Nutrition and Growth in Chronic Disease

Anat Guz-Mark, Raanan Shamir

Chronic disease during infancy childhood and adolescence can deeply affect the
child’s nutritional state, alter the full potential of growth, and modify body composition.
Moreover, nutritional status can influence the disease course, complications, and
outcomes. Growth impairment is a common feature of chronic diseases in children,
resulting from numerous contributing factors that include chronic inflammation, poor
or inadequate energy and nutrient intake, reduced physical activity, and high energy
In this chapter, some leading articles published on peer-review journals over the last
year are reviewed. The selected 10 articles represent various aspects of nutrition and
growth in 5 major chronic diseases of childhood: inflammatory bowel disease, celiac
disease, juvenile idiopathic arthritis, cystic fibrosis, and cerebral palsy. These articles
were selected for their enhancement and amplification of current knowledge regarding
aspects of pathophysiology, advanced nutritional evaluation, treatment strategies,
and contemporary challenges regarding nutrition and growth in pediatric chronic

Inflammatory Bowel Disease

The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction

Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn’s disease. It is unknown how faecal calprotectin changes during food re-introduction and the influence of maintenance enteral nutrition.
Aims: To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition. 
Methods: Children with Crohn’s disease were followed during exclusive enteral nutrition and during food-reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food-reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3.
Results: Sixty-six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn’s disease activity index < 12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1,433 [Q1: 946, Q3: 1,820] vs. 33 days: 844 [314, 1,438] vs. 54 days: 453 [165, 1,100]; p < 0.001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1,094 [660, 1,625] (both p < 0.02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non-users (651 [Q1: 271, Q3: 1,781] vs. 1,238 [749, 2,102], p = 0.049) and correlated inversely with maintenance enteral nutrition volume (rho –0.573, p = 0.041), kcals (rho –0.584, p = 0.036) and % energy intake (rho –0.649, p = 0.016). Maintenance enteral nutrition use was not associated with longer periods of remission (p = 0.7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission.
Conclusions: The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ∼ 18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.

Crohn’s disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial

Background and Aims: 
Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn’s disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier.
Methods: We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestlé) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n = 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n = 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12.
Results: Four patients withdrew from the study because of intolerance by 48 h, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (p = 0.002; OR for tolerance of CDED and PEN, 13.92; 95% CI 1.68–115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission versus 20 (59%) of 34 children given EEN (p = 0.38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid free
remission compared with 14 (45.1%) of 31 children given EEN and then PEN (p = 0.01; OR for remission in children given CDED and PEN, 3.77; CI 1.34–10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria.
Conclusion: CDED plus PEN was better tolerated than EEN in children with mild to moderate CD. Both diets were effective in inducing remission by week 6. The combination CDED plus PEN induced sustained remission in a significantly higher proportion of patients than EEN, and produced changes in the fecal microbiome associated with remission. These data support use of CDED plus PEN to induce remission in children with CD.

Treatment of active Crohn’s disease with an ordinary food-based diet that replicates exclusive enteral nutrition

Background and Aims: 
Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn’s disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD.
Methods: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five
children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment.
Results: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs. CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs. 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs. 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs. 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs. 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs. 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log 10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [ p = 0.015] and 1.0 for CD-TREAT [ p = 0.044] vs. chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; p = 0.002).
Conclusion: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD.
The pathogenesis of Crohn’s disease (CD) appears to involve alteration of the microbiome as well as a breakdown in barrier function with defective bacterial clearance.
Over the last decade, there is a growing body of evidence suggesting that dietary factors
may play a role in the generation of inflammation by modulating the microbiome, tight junctions, and mucous layer [1]. Treating active CD by modifying the patients’ diet has long been one of the most desirable therapeutic strategies, but until 2019 there were no randomized controlled studies demonstrating the efficacy of dietary treatment in the management of CD.
Dietary therapy by means of exclusive enteral nutrition (EEN), which is a liquid-only formula diet consumed for 6–8 weeks, is a highly effective treatment for achieving clinical remission and is recommended as the first-line treatment for active luminal disease in children [2].
Isocaloric partial enteral nutrition (PEN) with exposure to food was not effective
enough in inducing or maintaining remission in various previous studies [3, 4], suggesting that complete exclusion of food plays an important role in the success of EEN. The study of Logan et al. cited in this chapter reinforces the short-term effect of EEN on bowel inflammation as suggested by the rise in fecal calprotectin after food reintroduction. Notably, this study showed that the increase in fecal calprotectin, following EEN, occurs even more rapidly than previously recognized [5], with a significant increase within just 17 days of food reintroduction. The median daily rate of fecal calprotectin rise was evaluated as 20 mg/kg/day. PEN, which was practiced by 41% of patients after the period of EEN, was associated with a significantly lower fecal calprotectin levels compared to patients not using PEN. Despite this early positive effect,
there was no significant difference in relapse rate at either 6 or 12 months post-EEN
between patients with or without PEN supplementation. However, while previous studies aimed for PEN providing about 50% of daily amount of calories, the amount of PEN consumed by patients in this cohort was relatively low, with a median of 18% of their total energy intake.
Nonetheless, the early rise in fecal calprotectin observed in this study after cessation
of EEN highlights the potent role of early dietary inflammatory triggers within the early food reintroduction phase. This finding further supports the need for discovering other adjuvant dietary treatments with better tolerance and adherence profiles for long-term dietary management of CD.
The CD exclusion diet (CDED) is a whole-food diet coupled with PEN, designed to reduce exposure to dietary components, hypothesized to negatively affect the microbiome, intestinal barrier, and intestinal immunity, and was shown to be effective in remission induction in a non-randomized study in children and adults who failed biologic
therapy [6]. The multinational randomized controlled trial of Levine et al. [1] compared both the tolerability and the efficacy of CDED with those of EEN in pediatric patients with active mild-to-moderate CD. The remarkable results of this study showed not only better tolerance for CDED coupled with PEN but also a superior sustained remission and reduction in inflammation by week 12, compared to the standard of care therapy with EEN. Fecal calprotectin was evaluated in this study as well, on top of the clinical markers. Both groups demonstrated similar drops in fecal calprotectin during the induction 6-week period with no significant differences, whereas in the CDED + PEN group, the calprotectin continued to decline between week 6 and week 12.
The major importance of this study is it being the first randomized controlled trial to demonstrate the non-inferiority of the specific whole-food diet coupled with PEN in achieving remission, compared to EEN. Second, the differences between the groups after week 6, during the period of food reintroduction in the EEN group, showed superiority of CDED + PEN in obtaining sustained remission and continued drop of calprotectin by week 12. The microbiome analysis revealed a different pattern between the groups: while in the CDED + PEN group the microbiome continued to change between week 6 and 12, the microbiome of the EEN group generally rebounded to pretreatment levels at week 12. This could provide a plausible pathophysiologic explanation to the results, supporting the theory that exclusion of dietary components by EEN or CDED reduces microbiota species that are associated with CD [7] , with a rebound of the same proinflammatory microbiota patterns upon re-exposure to regular diet.
Despite its remarkable results, the study suffers from some major limitations: (1) From
week 6, the CDED group received the CDED diet (active treatment) with very partial
PEN (25%), while the control group received regular diet with very partial (25%) PEN
leaving them with a disadvantage in treatment. (2) The lack of endoscopic evaluation,
not allowing the determination of mucosal healing in any group, especially considering
the fact that calprotectin levels remained elevated in many patients in this study.
(3) The 40% remission at week 12 in the EEN group is significantly lower than the remission rate observed in EEN studies. (4) PEN is inferior to EEN but does have an effect on inducing remission. Thus, the contributing effect of the supplementation of PEN
on top of the CDED itself is yet to be determined.
The CD treatment-with-eating diet (CD-TREAT) described by Svolos et al. is another development of ordinary food diet, which is based on the composition of EEN. As the authors state, this diet recreates EEN by the exclusion of certain dietary components (egg, gluten, lactose, and alcohol) and matching of others (macronutrients, vitamins, minerals, and fiber) as closely as possible using ordinary food. The diet was tested in mice, healthy adult volunteers, and 5 children with active CD. The main findings included similar effects to those of EEN on the gut microbiome and metabolome of the healthy participants; reduced ileitis in the rat model of disease; and clinical remission with a decrease in fecal calprotectin in 3 of 5 children with active CD after 8 weeks of diet. The establishment of efficacy of CD-TREAT in patients with active CD requires replication in large clinical trials. Overall, a wide variability and sometimes contradiction exists across diets that are being tested for CD over the last few years. Paradoxically, even EEN that is the nutritional intervention with the strongest evidence for the induction of remission, contains emulsifiers, is commonly based on milk formula, and has a low amount of fibers all of which are presumed to promote dysbiosis and proinflammatory state [8]. This fascinating era of nutritional research in inflammatory bowel diseases holds a promise for better and safer treatment strategies in the future together with better understanding of the disease pathophysiology and environmental interactions.

Celiac Disease

The Relationship between Body Composition and a Gluten Free Diet in Children with Celiac Disease

The primary and proven therapy, in cases of celiac disease (CD), is a rigorous gluten-free diet (GFD). However, there are reports of its negative effects in the form of nutritional deficiencies, obesity, and adverse changes in body composition. The study aimed to assess the impact of a GFD on the body composition of children with CD. In a case-controlled study ( n = 41; mean age 10.81 y; SD = 3.96) children with CD, in various stages of treatment, underwent medical assessment. The control group consisted of healthy children and adolescents, strictly matched for gender and age in a 1: 1 casecontrol manner. More than half of the examined children ( n = 26) followed a GFD. CD children had significantly higher mean values of the fat free mass (FFM% = 80.68 vs. 76.66, p = 0.015), and total body water (TBW% = 65.22 vs. 60.47, p = 0.012), and lower mean values of the fat mass (FM% = 19.32 vs. 23.34, p = 0.015). Children who were on a GFD presented slightly higher, but not statistically significant, mean values of FM and FFM, than children who did not follow dietary recommendations (FM [kg] = 7.48 vs. 5.24, p = 0.064; FM% = 20.81 vs. 16.73, p = 0.087; FFM [kg] = 28.19 vs. 22.62, p = 0.110). After minimum 1 year of a GFD, CD children showed significantly higher values of FFM [kg] (p = 0.001), muscle mass (MM) [kg] (p < 0.001), TBW [L] (p < 0.001) and body cell mass (BCM) [kg] (p < 0.001). Furthermore, CD children who were on a GFD presented a significantly higher increase in weight (p = 0.034) and body mass index (BMI; p = 0.021). The children adhering to a GFD demonstrate a tendency towards higher indices of selected body composition components.
Celiac disease (CeD) is an immune-mediated enteropathy, affecting genetically susceptible individuals upon dietary exposure to gluten peptides. The immune response causes inflammatory damage to the intestinal mucosa, further evolving into villous atrophy and reduced absorptive and digestive capacity. Classical presentation of CeD can include symptoms of malabsorption, weight loss, failure to thrive, and delayed growth. The impact of CeD on different components of body composition had been assessed by several studies in the past, with conflicting results ranging between similar body composition compared to healthy controls [9, 10] and reduced fat mass and lean body mass compared to healthy controls [11, 12] . The main components reported to recover under gluten free diet (GFD) are the fat mass and body mass index (BMI) [13, 14] . There is a controversy regarding the long-term impact of GFD on nutritional status as well as body composition, with a concern regarding increased adiposity, high fat content of the diet, and nutritional imbalance in uncontrolled GFD [10, 15–17] . This study evaluated body composition of children with CeD, compared to case-controlled
healthy children. Body composition was assessed using bioelectric impedance. Although relatively small scale, the findings of this study are interesting. Children with CeD had different patterns of body composition compared to healthy controls, mainly lower fat mass and fat mass percentage, on the expense of higher fat-free mass percentage and total body water percentage. These trends were further emphasized in the comparison of GFD noncompliant to compliant patients. Patients with CeD who were not compliant with GFD had lower fat mass and higher fat free mass compared to compliant patients, although these differences did not reach statistical significance (possibly due to the small sample size). These findings suggest that children with CeD, and especially those who are not treated with appropriate GFD, have reduced body energy reserves reflected by their low fat mass.
A subset of patients in this study were followed with subsequent measurements after
a mean of 17 months. Of those, the small group of patients who did not adhere to GFD
showed a decrease in their BMI compared to an increase in the group of patients that
adhered to GFD, further demonstrating the negative impact of CeD on the nutritional
status and body composition of these children.
During a mean of 17-month follow-up in this study, patients with CeD demonstrated
an expected increase in weight, height, absolute fat mass, muscle mass, and fat-free
mass. There were no significant changes in any of the relative values, expressed as
percentage of body composition, during the follow-up. This important finding suggests
that components of body composition can remain stable under the maintenance
of GFD, although larger long-term studies, including follow-up into adulthood,
are needed to better assess the impact of GFD on body composition overtime.

Celiac disease and bone health in children and adolescents: a systematic review and meta-analysis

Celiac disease is characterized by deficits in bone mineral accrual and longitudinal growth.
Objective: The purpose of this study was to determine the differences in bone health and stature among children and adolescents with celiac disease versus healthy controls.
Data Sources: Articles published before February 27, 2018 were located using searches of the Physical Education Index (n = 186), PubMed (n = 180), Scopus (n = 3), SPORTDiscus (n = 3), and Web of Science (n = 4).
Study Selection: Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed via dual-energy X-ray absorptiometry, and height was measured using a stadiometer.
Data Extraction: Effect sizes (ES) were calculated as follows: the mean difference of the celiac disease group and healthy control group, divided by the pooled standard deviation. The inverse variance weight was used to calculate the overall mean ES. Random-effects models were used to aggregate a mean ES, 95% CIs and to identify potential moderators.
Results: The results of 30 effects gathered from 12 studies published between 1996 and 2017 indicated BMC (ES –0.54, 95% CI –0.69 to –0.40; p < 0.0001) and aBMD (ES –0.72, 95% CI –0.96 to –0.47; p < 0.0001) were lower in youth with celiac disease.
Limitations: These results were limited to only cross-sectional and baseline data from longitudinal studies reporting BMC and BMD, however did not assess changes in bone health over time.
Conclusion: Children and adolescents with celiac disease have suboptimal bone health and shorter stature.
Bone health is known to be negatively affected by CeD in various ways. Intestinal
malabsorption of micronutrients is a major determinant of poor bone mass accruement,
with the reduction of calcium and vitamin D absorption causing an elevation in parathyroid hormone and further bone loss [18]. Other nonintestinal factors associated with bone injury are mainly the result of the increased production of proinflammatory cytokines causing bone turnover and remodeling imbalance [19]. The majority of evidence regarding reduced bone mass in CeD is based on adult studies, with estimated prevalence of osteopenia in one-third and osteoporosis in another one-third of the patients [20]. There is also a reported increased risk of fractures [21]. The presence of bone disease and osteopenia in young age is of great importance, given the critical period for bone mass accrual in childhood and adolescence, and the known impact of bone health in childhood tracking into adulthood [22, 23].
In this comprehensive study, Fedewa et al. performed a meta-analysis of published data regarding bone mineral content (BMC) and areal bone mineral density (aBMD) in newly diagnosed children and adolescents with CeD, compared to healthy controls. Twelve studies met their inclusion criteria for analysis. The pulled results from this meta-analysis indicated a significant reduction of BMC and aBMD in children and adolescents with CD compared to healthy controls, with a mean Hedge’s effect size of –0.54 and –0.72, respectively (p < 0.0001). Notably, the finding of lower bone mass and density in children with CD was found to be stable regardless of the skeletal region assessed in the reported studies. A secondary outcome assessed in this analysis was the effect size of height and body weight that were found to be significantly lower in children with CeD compared to healthy controls (mean effect size for height = –0.79, 95% CI –1.11 to –0.47; mean effect size for body weight = –0.71, 95% CI –1.00 to 0.42; p < 0.0001). The close link between bone density and height in children [24] further emphasize the importance of acknowledging poor linear growth in pediatric patients with CeD.
The main limitation of this study is its cross-sectional nature and, therefore, the lack of
data on long-term bone status and the effect of GFD on bone health. Nevertheless, the
importance of this study is the incorporation and pooled analysis of data regarding bone
health in children with CeD. These findings reinforce the importance of the negative effects of CeD on both growth and bone mass in young age. More high-quality, controlled, longitudinal studies are further needed to assess long-term changes in bone health in patients with CeD overtime.

Juvenile Idiopathic Arthritis

Growth patterns in early juvenile idiopathic arthritis: Results from the Childhood Arthritis Prospective Study (CAPS)

To investigate early vertical growth patterns and factors associated with poor growth in a modern inception cohort of UK children with juvenile idiopathic arthritis (JIA) using data from the Childhood Arthritis Prospective Study (CAPS).
Methods: A study period of 3 years was chosen. Children included in this analysis had a physician diagnosis of JIA and had height measurements available at both baseline and at 3 years of followup. Height is presented as z-scores calculated using World Health Organisation growth standards for age and gender. Growth over the 3-year period was assessed using change in z-score and height velocity. Univariable and multivariable linear regressions were used to identify factors associated with height z-score at baseline and change of height z-score at 3 years.
Results: 568 patients were included; 65% female, median baseline age 7.4 years (interquartile range [IQR] 3.6 to 11.2), median symptom duration at presentation 5.5 months (IQR 3.1 to 11.6). Height z-score decreased significantly from baseline to 3 years (p ≤ 0.0001); baseline median height z-score was –0.02 (IQR –0.71 to 0.61), decreasing to –0.47 (IQR –1.12 to 0.24) at 3 years. Growth restriction, defined as change of height z-score ≤ –0.5, was observed in 39% of patients. At 3 years, higher baseline height z-score was the strongest predictor for a negative change in height z-score (–0.3 per
unit of baseline height z-score [95% CI –0.36 to –0.24], p < 0.0001).
Conclusions: Although overall height at 3 years after initial presentation to rheumatology is within the population norm, as a cohort, children with JIA experience a reduction of growth in height over the first 3 years of disease. Late presentation to paediatric rheumatology services is associated with lower height at presentation. However, patients with the lowest height z scores at presentation were also the most likely to see an improvement at 3 years. The impact of JIA on growth patterns is important to children and families and this study provides useful new data to support informed clinical care.
Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory
connective tissue diseases in childhood, with significant morbidity and the development
of disability over the disease course. Similar to any systemic chronic inflammatory
illness, growth impairment is an important complication of JIA, affecting up to a
third of JIA patients in early adulthood, dependent on the disease subtype [25] . The
reasons for poor growth in JIA are multifactorial and may relate to the degree of systemic inflammation, poor appetite and suboptimal nutrition, and the use of corticosteroids.
In this current longitudinal multicenter study from UK, the authors investigated early growth patterns over the first 3 years of disease presentation in children. In this large cohort, nearly half of the patients were classified as oligoarthritis. Forty-four percent
of the patients received systemic corticosteroids, and 21% received biologic therapy.
The most notable finding in this study is the significant decrease in height z scores across all JIA subtypes over the first few years of disease, although most prominent in
systemic JIA and psoriatic arthritis. BMI z-score did not change significantly at 3 years.
Total time on oral or intravenous steroids during the 3-year period was significantly
associated with decrease in height z -score. This association was observed even after
adjusting for disease activity, strengthening the independent negative effects of corticosteroids on linear growth in children with JIA, going far beyond the simple association between use of steroid treatment and disease severity [26] . This study emphasizes that even in the era of biologic treatments, corticosteroid use is still common in JIA and that growth failure continues to be a major challenge in the treatment of
these children. The identification of growth restriction developing early in the disease
course merits the discussion regarding early aggressive treatment regiments to prevent
irreversible growth delay with and compromised final height.

Body composition and phase angle as an indicator of nutritional status in children with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic, systemic autoimmune connective tissue disease diagnosed in children and adolescents. An important aspect of monitoring of children with JIA is a precise assessment of the nutritional status to identify children and adolescents at risk of malnutrition. The aim of the study was to assess the body composition and phase angle in children diagnosed with JIA in comparison to age and sex matched healthy children since there are scarce reports in paediatric patients.
Methods: A total of 46 children and adolescents aged 4–18 years, with JIA were included in the cross-sectional study. Controls were selected from the group of healthy children and adolescents. Children with diagnosed JIA and healthy children were strictly matched for age and gender. In both groups BIA with phase angle calculation was performed.
Results: Phase angle score was significantly lower in the study group compared to control group (5.45 ± 0.64 vs. 5.85 ± 0.80, p = 0.010). Also lower percentage of body cell mass (50.63 ± 3.46 vs. 52.70 ± 4.06, p = 0.010) and muscle mass (46.02 ± 6.32 vs. 49.53 ± 6.67, p = 0.005) were revealed. In the analysis of subtypes of JIA we found significant differences between children and adolescents with polyarthritis compared to control group, while no significant differences were found between patients with oligoarthritis and control group.
Conclusions: The obtained results indicate a higher risk of malnutrition in children and adolescents with JIA compared to healthy peers, predominantly in patients with polyarthritis.
As discussed earlier, there is an ongoing concern regarding nutritional status of children
with chronic systemic inflammatory illnesses as JIA, with conflicting evidence regarding the disease effects on various aspects of growth and body composition. In this study, Wiech et al. assessed parameters of body composition and phase angle (PhA) in children with JIA, using bioelectrical impedance analysis (BIA). PhA is a derived measure of BIA, calculated from the resistance and reactance obtained by this tool, which has been recognized as a measure of nutritional status. PhA reflects body cell mass and is one of the best indicators of cell membrane function [27]. It is considered
as a screening tool for the identification of risk patients with impaired nutritional and functional status [28]. In this current match-controlled study of children and adolescents with JIA, no significance differences were found in anthropometric parameters between study and control groups. Remarkably, the value of the PhA in children with JIA was significantly lower than in healthy controls. Parameters of muscle mass and body cell mass were also significantly lower in the JIA group compared to control. These significant differences between case and control groups were found only for polyarthritis and not oligoarthritis, probably reflecting the difference in systemic inflammatory effects between the disease subtypes (as was shown also in the previous article by McErlane et al.). This current study lacks stratification by pharmacological treatment and disease severity, which could have influenced the results, and in particular the discrepancies between the subgroups. Moreover, the use of BIA in the assessment of segmental components of body composition has its limitation (compared to dual-energy x-ray absorptiometry) and has been shown to underestimate fat mass and overestimate lean mass [29]. In children with chronic disease in particular, the reliability of BIA in the estimation of body composition may be limited [30].
Nonetheless, the significant differences reported in this study between children with JIA and controls indicate the need for close monitoring of nutritional status and body composition in the routine clinical practice of children with JIA. Also, it suggests a role
for BIA and PhA in this process.

Cystic Fibrosis

Early life growth patterns persist for 12 years and impact pulmonary outcomes in cystic fibrosis

 In children with cystic fibrosis (CF), recovery from growth faltering within 2 years of diagnosis (Responders) is associated with better growth and less lung disease at age 6 years. This study examined whether these benefits are sustained through 12 years of age.
Methods: Longitudinal growth from 76 children with CF enrolled in the Wisconsin CF Neonatal Screening Project was examined and categorized into 5 groups: R12, R6, and R2, representing Responders who maintained growth improvement to age 12, 6, and 2 years, respectively, and I6 and N6, representing Non-responders whose growth did and did not improve during ages 2–6 years, respectively. Lung disease was evaluated by % predicted forced expiratory volume in one second (FEV1) and chest radiograph (CXR) scores.
Results: Sixty-two percent were Responders. Within this group, 47% were R12, 28% were R6, and 25% were R2. Among Non-responders, 76% were N6. CF children with meconium ileus (MI) had worse lung function and CXR scores compared to other CF children. Among 53 children with pancreatic insufficiency without MI, R12 had significantly better FEV1 (97–99% predicted) and CXR scores during ages 6–12 years than N6 (89–93% predicted). Both R6 and R2 experienced a decline in FEV1 by ages 10–12 years.
Conclusions: Early growth recovery in CF is critical, as malnutrition during infancy tends to persist and catch-up growth after age 2 years is difficult. The longer adequate growth was maintained after early growth recovery, the better the pulmonary outcomes at age 12 years.

Nutritional status and pulmonary outcome in children and young people with cystic fibrosis

Nutrition is closely related to mortality and pulmonary and respiratory muscle function in cystic fibrosis (CF) patients. We initially validated results from a bioelectrical impedance device against dual energy x-ray absorptiometry (DEXA). We then determined whether fat free mass assessed by a portable impedance device rather than body mass index (BMI) better correlated with pulmonary function, respiratory muscle strength and exercise capacity in CF patients.
Methods: Eighteen young people and adults (median age 19, range 12–39 years) with CF had dual energy X-ray absorptiometry and direct segmental multi-frequency impedance analysis. Body composition, pulmonary function, respiratory muscle function and exercise tolerance using the impedance device were measured in 29 young people with CF with median age 15 (range 12–19) years.
Main Findings: There was a significant correlation between impedance and absorptiometry results (r2 = 0.947). Fat free mass correlated with the forced vital capacity z-score (r = 0.442, p = 0.016), maximal inspiratory pressure (r = 0.451, p = 0.014) and exercise tolerance (r = 0. 707, p < 0.001). BMI z-scores did not significantly correlate with pulmonary or respiratory muscle function. Subjects with a fat free mass z-score of ≤ 2 had a lower forced expiratory volume in 1 s z-score (p =
0.007), lower forced vital capacity z-score ( p = 0.001), higher residual volume z-score ( p = 0.042), lower maximal inspiratory pressure ( p = 0.039), more days of intravenous antibiotics per year (p = 0.016) and a higher rate of chronic infections (p = 0.006). Principal Conclusions: Fat-free mass measured by impedance correlated better with pulmonary and respiratory muscle function and exercise capacity than BMI.
Cystic fibrosis (CF) is strongly associated with poor nutritional status, resulting from
various factors including nutrient malabsorption, high energy needs, energy losses,
and chronic and recurrent inflammatory status. Advances in the acknowledgment of
the positive effects of early interventions on nutritional state of these patients, along
with the proven association between better nutritional status in early life and better
lung function in later years, has led to the development of professional guidelines for
nutritional management of patients with CF [31, 32].
Over the past decade, a significant improvement was observed in nutritional outcomes
of infants diagnosed by newborn screening. A study from Brazil published last
year [33] joins former publications from Europe [34], Australia [35] and the United
States [36], reporting better nutritional status in infants diagnosed with CF by newborn
The 2 current studies presented in this chapter represent the continuum challenge of
nutritional care in CF beyond the period of infancy and the importance of maintaining
adequate growth and nutrition during the life course of patients with the disease. The publication of Sanders et al. reports a follow-up of their longitudinal responders study. In the original study, infants with CF were defined as “responders” by a recovery from malnutrition and growth faltering as indicated by catch-up weight gain to the level comparable to their birth weight z-score within 2 years of diagnosis [37]. Consecutive anthropometric measurements, as well as pulmonary functions, were further evaluated after 6 and 12 years. The results of this study showed that most of the responders maintained their growth improvement by12 years of age, while only a minority of the nonresponders improved growth by 6 years of age and none of them maintained the improvement by the age of 12 years. These results demonstrate that growth patterns established early in life tend to persist and determine subsequent growth trajectories and that early catch-up growth in infants with CF could be detrimental for later nutritional status. As for the pulmonary status, the responders groups had significantly better lung functions at each time point by 12 years of age, demonstrating the strong association between adequate growth and pulmonary outcomes.
Finally, the study of Papalexopoulou et al. highlights the fact that growth trajectories are not necessarily the most important anthropometric predictors of pulmonary function in patients with CF and rather emphasizes the importance of body composition and fat-free mass. Among 29 adolescents with CF (age range between 12 and 19 years), BMI z-score was not significantly correlated with any pulmonary function, respiratory muscle function, or exercise indices. Alternatively, fat-free mass index demonstrated a good positive correlation with all aforementioned pulmonary outcomes and exercise tolerance. Continuous comprehensive assessment of all aspects of nutritional status, along with body composition and functional parameters, are all important components in the long-term care of patients with CF.

Cerebral Palsy

Food intake, nutritional status and gastrointestinal symptoms in children with
cerebral palsy

Cerebral palsy may be associated with comorbidities such as undernutrition, impaired growth and gastrointestinal symptoms. Children with cerebral palsy exhibit eating problems due to the effect on the anatomical and functional structures involved in the eating function resulting in malnutrition.
Objective: The aim of this study was to investigate the association between food intake, nutritional status and gastrointestinal symptoms in children with cerebral palsy.
Methods: Cross-sectional study that included 40 children with cerebral palsy (35 with spastic tetraparetic form and 5 with non-spastic choreoathetoid form of cerebral palsy, all requiring wheelchairs or bedridden) aged from 4 to 10 years. The dietary assessment with the parents was performed using the usual household food intake inquiry. Anthropometric data were collected. Gastrointestinal symptoms associated with deglutition disorders, gastroesophageal reflux and chronic constipation were also recorded.
Results: The median of height-for-age Z-score (–4.05) was lower ( p < 0.05) than the median of weightf-or-age (–3.29) and weight-for-height (–0.94). There was no statistical difference between weight-for-age and weight-for-height Z-scores. Three patients with cerebral palsy (7.5%) exhibited mild anemia, with normal ferritin levels in two. Symptoms of dysphagia, gastroesophageal reflux, and constipation were found in 82.5% ( n = 33), 40.0% ( n = 16), and 60.0% ( n = 24) of the sample, respectively. The patients with symptoms of dysphagia exhibited lower daily energy (1,280.2 ± 454.8 vs. 1,890.3 ± 847.1 kcal, p = 0.009), carbohydrate (median: 170.9 g vs. 234.5 g, p = 0.023) and fluid intake (483.1 ± 294.9 vs. 992.9 ± 292.2 mL, p = 0.001). The patients with symptoms of gastrointestinal reflux exhibited greater daily fluid intake (720.0 ± 362.9 mL) than the patients without symptoms of gastroesophageal reflux (483.7 ± 320.0 mL, p = 0.042) and a greater height-for-age deficit (Z-score: –4.9 ± 1.7 vs. 3.7 ± 1.5, p = 0.033). The patients with symptoms of constipation exhibited lower daily dietary fiber (9.2 ± 4.3 vs. 12.3 ± 4.3 g, p = 0.031) and fluid (456.5 ± 283.1 vs. 741.1 ± 379.2 mL, p = 0.013) intake.
Conclusions: Children with cerebral palsy exhibited wide variability in food intake which may partially account for their severe impaired growth and malnutrition. Symptoms of dysphagia, gastroesophageal reflux, and constipation are associated with different food intake patterns. Therefore, nutritional intervention should be tailored considering the gastrointestinal symptoms and nutritional
Cerebral palsy (CP) is a chronic nonprogressive encephalopathy, with a wide variation
in disease severity, patterns of motor involvement, and associated impairments [38] .
The most prevalent digestive tract disorders associated with CP are dysphagia, gastroesophageal reflux disease, and constipation [39]. Malnutrition and impaired
growth are prominent features of children with severe CP, resulting from multifactorial
etiology that includes feeding difficulties, increased energy requirement due to
spasticity and involuntary movements, and the high frequency of both recurrent infections and respiratory difficulties. There are many causes of feeding difficulties in
children with CP, including primarily oropharyngeal incoordination, vomiting, early
satiety, and communication defects [40]. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition offers comprehensive guidelines for the management of the gastroenterological and nutritional problems in children with neurological impairment [41].
This current study reports a cross-sectional assessment of both food intake and anthropometric measurements, together with the presence of gastrointestinal symptoms of children with CP. The study population included 40 children with severe CP, all requiring wheelchairs or were bedridden. Anthropometry included patients’ weight and estimated height based on tibia length, presented as z scores. Food intake was compared to the reference Recommended Dietary Allowance (RDA). The results showed severe stunting and wasting in this cohort, with height being the most profoundly affected measurement. Overall, the total energy intake was adequate to the
estimated energy requirement for the majority of patients, and protein and carbohydrate
intake were even above RDA in most patients. The important findings of this study are the differences in food intake according to gastrointestinal symptoms. Symptoms of dysphagia, gastroesophageal reflux, and constipation were common in this cohort, each characterized by different nutritional pattern. Patients with dysphagia had significantly lower energy intake and lower fluid intake, which could probably be associated with difficulties in swallowing and the need for fluid thickening to prevent aspirations. Intakes of all macronutrient groups were also reduced, reflecting the challenge of feeding this group of severely ill CP patients. Symptoms of gastroesophageal reflux were mainly associated with increased fluid intake, which in our opinion could be related to the common use of nutritional formula as well as enteral feeding that was not assessed in this study. The finding of reduced fiber intake in patients with constipation could be associated with reversed causality, as reduced fiber content in the diet is assumed to be a contributing factor for the development of constipation, although the evidence in children is weak [42].
In spite of the limitations of this descriptive study, not allowing for causation analysis, the results shed light on the unique patterns of food intake and nutritional deficits in patients with severe CP presenting various gastrointestinal challenges. This calls for better awareness and adjustment of nutritional interventions for the specific difficulties
experienced by this vulnerable population.