Associations between urinary paraben concentrations and measures of cardiometabolic risk in pre-school children of the ENVIRONAGE birth cohort

Background and Aim: Parabens are widely used as antimicrobial preservatives in personal care products. Endocrine-disrupting effects have been described previously, but studies investigating obesogenic or cardiovascular effects have shown discordant results. Cardiometabolic changes associated with paraben exposure and predictive for later life health conditions may already be visible in early life. Methods: Paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples from 4-6-year-old children of the ENVIRONAGE birth cohort. Values below the limit of quantification (LOQ) were imputed by censored likelihood multiple imputation. The association with anthropometric and cardiovascular measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) was analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. Results: The geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.50), and 4.82 (4.11) µg/L respectively. For BuP 97% of all measurements were below the LOQ. In adjusted models with log-transformed paraben values MeP was associated with central retinal venular equivalent (β = 1.33, p = 0.029) and inversely associated with BMI z-scores (β = -0.065, p = 0.019). PrP was associated with the retinal tortuosity index (β = 0.0018, p = 0.0034). Additionally, EtP was significantly associated with BMI z-scores in boys (β = 0.12, p = 0.012). Conclusions: The inverse association between MeP and BMI z-scores could illustrate underlying biological mechanisms related to endocrine-disrupting properties of parabens. Associations between parabens and retinal microvasculature in pre-school children may indicate adverse effects on cardiometabolic health even at a young age and provide a starting point for further research on paraben-related modes of action. Keywords: Parabens, BMI z-scores, blood pressure, retinal microvasculature, ENVIRONAGE birth cohort