Altered glucocorticoid action in obese pregnancy is modulated by diet and is associated with gestational weight gain but has similar influences on birthweight in males and females

Abstract

Rationale/statement of the problem : One in five UK women is obese at antenatal booking. Maternal obesity increases risk of offspring obesity, behavioural and metabolic disorders. Animal studies suggest male offspring are more vulnerable to these effects than females. We hypothesised that this is mediated by altered action of maternal glucocorticoids, key regulators of development and stimulators of appetite and weight gain. Methods : Serum cortisol levels were measured at 16, 28 and 36 weeks gestation in n=156 class III obese (BMI > 40 kg/m2) and n=87 lean (BMI < 25 kg/m2) pregnant women. mRNA levels of 11-beta hydroxysteroid dehydrogenase type 2 (11βHSD2), which inactivates cortisol, were measured in n=36 first trimester and n=61 term placental samples. Results : Cortisol levels were significantly lower throughout pregnancy in obese than lean (p<0.05) Obese reported similar appetite and total calorie intake to lean but had significantly less gestational weight gain (10.1±3.7 kg vs. 5.5±5.6 kg, p<0.01); this inversely correlated with cortisol levels (r = −0.27, p<0.01). Cortisol levels correlated positively with reported pregnancy intake of protein, fat, saturated fatty acids and sugars in lean (all p<0.05). Placental expression of 11βHSD2 increased in association with increasing obesity in early pregnancy (r=0.21, p<0.01) and was highest in term placenta in obese women with macrosomic (>4000 g) offspring (p<0.05). There were no gender-specific effects of maternal overnutrition on birthweight, placental gene expression or maternal glucocorticoid levels. Conclusions : Lower circulating cortisol levels in obese pregnancy, together with the more effective placental barrier to maternal glucocorticoids may be a mechanism contributing to higher birthweight in offspring of obese women. In lean women, dietary composition may regulate cortisol levels during pregnancy.

Keywords

• maternal obesity
• cortisol levels
• birthweight
• gestational weight gain