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

Susana Moreira da Silva Santos; Chalana Sol; Charissa van Zwol - Janssens; Elise Philips; AG Asimakopoulos; MP Martinez-Moral; K Kannan; Vincent Jaddoe; L Trasande

doi:10.1016/j.envint.2021.106443

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

Susana Moreira da Silva Santos, Chalana Sol, Charissa van Zwol - Janssens, Elise Philips, AG Asimakopoulos, MP Martinez-Moral, K Kannan, Vincent Jaddoe, L Trasande

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Abstract

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.

Original language	English
Article number	106443
Journal	Environmental International
Volume	151
DOIs	https://doi.org/10.1016/j.envint.2021.106443
Publication status	Published - Jun 2021

Bibliographical note

Funding Information:
The general design of the Generation R Study is made possible by financial support from the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, the Organization for Health Research and Development (ZonMw) and the Ministry of Health, Welfare and Sport. This study was supported by grants RO1ES-022972 and RO1ES-029779 from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement 874,583 (ATHLETE Project). VWVJ received additional grant from the European Research Council (ERC Consolidator Grant, ERC-2014-CoG-64916).

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Moreira da Silva Santos, S., Sol, C., van Zwol - Janssens, C., Philips, E., Asimakopoulos, AG., Martinez-Moral, MP., Kannan, K., Jaddoe, V., & Trasande, L. (2021). Maternal phthalate urine concentrations, fetal growth and adverse birth outcomes. A population-based prospective cohort study. Environmental International, 151, Article 106443. https://doi.org/10.1016/j.envint.2021.106443

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abstract = "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.",

author = "\{Moreira da Silva Santos\}, Susana and Chalana Sol and \{van Zwol - Janssens\}, Charissa and Elise Philips and AG Asimakopoulos and MP Martinez-Moral and K Kannan and Vincent Jaddoe and L Trasande",

note = "Funding Information: The general design of the Generation R Study is made possible by financial support from the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, the Organization for Health Research and Development (ZonMw) and the Ministry of Health, Welfare and Sport. This study was supported by grants RO1ES-022972 and RO1ES-029779 from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. This work was supported by the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement 874,583 (ATHLETE Project). VWVJ received additional grant from the European Research Council (ERC Consolidator Grant, ERC-2014-CoG-64916). Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = jun,

doi = "10.1016/j.envint.2021.106443",

language = "English",

volume = "151",

journal = "Environmental International",

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Moreira da Silva Santos, S, Sol, C , van Zwol - Janssens, C, Philips, E, Asimakopoulos, AG, Martinez-Moral, MP, Kannan, K, Jaddoe, V & Trasande, L 2021, 'Maternal phthalate urine concentrations, fetal growth and adverse birth outcomes. A population-based prospective cohort study', Environmental International, vol. 151, 106443. https://doi.org/10.1016/j.envint.2021.106443

TY - JOUR

T1 - Maternal phthalate urine concentrations, fetal growth and adverse birth outcomes. A population-based prospective cohort study

AU - Moreira da Silva Santos, Susana

AU - Sol, Chalana

AU - van Zwol - Janssens, Charissa

AU - Philips, Elise

AU - Asimakopoulos, AG

AU - Martinez-Moral, MP

AU - Kannan, K

AU - Jaddoe, Vincent

AU - Trasande, L

N1 - Funding Information: The general design of the Generation R Study is made possible by financial support from the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, the Organization for Health Research and Development (ZonMw) and the Ministry of Health, Welfare and Sport. This study was supported by grants RO1ES-022972 and RO1ES-029779 from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement 874,583 (ATHLETE Project). VWVJ received additional grant from the European Research Council (ERC Consolidator Grant, ERC-2014-CoG-64916). Publisher Copyright: © 2021 The Author(s)

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

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DO - 10.1016/j.envint.2021.106443

M3 - Article

C2 - 33610054

SN - 0160-4120

VL - 151

JO - Environmental International

JF - Environmental International

M1 - 106443

ER -

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

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