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Scope: Birth cohorts typically measure plasma folate in midgestation, but effects of folic acid supplementation are sometimes specific to the periconceptional period. The relationship between midgestation plasma folate and periconceptional supplementation is not known. We compared plasma folate at week 18 of gestation with self-report use of supplements comtaining folic acid from before pregnancy to week 17 of gestation., Methods and Results: The sample comprised 2911 women from The Norwegian Mother and Child Cohort Study. For women reporting continuous supplementation from gestational week -4 to 17 (N = 238), median plasma folate was 15.72 at week 18 (in nmol/L). This was about threefold higher than the median plasma folate of 5.67 for women reporting no supplementation from week -4 to 17 (N = 844), but only slightly higher than the median plasma folate of 13.34 for all women reporting supplementation in weeks 13-17 (N = 1158). Reported supplementation before week 8 was not associated with plasma folate at week 18, in an analysis that adjusted for continued supplementation after week 8., Conclusion: Overall we found a strong and coherent relationship between self-reported folic acid use and plasma folate at week 18. We also found that plasma folate at week 18 did not reflect self-reported supplementation before week 8. For periconceptional supplementation per se, self-report data may offer a better measure., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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. [ABSTRACT FROM AUTHOR]

Objective To study differences in ultrasound-based compared to menstrual-based term estimation in women with type 1 diabetes. Design Nationwide register study. Setting Norway. Population Deliveries in Norway 1999-2004 by women registered in the Norwegian Childhood Diabetes Registry ( n = 342) and the background population ( n = 307 248), with data on both ultrasound-based and menstrual-based gestational age notified in the Birth Registry of Norway. Births with major malformations were excluded. Methods Linkage of two nationwide registries, the Medical Birth Registry of Norway and the Norwegian Childhood Diabetes Registry. Main outcome measures Estimated gestational age at delivery based on routine second trimester ultrasound measurements and last menstrual period. Results In women with type 1 diabetes, the distribution of gestational age at delivery was shifted considerably towards a lower gestational age when using second trimester ultrasound data for estimation, compared with last menstrual period data. The difference between the two estimation methods was larger among women with type 1 diabetes, although also evident in the general population. One in four women with diabetes and a certain last menstrual period date had their ultrasound-calculated term postponed 1 week or more, while one in 10 had it postponed 2 weeks or more. Corresponding numbers in the background population were one in five and one in 20. Conclusions We found a systematic postponement of ultrasound-based compared with menstrual-based term estimation in women with type 1 diabetes. Relying solely on routine ultrasound-based term calculation for delivery decision may imply a risk of going beyond an optimal pregnancy length. [ABSTRACT FROM AUTHOR]

Purpose Antiepileptic drugs may cause congenital malformations. Less is known about the effect on development in infancy and childhood. The aim of this study was to examine whether exposure to antiepileptic drugs during pregnancy has an effect on early child development. Methods From mid-1999 through December 2008, children of mothers recruited at 13-17 weeks of pregnancy were studied in the ongoing prospective Norwegian Mother and Child Cohort Study. Information on birth outcomes were obtained from the Medical Birth Registry (108,264 children), and mothers reported on their child's motor development, language, social skills, and autistic traits using items from standardized screening tools at 18 months (61,351 children) and 36 months (44,147 children) of age. The relative risk of adverse outcomes in children according to maternal or paternal epilepsy with and without prenatal exposure to antiepileptic drugs was estimated as odds ratios ( ORs), using logistic regression with adjustment for maternal age, parity, education, smoking, depression/anxiety, folate supplementation, and child congenital malformation or low birth weight. Key Findings A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, the exposed children had increased risk of abnormal scores for gross motor skills (7.1% vs. 2.9%; OR 2.0, 95% confidence interval [ CI] 1.1-3.7) and autistic traits (3.5% vs. 0.9%; OR 2.7, CI 1.1-6.7) compared to children of parents without epilepsy. At 36 months, the exposed children had increased risk of abnormal score for gross motor skills (7.5% vs. 3.3%; OR 2.2, CI 1.1-4.2), sentence skills (11.2% vs. 4.8%; OR 2.1, CI 1.2-3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6-7.0). The drug-exposed children also had increased risk of congenital malformations (6.1% vs. 2.9%; OR 2.1, CI 1.4-3.4), but exclusion of congenital malformations did not affect the risk of adverse development. Children born to women with epilepsy who did not use antiepileptic drugs had no increased risks. Children of fathers with epilepsy generally scored within the normal range. Significance Exposure to antiepileptic drugs during pregnancy is associated with adverse development at 18 and 36 months of age, measured as low scores within key developmental domains rated by mothers. Exposures to valproate, lamotrigine, carbamazepine, or multiple antiepileptic drugs were associated with adverse outcome within different developmental domains. [ABSTRACT FROM AUTHOR]

Objective. To estimate the risk of congenital anomalies in offspring of women with type 1 diabetes in Norway during recent years. Design. Nationwide population-based study using the Medical Birth Registry of Norway and the Norwegian type 1 Diabetes Registry. Setting. All birth clinics in Norway. Participants. All births in Norway during 1999-2004 ( N = 350,961), of which 1,583 were births by a mother registered with pregestational type 1 diabetes. Main outcome measure. Congenital anomalies, excluding minor anomalies according to the EUROCAT system. Results. Anomalies were registered in 5.7% of offspring of women with type 1 diabetes, and in 2.9% among the background population (odds ratio 2.1, 95% CI: 1.7-2.6). Cardiovascular anomalies were registered in 3.2% in the diabetes group and 0.94% in the background population (odds ratio 3.5, 95% CI: 2.7-4.7). Results were similar when restricted to women identified with type 1 diabetes through the Diabetes Registry. Conclusions. Women in Norway with type 1 diabetes experience a significantly higher risk of congenital anomalies in their babies compared with the background population. [ABSTRACT FROM AUTHOR]

Background: Patterns and predictors of maternal folic acid supplement use have not been examined in large prospective studies of pregnant women. Objective: We examined the patterns and predictors of maternal folic acid supplement use from 2 mo before pregnancy through the eighth month of pregnancy. Design: Data from 22 500 women in the Norwegian Mother and Child Cohort Study with deliveries recorded in 2000-2003 were analyzed. Results: Folic acid supplement use increased from 11.8% at 2 mo before pregnancy to 46.9% at gestational month 3, but decreased to 26.0% at gestational month 8. Of 16 116 women (71.6%) who had taken folic acid supplements at some time before or during pregnancy, 72.4% had started use after becoming pregnant. Ten percent of the women had used supplements regularly from 1 mo before pregnancy throughout the first trimester. These women more frequently reported higher maternal and paternal education, planned pregnancies, infertility treatments, or chronic diseases. They were also more likely to be older, married, and nonsmokers and to have higher income and lower parity. Conclusions: Most women started folic acid supplementation too late with respect to the prevention of neural tube defects. More effective intervention programs to improve periconceptional intakes of folic acid are needed and should consider both demographic and socioeconomic factors. [ABSTRACT FROM AUTHOR]

Purpose: Methylenetetrahydrofolate reductase (MTHFR) is involved in the metabolism of folate and homocysteine; a polymorphism in the MTHFR gene (677C→T) has been associated with adverse outcomes of pregnancy. We studied whether two polymorphisms in the MTHFR gene (677C→T and 1298A→C) are associated with pregnancy complications, adverse outcomes, and birth defects.Methods: MTHFR polymorphisms were determined in blood collected in 1992 and 1993 from 5883 women aged 40 to 42 years, and linked with 14,492 pregnancies in the same women recorded in the Medical Birth Registry of Norway from 1967 to 1996.Results: The 677TT genotype in mothers was associated with increased risk of placental abruption (odds ratio [OR] = 2.6; 95% confidence interval [CI]: 1.4 to 4.8) compared with the CC variant. The risk of intrauterine growth restriction increased with number of T alleles (P for trend = 0.04). Compared with the 1298AA variant, the CC variant was associated with a reduced risk of very low birth weight infants (OR = 0.4; 95% CI: 0.2 to 0.8). No significant associations were found between MTHFR polymorphisms and birth defects.CONCLUSION: The maternal MTHFR 677C→T polymorphism was a risk factor for placental abruption. The unexpected protective effect of the 1298A→C polymorphism on very low birth weight needs further study. [Copyright &y& Elsevier]