Maternal caffeine consumption and risk of congenital limb deficiency malformations

Caffeine is commonly consumed by pregnant women in the US. Limb deficiencies (LD)s are one of the most observed birth defect resulting from high dose caffeine exposure in animal studies. No human epidemiologic studies have explored the relation between maternal caffeine consumption and LDs. Using data from National Birth Defects Prevention Study, this case-control study described patterns of maternal dietary caffeine consumption, assessed associations between maternal caffeine consumption and LD risks, and further explored interaction of the above association by maternal gene variants for caffeine metabolism. Smoking, alcohol consumption, vasoconstrictive medications, and folic acid supplement use were evaluated for effect modification.;The results showed that dietary caffeine was commonly consumed during pregnancy. Dietary caffeine was weakly associated with increased risk of LDs in general and specific LD subgroups. No dose-response pattern was observed. Maternal smoking was observed to be a less than additive effect modifier. Interactions between caffeine and selected SNPs of maternal CYP1A2 and NAT2 were not observed among non-smokers. This study used a limited sample for gene-caffeine interaction. Full analysis will be conducted when the more complete data are available.;Overall, the results of this study suggest a possible association between dietary caffeine and certain component subgroups of LD among a subgroup of the population with specific inherited or non-inherited characteristics.