Interaction between maternal caffeine intake during pregnancy and CYP1A2 C164A polymorphism affects infant birth size in the Hokkaido study.

BackgroundCaffeine, 1,3,7-trimethylxanthine, is widely consumed by women of reproductive age. Although caffeine has been proposed to inhibit fetal growth, previous studies on the effects of caffeine on infant birth size have yielded inconsistent findings. This inconsistency may result from failure to account for individual differences in caffeine metabolism related to polymorphisms in the gene for CYP1A2, the major caffeine-metabolizing enzyme.MethodsFive hundred fourteen Japanese women participated in a prospective cohort study in Sapporo, Japan, from 2002 to 2005, and 476 mother-child pairs were included for final analysis.ResultsCaffeine intake was not significantly associated with mean infant birth size. When caffeine intake and CYP1A2 C164A genotype were considered together, women with the AA genotype and caffeine intake of ≥300 mg per day had a mean reduction in infant birth head circumference of 0.8 cm relative to the reference group after adjusting for confounding factors. In a subgroup analysis, only nonsmokers with the AA genotype and caffeine intake of ≥300 mg per day had infants with decreased birth weight (mean reduction, 277 g) and birth head circumference (mean reduction, 1.0 cm).ConclusionNonsmokers who rapidly metabolize caffeine may be at increased risk for having infants with decreased birth size when consuming ≥300 mg of caffeine per day.