Wendy B. Warren

Elevated maternal plasma corticotropin-releasing hormone levels in pregnancies complicated by preterm labor

Objectives: We investigated whether maternal plasma levels of the placental hormone corticotropin-releasing hormone are elevated in pregnancies complicated by preterm labor. Study design: Mean maternal corticotropin-releasing hormone levels were studied in women who met specific criteria for preterm labor and in women with normal pregnancies. Levels were also compared in the latent and active phases during term labor. Results: In pregnancies complicated by preterm labor, maternal corticotropin-releasing hormone levels were higher than in normal pregnancies; this elevation occurred before labor was diagnosed clinically ( p Conclusion: Maternal plasma corticotropin-releasing hormone levels are elevated in association with preterm labor. This elevation does not appear to be due to labor itself and may reflect an early activation of the placenta before the onset of preterm labor.

Concentrations of corticotrophin-releasing hormone in the umbilical-cord blood of pregnancies complicated by pre-eclampsia

The effect of pre-eclampsia on concentrations of corticotrophin releasing hormone (CRH) in umbilical-cord blood of fetuses at delivery was studied in order to determine if fetal CRH is elevated in this disorder when compared with uncomplicated pregnancy. Placental CRH may be a regulator of fetal pituitary-adrenal function and we therefore also measured ACTH, cortisol and dehydroepiandrosterone sulfate (DHEAS) in the umbilical-cord blood. The mean umbilical-cord plasma CRH in the fetuses from pregnancies complicated by pre-eclampsia, 667 +/- 153 pg mL-1, was significantly higher than the plasma CRH in the fetuses from normotensive pregnancies, 185 +/- 22 pg mL-1 (P < 0.001). The mean fetal cortisol concentration was significantly higher in pre-eclampsia, than in the normotensive, pregnancies (pre-eclampsia, 13.5 +/- 1.8; normotensive, 7.6 +/- 1.3 micrograms dL-1; P < 0.001). Plasma DHEAS was 217 +/- 23 micrograms dL-1 in the umbilical-cord blood of the fetuses from pregnancies complicated by pre-eclampsia and 281 +/- 35 micrograms dL-1 in the normotensive pregnancies (P < 0.01). Placental CRH synthesis and release, in contrast to hypothalamic CRH, appears to be stimulated by glucocorticoids. In pregnancies complicated by uteroplacental insufficiency, as may occur in pre-eclampsia, placental CRH production may be enhanced by increased fetal glucocorticoids. In turn, placental CRH may modulate fetal pituitary-adrenal steroidogenesis to favour increased cortisol secretion. Thus, placental CRH may play an important role in the fetal response to a compromised intrauterine environment.

Placental Corticotropin-Releasing Hormone and Pituitary-Adrenal Function during Pregnancy

The placenta secretes large amounts of the hypothalamic releasing hormone, corticotropin-releasing hormone (CRH), into both the maternal and fetal circulation during pregnancy. We characterized the relationship between maternal plasma CRH and products of the pituitary and adrenal in order to investigate the physiologic role of placental CRH in modulating maternal pituitary-adrenal function. Plasma was obtained from 8 women at biweekly intervals between 21 and 40 weeks of full-term pregnancy for CRH, adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha MSH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) measurements by radioimmunoassay. Eighteen women were also studied once at 22-34 weeks of pregnancy with plasma CRH and 24-hour urinary free cortisol measurement. Eight nonpregnant women served as control subjects. Plasma CRH was undetectable in the nonpregnant subjects and rose over the time period studied in the pregnant women. Concentrations of afternoon ACTH and cortisol also rose during pregnancy while DHEAS levels declined in the pregnant women. The alpha-MSH levels were beneath the level of detection (< 20 pg/ml) in both the pregnant and nonpregnant subjects. The overall mean afternoon ACTH concentration was higher in the pregnant than in the nonpregnant women (11.4 +/- 1.8 vs. 5.9 +/- 1.8 pg/ml; p < 0.05), although the ACTH levels in both groups remained within the normal range. The mean plasma cortisol concentrations were higher in the pregnant women, while the mean DHEAS levels were lower in the pregnant women when compared to the nonpregnant subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of use of cocaine and other substances in an obstetric population

Increasing use of cocaine among pregnant women has been reported. This study was conducted to determine the prevalence of positive urine toxicologic screens for cocaine and other substances of patients admitted to the Sloane Hospital for Women. Urine samples were obtained from 509 women admitted to the delivery suite. The overall prevalence of cocaine was 10% (n = 51). Cocaine use was 10 times more prevalent in the clinic population (14%) than in the private population, (1.4%). In addition, women whose urine samples were positive for cocaine were more likely to have no prenatal care, previous induced abortions, to be human immunodeficiency virus-positive, and admitted previous use of cigarettes, alcohol, cocaine, and other drugs. Amphetamines were detected in 13% (n = 65) of patients. However, the screens did not distinguish between metabolites of amphetamines and other drugs such as cold medications. The medical history alone predicted only 37% (n = 19) of the cocaine-positive screens and none of the amphetamine-positive screens.

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension

OBJECTIVE We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. STUDY DESIGN Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. RESULTS Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. CONCLUSIONS Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

Elevated maternal plasma corticotropin releasing hormone levels in twin gestation

The placenta secretes large amounts of the hypothelamic hormone, corticotropin releasing hormone (CRH) into the maternal and fetal circulation during pregnancy. We and other investigators have shown that during normal pregnancy, maternal plasma CRH levels begin to rise in the second trimester with a dramatic increase in CRH levels during the 5-6 weeks preceding the onset of labor. This rise in maternal plasma CRH is parallel to the rise of placental CRH mRNA which has been reported to occur with gestational maturation. Mechanisms underlying the control of CRH secretion by the placenta have not yet been determined. In twin gestation, increased fetal-placental mass has been shown to be associated with elevated maternal levels of several placental hormones as compared to singleton gestation. We measured maternal plasma CRH in both twin and singleton gestation to investigate whether the larger size of the fetal-placental unit in twin gestation is associated with elevated maternal CRH levels. Seventy-six serial venous blood samples were collected from 20 women with twin gestation and 40 samples were obtained from 27 women with uncomplicated singleton gestation. Gestational age was determined by history of a known last menstrual period and first trimester clinical examination and confirmed by ultrasound examination. CRH was extracted from 1-2 ml plasma with SEP-Pak C18 cartridges and eluted with triethylamine-formic-acid propranolol. CRH was measured by radioimmunoassay (RIA) with human CRH standard and antiserum to human CRH raised in our laboratory. Mean CRH levels were calculated for four week intervals. In both singleton and twin gestation, the maternal plasma CRH levels increased with advancing gestational age. After 29 weeks of gestation, maternal plasma CRH levels in twin gestation were significantly higher than those in singleton gestation (p less than 0.01). At 37 to 40 weeks of gestation, mean maternal CRH was 1167 +/- 237 pg/ml in singleton gestation as compared to 6927 +/- 1725 pg/ml in twin gestation (p less than 0.05). In addition, the rapid rise in plasma CRH levels which occurs near term in singleton gestation, occurred earlier in twin gestation. This early rise in maternal CRH levels persisted when the data from twin pregnancies complicated by preterm labor were removed from the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of parturition on corticotropin releasing hormone and products of the pituitary and adrenal in term fetuses at delivery.

Corticotropin releasing hormone (CRH), a hypothalamic hormone which regulates pituitary-adrenal function, is also produced by the human placenta. We studied umbilical cord concentrations of CRH to determine whether placental secretion of this hormone into the fetal compartment is altered during parturition. We also measured adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandro-sterone sulfate (DHEAS) to determine whether levels of these pituitary and adrenal hormones were correlated to CRH in the fetal plasma. Blood was obtained from umbilical cords of 111 healthy term fetuses at delivery. Concentrations of CRH, ACTH, cortisol and DHEAS were measured by radio-immunoassay. Hormone levels were analyzed according to the presence of labor and delivery mode. In addition correlations between different hormones were determined. Fetal plasma CRH levels were similar for all conditions of labor and delivery as were levels of DHEAS. Fetal plasma ACTH and cortisol were increased after vaginal delivery. There were no significant correlations between placental CRH, ACTH and cortisol levels. However, an inverse correlation between fetal plasma CRH and DHEAS levels was found (r = -0.41, p < 0.001). Increases in ACTH during parturition are likely due to stimulated release by the fetal pituitary. Our data suggest that placental CRH does not mediate this acute response to the stress of parturition. We hypothesize that continuous stimulation of the pituitary and adrenal by circulating CRH during development may occur and the inverse correlation between fetal plasma CRH and DHEAS may be due to this chronic regulatory effect.