Evolution of circulating thyroid hormone levels in preterm infants during the first week of life: perinatal influences and impact on neurodevelopment

J Pediatr Endocrinol Metab. 2019 Jun 26;32(6):597-606. doi: 10.1515/jpem-2018-0537.


Background For several decades, transient hypothyroxinemia of prematurity (THOP) has been a topic of debate. The pathophysiology is incompletely understood and consensus on the therapeutic approach is lacking. This study aimed at gaining a better insight into the pathogenesis by studying the trends in thyroid hormone (TH) levels during the first week of life. Methods This single-center prospective observational study analyzed the plasma levels of total thyroxine (T4) and free thyroxine (fT4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH) and T4-binding globulin (TBG) in cord blood and at the end of the first week of life in 120 preterm infants (gestational age [GA] <37 weeks). The change over time was calculated (delta, ∆). The impact of perinatal and subsequently postnatal variables on ∆ was studied by hierarchical multiple regression. The impact of ∆ on the neurodevelopmental outcome at the corrected ages of 9 and 24 months, measured by the Bayley Scales of Infant Development (BSID)-II, was assessed by logistic regression. Results ∆fT4 levels were negatively affected by GA and use of dopamine, whereas only GA was associated with low ∆T3 levels. Negative ∆fT4 levels were present in 75% of the extremely low-for-gestational-age infants, whereas 23.5% had a negative ∆T3 level. There was an increased risk for an abnormal mental developmental score (<85) with decreasing ∆T3 at 9 months, corrected age, but not at 24 months. Conclusions A negative evolution in circulating TH levels is principally an immaturity phenomenon, whereas dopamine can further suppress the hypothalamic-pituitary-thyroid axis. There is at least a temporary negative effect of this evolution on the infants' neurodevelopment.

Keywords: neurodevelopment; preterm birth; thyroid hormones; transient hypothyroxinemia of prematurity.

Publication types

  • Clinical Trial
  • Observational Study

MeSH terms

  • Belgium / epidemiology
  • Biomarkers / blood*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Infant
  • Infant, Premature / blood
  • Infant, Premature / growth & development*
  • Infant, Premature, Diseases / physiopathology*
  • Male
  • Neurodevelopmental Disorders / blood
  • Neurodevelopmental Disorders / diagnosis
  • Neurodevelopmental Disorders / epidemiology*
  • Prognosis
  • Prospective Studies
  • Thyroid Diseases / blood
  • Thyroid Diseases / diagnosis
  • Thyroid Diseases / epidemiology*
  • Thyroid Function Tests
  • Thyroid Hormones / blood*


  • Biomarkers
  • Thyroid Hormones