Probiotic administration can prevent necrotizing enterocolitis in preterm infants: A meta-analysis

doi:10.1016/j.jpedsurg.2015.05.008

Journal of Pediatric Surgery

Volume 50, Issue 8, August 2015, Pages 1405-1412

https://doi.org/10.1016/j.jpedsurg.2015.05.008 Get rights and content

Abstract

Purpose

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants, affecting ~ 6–7% of very-low-birth-weight (VLBW) infants. Early intervention and aggressive treatment has improved clinical outcomes, but considerable morbidity continues to accrue to NEC survivors. This meta-analysis examines the impact of probiotics on the incidence of NEC and complications among VLBW infants.

Methods

A comprehensive literature search for all published randomized control trials (RCTs) assessing the use of probiotics to prevent NEC in VLBW infants was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (1966–2014). The incidences of NEC, sepsis, overall mortality, and time to reach full enteral feeds were analyzed.

Results

20 RCTs involving 5982 preterm VLBW infants were analyzed. Risk of NEC was reduced by 49.1% (RR = 0.509; 95% CI, 0.385–0.672; p < 0.001), and overall mortality by 26.9% among infants receiving probiotics (RR = 0.731; 95% CI, 0.577–0.926; p = 0.009). An 8.1% reduction in sepsis was also observed in infants receiving probiotics (RR = 0.919; 95% CI, 0.823–1.027; p = 0.137). Time to reach full enteral feeds was reduced by 1.2 days among infants receiving probiotics (MD: − 1.217; 95% CI, − 2.151 to − 0.283; p = 0.011).

Conclusion

The use of probiotic supplementation in preterm VLBW infants is associated with a significant reduction in the risk of NEC and overall mortality. Additional studies are required to determine the optimal genus, species, and dose of probiotic.

Section snippets

Study selection

A comprehensive search of all published RCTs evaluating probiotics to prevent NEC in VLBW infants was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (1966–2014). Additional citations were searched, using the references of the articles retrieved from prior publications. The last search was conducted on July 28, 2014 and only articles written in English were considered. Keywords searched included combinations of “probiotics”, “Lactobacillus”, “

Demographic characteristics of the studies

A total of 20 RCTs were identified, involving a total of 5982 preterm VLBW infants (Table 2) [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39]. 2983 of these infants received enteric probiotic supplementation, and 2999 infants received a placebo. Among infants who received probiotics, 1058 received Lactobacillus, 289 received Bifidobacterium, 239 received Saccharomyces, and 1397 received a mixture of probiotics.

Effects of probiotics on NEC stage ≥ 2

Data on definite NEC (Bell stage ≥ 2) in both

Discussion

NEC continues to be a clinically challenging disease for VLBW infants and the neonatologist who cares for them. As one of the most common gastrointestinal emergencies in newborn infants, affecting as many as 12% of VLBW infants, NEC is a leading cause of morbidity and mortality among preterm infants [3]. Although infants of any gestational age can develop NEC, the risk of developing NEC is inversely proportional to birth-weight. Numerous factors have been shown to contribute to the risk of

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Probiotic microbes are increasingly being given to infants with the intent of reducing the risk and severity of conditions associated with intestinal dysbiosis, such as necrotizing enterocolitis and late-onset sepsis in preterm infants and colic and antibiotic-associated diarrhea in those born at term. There is also some evidence that bacterial colonization and its alterations can affect the timing of onset and severity of atopy and asthma in children. Despite extensive and increasing evidence to support the use of probiotics, the decision of using live organisms in infants evokes some hesitation. There are also uncertainties regarding the timing of introduction and data for selection of the most appropriate product, dose, and target population. Additionally, the availability of specific probiotic products and regulatory oversight varies by country, raising concerns regarding the safety and efficacy of specific probiotic products. In this chapter, we have summarized the current information on the types of probiotics, timing of colonization, effects, likely mechanism(s) of action, and evidence for and against the impact of probiotics in infants with mucosal inflammatory disorders.
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Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in the neonatal period. Although NEC is primarily a disease of the convalescent premature infant, full-term babies can also be affected. Risk factors include prematurity, the immature innate immune system, intestinal barrier abnormalities, and alterations in the gut microbiome. Despite significant advances in the understanding of the pathogenesis of NEC, only small steps toward prevention of the disorder have been made. NEC rarely affects patients who have not been fed. However, early introduction of maternal breast milk rather than formula feeds is protective. There is currently a lack of diagnostic tools to allow the practitioner identification of the patient at the highest risk, but a number of promising biomarkers are under investigation. The long-term outcome of patients who develop NEC is dependent on whether surgical treatment is required during the acute illness. Patients in need for bowel resection are at risk for short gut syndrome and failure to thrive as well as abnormal neurodevelopment. NEC is one of the most common underlying diagnoses in pediatric patients requiring intestinal transplantation. Improving our understanding of the pathogenesis and genetic predisposition of particular patients may allow us to develop sensitive and specific biomarkers for risk stratification as well as identify effective preventative measures. Currently, the early initiation and exclusive use of maternal breast milk rather than commercial formula seem to be the most effective way to prevent significant morbidity and mortality caused by this potential devastating gastrointestinal disease of the premature infant.
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View all citing articles on Scopus

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Review ArticleProbiotic administration can prevent necrotizing enterocolitis in preterm infants: A meta-analysis

Abstract

Purpose

Methods

Results

Conclusion

Section snippets

Study selection

Demographic characteristics of the studies

Effects of probiotics on NEC stage ≥ 2

Discussion

Semin Neonatol

Lancet

Pathophysiology

Early Hum Dev

Early Hum Dev

J Pediatr

Am J Clin Nutr

Am J Clin Nutr

Pediatr Neonatol

Lancet

J Pediatr

J Pediatr

Necrotizing enterocolitis: the mystery goes on

Neonatology

Mortality of necrotizing enterocolitis expressed by birth weight categories

J Pediatr Surg

Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis

Pediatrics

Neurodevelopment of extremely preterm infants who had necrotizing enterocolitis with or without late bacteremia

J Pediatr

Sonographic and radiographic imaging features of the neonate with necrotizing enterocolitis: correlating findings with outcomes

Pediatr Radiol

Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging

Ann Surg

Investigation of the early intestinal microflora in premature infants with/without necrotizing enterocolitis using two different methods

Pediatr Res

Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method

Pediatrics

Early trophic feeding for very low birth weight infants

Cochrane Database Syst Rev

Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants

Cochrane Database Syst Rev

An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products

J Pediatr

Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants

Pediatrics

Inhibitors of gastric acid secretion drugs increase neonatal morbidity and mortality

J Matern Fetal Neonatal Med

Probiotics and prebiotics for the prevention of necrotizing enterocolitis

Curr Infect Dis Rep

A meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates

Braz J Med Biol Res

Probiotics for prevention of necrotizing enterocolitis in preterm infants

Cochrane Database Syst Rev

Review Article
Probiotic administration can prevent necrotizing enterocolitis in preterm infants: A meta-analysis