Evelyn J Ward, Lisa M Henry, Amanda J Friend, Simone Wilkins, Robert S Phillips

It is well documented that malnutrition is a common complication of paediatric malignancy and its treatment. Malnutrition can often be a consequence of cancer itself or a result of chemotherapy. Nutritional support aims to reverse malnutrition seen at diagnosis, prevent malnutrition associated with treatment and promote weight gain and growth. The most effective and safe forms of nutritional support in children and young people with cancer are not known. To determine the effects of any form of parenteral (PN) or enteral (EN) nutritional support, excluding vitamin supplementation and micronutrient supplementation, in children and young people with cancer undergoing chemotherapy and to determine the effect of the nutritional content of PN and EN. This is an update of a previous Cochrane review. We searched the following databases for the initial review: CENTRAL (The Cochrane Library, Issue 2, 2009), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), CINAHL (1982 to 2006), the National Research Register (2007) and Dissertations & Theses (2007). Experts in the field were also contacted for information on relevant trials. For this update, we searched the same electronic databases from 2006 to September 2013. We also scrutinised the reference lists of included articles to identify additional trials. Randomised or quasi-randomised controlled trials comparing any form of nutritional support with another, or control, in children or young people with cancer undergoing chemotherapy. Two authors independently selected trials. At least two authors independently assessed quality and extracted data. We contacted trialists for missing information. The current review included the eight trials from the initial review and six new trials which randomised 595 participants (< 21 years of age) with leukaemias or solid tumours undergoing chemotherapy. The trials were all of low quality with the exception of two of the trials looking at glutamine supplementation. One small trial found that compared to EN, PN significantly increased weight (mean difference (MD) 4.12, 95% CI 1.91 to 6.33), serum albumin levels (MD 0.70, 95% CI 0.14 to 1.26), calorie intake (MD 22.00, 95% CI 5.12 to 38.88) and protein intake (MD 0.80, 95% CI 0.45 to 1.15). One trial comparing peripheral PN and EN with central PN found that mean daily weight gain (MD -27.00, 95% CI -43.32 to -10.68) and energy intake (MD -15.00, 95% CI -26.81 to -3.19) were significantly less for the peripheral PN and EN group, whereas mean change in serum albumin was significantly greater for that group (MD 0.47, 95% CI 0.13 to 0.81, P = 0.008). Another trial with few participants found an increase in mean energy intake (% recommended daily amount) in children fed an energy dense feed compared to a standard calorie feed (MD +28%, 95% CI 17% to 39%). Three studies looked at glutamine supplementation. The evidence suggesting that glutamine reduces severity of mucositis was not statistically significant in two studies (RR 0.64, 95% CI 0.19 to 2.2 and RR 0.85, 95% CI 0.66 to 1.1) and differences in reduction of infection rates were also not significant in two studies (RR 1.0, 95% CI 0.72 to 1.4 and RR 0.98, 95% CI 0.63 to 1.51). Only one study compared olive oil based PN to standard lipid containing PN. Despite similar calorie contents in both feeds, the standard lipid formula lead to greater weight gain (MD -0.34 z-scores, 95% CI -0.68 to 0.00). A single study compared standard EN with fructooligosaccharide containing EN. There was no difference in weight gain between groups (mean difference -0.12, 95% CI -0.57 to 0.33), with adverse effects (nausea) occurring equally between the groups (RR 0.92, 95% CI 0.48 to 1.74). There is limited evidence from individual trials to suggest that PN is more effective than EN in well-nourished children and young people with cancer undergoing chemotherapy. The evidence for other methods of nutritional support remains unclear. Limited evidence suggests an energy dense feed increases mean daily energy intake and has a positive effect on weight gain. Evidence suggesting glutamine supplementation reduces incidence and severity of mucositis, infection rates and length of hospital stay is not statistically significant. Further research, incorporating larger sample sizes and rigorous methodology utilising valid and reliable outcome measures, is essential.