Associations of gestational and childhood exposure to lead, cadmium, and fluoride with cognitive abilities, behavior, and social communication at 4 years of age: NICE birth cohort study.

Background: Early-life lead exposure affects cognitive development and emerging evidence suggests similar effects of cadmium and fluoride.

Objective: To assess the impact of gestational and childhood exposure to lead, cadmium, and fluoride on cognitive abilities and behavioral and social communication problems.

Methods: We studied 470 pregnant women (gestational week 29) and their 4-year-old children from the NICE cohort in northern Sweden. Concentrations of erythrocyte lead and cadmium and urinary cadmium were measured using inductively coupled plasma mass spectrometry and urinary fluoride with an ion-selective electrode. Urinary concentrations were specific-gravity adjusted. Associations of log-transformed exposure concentrations with cognitive abilities (full-scale IQ and verbal comprehension by Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition), behavioral problems (Child Behavior Checklist), and social communication (Social Responsiveness Scale-Second Edition) were evaluated with multivariable-adjusted linear regression analysis.

Results: Both gestational and cord erythrocyte lead concentrations were non-significantly inversely associated with child cognitive abilities (full-scale IQ: B [95%CI]: -1.2 [-2.9, 0.5] and -1.6 [-3.7, 0.4], respectively; per doubling of exposure). Similarly, both gestational and child urinary cadmium were inversely associated with cognitive abilities (full-scale IQ: -1.1 [-2.5, 0.3] and -1.1 [-2.5, 0.4], verbal comprehension: -1.2 [-3.1, 0.6] and -1.4 [-3.4, 0.6], respectively). Urinary fluoride concentrations showed no association with cognitive abilities. However, gestational fluoride was associated with increasing externalizing problems (0.9 [-0.3, 2.0]) and ADHD raw scores (0.3 [0.0, 0.6]). Childhood erythrocyte lead and urinary cadmium were non-significantly associated with increased behavioral problems (lead with total problems: 1.2 [-0.4, 2.9] and internalizing problems: 1.5 [-0.4, 3.4]; cadmium with externalizing problems: 1.1 [-0.2, 2.4]).

Conclusion: Despite non-significant associations, both lead and cadmium exposure showed consistent inverse associations with cognitive abilities at 4 years, whereas associations with behavioral problems were less conclusive, especially for cadmium. Results on fluoride indicated association with externalizing problems, including ADHD, but prevalence of behavioral problems was low, increasing uncertainty.