Prenatal Predictors of Child and Adolescent Mental Health

Background: The foetal period is characterised by rapid growth, epigenetic fine-tuning, and adaptation to the foetal-maternal environment. Prenatal factors such as low birth weight have been acknowledged as correlates of subsequent mental illness for many decades. However, much of the literature has focused on group differences (e.g., “Normal” Vs “Low” birth weight) in the risk for subsequent mental disorder, and it is unclear whether prenatal variables such as birth weight can be used for individual-level prediction. In this thesis, we modelled the dose-response association between birth weight and a range of mental health outcomes in large samples of children. We explored a range of prenatal variables— birth weight, gestational age at birth, prenatal testosterone levels, obstetric complications, and maternal substance-use during pregnancy— as risk factors for subsequent mental health problems, with particular focus on age and sex as potential moderators. Methods: Secondary analysis was performed on existing cohort studies: (1) the Adolescent Brain Cognitive Development (ABCD) study based in the United States of America, (2) the Growing Up in Ireland (GUI) study, for which two cohorts were recruited born around 1998 and 2008 respectively, and (3) the Cambridge Child Development Project, based in the United Kingdom. The ABCD and GUI are large nationally representative studies of US and Irish children, respectively. Our statistical methods mostly consisted of general and generalised linear models, including random effects and interactions were necessary to model clustering and interdependencies within the data. Results: Birth weight was most strongly linked with attention problems around age 9. This dose-response association was significant after controlling for gestational age at birth, suggesting that variation in foetal growth drove the association (Chapters 2-3). Foetal growth variation had long-lasting associations with mental health from ages 9 to 17. Associations with ADHD-type issues were stable and pervasive across this period, but associations between foetal growth and emotional problems only became apparent in the later adolescent years (Chapter 3). Across two independent cohorts, we showed that the association between foetal growth restriction and ADHD-type issues could be statistically decomposed into that explained by familial background factors (income, education, demographics; 26-30%) and potentially modifiable prenatal factors (pregnancy complications, maternal substance-use; 13-26%; Chapter 4). Eight percent of the variance in age 9 ADHD symptoms could be explained using pre/perinatal factors alone (R2 95% CI = 5.6-11.5%), many of which were modifiable (Chapter 5). Throughout, sex differences were identified regarding the strength of association between prenatal factors and child mental health. Chapter 6 found that prenatal testosterone was not correlated with autistic traits in adolescence, and therefore could not alone explain the sex difference in this construct. Conclusions: The association between birth weight and subsequent mental health issues in childhood is small but significant and highly replicable across cohorts. The strength and specificity of this association to certain aspects of mental health depend in part on age and sex of the child. Males may be a particularly vulnerable group when it comes to restricted foetal growth and certain obstetric complications. Our ability to predict mental health outcomes from prenatal data is modest, however interactions between prenatal factors and existing familial/social vulnerabilities may improve predictive capacity. Birth weight is a widely available and generalisable predictor of childhood mental health issues. Conversely, the specific prenatal factors underlying this association (e.g. maternal smoking, nutrition level, infection) may be context-specific, and therefore should be identified and targeted in a context-specific manner.