Copper and zinc status in cord blood and breast milk and child's neurodevelopment at 18 months: Results of the Italian PHIME cohort

Background: Trace elements, including zinc (Zn) and copper (Cu), although toxic at higher concentrations are known to play important roles in the maintenance of human health and neurodevelopment. Few epidemiological studies have investigated the association between prenatal or early postnatal Cu and Zn levels and child neurodevelopment. The aim of this research is to assess the association between child neurodevelopment at 18 months of age and cord blood and breast milk concentrations of Cu and Zn in Italian mother-child pairs enrolled in the Italian Northern Adriatic Cohort II (NAC-II), a part of the “Public health impact of long-term, low-level, mixed element exposure in susceptible population strata” project PHIME. Methods: The study population consisted of 632 children, and their mothers, born within the NAC-II, who were tested with the Bayley Scales of Infant and Toddler Development third edition (BSID-III) at age 18 months. Cu and Zn concentrations were measured in cord blood and breast milk samples. Only children born at term (≥37 gestational week), who completed the BSID-III test and had at least 1 measure of Cu and Zn concentrations were included in the analysis. Information about socio-demographics and lifestyles were collected through questionnaires at different phases of follow-up. Cu and Zn concentrations were log2 transformed because of their skewed distribution. Multiple linear regression models were performed to study the association between each BSID-III composite score (cognitive, motor and language) and each metal concentration. Separate models were applied for each biological sample. The β coefficient (β) and its 95% confidence interval (95% CI) were estimated. Stratified analyses by child's sex were also conducted. Results: The mean ± standard deviation (SD) of cognitive, motor and language composite scores were respectively: 106 ± 8, 101 ± 5 and 97 ± 8. The mean ± SD of Cu and Zn concentrations (ng/g) were respectively 699.2 ± 129.0 and 2538 ± 589 in cord blood and 607 ± 498 and 3226 ± 1428 in breast milk. No association between metal concentration and cognitive composite score was found. A higher motor composite score was associated with higher Cu concentrations in cord blood (β = 4.31 95% CI 2.03; 6.59). No associations were found between language composite score and metal concentrations. The effect of Cu cord blood concentration on motor composite score was confirmed when stratified by sex: males (β = 5.49 95% CI 2.15; 8.36) and females (β = 3.11; 95% CI 0.00; 6.22). A direct association, in females only, was found between language composite score and Cu concentration in cord blood (β = 5.60 95% CI 0.63; 10.57) and in breast milk (β = 3.04 95% CI 1.06; 5.03), respectively. Conclusion: The results from this cohort study showed a strong direct association between prenatal Cu levels and child motor neurodevelopment at 18 months. However, for generalizability, future research on the effects of Zn and Cu on neurodevelopment should include a larger range of early-life concentration of trace elements.