Fetal phthalate exposure and asthma outcomes from infancy to adolescence: Individual participant data meta-analysis in the EU Child Cohort Network

Tarik Karramass; Liesbeth Duijts; Demetris Avraam; Sophia Blaauwendraad; Paula Carrasco; Nuria Güil-Oumrait; Amaia Irizar; Manik Kadawathagedara; Marianna Karachaliou; Maria Jose Lopez-Espinosa; Antonis Myridakis; Elke Rouxel; Amrit Kaur Sakhi; Cathrine Thomsen; Chloe Vainqueur; Martine Vrijheid; Charline Warembourg; Marieke Welten; Carlos Zabaleta; Leonardo Trasande; Vincent Jaddoe

doi:10.1016/j.envint.2026.110069

Fetal phthalate exposure and asthma outcomes from infancy to adolescence: Individual participant data meta-analysis in the EU Child Cohort Network

Tarik Karramass
, Liesbeth Duijts
, Demetris Avraam
, Sophia Blaauwendraad
, Paula Carrasco
, Nuria Güil-Oumrait
, Amaia Irizar
, Manik Kadawathagedara
, Marianna Karachaliou
, Maria Jose Lopez-Espinosa
, Antonis Myridakis
, Elke Rouxel
, Amrit Kaur Sakhi
, Cathrine Thomsen
, Chloe Vainqueur
, Martine Vrijheid
, Charline Warembourg
, Marieke Welten
, Carlos Zabaleta
, Leonardo Trasande

Vincent Jaddoe^*

^*Corresponding author for this work

University of Copenhagen
FISABIO
Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP)
Barcelona Institute for Global Health (ISGlobal)
University of the Basque Country
Biogipuzkoa Health Research Institute
Université Paris 13
Erasmus University Rotterdam
University of Crete School of Medicine
University of Valencia
Imperial College London
École des hautes études en santé publique
Norwegian Institute of Public Health
Pompeu Fabra University
Instituto de Investigación Sanitaria Biodonostia
Nuestra señora de la Antigua Hospital
New York University School of Medicine
New York University Wagner School of Public Service

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Objective:

Early-life exposure to phthalates, widely used in consumer products, may induce developmental lung adaptations and predispose to respiratory morbidity throughout childhood. We assessed the associations of fetal phthalate exposure with wheezing, asthma, and lung function from birth to adolescence.

Methods:

We performed 1-stage individual participant data meta -analyses with data from six European birth cohorts (3,745 mother–child pairs) to assess associations of pregnancy-averaged maternal urinary concentrations of 7 phthalate metabolites and 3 phthalate groups (high- and low-molecular-weight phthalate metabolites and sum of di-2-ethylhexyl phthalate metabolites) with wheezing in infancy (0–1 years) and at preschool age (1–5 years), and asthma and lung function at school age (5–12 years).

Results:

Higher maternal pregnancy urine phthalate concentrations were not associated with wheezing in infancy or preschool age. Higher maternal pregnancy urine mono-benzyl phthalate concentrations were associated with an increased risk of asthma at school age (odds ratio (95% confidence interval): 1.13 (1.01–1.26) per natural log interquartile range unit increase in concentration), but not with wheezing or lung function and attenuated into non-significance after multiple testing correction. Higher maternal pregnancy concentrations of mono-2-ethyl-5-hydroxyhexyl phthalate, mono- iso -butyl phthalate, mono-n-butyl phthalate and low-molecular-weight phthalate metabolites were associated with higher FEV_1, FEV₁/FVC and FEF₇₅ z-scores after multiple testing correction.

Conclusion:

Fetal exposure to higher phthalate concentrations is associated with lung function adaptations, while overall no consistent associations were observed with childhood wheezing or asthma. Future studies are needed to assess the causality of the observed associations, to identify the underlying mechanisms, and to assess potential respiratory consequences in adult life.

Original language	English
Article number	110069
Journal	Environment international
Volume	208
DOIs	https://doi.org/10.1016/j.envint.2026.110069
Publication status	Published - Feb 2026

Bibliographical note

Publisher Copyright:
© 2026 The Author(s).

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Fetal phthalate exposure and asthma outcomes from infancy to adolescenceFinal published version, 2.39 MBLicence: CC BY

Cite this

Karramass, T., Duijts, L., Avraam, D., Blaauwendraad, S., Carrasco, P., Güil-Oumrait, N., Irizar, A., Kadawathagedara, M., Karachaliou, M., Lopez-Espinosa, M. J., Myridakis, A., Rouxel, E., Sakhi, A. K., Thomsen, C., Vainqueur, C., Vrijheid, M., Warembourg, C., Welten, M., Zabaleta, C., ... Jaddoe, V. (2026). Fetal phthalate exposure and asthma outcomes from infancy to adolescence: Individual participant data meta-analysis in the EU Child Cohort Network. Environment international, 208, Article 110069. https://doi.org/10.1016/j.envint.2026.110069

@article{3253a1cdf77b4b9dabe9ba656f9744b7,

title = "Fetal phthalate exposure and asthma outcomes from infancy to adolescence: Individual participant data meta-analysis in the EU Child Cohort Network",

abstract = "Objective:Early-life exposure to phthalates, widely used in consumer products, may induce developmental lung adaptations and predispose to respiratory morbidity throughout childhood. We assessed the associations of fetal phthalate exposure with wheezing, asthma, and lung function from birth to adolescence. Methods:We performed 1-stage individual participant data meta -analyses with data from six European birth cohorts (3,745 mother–child pairs) to assess associations of pregnancy-averaged maternal urinary concentrations of 7 phthalate metabolites and 3 phthalate groups (high- and low-molecular-weight phthalate metabolites and sum of di-2-ethylhexyl phthalate metabolites) with wheezing in infancy (0–1 years) and at preschool age (1–5 years), and asthma and lung function at school age (5–12 years). Results:Higher maternal pregnancy urine phthalate concentrations were not associated with wheezing in infancy or preschool age. Higher maternal pregnancy urine mono-benzyl phthalate concentrations were associated with an increased risk of asthma at school age (odds ratio (95\% confidence interval): 1.13 (1.01–1.26) per natural log interquartile range unit increase in concentration), but not with wheezing or lung function and attenuated into non-significance after multiple testing correction. Higher maternal pregnancy concentrations of mono-2-ethyl-5-hydroxyhexyl phthalate, mono- iso -butyl phthalate, mono-n-butyl phthalate and low-molecular-weight phthalate metabolites were associated with higher FEV1, FEV1/FVC and FEF75 z-scores after multiple testing correction. Conclusion:Fetal exposure to higher phthalate concentrations is associated with lung function adaptations, while overall no consistent associations were observed with childhood wheezing or asthma. Future studies are needed to assess the causality of the observed associations, to identify the underlying mechanisms, and to assess potential respiratory consequences in adult life.",

author = "Tarik Karramass and Liesbeth Duijts and Demetris Avraam and Sophia Blaauwendraad and Paula Carrasco and Nuria G{\"u}il-Oumrait and Amaia Irizar and Manik Kadawathagedara and Marianna Karachaliou and Lopez-Espinosa, \{Maria Jose\} and Antonis Myridakis and Elke Rouxel and Sakhi, \{Amrit Kaur\} and Cathrine Thomsen and Chloe Vainqueur and Martine Vrijheid and Charline Warembourg and Marieke Welten and Carlos Zabaleta and Leonardo Trasande and Vincent Jaddoe",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s).",

year = "2026",

month = feb,

doi = "10.1016/j.envint.2026.110069",

language = "English",

volume = "208",

journal = "Environment international",

issn = "0160-4120",

publisher = "Elsevier Ltd.",

}

Karramass, T , Duijts, L, Avraam, D, Blaauwendraad, S, Carrasco, P, Güil-Oumrait, N, Irizar, A, Kadawathagedara, M, Karachaliou, M, Lopez-Espinosa, MJ, Myridakis, A, Rouxel, E, Sakhi, AK, Thomsen, C, Vainqueur, C, Vrijheid, M, Warembourg, C, Welten, M, Zabaleta, C, Trasande, L & Jaddoe, V 2026, 'Fetal phthalate exposure and asthma outcomes from infancy to adolescence: Individual participant data meta-analysis in the EU Child Cohort Network', Environment international, vol. 208, 110069. https://doi.org/10.1016/j.envint.2026.110069

TY - JOUR

T1 - Fetal phthalate exposure and asthma outcomes from infancy to adolescence

T2 - Individual participant data meta-analysis in the EU Child Cohort Network

AU - Karramass, Tarik

AU - Duijts, Liesbeth

AU - Avraam, Demetris

AU - Blaauwendraad, Sophia

AU - Carrasco, Paula

AU - Güil-Oumrait, Nuria

AU - Irizar, Amaia

AU - Kadawathagedara, Manik

AU - Karachaliou, Marianna

AU - Lopez-Espinosa, Maria Jose

AU - Myridakis, Antonis

AU - Rouxel, Elke

AU - Sakhi, Amrit Kaur

AU - Thomsen, Cathrine

AU - Vainqueur, Chloe

AU - Vrijheid, Martine

AU - Warembourg, Charline

AU - Welten, Marieke

AU - Zabaleta, Carlos

AU - Trasande, Leonardo

AU - Jaddoe, Vincent

PY - 2026/2

Y1 - 2026/2

N2 - Objective:Early-life exposure to phthalates, widely used in consumer products, may induce developmental lung adaptations and predispose to respiratory morbidity throughout childhood. We assessed the associations of fetal phthalate exposure with wheezing, asthma, and lung function from birth to adolescence. Methods:We performed 1-stage individual participant data meta -analyses with data from six European birth cohorts (3,745 mother–child pairs) to assess associations of pregnancy-averaged maternal urinary concentrations of 7 phthalate metabolites and 3 phthalate groups (high- and low-molecular-weight phthalate metabolites and sum of di-2-ethylhexyl phthalate metabolites) with wheezing in infancy (0–1 years) and at preschool age (1–5 years), and asthma and lung function at school age (5–12 years). Results:Higher maternal pregnancy urine phthalate concentrations were not associated with wheezing in infancy or preschool age. Higher maternal pregnancy urine mono-benzyl phthalate concentrations were associated with an increased risk of asthma at school age (odds ratio (95% confidence interval): 1.13 (1.01–1.26) per natural log interquartile range unit increase in concentration), but not with wheezing or lung function and attenuated into non-significance after multiple testing correction. Higher maternal pregnancy concentrations of mono-2-ethyl-5-hydroxyhexyl phthalate, mono- iso -butyl phthalate, mono-n-butyl phthalate and low-molecular-weight phthalate metabolites were associated with higher FEV1, FEV1/FVC and FEF75 z-scores after multiple testing correction. Conclusion:Fetal exposure to higher phthalate concentrations is associated with lung function adaptations, while overall no consistent associations were observed with childhood wheezing or asthma. Future studies are needed to assess the causality of the observed associations, to identify the underlying mechanisms, and to assess potential respiratory consequences in adult life.

AB - Objective:Early-life exposure to phthalates, widely used in consumer products, may induce developmental lung adaptations and predispose to respiratory morbidity throughout childhood. We assessed the associations of fetal phthalate exposure with wheezing, asthma, and lung function from birth to adolescence. Methods:We performed 1-stage individual participant data meta -analyses with data from six European birth cohorts (3,745 mother–child pairs) to assess associations of pregnancy-averaged maternal urinary concentrations of 7 phthalate metabolites and 3 phthalate groups (high- and low-molecular-weight phthalate metabolites and sum of di-2-ethylhexyl phthalate metabolites) with wheezing in infancy (0–1 years) and at preschool age (1–5 years), and asthma and lung function at school age (5–12 years). Results:Higher maternal pregnancy urine phthalate concentrations were not associated with wheezing in infancy or preschool age. Higher maternal pregnancy urine mono-benzyl phthalate concentrations were associated with an increased risk of asthma at school age (odds ratio (95% confidence interval): 1.13 (1.01–1.26) per natural log interquartile range unit increase in concentration), but not with wheezing or lung function and attenuated into non-significance after multiple testing correction. Higher maternal pregnancy concentrations of mono-2-ethyl-5-hydroxyhexyl phthalate, mono- iso -butyl phthalate, mono-n-butyl phthalate and low-molecular-weight phthalate metabolites were associated with higher FEV1, FEV1/FVC and FEF75 z-scores after multiple testing correction. Conclusion:Fetal exposure to higher phthalate concentrations is associated with lung function adaptations, while overall no consistent associations were observed with childhood wheezing or asthma. Future studies are needed to assess the causality of the observed associations, to identify the underlying mechanisms, and to assess potential respiratory consequences in adult life.

UR - https://www.scopus.com/pages/publications/105027761262

U2 - 10.1016/j.envint.2026.110069

DO - 10.1016/j.envint.2026.110069

M3 - Article

C2 - 41564604

AN - SCOPUS:105027761262

SN - 0160-4120

VL - 208

JO - Environment international

JF - Environment international

M1 - 110069

ER -

Fetal phthalate exposure and asthma outcomes from infancy to adolescence: Individual participant data meta-analysis in the EU Child Cohort Network

Abstract

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