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

Abstract

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

Iatrogenic vs. Spontaneous Preterm Birth: A Retrospective Study of Neonatal Outcome Among Very Preterm Infants

“…GA was established based on first-trimester ultrasound estimations in the majority of patients and in a few patients by the last menstrual bleeding before pregnancy. The following parameters were included in the analysis: small for gestational age (SGA, defined as birth weight < 10th percentile for gestational age), asphyxia ( 14 ), bronchopulmonary dysplasia (BPD, defined simply by considering the need for oxygen at 28 days after birth) ( 15 ), pneumonia, anemia ( 16 ), patent ductus arteriosus ( 17 ), persistent pulmonary hypertension ( 18 ), coagulopathy ( 19 ), retinopathy of prematurity ( 20 ), necrotizing enterocolitis (NEC, Bell's stage ≥ II) ( 16 ), intraventricular hemorrhage (IVH, diagnosed by intracranial ultrasound and graded from 1 to 4 on the Papile scale) ( 21 ), periventricular leukomalacia (PVL, diagnosed by intracranial ultrasound or brain magnetic resonance imaging) ( 22 ), pathoglycemia (blood sugar < 2.2 mmol/L or > 7 mmol/L), and neonatal death (died before 28 days of life).…”

“…GA was established based on first-trimester ultrasound estimations in the majority of patients and in a few patients by the last menstrual bleeding before pregnancy. The following parameters were included in the analysis: small for gestational age (SGA, defined as birth weight < 10th percentile for gestational age), asphyxia (14), bronchopulmonary dysplasia (BPD, defined simply by considering the need for oxygen at 28 days after birth) (15), pneumonia, anemia (16), patent ductus arteriosus (17), persistent pulmonary hypertension (18), coagulopathy (19), retinopathy of prematurity (20)…”

The association of severe anemia, red blood cell transfusion and necrotizing enterocolitis in neonates

“…In addition, Patel [17] performed a multicenter cohort study in 598 VLBW infants and found that severe anemia but not RBC transfusion was associated with an increased risk of NEC. Our previous clinical trial found that the improvement of severe anemia reduced the incidence of NEC in preterm infants, which also suggested the impact of anemia on the development of NEC [19]. A prospective cohort study showed that anemia was associated with intestinal injury [33].…”

“…Some studies highlighted that severe anemia, not the transfusion event, was associated with the risk of developing NEC [17,18]. Our previous study [19] indicated that erythropoietin treatment for severe anemia could decrease the incidence of NEC in preterm infants, which indirectly proves the association between severe anemia and NEC. Animal models suggested that anemia can induce intestinal inflammation and barrier disruption, and increase the risk for NEC [20,21].…”

Erythropoietin Improves Poor Outcomes in Preterm Infants with Intraventricular Hemorrhage

“…Baseline information were collected, including gestational age, birth weight, sex, delivery mode, Apgar score, mechanical ventilation, and maternal factors during the perinatal period. Complications during hospitalization such as retinopathy of prematurity (ROP) [ 31 ], necrotizing enterocolitis (NEC) [ 32 ], and bronchopulmonary dysplasia (BPD) [ 33 ] were recorded. Infants who developed rhEPO-related side effects, including large venous thrombus, polycythemia, or hypertension, were immediately taken off the rhEPO treatment and given emergency therapy.…”