Objective Hypothyroxinemia of prematurity occurs in ∼50% of preterm neonates and is associated with adverse neurodevelopmental outcomes. TH supplementation may improve outcome if the optimal dosing regimen were known.

Aim To determine a dosing protocol that could raise FT4 levels with the least TSH suppression.

Methods Neonates between 24–28 wks gestation were enrolled within 24 h of birth (Amsterdam, Madrid, NY) resulting in 168 subjects randomized to one of 6 treatment arms: placebo (D5W), potassium iodide (30 μg/kg/d) or continuous or bolus daily infusions of either 4 or 8 μg/kg/d of T4 for 42 ds+1 μg/kg/d T3×14 d in T4 Rx groups. FT4 (equilibrium dialysis), TT4, TSH, T3, (RIA) & TBG were measured on days 0, 3, 7, 14, 28, 42, & 56.

Results No significant differences were found across the groups for maternal or neonatal variables at enrollment. TT4 was elevated (p<0.03) and TSH was suppressed (<0.4 mU/L) in the first 14 days for supplemented groups compared to placebo/iodine. TT4 remained elevated >90 nM/L (7 μg/dl; p<0.01) in the treatment arms with the least suppression of TSH seen with 4 μg/kg/d T4 continuous infusion. Providing iodine supplements alone elevated FT4 (p<0.05) compared to placebo. No differences were seen in mortality. All subjects recovered to normal range by 2 weeks off study drug.

Conclusions Elevation of TT4 >50 nM/L with the least suppression of TSH, was achieved in neonates using a continuous supplement of 4 μg/kg/d for 42 d.