Endocrine Abstracts

Background: One in five women is obese at antenatal booking. Maternal obesity increases risk of offspring complications including higher birthweight. We hypothesised that this is mediated by altered action of maternal glucocorticoids, key regulators of fetal growth and development. We compared cortisol levels during pregnancy and placental glucocorticoid sensitivity in obese and lean women.

Methods: With ethical approval serum cortisol levels were measured at 16, 28 and 36 weeks gestation in n=173 class III obese (BMI 44.0±4.5 kg/m²) and n=107 lean (BMI 22.8±1.6 kg/m²) pregnant women. Serial corticosteroid binding globulin (CBG) concentrations were measured in a subset (n=39 lean, 26 obese) and free cortisol levels calculated using Coolen’s equation. Salivary cortisol was measured at bed-time, waking and 30 mins after waking. 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), which inactivates cortisol, and glucocorticoid receptor (GR) mRNAs were measured in first trimester (n=34) and term (n=56) placental samples.

Results: Cortisol levels rose similarly during pregnancy in obese and lean, but were significantly lower throughout pregnancy in obese women (P<0.05). The diurnal rhythm was maintained. CBG levels also increased, though change was lower in obese (1.21-fold (±0.32) vs 1.56-fold (±0.38), P<0.01). In obese, lower calculated free cortisol at 16 weeks gestation was associated with higher birth-weight after adjustment for confounders (r=−0.46, P<0.05). Placental expression of 11βHSD2 increased in association with increasing obesity in early pregnancy (r=0.46, P<0.01) and was highest in term placentas in obese women with macrosomic (>4000 g) offspring (P<0.05). Placental expression of GR also increased in association with increasing obesity in early pregnancy (r=0.45, P<0.01), but was lowest in term placenta from obese women with macrosomic offspring (P<0.05).

Conclusions: Lower circulating and bioavailable cortisol levels in early obese pregnancy, together with a greater placental barrier to maternal glucocorticoids may contribute to higher birth weight and macrosomia in offspring of obese women.

Declaration of funding: This work was supported by the Sir Jules Thorn Charitable Trust.