Andrew A. Calder

Placental 11β‐hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure

OBJECTIVE Placental 11β‐hydroxysteroid dehydrogenase (11β‐HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11β‐HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas.

Neutrophil activation in pregnancy-induced hypertension

Summary. Human neutrophil elastase may be a major mediator of vascular damage and could contribute to the vascular damage seen in women with pregnancy‐induced hypertension (PTH). Elevated plasma levels of this substance will reflect neutrophil activation in vivo. To determine neutrophil activation in PIH, we studied 30 normal nonpregnant women, 32 women with normal pregnancies, 19 with mild/moderate PIH and 16 with severe PIH between 28 and 39 weeks gestation. Plasma neutrophil elastase was measured by radioimmuno‐assay. There was a significantly higher concentration of plasma neutrophil elastase in both mild/moderate and severe PIH than in normotensive pregnancies and this may contribute to the vascular lesion associated with PIH. Concentrations were also significantly higher in normal pregnancy than in non‐pregnant women which suggests that neutrophil activation and degranulation are increased in normal pregnancy.

Choriodecidual production of interleukin-8 and mechanism of parturition

Both prostaglandins and antiprogestagens can induce labour and ripen the cervix, but the mechanisms are unclear. The collagenases that bring about cervical ripening are neutrophil derived. We examined the potential of uterine tissues to control neutrophil attraction by measuring interleukin-8 production. Choriodecidual cells in culture produced substantial amounts of interleukin-8; release was inhibited by progesterone and stimulated by the antiprogestagen mifepristone. Interleukin-8 production was similar in cells from spontaneously delivered placentas and from those obtained at caesarean section. Since prostaglandin E and interleukin-8 have synergistic effects, we suggest that interleukin-8 activity is the final common step of prostaglandin and antiprogestagen action in parturition.

Sleep-disordered breathing and upper airway size in pregnancy and post-partum

Sleep-disordered breathing and snoring are common in pregnancy. The aim of this study was to determine whether pregnancy was associated with upper airway narrowing. One-hundred females in the third trimester of pregnancy were recruited and 50 agreed to be restudied 3 months after delivery. One-hundred nonpregnant females were also recruited. Upper airway dimensions were measured using acoustic reflection. Snoring was less common in nonpregnant (17%) than pregnant females (41%; odds ratio (OR) 3.34; 95% confidence interval (CI) 1.65–6.74) and returned to nonpregnant levels after delivery (18%; OR 0.15; 95% CI 0.06–0.40). Pregnant females had significantly smaller upper airways than nonpregnant females at the oropharyngeal junction when seated (mean difference 0.12; 95% CI 0.008–0.25), and smaller mean pharyngeal areas in the seated (mean difference 0.14; 95% CI 0.001–0.28), supine (mean difference 0.11; 95% CI 0.01–0.22) and lateral postures (mean difference 0.13; 95% CI 0.02–0.24) compared with the nonpregnant females. Pregnant females had smaller mean pharyngeal areas compared with post-partum in the seated (mean difference 0.18; 95% CI 0.02–0.32), supine (mean difference 0.20; 95% CI 0.06–0.35) and lateral postures (mean difference 0.26; 95% CI 0.12–0.39). In conclusion, this study confirmed increased snoring and showed narrower upper airways during the third trimester of pregnancy.

Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A

BACKGROUND AND OBJECTIVE Prenatal maternal serum screening for Downs syndrome has become an important and established part of modern antenatal care. Previously it has been reported that non‐specific immunoreactive inhibin may be useful in this context. Using a novel assay we have evaluated dimeric inhibin A as a possible second trimester marker of Downs syndrome.

The effects of mifepristone on cervical ripening and labor induction in primigravidae.

Objective To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices. Methods This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were randomly assigned to one of three treatment groups. They were assessed at 24-hour intervals for 72 hours, after which labor was induced if it had not occurred spon-taneously. Results Two hundred milligrams of mifepristone resulted in a favorable cervix (with a Bishop score greater than 6 or in spontaneous labor) in significantly more women than placebo (P = .01). An improvement in cervical ripening was seen in the group given 50 mg of mifepristone, but this was not statistically significant. There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo, but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome. Conclusion Mifepristone, a progesterone antagonist, is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity. It is theoretically attractive for use as an adjunct in cervical priming and labor induction. In this study, 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo.

Recombinant human relaxin as a cervical ripening agent

Objective The aim of this study was to investigate the efficacy and safety of recombinant human relaxin (rhRIx) as a cervical ripening agent in women with an unfavourable cervix before induction of labour at term.

PROSTAGLANDINS AND THE UNFAVOURABLE CERVIX

The prostaglandins(PGs), unlike oxytocin, are powerful stimulants of uterine contractility in early, middle, and late pregnancy. This characteristic has led to the use of PGs as agents for termination of mid-trimester pregnancy. For this purpose, local routes of administration--extraamniotic or intraamniotic--have proven superior to intravenous administration. PGs have proven particularly useful in inducing labor in cases of fetal death in utero, fetal anomaly such as anencephaly, or in complications of pregnancy. PGE was administered extraamniotically to induce labor in cases of fetal death, anencephaly, and hydatidiform mole. The method was similar to that employed for 2nd trimester abortion, i.e., introduction of a Foley catheter through the cervix and retention of the catheter with a balloon. A similar method, minus the balloon, was used for 40 cases at or near term. These studies led to the conclusion that the Foley catheter might be particularly useful in inductions under unfavorable cervical conditions, i.e., cases where the cervix has not dilatated at all or hardly at all. Infusion of PGE2 in 7 cases with very low Bishop cervical scores proved successful in all cases. The exact infusion procedure is explained. The use of a Foley catheter with a balloon is known to have a ripening effect on the cervix. Combination with local PG administration seems to be particularly effective in causing cervical dilatation.

Transabdominal cervico-isthmic cerclage in the management of cervical incompetence

The use of transabdominal cervico-isthmic cerclage is described in 13 patients with a diagnosis of cervical incompetence. The patients were recruited from seven Scottish Maternity Units over a period of 10 years. The 13 patients have had a successful pregnancy in 86.6% of pregnancies with this procedure compared with a success rate of 16% in their previous pregnancies. In carefully selected cases transabdominal cervico-isthmic cerclage is a worthwhile procedure in patients with cervical incompetence when the cervix is so damaged that it would be impossible to insert a vaginal suture or when a vaginal suture has previously failed.

Prostaglandins and Biological Control of Cervical Function

Summary: The uterine cervix is a vital structure for the success of pregnancy. It must remain firmly closed to contain the developing conceptus within the uterus until the fetus has grown to a stage of maturity appropriate for extra‐uterine survival. During the birth process itself, the cervix must undergo the rapid opening known as dilatation to allow the fetus to travel through the birth canal with a minimum of stress and trauma.