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Background and aim: Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life.Methods: In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quanti-tation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms.Results: Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) mu g/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (beta = 1.23, p = 0.039) and PrP with the retinal tortuosity index (x103)(beta = 1.75, p = 0.0044). Furthermore, we identified inverse associations between MeP and n-ary sumation parabens with BMI z-scores (beta =-0.067, p = 0.015 and beta =-0.070, p = 0.014 respectively), and EtP with mean arterial pressure (beta =-0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (beta = 0.10, p = 0.060).Conclusions: Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature. The ENVIRONAGE birth cohort is supported by grants from European Research Council (ERC-2012-StG 310898), the Flemish Research Council (FWO G073315 N) and the STOP project (Grant No. 774548- H2020). BR and LR were financially supported by the University Research Fund (Bijzonder Onderzoeksfonds Universiteit Hasselt). The funding sources had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. We acknowledge the participating mothers and neonates, as well as the staff of the maternity ward, midwives, and the staff of the clinical laboratory of East-Limburg Hospital in Genk.

Introduction: During early childhood, neuronal networks are highly susceptible to environmental factors. Previous research suggests that green space exposure is beneficial for cognitive functioning. Here, we investigate the associations between residential green space exposure and behavioral problems and cognitive development in children aged four to six years. Method: We included children participating in the ENVIRONAGE birth cohort. Residential green spaces were calculated based on high-resolution land cover data within several buffers (50-1,000 m) around the residence. The children's behavior was assessed with the Strengths and Difficulties Questionnaire (SDQ) among 411 children. In addition, to evaluate cognitive function, 456 children completed four tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We used multivariate logistic and linear regression models while accounting for potential confounders and covariables. Results: An interquartile (IQR) increase of residential green space within 50 m was associated with a 38% (95% CI: 56;14) lower odds of a child having hyperactivity problems. Additionally, we found a beneficial influence of residential green space in close proximity (50-100 m) on the attention and psychomotor speed, represented by the Motor Screening Task. For example, we found a decrease of 0.45 (95% CI: -0.82;-0.09) pixel units from target center with an IQR increase of residential green space in a 50 m buffer. In addition, we observed an improved visual recognition/working memory, represented by the Delayed Matching to Sample Task within all included buffers (50-1000 m). For example, we observed a decrease of 4.91% (95 %CI: -7.46;-2.36) probability of an error occurring if the previous trial was correct and a 2.02% (95 %CI: 0.08; 3.97) increase of correct trials with an IQR increase of green space within a 100 m buffer. Conclusion: This study provides additional indications for a beneficial influence of green space exposure on the development of behavioral problems and cognitive function as young as four years of age. This investigation is supported by the EU research council “project ENVIRONAGE” (ERC-2012-StG 310890) and Flemish Scientific Fund (G073315N/G048420N). Lidia Casas is recipient of a post-doctoral fellowship a of the Research Foundation Flanders (FWO), grant number 12I1517N. Esm´ee M Bijnens holds a fellowship from the Marguerite-Marie Delacroix foundation. The authors thank all children and parents for taking part in the study. Graphical abstract was created with BioRender.com.