Nutritional and Post-Transplantation Outcomes of Enteral versus Parenteral Nutrition in Pediatric Hematopoietic Stem Cell Transplantation: A Systematic Review of Randomized and Nonrandomized Studies

Abstract

Background: Hematopoietic stem cell transplantation (HSCT) involves the administration of chemotherapy followed by the infusion of donor stem cells. After treatment, children can consequently experience nausea, vomiting, diarrhea, anorexia and mucositis, which negatively impact oral intake leading to rapid deterioration in nutritional status and risk of malnutrition. Nutrition support therefore becomes necessary to circumvent these adverse effects. This has traditionally been provided via parenteral nutrition (PN), but pediatric evidence is increasingly advocating enteral nutrition (EN) as a preferential alternative. The objective of this review is to determine the efficacy of any forms of EN vs. PN provided during admission to children ≤18 years undergoing HSCT. Primary outcomes considered efficacy in relation to various nutritional parameters, and secondary outcomes included a range of posttransplantation parameters. Methods: Data sources included English and non-English articles from the start date of MEDLINE, EMBASE, AMED, CINAHL and Cochrane Controlled Trials register, up to July 2018. Key journals were also hand searched, reference lists scanned, clinical experts contacted and grey literature searched using EThOS and Open Grey. Randomized and observational studies comparing any forms of EN vs.PN in children ≤18 years undergoing HSCT investigating nutritional or post-transplantation outcomes were eligible. Data were extracted from included studies using a custom extraction form that had previously been piloted. As included studies were observational, risk of bias was assessed using ROBINS-I. Results:As only a small number of heterogenous studies reporting a wide range of differently defined outcomes were included, meta-analyses were not performed and data were presented in narrative form.Conflicting results in favor of either method of nutrition support, or no difference between methods, were seen for duration of interventions, nutritional intakes, biochemical and anthropometric changes, mortality, infections, length of admission and neutrophil engraftment. EN may provide favorable benefits over PN regarding acute graft-versus-host-disease (aGvHD) and platelet engraftment. Discussion:A paucity of studies were found investigating the question posed by this review. Included studies were clinically heterogenous regarding populations, interventions and outcomes, at moderate to serious risk of bias due to the absence of randomization, confounding parameters, statistical control, retrospective designs and participant selection. Some studies were more than 15 years old.Conclusions: Despite the limited number and poor quality of identified studies, results support the growing body of pediatric evidence that EN is feasible during HSCT. Similar differences regarding many nutritional and post-transplantation outcomes were seen in both forms of nutrition support, but EN could provide benefits above PN including reduced incidence of aGvHD and faster platelet engraftment.

Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis

“…On the other hand, PN patients were found have blood culture positivity to several microorganisms (e.g., Staphylococcus, Enterococcus and Streptococcus genera), mainly from day 5 to 30 post-HSCT, leading to systemic infections and clinical complications. Our results regarding the clinical outcomes of EN patients were generally in line with most of the previous studies in literature conducted on adult cohorts post-HSCT [18][19][20][21][22][23]. However, we cannot fail to mention that other studies provide conflicting results for what concern the clinical outcomes of EN assumption in HSCT adult patients [52,53].…”

“…Although post-HSCT enteral feeding is being increasingly recommended [37][38][39], intravenous nutrient intake (PN) is still the first-line nutritional approach for the patients who received HSCT due to its compliance, but it has been associated with several clinical and microbiological adverse effects, including infections and GM dysbiosis [18][19][20][21][22][23][24]. So far, the central role of the GM composition and biodiversity in patients undergoing HSCT has been largely evaluated in several publications, highlighting the disruption of the gut microbial mutualistic asset after the transplant (i.e., until 30 days post-HSCT) compared to the baseline, due to all HSCT conventional treatments that can alter the GM recovery possibilities post-HSCT [4,5,7].…”

“…EN, also called "tube-feeding", is the method by which food is directly delivered inside the patient's gastrointestinal tract, while PN is an effective strategy of delivering nutrients directly into the bloodstream. Nowadays, it is well known that total PN, the first-line approach for HSCT patients, is associated with different clinical adverse effects such as infections [18][19][20] and metabolic disorders [21], as well as with gut mucosal atrophy [22], cell dysfunction [23], and alterations in GM composition [24]. Conversely, EN has been indicated as a possible solution to overcome all these adverse effects.…”

Enteral nutrition protects children undergoing allogeneic hematopoietic stem cell transplantation from blood stream infections

“…In the paediatric population, the few studies comparing EN to PN involving a limited number of patients, found that EN had potential benefits regarding aGvHD and platelet engrafment [24]. Considering the increasing knowledge concerning the role of gut microbiota dysbiosis in the development of main complications after HSCT, these benefits may be potentially explained by the maintenance of gut eubyosis and epithelium integrity in patients receiving EN [25].…”

Outcomes of an enteral feeding protocol in pediatric cancer patients: a non-randomized clinical trial

“…19,25 However, interpretations of these studies among children and adolescents with cancer are difficult because of study design limitations relating to numbers of patients, non-randomized trial designs, different diagnoses, concomitant parenteral nutrition and limitations on nutritional assessment methods. 2,24,25,[43][44][45][46][47] Furthermore, these studies did not describe the amount of tube feeding supplement intake.…”