Hypothyroxinemia of prematurity and the risk of cerebral white matter damage

J Pediatr. 1999 Jun;134(6):706-11. doi: 10.1016/s0022-3476(99)70285-4.


Objective: Infants with hypothyroxinemia of prematurity (HOP) are at increased risk for neurodevelopmental dysfunction. Infants born near the end of the middle trimester are also at increased risk for an echolucency (EL) in the cerebral white matter, which reflects white matter damage and is the cranial ultrasound abnormality that best predicts neurodevelopmental dysfunction. We postulated that some of the increased risk of neurodevelopmental problems associated with HOP reflects an increased risk of EL.

Study design: We studied 1414 infants weighing 500 to 1500 g who were born at 4 medical centers between 1991 and 1993. The infants had thyroxine blood levels measured during the first weeks of life, at least 1 of 3 cranial ultrasound scans performed at specified postnatal intervals, and their own and their mother's hospital charts reviewed. Infants were classified by whether or not their first thyroxine level placed them in the lowest quartile among all infants in this sample (ie, <67.8 nmol/L, our definition of HOP, equivalent to <5.3 micrograms/dL).

Results: After adjusting for such potential confounders as low gestational age and measures of illness severity, infants with HOP had twice the risk of EL as their peers with higher thyroxine levels.

Conclusion: Our findings are consistent with the hypothesis that a "normal" blood thyroxine level protects infants born near the end of the middle trimester against the risk of cerebral white matter damage.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain / embryology
  • Brain / growth & development
  • Brain / pathology*
  • Echoencephalography*
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature / blood*
  • Infant, Very Low Birth Weight
  • Odds Ratio
  • Placenta / pathology
  • Risk Factors
  • Severity of Illness Index
  • Thyroxine / blood*
  • Ultrasonography, Prenatal


  • Thyroxine