Julie Bang Hansen1, Niels Bilenberg2,3, Clara Amalie Gade Timmermann1, Richard Christian Jensen1, Hanne Frederiksen4,5, Anna-Maria Andersson4,5, Henriette Boye Kyhl6,7, Tina Kold Jensen8,9,10. 1. Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark. 2. Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. 3. Department of Child and Adolescent Psychiatry, Mental Health Services in the Region of Southern Denmark, Odense, Denmark. 4. Department of Growth and Reproduction, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 6. Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. 7. OPEN Patient data Explorative Network (OPEN), Odense, Denmark. 8. Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark. tkjensen@health.sdu.dk. 9. Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. tkjensen@health.sdu.dk. 10. OPEN Patient data Explorative Network (OPEN), Odense, Denmark. tkjensen@health.sdu.dk.
Abstract
BACKGROUND: Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive. OBJECTIVE: To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children. METHOD: In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score. RESULTS: BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03). CONCLUSION: Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.
BACKGROUND:Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive. OBJECTIVE: To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children. METHOD: In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score. RESULTS:BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03). CONCLUSION: Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.
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Authors: Courtney Scaramella; Joseph B Alzagatiti; Christopher Creighton; Samandeep Mankatala; Fernando Licea; Gabriel M Winter; Jasmine Emtage; Joseph R Wisnieski; Luis Salazar; Anjum Hussain; Faith M Lee; Asma Mammootty; Niyaza Mammootty; Andrew Aldujaili; Kristine A Runnberg; Daniela Hernandez; Trevor Zimmerman-Thompson; Rikhil Makwana; Julien Rouvere; Zahra Tahmasebi; Gohar Zavradyan; Christopher S Campbell; Meghna Komaranchath; Javier Carmona; Jennifer Trevitt; David Glanzman; Adam C Roberts Journal: eNeuro Date: 2022-05-17