Mother's Own Milk and Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

Villamor-Martínez, Eduardo; Pierro, Maria; Cavallaro, Giacomo; Mosca, Fabio; Villamor, Eduardo

doi:10.3389/fped.2019.00224

Cited by 54 publications

(50 citation statements)

References 59 publications

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“…Human milk feeding decreases the risk of NEC (28). Meta-analyses suggest a benefit in feeding mother's own milk (29) and pasteurized donor human milk (30) in the prevention of BPD. In organoids derived from the terminal ileum of mouse pups, human milk exosomes have been shown to attenuate LPS induced activation of TLR4 (31).…”

Section: Discussionmentioning

confidence: 99%

Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis

et al. 2020

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Background: In extremely premature infants, postnatal growth restriction (PNGR) is common and increases the risk of developing bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Mechanisms by which poor nutrition impacts lung development are unknown, but alterations in the gut microbiota appear to play a role. In a rodent model, PNGR plus hyperoxia causes BPD and PH and increases intestinal Enterobacteriaceae, Gram-negative organisms that stimulate Toll-like receptor 4 (TLR4). We hypothesized that intestinal dysbiosis activates intestinal TLR4 triggering systemic inflammation which impacts lung development. Methods: Rat pups were assigned to litters of 17 (PNGR) or 10 (normal growth) at birth and exposed to room air or 75% oxygen for 14 days. Half of the pups were treated with the TLR4 inhibitor TAK-242 from birth or beginning at day 3. After 14 days, pulmonary arterial pressure was evaluated by echocardiography and hearts were examined for right ventricular hypertrophy (RVH). Lungs and serum samples were analyzed by western blotting and immunohistochemistry. Results: Postnatal growth restriction + hyperoxia increased pulmonary arterial pressure and RVH with trends toward increased plasma IL1β and decreased IκBα, the inhibitor of NFκB, in lung tissue. Treatment with the TLR4 inhibitor attenuated PH and inflammation. Conclusion: Postnatal growth restriction induces an increase in intestinal Enterobacteriaceae leading to PH. Activation of the TLR4 pathway is a promising mechanism by which intestinal dysbiosis impacts the developing lung.

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Section: Discussionmentioning

confidence: 99%

Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis

et al. 2020

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“…Breast milk supply increases microbial diversity and enhances immunologic properties while antibiotic therapy is a major cause of microbial dysbiosis. In the context of lung development and lung injury, meta-analyses of breast milk supply display a relevant reduction in the incidence of BPD [ 21 , 22 ]. Furthermore, recent studies demonstrated that antibiotic therapy per se and its prolonged use was associated with an increased risk for BPD [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Bacterial Colonization within the First Six Weeks of Life and Pulmonary Outcome in Preterm Infants <1000 g

Lauer

Behnke

Oehmke

et al. 2020

JCM

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Bronchopulmonary dysplasia (BPD) is a multifactorial disease mainly provoked by pre- and postnatal infections, mechanical ventilation, and oxygen toxicity. In severely affected premature infants requiring mechanical ventilation, association of bacterial colonization of the lung and BPD was recently disclosed. To analyze the impact of bacterial colonization of the upper airway and gastrointestinal tract on moderate/severe BPD, we retrospectively analyzed nasopharyngeal and anal swabs taken weekly during the first 6 weeks of life at a single center in n = 102 preterm infants <1000 g. Colonization mostly occurred between weeks 2 and 6 and displayed a high diversity requiring categorization. Analyses of deviance considering all relevant confounders revealed statistical significance solely for upper airway colonization with bacteria with pathogenic potential and moderate/severe BPD (p = 0.0043) while no link could be established to the Gram response or the gastrointestinal tract. Our data highlight that specific colonization of the upper airway poses a risk to the immature lung. These data are not surprising taking into account the tremendous impact of microbial axes on health and disease across ages. We suggest that studies on upper airway colonization using predefined categories represent a feasible approach to investigate the impact on the pulmonary outcome in ventilated and non-ventilated preterm infants.

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“…Until recently, data suggesting a bene cial impact of maternal milk feeding on BPD were limited. Some investigators had concluded that maternal milk decreased incidence of BPD [7,[11][12][13][14], but others had not thought it useful [15]. Thus we can make two postulations: either high-volume maternal milk feeding daily directly impacts BPD or BPD has an obvious effect on volume maternal milk feeding .…”

Section: Discussionmentioning

confidence: 99%

The Dose Effect of Maternal Milk on Bronchopulmonary Dysplasia in Very Low Birth Weight Infants

Zhang

et al. 2020

Preprint

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Background Human breast milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, limited multicenter research has been reported on the association between the dose of maternal milk and BPD in China. In this study, we aimed to evaluate the dose effects of maternal milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. Methods We conducted a retrospective cohort study of preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. Multivariate analysis was performed to compare the effect on neonatal outcomes of daily graded doses of maternal milk throughout the first 4 weeks of life versus a reference group receiving no maternal milk. Models were adjusted for potential confounding variables. Results Of 964 included infants, 279 (28.9%) received exclusive preterm formula, another 128 (13.3%) received 1–24 ml/kg, 139 (14.4%) received 25–49 ml/kg, and 418 (43.4%) received ≥ 50 ml/kg maternal milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of maternal milk daily (≥ 50 ml/kg) had lower incidences of BPD (27.5% in ≥ 50 ml/kg maternal milk vs. 40.1% in formula), moderate and severe BPD (8.9% in ≥ 50 ml/kg maternal milk vs. 16.1% in formula), necrotizing enterocolitis (NEC; 3.8% in ≥ 50 ml/kg maternal milk vs. 10.8% in formula), late-onset sepsis (LOS; 9.3% in ≥ 50 ml/kg maternal milk vs. 19.7% in formula), and extrauterine growth retardation (EUGR; 38.5% in ≥ 50 ml/kg maternal milk vs. 57.6% in formula). Logistic regression indicated that those receiving ≥ 50 ml/kg/day maternal milk had lower odds of BPD (adjusted odds ratio [AOR] 0.453; 95% confidence interval [CI]: 0.309, 0.666), moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979). Conclusions A daily threshold amount of ≥ 50 ml/kg maternal milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. Trial registration: ClinicalTrials.gov Identifier: NCT03453502

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Mother's Own Milk and Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

Cited by 54 publications

References 59 publications

Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis

Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis

Bacterial Colonization within the First Six Weeks of Life and Pulmonary Outcome in Preterm Infants <1000 g

The Dose Effect of Maternal Milk on Bronchopulmonary Dysplasia in Very Low Birth Weight Infants

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