Protective Effect of Dual-Strain Probiotics in Preterm Infants: A Multi-Center Time Series Analysis

PLoS One. 2016 Jun 22;11(6):e0158136. doi: 10.1371/journal.pone.0158136. eCollection 2016.


Objective: To determine the effect of dual-strain probiotics on the development of necrotizing enterocolitis (NEC), mortality and nosocomial bloodstream infections (BSI) in preterm infants in German neonatal intensive care units (NICUs).

Design: A multi-center interrupted time series analysis.

Setting: 44 German NICUs with routine use of dual-strain probiotics on neonatal ward level.

Patients: Preterm infants documented by NEO-KISS, the German surveillance system for nosocomial infections in preterm infants with birth weights below 1,500 g, between 2004 and 2014.

Intervention: Routine use of dual-strain probiotics containing Lactobacillus acidophilus and Bifidobacterium spp. (Infloran) on the neonatal ward level.

Main outcome measures: Incidences of NEC, overall mortality, mortality following NEC and nosocomial BSI.

Results: Data from 10,890 preterm infants in 44 neonatal wards was included in this study. Incidences of NEC and BSI were 2.5% (n = 274) and 15.0%, (n = 1631), respectively. Mortality rate was 6.1% (n = 665). The use of dual-strain probiotics significantly reduced the risk of NEC (HR = 0.48; 95% CI = 0.38-0.62), overall mortality (HR = 0.60, 95% CI = 0.44-0.83), mortality after NEC (HR = 0.51, 95% CI = 0.26-0.999) and nosocomial BSI (HR = 0.89, 95% CI = 0.81-0.98). These effects were even more pronounced in the subgroup analysis of preterm infants with birth weights below 1,000 g.

Conclusion: In order to reduce NEC and mortality in preterm infants, it is advisable to add routine prophylaxis with dual-strain probiotics to clinical practice in neonatal wards.

Publication types

  • Multicenter Study

MeSH terms

  • Cross Infection / drug therapy
  • Enterocolitis, Necrotizing / drug therapy
  • Female
  • Humans
  • Infant, Extremely Low Birth Weight / physiology
  • Infant, Newborn
  • Infant, Premature / physiology*
  • Infant, Very Low Birth Weight / physiology
  • Interrupted Time Series Analysis*
  • Male
  • Probiotics / therapeutic use*
  • Proportional Hazards Models
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*


  • Protective Agents

Grant support

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.