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Association between toxic metals, vitamin D and preterm birth in the Maternal-Infant research on environmental chemicals study.

  • Fisher, Mandy1, 2
  • Marro, Leonora1
  • Arbuckle, Tye E1
  • Potter, Beth K2
  • Little, Julian2
  • Weiler, Hope3
  • Morisset, Anne-Sophie4
  • Lanphear, Bruce5
  • Oulhote, Youssef6
  • Braun, Joseph M7
  • Kumarathasan, Premkumari1
  • Walker, Mark8
  • Borghese, Michael M1
  • Ashley-Martin, Jillian1
  • Shutt, Robin1
  • Fraser, William D9
  • 1 Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada. , (Canada)
  • 2 University of Ottawa, School of Epidemiology and Public Health (SEPH), Ottawa, Ontario, Canada. , (Canada)
  • 3 Nutrition Research Division, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada. , (Canada)
  • 4 School of Nutrition, Laval University, Québec city, Québec, Canada. , (Canada)
  • 5 Simon Fraser University. Vancouver, British Columbia Canada, Vancouver, British Columbia, Canada. , (Canada)
  • 6 Department of Epidemiology and Biostatistics, School of Public Health and Health Sciences, University of Massachusetts Amherst, Boston, Massachusetts, USA.
  • 7 Department of Epidemiology, Brown University, Providence, Rhode Island, USA.
  • 8 The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. , (Canada)
  • 9 Centre de Recherche du CHUS, and Department of Obstetrics and gynecology, University of Sherbrooke, Sherbrooke, Québec, Canada. , (Canada)
Published Article
Paediatric and Perinatal Epidemiology
Wiley (Blackwell Publishing)
Publication Date
Jul 01, 2023
DOI: 10.1111/ppe.12962
PMID: 36864001


Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have examined low levels found in most Canadians. Vitamin D, which may have antioxidant activity, protects against PTB. In this study, we investigated the impact of toxic metals (lead, mercury, cadmium and arsenic) on PTB and examined if maternal plasma vitamin D concentrations modify these associations. We investigated whether concentrations of metals in whole blood measured in early and late pregnancy were associated with PTB (<37 weeks) and spontaneous PTB in 1851 live births from the Maternal-Infant Research on Environmental Chemicals Study using discrete time survival analysis. We also investigated whether the risk of PTB was modified by first-trimester plasma 25-hydroxyvitamin D (25OHD) concentrations. Of 1851 live births, 6.1% (n = 113) were PTBs and 4.9% (n = 89) were spontaneous PTB. A 1 μg/dL increase in blood lead concentrations during pregnancy was associated with an increased risk of PTB (relative risk [RR] 1.48, 95% confidence interval [CI] 1.00, 2.20) and spontaneous PTB (RR 1.71, 95% CI 1.13, 2.60). The risk was higher in women with insufficient vitamin D concentrations (25OHD <50 nmol/L) for both PTB (RR 2.42, 95% CI 1.01, 5.79) and spontaneous PTB (RR 3.04, 95% CI 1.15, 8.04). However, an interaction on the additive scale was not present. Arsenic was associated with a higher risk of PTB (RR 1.10, 95% CI 1.02, 1.19) and spontaneous PTB (RR 1.11, 95% CI 1.03, 1.20) per 1 μg/L. Gestational exposure to low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; individuals with insufficient vitamin D may be more susceptible to the adverse effects of lead. Given our relatively small number of cases, we encourage testing of this hypothesis in other cohorts, especially those with vitamin D-deficient populations. © 2023 His Majesty the King in Right of Canada and The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Health.

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