Abstract
Limited evidence on exposure to maternal air pollutants before and after conception and the risk of congenital limb defects (CLDs) in offspring is inconsistent. We explored the dose‒response relationship between maternal air pollutant exposure before and after conception and the risk of CLDs and their subtypes and further examined whether individual sociodemographic characteristics modify these associations. We carried out a population-based cohort study in Wuhan, China, based on the government registration system. The CLDs and daily air pollutant concentration data were collected. Individual exposure was assessed via the inverse distance weighting method on the basis of maternal residential addresses. Multivariate logistic regression models were applied to evaluate the relationship between maternal exposure to air pollutants and the risk of CLDs, adjusting for covariates. A total of 1,864 infants were diagnosed with CLD, with an incidence of 3.7/1,000. Maternal exposure to SO2 in the first, second and third month of conception significantly increased the risk of overall CLDs, with adjusted odd ratios (aORs) ranging from 1.033 to 1.043. However, no significant correlation was found between exposure to PM2.5, PM10, NO2, CO, or O3 and CLD risk. Significant links were found for SO2 exposure with polydactyly and limb shortening in the subgroup analyses. Several significant modifying effects of individual characteristics were also observed. This study confirmed that increased exposure to SO2 during the first three months after conception increased the risk of CLDs and their subtypes in offspring, and these associations were modified by individual characteristics.
Data availability
The datasets used in this study are available from the corresponding author on reasonable request.
References
Ephraim, P. L., Dillingham, T. R., Sector, M., Pezzin, L. E. & Mackenzie, E. J. Epidemiology of limb loss and congenital limb deficiency: a review of the literature. Arch. Phys. Med. Rehabil. 84 (5), 747–761 (2003).
Yang, E. et al. Analyzing the global burden of 11 subtypes of congenital birth defects: trends, sociodemographic correlates, and outcomes from 1990 to 2021. Ann. Med. 57 (1), 2519686 (2025).
Stallings, E. B. et al. National birth defects prevention Network. National population-based estimates for major birth defects, 2016–2020. Birth Defects Res. 116 (1), e2301 (2024).
Li, W. Y. et al. Temporal trends in the prevalence of major birth defects in china: a nationwide population-based study from 2007 to 2021. World J. Pediatr. 20 (11), 1145–1154 (2024).
Ahmad, Z. et al. Genetic overview of postaxial polydactyly: updated classification. Clin. Genet. 103 (1), 3–15 (2023).
Zhu, F., Wang, J., Jiao, J. & Zhang, Y. Exposure to acrylamide induces skeletal developmental toxicity in zebrafish and rat embryos. Environ. Pollut. 271, 116395 (2021).
Carmichael, S. L. et al. Limb deficiency defects, MSX1, and exposure to tobacco smoke. Am. J. Med. Genet. A. 125A (3), 285–289 (2004).
Hwang, S. J., Beaty, T. H., McIntosh, I., Hefferon, T. & Panny, S. R. Association between homeobox -containing gene MSX1 and the occurrence of limb deficiency. Am. J. Med. Genet. 75 (4), 419–423 (1998).
Xiong, S. et al. Maternal exposure to polystyrene nanoplastics during gestation and lactation impaired skeletal growth in progeny mice by inhibiting neutrophil extracellular trap formation. Ecotoxicol. Environ. Saf. 299, 118355 (2025).
Sun, W. et al. Evidence of the correlation between air pollution and different types of birth defects: based on a distribution-lag non-linear model. Front. Public. Health. 13, 1562461 (2025).
Wan, X. et al. The association between maternal air pollution exposure and the incidence of congenital heart diseases in children: A systematic review and meta-analysis. Sci. Total Environ. 892, 164431 (2023).
Zhen, S. et al. Maternal exposure to fine particulate matter before and during pregnancy, and the risk of birth defects: A population-based study. Ecotoxicol. Environ. Saf. 289, 117408 (2025).
Li, D. et al. Maternal air pollution exposure and neonatal congenital heart disease: A multii-city cross-sectional study in Eastern China. Int. J. Hyg. Environ. Health. 240, 113898 (2022).
Wright, C. Y. et al. The risk of orofacial cleft lip/palate due to maternal ambient air pollution exposure: A call for further research in South Africa. Ann. Glob Health. 89 (1), 6 (2023).
Zhang, D. et al. Maternal exposure to ambient air pollution and risk of congenital heart defects in offspring: A population-based cohort study in Wuhan, China. Int. J. Hyg. Environ. Health. 269, 114627 (2025).
Choi, G. et al. Maternal exposure to outdoor air pollution and congenital limb deficiencies in the National Birth Defects Prevention Study. Environ. Res. 179(Pt A), 108716 (2019) (179(Pt A)).
Jiang, W. et al. Modification of the effects of nitrogen dioxide and sulfur dioxide on congenital limb defects by meteorological conditions. Hum. Reprod. 36 (11), 2962–2974 (2021a).
Zhang, J. Y. et al. Association between maternal exposure to PM10 and polydactyly and syndactyly: A population-based case-control study in Liaoning province, China. Environ. Res. 187, 109643 (2020).
Jiang, Y. T. et al. Maternal exposure to ambient SO2 and risk of polydactyly and syndactyly: a population-based case-control study in Liaoning Province, China. Environ. Sci. Pollut Res. Int. 28 (9), 11289–11301 (2021b).
Lin, Y. T., Lee, Y. L., Jung, C. R., Jaakkola, J. J. & Hwang, B. F. Air pollution and limb defects: a matched-pairs case-control study in Taiwan. Environ. Res. 132, 273–280 (2014).
Cheng, Y. et al. Ambient air pollutants in the first trimester of pregnancy and birth defects: an observational study. BMJ Open. 13 (3), e063712 (2023).
Yang, W. et al. Combined effect of preconceptional and prenatal exposure to air pollution and temperature on childhood pneumonia: A case-control study. Environ. Res. 216 (Pt 4), 114806 (2023).
Yuan, X. et al. Maternal exposure to PM2.5 and the risk of congenital heart defects in 1.4 million births: A nationwide surveillance-based study. Circulation 147 (7), 565–574 (2023).
Tan, Y. et al. Prenatal ambient air pollutants exposure and the risk of stillbirth in Wuhan, central of China. Environ. Res. 228, 115841 (2023).
Tan, Y. et al. Prenatal exposure to PM2.5 and childhood body mass index growth trajectories from birth to 6 years old. Sci. Rep. 14 (1), 16936 (2024).
Zordão, O. P. et al. Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota. Front. Endocrinol. (Lausanne). 14, 1069243 (2023).
Honein, M. A. et al. The association between major birth defects and preterm birth. Matern Child. Health J. 13 (2), 164–175 (2009).
Vecoli, C., Pulignani, S. & Andreassi, M. G. Genetic and epigenetic mechanisms linking air pollution and congenital heart disease. J. Cardiovasc. Dev. Dis. 3 (4), 32 (2016).
Vrijheid, M. et al. Ambient air pollution and risk of congenital anomalies: a systematic review and meta-analysis. Environ. Health Perspect. 119 (5), 598–606 (2011).
Meng, Z., Qin, G., Zhang, B. & Bai, J. DNA damaging effects of sulfur dioxide derivatives in cells from various organs of mice. Mutagenesis 19 (6), 465–468 (2004).
Kim, S. E. et al. Seasonal analysis of the short-term effects of air pollution on daily mortality in Northeast Asia. Sci. Total Environ. 576, 850–857 (2017).
Li, R. et al. Effects of PM2.5 exposure in utero on heart injury, histone acetylation and GATA4 expression in offspring mice. Chemosphere 256, 127133 (2020).
Brokamp, C., LeMasters, G. K. & Ryan, P. H. Residential mobility impacts exposure assessment and community socioeconomic characteristics in longitudinal epidemiology studies. J. Expo Sci. Environ. Epidemiol. 26 (4), 428–434 (2016).
Bozzola, E. et al. The impact of indoor air pollution on children’s health and well-being: the experts’ consensus. Ital. J. Pediatr. 50 (1), 69 (2024).
Ji, W., Chen, Y., Huang, W., Zhou, H. & Xu, S. Trends and regional disparities in the global burden of disease attributable to household air pollution in 204 countries and territories, 1990–2021: an analysis of the global burden of disease study. BMJ Open. 15 (6), e092162 (2025).
Khajavi, A. et al. Short-term and lagged effects of ambient air pollutants on CVD hospitalization: A two-decade population-based study in Tehran. Int. J. Hyg. Environ. Health. 266, 114573 (2025).
Wu, Z. et al. The lag-effects of meteorological factors and air pollutants on child respiratory diseases in Fuzhou, China. J. Glob Health. 12, 11010 (2022).
Andersen, S. L., Olsen, J., Wu, C. & Laurberg, P. Severity of birth defects after propylthiouracil exposure in early pregnancy. Thyroid 24 (10), 1533–1540 (2014).
Gelder, M. et al. Rationale and design of the pregnancy and infant development (PRIDE) study. Paediatr. Perinat. Epidemiol. 27 (1), 34–43 (2013).
Funding
This work was supported by the Funding for Scientific Research Projects from Wuhan Municipal Health Commission (Grant Number. WX23B40) and the Natural Science Foundation of Hubei Province (Grant Number. 2024AFC054).
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YT and AP conceptualized and designed the study. YZ and YT analyzed the data and drafted the initial version of the manuscript, DZ, PX and XC collected the data and helped to interpret the findings. All the authors reviewed and approved the final version of the manuscript.
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The authors declare that this study was conducted in compliance with the Helsinki Declaration. Since all personal information of mothers and infants in the study was anonymous and no identifiable information was involved, the requirement for obtaining informed consent was waived and approved by the Institutional Review Board of Wuhan Children’s Hospital (No.2024R061E01).
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Zhang, Y., Tan, Y., Zhang, D. et al. Maternal exposure to ambient air pollution and risk of congenital limb defects in offspring. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36527-w
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DOI: https://doi.org/10.1038/s41598-026-36527-w
