Probiotic Supplementation in Preterm Infants Does Not Affect the Risk of Bronchopulmonary Dysplasia: A Meta-Analysis of Randomized Controlled Trials

Villamor-Martínez, Eduardo; Pierro, Maria; Cavallaro, Giacomo; Mosca, Fabio; Kramer, Boris W.; Villamor, Eduardo

doi:10.3390/nu9111197

Cited by 37 publications

(30 citation statements)

References 88 publications

(189 reference statements)

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“…A randomized controlled trial of probiotics in children with asthma reported a reduction in asthma severity in probiotic exposed children compared to placebo and Lactobacillus-based probiotics may also reduce nosocomial infections in children (44,46). Previous studies using enteral probiotics to reduce either necrotizing enterocolitis (NEC), a devastating gastrointestinal disease of prematurity, or late onset sepsis have not demonstrated a reduction in BPD (47). However, the influence of enteral probiotics on the airway microbiome has not been evaluated and randomized trials of aerosolized probiotics in preterm infants have never been conducted.…”

Section: Probiotics: a Plausible Therapeutic Option For Bpd?mentioning

confidence: 99%

Predicting BPD: Lessons Learned From the Airway Microbiome of Preterm Infants

Gentle

Lal

2020

Front. Pediatr.

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Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity with an operational definition, various different clinical phenotypes, and a complex, multifactorial etiology. Newer unbiased systems biology approaches have identified various "omic" factors associated with the pathogenesis and prediction of BPD. Recent microbi "omic" studies have discovered that airways of newborns harbor a low biomass but distinct microbiome signature as early as at the time of birth. This early airway microbiome may serve to prime the host immune system and may play a role in modulating the infant's future susceptibility to severe BPD development. Temporal changes are observed in airway microbiome of preterm infants from birth to the diagnosis of BPD, with an overall decrease in bacterial diversity, and development of a relative dysbiosis marked by increased Gammaproteobacteria and decreased Lactobacilli abundance. This review will summarize previous investigations of the airway microbiome in preterm infants, appraise the utility of using the airway microbiome to predict BPD development, discuss possible molecular mechanisms involved, and speculate on future microbiome-mediated therapeutics for BPD.

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Section: Probiotics: a Plausible Therapeutic Option For Bpd?mentioning

confidence: 99%

Predicting BPD: Lessons Learned From the Airway Microbiome of Preterm Infants

Gentle

Lal

2020

Front. Pediatr.

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“…Fourth, there was substantial heterogeneity among the studies in population, timing of initiation and duration of the intervention. An additional limitation, inherent to any meta-analysis on BPD, is the heterogeneity of the definition of the condition [46][47][48][49]. Finally, many studies were observational, which potentially reduced the reliability of the results.…”

Section: Discussionmentioning

confidence: 99%

Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

Villamor-Martínez

Pierro

Cavallaro

et al. 2018

Preprint

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Bronchopulmonary dysplasia (BPD) is the most common complication after preterm birth. Pasteurized donor human milk (DHM) has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF) if mother’s own milk (MOM) is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCT’s could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (3 studies, risk ratio [RR] 0.89, 95% confidence interval [CI] 0.60–1.32). However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67–0.90). An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (3 studies, RR 0.80, 95% CI 0.68–0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (2 studies, RR 0.77, 95% CI 0.62–0.96). In conclusion, our data suggest that DHM protects against BPD in very preterm infants, but pasteurization of human milk reduces the benefit.

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“…Even a large RCT that did not show benefits of probiotic supplementation acknowledged that short‐term safety of probiotics was good in preterm infants (Costeloe et al ., ). Recent meta‐analyses have shown that probiotics do not increase or decrease the risk of intraventricular haemorrhage, chronic lung disease, retinopathy of prematurity and neurodevelopmental outcomes in preterm non‐surgical infants (Cavallaro et al ., ; Villamor‐Martinez et al ., ; Upadhyay et al ., ).These findings provide reassurance regarding medium‐term safety of probiotics in preterm infants. However, there are few case reports of sepsis due to probiotic organisms (Ohishi et al ., ; Vallabhaneni et al ., ; Brecht et al ., ).…”

Section: Safety Of Probioticsmentioning

confidence: 99%

Probiotic research in neonates with congenital gastrointestinal surgical conditions – Now is the time

Rao

Patole

2018

Microbial Biotechnology

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Summary Neonates with congenital gastrointestinal surgical conditions ( CGISC ) receive parenteral nutrition, get exposed to multiple courses of antibiotics, undergo invasive procedures, and are nursed in intensive care units. They do not receive early enteral feeding and have limited opportunities for skin to skin contact with their mothers. Many of these infants receive gastric acid suppression therapies. All these factors increase the risk of gut dysbiosis in these infants. Gut dysbiosis is known to be associated with increased risk of infections and other morbidities in ICU patients. Experimental studies have shown that probiotics inhibit gut colonization with pathogenic bacteria, enhance gut barrier function, facilitate colonization with healthy commensals, protect from enteropathogenic infection through production of acetate, reduce antimicrobial resistance, enhance innate immunity, and increase the maturation of the enteric nervous system and promote gut peristalsis. Through these mechanisms, probiotics have the potential to decrease the risk of sepsis and inflammation, improve feed tolerance and minimise cholestasis in neonates with CGISC . Among preterm non‐surgical infants, evidence from more than 35 RCT s and multiple observational studies have shown probiotics to be safe and beneficial. A RCT in neonates (N=24) with gastroschisis found that probiotic supplementation partially attenuated gut dysbiosis. Two ongoing RCT s (total N=168) in neonates with gastrointestinal surgical conditions are expected to provide feasibility data to enable the conduct of large RCT s. Rigorous quality assurance of the probiotic product, ongoing microbial surveillance and clinical vigilance are warranted while conducting such RCT s.

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Probiotic Supplementation in Preterm Infants Does Not Affect the Risk of Bronchopulmonary Dysplasia: A Meta-Analysis of Randomized Controlled Trials

Cited by 37 publications

References 88 publications

Predicting BPD: Lessons Learned From the Airway Microbiome of Preterm Infants

Predicting BPD: Lessons Learned From the Airway Microbiome of Preterm Infants

Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

Probiotic research in neonates with congenital gastrointestinal surgical conditions – Now is the time

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