HYPOTHYROXINEMIA OF PREMATURITY AND NEURODEVELOPMENT

In this historical cohort study, neurologic disorder and development at age 2 years will be related to quantitative thyroxine levels obtained at newborn screening. The 760 subjects are the survivors of a representative population of 1105 infants less than or equal to 2000 grams at birth born in Central New Jersey (1984-1987). These subjects of an NIH-funded study of newborn brain hemorrhage (NBH) were intensively studied; in the newborn period by ultrasonographic brain scanning at specified intervals (4 hours, 24 hours, and 7 days) and using continuously recorded clinical data; at a 2 year follow up by systematic motor, sensory, cognitive, behavioral examination and history. Hypothyroxinemia, associated with normal or low thyrotropin levels, occurs in 15-80% of premature infants, depending on the gestational age(1-8). Quantitative and normalized levels of thyroxine and thyrotropin obtained at the time of newborn screening (initial and all repeat tests) will be obtained with the cooperation of the New Jersey State Department of Health. Repeat specimens were routinely requested when the initial thyroxine levels were low. In our preliminary analyses, low thyroxine levels at birth are significantly associated with subsequent cerebral palsy and with delay in cognitive development at age 2. The association with cerebral palsy has not previously been reported nor adequately tested. The sample size, the duration of follow up, and the wealth of information create a unique opportunity to investigate the antecedents and potential sequelae of hypothyroxinemia in prematures. The study will have extensive information about the perinatal course of low birth weight infants; it will be able to control for potential confounders and to examine interrelationships to other determinants of development and developmental disorders such as intraventricular hemorrhage and parenchymal brain lesions. Since thyroid hormone is important to pulmonary and gut maturation and to the control of thymulin, other outcomes such as bronchopulmonary dysplasia, necrotizing enterocolitis, and sepsis will be investigated. Testing newborns for total serum thyroxine levels is in general use in the United States. However, there is debate about whether thyrotropin should replace thyroxine as the initial screen for congenital hypothyroidism. If hypothyroxinemia of prematurity has other implications for health and well being, separate from the detection of congenital hypothyroidism, the results of this study would also contribute to the debate about how best to achieve mass screening.