Prenatal and early childhood critical windows for the association of nephrotoxic metal and metalloid mixtures with kidney function

产前和幼儿期是肾毒性金属和类金属混合物与肾功能关系的关键时期

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作者:Alison P Sanders, Chris Gennings, Marcela Tamayo-Ortiz, Shachi Mistry, Ivan Pantic, Mauro Martinez, Guadalupe Estrada-Gutierrez, Aurora Espejel-Nuñez, Libni Torres Olascoaga, Robert O Wright, Martha M Téllez-Rojo, Manish Arora, Christine Austin

Conclusions

Using tooth-matrix biomarkers, we identified discrete developmental exposure windows wherein Pb and metal(loid) mixtures were associated with altered preadolescent kidney function.

Methods

Participants included 353 children in the Programming Research in Obesity Growth, Environment and Social Stressors (PROGRESS) longitudinal birth cohort study based in Mexico City. Estimated glomerular filtration rate (eGFR) was assessed in 8-12 year old children using serum cystatin C measures. Pre- and postnatal metal(loid) concentrations were assessed in weekly increments by analyzing deciduous teeth with laser ablation-inductively coupled plasma-mass spectrometry. We used reverse distributed lag models (rDLMs) and lagged Weighted Quantile Sum (L-WQS) regression to examine time-varying associations between weekly perinatal metal(loid) exposure or metal(loid) mixtures and preadolescent eGFR while adjusting for age, sex, BMI z-score, SES and prenatal tobacco smoke exposure.

Results

We identified a critical window of susceptibility to Pb exposure, in the late 3rd trimester (5 weeks prior to birth) during which higher Pb exposure was associated with children's increased eGFR. When all elements were assessed as a mixture, we identified late 2nd/early 3rd trimester (weeks 8-17 of gestation) as a window of vulnerability associated with decreased eGFR, with Li and Cr contributing the greatest weights to the association. When stratified by sex, we observed stronger effects among boys than girls. Conclusions: Using tooth-matrix biomarkers, we identified discrete developmental exposure windows wherein Pb and metal(loid) mixtures were associated with altered preadolescent kidney function.

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