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Objectives: Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study., Subjects/methods: This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0-17.9 years, 5 adult subjects 18-75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively., Results: There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy., Conclusions: There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response., Competing Interests: V.A.S. reports consulting with AbbVie on unrelated topics. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ± 3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status., Competing Interests: and Sources of Funding: Supported by NIDDK (R44DK060302), and the Nutrition Center at the Children’s Hospital of Philadelphia. The project described was supported by the National Center for Research Resources, Grant UL1RR024134, and is now at the National Center for Advancing Translational Sciences, Grant UL1TR000003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. VAS, JIS, AM, BNA, MRM, KAD, KH, JR, and OUE have no financial disclosures or potential conflicts of interest. WAS, President of Avanti Polar Lipids, Inc. was the principal investigator of the NIH Small Business Innovation Research (SBIR) award.

Background: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status., Methods: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size., Results: A total of 110 subjects were enrolled (age 10.4 ± 3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident., Conclusions: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Objectives: Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based, and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI., Study Design: Serum B12 status was assessed in subjects (5-18 years) and categorized as elevated (serum B12 above reference range for age and sex [Hi-B12]) or within reference range (serum B12 within reference range for age and sex) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index z scores, pulmonary function, energy, and dietary and supplement-based vitamin intake were assessed., Results: A total of 106 subjects, mean age 10.4 ± 3.0 years, participated in the study. Median serum B12 was 1083 pg/mL, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intakes were both high representing 376% and 667% recommended dietary allowance (RDA), respectively. The Hi-B12 group had significantly greater supplement-based B12 intake than the serum B12 within reference range for age and sex group (1000% vs 583% RDA, P < 0.001). Multiple logistic regression analysis showed that high supplement-based B12 intake and age >12 years increased the risk of Hi-B12, whereas higher forced expiratory volume at 1 second (FEV1) decreased the risk (pseudo-R = 0.18, P < 0.001)., Conclusions: Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and forced expiratory volume at 1 second.

Objectives: The aim of the study was to assess the impact of LYM-X-SORB (LXS), an organized lipid matrix that has been shown to be absorbable without pancreatic enzyme therapy on fat-soluble vitamin status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI)., Methods: Children with CF and PI were randomized to daily LXS or an isocaloric placebo comparison supplement for 12 months. Serum vitamins A (retinol), D (25-hydroxyvitamin D[25D]), E (α-tocopherol, α-tocopherol:cholesterol ratio), and K (percentage of undercarboxylated osteocalcin [%ucOC] and plasma proteins induced by vitamin K absence factor II [PIVKA II]) were assessed at baseline and 12 months. Dietary intake was determined using 3-day weighed food records and supplemental vitamin intake by a comprehensive questionnaire., Results: A total of 58 subjects (32 boys, age 10.3 ± 2.9 years [mean ± standard deviation]) with complete serum vitamin, dietary and supplemental vitamin data were analyzed. After adjusting for dietary and supplemental vitamin intake, serum retinol increased 3.0 ± 1.4 μg/dL (coefficient ± standard error) (adjusted R2 = 0.02, P = 0.03) and vitamin K status improved as demonstrated by a decreased percentage of undercarboxylated osteocalcin of -6.0% ± 1.6% by 12 months (adjusted R2 = 0.15, P < 0.001). These changes occurred in both the LXS and placebo comparison groups. No changes in serum 25D or α-tocopherol were detected. Both nutrition interventions increased caloric intake a mean of 83 ± 666 kcal/day by 12 months., Conclusions: Vitamins A and K status improved, whereas vitamins D and E status was unchanged during 12 months of LXS and isocaloric placebo comparison supplement in children with CF and PI.

Objectives: Optimal vitamin D status is known to have beneficial health effects and vitamin D supplements are commonly used. It has been suggested that vitamin D supplementation may increase blood lead in children and adults with previous lead exposure. The objective was to determine the safety regarding lead toxicity during 12 weeks of high-dose vitamin D3 supplementation in children and young adults with human immunodeficiency virus (HIV)., Methods: Subjects with HIV (8-24 years) were randomized to vitamin D3 supplementation of 4000 or 7000 IU/day and followed at 6 and 12 weeks for changes in serum 25-hydroxy vitamin D (25D) and whole-blood lead concentration. This was a secondary analysis of a larger study of vitamin D3 supplementation in children and adolescents with HIV., Results: In 44 subjects (75% African American), the baseline mean ± standard deviation serum 25D was 48.3±18.6 nmol/L. Fifty percent of subjects had baseline serum 25D <50.0 nmol/L. Serum 25D increased significantly with D3 supplementation during the 12 weeks. No subject had a whole-blood lead >5.0 μg/dL at baseline or during subsequent visits. Whole-blood lead and 25D were not correlated at baseline, and were negatively correlated after 12 weeks of supplementation (P=0.014). Whole-blood lead did not differ between those receiving 4000 and 7000 IU of vitamin D3., Conclusions: High-dose vitamin D3 supplementation and the concomitant increased serum 25D did not result in increased whole-blood lead concentration in this sample of children and young adults living in a northeastern urban city.

Background and Objective: Children with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at risk for fatty acid (FA) abnormalities and essential FA deficiency, with low linoleic acid (LA) and docosahexaenoic acid (DHA) concentrations and abnormal triene:tetraene (T:T) and arachidonic acid (AA):DHA ratios. The aim of the article was to determine whether type of dietary fat predicted serum LA, DHA, T:T, and AA:DHA ratios in subjects with CF and PI as compared to an unaffected comparison group., Methods: Serum FA concentrations were assessed by capillary gas-liquid chromatography (mol%) and dietary intake by 7-day weighed food records; the 3-day coefficient of fat absorption was calculated. Total energy intake was expressed in kilocalories., Results: A total of 65 subjects with CF and PI (8.4 ± 1.0 years, 32 girls) and 22 controls (8.5 ± 1.1 years, 13 girls) were included. Despite greater energy, saturated fat, and LA intake, the subjects with CF had lower serum LA and DHA and higher T:T and AA:DHA than those in the comparison group. Dietary total fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), LA, total ω 6 polyunsaturated fatty acid (Tω6PUFA), and α-linolenic acid (ALA) intake positively predicted serum LA concentration. MUFA, total ω 3 polyunsaturated fatty acid (Tω3PUFA), and ALA intake positively predicted serum DHA concentration. Total dietary fat, MUFA, PUFA, Tω3PUFA, LA, and ALA intake negatively predicted serum T:T. ALA and Tω3PUFA intake negatively predicted serum AA:DHA., Conclusions: Dietary fat patterns influenced serum LA, DHA, T:T, and AA:DHA in children with CF and PI. These data suggest that changes in dietary practices may result in FA profiles associated with improved clinical outcomes.

Background: Children with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at increased risk for essential fatty acid (EFA) deficiency., Objectives: To investigate serum markers of EFA status in children with CF and PI and their association with growth, body composition, and lung function., Patients and Methods: Serum phospholipid fatty acid, growth, and forced expiratory volume at 1 second (FEV1, percentage predicted) status were assessed at baseline and 12 months in 77 children with CF and PI, 7 to 10 years old. Longitudinal mixed-effects models were used to compare associations of the triene:tetraene ratio (ratio of eicosatrienoic acid to arachidonic acid) and serum linoleic acid (as a molar percentage of total serum phospholipid fatty acids, or mol%) with the clinical outcomes. Controls for serum fatty acid were 23 healthy white age- and sex-matched children., Results: Children with CF and PI had higher median triene:tetraene ratio and lower linoleic acid than healthy controls. Depending on the triene:tetraene ratio cutoff point used (0.04 or 0.02), either 17% or 52% of the children with CF had EFA deficiency, respectively. Only linoleic acid was significantly and positively associated with z scores for weight, height, body mass index, upper arm muscle area, and FEV1 at baseline. Children with linoleic acid at 21 mol% or higher had significantly better growth and pulmonary status than those with lower concentrations., Conclusions: Serum phospholipid linoleic acid at 21 mol% or higher was associated with better growth, body composition, and FEV1. No clinical outcome associations were found with the triene:tetraene ratio. These findings suggest that linoleic acid concentration was a more clinically relevant biomarker of EFA status than the triene:tetraene ratio in children with CF and PI. Further research is warranted to validate this specific percentage of linoleic acid cutoff point as a new recommendation for clinical use.

Objectives: To describe the usual pattern of intake and adherence to cystic fibrosis (CF) food and pancreatic enzyme replacement therapy (PERT) recommendations in preadolescent children with CF and pancreatic insufficiency (PI)., Methods: Children, 8 to 11 years old, with CF and PI were assessed for PERT adherence ratio (number taken/number prescribed per day) and energy and fat intake for 7 days (weighed food records), adherence to PERT and dietary recommendations, pulmonary function, growth status and stool fat malabsorption. Using the PERT adherence ratio, children were divided into good (> or =80%), moderate (60% to 79%) and poor (<60%) adherence groups., Results: Of the 75 children (age, 9.3 +/- 1.0 years; forced expiratory volume in 1 s, 95 +/- 14% predicted), 61% consumed less than 120% of energy intake, and 72% consumed less than 40% of calories as fat recommended for CF. Using the PERT adherence ratio (mean +/- SD, 75 +/- 14%), 29%, 61% and 9% of children had good, moderate and poor adherence, respectively. Better adherence to PERT was significantly associated with missing fewer snacks, higher energy intake, greater fat content of snacks and poorer growth status. About 85% of the children were in the 500 to 4000 lipase unit (LU) of PERT (LU/g fat per day) and 500 to 2500 LU/kg per body weight per meal guidelines, whereas only 58% to 68% were within the guidelines for snacks. Eleven percent of children always took PERT at an inappropriate time after meals., Conclusions: Most preadolescent children with CF and PI did not meet dietary recommendations. Future educational and behavioral interventions focused on increasing PERT adherence with snacks, fat content of meals and snacks, appropriate timing of enzymes and adjustment of PERT and meal fat content are suggested.

Objective: To investigate plasma zinc status in relation to dietary and supplemental zinc intake, growth and pulmonary status in preadolescent children with cystic fibrosis (CF) and pancreatic insufficiency (PI)., Methods: Fasting plasma zinc was assessed in children (age, 8-11 years) with CF and PI. Food (7-day weighed records) and supplemental zinc intake, serum alkaline phosphatase and albumin, pulmonary function (spirometry), coefficient of fat absorption (%COA, 72-hour fecal fat) and growth status [height adjusted for genetic potential (AHAZ), weight (WAZ) and BMI Z scores (BMIZ)] were assessed., Results: For the 62 children (32 males), mean plasma zinc (+/-SD) was 16.8 +/- 3.1 micromol/L (110 +/- 20 ug/dL). Sixty-five percent of the subjects had levels above the study reference range of 9.2 to 15.3 micromol/L (60-100 ug/dL); no subjects had low zinc levels. Median (range) total daily zinc intake was 279% (83-988%) recommended dietary allowance, growth status was suboptimal (mean +/- SD: AHAZ, -0.8 +/- 1.0; WAZ, -0.5 +/- 1.2; BMIZ, -0.2 +/- 1.1), and forced expiratory volume at 1 second (FEV1) was 92 +/- 13% predicted. Plasma zinc was not correlated with growth, pulmonary or alkaline phosphatase status. Plasma zinc was correlated with serum albumin (r = 0.25, P < 0.05) and was inversely correlated with coefficient of fat absorption (as %; r = -0.30, P = 0.02)., Conclusions: Under current patterns of care in CF Centers, total zinc intake and plasma zinc status were adequate. These findings suggest that zinc was not a limiting micronutrient for preadolescent children with CF and PI and mild-to-moderate lung disease, and not likely contributing to their suboptimal growth status.

Objectives: To evaluate fecal elastase 1 (FE) levels in young children with cystic fibrosis and pancreatic insufficiency and to explore the relationship between FE and growth, nutrition, pulmonary status and fat absorption over a 24-month period., Methods: FE, indicating pancreatic lipase activity, was assessed in children (6.0 to 8.9 years of age) with cystic fibrosis and pancreatic insufficiency. FE >15 microg/g stool was defined as residual pancreatic activity, suggesting some pancreatic function, and FE

Background: Growth and body composition have not been well described in older children with biliary atresia or Alagille syndrome living with their native liver. To optimize nutritional management of these conditions it is essential to understand the normal growth characteristics., Objectives: The purpose of this study was to evaluate and compare the growth and body composition of children, particularly school-age children, with biliary atresia and Alagille syndrome., Methods: A single observer measured height, weight, arm anthropometry and skin fold thickness in subjects aged 1 to 12 years with biliary atresia or Alagille syndrome who had not undergone liver transplantation., Results: Forty-six subjects (10 biliary atresia/36 Alagille syndrome) were assessed. Biliary atresia subjects were below average in height for age with normal weight and elevated body mass index. Mean fat stores were mildly depressed. The z-scores for body mass index and weight for age were inversely correlated with age. Alagille subjects were stunted and had low body weight and reduced fat and muscle stores. Body mass index z-score was inversely correlated with age despite improved cholestasis., Conclusions: Children with Alagille syndrome had significant growth deficits as measured by weight, height and upper arm anthropometry at all ages studied. In contrast, subjects with biliary atresia had normal weights and heights. However, body mass index and weight for age z-scores were lower in the older biliary atresia subjects. Few studies of anthropometry in biliary atresia or Alagille syndrome have included the school-aged child. This study addresses this gap in knowledge and provides baseline data for nutritional interventions in these patients.

Objectives: To describe bone status in children with Alagille syndrome (AGS) and healthy control children adjusted for age, gender and height (HT), and to identify dietary intake and AGS-related factors associated with bone status., Methods: Prepubertal children with AGS and healthy controls comparable in age and ethnicity were evaluated. Subjects were > or =4 years of age, prepubertal and had whole body (WB) and/or lumbar spine (LS) dual energy X-ray absorptiometry (DXA) scans of acceptable quality. Anthropometric (weight, HT), diet and AGS-specific data (e.g., coefficient of fat absorption, labs, liver transplantation) were also collected. Bone area (BA), bone mineral content (BMC) and HT were log transformed for best fit. Bone data were analyzed unadjusted, adjusted for gender, age and HT, and as HT-specific z-scores., Results: AGS and control groups were similar in age, pubertal status and ethnicity. Children with AGS were small-for-age, had decreased BA and BMC-for-age, and decreased WB BA and BMC-for-HT z-scores compared to healthy controls. Prevalence of low BMC-for-HT z-scores (< -2) among AGS subjects was 20% for the WB and 39% for the LS. Bone mineralization was positively related to fat absorption but not dietary intake., Conclusions: Children with AGS have deficits in bone size and bone mass relative to body size. Modifiable factors, such as treatment of malabsorption should be explored as an early focus of AGS care to prevent bone fragility.

Objective: To characterize the energy and nutrient intake, and the degree of fat malabsorption in children with Alagille syndrome (AGS) and to examine their cross-sectional associations with growth and nutritional status., Methods: Prepubertal children with AGS were evaluated for dietary intake, growth, bone age, and body composition. Children and their families collected a three-day, weighed diet record at home. Stools were collected for 72 hours and the coefficient of fat absorption (COA) was determined., Results: Children (mean age 6.7 +/- 3.6 years) with AGS (n = 26) had low height-for-age z-scores (HAZ), weight-for-age z-scores (WAZ) (-1.9 +/- 1.3 and -1.7 +/- 1.1, respectively), and delayed skeletal maturation (-1.4 +/- 1.8 years). Fifty-eight percent of the subjects were less than the 5th percentile for height and 54% were less than the 5th percentile for weight. At least 20% of children with AGS had low dietary intake for several nutrients including: calories, fat, calcium, vitamin D, and vitamin E. Children who consumed <2/3 Dietary Reference Intake (DRI) for calcium (n = 6) had a statistically significantly lower HAZ (-3.2 +/- 1.3) than those who consumed >2/3 DRI (-1.5 +/- 1.0), (P < 0.003). Ninety-six percent of the subjects had steatorrhea with a mean COA of 75 +/- 16%., Conclusions: These data suggest that prepubertal children with AGS are at-risk for poor nutrient intake which, compounded with steatorrhea, may have a negative effect on growth and nutritional status. Intervention studies to increase energy and nutrient intake are needed to determine the effect of improved dietary intake on growth and nutritional status of children with AGS.

Objective: To examine growth, body composition, and nutritional status in a large sample of children, adolescents, and young adults with Crohn's disease (CD)., Methods: One hundred thirty-two subjects (48 females) with CD, aged 5 to 25 years, and 66 healthy control subjects (37 females) of similar age. Growth, nutritional status, and body composition were measured by anthropometry and dual-energy x-ray absorptiometry. Genetic potential of linear growth was predicted using the adjusted heights of Himes et al. Pubertal status and skeletal age were assessed. Average Pediatric Crohn's Disease Activity Index (PCDAI) and lifetime steroid exposure (in milligrams per day) were obtained from medical charts. The variables were examined in relation to gender and measures of disease activity., Results: Males and females with CD did not differ by age, disease duration, or PCDAI. Males with CD had significantly lower values for growth and nutritional status than control subjects (z-scores for weight: -0.66 +/- 1.18 vs. 0.26 +/- 0.95, P = 0.00002; height -0.81 +/- 1.14 vs. 0.28 +/- 0.93, P = 0.00001; adjusted height -1.05 +/- 1.03 vs. 0.40 +/- 1.03, P = 0.00001) and delayed skeletal age of 0.9 +/- 1.6 years. Impaired linear growth in the males was present regardless of pubertal stage. Associations between disease severity indicators and growth parameters were more consistent for females., Conclusions: Crohn's disease is associated with impaired growth. Despite similarities in disease duration, activity, and lifetime steroid exposure, growth in males was more impaired. Gender may confer risk for impaired growth in CD.

Bone density is related to body size and other factors including dietary calcium intake. The purpose of this study was to determine the effect of a low-lactose, low-calcium diet on the bone mineral content (BMC) of prepubertal children with documented lactose intolerance. Radial BMC was determined by single-photon absorptiometry. Dietary intake was assessed by 24-h recall and two 3-day food records, and weight and height were measured. The group of lactose-intolerant children was compared with a group of healthy children of similar age, gender, race, and size and to the prediction equations based on body size from Chan's Utah children. Nineteen children, ages 9.6 +/- 1.9 years, participated in the study. They were relatively short compared with standards (height Z score, -0.30 +/- 0.83). BMC was 0.428 +/- 0.081 g/cm in the study group versus 0.440 +/- 0.116 g/cm in the comparison group (n = 19; p > 0.05). Both the study group and the size-selected comparison group had lower BMC than the Utah children. The diet of the study group was low in calcium: 84% of the Recommended Dietary Allowance in children < 11 years old and 32% in children > 11. Calcium intake was associated (p = 0.03) with BMC in the study group after adjusting for body size. The low-lactose diet resulted in a low calcium intake, and BMC was associated with calcium intake in prepubertal children with lactose intolerance. Evaluation of dietary calcium intake should be considered in this group of patients, with follow-up dietary counseling, calcium supplementation (diet or medication), and bone density assessment when clinically indicated.