Transient hypothyroxinemia of prematurity is associated with abnormal cranial ultrasound and illness severity

Abstract

Transient hypothyroxinemia without elevated thyroid-stimulating hormone (TSH) levels is common in prematurity, especially in very-low-birth-weight (VLBW) infants. The transient hypothyroxinemia of prematurity (THOP) has been seen as a "benign" condition not requiring medical treatment. However, some recent large observational studies have revealed a relationship between THOP and abnormal neurodevelopment. Furthermore, one study showed THOP had twice the risk of brain echolucency, which was the best predictable neurodevelopmental dysfunction, than the premature infants with normal or higher thyroxine levels. The relationships among THOP, illness severity, and neurodevelopmental dysfunction remain unclear. We propose a hypothesis that THOP is associated with abnormal ultrasound and illness severity. We studied 54 infants who were admitted more than 14 days at our neonatal intensive care unit (NICU) with a birth weight <2000 g from March 1999 to March 2000. The infants received serum thyroxine (T4), free-T4, and TSH measurement during the first weeks of life. Most of them had serum thyroxine levels measured at approximately 2 weeks of age. The infants enrolled in the study were examined by at least 1 of 3 cranial ultrasounds during the first weeks of life, illness severity evaluation according to the neonatal therapeutic intervention scoring system (NTISS) score, as well as NICU hospital stay period. Infant were classified as THOP by T4 value <5.3 microg/dL (68 nmol/L), which is 2.6 SD below the mean for term infants in Massachusetts, without elevated TSH value (<20 microIU/mL). After adjusting for some confounding factors, such as gestational age, birth weight, duration of mechanical ventilation, infants with THOP were associated with abnormal cranial ultrasound, illness severity, and lower 1-minute Apgar score. In our studies, THOP was related with brain ultrasound anomaly, neonatal illness, and lower Apgar score at 1 minute. Does early thyroxine intervention improve the prognosis and neurodevelopmental dysfunction? This question requires further investigation.