Ambient air pollution and stillbirth: An updated systematic review and meta-analysis of epidemiological studies

Stillbirth has a great impact on contemporary and future generations. Increasing evidence show that ambient air pollution exposure is associated with stillbirth. However, previous studies showed inconsistent findings. To clarify the effect of maternal air pollution exposure on stillbirth, we searched for studies examining the associations between air pollutants, including particulate matter (diameter ≤ 2.5 μm [PM_2.5] and ≤10 μm [PM₁₀]) and gaseous pollutants (sulfur dioxide [SO₂], nitrogen dioxide [NO₂], carbon monoxide [CO] and ozone [O₃]), and stillbirth published in PubMed, Web of Science, Embase and Cochrane Library until December 11, 2020. The pooled effect estimates and 95% confidence intervals (CI) were calculated, and the heterogeneity was evaluated using Cochran's Q test and I² statistic. Publication bias was assessed using funnel plots and Egger's tests. Of 7546 records, 15 eligible studies were included in this review. Results of long-term exposure showed that maternal third trimester PM_2.5 and CO exposure (per 10 μg/m³ increment) increased the odds of stillbirth, with estimated odds ratios (ORs) of 1.094 (95% CI: 1.008-1.180) and 1.0009 (95% CI: 1.0001-1.0017), respectively. Entire pregnancy exposure to PM_2.5 was also associated with stillbirth (OR: 1.103, 95% CI: 1.074-1.131). A 10 μg/m³ increment in O₃ in the first trimester was associated with stillbirth, and the estimated OR was 1.028 (95% CI: 1.001-1.055). Short-term exposure (on lag day 4) to O₃ was also associated with stillbirth (OR: 1.002, 95% CI: 1.001-1.004). PM₁₀, SO₂ and NO₂ exposure had no significant effects on the incidence of stillbirth. Additional well-designed cohort studies and investigations regarding potential biological mechanisms are warranted to elaborate the suggestive association that may help improve intergenerational inequality.