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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.

Aims: Like most European countries, Norway has refrained from mandatory food fortification with folic acid to reduce the number of neural tube defects. We explored the role of folic acid and multivitamin supplements in the prevention of neural tube defects among newborn infants., Methods: We used data from the Medical Birth Registry of Norway, 1999-2013. A total of 528,220 women had 880,568 pregnancies resulting in 896,674 live- and stillborn infants, of whom 270 had neural tube defects. Relative risks were estimated with log-binomial regression., Results: From 1999 to 2013, intake of folic acid supplements increased from 4.8% to 27.4%. Vitamin supplement use was more frequent in older, married or cohabiting women and those with lower parity, as well as women who did not smoke during pregnancy. The overall adjusted relative risk of infant neural tube defects associated with maternal vitamin intake before pregnancy relative to no intake was 0.76 (95% confidence interval: 0.53-1.10). When we divided our study period in two (1999-2005 and 2006-2013), we found a significantly reduced risk of neural tube defects overall by vitamin use in the second time period, but not in the first: adjusted relative risk 0.54 (95% confidence interval: 0.31-0.91) and 1.02 (95% confidence interval: 0.63-1.65), respectively., Conclusions: OVER THE FULL STUDY PERIOD, WE FOUND NO STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN VITAMIN USE AND NEURAL TUBE DEFECTS OVERALL HOWEVER, VITAMIN USE WAS ASSOCIATED WITH A SIGNIFICANTLY LOWER RISK OF NEURAL TUBE DEFECTS IN THE SECOND HALF OF THE STUDY PERIOD, 2006-2013., (© 2016 the Nordic Societies of Public Health.)

Results from previous studies on maternal folic acid intake and infant oral clefts are inconclusive. The aim of the present study was to investigate the association between women's use of folic acid and/or multivitamin supplements and the risk for oral cleft in the newborn. We used data from the Medical Birth Registry of Norway based on all births in Norway from 1999 to 2013. A total of 528 220 women had 880 568 pregnancies, resulting in 896 674 live births and stillbirths, of which 1623 had oral clefts (isolated oral clefts, n 1311; non-isolated oral clefts, n 312). Altogether, 21·5% of women were vitamin supplement users before pregnancy. The birth prevalence of oral clefts was 1·81/1000 live births and stillbirths. Relative risks (RR) were estimated with log-binomial regression. For pregnancies with maternal use of vitamins, the adjusted RR for clefts overall was 0·90 (95% CI 0·79, 1·04). The adjusted RR for cleft palate only (n 586) was 0·84 (95% CI 0·66, 1·06) and that for cleft lip with or without cleft palate (n 1037) was 0·94 (95% CI 0·79, 1·13). Associations were stronger for cleft cases that occurred in combination with other malformations (adjusted RR 0·63; 95% CI 0·45, 0·88), although vitamin supplements provided no protection against isolated clefts (adjusted RR 0·98; 95% CI 0·84, 1·15). In conclusion, our study demonstrates no statistically significant association between vitamin use and isolated oral clefts. However, we found lower risk for oral clefts that occurred in combination with other malformations.

Background: The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs., Methods: Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression., Results: Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]., Conclusions: Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation., (© 2015 The Authors. Paediatric and Perinatal Epidemiology Published by John Wiley & Sons Ltd.)