Erythropoietin treatment is associated with a reduction in moderate to severe bronchopulmonary dysplasia in preterm infants. A regional retrospective study

Bui, Kevin; Kim, Romina; Abbasi, Afshan; Nguyen, Marielle; Villosis, Maria Fe; Chen, Qiaoling

doi:10.1016/j.earlhumdev.2019.104831

Cited by 9 publications

(8 citation statements)

References 33 publications

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“…rhEPO was originally used at a low dose to prevent anemia in preterm infants, and it is now widely accepted as a routine application for all preterm infants as a substitute for blood transfusion [ 49 – 51 ]. Recent studies showed that rhEPO has multiple beneficial effects on preterm infants [ 18 , 52 , 53 ]. Our previous study with repeated administration of as low as 500 U/kg of rhEPO for 2 weeks showed not only neuroprotection, but also a reduced incidence of NEC and sepsis, although the mechanisms behind this are not fully understood [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

et al. 2020

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Background: Necrotizing enterocolitis (NEC) is one of the most severe complications in very preterm infants, but there are currently no accepted methods to prevent NEC. Studies have shown that erythropoietin (EPO) has the potential to prevent NEC or improve outcomes of preterm NEC. This study aimed to determine whether recombinant human EPO (rhEPO) could protect against NEC in very preterm infants. Methods: The study was a prospective randomized clinical trial performed among four NICU centers. A total of 1327 preterm infants with gestational age ≤ 32 weeks were admitted to the centers, and 42 infants were excluded leaving 1285 eligible infants to be randomized to the rhEPO or control group. Infants in the rhEPO group were given 500 IU/ kg rhEPO intravenously every other day for 2 weeks, while the control group was given the same volume of saline. The primary outcome was the incidence of NEC in very preterm infants at 36 weeks of corrected gestational age. Results: A total of 1285 infants were analyzed at 36 weeks of corrected age for the incidence of NEC. rhEPO treatment significantly decreased the incidence of NEC (stage I, II and III) (12.0% vs. 17.1%, p = 0.010), especially confirmed NEC (stage II and III) (3.0% vs. 5.4%, p = 0.027). Meanwhile, rhEPO treatment significantly reduced the number of red blood cells transfusion in the confirmed NEC cases (1.2 ± 0.4 vs. 2.7 ± 1.0, p = 0.004). Subgroup analyses showed that rhEPO treatment significantly decreased the incidence of confirmed NEC at gestational age < 28 weeks (p = 0.019), and the incidence of all stages NEC in preterm infants with hemoglobin < 90 g/l (p = 0.000) and 5 min Apgar score > 5 (p = 0.028). Conclusion: Repeated low-dose rhEPO treatment is beneficial against NEC in very preterm infants. Trial registration The protocol was registered retrospectively at ClinicalTrials.gov (NCT03919500) on April 18, 2019. https ://clini caltr ials.gov/ct2/show/NCT03 91950 0

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Section: Discussionmentioning

confidence: 99%

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

et al. 2020

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“…Therefore, the ideal dose of rEPO to reduce lung injury, if any, is not known and requires further study. The retrospective study mentioned above, 54 demonstrated that the age at initiation of rEPO influenced the incidence of BPD outcome with the lowest BPD rate in infants who received rEPO before 2 weeks of age, and the odds of having moderate to severe BPD increased 20% with each week delay of rEPO treatment initiation. Altogether, these data suggest rEPO administration showed benefit only if rEPO was given in optimal dose, initiation time, and inflammatory status of infants' lungs.…”

Section: Discussionmentioning

confidence: 96%

“…Besides the effect on transfusion, NEC and sepsis prevention, there are some other mechanisms of action ascribed to rEPO which may directly counteract the disruption of lung development prompting BPD, namely rEPO (1) stimulates vasculogenesis by enhancing endothelial progenitor cells mobilization from bone marrow, 48 (2) promotes angiogenesis and alveolar development by activating on mature endothelial cells directly, 49–51 (3) decreases lung fibrosis during oxygen exposure through suppression of epithelial to mesenchymal transition (EMT) 52,53 . Two observational retrospective studies reported an association between a low‐dose strategy rEPO administration and a reduction of BPD 54,55 . In addition, recent studies shown that administration of bone marrow MSCs in combination with rEPO, which could suppress EMT process by inhibiting the transforming growth factor‐β1 signaling pathway, significantly attenuated hyperoxia‐induced lung damage and maybe a promising therapeutic strategy 53,56,57 .…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta‐analysis

Zhang

Hao

et al. 2022

Pediatric Pulmonology

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Background: Recombinant erythropoietin (rEPO) has erythropoiesis and anti-inflammatory properties that might help reduce lung injury in preterm infants.Objective: To conduct a systematic review and meta-analysis to evaluate the possible role of rEPO in altering the risk of bronchopulmonary dysplasia (BPD).Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched to identify randomized controlled trials (RCTs) that evaluated the effects of rEPO for the prevention of BPD in preterm infants.Results: Fourteen studies (3199 infants) were included. Our results could not demonstrate a significant effect of rEPO on the incidence of BPD36 (risk ratio[RR]: 0.97, 95% confidence interval [CI]: 0.87-1.09, p = 0.63, I 2 = 0, 12 RCTs, high-quality evidence), BPD28 (RR: 1.28, 95% CI: 0.91-1.79, p = 0.15, I 2 = 17%, three RCTs, low-quality evidence) and oxygen dependence days. The test for subgroup analysis by administration route of rEPO showed similar outcomes above. Some of the included trials reported a significant effect of intravenous rEPO on reduction of sepsis (RR: 0.82, 95% CI: 0.70-0.96, p = 0.01, I 2 = 0, high-quality evidence) and any stage necrotizing enterocolitis (NEC) (RR: 0.75, 95% CI: 0.59-0.94, p = 0.01, I 2 = 0, moderate-quality evidence). The incidence of mortality and stage II or higher NEC was comparable in rEPO and control infants. Conclusion:Our results suggest that rEPO does not affect the risk of developing BPD in preterm infants. Adequately powered RCTs are required to further confirm these findings.

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“… 54 , 55 Epoetin efficacy has been reported in studies but not in large randomized clinical trials or meta-analyses. 56 , 57 , 58 , 59 Fluid restriction is included in our care practices, but its value in preventing or treating BPD has not been well established. 60 , 61 Interventions we minimized that may increase BPD were treatment of PDA 62 , 63 , 64 and antibiotic use.…”

Section: Discussionmentioning

confidence: 99%

Rates of Bronchopulmonary Dysplasia Following Implementation of a Novel Prevention Bundle

et al. 2021

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IMPORTANCE Bronchopulmonary dysplasia (BPD) rates in the United States remain high and have changed little in the last decade. OBJECTIVE To develop a consistent BPD prevention bundle in a systematic approach to decrease BPD. DESIGN, SETTING, AND PARTICIPANTS This quality improvement study included 484 infants with birth weights from 501 to 1500 g admitted to a level 3 neonatal intensive care unit in the Kaiser Permanente Southern California system from 2009 through 2019. The study period was divided into 3 periods: 1, baseline (2009); 2, initial changes based on ongoing cycles of Plan-Do-Study-Act (2010-2014); and 3, full implementation of successive Plan-Do-Study-Act results (2015-2019).INTERVENTIONS A BPD prevention system of care bundle evolved with a shared mental model that BPD is avoidable. MAIN OUTCOMES AND MEASURESThe primary outcome was BPD in infants with less than 33 weeks' gestational age (hereafter referred to as BPD <33). Other measures included adjusted BPD <33, BPD severity grade, and adjusted median postmenstrual age (PMA) at hospital discharge.Balancing measures were adjusted mortality and adjusted mortality or specified morbidities. RESULTSThe study population included 484 infants with a mean (SD) birth weight of 1070 (277) g; a mean (SD) gestational age of 28.6 (2.9) weeks; 252 female infants (52.1%); and 61 Black infants (12.6%). During the 3 study periods, BPD <33 decreased from 9 of 29 patients (31.0%) to 3 of 184 patients (1.6%) (P < .001 for trend); special cause variation was observed. The standardized morbidity ratio for the adjusted BPD <33 decreased from 1.2 (95% CI, 0.7-1.9) in 2009 to 0.4 (95% CI, 0.2-0.8) in 2019. The rates of combined grades 1, 2, and 3 BPD decreased from 7 of 29 patients (24.1%) to 17 of 183 patients (9.3%) (P < .008 for trend). Grade 2 BPD rates decreased from 3 of 29 patients (10.3%) to 5 of 183 patients (2.7%) (P = .02 for trend). Adjusted median PMA at home discharge decreased by 2 weeks, from 38.2 (95% CI, 37.3-39.1) weeks in 2009 to 36.8 (95% CI, 36.6-37.1) weeks during the last 3 years (2017-2019) of the full implementation period. Adjusted mortality was unchanged, whereas adjusted mortality or specified morbidities decreased significantly. CONCLUSIONS AND RELEVANCEA sustained low rate of BPD was observed in infants after the implementation of a detailed BPD system of care.

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Erythropoietin treatment is associated with a reduction in moderate to severe bronchopulmonary dysplasia in preterm infants. A regional retrospective study

Cited by 9 publications

References 33 publications

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta‐analysis

Rates of Bronchopulmonary Dysplasia Following Implementation of a Novel Prevention Bundle

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