The relation between neonatal thyroxine levels and neurodevelopmental outcome at age 5 and 9 years in a national cohort of very preterm and/or very low birth weight infants

Transient neonatal hypothyroxinemia is very common in preterm infants. The literature on the effect of this hypothyroxinemia is, however, controversial, and large or long-term follow-up studies are not available, In a nationwide prospective follow-up study on very preterm and (or) very low birth weight infants (n = 717), we studied the relationship between thyroxine levels in the Ist wk of life and neurodevelopmental outcome at 5 y of age and school performance at 9 y of age. Thyroxine concentrations from filter paper eluates were determined in 717 infants: 32% had levels of more than 3 SD below the mean (<60 nmol/L). The percentage of infants with such low levels increased with decreasing gestational age. At the age of 5 y, 96% of survivors (n = 640) were available for extensive neurodevelopmental examination: 85 (13.3%) had a disability and 92 (14.3%) a handicap. At the age of 9 y, 83% of survivors (n = 552) answered a questionnaire on school performance: 300 (54.3%) were in mainstream education in a grade appropriate for age, 151 (27%) were in mainstream education with grade retention, and 101 (18.3%) were in special education. Both neurologic dysfunction at age 5 y and school failure at age 9 y were significantly related to lower neonatal thyroxine levels even after adjustment for other perinatal factors (odds ratio, 1.3). Whether this relationship is causal should be investigated, If a causal relationship exists, substitution therapy may at least partially prevent neurologic dysfunction and learning disabilities, both common sequelae of very preterm birth.