Abstract
BackgroundAnimal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans. MethodsUsing propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment - gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort – matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves – pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale. ResultsPrenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected. ConclusionsThis study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain.
Highlights
Cortisol, a naturally occurring glucocorticoid (GC), plays a vital role in fetal development [1]
As gestational age and pre-pregnancy body mass index (BMI) precede synthetic glucocorticoids (sGC) treatment, these covariates were included in the propensity-score model
The propensity-score-matched subsample showed that prenatal exposure to sGC treatment was significantly associated with the total Rutter and inattention scores in childhood, independent of relevant confounders – sex, birthweight, placental weight, socio-demographic factors and medical factors
Summary
A naturally occurring glucocorticoid (GC), plays a vital role in fetal development [1]. Animal models provide strong evidence that prenatal exposure to both elevated endogenous maternal GC and synthetic glucocorticoids (sGC) alter fetal brain development and impact upon behavior [6,10,11], including hyperactivity [12] and attention [13]. Results: Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Conclusions: This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain
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