Background.Both maternal obesity and disordered mood have adverse effects on pregnancy outcome. We hypothesized that maternal very severe obesity (SO) is associated with increased anxiety and depression (A&D) symptoms during pregnancy, with adverse effects on gestational weight gain (GWG), postpartum mood and postpartum weight retention (PPWR) and explored any mediation by circulating glucocorticoids.Method.We measured A&D symptoms with validated questionnaires at weeks 17 and 28 of pregnancy and 3 months postpartum in 135 lean [body mass index (BMI) ⩽25 kg/m2] and 222 SO (BMI ⩾40 kg/m2) pregnant women. Fasting serum cortisol was measured by radioimmunoassay; GWG and PPWR were recorded.Results.A&D symptoms were higher in the SO group during pregnancy and postpartum despite adjusting for multiple confounders including previous mental health diagnosis (p < 0.05), and were non-linearly correlated with total GWG (anxiety R2 = 0.06, p = 0.037; depression R2 = 0.09, p = 0.001). In the SO group only, increased maternal anxiety (β = 0.33, p = 0.03) and depression (β = 0.19, p = 0.04) symptoms at week 17 of pregnancy were associated with increased PPWR, independent of total GWG and breastfeeding. Anxiety symptoms at week 28 of pregnancy, but not depression, were non-linearly correlated with serum cortisol level at week 36 of pregnancy (R2 = 0.06, p = 0.02). Cortisol did not mediate the link between A&D symptoms and GWG.Conclusions.Maternal SO was associated with increased A&D symptoms, and with adverse effects on GWG and PPWR independent of circulating glucocorticoids. Strategies to optimize GWG and postpartum weight management in SO women should include assessment and management of maternal mood in early pregnancy.

Maternal emotional distress symptoms, including life satisfaction, anxiety and depressed mood, are worse in Severely Obese (SO) than lean pregnancy and may alter placental genes regulating fetal glucocorticoid exposure and placental growth. We hypothesised that the associations between increased maternal distress symptoms and changes in placental gene expression including IGF2 and genes regulating fetal glucocorticoid exposure are more pronounced in SO pregnancy. We also considered whether there were sex-specific effects. Placental mRNA levels of 11β-HSDs, NR3C1-α, NR3C2, ABC transporters, mTOR and the IGF2 family were measured in term placental samples from 43 lean (BMI≤25kg/m(2)) and 50 SO (BMI≥40kg/m(2)) women, in whom distress symptoms were prospectively evaluated during pregnancy. The mRNA levels of genes with a similar role in regulating fetal glucocorticoid exposure were strongly inter-correlated. Increased maternal distress symptoms associated with increased NR3C2 and IGF2 isoform 1(IGF2-1) in both lean and SO group (p≤0.05). Increased distress was associated with higher ABCB1 and ABCG2 mRNA levels in SO but lower ABCB1 and higher 11β-HSD1 mRNA levels in lean (p≤0.05) suggesting a protective adaptive response in SO placentas. Increased maternal distress associated with reduced mRNA levels of ABCB1, ABCG2, 11β-HSD2, NR3C1-α and IGF2-1 in placentas of female but not male offspring. The observed sex differences in placental responses suggest greater vulnerability of female fetuses to maternal distress with potentially greater fetal glucocorticoid exposure and excess IGF2. Further studies are needed to replicate these findings and to test whether this translates to potentially greater negative outcomes of maternal distress in female offspring in early childhood.