Ballard R A, Ballard P L, Creasy R K, Padbury J, Polk D H, Bracken M, Moya F R, Gross I
Department of Pediatrics, Mount Zion Hospital and Medical Center, San Francisco, California.
Lancet. 1992 Feb 29;339(8792):510-5. doi: 10.1016/0140-6736(92)90337-3.
Although prenatal glucocorticoid treatment reduces neonatal respiratory morbidity, respiratory distress syndrome and chronic lung disease (CLD) develop in many very-low-birthweight infants despite therapy. To investigate the effect of additional prenatal treatment with thyrotropin-releasing hormone (TRH), we did a multicentre, blinded, randomised trial. 404 women with threatened preterm delivery at less than 32 weeks' gestation received betamethasone plus TRH (4 doses of 400 micrograms 8-hourly) or betamethasone plus placebo. 103 infants who were fully treated and of less than 1500 g birthweight were evaluated during the neonatal period. TRH treatment (55 infants) did not affect the total incidence of respiratory distress syndrome (47% vs 58% in controls) or of severe respiratory distress syndrome (13% vs 25% in controls, p = 0.11). CLD (defined as requirement for supplemental oxygen at 28 days after birth) developed in significantly fewer TRH-treated infants (18% vs 44% of controls, p less than 0.01). The unadjusted relative risk of CLD with TRH therapy was 0.40 (95% CI 0.26-0.80, p less than 0.05), and this was not materially changed after adjustment for potentially modifying variables. There were significantly fewer adverse outcomes, defined as death or continuing oxygen requirement, in the TRH group than in the steroid-alone group both at 28 days and when infants reached 36 weeks' postconceptional age. The incidence of other complications of prematurity was similar in the two groups. Prenatal TRH reduces the incidence of chronic lung disease among betamethasone-treated infants.
尽管产前糖皮质激素治疗可降低新生儿呼吸疾病的发病率，但许多极低出生体重儿在接受治疗后仍会发生呼吸窘迫综合征和慢性肺病（CLD）。为了研究额外给予促甲状腺激素释放激素（TRH）进行产前治疗的效果，我们开展了一项多中心、双盲、随机试验。404名妊娠小于32周有早产风险的女性接受了倍他米松加TRH（4剂，每8小时400微克）或倍他米松加安慰剂治疗。对103名接受了全程治疗且出生体重小于1500克的婴儿在新生儿期进行了评估。TRH治疗组（55名婴儿）并未影响呼吸窘迫综合征的总发病率（47% 对比对照组的58%）或严重呼吸窘迫综合征的发病率（13% 对比对照组的25%，p = 0.11）。CLD（定义为出生后28天需要补充氧气）在接受TRH治疗的婴儿中发生率显著更低（18% 对比对照组的44%，p小于0.01）。TRH治疗CLD的未调整相对风险为0.40（95% CI 0.26 - 0.80，p小于0.05），在对潜在修正变量进行调整后，这一结果并无实质性改变。在出生后28天以及婴儿达到孕龄36周时，TRH组的不良结局（定义为死亡或持续需要氧气）显著少于仅使用类固醇激素的组。两组中早产的其他并发症发生率相似。产前TRH可降低倍他米松治疗的婴儿中慢性肺病的发病率。
