Abstract
["Systematic review and meta-analyses of randomized controlled trials (RCTs) show that probiotics reduce the risk of necrotizing enterocolitis (NEC\u00a0\u2265\u00a0Stage II), late onset sepsis (LOS), all-cause mortality, and feeding intolerance in preterm neonates. Data from observational studies is important to confirm probiotic effects in clinical practice. We aimed to compare outcomes before and after implementing routine probiotic supplementation (RPS) in preterm neonates (<37\u00a0weeks of gestation) by performing a systematic review of non-RCTs using Cochrane methodology. Databases including PubMed, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Cochrane Central library, and Google Scholar were searched in May 2020.\u00a0A meta-analysis was performed using a random effects model. Categorical measure of effect size was expressed as OR and 95% CI. Statistical heterogeneity was assessed by the chi-squared test, I2 statistic.\u00a0The level of evidence (LOE) was summarized using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) guidelines. Primary outcomes were NEC\u00a0\u2265\u00a0Stage II, LOS, and all-cause mortality. Secondary outcomes included probiotic sepsis. Thirty good-quality non-RCTs (n\u00a0=\u00a077,018) from 18 countries were included. The meta-analysis showed RPS was associated with significantly reduced: 1) NEC\u00a0\u2265\u00a0Stage II (30 studies, n\u00a0=\u00a077,018; OR: 0.60; 95% CI: 0.50, 0.73; P\u00a0<0.00001, I2: 65%; LOE: Moderate), 2) LOS: (21 studies, n\u00a0=\u00a065,858; OR: 0.85; 95% CI: 0.74, 0.97; P\u00a0=\u00a00.02, I2: 74%; LOE: Low), and 3) all-cause mortality (27 non-RCTs, n\u00a0=\u00a070,977; OR: 0.77; 95% CI: 0.68, 0.88; P\u00a0=\u00a00.0001, I2: 49%; LOE: Low). Subgroups: 1) extremely low birth weight (ELBW: birth weight\u00a0<1000 g)\u00a0neonates: RPS was associated with significantly reduced NEC\u00a0\u2265\u00a0Stage II (4.5%\u00a0compared with 7.9%). However, there was no difference in LOS and mortality. 2) Multistrain RPS was more effective than single strain. One study reported 3 nonfatal cases of probiotic sepsis. In summary, moderate- to low-quality evidence indicates that RPS was associated with significantly reduced NEC\u00a0\u2265\u00a0Stage II, LOS, and all-cause mortality in neonates <37\u00a0weeks of gestation and NEC\u00a0\u2265\u00a0Stage II in ELBW neonates.",{"copyright":"\u00a9 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition."}]
