母体邻苯二甲酸尿浓度、胎儿生长和不良出生结局。一项基于人群的前瞻性队列研究。
Maternal phthalate urine concentrations, fetal growth and adverse birth outcomes. A population-based prospective cohort study.
机构信息
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Wadsworth Center, New York State Department of Health, and Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Albany, NY 12201, United States; Department of Chemistry, the Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
出版信息
Environ Int. 2021 Jun;151:106443. doi: 10.1016/j.envint.2021.106443. Epub 2021 Feb 17.
IMPORTANCE
Exposure to phthalates may affect fetal growth, but previous studies are inconsistent and have not explored the trimester-specific effects of phthalates on repeated measures of fetal growth.
OBJECTIVE
To assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure.
DESIGN
Population-based prospective cohort study, the Generation R Study (2002-2006). Data analysis was performed from November 2019 to June 2020.
SETTING
Rotterdam, the Netherlands.
PARTICIPANTS
1379 pregnant women.
EXPOSURES
Maternal phthalate metabolites urine concentrations in first, second and third trimester.
MAIN OUTCOMES AND MEASURES
Fetal head circumference, length and weight measured in the second and third trimester by ultrasound and at birth and preterm birth and small size for gestational age at birth.
RESULTS
Higher pregnancy-averaged phthalic acid, low molecular weight phthalate (LMWP), high molecular weight phthalate (HMWP) and di-2-ethylhexylphthalate (DEHP) concentrations tended to be associated with lower fetal weight SDS across gestation. The associations of phthalic acid and LMWP with fetal weight became stronger as pregnancy progressed (differences -0.08 (95% CI -0.14 to -0.02) SDS and -0.09 (95% CI -0.16 to -0.02) SDS at 40 weeks per interquartile range increase in phthalic acid and LMWP, respectively). Higher concentrations of specific LMWP, HMWP and DEHP metabolites were also associated with smaller head circumference and lower length SDS at birth and an increased risk of preterm birth and small size for gestational age at birth (p-values < 0.05). We observed differences by timing of exposure in these associations.
CONCLUSIONS AND RELEVANCE
Higher maternal phthalate metabolites urine concentrations seem to be related with fetal growth restriction and preterm birth. Phthalates may have trimester specific effects on fetal growth and birth outcomes. Further studies are needed to explore the underlying mechanisms and long-term consequences.
重要性
接触邻苯二甲酸酯可能会影响胎儿生长，但先前的研究结果并不一致，并且没有探讨邻苯二甲酸酯对胎儿生长的各孕期具体影响。
目的
评估母体邻苯二甲酸酯代谢物尿液浓度与胎儿生长指标和出生结局的关系，并确定潜在的易暴露窗口期。
设计
基于人群的前瞻性队列研究，即“生育队列研究”（2002-2006 年）。数据分析于 2019 年 11 月至 2020 年 6 月进行。
地点
荷兰鹿特丹。
参与者
1379 名孕妇。
暴露
孕妇在妊娠第一、二、三期的邻苯二甲酸酯代谢物尿液浓度。
主要结局和措施
通过超声在妊娠第二和第三期以及在出生时测量胎儿头围、长度和体重，以及早产和出生时小于胎龄儿。
结果
孕期平均邻苯二甲酸、低分子量邻苯二甲酸（LMWP）、高分子量邻苯二甲酸（HMWP）和邻苯二甲酸二（2-乙基己基）酯（DEHP）浓度较高，与胎儿体重的生长曲线下面积（SDS）随妊娠进展而降低有关。随着妊娠的进展，邻苯二甲酸和 LMWP 与胎儿体重的相关性逐渐增强（每增加一个四分位距，邻苯二甲酸和 LMWP 分别降低 0.08（95%CI-0.14 至-0.02）SDS 和 0.09（95%CI-0.16 至-0.02）SDS）。特定的 LMWP、HMWP 和 DEHP 代谢物浓度较高，与出生时头围较小、长度 SDS 较低以及早产和出生时小于胎龄儿的风险增加有关（p 值均<0.05）。我们观察到这些关联存在时间暴露差异。
结论和相关性
母体邻苯二甲酸酯代谢物尿液浓度较高似乎与胎儿生长受限和早产有关。邻苯二甲酸酯可能对胎儿生长和出生结局具有特定孕期的影响。需要进一步的研究来探索潜在的机制和长期后果。
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