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©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Oct 7, 2014; 20(37): 13219-13233
Published online Oct 7, 2014. doi: 10.3748/wjg.v20.i37.13219
Published online Oct 7, 2014. doi: 10.3748/wjg.v20.i37.13219
Table 1 Summary of the main studies that were reviewed on nutritional concerns in pediatric Crohn’s disease
| Ref. | Type of study | Patients | Results | Conclusion |
| Vaisman et al[25], Nutrition 2006 | Prospective cohort study | 16 pts with CD; Age 19-57 yr Remission of disease (CDAI Activity Disease Index < 150); 2 groups (BMI 18.5 kg/m2 as a cutoff point) | Subjects with lower BMIs tended to have less lean body mass (P = 0.006), less bone mineral density (P = 0.006), and lower resting energy expenditure (P = 0.003); No correlation between BMI and energy intake, although percentage of malabsorption negatively correlated with BMI (P = 0.07) | In the presence of similar energy intake, resting energy expenditure does not seem to contribute to lower BMI, although nutrient malabsorption is higher in malnourished patients with CD in remission; Malabsorption should be evaluated in patients with CD who fail to gain Wt during disease remission, to establish their extra caloric requirements |
| Gupta et al[28], Inflamm Bowel Dis 2013 | Retrospective review | 43 IBD pts (mean age 12.8 yr; range 5.1-17.4 yr) 67% M 33% F | Reductions in erythrocyte sedimentation rate (P < 0.0001) and C-reactive protein (P < 0.02), and increases in albumin (P < 0.03); Mean PCDAI score 26.9 at baseline and 10, 2 at follow-up (P < 0.0001); Induction of remission achieved in 65% and response in 87% at a mean follow-up of 2 mo (1-4 mo) | Novel protocol for enteral nutrition (80%-90% of patient’s caloric needs) seems to be effective for the induction of remission in CD children; The protocol may result in improved EN acceptance and compliance and will be evaluated prospectively |
| Wiskin et al[29], J Hum Nutr Diet 2012 | Prospective cohort study | 46 IBD children | No children scored low risk with STAMP, STRONGkids or PNRS; 23 children scored low risk with PYMS; Good agreement between STAMP, STRONGkids, and PNRS (K > 0.6); Modest agreement between PYMS and the other scores (K = 0.3); No agreement between the risk tools and the degree of malnutrition based on anthropometric data (K < 0.1) | Relevance of nutrition screening tools for children with chronic disease is unclear; There is the potential to under recognize nutritional impairment (and therefore nutritional risk) in children with IBD |
| Valentini et al[30], Nutrition 2008 | Prospective, controlled, multicentric study | 94 pts with CD (CDAI 71 +/- 47) 61 F 33 M 50 UC (UCAI 3.1 +/- 1.5) 33 F 17 M 61 healthy control subjects 41 F 20 M from centers in Berlin (Germany), Vienna (Austria), and Bari (Italy) 47 well-nourished patients with IBD pair-matched to healthy controls by BMI, sex, and age | 74% IBD patients were well-nourished according to the SGA, BMI, and serum albumin; Body composition analysis demonstrated a decrease in BCM in patients with CD (P = 0.021) and UC (P = 0.041) compared with controls; Handgrip strength correlated with BCM (r = 0.703, P = 0.001) and was decreased in patients with CD (P = 0.005) and UC (P = 0.001) compared with controls; Lower BMC in patients with moderately increased serum CRP levels compared with patients with normal levels | In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening |
| Chan et al[31], Am J Gastroenterol 2013 | Prospective cohort study | 300724 participants (recruited into the European Prospective Investigation into Cancer and Nutrition study) 177 UC and 75 CD | No associations with the four higher categories of BMI compared with a normal BMI for UC (P trend = 0.36) or CD (P trend = 0.83); Lack of associations when BMI analyzed as a continuous or binary variable (BMI 18.5 kg/m2vs≥ 25 kg/m2); Physical activity and total energy intake not associated with UC (P trends 0.79-0.18) or CD (P trends 0.42-0.11) | Obesity as measured by BMI not associated with the development of incident UC or CD; Alternative measures of obesity required to further investigate the role of obesity in the development of incident IBD |
| Werkstetter et al[32], J Crohns Colitis 2012 | Prospective cohort study | 39 IBD children in remission; 27 CD, 12 UC 24 M; 39 healthy age-sex-matched controls | IBD pts vs controls: Lower Z-scores for phase angle α [-0.72; 95%CI: (-1.10-0.34)] Lower grip strength [-1.02 (-1.58-0.47) Lesser number of steps per day [-1339 (-2760-83)] Shorter duration of physical activity [-0.44 h (-0.94-0.06)], particularly in F and patients with mild disease. Quality of life and energy intake did not differ between patients and controls | In spite of quiescent IBD, lean body mass and physical activity were reduced; Interventions to encourage physical activity may be beneficial in this lifelong disease |
| Gerasimidis et al[33] Inflamm Bowel Dis 2013 | Prospective cohort study | 184 new pediatric IBD Dg 139 one year follow-up IBD children 84 children treated with EEN | 72% anemic at Dg; Anemic children with CD had shorter diagnosis delay, lower BMI, lower Dg delay (P < 0.001) and BMI Z-score, P = 0.003) than non-anemic patients; Extensive colitis associated with severe anemia in UC; After EEN, severe anemia decreased (32%-9%, P < 0.001) and hemoglobin concentration increased by 0.75 g/dL | Anemia is frequent at Dg and follow-up and should receive more attention from the clinical team; The focus should remain suppression of inflammatory process in active disease |
Table 2 Summary of the main studies that were reviewed on growth issues and bone health in pediatric Crohn’s disease
| Ref. | Type of study | Patients | Results | Conclusion |
| Abraham et al[21] J Clin Gastroenterol 2012 | Systematic review | 3505 CD, 2071 UC, and 461 IBD-U (age at onset < 18 yr) | Growth failure was reported in CD (10% and 56%) more often than UC (0%-10%) or non-IBD controls; Improvements in growth occurred after surgical resection in CD pts; Increase in disease reclassification over time from UC and IBD-U Dg to CD; CD pts had higher number of hospitalizations and hospital days per year vs UC pts in most studies; The reported surgery rates in CD ranged between 10% and 72%; the colectomy rates in UC ranged between 0% and 50% | Childhood-onset IBD pts had growth failure reported in pts with CD more often than those with UC, and had a reclassification of disease type to CD over time; Higher rates of surgery and hospitalizations were found with CD than with UC |
| Kim et al[45] Clin Endosc 2013 | Prospective cohort study | 44 IBD (21 aged < 30 yr; 23 aged > 30 yr) | Significant bone mass reduction at the LS in IBD patients aged < 30 yr vs patients aged > 30 yr (BMD P < 0.01; T-score P < 0.01; Z-score P < 0.01); Multivariate analysis: risk factor of bone mass reduction for patients < 30 yr → HR = 3.96, P = 0.06 | Bone mass reduction is more severe in patients diagnosed with IBD before the age of 30 yr |
| Schmidt et al[51] J Pediatr Gastroenterol Nutr 2012 | Longitudinal cohort study | 144 IBD pts 83 UC, 45 CD | Children with UC and CD had significantly lower mean BMD Z-scores for the LS at baseline and after 2 yr; The reduction in BMD was equally pronounced in patients with UC and CD; Neither group improved their Z-score during the follow-up period; Significantly lower mean BMD Z-scores for the LS were found at baseline in M (P < 0.001), but not in F; Lowest BMD values in the group of patients ages 17 to 19 yr in M and in F | The entire group of pediatric patients with IBD showed permanent decreases in their BMD Z-scores for the LS; however, afflicted children have the potential to improve their BMD by the time they reach early adulthood |
| Tsampalieros et al[53] J Clin Endocrinol Metab 2013 | Prospective cohort study | CD (age 5-21) | Disease activity improved over the study interval (P < 0.001); Trabecular BMD-Z improved over the first 6 mo; Increases associated with improved disease activity (P < 0.001), younger age (P = 0.005), and increases in vitamin D levels (P = 0.02); Greater increases in tibia length associated with greater increases in cortical area-Z (P < 0.001); Greater glucocorticoid doses and disease activity significantly associated with failure to accrue cortical area, and more pronounced with greater linear growth (interaction P < 0.05); Mean ± SD trabecular BMD and cortical area Z-scores significantly reduced at the final visit | CD was associated with persistent deficits in trabecular BMD; Younger participants demonstrated greater potential for recovery; Greater linear growth associated with greater recovery of cortical dimensions, especially among participants with lesser glucocorticoid exposure and inflammation; Younger age and concurrent growth provide a window of opportunity for skeletal recovery |
| Malik et al[54] J Crohns Colitis 2012 | Prospective cohort study | 36 children with CD (Male 22) | 28 (78%) CD children treated with adalimumab went into remission; Overall 42% of children showed catch-up growth, which was more likely in: Pts who achieved remission (P = 0.007); Pts who were on immunosuppression (P = 0.03); Pts whose indication for adalimumab was an allergic reaction to infliximab (P = 0.02); Pts who were on prednisolone when starting adalimumab, (P = 0.04) | Clinical response to adalimumab is associated with an improvement in linear growth in a proportion of children with CD; Improved growth is more likely in patients entering remission and on immunosuppression but is not solely due to a steroid sparing effect |
| Malik et al[55] Arch Dis Child 2012 | Retrospective cohort study | 116 CD children; 68 M; Mean age at diagnosis 10.8 yr (range 4.9-15.5); Mean age at maximum follow-up of 15.4 yr (9.4-19.3) | At T0, mean height SD score was -0.5 (-3.3-2.6) compared to a mid-parental mean height SD score of 0.2 (-2.0-1.4) (P = 0.002); At T1, T2, T3, and maximum follow-up, mean height SD score was -0.6 (-4.8-7.8), -0.6 (-2.9-2.2), -0.7 (-3.6- 2.5) and -0.5 (-3.5-2.9), respectively; Mean Ht velocity SDS at T1, T2, T3 and maximum follow-up was -1.4 (-7.4-7.4), -0.6 (-7.5-6.1), -0.1 (-6.6 -7.6) and 0.6 (-4.8-7.8), respectively (P < 0.05) | In final models: Mean Ht velocity SDS was associated negatively with the use of prednisolone (P = 0.0001), azathioprine (P = 0.0001), methotrexate (P = 0.0001), and weight SDS (WtSDS) P = 0.0001); Mean Ht velocity SDS was associated positively with age (P = 0.0001) and Wt SDS (P = 0.01); ΔHt SDS was associated negatively with use of prednisolone (P < 0.02) |
| Laakso et al[56] Calcif Tissue Int 2012 | Cross-sectional Cohort Study | 80 IBD pts (median age 14.9 yr, range 5-20), median disease duration 3.4 yr; 51 UC, 26 CD, and 3 IBD-U | IBD pts had lower bone age-adjusted LS and whole-body areal BMD (P < 0.001 for both) and whole-body composition adjusted for Ht (P = 0.02) than controls; Lean mass and fat mass Z-scores did not differ between the groups, but IBD patients had lower whole-body composition relative to muscle mass (P = 0.006); Vitamin D deficiency in 48%, despite vitamin D supplementation; In IBD cumulative weight-adjusted prednisolone dose > 150 mg/kg for the preceding 3 yr increased the risk for low whole-body areal BMD (OR = 5.5, 95 %CI: 1.3-23.3, P = 0.02). Vertebral fractures found in 11% of patients and in 3% of controls (P = 0.02) | IBD in childhood was associated with low areal BMD and reduced bone mass accrual relative to muscle mass; The risk for subclinical vertebral fractures may be increased; Careful follow-up and active preventive measures are needed |
| Ahmed et al[60] J Pediatr Gastroenterol Nutr 2004 | Prospective cohort study | 47 CD and 26 UC (median age of 13.5 yr - range, 5.5-18.2 yr) | Pts with CD were shorter than those with UC (P < 0.05); Median ppBone Area for LS and total body for the whole group was 85% and 81%, respectively; ppBone Area at both sites was directly related to height SDS and BMI SDS (r > 0.5; P < 0.005); Median BMD SDS for LS and total body was -1.6 and -0.9, respectively; Median ppBMC for LS and total bone was 98% and 101%, respectively; ppBMC showed no relationship to ppBone Area (r = 0.1, NS); Children with osteopenia 22% after adjustment for bone area | Children with IBD often have small bones for age because they have growth retardation; When DXA data are interpreted with adjustment for bone size, most children have adequate bone mass; Correct interpretation of DXA is important for identifying children who may be at a real risk of osteoporosis |
| Burnham et al[61] J Bone Miner Res 2004 | Prospective cohort study | 104 children and young adults with CD 233 healthy controls (age 4-26) | CD pts had significantly lower Ht Z-score, BMI Z-score, and lean mass relative to Ht compared with controls (all P < 0.0001); After adjustment for group differences in age, Ht, and race, the ratio of BMC in CD relative to controls was significantly reduced in M (0.86; 95%CI: 0.83-0.94) and F (0.91; 95%CI: 0.85-0.98) with CD; Adjustment for pubertal maturation did not alter the estimate; addition of lean mass to the model eliminated the bone deficit; Steroid exposure was associated with short stature but not bone deficits | Importance of considering differences in body size and composition when interpreting DXA data in children with chronic inflammatory conditions; Association between deficits in muscle mass and bone in pediatric CD |
| Boot et al[62] Gut 1998 | Prospective cohort study | 55 pts (34 M 21 F, age range 4-18 yr) 22 CD, 33 UC | Mean SDS of LS BMD and total body BMD were significantly lower than normal (-0.75 and -0.95, both P < 0.001); Height SDS and BMI SDS were decreased. The decrease in BMD SDS could not be explained by delay in bone maturation; The cumulative dose of prednisolone correlated negatively with LS BMD SDS (r = -0.32, P < 0.02); BMI SDS correlated positively with total body BMD SDS (r = 0.36, P < 0.02); CD pts had significantly lower LS and total BMD SDS than UC pts, even after adjustment for cumulative dose of prednisolone; In the longitudinal data cumulative dose of prednisolone between the measurements correlated negatively with the change in LS and total BMD SDS; Lean tissue mass measured by dual X-ray absorptiometry had a strong correlation with lean body mass measured by bioelectrical impedance analysis (r = 0.98) | IBD children have a decreased BMD; CD children have a higher risk of developing osteopenia than UC children; Corticosteroid therapy and nutritional status are important determinants of BMD in IBD pts |
Table 3 Summary of the main studies that were reviewed on management of growth and pubertal issues in pediatric Crohn’s disease
| Ref. | Type of study | Patients | Results | Conclusion |
| Mason et al[66] Horm Res Paediatr 2011 | Retrospective cohort study | IBD adolescents 41 with CD, 30 M 11 F 26 with UC, 14 M 12 F | Altered parameters of pubertal growth observed in the CD groups compared to the normal population: In the CD M group, median Ht at Dg was -0.56 (P = 0.001) and median age at peak Ht velocity was 14.45 yr (P = 0.004) In the CD F group, median Ht at Dg was -1.14 (P = 0.007) and Ht at peak Ht velocity was -0.79 (P = 0.039). Individually, 8/30 CD M cases had one or more parameter affected: In the whole group, age at peak Ht velocity showed an association with ESR (r = 0.4; P = 0.005) and an inverse association with BMI (r = 0.4; P = 0.001) | Disorders of pubertal growth are more likely to occur in CD (particularly M) |
| Tietjen et al[69] Turk J Gastroenterol 2009 | Prospective cohort study | 40 pts with CD 26 M, 14 F mean age 16,7 yr (median: 17 yr, range: 4-29 yr) | Urinary GH levels were found as normal in CD; Corticosteroid therapy did not appear to be the most responsible factor for growth failure in CD | Growth failure in patients with CD is not caused by GH deficiency; A high PCDAI score has an important impact on impaired growth in children and adolescents with CD |
| Wong et al[70] J Pediatr Endocrinol Metab 2007 | Retrospective data analysis | 7 pts with CD 5 M | Median chronological age and median difference between chronological age and bone age was 15.9 yr (range, 13.0-17.9 yr) and 1.7 yr (-0.7-3.3 yr), respectively; Median dose of rhGH at T+0 was 0.23 mg/wk (0.15-0.31); Pubertal status remained unchanged in 6/7 patients; Median albumin and C-reactive protein were similar at T+0 and T+6; Median height SDS at T+0, T+6 and T+12 was -2.2 (-4.0 to -1.5), -1.9 (-4.1 to -0.8), -1.9 (-4.1 to -0.7), respectively (NS). Median Ht velocity SDS at T+0 and T+6 was -2.5 (-4.8-1.4) and -0.9 (-5.3 to 3.4), respectively (NS); Positive correlation between percentage change in Ht velocity SDS at T+6 and dose of rhGH at T+0 (r = 0.8, P = 0.03) | Introduction of rhGH therapy was associated with a cessation in the deterioration in linear growth; An improvement in Ht SDS was not observed over the period of the study |
| Wong et al[71] Clin Endocrinol (Oxf) 2011 | Randomized controlled trial in 2 tertiary Children's Hospitals | 22 children with IBD 21 with CD | Median Ht velocity increased from 4.5 (range, 0.6-8.9) at baseline to 10.8 (6.1-15) cm/year at 6 mo (P = 0.003) in the rhGH group, whereas in the Ctrl group, it was 3.8 (1.4-6.7) and 3.5 cm/yr (2-9.6), respectively (P = 0.58); Median percentage increase in Ht velocity after 6 mo in the rhGH group was 140% (16.7%-916.7%) compared with 17.4% (-42.1%-97.7%) in the Ctrl group (P < 0.001). No significant differences in disease activity and proinflammatory cytokines at baseline and 6 mo in both groups | rhGH can improve short-term linear growth in children with CD; The clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis, and disease status |
- Citation: Gasparetto M, Guariso G. Crohn's disease and growth deficiency in children and adolescents. World J Gastroenterol 2014; 20(37): 13219-13233
- URL: https://www.wjgnet.com/1007-9327/full/v20/i37/13219.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i37.13219