Maternal concentrations of phthalates and Attention-Deficit Hyperactivity Disorder (ADHD-) related symptoms in children aged 2 to 4 years from Odense child cohort

Sarah Munk Andreasen; Hanne Frederiksen; Niels Bilenberg; Anna-Maria Andersson; Anders Juul; Henriette Boye Kyhl; Tina Kold Jensen

doi:10.1016/j.envint.2023.108244

Maternal concentrations of phthalates and Attention-Deficit Hyperactivity Disorder (ADHD-) related symptoms in children aged 2 to 4 years from Odense child cohort

Environ Int. 2023 Oct:180:108244. doi: 10.1016/j.envint.2023.108244. Epub 2023 Sep 29.

Authors

Sarah Munk Andreasen¹, Hanne Frederiksen², Niels Bilenberg³, Anna-Maria Andersson², Anders Juul⁴, Henriette Boye Kyhl⁵, Tina Kold Jensen⁶

Affiliations

¹ Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
² Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark.
³ Department of Child and Adolescent Psychiatry, Odense, Mental Health Services in Region of Southern Denmark, University of Southern Denmark, Odense, Denmark.
⁴ Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁵ Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; OPEN Patient data Explorative Network, Odense, Denmark.
⁶ Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark; Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; OPEN Patient data Explorative Network, Odense, Denmark. Electronic address: tkjensen@health.sdu.dk.

PMID: 37797478
DOI: 10.1016/j.envint.2023.108244

Abstract

Background: Phthalates are endocrine disrupting chemicals used in everyday consumer products. Several epidemiological studies have examined the association between prenatal phthalate concentration and Attention-Deficit Hyperactivity Disorder (ADHD) in offspring, but the findings have been inconclusive.

Objectives: To investigate the association between maternal urinary concentrations of phthalate metabolites during pregnancy and ADHD related symptoms in children at 2 to 4 years in a large prospective cohort.

Methods: In the Odense Child Cohort from Denmark were women recruited in early pregnancy from 2010 to 2012. Phthalate concentrations were measured in urine samples collected in 3rd trimester and separated into low and high weight phthalates. Parents filled in the Child Behavior Checklist for ages 1.5 to 5 years (CBCL/1½-5), including a 6-item ADHD symptom scale at children aged 2 to 4 years. Data were analysed by use of adjusted negative binomial regression.

Results: A total of 658 mother-child pairs were included. Urinary phthalate metabolite concentrations were generally low compared to previous cohorts. A doubling in maternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with lower ADHD symptoms score in children (IRR: 0.95 (95 % CI 0.91-0.98)), strongest in girls (IRR: 0.92 (0.87-0.98)). Sex differences were observed. High maternal phthalate metabolite concentrations were associated with lower ADHD symptom score in girls, significant trends across tertile of MCPP and MnBP (p = 0.018, p = 0.038, respectively). In boys, maternal concentrations of high-molecular-weight phthalates (MBzP, ∑DiNP and ∑DEHP) were associated with an almost significantly higher ADHD symptom score (IRR for a doubling in concentration: 1.04 (95 % CI: 0.99-1.10), IRR: 1.05 (95 % CI: 0.97-1.13), IRR: 1.04 (95 % CI: 0.99-1.10), respectively).

Conclusion: Maternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with a lower ADHD symptom score in children, strongest in girls. Maternal concentrations of high-molecular-weight phthalates were associated with non-significant increase in ADHD symptom score in boys.

Keywords: ADHD; Cohort study; Endocrine disrupting chemicals; Neurodevelopment; Neurotoxicology; Phthalates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / diagnosis
Attention Deficit Disorder with Hyperactivity* / epidemiology
Environmental Pollutants* / adverse effects
Environmental Pollutants* / urine
Female
Humans
Male
Overweight
Phthalic Acids* / adverse effects
Phthalic Acids* / urine
Pregnancy
Pregnancy Trimester, Third
Prenatal Exposure Delayed Effects*
Prospective Studies

Substances

phthalic acid
Phthalic Acids
Environmental Pollutants