ArticlePloS one2022
Association of maternal heavy metal exposure during pregnancy with isolated cleft lip and palate in offspring: Japan Environment and Children's Study (JECS) cohort study.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- A Systematic Literature Review on the Association Between Toxic and Essential Trace Elements and the Risk of Orofacial Clefts in Infants.Biological trace element research · 2024Pooled it
- Cohort profile: The Japan Environment and Children's Study.International journal of epidemiology · 2026Article
- Prenatal exposure to metal mixture and birth weight; a Bayesian kernel machine regression analysis of two cohort studies in Japan and Iran.Journal of environmental health science & engineering · 2025Article
- Article
- Fetal exposure to toxic metals (mercury, cadmium, lead, and arsenic) via intrauterine blood transfusions.Pediatric research · 2025Article
- Association between maternal heavy metal exposure and Kawasaki Disease, the Japan Environment and Children's Study (JECS).Scientific reports · 2024Article
- Heavy metals and trace elements in maternal blood and prevalence of congenital limb abnormalities among newborns: the Japan Environment and Children's Study.Environmental health and preventive medicine · 2024Article
- Association between exposure to environmental pollutants and increased oral health risks, a comprehensive review.Frontiers in public health · 2024Review
- Modifiable Risk Factors of Non-Syndromic Orofacial Clefts: A Systematic Review.Children (Basel, Switzerland) · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCleft lip and palate (cleft L/P) is one of the most common congenital anomalies and its etiology is assumed to be multifactorial. Recent epidemiological data involving a small number of participants suggested an association between perinatal exposure to heavy metals and cleft L/P in affected children. However, this association requires further investigation in a large cohort.
methodsThis nested case-control study used a dataset of The Japan Environment and Children's Study, which is an ongoing research project to investigate the association between environmental factors and mother-child health. Participants were enrolled between 2011 and 2014. From the records of fetuses/children, we extracted data of isolated cleft L/P cases and matched children without cleft L/P at a ratio of 1:10. The exposures of interest were in utero exposure to four metals (mercury [Hg], lead [Pb], cadmium [Cd], and manganese [Mn]), which were sampled from mothers in the second/third trimester. Conditional logistic regression was used to assess the association between heavy metal exposure and isolated cleft L/P. Three sensitivity analyses were conducted to test the robustness of the findings, including the change in case definition and statistical methods.
resultsOf 104,062 fetal records involving both live-birth and stillbirth, we identified 192 children with isolated cleft L/P and 1,920 matched controls. Overall, the blood metal levels were low (for example, median Pb level was 5.85, 6.22, and 5.75 μg/L in the total cohort, cases, and controls, respectively). Univariate and multivariate analyses showed that levels of none of the four heavy metals in the mother's blood during pregnancy were associated with the risk of cleft L/P in offspring; the adjusted odds ratios (per 1 μg/L increase) with 95% intervals were 0.96 (0.91-1.03), 1.01 (0.94-1.08), 1.00 (0.61-1.63) and 1.00 (0.97-1.03) for Hg, Pb, Cd and Mn, respectively. The results were consistent in all sensitivity analyses.
conclusionsExposure to these four metals during pregnancy was not associated with isolated cleft L/P at the low exposure level in our cohort.
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