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This version published online on March 3, 2009 Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-2257
Submitted on October 17, 2008 Patterns of Plasma Corticotrophin-Releasing Hormone, Progesterone, Estradiol and Estriol Change and the Onset of Human LaborROGER SMITH*,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 & 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; Northern Clinical School (W.B.G.), University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia * To whom correspondence should be addressed. E-mail: Roger.Smith{at}newcastle.edu.au.
Context. Clinical prediction of preterm delivery is largely ineffective and the mechanism mediating progesterone withdrawal and estrogen activation at the onset of human labor is unclear. Objectives. To determine associations of: rates-of-change of circulating maternal corticotrophin-releasing hormone (CRH) in mid-pregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy and pre-delivery changes in the ratios of E3, estradiol (E2) and progesterone (P). Design. A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000–2004. Setting. John Hunter Hospital, NSW, 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 percentage-daily-change in term and preterm singletons at 26 weeks. Ratios E3:E2, P:E3 and P:E2 and association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset). Results. CRH percentage-daily-change was significantly higher in preterm than term singletons at 26 weeks (medians: 3.09, 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 7.04–10.59, p<0.001; P:E3 1.55–0.98, p<0.001; P:E2 11.78–10.79, 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 progesterone supplementation. Key words: pregnancy • hormones • preterm birth • CRH • progesterone • estradiol • estriol • mathematical modeling
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