Phase 1 Trial of 4 Thyroid Hormone Regimens for Transient Hypothyroxinemia in Neonates of <28 Weeks' Gestation

BACKGROUND: Transiently low levels of thyroid hormones occur in similar to 50% of neonates born 24-28 weeks' gestation and are associated with higher rates of cerebral palsy and cognitive impairment. Raising hormone levels shows promise for improving neurodevelopmental outcome. OBJECTIVE: To identify whether any of 4 thyroid hormone supplementation regimens could raise T-4 and FT4 without suppressing TSH ( biochemical euthyroidism). METHODS: Eligible subjects had gestational ages between 24(0)/(7) and 27(6)/(7) weeks and were randomized < 24 hours of birth to one of six study arms (n = 20-27 per arm): placebo (vehicle: 5% dextrose), potassium iodide (30 mu g/kg/d) and continuous or bolus daily infusions of either 4 or 8 mu g/kg/d of T-4 for 42 days. T-4 was accompanied by 1 mu g/kg/d T-3 during the first 14 postnatal days and infused with 1 mg/mL albumin to prevent adherence to plastic tubing. RESULTS: FT4 was elevated in the first 7 days in all hormone-treated subjects; however, only the continuous 8 mu g/kg/d treatment arm showed a significant elevation in all treatment epochs (P < .002 versus all other groups). TT4 remained elevated in the first 7 days in all hormone-treated subjects (P < .05 versus placebo or iodine arms). After 14 days, both 8 mu g/kg/d arms as well as the continuous 4 mu g/kg/d arm produced a sustained elevation of the mean and median TT4, > 7 mu g/dL (90 nM/L; P < .002 versus placebo). The least suppression of THS was achieved in the 4 mu g/kg/d T-4 continuous infusion arm. Although not pre- hypothesized, the duration of mechanical ventilation was significantly lower in the continuous 4 mu g/kg/d T-4 arm and in the 8 mu g/kg/d T4 bolus arm (P < .05 versus remaining arms). ROP was significantly lower in the combined 4 thyroid hormone treatment arms than in the combined placebo and iodine arms (P < .04). NEC was higher in the combined 8 mu g/kg/d arms (P < .05 versus other arms). CONCLUSIONS: Elevation of TT4 with only modest suppression of TSH was associated with trends suggesting clinical benefits using a continuous supplement of low-dose thyroid hormone (4 mu g/kg/d) for 42 days. Future trials will be needed to assess the long-term neurodevelopmental effects of such supplementation. Pediatrics 2009; 124: e258-e268