Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Environ Int. 2022 Jun;164:107246. doi: 10.1016/j.envint.2022.107246. Epub 2022 Apr 15.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous chemicals with mechanisms of toxicity that include endocrine disruption. We examined associations of prenatal urinary PAH with spontaneous preterm birth (PTB) and gestational age (GA) at birth. We also assessed whether infant sex modifies the association of PAH exposure with spontaneous PTB and GA at birth.
Participants included 1,677 non-smoking women from three cohorts (CANDLE, TIDES, and GAPPS) in the ECHO PATHWAYS Consortium. Twelve monohydroxylated-PAHs were measured in second trimester maternal urine. Seven metabolites with >60% overall detection were included in analyses: 1-hydroxynaphthalene [1-OH-NAP], 2-hydroxynaphthalene [2-OH-NAP], 2-hydroxyphenanthrene [2-OH-PHEN], 3-hydroxyphenanthrene [3-OH-PHEN], 1/9-hydroxyphenanthrene [1/9-OH-PHEN], 2/3/9-hydroxyfluorene [2/3/9-OH-FLUO], and 1-hydroxypyrene [1-OH-PYR]. Logistic and linear regression models were fit for spontaneous PTB and GA among births ≥34 weeks, respectively, with log-transformed OH-PAH concentrations as the exposure, adjusted for specific gravity and suspected confounders. Effect modification by infant sex was assessed using interaction terms and marginal estimates.
Percent detection was highest for 2-OH-NAP (99.8%) and lowest for 1-OH-PYR (65.2%). Prevalence of spontaneous PTB was 5.5% (N = 92). Ten-fold higher 2-OH-NAP exposure was associated with 1.60-day (95% CI: -2.92, -0.28) earlier GA at birth. Remaining associations in the pooled population were null. Among females, we observed significant inverse associations between 1-OH-PYR and PTB (OR: 2.65 [95% CI: 1.39, 5.05]); and 2-OH-NAP with GA: -2.46 days [95% CI: -4.15, -0.77]). Among males, we observed an inverse association between 2/3/9-OH-FLUO and PTB (OR = 0.40 [95% CI: 0.17,0.98]). ORs for PTB were higher among females than males for 2-OH-PHEN (p = 0.02) and 1-OH-PYR (p = 0.02).
We observed inverse associations of 2-OH-NAP exposure with GA and null associations of remaining OH-PAHs with GA and PTB. Females may be more susceptible to spontaneous PTB or shorter GA following prenatal exposure to some OH-PAHs. This study is the first to assess sex-specific OH-PAH toxicity in relation to spontaneous PTB and GA.
多环芳烃(PAHs)是无处不在的化学物质,其毒性机制包括内分泌干扰。我们研究了产前尿液中多环芳烃与自发性早产(PTB)和出生时胎龄(GA)的关系。我们还评估了婴儿性别是否改变了 PAH 暴露与自发性早产和出生时 GA 的关联。
参与者包括来自 ECHO PATHWAYS 联盟中的三个队列(CANDLE、TIDES 和 GAPPS)的 1677 名不吸烟女性。在第二个三个月期间测量了 12 种单羟基多环芳烃。在分析中包含了总检出率超过 60%的七种代谢物:1-羟基萘[1-OH-NAP]、2-羟基萘[2-OH-NAP]、2-羟基菲[2-OH-PHEN]、3-羟基菲[3-OH-PHEN]、1/9-羟基菲[1/9-OH-PHEN]、2/3/9-羟基芴[2/3/9-OH-FLUO]和 1-羟基芘[1-OH-PYR]。使用逻辑回归和线性回归模型分别拟合自发性 PTB 和出生时 GA,出生时 GA 大于等于 34 周,以 OH-PAH 浓度的对数变换作为暴露量,按比重和可疑混杂因素进行调整。使用交互项和边缘估计值评估婴儿性别对效应的修饰作用。
2-OH-NAP 的检测率最高(99.8%),1-OH-PYR 的检测率最低(65.2%)。自发性早产的患病率为 5.5%(N=92)。2-OH-NAP 暴露量增加 10 倍与出生时 GA 提前 1.60 天有关(95%CI:-2.92,-0.28)。在合并人群中,其余关联均为阴性。在女性中,我们观察到 1-OH-PYR 与 PTB 之间存在显著的负相关(OR:2.65[95%CI:1.39,5.05]);2-OH-NAP 与 GA:-2.46 天[95%CI:-4.15,-0.77])。在男性中,我们观察到 2/3/9-OH-FLUO 与 PTB 之间存在负相关(OR=0.40[95%CI:0.17,0.98])。与男性相比,女性的 2-OH-PHEN(p=0.02)和 1-OH-PYR(p=0.02)的 PTB 比值更高。
我们观察到 2-OH-NAP 暴露与 GA 之间存在负相关,而其余 OH-PAH 与 GA 和 PTB 之间的关联均为阴性。女性在产前暴露于某些 OH-PAH 后,可能更容易发生自发性早产或更短的 GA。本研究首次评估了 OH-PAH 毒性与自发性早产和 GA 的性别特异性关系。