Impact of prenatal synthetic glucocorticoid exposure on the adolescent brain

Synthetic Glucocorticoids (sGC) are commonly prescribed in preterm risk pregnancies in order to improve fetal organ maturation. This administration greatly reduces perinatal and neonatal mortality and respiratory distress syndrome associated with prematurity, but preclinical evidence warns for an adverse effect of sGC in the developing brain. In this work we evaluated the long-term effects of prenatal exposure to sGC in the brain of 17 years-old adolescents using multimodal MRI. From 4607 birth registrations from Hospital de Braga - Portugal, we selected participants that were born with similar gestational age, but that were either exposed during pregnancy to sGC (n=21) or non-exposed (n=24). After obtaining a detailed clinical history, participants were subjected to an extensive neuropsychological evaluation, followed by structural and functional MRI. No differences were found in the performance on neuropsychological tests between sGC-exposed and non-exposed participants. Moreover, no differences were found in regional brain volumes. However, the sGC-exposed group presented reduced functional connectivity at rest in a network involving primarily sub-cortical, cerebellar and frontal nodes in comparison to the non-exposed group, even after controlling for confounding factors such as gestational age at birth, birth weight, and sex. Our results suggest that prenatal sGC-exposed adolescents present no significant deviations in neuropsychological performance in the dimensions that we evaluated, although they presented altered functional connectivity, highlighting the need for additional studies to understand the impact of these changes in brain functioning and in behavior. Highlights Prenatal synthetic glucocorticoid exposure does not lead to structural changes in the adolescent brain. Adolescents prenatally exposed to synthetic glucocorticoids present altered resting state network.