Probiotics Feeding in Prevention of Urinary Tract Infection, Bacterial Sepsis and Necrotizing Enterocolitis in Preterm Infants

Abstract

Background: It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. Methods: A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor^®, Dicofarm, Rome, Italy) in a dose of 6 × 10⁹ colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo. Results: Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. Conclusion: Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations.

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

“…In addition, questions regarding the safety and efficacy of delivering probiotic bacteria to pre-term infants have not been fully answered, since not all studies have shown beneficial effects of probiotics. In a study by Dani et al [21], infants treated with Lactobacillus were shown to have an increased incidence of sepsis, and the observed decrease in NEC incidence was not statistically significant. Similarly, Land et al [22] observed cases of Lactobacillus sepsis in infants treated with probiotics.…”

“…However, point E lies in the region where the model predicts that probiotic treatment can actually be harmful, lowering the level of B L (0) needed to induce disease, for a certain range of k. For this parameter set, probiotics contribute to threshold crossing in the model, enhancing the immune response and further increasing permeability in a way that is not resolved by subsequent decreases in luminal bacterial levels. The existence of such a region may help explain clinical studies in which probiotics did not reduce the incidence of NEC and in fact led to bacterial sepsis [21,22]. Figure 6D provides a summary of predicted health and disease regions in the (k,r 1 ) plane.…”

“…The larger the value of parameter k, the lower this necessary number of pathogenic bacteria becomes ( Figure 6C). Clinical studies have shown both positive and negative outcomes when probiotics are administered to premature infants [18][19][20][21][22]. Points A-E in Figure 6C have been selected to illustrate how outcomes of different treatment strategies could depend quite sensitively on the size of an initial pathogenic insult, the virulence of the pathogen, and the characteristic k of the probiotics.…”

Quantitative Risk–Benefit Analysis of Probiotic Use for Irritable Bowel Syndrome and Inflammatory Bowel Disease

“…These infants may be less likely to develop NEC (51)(52)(53), and while concern has long existed about probiotic strain-associated sepsis, this risk has not been born out in larger trials. However, studies overall have had mixed results (54,55). Infants do not develop IBS, and develop IBD only in extremely rare cases, but the apparent safety of probiotics in this group is reassuring that the risk for vulnerable or immunocompromised patients may be relatively low.…”

Probiotics and necrotizing enterocolitis

“…In 1999, Hoyos and colleagues reported the outcome of a cohort study, in which, probiotic administration was associated with a reduction in the incidence of necrotizing enterocolitis [53]. Between 2003 and 2006, several randomised studies reported a reduction in the incidence of NEC among preterm babies recruited to probiotic trials (and receiving the probiotic intervention) though not all these studies were designed to evaluate NEC as a primary outcome [54][55][56][57][58][59]. The first meta-analysis combining these results was published in 2007 and concluded that probiotics might reduce the risk of NEC in preterm babies born less 33 weeks gestation [60].…”