Maternal use of folic acid and multivitamin supplements and infant risk of birth defects in Norway 1999-2013.

The association between folic acid supplementation and birth defects other than neural tube defects (NTD) remains unclear. We used a log-binomial regression model to investigate if periconceptional folic acid and/or multivitamin use was associated with birth defects in Norway with prospectively collected data from the Medical Birth Registry of Norway (MBRN) during 1999-2013. We used the European Surveillance of Congenital Anomalies (EUROCAT) classification system to define eleven organ-specific major birth defect groups (nervous system, eye, ear-face-neck, cardiovascular system, respiratory system, oral clefts, digestive system, abdominal wall, urinary system, genital organs and limb), with additional subgroups. Fetuses or infants whose mothers used folic acid and/or multivitamin supplements before and during pregnancy were classified as exposed. During the years 1999-2013, 888 294 (99 center dot 0 %) live-born infants, 6633 (0 center dot 7 %) stillborn infants and 2135 (0 center dot 2 %) fetuses from terminated pregnancies due to fetal anomalies were registered in the MBRN. Among the live- and stillborn infants of women who used vitamin supplements compared with infants of non-users, the adjusted relative risk (aRR) was 0 center dot 94 (95 % CI 0 center dot 91, 0 center dot 98) for total birth defects (n18 382). Supplement use was associated with reduced risk of abdominal wall defects (aRR 0 center dot 58; 95 % CI 0 center dot 42, 0 center dot 80,n377), genital organ defects (aRR 0 center dot 81; 95 % CI 0 center dot 72, 0 center dot 91,n2299) and limb defects (aRR 0 center dot 81; 95 % CI 0 center dot 74, 0 center dot 90,n3409). Protective associations were also suggested for NTD, respiratory system defects and digestive system defects although CI included the null value of 1. During the full study period, statistically significant associations between supplement use and defects in the eye, ear-face-neck, heart or oral clefts were not observed.