Endocrine Abstracts

Background: Maternal cortisol levels increase during pregnancy and prenatal cortisol exposure have been linked to cognitive function in childhood. Higher activity of the enzyme 11β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2) downregulates the amount of maternal cortisol crossing the placenta by inactivation of cortisol to cortisone. In childhood, boys perform significantly poorer in tests of intelligence than girls.

Aim: To investigate associations between maternal 3rd trimester cortisol or cortisone and child IQ at 7-years-of-age, and to consider the impact of child sex.

Method: Odense Child Cohort is a prospective observational cohort study. In this current study, 943 mother-child dyads were included. Exposure was maternal 24 hour urine (u-) cortisol and cortisone, and fasting morning serum (s-) cortisol, obtained in 3rd trimester of pregnancy and measured by liquid chromatography–tandem mass spectrometry. Outcome was child intelligence at age 7 years assessed by trained psychologists using the Wechsler Intelligence Scale for Children version V. Estimations of full scale intelligence quotient (FSIQ) and verbal comprehension index (VCI) were calculated.

Results: Women carrying a boy had significantly lower s-cortisol levels than women carrying a girl (825 vs 865 nmol/l, P= 0.005). Girls had a significant higher score in FSIQ (101.2 vs 98.2, P< 0.001) and VCI (101.1 vs 98.9, P= 0.004) compared to boys. In girls, levels of maternal u-cortisone were positively associated with VCI (B (95%-CI) = 6.2 (1.2; 11.2). In boys, maternal s-cortisol was negatively associated with FSIQ (B (95%-CI) = -3.9 (-6.5; -1.3)) and VCI (B (95%-CI) = -4.4 (-7.0; -1.9)). Child sex had a significant interaction with u-cortisone and s-cortisol in the associations.

Conclusion: Lower prenatal cortisol exposure of the fetus seems beneficial for cognitive development at 7-years-of-age. Girls were protected against high cortisol exposure via the inactivation of cortisol to cortisone by 11β-HSD2, while boys were more susceptible to high maternal cortisol levels. Child sex differences in prenatal cortisol exposure and cognitive development should be considered in future studies.