Associations of pregnancy phthalate concentrations and their mixture with early adolescent bone mineral content and density: The Health Outcomes and Measures of the Environment (HOME) study
- PMID: 34740813
- PMCID: PMC8671261
- DOI: 10.1016/j.bone.2021.116251
Associations of pregnancy phthalate concentrations and their mixture with early adolescent bone mineral content and density: The Health Outcomes and Measures of the Environment (HOME) study
Abstract
Background: The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce.
Objectives: To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort.
Methods: We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26 weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12 years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation.
Results: In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: -0.13, 1.10) greater ultradistal radius BMD Z-score in females.
Discussion: In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.
Keywords: Adolescence; Bone mineral content; Bone mineral density; Phthalates; Pregnancy.
Copyright © 2021 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing financial interests
Dr. Braun’s institution was financially compensated for his services as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water; but he has not personally received any compensation for these services. Dr. Lanphear served as an expert witness in cases related to childhood lead poisoning, but he has not personally received any compensation for these services.
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