Gro D Villanger1, Eivind Ystrom1,2,3, Stephanie M Engel4, Matthew P Longnecker5, Rolf Pettersen6, Alexander D Rowe6, Ted Reichborn-Kjennerud1,7, Heidi Aase1. 1. Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway. 2. Department of Psychology, University of Oslo, Oslo, Norway. 3. PharmacoEpidemiology and Drug Safety Research Group, School of Pharmacy & PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway. 4. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. 5. Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Ramboll, Research Triangle Park, NC, USA. 6. Department of Newborn Screening, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 7. Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Abstract
BACKGROUND: Normal brain development is dependent on maternal, fetal and neonatal thyroid function. Measuring neonatal thyroid-stimulating hormone (TSH) 48-72 hours after birth screens for congenital hypothyroidism, allowing early treatment to avoid serious impairment. However, even within sub-clinical ranges, disrupted thyroid homeostasis during brain development has been linked to adverse neurodevelopmental outcomes, including attention-deficit/hyperactivity disorder (ADHD). OBJECTIVES: To estimate the association between neonatal TSH below threshold for potential congenital hypothyroidism and subsequent ADHD diagnosis using a population-based birth cohort. METHODS: Children with a diagnosis of ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa) were identified through linkage with the Norwegian Patient Registry using ICD-10 codes for hyperkinetic disorders. The study included 405 ADHD cases and 1,092 controls (born 2003-2008) with available neonatal TSH concentrations below 10 mU/L (cut-off for potential congenital hypothyroidism) measured in dried blood spots sampled 48-72 hours after birth. RESULTS: In multivariable, quintile models the relationship appeared to follow a U-shaped pattern with elevated odds ratios (ORs) at lower and higher TSH levels. Among children with TSH in the lowest quintile, odds of ADHD was approximately 1.5-fold higher than children in the middle quintile (OR = 1.60, 95% CI 1.09, 2.34), which was driven by substantially elevated risk among girls, with no association among boys (Pinteraction = 0.02; girls OR = 3.10, 95% CI 1.53, 6.30; boys OR = 1.16, 95% CI 0.73, 1.84). CONCLUSIONS: ADHD risk appeared to be elevated among newborns with low TSH levels (i.e. with hyperthyroid status), and this association was mainly found among girls. Because our findings are suggestive of increased risk at very low TSH concentrations, where analytical accuracy is low, future studies should employ highly sensitive assays capable of accurate quantitation at very low concentrations. Also, larger studies are needed to investigate these associations at higher neonatal TSH concentrations where data are more widely distributed.
BACKGROUND: Normal brain development is dependent on maternal, fetal and neonatal thyroid function. Measuring neonatal thyroid-stimulating hormone (TSH) 48-72 hours after birth screens for congenital hypothyroidism, allowing early treatment to avoid serious impairment. However, even within sub-clinical ranges, disrupted thyroid homeostasis during brain development has been linked to adverse neurodevelopmental outcomes, including attention-deficit/hyperactivity disorder (ADHD). OBJECTIVES: To estimate the association between neonatal TSH below threshold for potential congenital hypothyroidism and subsequent ADHD diagnosis using a population-based birth cohort. METHODS:Children with a diagnosis of ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa) were identified through linkage with the Norwegian Patient Registry using ICD-10 codes for hyperkinetic disorders. The study included 405 ADHD cases and 1,092 controls (born 2003-2008) with available neonatal TSH concentrations below 10 mU/L (cut-off for potential congenital hypothyroidism) measured in dried blood spots sampled 48-72 hours after birth. RESULTS: In multivariable, quintile models the relationship appeared to follow a U-shaped pattern with elevated odds ratios (ORs) at lower and higher TSH levels. Among children with TSH in the lowest quintile, odds of ADHD was approximately 1.5-fold higher than children in the middle quintile (OR = 1.60, 95% CI 1.09, 2.34), which was driven by substantially elevated risk among girls, with no association among boys (Pinteraction = 0.02; girls OR = 3.10, 95% CI 1.53, 6.30; boys OR = 1.16, 95% CI 0.73, 1.84). CONCLUSIONS:ADHD risk appeared to be elevated among newborns with low TSH levels (i.e. with hyperthyroid status), and this association was mainly found among girls. Because our findings are suggestive of increased risk at very low TSH concentrations, where analytical accuracy is low, future studies should employ highly sensitive assays capable of accurate quantitation at very low concentrations. Also, larger studies are needed to investigate these associations at higher neonatal TSH concentrations where data are more widely distributed.
Authors: Helle Margrete Meltzer; Tina Kold Jensen; Ondřej Májek; Hanns Moshammer; Maria Wennberg; Agneta Åkesson; Hanna Tolonen Journal: Int J Environ Res Public Health Date: 2022-05-06 Impact factor: 3.390