Newborn Screening TSH Values Less Than 15 mIU/L Are Not Associated With Long-term Hypothyroidism or Cognitive Impairment

Abstract

Background It is unclear whether newborns with mild TSH elevation (mTSHe) are at risk of neurocognitive impairment. We assessed whether mTSHe at birth persists during childhood and compared neurocognitive functioning to siblings. Methods This study encompassed children born in the Auckland region with a newborn screen TSH level 8–14 mIU/L blood, aged 6.9–12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and FT4) and neurocognitive assessments were performed, including intelligent quotient (IQ) via Wechsler Intelligence Scale for Children IV. Results Ninety-six mTSHe subjects were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L (range 8–14 mIU/L, blood) and 2.4 mIU/L at assessment (range 0.8–7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r=0.25; p=0.040), they were not associated with the magnitude of the IQ difference within sibling pairs (p=0.56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; p=0.36), with a minor isolated difference in motor co-ordination scores. Conclusions Our data do not demonstrate long-term negative effects of neonatal mild TSH elevation. TSH elevation below screen threshold appears largely transient and mid-childhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels where the diagnosis may not offer long-term benefit for those detected.

Predictors of transient congenital primary hypothyroidism: data from the German registry for congenital hypothyroidism (AQUAPE “HypoDok”)

“…Lowering the threshold of TSH concentrations in the neonatal screening prompted an increase of positive CH results [15] and more cases with mild hypothyroidism and transient courses were detected [15,16]. The decrease of the TSH threshold in all likelihood increased the laboratory and economic burden of neonatal screening programs as well as the concern of affected families, but it is not clear whether these patients actually benefit from early detection and treatment [17][18][19]. A lower TSH threshold in the neonate screening in other countries outside of Germany (> 15 mU/L) could explain the higher percentage of TCH in other studies [19,20].…”

Clinical survey of current practice regarding treatment of children with borderline thyroid abnormalities

“…For case study 1 with mild TSH elevation (serum TSH of 8.7 mU/L), in the UK, no clinicians would have treated this infant, but three paediatric endocrinologists (7%) trained in Australia answered that they would treat this infant with thyroxine (Table 1). Our survey and the UK survey of clinicians were carried out over 12 years apart and there have been a number of studies examining cognitive outcomes of untreated children with mildly elevated NBS TSH levels (8–15 mU/LWB) in the interim, however, studies show conflicting results 4–7 …”

“…Our survey and the UK survey of clinicians were carried out over 12 years apart and there have been a number of studies examining cognitive outcomes of untreated children with mildly elevated NBS TSH levels (8-15 mU/LWB) in the interim, however, studies show conflicting results. [4][5][6][7] For children with thyroid abnormalities identified with a newborn TSH level above NBS cut-offs, prompt initiation of treatment that normalises thyroid levels has been shown to result in mostly normal neurocognitive outcomes. 12 The recently updated European guidelines recommend monitoring treatment according to age-specific TSH and fT4 reference intervals; however, if TSH is in age-specific interval then 'fT4 concentrations above the upper limit of the reference interval can be accepted'.…”

Predictors of Transient Congenital Primary Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (AQUAPE "HypoDok")

“…Lowering the threshold of TSH concentrations in the neonatal screening prompted an increase of positive CH results (15) and more cases with mild hypothyroidism and transient courses were detected (15,16). The decrease of the TSH threshold in all likelihood increased the laboratory and economic burden of neonatal screening programs as well as the concern of affected families, but it is not clear whether these patients actually benefit from early detection and treatment (17,18,19). A lower TSH threshold in the neonate screening in other countries outside of Germany (>15mU/l) could explain the higher percentage of TCH in other studies (19,20).…”