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.

中文翻译：

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母体邻苯二甲酸盐尿液浓度，胎儿生长和不良分娩结果。基于人群的前瞻性队列研究

重要性

邻苯二甲酸盐的暴露可能会影响胎儿的生长，但是以前的研究并不一致，也没有探讨邻苯二甲酸盐对胎儿生长的重复测量的孕中期特异性作用。

客观的

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之间的关系，并确定易感性暴露的潜在窗口。

设计

基于人口的前瞻性队列研究，R一代研究（2002–2006年）。数据分析于2019年11月至2020年6月进行。

环境

荷兰鹿特丹。

参加者

1379名孕妇。

曝光量

孕期，孕中期和孕晚期孕妇的邻苯二甲酸酯代谢尿液浓度。

主要成果和措施

胎儿头围，身长和体重在超声检查的中期和中期以及在出生和早产时测量，并且在出生时的胎龄较小。

结果

较高的怀孕平均邻苯二甲酸，低分子量邻苯二甲酸酯（LMWP），高分子量邻苯二甲酸酯（HMWP）和二-2-乙基己基邻苯二甲酸酯（DEHP）浓度往往在整个妊娠期与较低的胎儿SDS有关。在每个四分位间距40周时，随着怀孕的进行，邻苯二甲酸和LMWP与胎儿体重的关联性变得更强（差异-0.08（95％CI -0.14至-0.02）SDS和-0.09（95％CI -0.16至-0.02）SDS。分别增加邻苯二甲酸和LMWP）。较高浓度的特定LMWP，HMWP和DEHP代谢物还与出生时头围较小和SDS长度降低以及早产风险增加和出生时胎龄较小有关（p值<0.05）。我们通过这些关联中的暴露时间观察了差异。

结论与相关性

孕妇邻苯二甲酸盐代谢产物的较高尿液浓度似乎与胎儿生长受限和早产有关。邻苯二甲酸盐可能对胎儿的生长和出生结局有特定的妊娠中期影响。需要进一步的研究以探索潜在的机制和长期后果。