Abstract
BackgroundStudies investigating the effects of prenatal alcohol exposure on childhood attention‐deficit hyperactivity disorder (ADHD) symptoms using conventional observational designs have reported inconsistent findings, which may be affected by unmeasured confounding and maternal and fetal ability to metabolize alcohol. We used genetic variants from the alcohol metabolizing genes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), as proxies for fetal alcohol exposure to investigate their association with risk of offspring ADHD symptoms around age 7–8 years.MethodsWe used data from 3 longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC), Generation R study (GenR), and the Norwegian Mother, Father and Child Cohort study (MoBa). Genetic risk scores (GRS) for alcohol use and metabolism using 36 single nucleotide polymorphisms (SNPs) from ADH and ALDH genes were calculated for mothers (N ALSPAC = 8196; NMOBA = 13,614), fathers (N MOBA = 13,935), and offspring (N ALSPAC=8,237; N MOBA=14,112; N GENR=2,661). Associations between maternal GRS and offspring risk of ADHD symptoms were tested in the full sample to avoid collider bias. Offspring GRS analyses were stratified by maternal drinking status.ResultsThe pooled estimate in maternal GRS analyses adjusted for offspring GRS in ALSPAC and MoBa was OR = 0.99, 95%CI 0.97–1.02. The pooled estimate in offspring GRS analyses stratified by maternal drinking status across all the cohorts was as follows: ORDRINKING = 0.98, 95% CI 0.94–1.02; ORNO DRINKING = 0.99, 95% CI 0.97–1.02. These findings remained similar after accounting for maternal genotype data in ALSPAC and maternal and paternal genotype data in MoBa.ConclusionsWe did not find evidence for a causal effect of fetal alcohol exposure on risk of ADHD symptoms in offspring. The results may be affected by limited power to detect small effects and outcome assessment.
Highlights
It is well documented that heavier alcohol consumption during pregnancy can negatively affect fetal development and later neurodevelopmental problems (Patra et al, 2011), but evidence is inconsistent regarding the effects of low prenatal alcohol exposure (PAE) (Mamluk et al, 2017)
The harmful neurodevelopmental effects resulting from PAE are collectively defined as fetal alcohol spectrum disorders (FASD), which include fetal alcohol syndrome (FAS), partial FAS, alcohol-related neurodevelopmental disorder (ARND), alcohol-related birth defects (ARBD), and neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE) (Mattson et al, 2019)
It is possible that these associations are due to genetic confounding or confounding by social factors, as both studies found that women who drank low or moderate levels during pregnancy had a higher socioeconomic position, which is negatively associated with attention-deficit hyperactivity disorder (ADHD) risk in the offspring
Summary
It is well documented that heavier alcohol consumption during pregnancy can negatively affect fetal development and later neurodevelopmental problems (Patra et al, 2011), but evidence is inconsistent regarding the effects of low prenatal alcohol exposure (PAE) (Mamluk et al, 2017). A systematic review by Easey and colleagues suggested that low and moderate alcohol consumption during pregnancy is associated with negative mental health outcomes in children, including anxiety/ depression, total behavioral problems, and conduct disorder (Easey et al, 2019) Another recent systematic review and meta- analysis focusing on offspring ADHD found little evidence to suggest an increased risk of ADHD symptoms in children whose mothers consumed moderate amounts of alcohol (up to 70 g a week) during pregnancy (Porter et al, 2019). Studies investigating the effects of prenatal alcohol exposure on childhood attention-deficit hyperactivity disorder (ADHD) symptoms using conventional observational designs have reported inconsistent findings, which may be affected by unmeasured confounding and maternal and fetal ability to metabolize alcohol. Associations between maternal GRS and offspring risk of ADHD symptoms were
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
