Prophylactic Probiotic Supplementation for Preterm Neonates—A Systematic Review and Meta-Analysis of Nonrandomized Studies

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 co...

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Published in:Advances in nutrition (Bethesda, Md.) Md.), 2021-07, Vol.12 (4), p.1411-1423
Main Authors: Deshmukh, Mangesh, Patole, Sanjay
Format: Article
Language:English
Subjects:
enterocolitis
Enterocolitis, Necrotizing - prevention & control
Humans
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases
low birth weight
meta-analysis
mortality
necrotizing enterocolitis
neonates
nutrition
outcomes
pregnancy
preterm infant
Probiotics
Review
risk reduction
Sepsis - prevention & control
systematic review
very low birth weight
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description 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 (
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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 (&lt;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 &lt;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 &lt;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. 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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 &lt;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 &lt;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. 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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 (&lt;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 &lt;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 &lt;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. 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source Oxford Journals Online; PubMed Central
subjects enterocolitis
Enterocolitis, Necrotizing - prevention & control
Humans
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases
low birth weight
meta-analysis
mortality
necrotizing enterocolitis
neonates
nutrition
outcomes
pregnancy
preterm infant
Probiotics
Review
risk reduction
Sepsis - prevention & control
systematic review
very low birth weight
title Prophylactic Probiotic Supplementation for Preterm Neonates—A Systematic Review and Meta-Analysis of Nonrandomized Studies
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