Maternal alcohol consumption during pregnancy and child development: Role of ADH1B and ALDH2 gene polymorphisms-The Yamanashi Adjunct Study of the Japan Environment and Children's Study.

Background: The role of polymorphisms in genes regulating alcohol metabolism, particularly those modulating the impact of prenatal alcohol exposure on the neurodevelopment of offspring, remains inconclusive. Herein, we aimed to determine the involvement of ADH1B and ALDH2 gene polymorphisms in maternal alcohol consumption during pregnancy and the risk of developmental delay in offspring in a Japanese population.

Methods: We analyzed 1727 mother-child pairs from the Yamanashi Adjunct Study of the Japan Environment and Children's Study. Maternal alcohol consumption during pregnancy was determined through a mid-pregnancy questionnaire and categorized into three groups: never-drinkers, those who quit drinking in early pregnancy, and current drinkers. Developmental delays in children were assessed in five domains using the Japanese version of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3) at 3 years of age. We conducted a logistic regression analysis to explore the relationship between maternal drinking status during pregnancy and developmental delays in offspring with respect to maternal ADH1B (rs1229984) or ALDH2 (rs671) gene polymorphisms.

Results: Children born to mothers who continued alcohol consumption during pregnancy had a higher risk of delayed communication skills at 3 years of age compared with children born to mothers who did not drink alcohol (adjusted odds ratio [OR], 5.82; 95% confidence interval, 1.84-18.38). Analysis by ALDH2 gene polymorphism revealed that alcohol consumption by mothers carrying the wild-type ALDH2 (*1/*1) increased the risk of delayed communication skills at 3 years of age, whereas alcohol consumption by mothers carrying a heterozygotic genotype of ALDH2 (*1/*2) enhanced the risk of developmental delay in all five domains of the J-ASQ-3. The impact of ADH1B gene polymorphism could not be clearly elucidated.

Conclusions: Our results suggest that alcohol consumption by pregnant females carrying the deficient variant ALDH2*2 genotype may increase the risk of developmental delay in their offspring.