Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan environment and children's study.

OBJECTIVE: We evaluated the relationship between prenatal folic acid supplementation and autism spectrum disorder (ASD) in 3-year-old offspring. METHODS: We used data from the Japan Environment and Children's Study, a nationwide prospective birth cohort study. We analyzed the data to determine the association between folic acid supplement use and the incidence of ASD in offspring, and classified participants into three groups based on the time of initiation of folic acid supplementation, as follows: (1) preconception users of folic acid supplements and (2) post-conception users, and (3) non-users. The dietary folate intake of study participants was also classified into three groups (<200 µg, 200 µg to <400 µg, ≥400 µg). RESULTS: Overall, 361 offspring of 96,931 participants with single pregnancies were diagnosed with ASD (0.37%). A total of 7,046 participants (7.3%) used folic acid supplements before conception, 29,984 (30.9%) took them after detection of pregnancy, and 59,901 (61.8%) never received them. Multivariate logistic regression analyses demonstrated no association between prenatal folic acid supplementation and ASD in offspring (preconception use: adjusted odds ratio [AOR], 1.189; 95% confidence interval [CI], 0.819-1.727 and post-conception use: AOR, 1.072; 95% CI, 0.840-1.368); additionally, no association was observed with the use of folic acid supplements and/or multivitamin supplements (preconception use: AOR, 1.273; 95% CI, 0.921-1.760 and post-conception use: AOR, 1.132; 95% CI, 0.885-1.449). Moreover, no significant association was observed in participants with combined prenatal supplement use and dietary folate intake. CONCLUSIONS: Maternal use of folic acid supplements from the pre- or post-conception period was not significantly associated with ASD in 3-year-old offspring in Japan. Evaluation of the dietary folate intake from preconception also showed no significant association.

Plasma and red blood cells distribution of total mercury, inorganic mercury, and selenium in maternal and cord blood from a group of Japanese women.

Fetuses are a high-risk group for methylmercury (MeHg) exposure. The main objective of this study was to compare the characteristic profiles of total mercury (THg), inorganic mercury (IHg), MeHg, and selenium in plasma and red blood cells (RBCs) between maternal and cord blood at parturition collected from a group of Japanese women. Furthermore, correlations of THg in RBCs, which is a biomarker of MeHg, and THg in plasma, which is an IHg exposure biomarker, were examined in maternal and cord blood. Fifty-five pairs of maternal and cord blood samples obtained at parturition were collected from pregnant women in Fukuoka, Japan. THg in RBCs and plasma were significant correlated between maternal and cord blood. THg in RBCs was 13.9 ng/mL for cord and 9.16 ng/mL for maternal blood, with a cord:maternal RBCs ratio for THg of 1.58, suggesting that MeHg is actively transferred from the mother to the fetus via the placenta. THg in plasma showed a positive correlation with THg in RBCs for maternal and cord blood. This result suggests that measuring THg in plasma can overestimate the exposure level to IHg in fish-eating populations. The percentages of IHg in cord plasma and RBCs were 31% and 1.7%, respectively, and those in maternal plasma and RBCs were 46% and 5.9%, respectively. These results suggest that cord blood is rich in MeHg and can easily transfer to the fetal brain. Selenium in cord plasma was 67 ng/mL and that in maternal plasma was 97 ng/mL, with a cord:maternal plasma ratio for Se of 0.69, suggesting that the protective effects of Se against MeHg toxicity in fetuses may be weaker than those expected in adult mothers.

Health Risk Assessment and Source Apportionment of Mercury, Lead, Cadmium, Selenium, and Manganese in Japanese Women: An Adjunct Study to the Japan Environment and Children's Study.

Toxic element pollution is a serious global health concern that has been attracting considerable research. In this study, we elucidated the major routes of exposure to three toxic elements (mercury, cadmium, and lead) and two essential elements (manganese and selenium) through diet, soil, house dust, and indoor air and assessed the potential health risks from these elements on women from the coastal area of Miyagi prefecture, Japan. Twenty-four-hour duplicate diet, house dust, soil, and indoor air samples were collected from 37 participants. Cd, Pb, Mn, and Se concentrations were measured using inductively coupled plasma mass spectrometry, and Hg concentrations using cold vapor atomic absorption spectrometry. We found that soil and house dust were the primary reservoirs of these elements. Diet contributed most strongly to the daily intake of these elements, with mean values of 0.72, 0.25, 0.054, 47, and 0.94 µg/kg/day for Hg, Cd, Pb, Mn, and Se, respectively. The mean hazard quotient of Hg was 1.53, indicating a high potential health risk from Hg exposure in daily lives. The intakes of other elements were below the tolerable limits. Future studies with a larger sample size are warranted to confirm our findings.

Update on the prevalence and determinants of folic acid use in Japan evaluated with 91,538 pregnant women: the Japan Environment and Children's Study.

Objective: To provide the latest and most promising evidence on the prevalence and determinants for folic acid supplementation in pregnant women in Japan, including differences in prevalence between interview years and determinants across regions.Materials and methods: The study participants were enrolled from 15 regional centers across Japan between January 2011 and March 2014. Information on the use of folic acid supplementation before and during pregnancy and the characteristics of the participants were collected using questionnaires, medical chart reviews, and interviews by research coordinators.Results: Data for 91,538 women who provided sufficient data on folic acid supplementation were analyzed. The prevalence of adequate users was 8.0%, which, although low, tended to improve over the 4-year recruitment period. Various kinds of sociodemographic factors, lifestyle habits, and obstetrical and medication use history were significant and independent determinants for folic acid use. Associations between adequate preconception folic acid use and its major determinants tended to be similar across regions.Conclusions: Although the prevalence of adequate folic acid use was low, it increased from 2011 to 2014. Reproductive-aged women who have determinants for inadequate folic acid use should be informed about the need for preconception folic acid supplementation to help prevent neural tube defects.

Associations of environmental exposures to methylmercury and selenium with female infertility: A case-control study.

BACKGROUND: Methylmercury exposure is a common health risk resulting from daily fish intake. However, studies addressing the link between methylmercury and infertility are limited and also inconsistent. In addition, no previous epidemiological studies have accounted for the interaction between methylmercury and selenium. We aimed to investigate the association between environmental exposures to metals and female fertility. METHODS: This case-control study included 98 infertile women receiving fertility treatment (infertile group) and 43 female workers in their thirties (control group) who provided blood samples and returned a questionnaire on lifestyles and dietary characteristics. Blood levels of mercury, lead, cadmium, arsenic, manganese, zinc, and selenium were compared between the groups. Spearman correlation analyses between anti-Müllerian hormone and the metals were conducted. RESULTS: The mean selenium level in blood (±â€¯SD) and the selenium/mercury molar ratio were significantly lower in the infertile group (189 ±â€¯25 µg/L and 94.6 ±â€¯44.3, respectively) than in the control group (200 ±â€¯25 µg/L and 118.4 ±â€¯70.5). By contrast, blood mercury levels after adjusting for blood selenium and age were significantly higher in the infertile group than in the control group. Multiple logistic regression analyses with the adjustment for the other metals and potential confounders confirmed significant associations of infertility with elevated mercury and reduced selenium levels. No significant correlations were observed between anti-Müllerian hormone and metals. CONCLUSIONS: Methylmercury and selenium exposures appear to have adverse and protective effects on female fertility, respectively. This is the first report to suggest the antagonistic interaction between methylmercury and selenium in relation to human female fertility.

Drug Use before and during Pregnancy in Japan: The Japan Environment and Children's Study.

Purpose: To elucidate drug use before and during pregnancy in Japan. Methods: The Japan Environment and Children's Study (JECS) is an ongoing nationwide birth cohort study. We analyzed data from JECS involving cases where drugs were used for 12 months before pregnancy was diagnosed, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy. Results: We analyzed data from 97,464 pregnant women. The percentages of pregnant women who had taken one or more drugs and supplements before diagnosis of pregnancy, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy, were 78.4%, 57.1%, and 68.8% respectively. Excluding iron supplements, folic acid, and other vitamins and minerals, the percentages of women taking supplements were 75.3%, 36.0%, and 51.7% at each respective time point. The following drugs and supplements were frequently used for 12 months before pregnancy diagnosis: Commercially available antipyretics, analgesics, and/or medicine for treating common cold (34.7%), antipyretics, analgesics, and/or medicine for treating common colds, which were prescribed in hospitals (29.8%), antimicrobial drugs (14.0%), and anti-allergy drugs (12.5%). The following drugs and supplements were frequently used from the time of pregnancy diagnosis until week 12 of pregnancy, and after week 12 of pregnancy: folic acid (28.9% and 26.2%), antipyretics, analgesics and/or medicines for treating common cold, that were prescribed in hospitals (7.8% and 13.3%), Chinese herbal medicines (6.0% and 9.4%, and uterine relaxants (5.1% and 15.2%). Conclusions: The analysis of a nationwide cohort study showed that a high percentage of Japanese pregnant women were taking medicinal drugs. Further research is required to elucidate the relationship between drug use during pregnancy and birth defects in Japan.

Prevalence and determinants of inadequate use of folic acid supplementation in Japanese pregnant women: the Japan Environment and Children's Study (JECS).

OBJECTIVE: The aim of the study was to clarify the prevalence and determinants of inadequate use of folic acid supplementation in pregnant Japanese women. METHODS: This study was part of the Japan Environment and Children's Study, a nationwide and government-funded birth cohort study. We collected information on the use of folic acid supplementation before and during pregnancy and characteristics of participants using self-administered questionnaire. RESULTS: Among 9849 women who completed the data collection for this study, the prevalence of inadequate users was 92.6% of the total population and varied from 84.5% to 96.2% among regions. On the basis of multivariate logistic regression analysis, younger age, not married, lower family income, multipara, natural conception and no history of spontaneous abortion were found to be determinants for inadequate users of folic acid supplementation. CONCLUSION: Most Japanese pregnant women show inadequate folic acid supplementation use. Japanese women of child-bearing age need to be specifically informed about the need for periconceptional intake of folic acid to prevent neural tube defects.