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Background Low red blood cell folate concentrations during early pregnancy might cause neural tube defects. However, the association between folate concentrations and birth defects of other neural crest cell-derived organs remains unknown. We investigated the associations between birth defects and first-trimester serum folate concentrations in a birth-cohort study in Japan. Methods In total, 14,896 women who were prior to 13 weeks of gestation were enrolled from 2003 through 2012. Birth defect information was obtained from medical records and questionnaires. The association between folate levels in the first trimester and birth defects categorized as ICD-10 cord defects and neural crest cell-derived organ defects was examined. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per log-transformed folate concentration were calculated using logistic regression. Results Blood samples were obtained at a mean of 10.8 weeks of gestation. Median serum folate level was 16.5 (interquartile range, 13.4-21.5) nmol/L, and the deficiency level (less than 6.8 nmol/L) was 0.7%. There were 358 infants with birth defects. The adjusted odds ratio for any birth defect, ventricular septal defects, and cleft lip was 0.99 (95% CI, 0.74-1.32), 0.63 (95% CI, 0.30-1.33), and 4.10 (95% CI, 0.96-17.58), respectively. There were no significant associations between first-trimester maternal serum folate and the risk of birth defects. Conclusions We were unable to demonstrate a relationship between maternal serum folate in the first trimester and birth defects. Potential confounding factors may have influenced our results.

Background Prevalence rates of all anomalies classified as birth defects, including those identified before the 22nd gestational week, are limited in published reports, including those from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). In our birth cohort study, we collected the data for all birth defects after 12 weeks of gestation. Methods Subjects in this study comprised 19,244 pregnant women who visited one of 37 associated hospitals in the Hokkaido Prefecture from 2003 through 2012, and completed follow-up. All birth defects after 12 weeks of gestation, including 55 marker anomalies associated with environmental chemical exposures, were recorded. We examined parental risk factors for birth defects and the association between birth defects and risk of growth retardation. Results Prevalence of all birth defects was 18.9/1,000 births. The proportion of patients with birth defects delivered between 12 and 21 weeks of gestation was approximately one-tenth of all patients with birth defects. Among those with congenital malformation of the nerve system, 39% were delivered before 22 weeks of gestation. All patients with anencephaly and encephalocele were delivered before 22 weeks of gestation. We observed different patterns of parental risk factors between birth defect cases included in ISBDSR and cases not included. Cases included in ISBDSR were associated with an increased risk of preterm birth. Cases not included in ISBDSR were associated with an increased risk of being small for gestational age at term. Conclusions Data from our study complemented the data from ICBDSR. We recommend that birth defects not included in ICBDSR also be analyzed to elucidate the etiology of birth defects.

Background: The impact of long working hours on diabetes is controversial; however, shift work is known to increase the risk of diabetes. This study aimed to investigate the association between long working hours and diabetes among civil servants in Japan separately by shift work schedules. Methods: A prospective cohort study was conducted from April 2003 to March 2009. A total of 3195 men aged >= 35 years who underwent an annual health checkup at baseline were analyzed by shift work schedules (2371 nonshift workers and 824 shift workers). Self-reported working hours were categorized as 35-44 and >= 45 hours per week. The incidence of diabetes was confirmed by fasting plasma glucose concentration >= 126mg/dL and/or self-reported medical diagnosis of diabetes at the annual checkup. A Cox proportional model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing diabetes associated with long working hours. Results: The median follow-up period of non-shift and shift workers was 5.0 and 4.9 years, respectively. During this period, 138 non-shift workers and 46 shift workers developed diabetes. A decreased HR was found among nonshift workers working >= 45 hours per week (HR 0.84; 95% CI, 0.57-1.24); however, shift workers working >= 45 hours per week had a significantly increased risk of diabetes (HR 2.43; 95% CI, 1.21-5.10) compared with those working 35-44 hours per week. An analysis restricted to non-clerical workers also showed similar results. Conclusions: The risk of diabetes associated with long working hours differed by shift work schedules.

Background: Use of fuel heaters is associated with childhood asthma. However, no studies have evaluated the associations of flue use and mechanical ventilation (ventilation) with asthma symptoms in schoolchildren. Methods: This cross-sectional study investigated schoolchildren in grades 1 through 6 (age 6–12 years) in Sapporo, Japan. From November 2008 through January 2009, parents completed questionnaires regarding their home environment and their children’s asthma symptoms. Results: In total, 4445 (69.5%) parents of 6393 children returned the questionnaire. After excluding incomplete responses, data on 3874 children (60.6%) were analyzed. The prevalence of current asthma symptoms and ever asthma symptoms were 12.8% and 30.9%, respectively. As compared with electric heaters, current asthma symptoms was associated with use of flued heaters without ventilation (OR = 1.62; 95% CI, 1.03–2.64) and unflued heaters with ventilation (OR = 1.77; 95% CI, 1.09–2.95) or without ventilation (OR = 2.23; 95% CI, 1.31–3.85). Regardless of dampness, unflued heaters were significantly associated with current asthma symptoms in the presence and absence of ventilation. Conclusions: Use of unflued heaters was associated with current asthma symptoms, regardless of dampness. In particular, the prevalence of current asthma symptoms was higher in the absence of ventilation than in the presence of ventilation. Ever asthma symptoms was only associated with use of unflued heaters without ventilation. Consequently, use of fuel heaters, especially those that have no flue or ventilation, deserves attention, as their use might be associated with childhood asthma symptoms.

Background: Intracellular folate hemostasis depends on the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Because 5,10-MTHFR 677TT homozygosity and tobacco smoking are associated with low folate status, we tested the hypothesis that smoking in mothers with 5,10-MTHFR C677T or A1298C polymorphisms would be independently associated with lower birth weight among their offspring. Methods: We assessed 1784 native Japanese mother-child pairs drawn from the ongoing birth cohort of The Hokkaido Study on Environment and Children's Health. Data (demographic information, hospital birth records, and biological specimens) were extracted from recruitments that took place during the period from February 2003 to March 2006. Maternal serum folate were assayed by chemiluminescent immunoassay, and genotyping of 5,10-MTHFR C677T/A1298C polymorphisms was done using a TaqMan allelic discrimination assay. Results: The prevalence of folate deficiency (< 6.8 nmol/L) was 0.3%. The 5,10-MTHFR 677CT genotype was independently associated with an increase of 36.40 g (95% CI: 2.60 to 70.30, P = 0.035) in mean infant birth weight and an increase of 90.70 g (95% CI: 6.00 to 175.50, P = 0.036) among male infants of nonsmokers. Female infants of 677TT homozygous passive smokers were 99.00 g (95% CI: -190.26 to -7.56, P = 0.034) lighter. The birth weight of the offspring of smokers with 5,10-MTHFR 1298AA homozygosity was lower by 107.00 g (95% CI: -180.00 to -33.90, P = 0.004). Conclusions: The results suggest that, in this population, maternal 5,10-MTHFR C677T polymorphism, but not the 5,10-MTHFR A1298C variant, is independently associated with improvement in infant birth weight, especially among nonsmokers. However, 5,10-MTHFR 1298AA might be associated with folate impairment and could interact with tobacco smoke to further decrease birth weight.

BACKGROUND: Hypospadias is one of the most common congenital anomalies in the world. Recently, increases in the prevalence of hypospadias have been reported in various countries including Japan. In this study, we examined whether the prevalence of hypospadias in Hokkaido, Japan, increased or not, using standardized diagnostic criteria. We also investigated the degree of its severity. METHODS: We calculated prevalence of hypospadias using hospital records of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by dividing the number of patients obtained from hospital records by the number of births. RESULTS: The average prevalence of hypospadias in Hokkaido was 3.9 per 10,000 births, and did not significantly changed (p=0.7). The average proportions of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively. The decrease in the proportion of the proximal type was statistically significant (p=0.05) for the entire time period, whereas the proportion of the distal type did not have a significant upward trend for the observed 13 years (p=0.1). CONCLUSION: No significant changes in the prevalence of hypospadias existed in Hokkaido.

Objective: To investigate whether changes at computed tomography (CT) imaging in the ageing brain are associated with future risks for functional dependence. Subjects: 160 residents aged 69 years and older at the cranial CT and were independently living in a rural community in Hokkaido, Japan. Methods: Cranial CT was performed between 1991 and 1993, graded for ventricular enlargement, sulcal enlargement, white matter change, and small infarction. Functional status was reassessed in 1998 in each participant. Multiple logistic regression analysis was performed to estimate the association of CT changes in the ageing brain with development of functional dependence over six years. Results: Functional dependence was found in 19 residents at the second survey. After adjusting for age, sex, medical conditions, and cognitive functioning, small infarction and ventricular enlargement were significantly associated with development of functional dependence (adjusted odds ratio = 9.27 and 4.62). Conclusions: After controlling for age, the age-related changes on cranial CT have significant association on development of functional dependence.

The effects of long-term blood pressure (BP) levels on cerebrovascular changes were analyzed in a community-based healthy elderly population. Cranial computed tomography (CT) was performed for 300 residents aged 69 years and older. Long-term BP during the ten years prior to CT was assessed, and the cerebrovascular changes were compared among different patterns of long-term blood pressure variability. White matter lesions (WML) and/or silent infarctions (SI) were found in 73 subjects (23.6%). Multiple logistic regression analysis showed that subjects with long-term diastolic hypertension (DHT) had the highest risk of cerebrovascular changes (adjusted odds ratio (OR), 95% confidence interval (CI); 7.1, 2.4-21.6, for WML; 7.2, 2.7-19.4, for SI), and that long-term isolated systolic hypertension (ISHT) was significantly associated with SI (adjusted OR, 95%Cl, 2.3, 1.1-4.9), but not with WML (adjusted OR, 95%CI, 1.3, 0.5-3.3). Efforts to prevent both DHT and ISHT would be beneficial, though different underlying mechanisms for WML and SI were suggested.J Epidemiol, 2001 ; 11 : 190-198