Objective To compare rates of necrotising enterocolitis (NEC), late-onset sepsis, and mortality in 5-year epochs before and after implementation of routine daily multistrain probiotics administration in high-risk neonates. Design Single-centre retrospective observational study over the 10-year period from 1 January 2008 to 31 December 2017. Setting Level 3 neonatal intensive care unit (NICU) of the Norfolk and Norwich University Hospital, UK. Patients Preterm neonates at high risk of NEC: admitted to NICU within 3 days of birth at 32 weeks’ gestation or at 32–36 weeks’ gestation and of birth weight 1500 g. Intervention Prior to 1 January 2013 probiotics were not used. Thereafter, dual-species Lactobacillus acidophilus and Bifidobacterium bifidum combination probiotics were routinely administered daily to high-risk neonates; from April 2016 triple-species probiotics ( L. acidophilus, B. bifidum, and B. longum subspecies infantis ) were used. Main outcome measures Incidence of NEC (modified Bell’s stage 2a or greater), late-onset sepsis, and mortality. Results Rates of NEC fell from 7.5% (35/469 neonates) in the pre-implementation epoch to 3.1% (16/513 neonates) in the routine probiotics epoch (adjusted sub-hazard ratio=0.44, 95% CI 0.23 to 0.85, p=0.014). The more than halving of NEC rates after probiotics introduction was independent of any measured covariates, including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p0.0001), and there was no episode of sepsis due to Lactobacillus or Bifidobacterium . All-cause mortality also fell in the routine probiotics epoch, from 67/469 (14.3%) to 47/513 (9.2%), although this was not statistically significant after multivariable adjustment (adjusted sub-hazard ratio=0.74, 95%?CI 0.49 to 1.12, p=0.155). Conclusions Administration of multispecies Lactobacillus and Bifidobacterium probiotics has been associated with a significantly decreased risk of NEC and late-onset sepsis in our neonatal unit, and no safety issues. Our data are consistent with routine use of Lactobacillus and Bifidobacterium combination probiotics having a beneficial effect on NEC prevention in very preterm neonates.
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机译：目的比较前，在高风险的新生儿实施了日常multistrain益生菌给药后坏死性小肠结肠炎（NEC），晚发性败血症，死亡率在5年时期的利率。设计单中心在10年的回顾性观察研究从2008年一月1日至12月31日2017年设定的诺福克和诺威奇大学医院，英国3级新生儿重症监护病房（NICU）。患者早产新生儿在NEC的高风险：在<32周妊娠或在32-36周妊娠和出生体重<1500克在出生后3天承认NICU。不用于干预之前，2013年1月1日益生菌。此后，双物种嗜酸和双歧杆菌两歧双歧杆菌的益生菌组合常规地每天施用到高风险新生儿;从2016年4月三种益生菌（嗜酸乳杆菌，两歧双歧杆菌，以及长双歧杆菌婴儿亚种）的使用。 NEC的主要观察指标发病率（修改贝尔的阶段2a或更高），晚发性败血症和死亡率。 NEC的结果率从7.5％（469分之35新生儿）在执行前历元在常规益生菌历元（调节子风险比= 0.44，95％CI 0.23下降到3.1％（513分之16新生儿）至0.85， p = 0.014）。超过NEC率减半后益生菌介绍是独立于任何测量协变量，包括母乳喂养速率。迟发性败血症的情况下从469分之106（22.6％）下降到五百十三分之五十九（11.5％）（P <0.0001），并且有由于乳杆菌或双歧杆菌没有败血症的发作。所有原因的死亡率也下降在常规益生菌时期，从469分之67（14.3％），以五百一十三分之四十七（9.2％），虽然经过多变量调整（调节子风险比= 0.74，95％这不是统计学显著？ CI 0.49至1.12，p = 0.155）。多物种的乳酸菌和双歧杆菌益生菌结论当局一直与NEC的显著风险降低和新生儿我们单位迟发性败血症，并没有安全问题有关。我们的数据与常规使用具有非常早产儿在NEC预防有益效果乳酸菌和双歧杆菌益生菌组合一致。
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