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RESEARCH PRODUCT

Maternal Iodine Status During Pregnancy Is Not Consistently Associated with Attention-Deficit Hyperactivity Disorder or Autistic Traits in Children

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Background: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood. Objectives: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits. Methods: This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 μg/g-in all mother-child pairs, and in those with a urinary-iodine measurement at ≤18 weeks and ≤14 weeks of gestation-with the risk of ADHD or a high autistic-trait score (≥93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits. Results: UI/Creat <150 μg/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 μg/g in early pregnancy (i.e., ≤18 weeks or ≤14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status. Conclusions: There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits. Supported by the European Union's Horizon 2020 research and innovation program under grant agreement 634453 (to DL, MG, SCB, TIMK, MD, MPR, JS, RPP, and HT). The Generation R study is conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The Generation R Study is supported by the Erasmus Medical Center, Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organization for Scientific Research; and the Ministry of Health, Welfare and Sport. A grant from the Sophia Children's Hospital Research Funds supports the neurodevelopmental work on thyroid; RPP is supported by a ZonMw VIDI grant, project number 1717331. HT is supported by a ZonMw VICI grant with personal grant number 016.VICI.170.200. The INMA study was funded by UE grants FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1; Spain: Instituto de Salud Carlos III grants Red INMA G03/176; CB06/02/0041; FIS-FEDER PI041436, PI05/1079, PI06/0867, PI081151, PI09/00090, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, and MS13/00054; and Miguel Servet-FSE MS15/0025 and MSII16/0051; the Alicia Koplowitz Foundation 2017; Generalitat Valenciana: FISABIO grants UGP-15-230, UGP-15-244, and UGP-15-249; Generalitat de Catalunya-CIRIT grant 1999SGR 00241; Fundació La marató de TV3 grant 090430; Department of Health of the Basque Government grants 2005111093 and 2009111069; and Provincial Government of Gipuzkoa grants DFG06/004 and DFG08/001. The Avon Longitudinal Study of Parents and Children (ALSPAC) is supported by the UK Medical Research Council and Wellcome Trust grant 102215/2/13/2, and by the University of Bristol who provide core support for ALSPAC. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The existing iodine measurements in ALSPAC were funded from 1) the NUTRIMENTHE project, which received a research grant from the European Community's 7th Framework Programme (FP7/2008–2013) under grant agreement 212652; and 2) a Ph.D. studentship that was funded by Wassen International and the Waterloo Foundation (2009–2012).