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N Engl J Med. 1996 Mar 28;334(13):821-7.

The relation of transient hypothyroxinemia in preterm infants to neurologic development at two years of age.

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Sergievsky Center, Columbia University, New York, USA.



Transient hypothyroxinemia, a common finding in premature infants, is not thought to have long-term sequelae or to require treatment. We investigated whether hypothyroxinemia in premature infants is a cause of subsequent motor and cognitive abnormalities.


In this historical cohort study, we retrieved blood thyroxine values, obtained on routine screening in the first week of life, from state screening records on children who weighted 2000 g or less at birth, who were born at 33 weeks' gestation or earlier, and who were enrolled in a population-based study of the late sequelae of neonatal brain hemorrhage. We investigated the relation of these values to the odds for disabling cerebral palsy among 463 subjects for whom data were available and to the mental-development score on the Bayley Scales of Infant Development or the Stanford-Binet Intelligence Scales for Children at the age of two years in 400 subjects. The effects of severe hypothyroxinemia, defined as a blood thyroxine value more than 2.6 SD below the mean for New Jersey newborns, were assessed before and after adjustment for gestational age and potentially confounding variables.


In analyses adjusted for gestational age, infants with severe hypothyroxinemia had a risk of disabling cerebral palsy that was nearly 11 times that of infants without hypothyroxinemia (odds ratio, 10.8; 95 percent confidence interval, 3.0 to 39.3) and a mean mental-development score at the age of two that was 15.4 points lower (95 percent confidence interval, 8.1 to 22.6 points) than the mean score of children with normal neonatal blood thyroxine concentrations. After adjustment for gestational age and multiple prenatal, perinatal, and early and last neonatal variables, severe hypothyroxinemia was still associated with an increased risk of disabling cerebral palsy (odds ratio, 4.4; 95 percent confidence interval, 1.0 to 18.6) and a reduction of nearly 7 points (95 percent confidence interval, 0.3 to 13.2 points) in the mental-development score.


Severe hypothyroxinemia in preterm infants may be an important cause of problems in neurologic and mental development detected at the age of two years.

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