Research Letters

Fetal exposure to maternal cortisol

This study investigates the impact of the timing of initial exposure to maternal depression on a comprehensive measure of children's school readiness that incorporates multidimensional developmental domains underlying school adaptation and later success. The Early Development Instrument scores of 59,413 children were linked to their mothers, who were observed from five years before the child's birth to the child's fifth birthday. Exposure to maternal depression was associated with developmental vulnerability in emotional, physical, social, and cognitive domains, and the effects were strongest if the child was first exposed during pregnancy or the preschool period. When controlling for health at birth, health of the child during early childhood, mother's health prior to pregnancy, and the family environment however, the effects of exposure to maternal depression were attenuated. Thus, although maternal depression is a risk factor for children's school readiness, their health and environment compound this effect. A number of different stratifications, variable definitions and robustness checks support the reliability of the findings. The results suggest that mitigating the effects of maternal depression on school readiness is important at any age, and that the programs to address this are likely to lead to improvements far beyond those for maternal depression alone.

Prenatal cortisol exposure is essential for neurodevelopment. Maternal cortisol levels could be associated with offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).

To investigate associations between maternal 3rd trimester cortisol and offspring traits of ASD and ADHD.

Mother-child pairs were included from the prospective study Odense Child Cohort. Morning serum cortisol and 24-hour urine cortisol/cortisone were collected at gestational week 27–30. Offspring ASD and ADHD traits were assessed at age three and five years using the Child Behavior Checklist. Maternal cortisol measurements and offspring ASD and ADHD traits assessment were available in (n = 1131; 52% boys) mother-child pairs at age three and (n = 717; 54% boys) at five years of age. Maternal 24-hour urine measurement was available in a subset, at offspring three years of age (n = 300) and at five years of age (n = 217). Associations between maternal cortisol (continuous and tertiles) and offspring ASD or ADHD traits were examined in regression models adjusted for offspring sex, maternal age, pre-pregnancy BMI, parity, maternal education level, parental psychiatric disorders, and maternal smoking and stratified for offspring sex.

Maternal mean age ( ± SD) was 30 years ( ± 4.4) and median BMI (25%; 75% percentiles) 23.5 kg/m² (21.3; 26.6). Higher maternal serum cortisol levels were associated with higher prevalence of offspring ASD traits at three years of age in the total study cohort and in boys after stratifying for offspring sex. In the total population, tertiles of serum cortisol showed a significant dose-response relationship to ASD traits in unadjusted and adjusted models (p-values for linear trend, p < 0.01 and p = 0.02, respectively). In offspring at five years, associations between maternal cortisol and offspring ASD traits were non-significant (all p-values > 0.2). Maternal cortisol was not associated with offspring ADHD traits (all p-values > 0.07) in offspring at three and five years. Maternal 24-hour urine cortisol, cortisone, or cortisol/cortisone ratio were not associated with offspring ASD or ADHD traits.

Higher maternal serum cortisol in 3rd trimester was associated with offspring ASD traits at three years of age in the whole study cohort and in boys, but not in girls. This association was non-significant at five years of age.

Glucocorticoids – commonly known as stress hormones - belong to the family of steroid hormones and regulate numerous life essential physiological processes. As lipophilic molecules, glucocorticoids are known to cross the placental barrier in mammals, which – applied for therapeutic reasons or arising from environmental influences – illustrates the role of prenatal stress during embryonic developmental processes. The hormones employ their functions by binding to the glucocorticoid receptor (GR) and thus are involved in regulating the transcription of thousands of genes. Therefore, the aim of this study was to investigate the spatiotemporal expression pattern of the GR during early embryonic vertebrate development, using the chicken embryo as a model organism. The results should contribute to enhance and expand the current understanding of glucocorticoid signaling. By performing in-situ hybridization on whole mount chicken embryos from stage HH10 to HH29 and analyzing vibratome sections of hybridized embryos, we described the spatiotemporal expression pattern of the GR during early embryogenesis. Moreover, we compared the expression pattern of the GR with other developmental markers such as Pax7, Desmin, MyoD and HNK-1 using double in-situ hybridization and immunohistochemistry. We were able to determine the first emergence of GR expression in stage HH13 of chicken development in the cranial area, especially in the muscle anlagen of the branchial arches and of non-somitic neck muscles. Furthermore, we monitored the extension of GR expression pattern throughout later stages and found transcripts of GR during somitogenesis, limb development, myogenesis, neurulation and neural differentiation and moreover during organogenesis of the gastrointestinal organs, the heart, the kidneys and the lungs. Toward later stages, GR expression transitioned from more distinct areas of expression to an increasingly ubiquitous expression pattern. Our results support the notion of an enormous relevance of glucocorticoid signaling during vertebrate embryonic development and contribute to a better understanding of the consequences of prenatal stress and the clinical administration of prenatal glucocorticoids.

Despite widespread acceptance that prenatal symptoms of depression in mothers are detrimental to infants’ long-term emotional and cognitive development, little is known about the mechanisms that may integrate outcomes across these domains. Rooted in the integrative perspective that emotional development is grounded in developing cognitive processes, we hypothesized that prenatal symptoms of depression in mothers would be associated with delays in neural maturation that support sociocognitive function in infants, leading to more problematic behaviors. We used a prospective longitudinal study of mothers (N = 92) and their infants to test whether self-reported symptoms of depression in mothers during the second and third trimesters were associated with neural development and infant outcomes at 4 months of age. While controlling for postpartum symptoms of depression, more prenatal symptoms of depression in mothers predicted less neural maturation in the parietal region of 4-month-old infants. Less neural maturation, in turn, was associated with greater infant negativity, suggesting neural maturation as a putative mechanism linking maternal symptoms of depression with infant outcomes. Differences in neural regions and developmental timing are also discussed.

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)¹ at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth mixture modeling (GGMM)² and then used to predict child growth patterns using multilevel modeling. Infants of mothers who had flat cortisol trajectories, characterized by relatively high cortisol in early gestation that plateaus by mid-gestation, experienced more rapid increases in BMIP from birth to 6 months, and had higher BMIPs at 3 and 6 months, than infants whose mothers had the typical slow cortisol rise over gestation, or steep (rapidly accelerating) trajectories. These results suggest that it is not just the total amount of maternal cortisol in pregnancy that shapes early infant growth, but instead the timing and trajectory of prenatal cortisol exposure. To better understand the early origins of obesity risk, future research is needed to investigate the factors that shape mothers’ prenatal cortisol trajectories.

Mental health problems during pregnancy affect around 20% of mothers and may have lasting impacts on children’s health, cognitive and socio-emotional skills, educational attainment, and future labour market outcomes. We identify the causal effect of mothers’ prenatal mental health on a range of child psychological, socio-emotional and cognitive outcomes. Our methodology exploits shocks to mothers’ mental health that are induced by illness of the mother’s friends or relatives, whilst accounting for the non-randomness of exposure to illness. We find that mothers’ mental health problems negatively affect children’s psychological and socio-emotional skills in early childhood, but these fade-out between the ages of 11-13. There is no effect on children’s cognitive outcomes. Hence, our findings suggest that maternal prenatal mental health may have a limited direct effect on children’s future labour market outcomes.