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Arsenic Exposure, Periconceptional Folic Acid Supplementation, and the Risk for Neural Tube Defects: A Case–Control Study

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Abstract

Arsenic induces neural tube defects (NTDs) in laboratory animals, but evidence in human populations is scarce. We examined the association between arsenic exposure and the risk for NTDs and explored whether folic acid supplementation could attenuate the risk posed by arsenic exposure. Based on a population-based birth defects surveillance program, this case–control study of 408 women with NTD-affected pregnancies and 593 women with healthy pregnancies was recruited in northern China between 2003 and 2016. Arsenic concentrations in placental tissues were quantified by inductively coupled plasma–mass spectrometers. The odds ratio (OR) with 95% confidence interval (95% CI) was calculated with logistic regression to evaluate the association between arsenic exposure and the occurrence of NTDs while adjusting for confounding factors. Potential modification effects of folic acid supplementation on the association between arsenic exposure and NTD risk were examined. Placental median arsenic concentrations were higher in NTD cases (13.32 ng/g) than in controls (10.51 ng/g). An arsenic concentration above the median of all participants was associated with an increased risk for NTDs with an OR of 1.63 (95% CI 1.13–2.35). Among women who reported not taking folic acid supplements during the periconceptional period, arsenic exposure showed an NTD risk of 1.68 (95% CI 1.09–2.58), while there was no association between arsenic exposure and NTD risk among women who reported taking folic acid supplements [adjusted OR (95% CI) 1.30 (0.58–2.92)]. Arsenic exposure is a risk factor for NTDs, but this risk could be alleviated by folic acid supplementation.

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Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due to ethical and legal reasons but are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the women who participated and the local healthcare staff who collected data and samples in the study.

Funding

This work was supported by the National Key Research and Development Program, Ministry of Science and Technology of the People's Republic of China (Grant Numbers 2021YFC2701001 and 2021YFC2701101).

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Contributions

AR contributed to the study conception and design. Material preparation was performed by XP, CW, and SY. Data collection was performed by LJ, ZL, LW, JL, and YZ. Data analysis was performed by XP. The first draft of the manuscript was written by XP and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Aiguo Ren.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical Approval

All participants provided informed consent for the study that was approved by the Ethics Review Committee of Peking University (Beijing, China).

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Pi, X., Wang, C., Yin, S. et al. Arsenic Exposure, Periconceptional Folic Acid Supplementation, and the Risk for Neural Tube Defects: A Case–Control Study. Expo Health 15, 245–254 (2023). https://doi.org/10.1007/s12403-022-00487-z

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  • DOI: https://doi.org/10.1007/s12403-022-00487-z

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