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

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Preterm infants have transiently lowered thyroid hormone levels during the early postnatal period. Past research suggests that low thyroid hormone levels are related to cognitive and developmental deficits in children born preterm. WHAT THIS STUDY ADDS:Contrary to expectations, in this study of children born ,30 weeks' gestation, higher concentrations of free thyroxine over the first 6 weeks of life were associated with poorer cognitive function at 7 years of age. abstract BACKGROUND AND OBJECTIVES: Preterm infants commonly have transient hypothyroxinemia of prematurity after birth, which has been associated with deficits in general intellectual functioning, memory, attention, and academic achievement. However, research has predominantly focused on thyroxine levels in the first 2 weeks of life and outcomes are limited to the preschool period. Our objective was to evaluate the relationships between free thyroxine (fT 4 ) levels over the first 6 weeks after very preterm (VPT) birth with cognitive functioning and brain development at age 7 years. METHODS:A total of 83 infants born VPT (,30 weeks' gestation) had fT 4 concentrations measured postnatally and 2-and 6-week area under the curve (AUC) summary measures were calculated. Follow-up at age 7 years included a neuropsychological assessment and brain MRI. Univariable and multivariable regression modeling was used where AUC for fT 4 was the main predictor of neurodevelopmental outcome at age 7 years.RESULTS: Multivariable modeling revealed that higher, not lower, postnatal fT 4 levels (2-week AUC) were associated with poorer cognitive performances at age 7 years on tasks of verbal learning (P = .02), verbal memory (P = .03), and simple reaction time (P , .001). A similar pattern of results was found when the 6-week AUC was examined. No significant associations between postnatal fT 4 levels and brain volumes at age 7 years were identified. CONCLUSIONS:Results are contradictory to previous observations and suggest that after adjustment for confounders, higher postnatal fT 4 levels in VPT infants, rather than lower levels, may be a marker of adverse neuropsychological development in childhood. Dr Scratch conceptualized and designed the study, analyzed the data, and drafted the initial manuscript; Dr Hunt collected the blood specimens for hormone analysis, was involved in initial cerebral MRI interpretation, assisted with the conceptualization and design of the study, supervised data collection at all time points, and reviewed and revised the manuscript; Dr Thompson supervised the collection and analysis of the MRI scans and reviewed and revised the manuscript; Ms Ahmadzai performed the post-acquisition analysis of the MRI scans and reviewed and revised the manuscript; Dr Doyle assisted with the conceptualization and design of the study, supervised data collection at all time points, and reviewed and revised the manuscript; Dr Inder was involved in initial cerebral MRI interpretation, assisted with the conceptualization and design of the ...

Revisiting thyroid hormone treatment to prevent brain damage of prematurity

“…Since preparing this commentary two new papers have been published on the role of TH in brain development that point further to the importance of gestational age and inflammatory state. In brief, in agreement with data from the Vose study, higher levels of free T4 in infants of 27 weeks gestational age appear to associate negatively with outcome in a study of 80 infants in Australia (Scratch et al, ). The second study, of 786 infants of 25 and 26 weeks gestation (the Elgan study) found a negative relationship with apparent decreased TH signalling (via a surrogate marker, hyperthyrotropinemia) only in infants with intermittent or sustained systemic inflammation (Korzeniewski et al, ).…”

Adrenal and thyroid function in the fetus and preterm infant

“…The estimated incidence of delayed TSH elevation is up to 12% in preterm infants63,64). Although the timing of this elevation varies, it usually develops between 2 and 6 weeks of age in most cases.…”

Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?

“…They also lead to the inference that HTT and ISSI are probably influenced by each other’s capacity to convey risk information or to damage the brain. They also raise the possibility that the failure to identify an association between indicators of thyroid dysfunction and neurodevelopmental outcomes in some studies of very preterm neonates [6–12] is attributable, at least in part, to the lack of consideration for ISSI.…”

“…Preterm newborns with elevated TSH levels (hyperthyrotropinemia) have at times appeared to be at increased risk of brain damage [3–5], but not always [6–12]. These inconsistent findings, the apparent failure, so far, of thyroid hormone treatment to reduce the risk of brain damage [13], and the potential confounding of thyroid hormone levels by inflammation [14–16] raise the possibility that indicators of thyroid dysfunction may be an epiphenomenon [17].…”