Address for Correspondence:


Girish C. Deshpande, Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, 374 Bagot Road, Subiaco, Perth, Western Australia 6008. E-mail: girish.deshpande@health.wa.gov.au

Systematic review of Randomised controlled trials of probiotics in preterm neonates
Dani et al have evaluated the effectiveness of probiotics supplementation in reducing the incidence of urinary tract infections (UTI), sepsis and NEC in preterm neonates.(8) Total 585 preterm VLBW neonates were randomized to receive standard milk feed supplemented with Lactobacillus GG or placebo. Although UTI and NEC were less frequent in the probiotics vs. control group, the differences were not statistically significant. Lin HC et al evaluated the efficacy of probiotics in reducing death or ³ stage II NEC (primary outcome) in a masked trial in VLBW neonates who were commenced enteral feeds and survived beyond the 7th day after birth. (12) Total 367 preterm VLBW neonates were randomised to either probiotics (Infloran: Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharge or breast milk alone. The incidence of death or ³ stage II NEC was significantly lower (60%) in the probiotics group. Bin-Nun et al looked at efficacy of prophylactic probiotics in reducing the incidence and severity of NEC in preterm neonates (11). Total of 145 preterm VLBW neonates were randomised either to receive probiotics (Bifidobacteria infantis, Streptococcus thermophilus, and Bifidobacteria bifidus) of 109 colony forming units per day or placebo. The gestation, birth weight and time to reach full feeds were comparable. The incidence of NEC was reduced significantly in the probiotics group (4% vs. 16.4% in control group, p=0.03). NEC was less severe in the probiotics group and all NEC-related deaths (3/15) occurred in the control group (11).

The results of a systematic review indicate that probiotic supplementation has a significant role in prevention/minimisation of all cause mortality and morbidity (specifically NEC, late onset sepsis, and feed intolerance of prematurity) in preterm VLBW neonates.(29) Deshpande et al systematically reviewed the RCTs evaluating efficacy and safety of any probiotic supplementation (Started within first 10 days, duration: ³ 7 days) in preventing ³ stage II NEC in preterm VLBW (gestation < 33 weeks, birth weight < 1500 grams) neonates (29). A total of 7 out of 12 retrieved RCTs (N=1393) were eligible for inclusion in the analysis. Meta-analysis using a fixed effects model (7 trials, N=1393) estimated a lower risk of ³ Stage II NEC [RR: 0.36(95% CI: 0.20, 0.65)] in the probiotic group. The numbers needed to treat (NNT) with probiotics to prevent one case of NEC was 25 [95% CI: 17, 50]. The risk of blood culture positive sepsis (6 trials, N=1355) did not differ significantly between groups [RR: 0.94 (95% CI: 0.74, 1.20)]. The risk of death (5 trials, N=1268) was reduced significantly in the probiotic vs. control group [RR: 0.47(95% CI: 0.30, 0.73)] NNT to prevent one death by treatment with probiotics was 20 [95% CI: 12, 50]. However there was no significant difference in mortality due to NEC or sepsis. Additionally the time to full enteral feeds (3 trials, N= 316) was significantly shorter in the probiotic group [WMD=-2.74 days (95% CI: -4.98, -0.51]. Overall the results indicated that probiotics may significantly reduce the risk of all cause mortality and ³ Stage II NEC in preterm neonates <33 week's gestation while significantly shortening the time to full enteral feeds.

Safety :
Safety of probiotic supplements is an important issue in preterm neonates. Sepsis by the specific organism/s in the probiotic supplement was not reported in any of the trials included in the systematic review.(29) However caution is necessary before adopting probiotics for prophylaxis in immunocompromised hosts such as preterm neonates given that neonatal lactobacillus sepsis has already been reported.(30,31)

Unanswered Issues :
The unanswered issues include the dose, duration, and type of probiotic agent/s (species, strain, single versus combined, live versus killed) used for supplementation. The remarkably consistent results (29), despite the distinct differences in dose, timing, and type of organisms used, suggest that substantial latitude might be available in the choice of an effective probiotic regimen in the design of further trials. If further large well-designed trial confirms the results of the systematic review by Deshpande et al (29) it is possible that probiotics could be used as a routine in preterm neonates. Given that prematurity is the single most important and unpreventable risk factor, probiotic supplementation alone might not turn out to be the single magic bullet for death and diseases like sepsis, and NEC in preterm neonates.

References :

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How to cite this url :

Deshpande GC.The Role of Probiotics in Preterm Neonates . Pediatric Oncall [serial online] 2007 [cited 2007 December 1];4. Art # 49. Available from:

http://www.pediatriconcall.com/fordoctor/diseasesandcondition/Neonatology/probiotics.asp