Maternal smoking, alcohol and caffeine use during pregnancy and attention-deficit hyperactivity disorder (ADHD) risk in offspring

: Is the association causal?

Abstract

Observational studies have shown evidence for a positive association between maternal prenatal smoking, alcohol and caffeine consumption and attention-deficit hyperactivity disorder (ADHD) in offspring. However, it is still unclear whether these associations reflect a causal effect or are due to unmeasured and residual confounding. Although evidence from previous studies suggest that the association between maternal prenatal smoking and ADHD is unlikely to be causal, findings are still inconsistent regarding alcohol and caffeine exposure.
In this thesis I used different epidemiological methods and triangulated findings across these methods to find evidence to support a causal effect of maternal prenatal substance use on offspring ADHD risk. The methods used in this thesis included a systematic review, a targeted Phenome-Wide Association Study (PheWAS) approach, a negative control design by using paternal substance use as a negative control, and polygenic risk score analyses. Throughout this thesis I used data from three longitudinal birth cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Generation R (GenR), and the Norwegian Mother, Father and Child Cohort study (MoBa). A triangulation approach illustrated how important it is to apply different methods to infer causality as each method has its own sources of bias, but it is unlikely that different methods are biased in the same way. Therefore, comparing findings from various methods can provide more support on whether a causal relationship exists.
My findings did not provide strong evidence for a causal effect of maternal prenatal substance use on offspring ADHD risk in any of the prenatal exposures. My findings on smoking exposure are in line with existing evidence indicating that the association is explained by genetic confounding. However, my results also suggest that future studies should focus on better phenotyping of ADHD and use bigger samples to detect whether a true causal effect still exists.

Date of Award	24 Jun 2021
Original language	English
Awarding Institution	University of Bristol
Supervisor	Marcus R Munafo (Supervisor), Hannah M Sallis (Supervisor) & Luisa Zuccolo (Supervisor)