Maternal Total Cortisol Levels in Early Pregnancy Depends on Fetal Sexual Dimorphism. But Finally No Association With Birth Weight

Enhanced maternal cortisol levels may have a negative impact on fetal development with a higher risk for diseases later in life, e.g. premature cardiovascular disease and type 2 diabetes. Prior studies do assume even a sex specific impact. Currently, it is unknown whether sexual dimorphism in the fetus could display a different maternal cortisol level that is associated with intra uterine growth. In the present study (performed in the Amsterdam Born Children and their Development (ABCD) –cohort), we evaluated in 3049 pregnant women (in early pregnancy) whether fetal sex is related to the level of maternal serum total cortisol and whether this contributes to fetal growth. Maternal serum total cortisol levels increased along early pregnancy from on average 390±22 nmol/L (at 5th week of pregnancy) to 589±15 nmol/L (at 20th week of pregnancy). The presence of a female fetus was associated with higher maternal total cortisol level in a distinctive time interval along early pregnancy; before 11th week of pregnancy, no difference, and from the 12th week of pregnancy a difference of 15 (SE:7) nmol/L between mothers carrying a male vs female fetus was found and that difference increased to 45 (22) nmol/L at 20th week of pregnancy (p-for-interaction=0.05). Maternal serum total cortisol levels were negatively associated with maternal age, pBMI, smoking and parity, the last one also increasing with pregnancy duration. After adjusting for these factors, the association between fetal sex and maternal cortisol remained Maternal serum total cortisol levels were significantly associated with birth weight, standardized for pregnancy duration (ß -.22; SE:0.06; P < 0.001). Girls had a significantly lower birth weight (-132 SE:16 gram) compared to males, however, maternal cortisol did not alter the association between fetal sex and birth weight to a relevant degree indicating no mediation by maternal cortisol. In early pregnancy, the maternal total cortisol levels are related to fetal sex. However this difference in maternal total cortisol level was finally not related to birth weight.