What Is Known
- Nutritional deficiencies are prevalent in children and adolescents with inflammatory bowel diseases.
- Dietary intake in children with inflammatory bowel disease has been reported to be poor.
What Is New
- Comparison of actual food intake of children and adolescents with inflammatory bowel disease with sex- and age-adjusted food intake of healthy children from a national survey or data from recommended daily allowance showed disparate results.
- Compared with children not supplemented, children on exclusive enteral nutrition or nutritional supplements had significantly better intakes of all nutrients, including energy, minerals, and iron
Impaired nutritional status is common in patients with inflammatory bowel diseases (IBDs). Both children and adults suffer from malnutrition, growth faltering, specific micronutrient deficiencies, and sometimes from overweight and obesity (1,2). The abnormal nutritional status is the result of complex pathophysiological processes. These include interactions between poor food intake, malabsorption, increased losses, and increased needs associated with inflammation. These are augmented by disturbances of the growth hormone/insulin-like growth factor axis, and the use of drugs such as corticosteroids, antacids, laxatives, and nonsteroidal anti-inflammatory drugs (3).
In addition to protein-energy malnutrition, anemia (54%–80%), hypoalbuminemia (25%–80%), and micronutrient deficiencies, such as iron, copper, selenium, magnesium, zinc, vitamins, and antioxidants (vitamins C, E, beta carotene, glutathione, taurine), have also been reported (4–11), even during clinical remission. Presence of nutritional deficiencies can influence clinical outcomes and affect the immune system, tissue repair, oxidative stress defense mechanism, growth and sexual maturation in children, nitrogen balance, bone accrual, and postoperative morbidity (3).
The aims of the present study were to assess the dietary intake of ambulatory patients with Crohn disease and investigate whether their dietary intakes of macro- and micronutrients meet the recommended daily allowances (RDAs). The dietary intakes of children and adolescents with IBD were also compared with nutrient intakes of age- and sex-matched healthy Israeli children reported by “Mabat Tzair” nutritional Israeli survey. Furthermore, we investigated the relation between patients’ dietary intakes, nutritional status, and disease activity.
Consecutive children and adolescents with IBD were prospectively recruited from the outpatient Gastroenterology clinic at the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel. The Research Ethics Board of the Rabin Medical Center approved the study protocol, and all subjects’ parents/guardians gave their informed written consent. Patients older than 8 years gave oral assent before the start of the study.
The diagnosis of CD and UC was based on the clinical, endoscopic, and histological criteria according to ESPGHAN guidelines (12). The CD and UC disease activity was determined by PCDAI (Pediatric Crohn Disease Activity Index) and PUCAI (Pediatric Ulcerative Colitis Activity Index), respectively (13,14). Remission was defined as the absence of clinical symptoms and PCDAI score of <10 for patients with CD and PUCAI score <10 for patients with UC. Disease activity was categorized as none (1–10), mild (11–30), and moderate to severe (>30). The site of the disease was classified by the modified Montreal-Paris classification (15).
Evaluation of each participant involved a thorough history and physical examination, including anthropometry, food intake, along with laboratory tests to evaluate disease activity (eg, complete blood count, erythrocyte sedimentation rate, serum albumin), and nutritional state (eg, serum ferritin, vitamin B12, iron and vitamin D levels, red blood cell folate, and plasma zinc levels).
Patients’ weight and height were measured using standard anthropometric techniques (16). Weight for age z score (WTz), height for age z score, and BMI z score (BMIz) were calculated using the Epi Info Database and Statistics software for public health professionals (Centers for Disease Control and Prevention, Atlanta, GA) software. Skinfold thickness (SFT) measurements were taken in triplicate from the nondominant side of the body using a skinfold calliper (Holtain Ltd, Crymych, UK) and results were compared with the reference values. Mid-upper arm circumference (MUAC) was measured using measurement tape, and the results were compared with the reference values. Lean body mass (LBM) was calculated using Peters formula (17) for children younger than 15 years and James formula (18) for older children using CalculatorNet Web site http://www.calculator.net/lean-body-mass-calculator.html. z scores for LBM were calculated using the reference UK data (19). Underweight was defined as a BMIz and/or WTz −2 SD or less for age, and overweight was a BMI of at least +2 SD for age.
The dietary intake was assessed using a 3-day food diary record. The patients were asked to record everything they ate and drank immediately after consumption (if possible), including the amounts consumed (in household measures), the method of cooking and the brand names of any products used. Data from the diaries were analyzed for energy and macro- and micronutrient intake, using nutrient analysis software “Tzameret” version 2.0 2007, an Israeli food composition tables published and validated by the Ministry of Health. Mineral and vitamin supplements were not added to daily nutrient intake but recorded separately in the questionnaire. The nutrient intake of patients with IBD was compared with nutritional data obtained from an Israeli reference population, “Mabat Tzair,” a study of nutrient intake of 6274 Israeli children and adolescents of 9 to 18 years age carried out in 2003/2004. The nutrient intakes were also compared with recommended RDA references for energy, macro-, and micronutrients (https://ods.od.nih.gov/Health_Information/Dietary_Reference_Intakes.aspx). The participants’ intakes and/or supplements were taken on a regular basis for least 60% to 80% of the days at least 2 months before the dieticians’ evaluation. The reported intakes were expressed as percentage of the RDA and “Mabat Tzair” intake for healthy children matched for age and sex.
Continuous variables were expressed either as means and standard deviation (SD) or with medians and numbers (percentages) depending on the distribution of the data. Differences between groups were assessed with 2-sample t test and analysis of variance for parametric variables and Mann-Whitney U test or Kruskal-Wallis for nonparametric data. Differences in categorical data were assessed with χ2 or Fisher exact test for 2 × 2 tables. Correlations between continuous variables were assessed by Pearson or Spearman correlations. A P <0.05 was considered statistically significant. Statistical analysis was carried out using SPSS v 23.0 (SPSS Inc, Chicago, IL).
Table 1 summarizes the demographic and disease characteristics of the 68 enrolled patients. An additional 30 patients were approached but refused participation. Three children were seen 2 months after diagnosis. The maximal follow-up before the evaluation was 8.9 years. Median follow-up, overall, was 2.3 years. Most patients had CD (n = 57), all nonpenetrating, nonstricturing disease, all patients with UC (n = 11) had pancolitis. Based on the PCDAI/ PUCAI scoring, 26 of 68 (38%) had no active disease and 16 of 68 (23%) had moderate to severe disease. The main medication used for maintaining remission were immunosuppressive drugs, azathioprine, or 6-mercaptopurine in 30 of 68 (44%) and methotrexate in 4 of 68 (6%). The patients used different nutritional supplements, according to dietician or physician in charge recommendations, however with the exception of vitamin D; the other supplements were seldom taken compared with the prevalence of deficiencies.
Judging by anthropometry indexes, the participants’ nutritional status was fairly good, with only 10% undernourished by BMI z score. Two percent and 16% were, however, malnourished based on MUAC and SFT <5%, respectively. Three children were stunted, and only 1 was overweight. Mean ± SD LBM in the whole group was 39 ± 30 kg/BW (median 37.8) corresponding to −0.3 ± 1.1 (median −0.6) SD. Six patients (11%) had <−2 SD LBM. Patients’ nutrition and inflammatory laboratory data are presented in Table 2. The most frequent nutrition deficiency was anemia (51%). The second most frequent nutritional deficiencies were vitamin D (25%) and zinc deficiency (17%). Vitamin B12 and folic acid deficiency were rare (only 1 patient for each).
The average ± SD intake of energy, macro- and micronutrients, as well as the absolute numbers of children with poor and excessive intake is shown in Table 3. The frequencies of low (<80% RDA) and remarkably high (>150% RDA) intakes are also presented. Overall, poor intake (<80% RDA) was recorded for carbohydrates (CHO) and most minerals and micronutrients but was notably poor for calcium, magnesium, vitamin A, E, and fiber. Excessive intake (>150% RDA and in some even >200% RDA) was recorded for protein and most water-soluble vitamins.
There were significant differences in the reported intakes of the patients with IBD included in the study and the reference intakes from RDA and National nutritional survey for almost all dietary components, Figure 1A–E. Compared with RDA, the intake of patients with IBD was significantly lower in CHO (75%), calcium (49%), magnesium (76%), vitamin A (72%), vitamin E (57%), and fiber (44%) and significantly higher in protein (175%), iron (112%), vitamin C (123%), B1 (118%), B2 (161%), B6 (158%), and B12 (189%). Compared with the National Survey, “Mabat Tzair,” the intake of our cohort was higher only for B12 (141%) but lower for calories (78%), CHO (61%), magnesium (67%), vitamin C (34%), and fiber (54%). There was no significant difference in the intake of children in remission compared with children with active disease at the time of the evaluation. Disease activity was significantly and positively associated with hemoglobin (12.4 ± 1.3 vs 11.2 ± 1.1, P < 0.05), hematocrit (38 ± 3.8 vs 35 ± 3.3, P < 0.05), CRP (0.5 ± 0.7 vs 2.5 ± 2.2, P < 0.05), erythrocytes sedimentation rate (20 ± 12 vs 38 ± 18, P < 0.05), and serum albumin levels (4.3 ± 0.3 vs 3.7 ± 0.5, P < 0.05), as specified by the PCDAI index but not with the anthropometry indexes or other serum biochemistry/nutritional biochemistry.
The type of food intake varied within the group: 50 patients consumed regular foodstuff, 11 consumed regular food and also consumed different nutritional supplements formulas that added between 250 and 850 kcal/day to their diet, and 7 patients just completed 6 weeks of exclusive enteral nutrition (EEN) for induction (3/7) or reinduction of remission for CD. Thinner children were more frequently supplemented, as 7 of 18 (39%) but only 6 of 50 (8%) of children in the supplemented and nonsupplemented groups, respectively, had weight z scores <−1.5 SD (P = 0.03). Compared with children on regular diet, the children taking nutritional supplements either as EEN or formula supplements added to the regular diet were significantly thinner and shorter (WTz −1.25 ± 1.1 vs −0.13 ± 1.1, P = 0.02, BMIz −1.25 ± 0.9 vs −0.01 ± 1.1, P = 0.000, height for age z score −0.63 ± 1.0 vs −0.14 ± 0.8, P = 0.04). They also had significantly lower serum albumin (3.7 ± 0.6 vs 4.1 ± 0.6, P = 0.03) and significantly higher CRP (2.0 ± 1.9 vs 1.4 ± 3.0, P = 0.04), ferritin (37.2 ± 23.7 vs 19.8 ± 10.7, P = 0.019) and zinc (67.8 ± 17.4 vs. 50.9 ± 24.0, P = 0.021) serum levels. Intake of patients with active disease was not significantly different from intake of children in remission, for none of the diet components. A similar number of supplementated children had active disease (5/18, 27%) compared with nonsupplemented children (10/50, 20%). No significant difference in disease activity (PCDAI or PUCAI) and other laboratory values was observed between supplemented and nonsupplemented children.
Table 4 presents the intake of children on regular diet compared with children who consumed nutritional supplements, either in addition to their regular diet or as EEN (18/68). The intake of children taking nutritional supplements was significantly better compared with the intake of children and adolescents on regular diet, especially for calcium, vitamin A, and vitamin E intake. One exception was fiber intake that was poorer in patients supplemented with nutritional formula, because of use of formula without added fiber.
The present study is a comprehensive analysis of nutritional status and food intake adequacy in children and adolescents with IBD. In this study, undernutrition and short stature were not prevalent, but micronutrients deficiencies including iron, zinc, and vitamin D were common. The study revealed that children and adolescents with IBD have peculiar food intake patterns, because some of macro- and micronutrients were consumed in excess whether others were exceedingly deficient in their diets. The intake of children taking nutritional supplements was significantly better especially with regard to minerals and fat-soluble vitamins.
A systematic review reported that growth failure was present in 13% to 33% of patients at diagnosis and 10% to 29% at follow-up in studies published before 2000, but only 9.5% at diagnosis and 6.9% to 27% at follow-up among unselected patients with CD, in studies published after 2005 (20). The prevalence of undernutrition and overweight in our cohort was considerably lower, although almost two thirds of the patients had active disease and about one quarter had severe disease activity. Possible, abnormal body composition, indicated by low MUAC and SFT, was more widespread, because average anthropometry indexes do not rule out the deviant distribution of lean muscle mass and fat stores.
Anemia and iron deficiency are among the most frequent nutritional deficiencies in children and adolescents with IBD (4–6). The reported prevalence varies depending on timing in relation to diagnosis, but is common both at diagnosis (63%–100%) and during disease course (55%–40%) and often resistant to treatment. The presence of anemia is related to both iron intake, disease activity, and upper gastrointestinal involvement (5,21,22). Anemia was present in 50% of our patients. Iron intake in our cohort was relatively good and correlation studies showed significant relation with disease activity only. Iron treatment was more readily given to patients presenting with anemia, but hemoglobin levels did not differ between patients with or without iron supplements.
Inadequate serum vitamin D levels are prevalent in both healthy children and children with IBD, and vary depending on whether insufficiency or deficiency is investigated. Pappa et al (23) reported that 58.3% of pediatric patients with IBD had suboptimal serum 25OHD concentration (25OHD <32 ng/mL) and 14.3% had serum 25OHD level at or <20 ng/mL. The serum vitamin D levels in our group were fairly appropriate to the serum vitamin D levels reported in healthy European and American children (24,25) and similar to those reported in healthy Israeli children and adults (26,27), despite of routine surveillance and supplementation.
Food intake in children and adolescents with IBD has been the topic of few papers (28–30). In spite of the differences in the patients studied and the controls chosen for comparison, most studies reported poor energy and macronutrients intake. Moreover, all studies reported were of less than adequate minerals, especially calcium, fiber, and some vitamins (7,31–34). The 40 patients on EEN described by Gavin et al (28) had a median energy intake of 117.5% (interquartile range 102.5%–125.5%) and 82% were consuming more than 100% estimated average requirements. The children with active CD studied by Thomas et al (29) consumed on average 420 kcal less than their siblings (matched for age, sex, and weight/ height), and 21% of patients had energy intakes lower than estimated average requirements compared with only 10% in the control group. Energy intake improved after induction of remission. Pons et al compared the dietary intakes of 63 children with CD in remission or with active disease with a group of healthy controls. They reported that energy intakes of all children with CD were significantly lower than the estimated energy requirements calculated by Schoefield equation and especially lower in children with active CD (active CD P = 0.001, CD in remission P = 0.03) (30).
We compared dietary intakes of our patients with published RDA for children and adolescents but also with the nutrients intake as reported by a National survey in healthy children, because local environmental, social, cultural, educational, and genetic factors may vary in different populations. This comparison uncovered inconsistencies for energy, protein, and vitamin C, A, and E intakes. Energy intake was appropriate in children with IBD when compared with RDA but significantly lower compared with the average energy intake of healthy Israeli children. A cross-sectional study of 517 schoolchildren of 13 to 14 years age, performed during the same years as the nutritional survey, identified that overweight and obesity were present in 10.3% and 3.5% of girls and 8.9% and 5.3% of boys, respectively, figures much lower than these reported in American children and teenagers (31). Therefore, the higher energy intake is not related to increase in overweight and obesity prevalence in Israeli children and is probably appropriate for this population. Other inconsistencies were detected with regard to protein intake that was significantly higher by the standards of RDA but similar compared with local children protein intake.
Children with active CD have also poor intake of minerals, especially calcium and micronutrients. Thomas et al (29) found that few children with active CD achieved the requirements for copper, zinc, folate, and vitamin C compared with a matched group of their healthy siblings. Iron and calcium intake was also suboptimal in children with active CD, but in those in clinical remission. Compared with RDA, many children had <80% intakes for many nutrients, but remarkably poor intake of calcium was noticed as the intake of 50% of children was <50% of RDA. Because RDA has been developed as a standard for nutrition recommendations for the general population according to age and sex, comparison of our group with the intakes of healthy, local children is more appropriate. Looking at the comparison with healthy Israeli children, intake of patients with IBD was low in energy, CHO, calcium, magnesium, vitamin C, and fiber, and appropriate for protein, iron, zinc, folic acid, vitamin A, and vitamin E.
Why are there differences between the National Survey and the RDA? The difference comes from the dissimilar information provided by the 2 tools: The National survey reports the “real life” food intake habits of the Israeli children of 9 to 18 years as collected in 2003/2004, whereas the RDA presents the recommended nutrients’ intakes considered adequate according to our best scientific knowledge to meet the known nutrient needs of healthy people. This finding raises 2 questions: the first is which data should we compare our children to? If we only compare them with RDA, and we should to avoid deficiencies, we miss the comparison of how do they differ from healthy children. The second question: Are “control” groups appropriate for use for nutritional studies, if they are so different of RDA? Although RDA should continue to be our reference tool, it is suggested that we should also examine the intake information of the studied group in comparison to local/ national data, as national food habits may be quite different and this is important for the health care provider giving dietary advice.
Most studies have reported low energy and nutrients intakes during the periods of active disease and improved food intake during remission, but our patients’ intake showed no correlation with disease activity. Nutritional status was, however, significantly associated with patients’ intake. Underweight children ate significantly better, which may be surprising in some way, but probably accounted for the fact that physicians/dieticians as well as underweight children and adolescents and their families were more likely to recommend and accept the use of nutritional supplements. This was especially true for children on EEN for remission induction/ reinduction, for which the alternative is use of corticosteroids and adverse effect on growth.
Provision of some nutritional formula either to regular diet or as EEN significantly improved nutrients’ intake, because all formulas contain added minerals and micronutrients, and also serum zinc. Gerasimides recorded significant changes in micronutrient concentrations during EEN. In their study, plasma concentrations for many micronutrients improved at the end of EEN (35). The strong effect of EEN on micronutrient status was also confirmed by the observation that within a short period of EEN cessation, the majority of micronutrients reversed or tended to reverse to pre-EEN concentrations.
The limitations of the study are related to the small number and heterogeneity of participants and incompleteness of data of biochemistry as well as the limited number of nutritional biochemistry parameters evaluated. In addition, any evaluation of energy intake by comparison to standard recommendation or calculated using different equations is misleading and any assumptions of nutritional status without knowledge of body composition are at best educated guessing.
Our study provides recent information on the nutritional status and dietary intake of pediatric patients with IBD. The study envisages the complexity of the relation between nutritional status, disease activity, and nutrients’ intake in patients with IBD. Furthermore, our study hints to the need for evaluating the intake of sick children to the healthy population as the differences between such comparisons provides different information compared with RDA-related evaluations.
In conclusion, knowledge of the extent to which decreased or inadequate food intake contributes to the nutrition deficiencies seen in IBD assists in determining if and how much nutrient supplementation is required. Quantifying nutrient intake in the context of the overall nutrition status assists in determining if patients with IBD are meeting recommended levels of nutrient intake, and to what extent subjects require supplementation.
The authors thank patients and their families for accepting to participate in the study. They also thank the other physicians and dieticians who help to accomplish this project: Amit Assa MD, Neta Biran, Vered Nahmias-Friedlander MD, Dana Reznik, Firas Rinawi MD, Yoram Rosenbach MD, Rivka Shapiro MD, Eyal Zifman MD, Shelly Steiling.
1. Kugathasan S, Judd RH, Hoffman RG, et al Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease
in Wisconsin: a state wide population-based study. J Pediatr
2. Long MD, Crandall WV, Leibowitz IH, et al ImproveCareNow Collaborative for Pediatric IBD. Prevalence and epidemiology of overweight and obesity in children with inflammatory bowel disease
. Inflamm Bowel Dis
3. Gerasimidis K, McGrogan P, Edwards CA. The aetiology and impact of malnutrition in paediatric inflammatory bowel disease
. J Hum Nutr Diet
4. Gerasimidis K, Barclay A, Papangelou A, et al The Epidemiology of Anemia in pediatric inflammatory bowel disease
: prevalence and associated factors at diagnosis and follow-up and the impact of exclusive enteral nutrition. Inflamm Bowel Dis
5. Goodhand JR, Kamperidis N, Rao A, et al Prevalence and management of anemia in children, adolescents, and adults with inflammatory bowel disease
. Inflamm Bowel Dis
6. Wiskin AE, Fleming BJ, Wootton SA, et al Anaemia and iron deficiency in children with inflammatory bowel disease
. J Crohns Colitis
7. Bousvaros A, Zurakowski D, Duggan C, et al Vitamins A and E serum levels in children and young adults with inflammatory bowel disease
: effect of disease activity. J Pediatr Gastroenterol Nutr
8. Hoffenberg EJ, Deutsch J, Smith S, et al Circulating antioxidant concentrations in children with inflammatory bowel disease
. Am J Clin Nutr
9. Levy E, Rizwan Y, Thibault L, et al Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease. Am J Clin Nutr
10. Ojuawo A, Keith L. The serum concentrations of zinc, copper and selenium in children with inflammatory bowel disease
. Cent Afr JMed
11. Thomas AG, Miller V, Shenkin A, et al Selenium and glutathione peroxidase status in paediatric health and gastrointestinal disease. J Pediatr Gastroenterol Nutr
12. Levine A, Koletzko S, Turner D, et al European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease
in children and adolescents. J Pediatr Gastroenterol Nutr
13. Hyams JS, Ferry GD, Mandel FS, et al Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr
14. Turner D, Otley AR, Mack D, et al Development, validation, and evaluation of a Pediatric Ulcerative Colitis Activity Index: a prospective multicenter study. Gastroenterology
15. Levine A, Griffiths A, Markowitz J, et al Pediatric modification of the Montreal classification for inflammatory bowel disease
: the Paris classification. Inflamm Bowel Dis
16. Cameron N. Faulkner F, Tanner JM. The Methods of Auxological Anthropometry. Human Growth. Postnatal growth
. New York, NY: Plenum; 1978. 35–87.
17. Peters AM, Snelling HLR, Glass DM, et al Estimation of lean body mass in children. Br J Anesth
18. Absalom AR, Mani V, DeSmet T, et al Pharmacokinetic models for propofol-defining and illuminating the devil in the detail. Br J Anaesth
19. Wells JCK, Williams JE, Chomtho S, et al Body-composition reference data for simple and reference techniques and a 4-component model: a new UK reference child. Am J Clin Nutr
20. Abraham BP, Mehta S, El-Serag HB. Natural history of pediatric-onset inflammatory bowel disease
: a systematic review. J Clin Gastroenterol
21. Mack DR, Langton C, Markowitz J, et al Laboratory values for children with newly diagnosed inflammatory bowel disease
22. Gryboski JD. Crohn's disease in children 10 years old and younger: comparison with ulcerative colitis. J Pediatr Gastroenterol Nutr
23. Pappa HM, Grand RJ, Gordon CM. Report on the vitamin D status of adult and pediatric patients with inflammatory bowel disease
and its significance for bone health and disease. Inflamm Bowel Dis
24. González-Gross M, Valtueña J, Breidenassel C, et al HELENA Study Group. Vitamin D status among adolescents in Europe: the healthy lifestyle in Europe by nutrition in adolescence study. Br J Nutr
25. Kumar J, Muntner P, Kaskel FJ, et al Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES. Pediatrics
26. Korchia G, Amitai Y, Moshe G, et al Vitamin D deficiency in children in Jerusalem: the need for updating the recommendation for supplementation. Isr Med Assoc J
27. Oren Y, Shapira Y, Agmon-Levin N, et al Vitamin D insufficiency in a sunny environment: a demographic and seasonal analysis. Isr Med Assoc J
28. Gavin J, Anderson CE, Bremner AR, et al Energy intakes of children with Crohn's disease treated with enteral nutrition as primary therapy. J Hum Nutr Diet
29. Pons R, Whitten KE, Woodhead H, et al Dietary intakes of children with Crohn's disease. Br J Nutr
30. Thomas AG, Taylor F, Miller V. Dietary intake
and nutritional treatment in childhood Crohn's disease. J Pediatr Gastroenterol Nutr
31. Linhart Y, Romano-Zelekha O, Shohat T. Validity of self-reported weight and height among 13-14 year old schoolchildren in Israel. Isr Med Assoc J
32. Mishkin S. Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory bowel disease
. Am J Clin Nutr
33. Lopes LH, Sdepanian VL, Szejnfeld VL, et al Risk factors for low bone mineral density in children and adolescents with inflammatory bowel disease
. Dig Dis Sci
34. Tsiountsioura M, Wong JE, Upton J, et al Detailed assessment of nutritional status and eating patterns in children with gastrointestinal diseases attending an outpatients clinic and contemporary healthy controls. Eur J Clin Nutr
35. Gerasimidis K, Talwar D, Duncan A, et al Impact of exclusive enteral nutrition on body composition and circulating micronutrients in plasma and erythrocytes of children with active Crohn's disease. Inflamm Bowel Dis
36. Dallman PR, Siimes MA. Percentile curves for hemoglobin and red cell volume in infancy and childhood. J Pediatr