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

Abstract

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 1st 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.

Gestational thyroid function abnormalities in conditions of mild iodine deficiency: early screening versus continuous monitoring of maternal thyroid status

“…Conversely, present clinical and experimental evidence seems to suggest that early and prolonged (until week 24) maternal hypothyroxinemia is a risk factor for impaired foetal brain development (3,22,(24)(25)(26). Moreover, other reports of poor developmental outcome in preterm babies indicate that a normal supply of maternal T 4 continues to have an important protective role after midgestation (27,28). Because of the potential irreversibility of foetal brain damage, we decided arbitrarily to give substitutive L-T 4 treatment to women experiencing IH, in order to ensure FT 4 levels similar to those observed in adequately iodine supplemented women at the same stage of pregnancy.…”

Neonatal Hypothyroxinemia: Effects of Iodine Intake and Premature Birth

“…For years their alterations in circulating parameters of thyroid function have been considered an expression of their physiological hypophyseal-pituitarythyroid immaturity or a manifestation of nonthyroidal illness, but 2 recent follow-up studies of 640 PT children up to 5 and 9 yr of age (10) and of 400 premature infants up to 2 yr of age (11) have confirmed that severe hypothyroxinemia plays an important causative role in their frequently impaired mental development and disabling cerebral palsy.…”

Free Thyroxine Levels After Very Preterm Birth and Neurodevelopmental Outcomes at Age 7 Years

“…19 Consistent with this literature, the low levels of T 4 associated with THOP have been found to be related to neurodevelopmental deficits in children born preterm, such as delayed development of motor, cognitive, language, and educational skills. [20][21][22][23][24] Research to date has predominantly focused on TH levels in the first 2 weeks of life, and in most studies outcome assessments have been limited to infancy and the preschool period. The current study aimed to examine the relationship between fT 4 over the first 6 weeks after VPT birth and cognitive functioning and brain development at age 7 years.…”