Manzoni Paolo, Meyer Michael, Stolfi Ilaria, Rinaldi Matteo, Cattani Silvia, Pugni Lorenza, Romeo Mario Giovanni, Messner Hubert, Decembrino Lidia, Laforgia Nicola, Vagnarelli Federica, Memo Luigi, Bordignon Linda, Maule Milena, Gallo Elena, Mostert Michael, Quercia Michele, Bollani Lina, Pedicino Roberto, Renzullo Livia, Betta Pasqua, Ferrari Fabrizio, Alexander Tanith, Magaldi Rosario, Farina Daniele, Mosca Fabio, Stronati Mauro
Neonatology and NICU, S. Anna Hospital; Torino, Italy.
Neonatology and NICU, Middlemore Hospital; Auckland, New Zealand.
Early Hum Dev. 2014 Mar;90 Suppl 1:S60-5. doi: 10.1016/S0378-3782(14)70020-9.
NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW, <1500 g at birth). Probiotics including lactobacillus rhamnosus GG (LGG) proved effective in preventing NEC in preterm infants in several RCTs.
Lactoferrin, a mammalian milk glycoprotein involved in innate immune host defences, can reduce the incidence of NEC in animal models, and its action is enhanced by LGG. We tried to assess whether bovine lactoferrin (BLF), alone or with the probiotic LGG, has a similar effect in human infants, something that has not yet been studied.
An international, multicenter, randomized, double-blind, placebo-controlled trial conducted from October 1st, 2007 through July 31st, 2010.
Thirteen Italian and New Zealand tertiary neonatal intensive care units.
743 VLBW neonates were assessed until discharge for development of NEC.
Infants were randomly assigned to receive orally either BLF (100 mg/day) alone (group LF; n = 247) or with LGG (at 6×10(9) CFU/day; group BLF + LGG; n = 238), or placebo (Control group; n = 258) from birth until day 30 of life (45 for neonates <1000 g at birth).
≥ stage 2 NEC; death-and/or-≥ stage 2 NEC prior to discharge.
Demographics, clinical and management characteristics of the 3 groups were similar, including type of feeding and maternal milk intakes. NEC incidence was significantly lower in groups BLF and BLF + LGG [5/247 (2.0%)] and 0/238 (0%), respectively] than in controls [14/258 (5.4%)] (RR = 0.37; 95% CI: 0.136-1.005; p = 0.055 for BLF vs. control; RR = 0.00; p < 0.001 for BLF + LGG vs. control). The incidence of death-and/or-NEC was significantly lower in both treatment groups (4.0% and 3.8% in BLF and BLF + LGG vs. 10.1% in control; RR = 0.39; 95% CI: 0.19-0.80; p = 0.008. RR = 0.37; 95% CI: 0.18-0.77; p = 0.006, respectively). No adverse effects or intolerances to treatment occurred.
Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death-and/or ≥ stage 2 NEC in VLBW neonates. BLF might be a promising strategy to prevent NEC in NICU settings. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical settings.
ISRCTN53107700-http://www.controlled-_trials.com/ISRCTN53107700.
坏死性小肠结肠炎（NEC）是早产儿尤其是极低出生体重儿（出生体重<1500g）常见且严重的并发症。多项随机对照试验（RCT）证明，包括鼠李糖乳杆菌GG（LGG）在内的益生菌对预防早产儿坏死性小肠结肠炎有效。
乳铁蛋白是一种参与固有免疫宿主防御的哺乳动物乳糖蛋白，在动物模型中可降低坏死性小肠结肠炎的发病率，且LGG可增强其作用。我们试图评估牛乳铁蛋白（BLF）单独使用或与益生菌LGG联合使用对人类婴儿是否有类似效果，此前尚未有相关研究。
一项国际多中心随机双盲安慰剂对照试验，于2007年10月1日至2010年7月31日进行。
13家意大利和新西兰的三级新生儿重症监护病房。
743例极低出生体重儿在出院前接受坏死性小肠结肠炎发生情况评估。
婴儿从出生至出生后30天（出生体重<1000g的新生儿为45天）被随机分配，分别口服单独的BLF（100mg/天）（LF组；n = 247）、BLF与LGG联合使用（6×10⁹CFU/天；BLF + LGG组；n = 238）或安慰剂（对照组；n = 258）。
≥2期坏死性小肠结肠炎；出院前死亡和/或≥2期坏死性小肠结肠炎。
三组的人口统计学、临床和管理特征相似，包括喂养方式和母乳摄入量。BLF组和BLF + LGG组的坏死性小肠结肠炎发病率显著低于对照组，分别为5/247（2.0%）和0/238（0%），而对照组为14/258（5.4%）（相对危险度（RR）= 0.37；95%置信区间（CI）：0.136 - 1.005；BLF组与对照组比较，p = 0.055；RR = 0.00；BLF + LGG组与对照组比较，p < 0.001）。两个治疗组的死亡和/或坏死性小肠结肠炎发病率均显著低于对照组（BLF组和BLF + LGG组分别为4.0%和3.8%，对照组为10.1%；RR = 0.39；95%CI：0.19 - 0.80；p = 0.008。RR = 0.37；95%CI：0.18 - 0.77；p = 0.006）。未发生治疗相关的不良反应或不耐受情况。
与安慰剂相比，单独补充BLF或与LGG联合补充可降低极低出生体重儿≥2期坏死性小肠结肠炎以及死亡和/或≥2期坏死性小肠结肠炎的发病率。在新生儿重症监护病房中，BLF可能是预防坏死性小肠结肠炎的一种有前景的策略。在BLF能够广泛应用于临床之前，需要更多大样本量的数据。
ISRCTN53107700 - http://www.controlled - _trials.com/ISRCTN53107700
