Objective. Preterm neonates undergoing intensive care have high morbidity from sepsis. These infants also frequently develop neutropenia, and when this is associated with sepsis, mortality is high. This study investigates the potential for granulocyte-macrophage colony-stimulating factor (GM-CSF) to effect a clinically relevant increase in neutrophil number when used prophylactically in high-risk preterm neonates, and assesses its safety in this population.Design. In an open, randomized, controlled study, 75 neonates (25 small for gestational age) 32 weeks gestation were randomized to receive GM-CSF (10 μg/kg/d) by subcutaneous injection for 5 days from 72 hours after birth, or to a control group. The primary outcome measure was the neutrophil count during 14 days from study entry. The infants were monitored for potential toxicity. Clinical outcomes, sepsis, and mortality, were recorded, but this initial study was not designed to address clinical benefit.Results. Prophylactic GM-CSF therapy completely abolished neutropenia in treated infants, when both well and septic, throughout the period of study. Neutropenia (≤1.7 × 109/L) developed in 16 of 39 control infants. Five control infants experienced an acute decrease in neutrophil count coincident with the onset of sepsis. There was no evidence of hematologic, respiratory, or gastrointestinal toxicity in treated infants. Treated infants had a trend to fewer symptomatic, blood culture positive septic episodes than controls during 2 weeks from study entry (11/36 vs 18/39).Conclusion. Five-day prophylactic GM-CSF completely abolishes postnatal neutropenia and sepsis-induced neutropenia in preterm neonates at high risk of sepsis, and so removes an important risk factor for sepsis and sepsis-related mortality.GM-CSF, preterm neonates, neutropenia, sepsis.
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机译：目的。接受重症监护的早产儿因败血症而发病率很高。这些婴儿还经常发展中性粒细胞减少症，当这与败血症相关时，死亡率很高。这项研究调查了在高危早产儿中预防性使用粒细胞巨噬细胞集落刺激因子（GM-CSF）可能会引起临床上相关的嗜中性粒细胞数量增加，并评估其在该人群中的安全性。在一项开放，随机，对照的研究中，从出生后<72小时开始，皮下注射75例新生儿（胎龄小于32周的25例）<32周，随机分配接受GM-CSF（10μg/ kg / d），或对照组。主要结果指标是研究开始后14天内的中性粒细胞计数。监测婴儿的潜在毒性。记录了临床结局，败血症和死亡率，但该初始研究并非旨在解决临床获益。在整个研究期间，预防性的GM-CSF治疗在健康和败血症的情况下都完全消除了接受治疗的婴儿的中性粒细胞减少。 39名对照婴儿中有16名出现中性粒细胞减少（≤1.7×109 / L）。五名对照婴儿的中性粒细胞计数急剧下降，与脓毒症发作同时发生。没有证据表明接受治疗的婴儿有血液，呼吸或胃肠道毒性。在进入研究的两周内，接受治疗的婴儿的症状，血培养阳性败血症发生率比对照组少（11/36 vs 18/39）。五天预防性GM-CSF完全消除了败血症高危早产儿的产后中性粒细胞减少和败血症诱发的中性粒细胞减少，从而消除了败血症和败血症相关死亡率的重要危险因素。 。
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