Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials.
BACKGROUND
Results of recent clinical trials suggest that probiotic supplementation reduces the risk of necrotising enterocolitis in preterm neonates. We aimed to systematically review randomised controlled trials evaluating efficacy and safety of any probiotic supplementation (started within first 10 days, duration > or =7 days) in preventing stage 2 or greater necrotising enterocolitis in preterm neonates (gestation <33 weeks) with very low birthweight (<1500 g).


METHODS
We followed the standard search strategy of the Cochrane Neonatal Review Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL databases, and proceedings of the Pediatric Academic Society meetings (from 1980) and Pediatric Gastroenterology conferences (from 1980) in November, 2006.


RESULTS
Seven of 12 randomised controlled trials retrieved (n=1393) were eligible for inclusion in the analysis. Meta-analysis using a fixed effects model estimated a lower risk of necrotising enterocolitis (relative risk 0.36, 95% CI 0.20-0.65) in the probiotic group than in controls. Risk of sepsis did not differ significantly between groups (0.94, 0.74-1.20). Risk of death was reduced in the probiotic group (0.47, 0.30-0.73). The time to full feeds was significantly shorter in the probiotic group (weighted mean difference -2.74 days, 95% CI -4.98 to -0.51) than in controls.


CONCLUSIONS
Probiotics might reduce the risk of necrotising enterocolitis in preterm neonates with less than 33 weeks' gestation. However, the short-term and long-term safety of probiotics needs to be assessed in large trials. Unanswered questions include the dose, duration, and type of probiotic agents (species, strain, single or combined, live or killed) used for supplementation.
Deshpande
Girish
G
Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, Subiaco, WA, Australia.
Rao
Shripada
S
Patole
Sanjay
S
D004311:Double-Blind Method; D004750:Enteral Nutrition; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D005865:Gestational Age; D006801:Humans; D041943:Infant Formula; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D015201:Meta-Analysis as Topic; D019936:Probiotics / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic