Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood

Abstract

Glucocorticoids (cortisol in humans) are the end product of the hypothalamic-pituitary-adrenocortical (HPA) axis and are proposed as a key mechanism for programming fetal brain development. The present prospective longitudinal study evaluates the association between prenatal maternal cortisol concentrations and child neurodevelopment. Participants included a low risk sample of 91 mother-child pairs. Prenatal maternal plasma cortisol concentrations were measured at 19 and 31 gestational weeks. Brain development and cognitive functioning were assessed when children were 6–9 years of age. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child cognitive functioning was evaluated using standardized measures (Wechsler Intelligence Scale for Children IV and Expressive Vocabulary Test, Second Edition). Higher maternal cortisol concentrations during the third trimester were associated with greater child cortical thickness primarily in frontal regions. No significant associations were observed between prenatal maternal cortisol concentrations and child cortical thinning. Elevated third trimester maternal cortisol additionally was associated with enhanced child cognitive performance. Findings in this normative sample of typically developing children suggest that elevated maternal cortisol during late gestation exert lasting benefits for brain development and cognitive functioning 6–9 years later. The benefits of fetal exposure to higher maternal cortisol during the third trimester for child neurodevelopment are consistent with the role cortisol plays in maturation of the human fetus. It is plausible that more extreme elevations in maternal cortisol concentrations late in gestation, as well as exposure to pharmacological levels of synthetic glucocorticoids, may have neurotoxic effects on the developing fetal brain.

Prenatal maternal cortisol measures predict learning and short‐term memory performance in 3‐ but not 5‐month‐old infants

“…However, the direction of the associations they reported is the reverse of those found in the present study. Interestingly, the present results are consistent with the direction of the effects reported by Davis and Sandman (2010), who found that elevated levels in later pregnancy predicted higher levels of mental development scores (see also Davis et al, 2017). However, unlike our results and those of Huizink et al (2003), significant associations between higher late-pregnancy cortisol and greater mental development scores were not apparent until the age of 12-months in Davis and Sandman’s (2010) study.…”

“…In this case, the effect was conjectured to depend on early versus late fetal exposure to GCs due to the sensitivity of hippocampal differentiation occurring around 16 weeks of gestation and synaptic pruning in the prefrontal cortex occurring between 26 and 34 weeks of gestation (Waters, West, & Mendes, 2014). Similarly, higher levels of maternal cortisol in the third trimester, especially, were found to be associated with increased cortical thickness, particularly in areas of the frontal lobe, in their 6- to 9-year-old children (Davis, Head, Buss, & Sandman, 2017). Higher levels of third trimester maternal cortisol were also associated with better performance on the Wechsler Intelligence Scale for Children IV and the Expressive Vocabulary Test, Second Edition (Wechsler, 2002; Williams, 2007; Davis et al, 2017).…”

“…Similarly, higher levels of maternal cortisol in the third trimester, especially, were found to be associated with increased cortical thickness, particularly in areas of the frontal lobe, in their 6- to 9-year-old children (Davis, Head, Buss, & Sandman, 2017). Higher levels of third trimester maternal cortisol were also associated with better performance on the Wechsler Intelligence Scale for Children IV and the Expressive Vocabulary Test, Second Edition (Wechsler, 2002; Williams, 2007; Davis et al, 2017). Conversely, another study found a negative association between maternal prenatal serum cortisol in the third trimester and full-scale IQ in 7-year-olds, especially verbal subscales (LeWinn et al, 2009).…”

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

“…Maternal depression was negatively associated with cortical thickness with the association significantly stronger in girls than boys [52]. Finally, Davis et al ( N  = 91) found significant associations between third trimester maternal cortisol concentrations and brain development, but no evidence of sex dependence [33]. …”

“…Investigators from the Rhea Study ( N  = 288) found no evidence for sex dependence in the association between PNMS and child cognitive development at age 4 [27]. Davis et al ( N  = 91) found no evidence of a sex-dependent association between maternal prenatal plasma cortisol concentrations and child (ages 6–9) cognitive functioning [33]. Finally, data from two independent cohorts ( N = 6969 and N  = 425) provided no evidence of sex dependence in an association between prenatal maternal anxiety and offspring working memory [23].…”