Gestational age modifies the association between exposure to fine particles and fetal death: findings from a nationwide epidemiological study in the contiguous United States

BACKGROUNDS: The vulnerability of fetuses differs at different developmental stages, in response to environmental stressors such as fine particulate matter (PM(2.5)), a ubiquitous air pollutant. Whether gestational age (GA) modifies the association between prenatal fine particulate matter (PM(2.5)) exposure and fetal death remains unclear. METHODS: We selected approximately 47.8 million eligible United States (US) livebirth and fetal death (defined as a termination at a GA of 20–43 weeks) records from 1989 to 2004. For each record, we took the level of prenatal exposure to PM(2.5) as the average concentration in the mother’s residential county during the entire gestational period, or a specific trimester (i.e., GA-specific exposure), according to well-established estimates of monthly levels across the contiguous US. First, we evaluated the associations between PM(2.5) exposure and fetal death at a specific GA (i.e., GA-specific outcome) using five different logit models (unadjusted, covariate-adjusted, propensity-score, double robust, and diagnostic-score models). Double robust model was selected as the main model due to its advantages in causal inference. Then, we conducted meta-analyses to pool the estimated GA-specific associations, and explored how the pooled estimates varied with GA. RESULTS: According to the meta-analysis, all models suggested gestational PM(2.5) exposure was associated with fetal death. However, there was slight heterogeneity in the estimated effects, as different models revealed a range of 3.6–10.7% increase in the odds of fetal death per 5-µg/m(3) increment of PM(2.5). Each 5-µg/m(3) increase in PM(2.5) exposure during the entire gestation period significantly increased the odds of fetal death, by 8.1% (95% confidence interval [CI]: 5.1–11.2%). In terms of GA-specific outcomes, the odds of fetal death at a GA of 20–27, 28–36, or ≥ 37 weeks increased by 11.0% (5.9–16.4%), 5.2% (0.4–10.1%), and 8.3% (2.5–14.5%), respectively. In terms of GA-specific exposure, the odds of fetal death increased by 6.0% (3.9–8.2%), 4.1% (3.9–8.2%), and 4.3% (0.5–8.2%) with 5-µg/m(3) increases in PM(2.5) exposure during the first, second, and third trimester, respectively. The association had the largest effect size (odds ratio = 1.098, 95% CI: 1.061–1.137) between PM(2.5) exposure during early gestation (i.e., first trimester) and early fetal death (i.e., 20–27 weeks). CONCLUSIONS: Prenatal exposure to PM(2.5) was significantly associated with an increased risk of fetal death. The association was varied by gestational-age-specific exposures or outcomes, suggesting gestation age as a potential modifier on the effect of PM(2.5). The fetus was most vulnerable during the early stage of development to death associated with PM(2.5) exposure. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12940-023-01016-4.