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

Background: Phthalates are endocrine disrupting chemicals used in everyday consumer products. Several epidemiological studies have examined the association between prenatal phthalate concentration and AttentionDeficit 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/11/2-5), 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 highmolecular-weight phthalates (MBzP, n-ary sumation DiNP and n-ary sumation 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-molecularweight phthalates were associated with non-significant increase in ADHD symptom score in boys.