Treatments in Endocrinology

, Volume 5, Issue 6, pp 335–346

Neonatal Thyroxine Supplementation for Transient Hypothyroxinemia of Prematurity

Beneficial or Detrimental?
  • Edmund F. La Gamma
  • Aleid G. van Wassenaer
  • Sergio G. Golombek
  • Gabriella Morreale de Escobar
  • Joke H. Kok
  • Jose Quero
  • Susana Ares
  • Nigel Paneth
  • Delbert Fisher
Current Opinion


Extremely low birth-weight newborns (<1000g) experience low levels of thyroid hormone that vary inversely with the severity of neonatal illness and the extent of developmental immaturity with levels reaching a nadir at ≈7 days after birth; this phenomenon can persist for several weeks. In the absence of transplacental passage, 30–50% of these neonates cannot generate sufficient quantities of thyroid hormone to meet postnatal demands, placing them at an increased risk for developmental delay and cerebral palsy. Population surveys and interventional trials suggest that a therapeutic opening exists during a ‘window of opportunity’ corresponding to this period of diminished capacity. Variables to consider before intervention focus on the consideration that supplementation of both the substrate thyroxine and the active hormone triiodothyronine may be necessary in quantities that do not suppress thyroid-stimulating hormone release, yet overcome the persistence of increased conversion to 3,3′5′-triodo-L-thyronine, terminal deiodination, and activity of the sulfation inactivation pathways, as well as the diminished capacity of the newborn to accommodate postnatal physiologic changes. Single daily replacement doses may suppress levels of converting enzymes in the brain, suggesting that physiologic ‘mimicry’ provided by a constant infusion may be the preferred dosing option. Properly powered clinical trials targeting long-term developmental outcomes are needed to discern whether these interventions will do more than simply elevate blood levels of thyroid hormones to the target values of either the fetus or developing neonate. Identifying the appropriate indications for supplementation may alleviate individual pain and distress due to disability for several hundred extremely low birth-weight neonates each year in the US alone, and save society a pro-rated lifetime cost of nearly $US1 million per child.


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Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Edmund F. La Gamma
    • 1
  • Aleid G. van Wassenaer
    • 2
  • Sergio G. Golombek
    • 1
  • Gabriella Morreale de Escobar
    • 3
  • Joke H. Kok
    • 2
  • Jose Quero
    • 4
  • Susana Ares
    • 4
  • Nigel Paneth
    • 5
  • Delbert Fisher
    • 6
  1. 1.The Regional Neonatal Center, Maria Fareri Children’s Hospital at Westchester Medical CenterNew York Medical CollegeValhallaUSA
  2. 2.Academic Medical CenterEmma Children’s HospitalAmsterdamThe Netherlands
  3. 3.Instituto de Investigaciones Biomedicas ‘Alberto Sols’ — Laboratorio B-16-Arturo DuperierAutonomous University of MadridMadridSpain
  4. 4.Neonatology Unit, University Hospital La PazAutonomous University of MadridMadridSpain
  5. 5.Departments of Epidemiology and Pediatrics and Human DevelopmentMichigan State UniversityEast LansingUSA
  6. 6.Quest Diagnostics Nichols InstituteSan Juan CapistranoUSA

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