15 women in the luteal phase of the menstrual cycle. A single-dose randomized double-blind study was performed, each woman receiving a placebo, 50mg of Epostane, or 100mg of Epostane. In the pregnant group, there was a significant decline in the serum P concentration after both 50mg and 100mg of Epostane. The percentage fall increased with both drug dosage and advancing gestation. A similar fall in serum E 2 was observed. Both of these effects were temporary. In the luteal phase group, a significant decline in serum P was observed after 100mg of Epostane, but the serum E 2 was not significantly different from the pretreatment concentration. Serum cortisol did not differ significantly from control values. These findings suggest that Epostane is an effective inhibitor of placental and ovarian 3 β -HSD, which may have a role as an interceptive agent.

A comparison of the effects of four intravenous solutions for the treatment of ketonuria during labour

Summary. Forty women in whom ketonuria was detected during the first stage of labour were allocated randomly to intravenous treatment with one litre of either normal saline. Hartmanns solution, 5% dextrose or 10% dextrose. The solutions were administered over 1 h and blood was taken immediately beforehand and thereafter at 30‐min intervals for 90 min to assess their effect on intermediary metabolism, plasma osmolality and acid‐base status. Although both the 5 and 10% dextrose infusions caused a rapid decline in whole blood d‐3‐hydroxybutyrate concentrations, they also produced pathological degrees of maternal hyperglycaemia and hyperinsulinaemia and a marked elevation in the mean blood lactate and pyruvate concentrations. Administration of 10% dextrose was also associated with a significant increase in serum osmolality. Hartmanns solution produced significantly higher mean whole blood lactate and pyruvate concentrations than did normal saline. There was a significant increase in the venous base deficit in the group infused with 10% dextrose, indicating that the buffering capacity of the blood had been exceeded. It is concluded that rapid infusions of dextrose or Hartmanns solution should not be administered during labour. Normal saline should be used for rehydration and if dextrose therapy is deemed necessary the dose administered should not exceed physiological requirements.

Myometrial activity in first trimester human pregnancy after Epostane therapy. Effect of intravenous oxytocin.

Summary. The effect on myometrial activity of Epostane, a competitive inhibitor of the 3β‐hydroxy steroid dehydrogenase enzyme system (3β‐HSD) has been studied in 20 women awaiting termination of pregnancy. The women were randomly allocated by a double‐blind procedure into two groups. In the Epostane‐treated group there were significant falls in serum progesterone and oestradiol concentrations after 3 days of treatment. The placcbo‐treated group showed a small but significant decline in serum progesterone concentration. Insertion of an intrauterine balloon catheter for pressure measurements produced significantly greater uterine activity in the Epostane‐treated group. The oxytocin response was variable and there was no significant difference between the two groups. A small rise in the peripheral plasma concentration of a prostaglandin F20r metabolite (PGFM) was observed in the placebo group following oxytocin injection. There was a significant inverse correlation between post treatment progesterone values and uterine activity. Epostane appears to sensitize the myometrium to endogenous oxytocics and this probably results from progresterone ‘withdrawal’. This effect may prove useful in potentiating the action of exogenous myometrial stimulant5, such as prostaglandins, and may have a role in the termination of early pregnancy.