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 (99·0 %) live-born infants, 6633 (0·7 %) stillborn infants and 2135 (0·2 %) 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 0·94 (95 % CI 0·91, 0·98) for total birth defects (n 18 382). Supplement use was associated with reduced risk of abdominal wall defects (aRR 0·58; 95 % CI 0·42, 0·80, n 377), genital organ defects (aRR 0·81; 95 % CI 0·72, 0·91, n 2299) and limb defects (aRR 0·81; 95 % CI 0·74, 0·90, n 3409). 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.

中文翻译：

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1999-2013 年挪威孕产妇使用叶酸和多种维生素补充剂与婴儿出生缺陷的风险

叶酸补充与神经管缺陷（NTD）以外的出生缺陷之间的关联仍不清楚。我们使用对数二项式回归模型来研究围孕期叶酸和/或多种维生素的使用是否与挪威出生缺陷相关，前瞻性收集了挪威医学出生登记处 (MBRN) 在 1999 年至 2013 年期间的数据。我们使用欧洲先天性异常监测 (EUROCAT) 分类系统来定义 11 个器官特异性主要出生缺陷组（神经系统、眼睛、耳-面-颈、心血管系统、呼吸系统、口腔裂隙、消化系统、腹壁、泌尿系统、生殖器官和肢体），还有其他亚组。母亲在怀孕前和怀孕期间使用叶酸和/或多种维生素补充剂的胎儿或婴儿被归类为暴露。在 1999 年至 2013 年期间，在 MBRN 登记了 888 294 (99·0 %) 活产婴儿、6633 (0·7 %) 死产婴儿和 2135 (0·2 %) 因胎儿异常而终止妊娠的胎儿. 在使用维生素补充剂的妇女的活产和死产婴儿中，与未使用维生素补充剂的婴儿相比，总出生缺陷的调整相对风险 (aRR) 为 0·94 (95 % CI 0·91, 0·98) (n18 382）。使用补充剂与降低腹壁缺陷的风险相关（aRR 0·58；95 % CI 0·42、0·80、n377), 生殖器官缺陷 (aRR 0·81; 95 % CI 0·72, 0·91,n2299) 和肢体缺陷 (aRR 0·81; 95 % CI 0·74, 0·90,n3409）。尽管 CI 包括 1 的空值，但也建议 NTD、呼吸系统缺陷和消化系统缺陷具有保护性关联。在整个研究期间，补充剂使用与眼睛、耳-脸-颈部、心脏或未观察到口裂。