title: Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained.
  
  
  METHODS
  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.
authors.affiliation: Mothers and Babies Research Centre, University of Newcastle, Endocrine Unit, John Hunter Hospital, Newcastle, NSW 2305, Australia. Roger.Smith@newcastle.edu.au
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.forename: Julia I
authors.initials: JI
authors.lastname: Smith
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Shen
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Engel
authors.forename: Maria E
authors.initials: ME
authors.lastname: Bowman
authors.forename: Shaun A
authors.initials: SA
authors.lastname: McGrath
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Bisits
authors.forename: Patrick
authors.initials: P
authors.lastname: McElduff
authors.forename: Warwick B
authors.initials: WB
authors.lastname: Giles
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
mesh_terms: D015331:Cohort Studies; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D004964:Estriol / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007745:Labor Onset / Q000097:blood*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011272:Pregnancy, Multiple / Q000097:blood; D047928:Premature Birth / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D011374:Progesterone / Q000008:administration & dosage / Q000097:blood*; D011379:Prognosis; D047929:Term Birth / Q000097:blood; D014427:Twins
chemical_list: D011374:Progesterone; D004958:Estradiol; D003346:Corticotropin-Releasing Hormone; D004964:Estriol