Serum inhibin A and activin A concentrations increase in pre-eclampsia. We investigated the time courses of the changes in relation to the onset of the maternal syndrome and if their measurement could be useful for clinical prediction particularly in relation to early onset disease, the most severe of the clinical presentations. Serial samples were taken from 1496 healthy nulliparae. Changes in activin A and inhibin A were analysed in women with: early onset pre-eclampsia (n = 11), pre-eclampsia delivering at 34-36 weeks (n = 14), term pre-eclampsia (n = 25) and gestational hypertension (n = 25); and in a subset with uncomplicated pregnancies (n = 25). Serum inhibin A and activin A were increased in all groups prior to pre-eclampsia, before 20 weeks in those with early onset pre-eclampsia. Screening efficacy was determined at 15-19 and 21-25 weeks in all women who developed pre-eclampsia (n = 70) and randomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for early onset pre-eclampsia: 67 and 44% at 15-19 weeks and 89 and 89% at 21-25 weeks for inhibin A and activin A respectively. Hence, serum inhibin A and activin A concentrations increase before the onset of pre-eclampsia at gestational ages that depend on when pre-eclampsia develops. On their own such measures are unlikely to prove efficient for screening.

Objectives To determine: 1. whether an alternative definition of gestational hypertension and preeclampsia stratifies women according to their risk of maternal and fetal complications; 2. whether pregnancy outcome in women with gestational hypertension differs in the presence or absence of '+' proteinuria; and 3. whether a blood pressure rise of 2 30/15 mmHg during pregnancy is associated with adverse outcome in women who remain normotensive.Design Prospective, nested case-control study.Setting Community based.Population Healthy, nulliparous women (n = 1496).Methods Women recruited into a study investigating serum markers predictive of pre-eclampsia were classified as having gestational hypertension (systolic blood pressure 2 140 mmHg with a rise of 2 30 mmHg and/or diastolic blood pressure 2 90 mmHg with a rise of 2 15 mmHg) or pre-eclampsia (gestational hypertension plus proteinuria 2 2+on dipstick or > 0.3 g/24 h). Maternal and fetal complications in gestational hypertension or pre-eclampsia were compared with a control group of 223 randomly selected normotensive women. The main outcome measures were severe maternal disease, preterm birth and small for gestational age infant.Results A stepwise increase in adverse maternal and fetal outcomes occurred in gestational hypertension ( n = 117,743%) and pre-eclampsia (n = 71,4.8%). Severe maternal disease developed in 26.5% (2 1.4% severe hypertension alone, 5.1 % multisystem disease) of women with gestational hypertension and 63.4% (21.1% severe hypertension alone, 42.3% multisystem disease) of women with preeclampsia (OR 4.8; 95% CI 2.49.5). Preterm birth and small for gestational age infants were more frequent in gestational hypertension (OR 1.7; 95% CI 0.5-5.4, and OR 2.0; 95% CI 1.0-3.7, respectively) and pre-eclampsia (OR 14.6; 95% CI 5.8-37.8, and OR 2.6; 95% CI 1.2-5.3) than in the normotensive group. Among women with gestational hypertension severe maternal disease was more common in women with '+' proteinuria (41.7%) than in those with no proteinuria (15.9%): OR 3-8; 95% CI 1.5-9.8. Pregnancies were uncomplicated in the 27% of normotensive women who had a rise of 2 30 mmHg systolic blood pressure and/or 2 15 mmHg rise in diastolic blood pressure. ConclusionsIn the nulliparous population studied our definition of gestational hypertension and preeclampsia identified women at increasing risk of maternal and fetal complications. In gestational hypertension, the presence of proteinuria '+' was associated with a 3.8-fold increase in severe maternal disease. Normotensive women who have a rise in blood pressure 2 30/15 mmHg had uncomplicated pregnancies.

The effects of fetal infusions of cortisol and thyrotropin-releasing hormone (TRH) singly and together on pressure-volume relationships and saturated phosphatidylcholine (SPC) concentrations in the lungs were studied in 28 fetal sheep delivered at 128 days of gestation. Four groups each of 7 fetuses were infused with either saline (for 156 h), TRH (25 micrograms/h in 60-s pulses for 156 h), TRH (for 156 h) combined with cortisol (1 mg/h for 84 h), or cortisol (for 84 h). Cortisol had no effect on SPC concentrations, whereas both TRH and cortisol plus TRH increased the concentration of SPC in lavage fluid but not lung tissue. Neither cortisol nor TRH significantly affected lung distensibility [V40; 0.64 +/- 0.04 and 0.57 +/- 0.10 (SE) ml/g, respectively, vs. 0.41 +/- 0.03 ml/g in controls] or stability (V5; 0.24 +/- 0.01 and 0.35 +/- 0.07 ml/g vs. 0.24 +/- 0.03 ml/g), whereas treatment with a combination of the two hormones was associated with a fourfold increase in V40 (1.70 +/- 0.16 ml/g) and V5 (1.03 +/- 0.15 ml/g). Since raised concentrations of cortisol, triiodothyronine, and estradiol-17 beta (treatment with cortisol) had no effect on V40 and V5, whereas similar hormonal changes associated with elevated prolactin levels (treatment with cortisol plus TRH) had marked effects, we conclude that prolactin plays an essential part in the synergism of cortisol and TRH.

Cortisol has minimal effects on lung maturation in fetal sheep before 130 days gestation. To test whether there is enhancement of cortisol action by other hormones, cortisol (F), triiodothyronine (T3), epinephrine (E), prolactin (PRL), and epidermal growth factor (EGF), alone or in combination, were infused into fetal sheep for 84 h between 124 and 128 days gestation. A mixture of F + T3 + PRL, but not any combination of two hormones, increased both distensibility [1.71 +/- 0.12 (SE) ml of air/g wet wt at 40 cmH2O, V40] and stability (1.16 +/- 0.09 ml of air per g wet wt at 5 cmH2O, V5) to near full-term values, above values resulting from treatment with F alone (0.91 +/- 0.12 and 0.43 +/- 0.09 ml/g, P less than 0.01). Only F had an effect when given alone, V40 increasing (P less than 0.05). Treatment with F + T3 (0.81 +/- 0.18 ml/g) and F + E (0.77 +/- 0.07 ml/g) increased V5 above values obtained with F alone (P less than 0.05). Alveolar saturated phosphatidylcholine (SPC) was higher after treatment with F + T3 (161 +/- 52 micrograms/g), F + T3 + PRL (156 +/- 53 micrograms/g, P less than 0.05), and F + E (113 +/- 40 micrograms/g, P = 0.07) than after F (12 +/- 3 micrograms/g). We conclude that F, T3, and PRL have a synergistic effect on the development of distensibility and stability of the ovine fetal lung.

ABSTRACT. The ontogenesis of elastin and collagen accumulation and growth of the lung were studied in Wistar rats from day 18 of gestation until day 30 postnatally. Dexamethasone phosphate 0.1 mg or normal saline solution every 8 h for three doses was injected into pregnant rats on day 17. The effects of treatment, age, and sex on lung wet weight, lung dry weight, body weight, DNA, protein and desmosine (estimated by radioimmunoassay), and hydroxyproline were determined in the offspring. Dexamethasone inhibited lung growth and, to a lesser extent, body weight gain. While lung wet weight, lung dry weight, and body weight remained significantly reduced until postnatal day 15, the lung weightlbody weight ratio was depressed only until postnatal day 5. The lung dry weight/ lung wet weight ratio was decreased on day 20 of gestation and at birth. DNA concentration remained slightly but significantly reduced throughout the study period. Exogenous glucocorticoids accelerate fetal lung maturation in many species including humans (1) and rats (2) and are used to advance lung maturation in the human fetus at risk of preterm delivery. Inhibition of lung growth after prenatal exposure to glucocorticoids has been observed in rabbits (3), rats (4, 5 ) , and monkeys (6) and has given rise to concern for the human fetus exposed to such therapy.One question that arises from these findings in animals is whether "catch-up growth" occurs after the inhibitory effect of glucocorticoids on growth has ceased. Investigations of weight and DNA concentrations have led to the conclusion that catchup growth of the lung occurs after glucocorticoid administration in the pseudoglandular phase in the rabbit (3) and in the canalicular-saccular period in the rat (7). However, to establish whether catch-up growth entails normal structural differentiation, mor-