Probiotic Supplementation and Late-Onset Sepsis in Preterm Infants: A Meta-analysis

Abstract

CONTEXT: Late-onset sepsis (LOS) is a major cause of mortality and morbidity in preterm infants. Despite various preventive measures, its incidence continues to remain high, hence the urgent need for additional approaches. One such potential strategy is supplementation with probiotics. The updated Cochrane Review (2014) did not find benefits of probiotics in reducing the risk of LOS in preterm infants (19 studies, N = 5338). Currently there are >30 randomized controlled trials (RCTs) of probiotics in preterm infants that have reported on LOS. OBJECTIVES:To conduct a systematic review including all relevant RCTs.DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and E-abstracts from the Pediatric Academic Society meetings and other pediatric and neonatal conference proceedings were searched in June and August 2015.STUDY SELECTION: RCTs comparing probiotics versus placebo/no probiotic were included. DATA EXTRACTION:Relevant data were extracted independently by 3 reviewers. RESULTS:Pooled results from 37 RCTs (N = 9416) using fixed effects model meta analysis showed that probiotics significantly decreased the risk of LOS (675/4852 [13.9%] vs 744/4564 [16.3%]; relative risk, 0.86; 95% confidence interval, 0.78-0.94; P = .0007; I 2 = 35%; number needed to treat, 44). The results were significant even after excluding studies with high risk of bias. CONCLUSIONS: Probiotic supplementation reduces the risk of LOS in preterm infants.a Neonatal ICU, King Edward Memorial Hospital for Women, Perth, Western Australia; b Neonatal ICU, Princess Margaret Hospital for Children, Perth, Western Australia; c Centre for Neonatal Research and Education, School of Pediatrics and Child Health, University of Western Australia, Perth, Western Australia; d Neonatal ICU, Nepean Hospital, Kingswood, NSW, Australia; and e Sydney Medical School, Nepean, University of Sydney, Australia Dr Rao conceptualized and designed the study, performed an independent literature search, selected studies for inclusion, extracted and interpreted data, assessed risk of bias of included studies, handled the meta-analysis software, and wrote the fi rst and fi nal drafts of the manuscript; Dr Athalye-Jape performed an independent literature search, selected studies for inclusion, contacted authors for additional information where necessary, extracted and interpreted the data, checked the data entered by S.C.R. on the meta-analysis software, assessed the risk of bias of included studies, and helped with the fi rst and the fi nal draft of the manuscript; Dr Deshpande performed an independent literature search, selected studies for inclusion, verifi ed the extracted data, assessed risk of bias, interpreted data, and oversaw translation of manuscripts in the Chinese language; Dr Simmer supervised the project, interpreted the data, and supervised the fi rst and fi nal versions of the manuscript; Dr Patole supervised the project, acted as referee author in case of d...

Risk Factors for Late-Onset Sepsis in Preterm Infants: A Multicenter Case-Control Study

“…This phenomenon might lead to the development of strategies aimed at early manipulation of the microbiota to prevent LOS development, for example by administration of probiotics instead of antibiotic prophylaxis, reducing the risk for colonization with multi-resistant pathogens [21]. It has been demonstrated that probiotic supplementation significantly reduced the risk of LOS in preterm infants ( n = 9,416) [22]. However, additional studies are needed to evaluate the optimal dosage, duration, and identification of the best suitable bacterial strains for supplementation.…”

Gut bacteria and late-onset neonatal bloodstream infections in preterm infants

“…Zhang et al [46] proposed that probiotics might prevent bloodstream infections in low birthweight infants, but no effect was seen in children weighing <1000 g at birth. Rao et al also concluded that probiotics had a preventive effect [47] and likewise found that infants in a subgroup analysis (those born at <28 weeks' gestation and/or weighing <1000 g at birth) did not benefit from this intervention. Late-onset neonatal bloodstream infections were an outcome in the large probiotic study recently reported by Costeloe et al [48].…”

The Canadian Preterm Birth Network: a study protocol for improving outcomes for preterm infants and their families

“…Probiotic administration to preterm neonates may reduce rates of necrotizing enterocolitis 27 and nosocomial infection, 28 yet only 30% of Canadian neonates receive probiotics. 16 We will attempt to link receipt of probiotics during the neonatal intensive care unit stay as well as type, form (powder v. liquid), duration and timing of probiotic use with neonatal and neurodevelopmental outcomes.…”