Maternal phthalate urine concentrations, fetal growth and adverse birth outcomes. A population-based prospective cohort study

Susana Santos,Chalana M Sol,Charissa Van Zwol – Janssens,Elise M Philips,Alexandros G Asimakopoulos,Maria-Pilar Martinez-Moral,Kurunthachalam Kannan,Vincent W.V Jaddoe,Leonardo Trasande

doi:10.1016/j.envint.2021.106443

Abstract

ImportanceExposure 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. ObjectiveTo assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure. DesignPopulation-based prospective cohort study, the Generation R Study (2002–2006). Data analysis was performed from November 2019 to June 2020. SettingRotterdam, the Netherlands. Participants1379 pregnant women. ExposuresMaternal phthalate metabolites urine concentrations in first, second and third trimester. Main outcomes and measuresFetal 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. ResultsHigher 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 relevanceHigher 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.

Highlights

Phthalates are endocrine disrupting chemicals and are widespread as plasticizers in polyvinyl chloride plastics, personal care products and some medical devices (Hauser and Calafat, 2005)
A case-control study among 130 pre term children and 352 random term singleton controls showed that cumulative exposure to mono-2-ethyl-5-carboxypentyl phthalate, monobenzyl phthalate and sum of di-2-ethylhexyl phthalate (DEHP) metab olites was associated with lower growth of head circumference, femur length and estimated weight between 26 and 35 weeks (Ferguson et al, 2016)
In a prospective cohort study among 390 mother–child pairs, fetal mono-benzyl phthalate exposure was associated with increased femur length growth from 20 to 34 weeks, while fetal mono-n-butyl phthalate exposure was associated with lower head circumference growth from 12 to 20 weeks (Casas et al, 2016)

Summary

Introduction

Phthalates are endocrine disrupting chemicals and are widespread as plasticizers in polyvinyl chloride plastics, personal care products and some medical devices (Hauser and Calafat, 2005). Previous studies on the associations of maternal phthalate metabo lites concentrations during pregnancy with fetal weight, length and head circumference measurements during pregnancy or at birth showed inconsistent results (Kamai et al, 2019; Kalloo et al, 2020; Bloom et al, 2019; Noor et al, 2019; Botton et al, 2016; Ferguson et al, 2016; Casas et al, 2016) Fetal exposure to phthalates seems to be associated with an increased risk of preterm birth (Kalloo et al, 2020; Bloom et al, 2019; Chin et al, 2019; Ferguson et al, 2014; Gao et al, 2019; Boss et al, 2018; Zhang et al, 2020; Ferguson et al, 2019). The trimester-specific effects of phthalates on repeated measures of fetal growth and birth outcomes remain largely unknown (Ferguson et al, 2016)

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