Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression

Virissa Lenters; Lützen Portengen; Anna Rignell-Hydbom; Bo A G Jönsson; Christian H Lindh; Aldert H Piersma; Gunnar Toft; Jens Peter Bonde; Dick Heederik; Lars Rylander; Roel Vermeulen

doi:10.1289/ehp.1408933

Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression

Virissa Lenters, Lützen Portengen, Anna Rignell-Hydbom, Bo A G Jönsson, Christian H Lindh, Aldert H Piersma, Gunnar Toft, Jens Peter Bonde, Dick Heederik, Lars Rylander, Roel Vermeulen

Department of Public Health

115 Citations (Scopus)

Abstract

Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´‑DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.

Original language	English
Journal	Environmental Health Perspectives
Volume	124
Issue number	3
Pages (from-to)	365-72
Number of pages	8
ISSN	0091-6765
DOIs	https://doi.org/10.1289/ehp.1408933
Publication status	Published - Mar 2016

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Lenters, V., Portengen, L., Rignell-Hydbom, A., Jönsson, B. A. G., Lindh, C. H., Piersma, A. H., Toft, G., Bonde, J. P., Heederik, D., Rylander, L., & Vermeulen, R. (2016). Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression. Environmental Health Perspectives, 124(3), 365-72. https://doi.org/10.1289/ehp.1408933

Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts : Multi-Pollutant Models Based on Elastic Net Regression. / Lenters, Virissa; Portengen, Lützen; Rignell-Hydbom, Anna et al.

In: Environmental Health Perspectives, Vol. 124, No. 3, 03.2016, p. 365-72.

Research output: Contribution to journal › Journal article › Research › peer-review

Lenters, V, Portengen, L, Rignell-Hydbom, A, Jönsson, BAG, Lindh, CH, Piersma, AH, Toft, G, Bonde, JP, Heederik, D, Rylander, L & Vermeulen, R 2016, 'Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression', Environmental Health Perspectives, vol. 124, no. 3, pp. 365-72. https://doi.org/10.1289/ehp.1408933

@article{b001687c46374e43a42d572eb6cc59ca,

title = "Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression",

abstract = "Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´‑DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.",

author = "Virissa Lenters and L{\"u}tzen Portengen and Anna Rignell-Hydbom and J{\"o}nsson, {Bo A G} and Lindh, {Christian H} and Piersma, {Aldert H} and Gunnar Toft and Bonde, {Jens Peter} and Dick Heederik and Lars Rylander and Roel Vermeulen",

year = "2016",

month = mar,

doi = "10.1289/ehp.1408933",

language = "English",

volume = "124",

pages = "365--72",

journal = "Environmental Health Perspectives",

issn = "0091-6765",

publisher = "National Institute of Environmental Health Sciences",

number = "3",

}

TY - JOUR

T1 - Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts

T2 - Multi-Pollutant Models Based on Elastic Net Regression

AU - Lenters, Virissa

AU - Portengen, Lützen

AU - Rignell-Hydbom, Anna

AU - Jönsson, Bo A G

AU - Lindh, Christian H

AU - Piersma, Aldert H

AU - Toft, Gunnar

AU - Bonde, Jens Peter

AU - Heederik, Dick

AU - Rylander, Lars

AU - Vermeulen, Roel

PY - 2016/3

Y1 - 2016/3

N2 - Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´‑DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.

AB - Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´‑DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.

U2 - 10.1289/ehp.1408933

DO - 10.1289/ehp.1408933

M3 - Journal article

C2 - 26115335

SN - 0091-6765

VL - 124

SP - 365

EP - 372

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

IS - 3

ER -

Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression

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