Association between preconception and early pregnancy exposure to fine particulate matter and neural tube defects: A nested case-control study

Background Although several environmental factors may increase the risk of neural tube defects (NTDs), the association between exposure to particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM 2.5 ) and NTDs is not completely understood. Objectives This study aimed to exam the association between expoure to PM 2.5 and NTDs during preconception and early pregancy and determine the crucial time windows. Method We conducted a nested case-control study from the Taiwan Maternal and Child Health Database between 2004 and 2017. We applied satellite-based models with a 1 km resolution to estimate the weekly average PM 2.5 from 3 months before conception to the first trimester of pregnancy. We used conditional logistic regression with distributed lag nonlinear models (DLNMs) to assess the effects of weekly average PM 2.5 on the risk of NTDs and exposure-response relationships. Results We identified 13,676 incident NTD cases in 2,640,709 participants. There were significant associations between exposure to PM 2.5 from 3 months before conception to the first trimester of gestation and the risk of NTDs (odds ratio [OR]: 1.16; 95% confidence incidence [CI]: 1.13, 1.18 per 10 µg/m3 changes), anencephaly (OR: 1.38; 95% CI: 1.08, 1.75 per 10 µg/m3 changes), encephalocele (OR: 1.72; 95% CI: 1.57, 1.87 per 10 µg/m3 changes), and hydrocephalus (OR: 1.12; 95% CI: 1.06, 1.19 per 10 µg/m3 changes). In DLNMs, the risk of NTDs increased from 10 weeks before conception to 19 weeks of gestation. The effects of preconception and early pregnancy exposure to PM 2.5 on the risk of NTDs were considerably stronger in pregnant women with diabetes and preeclampsia and infants with low birth weight (< 2,500 g) than those without these conditions. Conclusion Our findings suggest that exposure to PM 2.5 during preconception and early pregnancy may increase the risk of NTDs in offspring. Moreover, low birth weight, gestational diabetes, and preeclampsia increase the risk of NTDs associated with maternal exposure to PM 2.5 .