New approaches to the diagnosis of preterm labor.

There is a pressing need to develop accurate methods of diagnosing true preterm labor because of the availability of potent tocolytic drugs and the known beneficial effects of antenatal glucocorticoid administration on neonatal outcomes of premature infants. Maternal plasma corticotropin-releasing hormone concentrations are elevated in women with threatened preterm labor between 28 and 36 weeks' gestation who give birth within 24 hours. In addition, the ratio of cortisol to corticosteroid binding capacity is elevated in the plasma of women who give birth within 24 hours. These data support the design and conduct of a prospective clinical trial to determine the positive and negative predictive values of these markers for preterm birth in women with symptoms.

Antenatal glucocorticoid administration increases corticotrophin-releasing hormone in maternal plasma.

OBJECTIVE: This study was designed to determine whether maternal corticotrophin-releasing hormone (CRH) concentrations are altered after maternal betamethasone administration for fetal lung maturity in women with threatened preterm labour and whether these effects are dependent on gestational age. METHODS: Our study included 49 women with threatened preterm labour who received prenatal betamethasone for fetal lung maturity between 24 and 31 weeks of gestational age and 11 women who did not. Maternal blood was taken before and after glucocorticoid administration or at 24 hours after initial sampling. Plasma CRH, adrenocorticotrophin (ACTH) and cortisol concentrations were determined by radioimmunoassays. The women were stratified into 24-25 weeks, 26-27 weeks, 28-29 weeks, and 30-31 weeks completed gestation. RESULTS: At each gestational age, maternal cortisol concentrations decreased by approximately 85% after glucocorticoid administration. Overall mean cortisol values fell from 580.0 (SD, 351.8) to 89.7 (96.6) nmol/L (n = 40, P < 0.001). Overall mean ACTH values decreased from 9.9 (4.7) to 5.0 (3.4) pmol/L (n = 43, P < 0.001), and the approximate 50% decrease was similar at each gestational age. In marked contrast, overall mean CRH values increased from 58.0 (37.0) to 87.8 (68.6) pmol/L (n = 49, P < 0.001) after betamethasone administration. There was no change in maternal cortisol, ACTH or CRH values over 24 hours in women who did not receive betamethasone. CONCLUSIONS: We conclude that maternal betamethasone administration increases maternal plasma CRH values between 24 and 31 completed weeks of gestation.

Maternal corticotropin-releasing hormone is increased with impending preterm birth.

The objective of this study was to test the hypothesis that maternal CRH concentrations are elevated in women experiencing threatened preterm labor who subsequently give birth within 24 h compared to those in women who do not. We also characterized the changes in maternal plasma cortisol, ACTH, corticosteroid binding capacity (CBC), and CRH concentrations in 28 healthy pregnant women between 20-38 weeks gestation. Overall, maternal plasma CRH concentrations were significantly greater (P < 0.05) in those women giving birth within 24 h (1343.3 +/- 143.9 pg/mL; n = 81) compared to those in women who did not (714.5 +/- 64.8 pg/mL; n = 144) or those in normal subjects. This difference was present between 28-36 weeks, but not 24-28 weeks gestation. The ratio of maternal cortisol to CBC was also significantly greater (P < 0.05; 0.65 +/- 0.04; n = 82) in women giving birth within 24 h than in those who did not (0.55 +/- 0.02; n = 136). This difference was significant at all gestational ages studied. Elevated CRH concentrations and bioavailability of free cortisol may both be implicated in the pathogenesis of preterm labor in some women. Further prospective clinical trials are warranted to determine the positive and negative predictive values of maternal CRH concentrations and/or the ratio of cortisol/CBC for identifying women with threatened preterm labor destined to give birth within 24 h.

Effect of betamethasone in vivo on placental corticotropin-releasing hormone in human pregnancy.

OBJECTIVE: The objective was to determine the effects of in vivo administration of prenatal betamethasone in patients at 26 to 35 weeks' gestation on corticotropin-releasing hormone concentrations in maternal and fetal plasma and amniotic fluid, and on corticotropin-releasing hormone localization in placenta and fetal membranes. STUDY DESIGN: A total of 49 pregnant women at risk for preterm delivery between 26 and 35 weeks' gestation were studied. Twenty-six patients received betamethasone (12 mg intramuscularly) for stimulation of fetal lung maturity. Cord blood, amniotic fluid, placental tissue, and fetal membranes were obtained from 22 of these patients at delivery by elective cesarean section at 33.8+/-2.4 weeks' gestation. In control patients (n=23) at comparable gestational age, blood samples were taken for hormone analysis (n=8), and cord blood, amniotic fluid, and tissues were collected at elective cesarean section at 34.1+/-2.3 weeks' gestation. Concentrations of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol were determined by radioimmunoassay. Localization of tissue immunoreactive corticotropin-releasing hormone was assessed by immunohistochemistry. RESULTS: Betamethasone caused approximately 90% reduction in maternal cortisol and 50% reduction in maternal plasma adrenocorticotropic hormone. In patients at >30 weeks' gestation, there was a significant increase in maternal plasma corticotropin-releasing hormone concentrations after betamethasone; maternal corticotropin-releasing hormone was not altered significantly in untreated patients. Corticotropin-releasing hormone levels were raised in umbilical cord blood by 48 hours and in amniotic fluid 1 week after betamethasone administration. There was increased immunohistochemical staining for corticotropin-releasing hormone in placental syncytiotrophoblast and in fetal membranes of patients treated with betamethasone. CONCLUSIONS: These studies provide the first evidence for in vivo stimulation of plasma corticotropin-releasing hormone, likely of placental origin, by glucocorticoids in third trimester human pregnancy. The results suggest that increases in endogenous cortisol during normal gestation may contribute to placental corticotropin-releasing hormone output and to the rise in maternal plasma corticotropin-releasing hormone concentrations during late pregnancy.