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

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, FEV 1 /FVC and FEF 75 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.