Fetal exposure to phthalates and bisphenols could be associated with kidney function. We aim to assess the association between maternal urine concentrations of phthalates and bisphenols during pregnancy and kidney function and size during childhood. In 1366 pregnant women from a prospective population-based cohort, we measured urine concentrations of phthalates, more specifically phthalic acid and metabolites of low molecular weight phthalates (LMWP) and high molecular weight phthalates (HMWP), with its subgroups of di-2-ethylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) metabolites, and bisphenol A, S and F during first, second and third trimester. We explored three methods of adjustment for maternal hydration status: creatinine standardization, covariate adjustment for creatinine and covariate-adjusted creatinine standardization plus covariate adjustment. We measured kidney size, calculated estimated glomerular filtration rate (eGFR) and the albumin/creatinine ratio in urine and assessed microalbuminuria at 6 years old. When applying creatinine standardization, we found some associations of higher maternal second trimester urine phthalic acid and overall mean phthalic acid and LMWP concentrations with higher eGFR. These associations were lessened when applying other methods of creatinine adjustment. The associations found when we applied the covariate adjustment for creatinine method were also lessened when applying other methods of creatinine adjustment. Only the association of higher second trimester phthalic acid maternal urine concentrations with higher eGFR at 6 years old remained significant irrespective of the method of creatinine adjustment. There were no consistent associations of maternal bisphenol A, S and F urine concentrations with childhood kidney function. There were no associations of maternal phthalate or bisphenol urine concentrations with kidney volume in children at 6 years old. Concluding, no consistent associations of maternal phthalate or bisphenol urine concentrations with childhood kidney function or volume could be found. Furthermore, the method of adjusting maternal urine phthalate and bisphenol concentrations for urinary dilution had a substantial effect on the associations with childhood kidney function, as it changed the conclusions about the directionality of the associations. Future studies including maternal kidney function are needed to further elucidate these association in humans.
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We gratefully acknowledge the contribution of the participating children, their mothers, general practitioners, hospitals, midwives, and pharmacies in Rotterdam.
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 Grant R01-ES022972 and R01-ES029779 from the National Institutes of Health (NIH), 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 874583 (ATHLETE Project). VWVJ received an additional Grant from the European Research Council (ERC Consolidator Grant, ERC-2014-CoG-64916).
The authors have no relevant financial or non-financial interests to disclose.
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Sol, C.M., Santos, S., Kannan, K. et al. Prenatal Exposure to Phthalates and Bisphenols and Childhood Kidney Function: A Prospective Cohort Study. Expo Health 15, 699–720 (2023). https://doi.org/10.1007/s12403-022-00517-w