Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.
Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.
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DOI：
10.1016/j.envres.2023.115975
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发表时间：
2023-04
影响因子：
8.3
通讯作者：
D. Stevens;E. Rosen;Kimi Van Wickle;E. McNell;P. Bommarito;A. Calafat;J. Botelho;E. Sinkovskaya;Ann Przybylska;G. Saade;A. Abuhamad;K. Ferguson
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文献类型：
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作者：
D. Stevens;E. Rosen;Kimi Van Wickle;E. McNell;P. Bommarito;A. Calafat;J. Botelho;E. Sinkovskaya;Ann Przybylska;G. Saade;A. Abuhamad;K. Ferguson
背景孕妇无处不在地接触邻苯二甲酸盐，而且越来越多地接触到用来取代邻苯二甲酸盐的化学物质。在怀孕早期，接触这些化学物质可能会扰乱胎儿的形成和发育，表现出不利的胎儿生长。以前的研究依赖于单一的现场尿液测量，而没有调查替代化学物质。目的研究怀孕早期尿邻苯二甲酸盐和替代生物标志物与胎儿生长结果的关系。方法在2017-2020年招募的前瞻性队列人类胎盘和邻苯二甲酸盐研究中，对254名孕妇进行分析。暴露是在怀孕12周和14周左右收集的两个现场尿样中邻苯二甲酸盐和替代生物标记物的几何平均浓度。结果是在每个三个月收集的胎儿超声生物测量(头部和腹围，股骨长度，估计的胎儿体重)，并转换为z分数。具有参与者特定随机效应的调整线性混合效应(单一污染物)和分位数g计算(混合)模型平均估计单个(单一污染物)或所有(混合)怀孕早期邻苯二甲酸酯和替代生物标记物增加一个四分位数范围(IQR)时胎儿纵向生长的差异。结果邻苯二甲酸单羧异酸酯和邻苯二甲酸二正丁酯、二异丁酯和邻苯二甲酸二乙基己酯的代谢物总和与胎儿头和腹围z分数呈负相关。邻苯二甲酸盐和替代生物标记物混合物的智商增加1与胎儿头围(β：-0.36[95%可信区间：-0.56，−0.15])和腹围(−0.31[-0.49，−0.12])z得分呈负相关。这种关联主要是由邻苯二甲酸盐生物标记物驱动的。结论妊娠早期尿中邻苯二甲酸盐生物标记物的浓度与胎儿生长减退有关，而与替代生物标记物无关。尽管这些差异的临床意义尚不清楚，但胎儿生长减少在整个生命过程中会导致过高的发病率和死亡率。鉴于全球普遍暴露于邻苯二甲酸盐，研究结果表明，怀孕早期暴露于邻苯二甲酸盐会造成相当大的人口健康负担。
BackgroundPregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals.ObjectiveCharacterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes.MethodsAnalyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017–2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers.ResultsMono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (β: -0.36 [95% confidence interval: -0.56, −0.15]) and abdominal circumference (−0.31 [-0.49, −0.12]) z-scores. This association was mainly driven by phthalate biomarkers.ConclusionsUrine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure.