Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns
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.
No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2022
OBJECTIVES Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. MATERIAL AND METHODS PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. RESULTS A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92;95% CI[-3.35,1.52]; p=0.46; I(2)=0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI[-236.16,430.77]; p=0.57; I(2)=0) and 12 months (WMD: 46.99; 95% CI[-191.42,285.40]; p=0.70; I(2)=0) respectively. CONCLUSION Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.
A systematic review of adherence to iron chelation therapy among children and adolescents with thalassemia
Annals of medicine. 2022;54(1):326-342
INTRODUCTION Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents. METHODS This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria. RESULTS Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report (n = 15/36, 41.7%), and pill count (n = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills (n = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence (n = 29) or "quantitatively" as a percentage of medication taken out of those prescribed (n = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis. CONCLUSIONS Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients.Key messagesPredictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort.Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes.Inadequate adherence to ICT is associated with increased lifetime health costs.There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients.
Feeding Practices and Effects on Transfusion-Associated Necrotizing Enterocolitis in Premature Neonates
Advances in neonatal care : official journal of the National Association of Neonatal Nurses. 2021
BACKGROUND Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development. PURPOSE To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions. METHODS/SEARCH STRATEGY Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates. FINDINGS Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes. IMPLICATIONS FOR PRACTICE To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation. IMPLICATIONS FOR RESEARCH It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes.
Psychological intervention in children with transfusion-dependent β-thalassaemia
Vox sanguinis. 2021
BACKGROUND AND OBJECTIVES Transfusion-dependent β-thalassaemia can lead to severe psychological issues in paediatric and adolescent patients. However, the psychological interventions for these patients are limited in clinical practice. We aimed to investigate the impact of a 3-month psychological intervention on the quality of life (QOL) of children with β-thalassaemia (12-18 years old) who relied on blood transfusion in this study. MATERIALS AND METHODS In the current randomized controlled trial, a total of 143 paediatric or adolescent patients (12-18 years old) with transfusion-dependent β-thalassaemia were recruited. They were randomized into the control group (n = 71) who received standard physiological treatment and the intervention group (n = 72) who received a 3-month intervention in addition to standard physiological treatment. The effects of the interventions on the QOL and psychological outcomes of these participants were analysed. RESULTS The 3-month intervention significantly improved the scores of PedsQoL 4.0 Generic Core Scales of paediatric patients with transfusion-dependent β-thalassaemia. It also significantly improved the psychological status and alleviated the depression among children and adolescent patients by alleviating anhedonia, negative mood and negative self-esteem among them. CONCLUSION Psychological intervention has positive effects on the treatment for children with transfusion-dependent β-thalassaemia.
Effect of blood transfusions on cognitive development in very low birth weight infants
Journal of perinatology : official journal of the California Perinatal Association. 2021
OBJECTIVE Preterm infants frequently receive red cell transfusions; however, the effect of transfusions on cognition is unclear. We evaluated the relationship between transfusions and cognitive outcomes in preterm infants enrolled in a randomized trial of erythropoiesis stimulating agents (ESAs). STUDY DESIGN Preterm infants were randomized to ESAs or placebo during initial hospitalization, and transfusions recorded. Children were evaluated using standard developmental tests of cognition at 18-22 months (56 ESA, 24 placebo) and 3.5-4 years (39 ESA, 14 placebo). RESULTS Cognitive scores at 18-22 months were inversely correlated with transfusion volume (p = 0.02). Among those receiving ≥1 transfusion, cognitive scores were significantly higher in the ESA-treated group (p = 0.003). At 3.5-4 years, transfusions were not correlated with cognitive scores. CONCLUSIONS In the placebo group, transfused children had lower cognitive scores than did non-transfused children at 18-22 months. In the ESA group, cognitive scores did not differ by transfusion status, suggesting ESAs might provide neuroprotection.
Clinical Usefulness of Furosemide to Prevent Volume Overload Among Children and Young Adults with Transfusion-Dependent Thalassemia: A Randomized, Open-Label, Crossover Study
Journal of blood medicine. 2020;11:503-513
PURPOSE Red blood cell transfusion is a key element of treatment among patients with transfusion-dependent thalassemia (TDT). Volume overload and HCC syndrome (hypertension, convulsion, and intracranial hemorrhage) are fatal complications related to transfusion. Furosemide has been widely used to prevent hypertension secondary to volume overload with unclear supportive evidence. This study aimed to evaluate the efficacy of furosemide to prevent volume overload among children and young adults diagnosed with TDT. METHODS Patients diagnosed with TDT were enrolled and randomized to receive either furosemide pretransfusion or no furosemide pretransfusion. After 3 weeks to 4 months of wash-out periods, those patients underwent the alternate regimens as per crossover design of the study. Clinical and laboratory parameters including blood pressure and NT-proBNP levels were measured before and after each transfusion. The difference of those parameters between two randomized groups and their potential associated factors were analyzed. RESULTS In all, 30 patients undergoing 60 red blood cell transfusions were enrolled in the study. All were randomized and crossover was designed as receiving and not receiving furosemide pretransfusion. No transfusion reactions, symptoms of volume overload and HCC syndrome were observed. No statistically significant correlation was found between pretransfusion furosemide and the difference between pre- and posttransfusion systolic blood pressure (2 mmHg systolic blood pressure difference in pretransfusion furosemide and 1.5 mmHg in no pretransfusion furosemide; p-value = 0.721), as well as between pretransfusion furosemide and the difference between pre- and posttransfusion NT-proBNP levels (-3.8 pg/mL NT-proBNP level difference in pretransfusion furosemide and -2.4 pg/mL in no pretransfusion furosemide; p-value = 0.490). No significant correlation was also observed even in selected patients with high NT-proBNP levels (p-value = 0.262). Associated factors affecting the difference between pre- and posttransfusion NT-proBNP levels were analyzed, and none of those were affected concerning the difference in the levels. CONCLUSION Furosemide has been included in standard transfusion guidelines in many institutions. Our study provided important evidence of the unnecessary use of the drug in preventing volume overload particularly in pediatric and young adult patients with TDT. THAI CLINICAL TRIALS REGISTRY TCTR NUMBER TCTR20180209001. Registered 6 February 2018, https://www.clinicaltrials.in.th/.
Recent insight on improving the iron chelation efficacy of deferasirox by adjuvant therapy in transfusion dependent beta thalassemia children with sluggish response
Expert opinion on drug metabolism & toxicology. 2020
Background: Deferasirox is the first line of treatment in iron overload. In spite of the many studies concerning the efficacy of deferasirox, some patients remain unresponsive to deferasirox.Methods: One hundred and sixty patients were enrolled in stratified randomized controlled study. Patients were randomly divided into four regimens, group I (n=40) received 30 mg/kg deferasirox, group II (n=40) received 20 mg omeprazole and 30 mg/kg deferasirox, group III (n=40) received 400 mg vitamin E and 30 mg/kg deferasirox and group IV (n=40) received 420 mg silymarin and 30 mg/kg deferasirox. Blood specimens were collected from each patient for up to 24 h, and then plasma deferasirox concentrations were inspected.Results: Silymarin, Vitamin E and omeprazole significantly increased the peak plasma concentration of deferasirox (P<0.001) by 27.9, 14.9 and 2.4 fold respectively as compared to deferasirox alone. The bioavailability of deferasirox was improved up to 3.03, 3.57 and 4.98-fold, respectively, following administration of omeprazole, vitamin E and silymarin compared to deferasirox alone.Conclusion: Silymarin, vitamin E and omeprazole represent promising adjuvant therapy to improve the chelation efficacy of deferasirox that might also be further applied to enhance the pharmacokinetics of deferasirox to overcome the lack of response.
Transfusion dependent beta thalassemia children with sluggish response (n=160).
Group I 30 mg/kg deferasirox. (n=40).
Group II 20 mg omeprazole and 30 mg/kg deferasirox (n=40); group III 400 mg vitamin E and 30 mg/kg deferasirox (n=40); group IV 420 mg silymarin and 30 mg/kg deferasirox (n=40).
Silymarin, Vitamin E and omeprazole significantly increased the peak plasma concentration of deferasirox by 27.9, 14.9 and 2.4 fold respectively as compared to deferasirox alone. The bioavailability of deferasirox was improved up to 3.03, 3.57 and 4.98-fold, respectively, following administration of omeprazole, vitamin E and silymarin compared to deferasirox alone.
Randomized controlled trial of effect of N-acetylcysteine as an antioxidant on iron overload in children with thalassemia major
Clinical and experimental pediatrics. 2020
BACKGROUND β-Thalassemias are characterized by the presence of mutations in the globin gene that result in the absence or reduced synthesis of β-globin chains of the hemoglobin tetramer. Several studies have reported increased oxidative stress in β-thalassemia major (β-TM) patients. N-acetylcysteine (NAC), a derivative of L-cysteine amino acid, is commonly used as a mucolytic drug. Numerous studies have reported efficient antioxidant activity of NAC. PURPOSE To evaluate the effects of NAC on oxidative stress status and hemoglobin levels in children with β-TM. METHODS This study was conducted between June and December 2019. One hundred β-TM patients were divided into two groups: 50 received NAC 10 mg/kg orally for 3 months (treatment group), while the other 50 received no treatment (non-treatment group). Total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and hemoglobin (Hb) and ferritin levels were measured and compared between groups. RESULTS At the end of the study period, Hb and TAC levels were significantly higher in the treatment group than in the non-treatment group (P < .001 and .01, respectively). On the other hand, serum ferritin levels, TOS, and OSI were significantly lower (P = .004, .01, and .001, respectively) in the treatment group. CONCLUSION NAC can effectively reduce the oxidative status and increase the pre-transfusion Hb levels in children with β-TM. Furthermore, NAC could reduce iron overload in these patients.
Transfusion-Associated Circulatory Overload in ICUs: A Scoping Review of Incidence, Risk Factors, and Outcomes
Critical care medicine. 2019
Transfusion-associated circulatory overload is the most frequent serious adverse transfusion reaction, with an incidence close to 1% of transfused patients in the general adult population. Patients in ICUs are probably more at risk of transfusion-associated circulatory overload as they are more frequently transfused and associated with more comorbidities. However, the epidemiology of transfusion-associated circulatory overload in ICU is not well characterized, leading to a risk of underdiagnosis. OBJECTIVES We conducted a scoping review to describe the incidence, risk factors, and outcomes of transfusion-associated circulatory overload in PICU and adult ICU. DATA SOURCES PubMed, Ovid Medline, Ovid All EBM Reviews, Ovid Embase, and EBSCO CINAHL COMPLETE. STUDY SELECTION Two reviewers independently screened each article for inclusion criteria. Studies were eligible if they reported data on incidence, risk factors, or outcomes of transfusion-associated circulatory overload in at least 10 ICU patients. DATA SYNTHESIS Among 5,926 studies identified, nine were included. Five studies were prospective, and four were retrospective. The definition of transfusion-associated circulatory overload varied among studies. The pooled incidence of transfusion-associated circulatory overload was of 5.5% (95% CI, 2.6-9.4%) in adult ICUs (four studies, 2,252 patients, high heterogeneity). In PICUs, two studies (345 patients) reported 0 cases, and a third study (136 patients) reported variable incidences between 1.5% and 76%, depending on diagnostic criteria. Risk factors for transfusion-associated circulatory overload included positive fluid balance, the number and type of products transfused, rate of transfusion, and cardiovascular and renal comorbidities. Transfusion-associated circulatory overload was associated with increased ICU and hospital lengths of stay, whereas the association with mortality was not consistent. CONCLUSIONS Transfusion-associated circulatory overload is frequent in ICU patients and is associated with adverse outcomes. The lack of a pediatric-adjusted definition of transfusion-associated circulatory overload may lead to a risk of underdiagnosis of this condition in PICUs. Further research is warranted to improve the knowledge of transfusion-associated circulatory overload and the safety of transfusion in ICU patients.