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Published on: January 27, 2019
Prophylactic Probiotic Supplementation for Preterm Neonates-A Systematic Review and Meta-Analysis of Nonrandomized
Mangesh Deshmukh1,2, Sanjay Patole3,4
1Department of Neonatology, Fiona Stanley Hospital, Perth, Western Australia.
Insights
Routine probiotic supplementation significantly reduces necrotizing enterocolitis (NEC), late onset sepsis (LOS), and mortality in preterm neonates. Multistrain probiotics showed greater efficacy, with moderate to low evidence supporting these findings.
Area of Science:
- Neonatal Medicine
- Gastroenterology
- Microbiology
Background:
- Randomized controlled trials (RCTs) indicate probiotics reduce risks of necrotizing enterocolitis (NEC), late onset sepsis (LOS), all-cause mortality, and feeding intolerance in preterm neonates.
- Observational data is crucial for confirming probiotic efficacy in clinical practice.
- Implementing routine probiotic supplementation (RPS) in preterm infants necessitates evaluating its impact on key neonatal outcomes.
Purpose of the Study:
- To systematically review non-RCTs and compare outcomes before and after the implementation of routine probiotic supplementation (RPS) in preterm neonates (<37 weeks gestation).
- To assess the association of RPS with necrotizing enterocolitis (NEC ≥ Stage II), late onset sepsis (LOS), and all-cause mortality.
- To evaluate the impact of RPS on extremely low birth weight (ELBW) neonates and compare the efficacy of single-strain versus multistrain probiotics.
Main Methods:
- Systematic review of non-randomized controlled trials (non-RCTs) using Cochrane methodology, searching databases like PubMed, CINAHL, Embase, Cochrane Central, and Google Scholar (May 2020).
- Meta-analysis conducted using a random effects model, with effect size measured by Odds Ratio (OR) and 95% Confidence Interval (CI).
- Level of Evidence (LOE) assessed using GRADE guidelines; heterogeneity evaluated using chi-squared test and I² statistic.
Main Results:
- Thirty good-quality non-RCTs (n=77,018) indicated RPS significantly reduced NEC ≥ Stage II (OR: 0.60; 95% CI: 0.50-0.73; LOE: Moderate).
- RPS was associated with significant reductions in LOS (OR: 0.85; 95% CI: 0.74-0.97; LOE: Low) and all-cause mortality (OR: 0.77; 95% CI: 0.68-0.88; LOE: Low).
- In ELBW neonates, RPS significantly reduced NEC ≥ Stage II (4.5% vs 7.9%), but no differences were observed in LOS or mortality. Multistrain probiotics were more effective than single strains; 3 nonfatal cases of probiotic sepsis were reported.
Conclusions:
- Moderate- to low-quality evidence suggests RPS significantly reduces NEC ≥ Stage II, LOS, and all-cause mortality in preterm neonates (<37 weeks gestation).
- RPS is also associated with a significant reduction in NEC ≥ Stage II among ELBW neonates.
- Multistrain probiotic supplementation appears more effective than single-strain regimens for improving neonatal outcomes.
Abstract:
Systematic review and meta-analyses of randomized controlled trials (RCTs) show that probiotics reduce the risk of necrotizing enterocolitis (NEC ≥ Stage 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 weeks 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. A 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. The level of evidence (LOE) was summarized using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) guidelines. Primary outcomes were NEC ≥ Stage II, LOS, and all-cause mortality. Secondary outcomes included probiotic sepsis. Thirty good-quality non-RCTs (n = 77,018) from 18 countries were included. The meta-analysis showed RPS was associated with significantly reduced: 1) NEC ≥ Stage II (30 studies, n = 77,018; OR: 0.60; 95% CI: 0.50, 0.73; P <0.00001, I2: 65%; LOE: Moderate), 2) LOS: (21 studies, n = 65,858; OR: 0.85; 95% CI: 0.74, 0.97; P = 0.02, I2: 74%; LOE: Low), and 3) all-cause mortality (27 non-RCTs, n = 70,977; OR: 0.77; 95% CI: 0.68, 0.88; P = 0.0001, I2: 49%; LOE: Low). Subgroups: 1) extremely low birth weight (ELBW: birth weight <1000 g) neonates: RPS was associated with significantly reduced NEC ≥ Stage II (4.5% compared 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 ≥ Stage II, LOS, and all-cause mortality in neonates <37 weeks of gestation and NEC ≥ Stage II in ELBW neonates.
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