Thea S Skogheim1, Gro D Villanger2, Kjell Vegard F Weyde2, Stephanie M Engel3, Pål Surén2, Merete G Øie4, Annette H Skogan5, Guido Biele2, Pål Zeiner6, Kristin R Øvergaard7, Line S Haug2, Azemira Sabaredzovic2, Heidi Aase2. 1. Norwegian Institute of Public Health, PO Box 222, Skøyen, N-0213, Oslo, Norway. Electronic address: thea.skogheim@fhi.no. 2. Norwegian Institute of Public Health, PO Box 222, Skøyen, N-0213, Oslo, Norway. 3. Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 2104C McGavran-Greenberg Hall CB 7435, Chapel Hill, NC, 27599, USA. 4. Department of Psychology, University of Oslo, PO Box 1094, Blindern, N-0317, Oslo, Norway; Research Department, Innlandet Hospital Trust, PO Box 104, N-2381, Brumunddal, Norway. 5. The National Centre for Epilepsy, PO Box 4956, Nydalen, N-0424, Oslo, Norway. 6. Division of Mental Health and Addiction, Oslo University Hospital, PO Box 4956, Nydalen, N-0424, Oslo, Norway; Department of Clinical Medicine, University of Oslo, PO Box 1171, N-0318, Oslo, Norway. 7. Division of Mental Health and Addiction, Oslo University Hospital, PO Box 4956, Nydalen, N-0424, Oslo, Norway.
Abstract
BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent organic pollutants that are suspected to be neurodevelopmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We investigated the associations between prenatal exposure to PFASs and symptoms of attention-deficit/hyperactivity disorder (ADHD) and cognitive functioning (language skills, estimated IQ and working memory) in preschool children, as well as effect modification by child sex. MATERIAL AND METHODS: This study included 944 mother-child pairs enrolled in a longitudinal prospective study of ADHD symptoms (the ADHD Study), with participants recruited from The Norwegian Mother, Father and Child Cohort Study (MoBa). Boys and girls aged three and a half years, participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview, Child Development Inventory and Stanford-Binet (5th revision). Prenatal levels of 19 PFASs were measured in maternal blood at week 17 of gestation. Multivariable adjusted regression models were used to examine exposure-outcome associations with two principal components extracted from the seven detected PFASs. Based on these results, we performed regression analyses of individual PFASs categorized into quintiles. RESULTS: PFAS component 1 was mainly explained by perfluoroheptane sulfonate (PFHpS), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorooctanoic acid (PFOA). PFAS component 2 was mainly explained by perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and perfluorononanoic acid (PFNA). Regression models showed a negative association between PFAS component 1 and nonverbal working memory [β = -0.08 (CI: -0.12, -0.03)] and a positive association between PFAS component 2 and verbal working memory [β = 0.07 (CI: 0.01, 0.12)]. There were no associations with ADHD symptoms, language skills or IQ. For verbal working memory and PFAS component 2, we found evidence for effect modification by child sex, with associations only for boys. The results of quintile models with individual PFASs, showed the same pattern for working memory as the results in the component regression analyses. There were negative associations between nonverbal working memory and quintiles of PFOA, PFNA, PFHxS, PFHpS and PFOS and positive associations between verbal working memory and quintiles of PFOA, PFNA, PFDA and PFUnDA, with significant relationships mainly in the highest concentration groups. CONCLUSIONS: Based on our results, we did not find consistent evidence to conclude that prenatal exposure to PFASs are associated with ADHD symptoms or cognitive dysfunctions in preschool children aged three and a half years, which is in line with the majority of studies in this area. Our results showed some associations between PFASs and working memory, particularly negative relationships with nonverbal working memory, but also positive relationships with verbal working memory. The relationships were weak, as well as both positive and negative, which suggest no clear association - and need for replication.
BACKGROUND:Perfluoroalkyl substances (PFASs) are persistent organic pollutants that are suspected to be neurodevelopmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We investigated the associations between prenatal exposure to PFASs and symptoms of attention-deficit/hyperactivity disorder (ADHD) and cognitive functioning (language skills, estimated IQ and working memory) in preschool children, as well as effect modification by child sex. MATERIAL AND METHODS: This study included 944 mother-child pairs enrolled in a longitudinal prospective study of ADHD symptoms (the ADHD Study), with participants recruited from The Norwegian Mother, Father and Child Cohort Study (MoBa). Boys and girls aged three and a half years, participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview, Child Development Inventory and Stanford-Binet (5th revision). Prenatal levels of 19 PFASs were measured in maternal blood at week 17 of gestation. Multivariable adjusted regression models were used to examine exposure-outcome associations with two principal components extracted from the seven detected PFASs. Based on these results, we performed regression analyses of individual PFASs categorized into quintiles. RESULTS:PFAS component 1 was mainly explained by perfluoroheptane sulfonate (PFHpS), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorooctanoic acid (PFOA). PFAS component 2 was mainly explained by perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and perfluorononanoic acid (PFNA). Regression models showed a negative association between PFAS component 1 and nonverbal working memory [β = -0.08 (CI: -0.12, -0.03)] and a positive association between PFAS component 2 and verbal working memory [β = 0.07 (CI: 0.01, 0.12)]. There were no associations with ADHD symptoms, language skills or IQ. For verbal working memory and PFAS component 2, we found evidence for effect modification by child sex, with associations only for boys. The results of quintile models with individual PFASs, showed the same pattern for working memory as the results in the component regression analyses. There were negative associations between nonverbal working memory and quintiles of PFOA, PFNA, PFHxS, PFHpS and PFOS and positive associations between verbal working memory and quintiles of PFOA, PFNA, PFDA and PFUnDA, with significant relationships mainly in the highest concentration groups. CONCLUSIONS: Based on our results, we did not find consistent evidence to conclude that prenatal exposure to PFASs are associated with ADHD symptoms or cognitive dysfunctions in preschool children aged three and a half years, which is in line with the majority of studies in this area. Our results showed some associations between PFASs and working memory, particularly negative relationships with nonverbal working memory, but also positive relationships with verbal working memory. The relationships were weak, as well as both positive and negative, which suggest no clear association - and need for replication.
Keywords:
Attention-deficit/hyperactivity disorder (ADHD); Cognitive functions; Father and Child Cohort Study (MoBa); Perfluoroalkyl substances (PFASs); Prenatal; The Norwegian Mother
Authors: Kristine Bjerve Gützkow; Line Småstuen Haug; Cathrine Thomsen; Azemira Sabaredzovic; Georg Becher; Gunnar Brunborg Journal: Int J Hyg Environ Health Date: 2011-09-19 Impact factor: 5.840
Authors: Stephen V Faraone; Roy H Perlis; Alysa E Doyle; Jordan W Smoller; Jennifer J Goralnick; Meredith A Holmgren; Pamela Sklar Journal: Biol Psychiatry Date: 2005-01-21 Impact factor: 13.382
Authors: Joanna Martin; Mark J Taylor; Mina Rydell; Lucy Riglin; Olga Eyre; Yi Lu; Sebastian Lundström; Henrik Larsson; Anita Thapar; Paul Lichtenstein Journal: J Child Psychol Psychiatry Date: 2018-02-16 Impact factor: 8.982
Authors: Manhai Long; Mandana Ghisari; Lisbeth Kjeldsen; Maria Wielsøe; Bent Nørgaard-Pedersen; Erik Lykke Mortensen; Morsi W Abdallah; Eva C Bonefeld-Jørgensen Journal: Mol Autism Date: 2019-01-09 Impact factor: 7.509
Authors: Ann M Vuong; Glenys M Webster; Kimberly Yolton; Antonia M Calafat; Gina Muckle; Bruce P Lanphear; Aimin Chen Journal: Environ Res Date: 2021-02-02 Impact factor: 6.498