title: Altered maternal hypothalamic-pituitary-adrenal axis activity in obese pregnancy is associated with macrosomia and prolonged pregnancy.
abstract: BACKGROUND
  The hypothalamic-pituitary-adrenal (HPA) axis is important for fetal growth and timing of parturition. Maternal obesity is associated with macrosomia (birthweight ⩾4000g) and prolonged pregnancy (⩾41weeks). We aimed to characterise HPA axis hormones in obese pregnancy and to test associations with these pregnancy outcomes.
  
  
  METHODS
  Fasting cortisol was measured by radioimmunoassay in venous blood at 16, 28 and 36 weeks of gestation in 286 obese (BMI 44.05±3.98kg/m(2)) and 137 lean (BMI 22.71±1.66kg/m(2)) pregnant women. In subsets (n=20 obese, 20 lean) we measured corticosteroid binding globulin (CBG) and CRH by radioimmunoassay; progesterone, estradiol (E2), estriol (E3) and sex-hormone-binding-globulin (SHBG) by ELISA; and albumin by bromocresol green binding. Free cortisol levels were calculated using Coolen's equation.
  
  
  RESULTS
  Cortisol, CBG, calculated free cortisol, CRH, E2, E3, progesterone and SHBG levels rose similarly during pregnancy in obese and lean, but were significantly lower in obese (p<0.05). In obese, lower free cortisol at 16 weeks was associated with higher birthweight (r=-0.46, p<0.05). Cortisol was not associated with labour onset. CRH was significantly lower at 36 weeks in women who delivered at ⩾41weeks and in women with macrosomic babies (p<0.05); and correlated negatively with gestation at delivery in obese (r=-0.557, p<0.05).
  
  
  CONCLUSIONS
  Our findings suggest that decreased HPA axis activity in obese pregnancy may be a mechanism underlying macrosomia and prolonged pregnancy.
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: L I
authors.initials: LI
authors.lastname: Stirrat
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: J R
authors.initials: JR
authors.lastname: O'Reilly
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: S C
authors.initials: SC
authors.lastname: Riley
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: A F
authors.initials: AF
authors.lastname: Howie
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: G J
authors.initials: GJ
authors.lastname: Beckett
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: J E
authors.initials: JE
authors.lastname: Norman
authors.affiliation: Tommy's Centre for Maternal & Fetal Health, Queen's Medical Research Institute Edinburgh, United Kingdom.
authors.forename: R M
authors.initials: RM
authors.lastname: Reynolds