Comparative effectiveness of prophylactic therapies for necrotizing enterocolitis in preterm infants: Protocol for a network meta-analysis of randomized trials

Sadeghirad, Behnam; Flórez, Iván D.; Chang, Yaping; Forutan, Farid; Zeraatkar, Dena; Shahid, Shaneela; Bała, Małgorzata M; Beyene, Joseph; Offringa, Martin; Adams‐Webber, Thomasin; Sherman, Philip M.; El-Gouhary, Enas; Guyatt, Gordon; Johnston, Bradley C.

doi:10.4103/ijpvm.ijpvm_328_17

Cited by 5 publications

(1 citation statement)

References 49 publications

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“…Some advanced cases can involve extensive intestinal necrosis, and the complications after surgery can be fatal. Most treatment strategies for the disease are achieved by the pharmacological and clinical support of vital signs and/or surgery [22][23][24]. The choice of treatment depends on the stage of NEC.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota and Immune System in Necrotizing Enterocolitis and Related Sepsis

Jirillo,

Topi,

Charitos

et al. 2024

Gastrointestinal Disorders

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A severe condition of sepsis can be a complication of necrotizing enterocolitis (NEC), which can occur in premature infants and becomes a medical challenge in the neonatal intensive care unit (NICU). It is a multifactorial intestinal disease (can affect both the small and large intestine) that can lead to ischemia of the intestinal tissues that evolves into acute organ necrosis. One of these factors is that different types of nutrition can influence the onset or the progression of the disease. Cow-milk-based infant formulas have been shown to cause it in premature infants more frequently than human milk. Recently, nutrition has been shown to be beneficial after surgery. Several issues still under study, such as the pathogenesis and the insufficient and often difficult therapeutic approach, as well as the lack of a common and effective prevention strategy, make this disease an enigma in daily clinical practice. Recent studies outlined the emerging role of the host immune system and resident gut microbiota, showing their close connection in NEC pathophysiology. In its initial stages, broad-spectrum antibiotics, bowel rest, and breastfeeding are currently used, as well as probiotics to help the development of the intestinal microbiota and its eubiosis. This paper aims to present the current knowledge and potential fields of research in NEC pathophysiology and therapeutic assessment.

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Section: Introductionmentioning

confidence: 99%

Gut Microbiota and Immune System in Necrotizing Enterocolitis and Related Sepsis

Jirillo,

Topi,

Charitos

et al. 2024

Gastrointestinal Disorders

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Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants

Wang,

Florez,

Morgan

et al. 2023

JAMA Pediatr

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ImportanceModulation of intestinal microbiome by administering probiotics, prebiotics, or both may prevent morbidity and mortality in premature infants.ObjectiveTo assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials.Data SourcesMEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023.Study SelectionEligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants.Data Extraction and SynthesisA frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach.Main Outcomes and MeasuresAll-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization.ResultsA total of 106 trials involving 25 840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], −1.7%; 95% CI, −2.4% to −0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, −3.7%; 95% CI, −4.1% to −2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, −5.1%; 95% CI, −5.6% to −3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, −10.7%; 95% CI, −13.7% to −3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, −10.0%; 95% CI, −13.9% to −5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, −14.1%; 95% CI, −18.3% to −8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, −10.0%; 95% CI, −12.6% to −7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, −1.94 days; 95% CI, −2.96 to −0.92) and multistrain probiotics (MD, −2.03 days; 95% CI, −3.04 to −1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, −3.31 days; 95% CI, −5.05 to −1.58; and MD, −2.20 days; 95% CI, −4.08 to −0.31, respectively).Conclusions and RelevanceIn this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.

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Amino acids for the prevention of mortality and morbidity in preterm infants: a systematic review and network meta-analysis

Wang

Sadeghirad

Zeratkaar

et al. 2022

Sci Rep

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To determine the effectiveness and safety of amino acids in preventing the mortality and morbidity among preterm infants. We conducted a systematic review and network meta-analysis. We searched MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, Cochrane, and Google Scholar, and grey literature, from databases inception to January 2021. We included randomized trials that evaluated any amino acids on preterm or low-birth weight infants. We performed frequentist pairwise and network meta-analyses and used the GRADE methodology to assess the certainty of the evidence and provide a summary of the results.We included 18 trials (3702 infants). Low certainty evidence showed that there seems to be no benefit for arginine, glutamine, or N-acetylcysteine in reducing all-cause mortality. Oral arginine likely results in reduction of necrotizin enterocolitis (NEC) stage ≥ II (OR 0.48; 95% CI 0.26–0.90; moderate certainty). Oral glutamine may reduce the likelihood of developing late-onset sepsis (LOS) compared to placebo (OR 0.62; 95% CI 0.47–0.82; low certainty); and likely reduces time to reach full enteral feeding (MD = − 2.63 days; 95% CI − 4.99 to − 0.27; moderate certainty). Amino acids may have no effect on mortality. Oral arginine may reduce severe NEC, and oral glutamine may reduce LOS and the time to reach full feeding.Systematic review registration: PROSPERO registration number: CRD4201603873.

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Comparative effectiveness of prophylactic therapies for necrotizing enterocolitis in preterm infants: Protocol for a network meta-analysis of randomized trials

Cited by 5 publications

References 49 publications

Gut Microbiota and Immune System in Necrotizing Enterocolitis and Related Sepsis

Gut Microbiota and Immune System in Necrotizing Enterocolitis and Related Sepsis

Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants

Amino acids for the prevention of mortality and morbidity in preterm infants: a systematic review and network meta-analysis

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