Maternal serum cortisol levels during pregnancy differ by fetal sex

Background: Males and females have different patterns of fetal growth, resulting in different sizes at birth. Increased maternal cortisol levels in pregnancy negatively impact fetal growth. However, it is unknown whether sexual dimorphism displays differences in maternal cortisol levels already during early pregnancy and to what extent it explains sex differences in intra-uterine growth. The present cross-sectional study investigated whether fetal sex was associated with the level of maternal serum total cortisol in first half of pregnancy and its contribution to sex differences in fetal growth. Method: The study population comprised 3049 pregnant women from the Amsterdam Born Children and their Development (ABCD)–cohort). Total serum cortisol levels were determined during pregnancy. Multivariable linear regression was used to determine fetal sex differences in maternal cortisol levels and its association with sex differences in fetal growth measured as birth weight standardized for gestational age, parity and sex. Results: Maternal serum total cortisol increased during pregnancy from on average 390 ± 22 nmol/L (at 5th week) to 589 ± 15 nmol/L (at 20th week). Women carrying a female fetus had higher maternal total cortisol levels. This sex difference was not significant before the 11th week; at the 12th week the difference was 15 ± 7 nmol/L which increased to 45 ± 22 nmol/L at the 20th week (p-for-interaction=0.05). Maternal total cortisol levels were associated with birth weight (ß:−0.22;P < 0.001). However, sex differences in birth weight were not explained by related maternal total cortisol levels. Conclusion: The sexual dimorphic maternal serum total cortisol levels are apparent after the first trimester but do not explain the different patterns of fetal growth.