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Maternal exposure to ambient levels of sulfur dioxide and risk of neural tube defects in 14 cities in Liaoning province, China: a population-based case–control study

Abstract

Epidemiological studies on the association of sulfur dioxide (SO2) with neural tube defects (NTDs) are lacking. The purpose of this study was to assess the aforementioned association through a population-based case–control study. This study involved 1457 NTDs cases and 7950 randomly selected healthy infants born in 14 cities in Liaoning province between 2010 and 2015. Ambient SO2 levels were acquired from 75 monitoring stations. The exposure assessment was based on the mean concentration of all stations in mother’s residential city. We used logistic regression models to assess the associations. In multivariable models adjusted for the confounding variables selected based on the 10 percent change-in-estimate method, we found that maternal SO2 exposure was positively associated with an increased risk of NTDs during the first month after conception (per 10 μg/m3 increase: adjusted odds ratio [aOR] = 1.02, 95% confidence interval [CI]: 1.00–1.04; highest versus lowest quartile: aOR = 2.55, 95% CI: 1.97–3.31) and the second month after conception (per 10 μg/m3 increase: aOR = 1.02, 95% CI: 1.00–1.04; highest versus lowest quartile: aOR=2.31, 95% CI: 1.77–3.00). For other exposure windows, positive associations also emerged in high- versus low-exposure analyses, except for the third month before conception; however, we could not further confirm significant findings from the continuous exposure analyses. Our study provides a new evidence that SO2 exposure may increase the risk of NTDs.

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Fig. 1: Geographic locations of air monitoring stations in 14 cities in Liaoning province, China.
Fig. 2: Monthly mean SO2 levels in Liaoning province, China, 2010–2015.
Fig. 3: Seasonal mean SO2 levels in Liaoning province, China, 2010–2015.

References

  1. Greene ND, Copp AJ. Neural tube defects. Annu Rev Neurosci. 2014;37:221–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mitchell LE. Epidemiology of neural tube defects. Am J Med Genet C Semin Med Genet. 2005;135C:88–94.

    Article  PubMed  Google Scholar 

  3. Copp AJ, Stanier P, Greene ND. Neural tube defects: recent advances, unsolved questions, and controversies. Lancet Neurol. 2013;12:799–810.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kancherla V, Black RE. Historical perspective on folic acid and challenges in estimating global prevalence of neural tube defects. Ann NY Acad Sci. 2018;1414:20–30.

    Article  PubMed  Google Scholar 

  5. Padmanabhan R. Etiology, pathogenesis and prevention of neural tube defects. Congenit Anom. 2006;46:55–67.

    Article  CAS  Google Scholar 

  6. World Health Organization. Ten threats to Global Health in 2019. https://www.who.int/emergencies/ten-threats-to-global-health-in-2019.

  7. McConnell R, Islam T, Shankardass K, Jerrett M, Lurmann F, Gilliland F, et al. Childhood incident asthma and traffic-related air pollution at home and school. Environ Health Perspect. 2010;118:1021–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zmirou D, Gauvin S, Pin I, Momas I, Sahraoui F, Just J, et al. Traffic related air pollution and incidence of childhood asthma: results of the Vesta case-control study. J Epidemiol Community Health. 2004;58:18–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ko FW, Hui DS. Air pollution and chronic obstructive pulmonary disease. Respirology. 2012;17:395–401.

    Article  PubMed  Google Scholar 

  10. Sunyer J, Ballester F, Tertre AL, Atkinson R, Ayres JG, Forastiere F, et al. The association of daily sulfur dioxide air pollution levels with hospital admissions for cardiovascular diseases in Europe (The Aphea-II study). Eur Heart J. 2003;24:752–60.

    Article  CAS  PubMed  Google Scholar 

  11. Pope CR, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA. 2002;287:1132–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bové H, Bongaerts E, Slenders E, Bijnens EM, Saenen ND, Gyselaers W, et al. Ambient black carbon particles reach the fetal side of human placenta. Nat Commun. 2019; 10.

  13. Pedersen M, Giorgis-Allemand L, Bernard C, Aguilera I, Andersen AM, Ballester F, et al. Ambient air pollution and low birth weight: a European cohort study (ESCAPE). Lancet. Respir Med. 2013;1:695–704.

    CAS  Google Scholar 

  14. Hao H, Chang HH, Holmes HA, Mulholland JA, Klein M, Darrow LA, et al. Air pollution and preterm birth in the U.S. state of Georgia (2002–2006): Associations with concentrations of 11 ambient air pollutants estimated by combining Community Multiscale Air Quality Model (CMAQ) simulations with stationary monitor measurements. Environ Health Perspect. 2016;124:875–80.

    Article  CAS  PubMed  Google Scholar 

  15. Heft-Neal S, Burney J, Bendavid E, Burke M. Robust relationship between air quality and infant mortality in Africa. Nature. 2018;559:254–8.

    Article  CAS  PubMed  Google Scholar 

  16. Xiong LL, Xu ZH, Wang H, Liu ZY, Xie DH, Wang AH, et al. The association between ambient air pollution and birth defects in four cities in Hunan province, China, from 2014 to 2016. Medicine. 2019;98:e14253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yao CJ, Chen YY, Zhu XX, Liu Y, Zhang J, Hou LJ, et al. Air pollution and the risk of birth defects in Anqing city. China J Occup Environ Med 2016;58:e124–e127.

    Article  CAS  PubMed  Google Scholar 

  18. Marshall EG, Harris G, Wartenberg D. Oral cleft defects and maternal exposure to ambient air pollutants in New Jersey. Birth Defects Res A Clin Mol Teratol. 2010;88:205–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang LL, Xiang XM, Mi BB, Song H, Dong M, Zhang SP, et al. Association between early prenatal exposure to ambient air pollution and birth defects: evidence from newborns in Xi’an, China. J Public Health. 2018;41:494–501.

    Article  Google Scholar 

  20. Dolk H, Armstrong B, Lachowycz K, Vrijheid M, Rankin J, Abramsky L, et al. Ambient air pollution and risk of congenital anomalies in England, 1991–1999. Occup Environ Med. 2010;67:223–7.

    Article  CAS  PubMed  Google Scholar 

  21. Zhu Y, Zhang C, Liu D, Grantz KL, Wallace M, Mendola P. Maternal ambient air pollution exposure preconception and during early gestation and offspring congenital orofacial defects. Environ Res. 2015;140:714–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huang CC, Pan SC, Chen BY, Guo YL. Periconceptional exposure to air pollution and congenital hypospadias among full-term infants. Environ Res. 2020;183:109151.

    Article  CAS  PubMed  Google Scholar 

  23. Klimont Z, Smith SJ, Cofala J. The last decade of global anthropogenic sulfur dioxide: 2000–2011 emissions. Environ Res Lett. 2013;8:14003.

    Article  CAS  Google Scholar 

  24. Lu Z, Streets DG, Zhang Q, Wang S, Carmichael GR, Cheng YF, et al. Sulfur dioxide emissions in China and sulfur trends in East Asia since 2000. Atmos Chem Phys. 2010;10:6311–31.

    Article  CAS  Google Scholar 

  25. Zheng B, Tong D, Li M, Liu F, Hong C, Geng G, et al. Trends in China’s anthropogenic emissions since 2010 as the consequence of clean air actions. Atmos Chem Phys. 2018;18:14095–111.

    Article  CAS  Google Scholar 

  26. Liu F, Zhang Q, Tong D, Zheng B, Li M, Huo H, et al. High-resolution inventory of technologies, activities, and emissions of coal-fired power plants in china from 1990 to 2010. Atmos Chem Phys. 15:18787–837.

  27. Zhang JY, Wu QJ, Huang YH, Li J, Liu S, Chen YL, et al. Association between maternal exposure to ambient PM10 and neural tube defects: a case-control study in Liaoning Province, China. Int J Hyg Environ Health. 2020;225:113453.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang T, Gong T, Chen Y, Wu Q, Zhang Y, Jiang C, et al. Time trends in the prevalence and epidemiological characteristics of neural tube defects in Liaoning Province, China, 2006–2015: a population-based study. Oncotarget. 2017;8:17092.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gong TT, Wu QJ, Chen YL, Jiang CZ, Li J, Li LL, et al. Evaluating the time trends in prevalence of exomphalos in 14 cities of Liaoning province, 2006 to 2015. Sci Rep. 2016;6:32901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li N, Chen YL, Li J, Li LL, Jiang CZ, Zhou C, et al. Decreasing prevalence and time trend of gastroschisis in 14 cities of Liaoning Province: 2006–2015. Sci Rep. 2016;6:33333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Xu LL, Li XH, Dai L, Yuan XQ, Liang J, Zhou GX, et al. Assessing the trend of gastroschisis prevalence in China from 1996 to 2007 using two analytical methods. Birth Defects Res A Clin Mol Teratol. 2011;91:177–84.

    Article  CAS  PubMed  Google Scholar 

  32. Ji X, Meng X, Liu C, Chen R, Ge Y, Kan L, et al. Nitrogen dioxide air pollution and preterm birth in Shanghai, China. Environ Res. 2019;169:79–85.

    Article  CAS  PubMed  Google Scholar 

  33. Sadler TW. Mechanisms of neural tube closure and defects. Ment Retard Dev Disabil Res Rev. 1998;4:247–53.

    Article  Google Scholar 

  34. Huang C, Chen B, Pan S, Ho Y, Guo YL. Prenatal exposure to PM2.5 and congenital heart diseases in Taiwan. Sci Total Environ. 2019;655:880–6.

    Article  CAS  PubMed  Google Scholar 

  35. Jin L, Qiu J, Zhang Y, Qiu W, He X, Wang Y, et al. Ambient air pollution and congenital heart defects in Lanzhou, China. Environ Res Lett. 2015;10:074005.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Ritz B, Yu F, Fruin S, Chapa G, Shaw GM, Harris JA. Ambient air pollution and risk of birth defects in Southern California. Am J Epidemiol. 2002;155:17–25.

    Article  PubMed  Google Scholar 

  37. Rice D, Barone SJ. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000;108:511–33.

    PubMed  PubMed Central  Google Scholar 

  38. Hassler JA, Moran DJ. Effects of ethanol on the cytoskeleton of migrating and differentiating neural crest cells: possible role in teratogenesis. J Craniofac Genet Dev Biol Suppl. 1986;2:129–36.

    CAS  PubMed  Google Scholar 

  39. Meng Z, Qin G, Zhang B. DNA damage in mice treated with sulfur dioxide by inhalation. Environ Mol Mutagen. 2005;46:150–5.

    Article  CAS  PubMed  Google Scholar 

  40. Meng Z. Oxidative damage of sulfur dioxide on various organs of mice: sulfur dioxide is a systemic oxidative damage agent. Inhal Toxicol. 2003;15:181–95.

    Article  CAS  PubMed  Google Scholar 

  41. Lupo PJ, Symanski E, Waller DK, Chan W, Langlois PH, Canfield MA, et al. Maternal exposure to ambient levels of benzene and neural tube defects among offspring: Texas, 1999–2004. Environ Health Perspect. 2011;119:397–402.

    Article  PubMed  Google Scholar 

  42. Ren A, Qiu XH, Jin L, Ma J, Li ZW, Zhang L, et al. Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects. Proc Natl Acad Sci USA. 2011;108:12770–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wigle DT, Arbuckle TE, Turner MC, Berube A, Yang Q, Liu S, et al. Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants. J Toxicol Environ Health B Crit Rev. 2008;11:373–517.

    Article  CAS  PubMed  Google Scholar 

  44. Schembari A, Nieuwenhuijsen MJ, Salvador J, de Nazelle A, Cirach M, Dadvand P, et al. Traffic-related air pollution and congenital anomalies in Barcelona. Environ Health Perspect. 2014;122:317–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Padula AM, Tager IB, Carmichael SL, Hammond SK, Lurmann F, Shaw GM. The association of ambient air pollution and traffic exposures with selected congenital anomalies in the San Joaquin Valley of California. Am J Epidemiol. 2013;177:1074–85.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Vrijheid M, Martinez D, Manzanares S, Dadvand P, Schembari A, Rankin J, et al. Ambient air pollution and risk of congenital anomalies: a systematic review and meta-analysis. Environ Health Perspect. 2011;119:598–606.

    Article  CAS  PubMed  Google Scholar 

  47. Agay-Shay K, Friger M, Linn S, Peled A, Amitai Y, Peretz C. Air pollution and congenital heart defects. Environ Res. 2013;124:28–34.

    Article  CAS  PubMed  Google Scholar 

  48. Zhang B, Liang S, Zhao J, Qian Z, Bassig BA, Yang R, et al. Maternal exposure to air pollutant PM2.5 and PM10 during pregnancy and risk of congenital heart defects. J Expo Sci Environ Epidemiol. 2016;26:422–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Huang CC, Wen HJ, Chen PC, Chiang TL, Lin SJ, Guo YL. Prenatal air pollutant exposure and occurrence of atopic dermatitis. Br J Dermatol. 2015;173:981–8.

    Article  CAS  PubMed  Google Scholar 

  50. Bell ML, Belanger K. Review of research on residential mobility during pregnancy: consequences for assessment of prenatal environmental exposures. J Expo Sci Environ Epidemiol. 2012;22:429–38.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript.

Funding

This study was supported by the Liaoning Providence science and technology project (2015225025 for Yan-Hong Huang) and the Shenyang science and technology project (F15-139-9-09 for Yan-Hong Huang).

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Zhang, JY., Dai, HX., Wu, QJ. et al. Maternal exposure to ambient levels of sulfur dioxide and risk of neural tube defects in 14 cities in Liaoning province, China: a population-based case–control study. J Expo Sci Environ Epidemiol 31, 266–275 (2021). https://doi.org/10.1038/s41370-020-00273-6

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  • DOI: https://doi.org/10.1038/s41370-020-00273-6

Keywords

  • Air pollution
  • Birth defects
  • Neural tube defects
  • Sulfur dioxide

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