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Background <p>Previous studies on fluoride in drinking water and birth outcomes have yielded inconsistent findings. Furthermore, the association between fluoride exposure and gestational age (the duration of pregnancy), along with offspring characteristics at birth, has not been thoroughly explored. Given the widespread occurrence of drinking water fluorosis in China, this large-scale study aims to explore the associations between fluoride and birth outcomes.</p> Methods <p>We conducted a database study involving 352,973 participants in China from 2016 to 2022. Generalized linear models and restricted cubic spline curves were employed for the analysis, and the mediating effects on gestational age were systematically evaluated.</p> Results <p>The average fluoride concentration was 0.41 ± 0.16&#xa0;mg/L. Each unit increase in fluoride was associated with a 0.36-week (95% confidence intervals [<i>CI</i>]: 0.34, 0.39) increase in gestational age and a 43.56&#xa0;g (95% <i>CI</i>: 33.56, 53.57) increase in birth weight. Fluoride exposure exhibited dual effects: it was protective against preterm birth (odds ratio [<i>OR</i>] = 0.74; 95% <i>CI</i>: 0.67, 0.82) and low birth weight (<i>OR</i> = 0.69; 95% <i>CI</i>: 0.61, 0.78), while simultaneously elevating the risks of macrosomia (<i>OR</i> = 2.56; 95% <i>CI</i>: 2.40, 2.74), small-for-gestational age (<i>OR</i> = 1.72; 95% <i>CI</i>: 1.58, 1.88), and large-for-gestational age (<i>OR</i> = 1.27; 95% <i>CI</i>: 1.20, 1.34). Nonlinear exposure-response relationships were observed for all outcomes except low birth weight. Mediation analysis indicated that gestational age served as a significant mediator in the associations between fluoride and birth weight, as well as low birth weight and macrosomia—suggesting that fluoride may increase birth weight and reduce the risk of low birth weight through prolonged pregnancy. Notably, gestational age was not analyzed as a mediator for small-for-gestational age and large-for-gestational age due to its distinct growth deviation nature. However, its paradoxical associations with both fetal growth restriction and overgrowth (macrosomia/large-for-gestational age) warrant clinical attention, although these observational links do not establish definitive causality.</p> Conclusion <p>Prenatal fluoride exposure exhibits dual effects in China: prolonging gestational age and reducing preterm birth and low birth weight risks, while increasing risks of abnormal fetal growth. These findings underscore the necessity for region-specific fluoride monitoring and prenatal counseling.</p>

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Protective versus risky: the complex relationship between prenatal fluoride exposure and birth outcomes in a Chinese large-scale population study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月28日

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  • Liu Yang,
  • Feifei Yan,
  • Xiumiao Peng,
  • Zhonghua Meng,
  • Xingyi Geng,
  • Wei Wei

摘要

Background

Previous studies on fluoride in drinking water and birth outcomes have yielded inconsistent findings. Furthermore, the association between fluoride exposure and gestational age (the duration of pregnancy), along with offspring characteristics at birth, has not been thoroughly explored. Given the widespread occurrence of drinking water fluorosis in China, this large-scale study aims to explore the associations between fluoride and birth outcomes.

Methods

We conducted a database study involving 352,973 participants in China from 2016 to 2022. Generalized linear models and restricted cubic spline curves were employed for the analysis, and the mediating effects on gestational age were systematically evaluated.

Results

The average fluoride concentration was 0.41 ± 0.16 mg/L. Each unit increase in fluoride was associated with a 0.36-week (95% confidence intervals [CI]: 0.34, 0.39) increase in gestational age and a 43.56 g (95% CI: 33.56, 53.57) increase in birth weight. Fluoride exposure exhibited dual effects: it was protective against preterm birth (odds ratio [OR] = 0.74; 95% CI: 0.67, 0.82) and low birth weight (OR = 0.69; 95% CI: 0.61, 0.78), while simultaneously elevating the risks of macrosomia (OR = 2.56; 95% CI: 2.40, 2.74), small-for-gestational age (OR = 1.72; 95% CI: 1.58, 1.88), and large-for-gestational age (OR = 1.27; 95% CI: 1.20, 1.34). Nonlinear exposure-response relationships were observed for all outcomes except low birth weight. Mediation analysis indicated that gestational age served as a significant mediator in the associations between fluoride and birth weight, as well as low birth weight and macrosomia—suggesting that fluoride may increase birth weight and reduce the risk of low birth weight through prolonged pregnancy. Notably, gestational age was not analyzed as a mediator for small-for-gestational age and large-for-gestational age due to its distinct growth deviation nature. However, its paradoxical associations with both fetal growth restriction and overgrowth (macrosomia/large-for-gestational age) warrant clinical attention, although these observational links do not establish definitive causality.

Conclusion

Prenatal fluoride exposure exhibits dual effects in China: prolonging gestational age and reducing preterm birth and low birth weight risks, while increasing risks of abnormal fetal growth. These findings underscore the necessity for region-specific fluoride monitoring and prenatal counseling.