Paper reading (九十二)：routine prophylactic Lactobacillus and Bifidobacterium probiotics

论文题目：Incidence of necrotising enterocolitis before and after introducing routine prophylactic Lactobacillus and Bifidobacterium probiotics

scholar 引用：0

页数：7

发表时间：24 September 2019

发表刊物：Archives of Disease in Childhood: Fetal(胎儿的) and Neonatal Edition(新生儿期)

作者：Robertson, Claire Savva, ..., Paul

作者单位：Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK

摘要：

Abstract
Objective To compare rates of necrotising enterocolitis (NEC, 坏死性小肠结肠炎), late-onset sepsis (晚发败血症), and mortality(死亡率) in 5-year epochs before and after implementation of routine daily multistrain(多菌群) probiotics administration in high-risk neonates(新生儿).

Design Single-centre retrospective observational study(单中心回顾性观察研究) over the 10-year period from 1 January 2008 to 31 December 2017.

Setting Level 3 neonatal intensive care unit (NICU, 新生儿重症监护室) of the Norfolk and Norwich University Hospital, UK.

Patients Preterm neonates(早产儿) at high risk of NEC: admitted to NICU within 3 days of birth at <32 weeks’ gestation(妊娠期) 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(双物种嗜酸乳杆菌) and Bifidobacterium bifidum(双歧双歧杆菌) combination probiotics were routinely administered daily to high-risk neonates; from April 2016 triple-species probiotics (L.acidophilus(嗜酸乳杆菌),B.bifidum(双歧杆菌), and B.longum subspecies infantis(婴儿双歧杆菌)) 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(亚危险) 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(协变量), including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p<0.0001), 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.

正文组织架构：

1. Introduction

2. Methods

2.1 Eligible population

2.2 Study period

2.3 Enteral feeding practices

2.4 Oxygen saturation limits

2.5 Identification and classfication of NEC cases

2.6 Identification and classification of late-onset sepsis

2.7 Outcome measures

2.8 Statistical analysis

3. Results

3.1 Descriptive analysis

3.2 NEC incidence according to diagnostic system used

3.3 Cumulative incidence of NEC from birth

3.4 All-cause mortality and NEC-associated rate of death within epoches

3.5 Regression discontinuity analysis

3.6 Sensitivity analysis

3.7 Incidence of late-onset sepsis

4. Discussion 

4.1 Summary of findings 

4.2 Strengths of limitations

正文部分内容摘录：

1. 健康还是特定疾病？多少个体和组别？就是说这些组别的个体是对健康个体进行干预，还是特定疾病的人在干预？

• Patients Preterm neonates(早产儿) at high risk of NEC: admitted to NICU within 3 days of birth at <32 weeks’ gestation(妊娠期) or at 32–36 weeks’ gestation and of birth weight <1500 g.
• 982 high-risk neonates
• Pre-probiotics epoch n=469
• Routine probiotics epoch n=513
• The sample included 982 eligible neonates: 469 born in the pre-probiotics epoch and 513 in the routine probiotics epoch 

2. 有哪些组学数据可利用？组学数据的下载ID是什么？

• Data availability statement: Data are available on reasonable request.
• Correspondence to Prof Paul Clarke, Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK; paul. clarke@ nnuh. nhs. uk

3. 研究的干预基本结果和结论是什么？

• 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(亚危险) 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(协变量), including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p<0.0001), 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.
• Routine daily dosing with Lactobacillus and Bifidobacterium probiotics was a cheap, simple intervention associated with significantly decreased NEC, surgical NEC and late-onset sepsis in our neonatal unit.
• No episode of sepsis due to Lactobacillus or Bifidobacterium occurred in the routine probiotic supplementation epoch.
• The apparent impact of reduced NEC incidence with probiotics was particularly pronounced in the first 2 weeks postnatal, implying that achieving early probiotic bacterial gut colonisation is crucial.
• Limitations: Being retrospective and observational, our findings only support an association and cannot conclusively determine that probiotics caused the observed markedly reduced NEC incidence; unmeasured confounders might underlie observed differences between epochs.