Fetal Glucocorticoid Exposure Is Associated with Preadolescent Brain Development

Abstract

Background Glucocorticoids play a critical role in normative regulation of fetal brain development. Exposure to excessive levels may have detrimental consequences and disrupt maturational processes. This may especially be true when synthetic glucocorticoids are administered during the fetal period, as they are to women in preterm labor. The present study investigated the consequences for brain development and affective problems of fetal exposure to synthetic glucocorticoids. Methods Brain development and affective problems were evaluated in fifty-four children (56% female), ages 6 to 10, who were full term at birth. Children were recruited into two groups: those with and without fetal exposure to synthetic glucocorticoids. Structural magnetic resonance imaging (MRI) scans were acquired and cortical thickness was determined. Child affective problems were assessed using the Child Behavior Checklist. Results Children in the fetal glucocorticoid exposure group showed significant and bilateral cortical thinning. The largest group differences were in the rostral anterior cingulate cortex (rACC). Over 30% of the rACC was thinner among children with fetal glucocorticoid exposure. Further, children with more affective problems had a thinner left rACC. Conclusions Fetal exposure to synthetic glucocorticoids has neurological consequences that persist for at least 6 to 10 years. Children with fetal glucocorticoid exposure had a thinner cortex primarily in the rACC. Our data indicating that the rACC is associated with affective problems in conjunction with evidence that this region is involved in affective disorders raises the possibility that glucocorticoid associated neurological changes increase vulnerability to mental health problems.

Intergenerational Transmission of Stress in Humans

“…Specifically, children aged 6-10 years old with synthetic fetal glucocorticoid exposure were found to have a thinner cortex primarily in the rostral anterior cingulate cortex (rACC). Separately, studies have reported that the thinner left rACC cortex was associated with offspring affective problems (Davis et al, 2013) and that prenatal synthetic glucocorticoid treatment was associated with offspring general psychiatric disturbance (Khalife et al, 2013). These data support the hypothesis that aberrant glucocorticoid signaling in the fetal environment, potentially associated with prenatal stress in mothers, alters neuroanatomical development, contributing to behavioral problems in offspring.…”

Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep

“…The fact that Davis et al [24, 25] reported harmful side effects after 1 course of ACS treatment as well as the subgroup analysis in our study that showed an effect on myelin, even in the STG, further reinforces the need to carefully balance the benefits and risks of ACS treatment.…”

“…Late preterm- or term-born infants after ACS exposure might therefore more specifically reveal effects from ACS as they are less likely to have deficits. Davis et al [24] reported that children who were full term at birth and had been exposed to 1 course of ACS had significant bilateral cortical thinning at 6–10 years of age.…”

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

“…These studies reported delayed overall brain growth, limbic systemspecific volumetric changes, and white matter abnormalities (Li et al, 2012;Lou et al, 1994;Qiu et al, 2013Qiu et al, , 2015Rifkin-Graboi et al, 2013). Such early observations appear to persist into childhood and adolescence, are correlated with affective problems, and may contribute to symptoms in patients with schizophrenia and autism (Buss et al, 2010(Buss et al, , 2012Davis et al, 2013;Du et al, 2013;Sarkar et al, 2014;Zikopoulos and Barbas, 2010).…”