Association between maternal exposure to ambient PM10 and neural tube defects: A case-control study in Liaoning Province, China
Introduction
Neural tube defects (NTDs), including anencephaly and spina bifida, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely (Greene and Copp, 2014). NTDs affect approximately one in every 1000 established pregnancies worldwide, although variations in prevalence have been reported, ranging from 0.2 to 10 per 1000 in different geographical locations (Copp et al., 2013). The development of NTDs is a multistep process controlled by several genes and environmental factors (Padmanabhan, 2006). The genetic basis is not yet well understood, but association with risk of NTDs has been reported for several non-genetic factors including maternal diabetes (Soler et al., 1976), obesity (Huang et al., 2017) and hyperthermia (Moretti et al., 2005).
The burden of disease caused by air pollution is considerable. In 2017, 5.25% deaths were attributable to ambient particulate matter (PM) pollution, making it the eighth leading risk factor for mortality contributing to a total of 2.94 million deaths globally (Stanaway et al., 2018). Fetal development is a critical window of exposure-related susceptibility and is therefore particularly vulnerable to environmental exposures (Karr et al., 2006). A number of studies have indicated associations between prenatal ambient air pollution exposure and adverse birth outcomes. For example, PM is linked to low birth weight (Coker et al., 2015), intrauterine growth retardation (Maisonet et al., 2004), and preterm birth (Chang et al., 2012). Worldwide evidence from epidemiological studies, animal models, and mechanistic explorations supports the hypothesis that maternal exposure to ambient PM during pregnancy may be an important etiologic factor for the development and progression of certain types of birth defects (Teng et al., 2016). Associations between in utero exposure to PM with aerodynamic diameters ≤10 μm (PM10) and cardiac and orofacial defects have further been established (Girguis et al., 2016; Jin et al., 2015; Stingone et al., 2014; Zhu et al., 2015). However, only a few studies to date have described the impact of PM10 on risk of NTDs, with inconsistent findings.
Liaoning Province, which lies in the south of northeast China and covers an area of 148,600 square kilometers, has recently experienced rapid economic development accompanied by severe air pollution. In this large population-based case-control study, we sought to evaluate possible associations between maternal PM10 exposure during three months preconception and the first trimester and the risk of NTDs in offspring using six years of birth defects data from the Maternal and Child Health Certificate Registry of Liaoning Province and air pollutant monitoring data from the Environment Protection Bureau of each city in Liaoning Province. To our knowledge, this is the first study investigating the association between PM10 and NTDs at a provincial level in China.
Section snippets
Study population
Data on live births, stillbirths, and electively terminated fetuses with NTDs delivered between January 1, 2010 and December 31, 2015 were obtained from the Maternal and Child Health Certificate Registry of Liaoning Province. This registry covers all 14 cities of the province (Shenyang, Dalian, Anshan, Fushun, Benxi, Dandong, Jinzhou, Yingkou, Fuxin, Liaoyang, Panjing, Tieling, Chaoyang, and Huludao), with approximately 273,000 newborns per year during the study period. Liaoning is one of the
Result
The study population consisted of 2736 cases and 7950 controls (Table 1). In addition, the number of cases with NTDs and air monitoring stations in 14 cities in Liaoning Province during study period is shown in Supplemental Table 1. Chi-square tests were conducted to examine the distributions of selected characteristics in the cases and controls. Except for infant sex, the proportion of the other characteristics did not differ between the two groups. PM10 concentrations in each birth year,
Discussion
To our knowledge, this is the first report to investigate the associations of maternal exposure to ambient PM10 with NTDs at a provincial level in China. Based on the relatively high PM10 concentrations in study area, our results show a tendency towards a higher risk of NTDs in offspring among mothers exposed to higher levels of ambient PM10 during both three months preconception and early pregnancy. Mechanistic understanding is still speculative, and several biologically plausible reasons,
Conclusions
Our study suggests that, in areas with relatively severe air pollution, maternal exposure to ambient PM10 during both preconception and early pregnancy is positively associated with the risk of NTDs. Future research should focus on improving the accuracy of calculation of maternal air pollutant exposure levels (e.g., with the use of land-use regression or dispersion models) and clarifying association with risk for different NTD subtypes.
Consent for publication
The manuscript is reviewed and approved by all authors.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Funding
This study was supported by the Liaoning Providence science and technology project (2015225025 for Yan-Hong Huang), the Shenyang science and technology project (F15-139-9-09 for Yan-Hong Huang).
Authors’ contributions
Study conceptualization and design: WQ, HY, LJ, and LS; Data collection: HY, LJ, LS, CY, LL, and JC; Data cleaning and discrepancy checks: ZJ, WQ, and HY; Analytic strategy: ZJ, WQ, HY, and CZ; Analysis and interpretation of data: ZJ, HY, CY, and JC; Manuscript preparation: ZJ and WQ; Final approval of manuscript: ZJ, WQ, HY, LJ, LS, CY, LL, JC, and CZ. All authors read and approved the final manuscript. Jia-Yu Zhang and Qi-Jun Wu contributed equally to this work.
Declaration of competing interest
The authors declare that they have no competing interests.
Acknowledgments
We thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript.
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