title: Association between borderline neonatal thyroid-stimulating hormone concentrations and educational and developmental outcomes: a population-based record-linkage study.
abstract: Congenital hypothyroidism causes intellectual delay unless identified and effectively treated soon after birth. Newborn screening has almost eliminated intellectual disability associated with congenital hypothyroidism. However, clinical uncertainty remains about infants with thyroid-stimulating hormone (TSH) concentrations less than the newborn screening cutoffs. We assessed the association between neonatal TSH concentrations and educational and developmental outcomes.
  
  
  
  We did a population-based record-linkage study of all liveborn infants undergoing newborn screening from 1994 to 2008 in New South Wales, Australia, with assessments of childhood development or school performance. Very-low-birthweight babies (<1500 g) were excluded. Developmental and educational outcomes were obtained and these were linked to individual records by the New South Wales Centre for Health Record Linkage. The primary educational outcome was the proportion of students with National Assessment Program Literacy and Numeracy (NAPLAN) results lower than the national minimum standard in reading or numeracy measured at all ages, and the primary developmental outcome was the proportion of children who were classified as being developmentally high risk (vulnerable in two or more of the five developmental domains assessed by the Australian Early Development Census) at age 4-6 years. The proportions of infants with each outcome were calculated per percentile (0-100) of TSH concentration. Multivariable logistic regression was used to account for potential confounding by maternal and fetal variables known to affect neonatal TSH concentrations or neurodevelopmental outcomes.
  
  
  
  503 706 infants had a neonatal TSH result that linked to a developmental or educational outcome. 149 569 infants born between 2002 and 2008 were linked to an Australian Early Development Census developmental outcome and 354 137 were linked to a NAPLAN educational outcome. Median follow-up for educational outcome was 10 years (IQR 8-12) and for developmental outcome was 5 years (5-6). 5·5% (14 137 of 257 752) of infants scored less than the national minimum standard for numeracy in percentiles lower than the 75th percentile and this increased with each increase of percentile group to 11·3% (15 of 133) of infants with a TSH concentration between the 99·90th and 99·95th percentile. Infants with a neonatal TSH concentration in the 99·95th percentile or higher (above newborn screening cutoff) and likely to have diagnosed and treated congenital hypothyroidism had similar results to infants with a TSH concentration lower than the 75th percentile for both educational and developmental outcomes. Infants with a neonatal TSH concentration between the 99·5th and 99·9th percentile were more likely to have special needs (adjusted odds ratio [aOR] 1·68, 95% CI 1·23-2·30), poor numeracy performance (aOR 1·57, 1·29-1·90), and developmentally high risk (aOR 1·52, 1·20-1·93).
  
  
  
  We found an association between neonatal TSH concentrations lower than the present newborn screening thresholds and poor educational and developmental outcomes. This association needs further investigation to assess whether assessment and treatment of these infants might improve their long-term cognitive outcomes.
  
  
  
  Australian National Health and Medical Research.
authors.affiliation: Clinical and Population Perinatal Health Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia; Sydney Medical School Northern, University of Sydney, Sydney, NSW, Australia; Child Health Research, Menzies Centre for Health Policy, Sydney School of Public Health Sydney, NSW, Australia. Electronic address: samantha.lain@sydney.edu.au.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Lain
authors.affiliation: Clinical and Population Perinatal Health Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia; Child Health Research, Menzies Centre for Health Policy, Sydney School of Public Health Sydney, NSW, Australia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Bentley
authors.affiliation: Disciplines of Genetic Medicine and Paediatrics and Child Health, University of Sydney, Sydney, NSW, Australia; NSW Newborn Screening Programme, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Veronica
authors.initials: V
authors.lastname: Wiley
authors.affiliation: Clinical and Population Perinatal Health Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia; Sydney Medical School Northern, University of Sydney, Sydney, NSW, Australia.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Roberts
authors.affiliation: Sydney Medical School Northern, University of Sydney, Sydney, NSW, Australia; Department of Paediatric Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Jack
authors.affiliation: Disciplines of Genetic Medicine and Paediatrics and Child Health, University of Sydney, Sydney, NSW, Australia.
authors.forename: Bridget
authors.initials: B
authors.lastname: Wilcken
authors.affiliation: Clinical and Population Perinatal Health Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia; Sydney Medical School Northern, University of Sydney, Sydney, NSW, Australia; Child Health Research, Menzies Centre for Health Policy, Sydney School of Public Health Sydney, NSW, Australia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Nassar
mesh_terms: D002648:Child; D002657:Child Development; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000097:blood*; D004522:Educational Status; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D015997:Neonatal Screening; D012189:Retrospective Studies; D013972:Thyrotropin / Q000097:blood*
chemical_list: D013972:Thyrotropin