Association Between Maternal Serum Folate Concentrations in the First Trimester and the Risk of Birth Defects: The Hokkaido Study of Environment and Children’s Health

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  • Ito Kumiko
    Department of Public Health, Hokkaido University Graduate School of Medicine Hokkaido University Center for Environmental and Health Sciences Department of Nursing, Faculty of Health Science, Hokkaido University of Science
  • Hanaoka Tomoyuki
    Hokkaido University Center for Environmental and Health Sciences
  • Tamura Naomi
    Hokkaido University Center for Environmental and Health Sciences Department of Health Sciences, Hokkaido University Graduate School of Medicine
  • Sasaki Seiko
    Department of Public Health, Hokkaido University Graduate School of Medicine
  • Miyashita Chihiro
    Hokkaido University Center for Environmental and Health Sciences
  • Araki Atsuko
    Hokkaido University Center for Environmental and Health Sciences
  • Ito Sachiko
    Hokkaido University Center for Environmental and Health Sciences
  • Minakami Hisanori
    Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine
  • Cho Kazutoshi
    Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine
  • Endo Toshiaki
    Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University
  • Baba Tsuyoshi
    Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University
  • Miyamoto Toshinobu
    Department of Obstetrics and Gynecology, Asahikawa Medical University
  • Sengoku Kazuo
    Department of Obstetrics and Gynecology, Asahikawa Medical University
  • Tamakoshi Akiko
    Department of Public Health, Hokkaido University Graduate School of Medicine
  • Kishi Reiko
    Hokkaido University Center for Environmental and Health Sciences

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Abstract

<p>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.</p><p>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.</p><p>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.</p><p>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.</p>

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