Maternal dietary folate intake with folic acid supplements and wheeze and eczema in children aged 2 years in the Japan Environment and Children's Study.

Maternal intake of folic acid supplements is reportedly associated with the risk of early-onset allergies in offspring. However, only a few studies have considered the intake of both folic acid supplements and dietary folate. Here, the relationship between maternal intake of folic acid supplements and allergic symptoms such as wheeze and eczema in offspring was analyzed while considering dietary folate intake. We examined 84,361 mothers and 85,114 children in the Japan Environment and Children's Study. The participants were divided into three groups depending on maternal folic acid supplementation ("no use," "occasional use," and "daily use"). Each group was then subdivided into three groups based on total folic acid and dietary folate intake. Outcomes were determined considering the wheeze and eczema status of each child at the age of 2 years. The status was based on the International Study of Asthma and Allergies in Childhood. It was found that 22.1% of the mothers took folic acid supplements daily. In contrast, 56.3% of the mothers did not take these supplements. Maternal intake of folic acid supplements was not associated with wheeze and eczema in the offspring. In contrast, only dietary folate intake was positively associated with wheeze at the age of 2 (adjusted odds ratio, 1.103; 95% confidence interval, 1.003-1.212). However, there is no scientific evidence of a biological mechanism that clarifies this result. Potential confounders such as other nutrition, outdoor/indoor air pollution, and genetic factors may have affected the results. Therefore, further studies on the association between maternal intake of folic acid and allergic symptoms at the age of 3 or above are needed to confirm the results of this study. Trial registration UMIN Clinical Trials Registry (number: UMIN000030786).

Population Attributable Fractions of Modifiable Risk Factors for Nonsyndromic Orofacial Clefts: A Prospective Cohort Study From the Japan Environment and Children's Study.

BACKGROUND: Population impact of modifiable risk factors on orofacial clefts is still unknown. This study aimed to estimate population attributable fractions (PAFs) of modifiable risk factors for nonsyndromic cleft lip with or without cleft palate (CL±P) and cleft palate only (CP) in Japan. METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. We estimated the PAFs of maternal alcohol consumption, psychological distress, maternal active and passive smoking, abnormal body mass index (BMI) (<18.5 and ≥25 kg/m2), and non-use of a folic acid supplement during pregnancy for nonsyndromic CL±P and CP in babies. RESULTS: A total of 94,174 pairs of pregnant women and their single babies were included. Among them, there were 146 nonsyndromic CL±P cases and 41 nonsyndromic CP cases. The combined adjusted PAF for CL±P of the modifiable risk factors excluding maternal alcohol consumption was 34.3%. Only maternal alcohol consumption was not associated with CL±P risk. The adjusted PAFs for CL±P of psychological distress, maternal active and passive smoking, abnormal BMI, and non-use of a folic acid supplement were 1.4% (95% confidence interval [CI], -10.7 to 15.1%), 9.9% (95% CI, -7.0 to 26.9%), 10.8% (95% CI, -9.9 to 30.3%), 2.4% (95% CI, -7.5 to 14.0%), and 15.1% (95% CI, -17.8 to 41.0%), respectively. We could not obtain PAFs for CP due to the small sample size. CONCLUSIONS: We reported the population impact of the modifiable risk factors on CL±P, but not CP. This study might be useful in planning the primary prevention of CL±P.

Prevalence of childhood wheeze and modified DNA methylation at 7 years of age according to maternal folate levels during pregnancy in the Hokkaido Study.

BACKGROUND: A high dose of folic acid during pregnancy may increase the risk of asthma, wheezing, and respiratory disease in childhood. Folate acid can modify inflammation and immune susceptibility of offspring with some epigenetic differentiation, including DNA methylation. This study evaluated associations between maternal folate levels during pregnancy and childhood wheezing; furthermore, the study assessed whether maternal folate-modified DNA methylation is related to asthma. Methods Participants in the current study were 6651 mother-child pairs who had complete data on characteristics and who had completed at least one of the International Study of Asthma and Allergies in Childhood questionnaires when the child was 1, 2, 4, and 7 years of age. Moreover, a case-control study to assess DNA methylation at 7 years of age was conducted among 136 children who experienced wheezing and a control group of 139 children with no history of allergies. Results The median of maternal serum was 16.76 nmol/L, assayed by chemiluminescent immunoassay. We found significantly increased adjusted odds ratios of childhood wheezing at 2 years age according to maternal folate levels, compared with the lowest folate quartile (odds ratio [95% confidence interval] = highest; 1.27 [1.03, 1.56], and second, 1.27 [1.05, 1.55]); however, no changes were observed at 1, 4, and 7 years of age. In a case-control study, no association of maternal folate levels with DNA methylation was observed. Conclusion Our results suggest that maternal folate did not affect persistent wheezing in school-aged children, or DNA methylation of gasdermin B, orosomucoid-like 3, and Ikaros family zinc finger 3 at 7 years of age.

Association of blood mercury levels during pregnancy with infant birth size by blood selenium levels in the Japan Environment and Children's Study: A prospective birth cohort.

BACKGROUND: It is necessary to determine whether there are adverse health effects of prenatal exposure to long-term, low levels of mercury and selenium. However, there are limited that reports on the association between mercury levels by selenium levels and birth size. Therefore, we examined whether maternal mercury levels during pregnancy had any effect on infant birth size, and size, and whether selenium levels influenced this relationship. OBJECTIVES: To examine the association between mercury and selenium levels during pregnancy with infant birth size. METHODS: The Japan Environment and Children's Study is a prospective birth cohort conducted between 2011 and 2014. Total mercury levels and total selenium levels in maternal blood during the second and third trimesters were measured using Inductively Coupled Plasma-Mass Spectrometry. Birth weight and small-for-gestational-age were confirmed by medical records. Small-for-gestational-age was defined as birth weight below the 10th percentile according to standard percentile for gender, parity, and gestational age. Multiple linear and logistic regression analyses were used to examine the association between maternal mercury exposure and birth weight or small-for-gestational-age adjusted for confounders (including maternal age and body mass index pregnancy). RESULTS: Overall, 15,444 pregnant women were included in this study. Median (inter-quartile range) of blood mercury and selenium levels were 3.66 (2.59-5.18) ng/g and 170.0 (158.0-183.0) ng/g, respectively. Compared to infants of mothers with the highest blood selenium level, those of mothers with the lowest blood selenium level had neither a significant birth weight increase (9 g, 95% confidence interval: -6, 25) nor a significant odds ratio for small-for-gestational-age (0.903, 95% confidence interval: 0.748, 1.089). Compared to infants of mothers with the lowest blood mercury level, those of mothers with the highest blood mercury level had neither a significant birth weight reduction (-12 g, 95% confidence interval: -27, 4) nor a significant odds ratio for small-for-gestational-age (0.951, 95% confidence interval: 0.786, 1.150). Compared to infants of mothers with the lowest quartile of maternal blood mercury level, all infants of mothers with the highest quartile of maternal blood mercury level had a reduced birth head circumference of 0.073 cm (95% confidence interval: -0.134, -0.011). CONCLUSIONS: There was no association between maternal blood mercury levels and small-for-gestational-age and birth weight among 15,444 pregnant women. In a Japanese population, which has a relatively higher blood mercury level than reported in Western population, reduced birth size was not found to be associated with blood mercury levels, with the exception of birth head circumference.