Deciphering the link and direction between attention-deficit/hyperactivity disorder symptoms and obesity : common behavioural or prenatal pathways?

Background: Animal 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. Methods: Using 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 prepregnancy 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. 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. Using the propensity-scorematched 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. 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. Citation: Khalife N, Glover V, Taanila A, Ebeling H, Järvelin M-R, et al. (2013) Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents. PLoS ONE 8(11): e81394. doi:10.1371/journal.pone. 0081394 Editor: James G. Scott, The University of Queensland, Australia Received May 22, 2013; Accepted October 13, 2013; Published November 22, 2013 Copyright: © 2013 Khalife et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding was received from the following: Academy of Finland (103451); Sigrid Juselius Foundation, Finland; Thule Institute, University of Oulu, Finland; the National Institute of Mental Health (MH63706); and EURO-BLCS. Prof Rodriguez received funding partly from the Swedish Council for Working Life and Social Research (FAS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. * E-mail: a.rodriguez@imperial.ac. uk