Abstract

Highlights

  • Early-life low-level cadmium exposure appeared associated with decreased cognitive abilities.
  • More expected, low-level prenatal lead exposure was linked to reduced cognitive development.
  • Fluoride exposure was not associated with child full-scale or verbal cognition.
  • Cadmium associations with behavioral and social communication problems were inconclusive.
  • Fluoride and lead were not associated with social communication but were indicative of behavioral problems.

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 log2-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.

EXCERPTS:

… In Sweden, fluoride is not added to drinking water, but concentrations have been shown to vary naturally (Aggeborn and Öhman, 2021; Aneblom et al., 2005).

… NICE (Nutritional Impact on the Immunological Maturation during Childhood in relation to the Environment) is a prospective birth-cohort in the Norrbotten county, northern Sweden, established by recruitment of pregnant women between 2015 and 2018 (NCT05809479) (Barman et al., 2018). The main objectives are to assess the impact of early-life environment on immune maturation, allergy development, growth, cognitive and behavioral development, and oral health. During the first visit to the local maternity units, expecting parents were given information about the NICE study.

… The distribution characteristics of maternal and child lead, cadmium, and fluoride concentrations, as well as of the lead and cadmium cord blood concentrations for all children are presented in Table 2. All cord blood and child concentrations are also

presented for boys and girls separately (Table 2). There were no differences in child metal and fluoride concentrations by child sex.

…Urinary fluoride concentrations were slightly higher in women with a university degree compared to those who had not completed university (median: 0.74 mg/L vs 0.68 mg/L, P=0.003).

Table 2. Lead, cadmium, and fluoride concentrations in mothers during pregnancy (=gestational week 29) and children at 4 years of age; for all children, and for girls and boys separately.

Empty Cell All participants 5th-95th perc. Range Girls Boys P-value a
N Median N Median N Median
Gestational erythrocyte lead (ug/kg) 456 11.2 5.9–25.3 3.8–147.8
Cord blood erythrocyte lead (ug/kg) 314 7.8 4.0–18.8 2.5–37.0 172 7.8 142 8.0 0.653
Child erythrocyte lead (ug/kg) 250 16.0 7.8–41.4 5.4–85.7 139 15.6 111 16.4 0.882
Gestational urinary cadmium (ug/L)b 454 0.10 0.04–0.27 0.02–0.97
Gestational erythrocyte cadmium (ug/kg) 456 0.29 0.14–0.68 0.05–5.69
Cord blood erythrocyte cadmium (ug/kg) 314 0.04 0.002–0.131 0.002–1.094 172 0.04 142 0.04 0.636
Child urinary cadmium (ug/L)b 398 0.04 0.02–0.10 0.003–0.36 203 0.04 195 0.04 0.128
Child erythrocyte cadmium (ug/kg) 250 0.15 0.06–0.26 0.01–0.34 139 0.15 111 0.16 0.509
Gestational urinary fluoride (mg/L)b 441 0.72 0.3–1.88 0.07–6.4
Child urinary fluoride (mg/L)b 397 0.86 0.31–2.26 0.04–5.7 203 0.81 194 0.90 0.525
Abbreviations: IQR: interquartile range; perc: percentile.
P-values for differences between girls and boys were obtained using the Mann-Whitney test.
b  Urinary cadmium and fluoride concentrations are adjusted to the median specific gravity (1.017 for the mothers and 1.016 for the children).

… Gestational and child urinary fluoride concentrations were not associated with cognitive outcomes (Table 3, Supplemental Table 6).

… Urinary fluoride concentrations were not associated with CBCL scores (Table 4 & Supplemental Table 10), except for a potential association of gestational urinary fluoride concentrations with increasing externalizing problems B [CI 95% CI]: 0.9 [-0.3, 2.0]), per doubling (Table 4). Additional analyses using the ADHD scale of the CBCL showed an association of gestational urinary fluoride concentrations with slightly higher ADHD raw scores (B [CI 95% CI]: 0.3 [0.0, 0.6], per doubling, Table 5; B [CI 95% CI]: 0.1 [-0.0, 0.3], per 0.5 mg/L increase, Supplemental Table 11). The SRS-2 total score appeared unrelated to cadmium, lead, and fluoride exposure (Table 6 & Supplemental Table 12). Child sex did not modify the association between lead, cadmium, and fluoride and SRS-2 outcomes in any meaningful or consistent way (Table 6).

Appendix A. Supplementary data

The following is the Supplementary data to this article:

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