NEW YORK (Reuters Health) – The “dramatic benefits” of probiotic supplements for reducing death and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) preterm neonates have been confirmed by a meta-analysis published online today in Pediatrics, the study authors say.

“Given the totality of the evidence, additional placebo-controlled trials are unnecessary if a suitable probiotic product is available,” according to the researchers, all of whom are based in Perth, Western Australia.

Co-author Dr. Sanjay Patole, from King Edward Memorial Hospital for Women, told Reuters Health by email, “It is high time we acknowledge the elephant in the room and move on to the next and perhaps the most important step — making safe and effective probiotic products easily available following very rigorous quality control and quality assurance practices. Without this it will mean, ‘all dressed up and nowhere to go.'”

The original meta-analysis, published in 2007, included seven randomized controlled trials of probiotic supplementation in 1393 preterm VLBW neonates. Babies given the supplements had a 53% lower risk of death, a 64% lower risk of NEC, and a significantly shorter time to full milk feeding (by a mean of 3 days) compared with the control group.

The updated meta-analysis released today pools the data from those seven trials plus four new ones published since then, bringing the total number of neonates to 2176.

Data from nine trials showed a 58% reduced relative risk for death from any cause in the probiotic vs control group (p < 0.00001), with a need to treat 20 of these tiny newborns in order to prevent one death from any cause.

Definite NEC, as reported by all 11 trials, developed in 26 of 1094 neonates (2.37%) who received probiotics and in 71 of 1082 controls (6.56%). Probiotics reduced the relative risk for definite NEC by 65% (RR, 0.35; p < 0.00001). The number needed to treat to prevent one case of NEC was 25.

Trial sequential analysis showed a 30% reduction in the incidence of NEC with probiotic supplementation.

Probiotics did not reduce the risk of sepsis in the updated analysis (RR, 0.98), nor did it significantly shorten the time to full milk feeding.

At this point, “withholding probiotics from high-risk neonates is now almost unethical,” the researchers say. They point to the strengths of their study: its significant effect size and precision, the consistency of the results across all trials, extremely low P values (“almost ruling out the role of chance alone”), low risk for publication bias, absence of statistical heterogeneity, and the trial sequential analysis showing at least a 30% reduction in the incidence of NEC.

Dr. Patole told Reuters Health, “Though it has not happened in a proper sequence, this intervention has completed a full circle, from basic science to conclusive meta analysis, followed by routine use and follow up. All as yet unanswered questions could be handled by further trials without a placebo. We seriously doubt, based on the current evidence, that parents will accept allocation of their baby to a placebo.”

The probiotics used (alone or in combination) in the 11 analyzed studies included Bifidobacterium breve; Lactobacillus GG; Saccharomyces boulardii; B. infantis; Streptococcus thermophilus; B. bifidus; L. acidophilus; L. casei; B. lactis; and B. longum.

A related article, also published online today in Pediatrics, reports on a placebo-controlled trial in which Lactobacillus GG (LGG) decreased the risk for nosocomial GI and respiratory tract infections in hospitalized children.

Lead author Dr. Iva Hojsak from Children’s Hospital Zagreb in Croatia and colleagues randomly allocated 742 hospitalized children aged 12 months or older to receive 100 mL of a fermented milk product either with (n = 376) or without (n = 366) a dose of 1 million colony-forming units of Lactobacillus rhamnosus strain GG. Both groups received their assigned treatments for the duration of hospitalization.

In the treatment group, the risk of GI and respiratory infections was approximately 60% lower (RR, 0.40 and 0.38, respectively) than in the placebo group. Secondary end points related to GI infections, including vomiting and diarrhea, were also significantly reduced in the LGG group.

Dr. Hojsak’s team reports that the odds of acquiring a GI infection were 2.89 times higher in the placebo group than in the LGG group, and this risk increased with the duration of hospitalization. The odds of acquiring a respiratory infection were 3.17 times higher in the placebo group; this risk also increased with time in the hospital.

Based on their findings, the authors believe LGG administration in pediatric facilities is a “valid” means of decreasing the burden of these infections. The researchers encourage further study of LGG use in hospitalized children younger than 12 months, as well as analysis of cost-effectiveness.

Pediatrics 2010;125:921-930, e1171-e1176.