Cognitive Performance and Exposure to Organophosphate Flame Retardants in Children: Evidence from a Cross-Sectional Analysis of Two European Mother–Child Cohorts

Author:

Rosolen Valentina1ORCID,Giordani Elisa2ORCID,Mariuz Marika2,Parpinel Maria2ORCID,Mustieles Vicente345ORCID,Gilles Liese6ORCID,Govarts Eva6ORCID,Rodriguez Martin Laura6,Baken Kirsten7,Schoeters Greet8ORCID,Sepai Ovnair9,Sovcikova Eva10,Fabelova Lucia10ORCID,Kohoutek Jiři11,Jensen Tina Kold12,Covaci Adrian13ORCID,Roggeman Maarten13,Melymuk Lisa11ORCID,Klánová Jana11,Castano Argelia14ORCID,Esteban López Marta14ORCID,Barbone Fabio15

Affiliation:

1. Central Directorate for Health, Social Policies and Disability, Friuli Venezia Giulia Region, Via Cassa Di Risparmio 10, 34121 Trieste, Italy

2. Department of Medicine, University of Udine, Via Colugna 50, 33100 Udine, Italy

3. Center for Biomedical Research, University of Granada, 18012 Granada, Spain

4. Instituto de Investigación Biosanitaria de Granada, 18012 Granada, Spain

5. Consortium for Biomedical Research in Epidemiology and Public Health, 28029 Madrid, Spain

6. VITO Health, Flemish Institute for Technological Research (VITO), 2400 Mol, Belgium

7. BrabantAdvies, Brabantlaan 3, 5216 TV ‘s-Hertogenbosch, The Netherlands

8. Department of Biomedical Sciences & Toxicological Centre, University of Antwerp—Campus Drie Eiken, Universiteitsplein 1, Wilrijk, 2610 Antwerp, Belgium

9. Toxicology Department, Science Group, UK Health Security Agency, Harwell Science and Innovation Campus, Didcot OX11 0RQ, UK

10. Department of Environmental Medicine, Faculty of Public Health, Slovak Medical University, 83303 Bratislava, Slovakia

11. RECETOX, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic

12. Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, 5000 Odense, Denmark

13. Toxicological Centre, University of Antwerp, Wilrijk, 2610 Antwerp, Belgium

14. National Centre for Environmental Health, Instituto de Salud Carlos III, 28220 Majadahonda, Spain

15. Department of Medicine, Surgery and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149 Trieste, Italy

Abstract

The knowledge of the effects of organophosphate flame retardants on children’s neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children’s neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children’s urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = −1.30; 95%CI = −2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = −0.98; 95%CI = −2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = −1.42; 95% CI = −2.70; −0.06; p-value = 0.04) and no clear association with DPHP (β = −1.09; 95% CI = −2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was −0.49 (95%CI = −1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was −0.35 (95%CI = −1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.

Funder

European Union’s Horizon 2020 research and innovation program

Danish Research Council

Novo Nordisk Foundation, Denmark

Health Insurance Denmark

Slovak Research and Development Agency

Ministry of Health of the Slovak Republic

Publisher

MDPI AG

Subject

Chemical Health and Safety,Health, Toxicology and Mutagenesis,Toxicology

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