BACKGROUND: Transiently low levels of thyroid hormones occur in ∼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 T4 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 μg/kg/d) and continuous or bolus daily infusions of either 4 or 8 μg/kg/d of T4 for 42 days. T4 was accompanied by 1 μg/kg/d T3 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 μg/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 μg/kg/d arms as well as the continuous 4 μg/kg/d arm produced a sustained elevation of the mean and median TT4, >7 μg/dL (90 nM/L; P < .002 versus placebo). The least suppression of THS was achieved in the 4 μg/kg/d T4 continuous infusion arm. Although not pre-hypothesized, the duration of mechanical ventilation was significantly lower in the continuous 4 μg/kg/d T4 arm and in the 8 μg/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 μg/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 μg/kg/d) for 42 days. Future trials will be needed to assess the long-term neurodevelopmental effects of such supplementation.

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