This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Google Scholar Articles by Smith, R. Articles by Smith, D. W. PubMed PubMed Citation Articles by Smith, R. Articles by Smith, D. W. Related Collections Pediatric Endocrinology Female Endocrinology

Patterns of Plasma Corticotropin-Releasing Hormone, Progesterone, Estradiol, and Estriol Change and the Onset of Human Labor

Mothers and Babies Research Centre (University of Newcastle)/Endocrine Unit (R.S., J.I.S., P.J.E., M.E.B., S.A.M.), Division of Obstetrics and Gynaecology (A.M.B.), and Hunter Medical Research Institute (P.M.), John Hunter Hospital, Newcastle, NSW 2305, Australia; Melbourne School of Engineering (X.S.), University of Melbourne, VIC 3010, Australia; Faculty of Engineering, Computing and Mathematics (D.W.S.), University of Western Australia, Crawley, WA 6009, Australia; and Northern Clinical School (W.B.G.), University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia

Address all correspondence and requests for reprints to: Roger Smith, Endocrine Unit, John Hunter Hospital, Newcastle, NSW 2305, Australia. E-mail: Roger.Smith{at}newcastle.edu.au.

Context: Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear.

Objectives: Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P.

Design and Setting: A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000–2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital.

Patients: Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained.

Main Outcome Measures: CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed.

Results: CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73; P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001; P/E3, 1.55 and 0.98, P < 0.001; P/E2, 11.78 and 10.79, P = 0.07).

Conclusions: The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.

This article has been cited by other articles:

				B. F. Mitchell and M. J. Taggart Are animal models relevant to key aspects of human parturition? Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R525 - R545. [Abstract] [Full Text] [PDF]

				E. R. Norwitz A Blood Test to Predict Preterm Birth: Don't Mess with Maternal-Fetal Stress J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 1886 - 1889. [Full Text] [PDF]