Are effects of drinking in pregnancy modified by ADH1B and ALDH2 genotype? A longitudinal analysis in the Norwegian Mother, Father and Child Cohort Study (MoBa)
- 1University of Bristol
Abstract
BackgroundRecent evidence from a Japanese study suggests that adverse impacts of prenatal alcohol exposure (PAE) on child development are substantially modified by maternal genotype for rs671, a variant in the aldehyde dehydrogenase 2 gene (ALDH2) which impacts alcohol metabolism. This specific null variant is largely restricted to East Asian populations. Whether variants impacting alcohol metabolism in other ancestral groups could have similar effects is unclear.
MethodsUsing data from the Norwegian Mother, Father, and Child Cohort Study (N=68,325 mother-child duos, data collected 2000-2011) we explored whether maternal drinking in early (1-15 weeks) or mid-pregnancy (13-30 weeks) was associated with childrens development. We considered the childs language and motor skills at 18 and 36 months and the age when the child first walked unaided, as reported by mothers in questionnaires. Stratification by maternal and child genotypes linked to alcohol metabolism (rs1229984, rs886205 or rs440) examined effect modification.
ResultsIn minimally-adjusted models, children exposed to alcohol in early pregnancy (week 1-15) had slightly increased odds of delayed language skills at 18 months (OR=1.16 (95% CI: 1.01,1.33). This attenuated slightly with adjustment for confounders (OR=1.14 (95% CI: 0.99,1.31). Similar associations were seen for drinking in weeks 13-30, and there was little evidence of other harmful effects. In genetically-stratified models, there was little evidence that either the mothers or childs own genotype modified associations, but estimates for smaller genotype groups were imprecise.
ConclusionsResults suggest that in European ancestry populations, maternal or child rs1229984, rs886205 or rs440 genotype is unlikely to substantially modify consequences of prenatal alcohol exposure for early child development. Further work is required in European and other ancestry cohorts, including in countries where prevalence of drinking in pregnancy is higher.
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BibTeX
@misc{hughes2026effects,
title = {{Are effects of drinking in pregnancy modified by ADH1B and ALDH2 genotype? A longitudinal analysis in the Norwegian Mother, Father and Child Cohort Study (MoBa)}},
author = {A. M. Hughes and C. Slaney and K. Tilling and P. Madley-Dowd and A. Havdahl and G. Davey Smith},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.26365709},
url = {https://www.medrxiv.org/content/10.64898/2026.10.20.26365709v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Are effects of drinking in pregnancy modified by ADH1B and ALDH2 genotype? A longitudinal analysis in the Norwegian Mother, Father and Child Cohort Study (MoBa)
AU - A. M. Hughes
AU - C. Slaney
AU - K. Tilling
AU - P. Madley-Dowd
AU - A. Havdahl
AU - G. Davey Smith
PY - 2026
DA - 2026/10/20
PB - medRxiv
DO - 10.64898/2026.10.20.26365709
UR - https://www.medrxiv.org/content/10.64898/2026.10.20.26365709v1
AB - BackgroundRecent evidence from a Japanese study suggests that adverse impacts of prenatal alcohol exposure (PAE) on child development are substantially modified by maternal genotype for rs671, a variant in the aldehyde dehydrogenase 2 gene (ALDH2) which impacts alcohol metabolism. This specific null variant is largely restricted to East Asian populations. Whether variants impacting alcohol metabolism in other ancestral groups could have similar effects is unclear. MethodsUsing data from the Norwegian Mother, Father, and Child Cohort Study (N=68,325 mother-child duos, data collected 2000-2011) we explored whether maternal drinking in early (1-15 weeks) or mid-pregnancy (13-30 weeks) was associated with childrens development. We considered the childs language and motor skills at 18 and 36 months and the age when the child first walked unaided, as reported by mothers in questionnaires. Stratification by maternal and child genotypes linked to alcohol metabolism (rs1229984, rs886205 or rs440) examined effect modification. ResultsIn minimally-adjusted models, children exposed to alcohol in early pregnancy (week 1-15) had slightly increased odds of delayed language skills at 18 months (OR=1.16 (95% CI: 1.01,1.33). This attenuated slightly with adjustment for confounders (OR=1.14 (95% CI: 0.99,1.31). Similar associations were seen for drinking in weeks 13-30, and there was little evidence of other harmful effects. In genetically-stratified models, there was little evidence that either the mothers or childs own genotype modified associations, but estimates for smaller genotype groups were imprecise. ConclusionsResults suggest that in European ancestry populations, maternal or child rs1229984, rs886205 or rs440 genotype is unlikely to substantially modify consequences of prenatal alcohol exposure for early child development. Further work is required in European and other ancestry cohorts, including in countries where prevalence of drinking in pregnancy is higher.
ER -