Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation.

Author(s): La Gamma EF, van Wassenaer AG, Ares S, Golombek SG, Kok JH, Quero J, Hong T, Rahbar MH, de Escobar GM, Fisher DA, Paneth N

Affiliation(s): Department of Neonatal-Perinatal Medicine, Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, New York Medical College, Valhalla, New York 10595, USA. Edmund_lagamma@nymc.edu

Publication date & source: 2009-08, Pediatrics., 124(2):e258-68. Epub 2009 Jul 5.

Publication type: Clinical Trial, Phase I; Comparative Study; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural

BACKGROUND: Transiently low levels of thyroid hormones occur in approximately 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 FT(4) without suppressing TSH (biochemical euthyroidism). METHODS: Eligible subjects had gestational ages between 24 07 and 2767 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 microg/kg/d) and continuous or bolus daily infusions of either 4 or 8 microg/kg/d of T(4) for 42 days. T(4) was accompanied by 1 microg/kg/d T(3) during the first 14 postnatal days and infused with 1 mg/mL albumin to prevent adherence to plastic tubing. RESULTS: FT(4) was elevated in the first 7 days in all hormone-treated subjects; however, only the continuous 8 microg/kg/d treatment arm showed a significant elevation in all treatment epochs (P < .002 versus all other groups). TT(4) remained elevated in the first 7 days in all hormone-treated subjects (P < .05 versus placebo or iodine arms). After 14 days, both 8 microg/kg/d arms as well as the continuous 4 microg/kg/d arm produced a sustained elevation of the mean and median TT(4), >7 microg/dL (90 nM/L; P < .002 versus placebo). The least suppression of THS was achieved in the 4 microg/kg/d T(4) continuous infusion arm. Although not pre-hypothesized, the duration of mechanical ventilation was significantly lower in the continuous 4 microg/kg/d T(4) arm and in the 8 microg/kg/d T(4) 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 microg/kg/d arms (P < .05 versus other arms). CONCLUSIONS: Elevation of TT(4) with only modest suppression of TSH was associated with trends suggesting clinical benefits using a continuous supplement of low-dose thyroid hormone (4 microg/kg/d) for 42 days. Future trials will be needed to assess the long-term neurodevelopmental effects of such supplementation.