title: Decreased maternal hypothalamic-pituitary-adrenal axis activity in very severely obese pregnancy: Associations with birthweight and gestation at delivery.
abstract: BACKGROUND
  The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes dramatic activation during pregnancy. Increased cortisol and corticotrophin-releasing-hormone (CRH) associate with low birthweight and preterm labor. In non-pregnant obesity, the HPAA is activated but circulating cortisol levels are normal or lower than in lean women. We hypothesized that maternal cortisol levels would be lower in obese pregnancy, and would associate with increased fetal size and length of gestation.
  
  
  METHODS
  Fasting serum cortisol was measured at 16, 28 and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135 lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol, estriol, and progesterone). Urinary glucocorticoid metabolites were measured in pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects.
  
  
  RESULTS
  Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total urinary glucocorticoid metabolites increased significantly in lean pregnancy, but not in obese. Lower maternal cortisol in obese tended to be associated with increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated inversely with gestational length (r=-0.49, p=0.04), and independently predicted gestational length after adjustment for confounding factors (mean decrease in CRH of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation).
  
  
  CONCLUSIONS
  In obese pregnancy, lower maternal cortisol without an increase in urinary glucocorticoid clearance may indicate a lesser activation of the HPAA than in lean pregnancy. This may offer a novel mechanism underlying increased birthweight and longer gestation in obese pregnancy.
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom; Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom.
authors.forename: Laura I
authors.initials: LI
authors.lastname: Stirrat
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom.
authors.forename: James R
authors.initials: JR
authors.lastname: O'Reilly
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom; Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Barr
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom; Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Riley
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Howie
authors.affiliation: Mothers and Babies Unit, University of Newcastle, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Bowman
authors.affiliation: Mothers and Babies Unit, University of Newcastle, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: John G
authors.initials: JG
authors.lastname: Lewis
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom; Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Denison
authors.affiliation: Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom; University/BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom.
authors.forename: Shareen
authors.initials: S
authors.lastname: Forbes
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.affiliation: Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom; University/BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom; Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom; Tommy's Centre for Maternal and Fetal Health, University of Edinburgh, United Kingdom; University/BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom. Electronic address: R.Reynolds@ed.ac.uk.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D001724:Birth Weight; D016022:Case-Control Studies; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003348:Cortisone / Q000652:urine; D004958:Estradiol / Q000378:metabolism; D004964:Estriol / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D009767:Obesity, Morbid / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D011278:Pregnanes / Q000652:urine; D011374:Progesterone / Q000378:metabolism; D013760:Tetrahydrocortisol / Q000652:urine; D014156:Transcortin / Q000378:metabolism
chemical_list: D011278:Pregnanes; C003545:cortolone; D011374:Progesterone; D004958:Estradiol; C003544:cortol; D013760:Tetrahydrocortisol; D014156:Transcortin; D003346:Corticotropin-Releasing Hormone; D004964:Estriol; D003348:Cortisone; D006854:Hydrocortisone
keywords: Cortisol; HPA axis; Obesity; Pregnancy