Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation.
Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation.
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DOI：
10.1542/peds.2008-2837
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发表时间：
2009-08
期刊：
影响因子：
8
通讯作者：
Paneth N
中科院分区：
文献类型：
--
作者：
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
在妊娠24-28周出生的新生儿中，有50%的∼会出现短暂的低甲状腺激素水平，并与较高的脑性瘫痪和认知障碍的发生率有关。提高荷尔蒙水平显示出改善神经发育结果的希望。探讨4种甲状腺激素补充方案是否能在不抑制TSH的情况下提高T4、FT4水平。符合条件的受试者孕周在240/7到276/7周之间，出生后24小时被随机分配到六个研究组中的一个(n=20-27)：安慰剂(5%葡萄糖)，碘化钾(30μg/kg/d)，连续或连续每日滴注T4 4或8μg/kg/d，共42天。T4在出生后14天内加入1μg/kg/d T3，并输注1 mg/mL白蛋白以防止粘连塑料管。在所有激素治疗的受试者中，FT4在前7天都升高了；然而，只有连续8μg/kg/d的治疗组在所有治疗时期都有显著的升高(与所有其他组相比P<；.002)。在所有接受激素治疗的受试者中，TT4在前7天仍然升高(P<；0.05与安慰剂或碘对照组相比)。14天后，8μg/kg/d组和连续4μg/kg/d组的TT4、GT；7μg/dL的平均值和中位数持续升高(90 NM/L；P<；.002与安慰剂组相比)。4μg/kg/d T4持续输液臂对THS的抑制作用最小。尽管不是预先假设的，但持续4μg/kg/d T4组和8μg/kg/d T4推注组的机械通气持续时间显著缩短(P<；0.05与其余组相比)。联合使用4种甲状腺激素治疗组的ROP显著低于联合使用安慰剂和碘化组(P<；.04)。NEC在合计8μg/kg/d组较高(P<；0.05与其他组相比)。低剂量甲状腺激素(4μg/kg/d)持续补充42天后，Tt4升高，而促甲状腺激素仅有轻微抑制，与临床疗效相关。未来需要进行试验来评估这种补充剂对神经发育的长期影响。
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. To identify whether any of 4 thyroid hormone supplementation regimens could raise T4 and FT4 without suppressing TSH (biochemical euthyroidism). Eligible subjects had gestational ages between 240/7 and 276/7 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. 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). 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.