Research in context
Evidence before this study
We searched PubMed for relevant English language studies using the terms “(neonatal thyroid stimulating hormone) and (cognitive development)” for articles published before December 2015. We also examined reference lists from suitable studies found. Two small retrospective cohort studies were found that examined neurodevelopmental outcomes for healthy infants with neonatal thyroid stimulating hormone (TSH) concentrations lower than the newborn screening cutoff used for diagnosis of congenital hypothyroidism. One study found, in a cohort of 178 boys, that a neonatal TSH concentration in the upper quartile was associated with poorer cognitive and memory scores at age 4 years, whereas another study did not find a significant association between elevated neonatal TSH concentrations and verbal scores at age 4 to 6 years, after adjustment for demographic and socioeconomic factors. Both studies had the limitation of low numbers of infants with neonatal TSH concentrations slightly lower than the newborn screening cutoffs.
Added value of this study
Our study is the largest population-based study examining infants with neonatal TSH concentrations lower than the newborn screening cutoff for congenital hypothyroidism, with more than 500 000 infants followed up to school-age. This comprehensive and systematic assessment allowed examination of the association between neonatal TSH concentrations and later developmental and educational outcomes. We have shown that infants with a neonatal TSH concentration lower than the newborn screening cutoff (20 mU/L in whole blood) but in the top quartile of the population have an increased likelihood of poor neurodevelopmental outcomes at school age.
Implications of all the available evidence
These results are relevant to international newborn screening programmes and provide much needed information about infants with a mild increase in TSH concentrations at screening. Further research is required into causation and to assess whether early assessment and treatment of these infants will improve long-term cognitive outcomes.