Childhood exposures to environmental chemicals and neurodevelopmental outcomes in congenital heart disease

Abstract

Background Children with congenital heart defects have an increased risk of neurodevelopmental disability. The impact of environmental chemical exposures during daily life on neurodevelopmental outcomes in toddlers with congenital heart defects is unknown. Methods This prospective study investigated the impacts of early childhood exposure to mixtures of environmental chemicals on neurodevelopmental outcomes after cardiac surgery. Outcomes were assessed at 18 months of age using The Bayley Scales of Infant and Toddler Development-III. Urinary concentrations of exposure biomarkers of pesticides, phenols, parabens, and phthalates, and blood levels of lead, mercury, and nicotine were measured at the same time point. Bayesian profile regression and weighted quantile sum regression were utilized to assess associations between mixtures of biomarkers and neurodevelopmental scores. Results One-hundred and forty infants were enrolled, and 110 (79%) returned at 18 months of age. Six biomarker exposure clusters were identified from the Bayesian profile regression analysis; and the pattern was driven by 15 of the 30 biomarkers, most notably 13 phthalate biomarkers. Children in the highest exposure cluster had significantly lower adjusted language scores by -9.41 points (95%CI: -17.2, -1.7) and adjusted motor scores by -4.9 points (-9.5, -0.4) compared to the lowest exposure. Weighted quantile sum regression modeling for the overall exposure-response relationship showed a significantly lower adjusted motor score (β = -2.8 points [2.5th and 97.5th percentile: -6.0, -0.6]). The weighted quantile sum regression index weights for several phthalates, one paraben, and one phenol suggest their relevance for poorer neurodevelopmental outcomes. Conclusions Like other children, infants with congenital heart defects are exposed to complex mixtures of environmental chemicals in daily life. Higher exposure biomarker concentrations were associated with significantly worse performance for language and motor skills in this population.

Anesthesia and Sedation Exposure and Neurodevelopmental Outcomes in Infants Undergoing Congenital Cardiac Surgery: A Retrospective Cohort Study

“…Last, no standard pre-or perioperative assessment of baseline neurologic abnormalities was performed; these data were not collected as part of the primary study. 12 conclusions In infants undergoing corrective and palliative surgery for major congenital heart disease, cumulative volatile anesthetic exposures were not associated with lower neurodevelopmental assessment scores at 18-month follow-up after adjusting for nonmodifiable patient factors and length of stay. These findings contrast with studies that have shown volatile anesthetic exposure to be associated with worse neurodevelopmental outcomes in infants.…”

“…As previously demonstrated, nonmodifiable patient factors such as race and presence of a genetic anomaly were associated with lower neurodevelopmental scores at 18-month follow-up. 12 We specifically focused this analysis on a patient population that experiences a substantial burden of cumulative anesthetic and sedative exposures early in life, as a meta-analysis of animal and human data suggested a dose dependency of deleterious outcomes. 23 In accordance with these findings, infants in this study were exposed to substantial cumulative anesthetic doses and considerable polypharmacy during perioperative and intensive care, with all receiving an inhaled anesthetic and a majority being exposed to opioids, ketamine, benzodiazepines, and barbiturates by 18 months of age.…”

“…Many of these chemicals are known endocrine-disrupting compounds and/or neurotoxicants, and we identified a greater adverse effect in girls compared to boys. 12 Periodic developmental surveillance, screening, and evaluation in children with congenital heart disease may enhance identification of significant deficits and enable appropriate education and therapy to improve neurodevelopment and functioning. 8 Novel intervention opportunities are being explored to improve neurodevelopmental outcomes in children with congenital heart disease during the perioperative period, through the utilization of new stratification schemata and cognitive interventions.…”

“…Last, no standard pre- or perioperative assessment of baseline neurologic abnormalities was performed; these data were not collected as part of the primary study. 12…”

“…The table includes data for the complete study cohort (n = 110), including live patients lost to follow-up (live nonreturners, n = 20). 12 Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.…”