BACKGROUND Gestational exposure to fine particulate matter (PM2.5) has been reported to be associated with an increased risk of fetal death in recent studies, but earlier studies in the past century have usually reported a non-significant association. As such, it remains unknown whether this adverse effect of PM2.5 exposure varies with time. METHODS Nearly 49.2 million eligible birth and fetal death records from 1989 to 2004 were selected from the United States (US) birth and fetal death certificate datasets. For each record, the level of prenatal exposure to PM2.5 was taken as the average concentration in the mother's residential county during the entire gestational period, according to well-established estimates of monthly levels across the contiguous US. We first stratified the dataset by the month of the last menstrual period (LMP) and then independently evaluated the nationwide association between PM2.5 exposure and fetal death within each stratum using five typical logit models: unadjusted, covariate-adjusted, propensity-score, double robust, and diagnostic-score models. Finally, we conducted a meta-analysis to pool estimated LMP-specific associations and explored how the overall association varied by LMP month. RESULTS Different models showed temporal heterogeneity in the estimated association between PM2.5 exposure and fetal death. According to the meta-analysis, double robust model estimates were more homogeneous than the rest, and thus the model outcome was recognized as the main result. For each 1-µg/m3 increase in prenatal exposure to PM2.5, the pooled odds ratio (OR) of fetal death was estimated to be 1.08 [95% confidence interval (CI): 1.05, 1.10]. The LMP-specific ORs exhibited a slightly increasing trend and a significant seasonal pattern. Compared with the pooled OR among samples with the LMP in spring, the estimates for summer, fall and winter were higher by 11.1% (95% CI: 6.2%, 16.3%), 27.8% (95% CI: 22.1%, 33.8%) and 28.8% (95% CI: 23.7%, 34.1%), respectively. We also found that temporal patterns in the association between PM2.5 exposure and fetal death could be explained by several population-level indicators or modifiers (i.e. ethnicity, maternal age, gestational weight gain, previous pregnancy of abnormal termination and diabetes). CONCLUSIONS Prenatal exposure to PM2.5 can increase the risk of fetal death. The effects of PM2.5 exposure may be modified by complex factors, which leads to a time-varying association.

中文翻译：

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胎儿死亡与妊娠期暴露于环境细颗粒物之间随时间变化的关联：1989 年至 2004 年对美国本土 4900 万胎儿进行的全国流行病学研究。

背景 在最近的研究中，据报道妊娠期接触细颗粒物 (PM2.5) 与胎儿死亡风险增加有关，但上个世纪的早期研究通常报告的关联不显着。因此，尚不清楚 PM2.5 暴露的这种不利影响是否随时间变化。方法 从 1989 年到 2004 年，从美国 (US) 出生和胎儿死亡证明数据集中选择了近 4920 万符合条件的出生和胎儿死亡记录。对于每条记录，根据对美国邻近地区月度水平的公认估计，产前暴露于 PM2.5 的水平被视为整个妊娠期间母亲居住县的平均浓度。我们首先按末次月经 (LMP) 的月份对数据集进行分层，然后使用五个典型的 logit 模型独立评估每个层中 PM2.5 暴露与胎儿死亡之间的全国关联：未调整、协变量调整、倾向评分、双稳健和诊断评分模型。最后，我们进行了一项荟萃分析，以汇总估计的 LMP 特定关联，并探讨整体关联如何随 LMP 月份而变化。结果 不同模型显示 PM2.5 暴露与胎儿死亡之间估计关联的时间异质性。根据荟萃分析，双稳健模型估计比其余模型更均匀，因此模型结果被认为是主要结果。产前接触 PM2.5 每增加 1 µg/m3，胎儿死亡的合并比值比 (OR) 估计为 1.08 [95% 置信区间 (CI)：1.05, 1.10]。LMP 特定的 OR 表现出略微增加的趋势和显着的季节性模式。与春季 LMP 样本的汇总 OR 相比，夏季、秋季和冬季的估计值分别高出 11.1%（95% CI：6.2%、16.3%）、27.8%（95% CI：22.1%、33.8%） ) 和 28.8% (95% CI: 23.7%, 34.1%)。我们还发现，PM2.5 暴露与胎儿死亡之间关联的时间模式可以用几个人口水平指标或修饰符（即种族、产妇年龄、妊娠体重增加、先前妊娠异常终止和糖尿病）来解释。结论 产前接触 PM2.5 会增加胎儿死亡的风险。PM2.5 暴露的影响可能会受到复杂因素的影响，