Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns
Garcia MR, Comstock BA, Patel RM, Tolia VN, Josephson CD, Georgieff MK, Rao R, Monsell SE, Juul SE, Ahmad KA
Pediatric research. 2022
BACKGROUND The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.
Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients: A Randomized Clinical Trial
Spinella PC, Tucci M, Fergusson DA, Lacroix J, Hebert PC, Leteurtre S, Schechtman KB, Doctor A, Berg RA, Bockelmann T, et al
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Importance: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial. Objective: To determine if the transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children. Design, Setting, and Participants: The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15568 patients were screened, and 13308 were excluded. Interventions: Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group. Main Outcomes and Measures: The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death. Results: Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34). Conclusions and Relevance: Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells. Trial Registration: ClinicalTrials.gov Identifier: NCT01977547.
Critically ill paediatric patients between the ages of 3 days and 16 years, (n=1461).
Red blood cells stored </=y days (Fresh red blood cell group, (n=728).
Delivery of oldest compatible red cell units available (Standard-issue red blood cells, (n=733).
There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group.
Effects of red-cell storage duration on patients undergoing cardiac surgery
Steiner ME, Ness PM, Assmann SF, Triulzi DJ, Sloan SR, Delaney M, Granger S, Bennett-Guerrero E, Blajchman MA, Scavo V, et al
New England Journal of Medicine. 2015;372((15):):1419-29.
BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion.METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge.RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group.CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).
Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia
Josephson CD, Granger S, Assmann SF, Castillejo MI, Strauss RG, Slichter SJ, Steiner ME, Journeycake JM, Thornburg CD, Bussel J, et al
Age-group analyses were conducted of patients in the prophylactic platelet dose trial (PLADO), which evaluated the relation between platelet dose per transfusion and bleeding. Hospitalized patients with treatment-induced hypoproliferative thrombocytopenia were randomly assigned to 1 of 3 platelet doses: 1.1 × 10 (11), 2.2 × 10 (11), or 4.4 × 10 (11) platelets/m (2) per transfusion, given for morning counts of <= 10 000 platelets/µL. Daily hemostatic assessments were performed. The primary end point (percentage of patients who developed grade 2 or higher World Health Organization bleeding) was evaluated in 198 children (0-18 years) and 1044 adults. Although platelet dose did not predict bleeding for any age group, children overall had a significantly higher risk of grade 2 or higher bleeding than adults (86%, 88%, 77% vs 67% of patients aged 0-5 years, 6-12 years, 13-18 years, vs adults, respectively) and more days with grade 2 or higher bleeding (median, 3 days in each pediatric group vs 1 day in adults; P < .001). The effect of age on bleeding differed by disease treatment category and was most pronounced among autologous transplant recipients. Pediatric subjects were at higher risk of bleeding over a wide range of platelet counts, indicating that their excess bleeding risk may be because of factors other than platelet counts.
Dose of prophylactic platelet transfusions and prevention of hemorrhage
Slichter SJ, Kaufman RM, Assmann SF, McCullough J, Triulzi DJ, Strauss RG, Gernsheimer TB, Ness PM, Brecher ME, Josephson CD, et al
The New England Journal of Medicine. 2010;362((7):):600-13.
BACKGROUND We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia. METHODS We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1. 1x10(11), 2. 2x10(11), or 4. 4x10(11) platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria). RESULTS In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9. 25x10(11)) than in the medium-dose group (11. 25x10(11)) or the high-dose group (19. 63x10(11)) (P=0. 002 for low vs. medium, P<0. 001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0. 001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0. 001). CONCLUSIONS Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1. 1x10(11) and 4. 4x10(11) platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials. gov number, NCT00128713. )