Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation.

BACKGROUND: Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD. OBJECTIVES: The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects. METHODS: Composite plasma [13C10]retinol response data collected from 22 subjects with SCD-HbSS for 28 d after isotope ingestion were analyzed using population-based compartmental modeling ("super-subject" approach); TBS and retinol kinetics were quantified for the group. TBS was also calculated for the same individuals using RID, as well as for healthy peers (n = 20) and for the subjects with SCD-HbSS after 8 wk of daily vitamin A supplements (3.15 or 6.29 µmol retinol/d [900 or 1800 µg retinol activity equivalents/d]). RESULTS: Model-predicted group mean TBS for subjects with SCD-HbSS was 428 µmol, equivalent to ∼11 mo of stored vitamin A; vitamin A disposal rate was 1.3 µmol/d. Model-predicted TBS was similar to that predicted by RID at 3 d postdosing (mean, 389 µmol; ∼0.3 µmol/g liver); TBS predictions at 3 compared with 28 d were not significantly different. Mean TBS in healthy peers was similar (406 µmol). RID-predicted TBS for subjects with SCD-HbSS was not significantly affected by vitamin A supplementation at either dose. CONCLUSIONS: Despite differences in plasma retinol concentrations, TBS was the same in subjects with SCD-HbSS compared with healthy peers. Because 56 d of vitamin A supplementation at levels 1.2 to 2.6 times the Recommended Dietary Allowance did not increase TBS in these subjects with SCD-HbSS, further work will be needed to understand the effects of SCD on retinol metabolism. This trial was registered as NCT03632876 at clinicaltrials.gov.

Reproductive Hormone Concentrations and Associated Anatomical Responses: Does Soy Formula Affect Minipuberty in Boys?

CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. METHODS: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow milk formula, or breast milk feeding during study follow-up. In the 147 infant boy participants, serum testosterone, luteinizing hormone, stretched penile length, anogenital distance, and testis volume were longitudinally assessed from birth to 28 weeks. We examined feeding-group differences in age trajectories for these outcomes using mixed-effects regression splines. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks (176 ng/dL [quartiles: 124, 232]) and remained in this range until 12 weeks in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n = 55) and boys fed cow milk formula (n = 54). Compared with breastfed boys (n = 38), soy formula-fed boys had a more rapid increase in penile length (P = .004) and slower initial lengthening of anogenital distance (P = .03), but no differences in hormone trajectories. CONCLUSION: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

Developing equations to predict waist circumference measurements based on the National Heart, Lung, and Blood Institute method from the World Health Organization method.

PURPOSE: The purpose of the study was to convert waist circumference (WC) measurements obtained by the World Health Organization (WHO-WC) method to the National Heart, Lung, and Blood Institute (NHLBI-WC) method. METHODS: During 2016, the National Health and Nutrition Examination Survey participants aged 20 years and older had two different WC measurements taken (n = 2405). The mean differences in the WC between the NHLBI-WC and WHO-WC measurements were calculated. Multivariable prediction models were developed to predict the NHLBI-WC from the measured WHO-WC. Sensitivity and specificity of the abdominal obesity classification (AOC) were calculated for the measured WHO-WC and the predicted NHLBI-WC. Kappa coefficients were calculated to evaluate the agreements between the AOC derived from the NHLBI-WC and from the WHO-WC and the predicted NHLBI-WC. RESULTS: The mean differences between the NHLBI-WC and WHO-WC were 0.8 cm for males and 3.2 cm for females (P ≤ .05). Sensitivity of the AOC for the measured WHO-WC was 93% for males and 87% for females, and the specificity of the AOC was 97% or greater for both genders. Sensitivity and specificity of the AOC for the predicted NHLBI-WC were 95% or greater for both genders. The AOC derived from the predicted NHLBI-WC had higher agreements for both genders. CONCLUSIONS: The prediction equations provided may be used to predict the NHLBI-WC from the WHO-WC for comparability in WC estimates across studies.

Endocrine-sensitive physical endpoints in newborns: ranges and predictors.

BACKGROUND: In neonates, endocrine-sensitive physical endpoints, including breast and reproductive tissues, may reflect effects of fetal environmental exposure. Studies using standardized measurement techniques that describe demographic and clinical variability in these endpoints are lacking. METHODS: Three hundred and eighty-eight healthy term newborns <3 days old were evaluated, 69% African American and 25% White. Measures included breast bud diameter, anogenital distance (AGD), stretched penile length (SPL), and testicular volume (TV). RESULTS: Breast buds were larger in females than males bilaterally (right: 13.0 ± 4.0 vs. 12.0 ± 4.0 mm, p = 0.008; left: 13.0 ± 4.0 vs. 11.0 ± 3.0 mm, p < 0.001). Breast bud size correlated positively with gestational age (regression coefficient = 0.46 ± 0.12 mm, p < 0.001) and weight Z-score (0.59 ± 0.24 mm, p = 0.02), and negatively with White race (-1.00 ± 0.30 mm, p = 0.001). AGD was longer in males (scrotum-to-anus) than females (fourchette-to-anus) (21.0 ± 4.0 vs. 13.0 ± 2.0 mm, p < 0.001) and did not differ by race. SPL was shorter in White infants (35.0 ± 5.0 vs. 36.0 ± 5.0 mm, p = 0.04). Median TV was 0.5 cm3, and larger in White males (odds ratio 1.71, 95% confidence interval: 1.02-2.88) CONCLUSIONS: This study provides a range of physical measurements of endocrine-sensitive tissues in healthy infants from the United States, and the associations with demographic and clinical characteristics. IMPACT: This study reports physical measurements for endocrine-sensitive endpoints in healthy US newborns, including breast buds, AGD, SPL, and TV. Associations of measurements to demographic and clinical factors (including race, gestational age, and newborn length and weight) are presented. Contemporary ranges and identification of predictive factors will support further study on effects of pre- and postnatal exposures to endocrine-sensitive tissues in the infant.

Correction: Improved residual fat malabsorption and growth in children with cystic fibrosis treated with a novel oral structured lipid supplement: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0232685.].

Vitamin D status, nutrition and growth in HIV-infected mothers and HIV-exposed infants and children in Botswana.

BACKGROUND: Poor vitamin D status is a global health problem and common in patients with human immunodeficiency virus (HIV) in high-income countries. There is less evidence on prevalence of vitamin D deficiency and nutrition and growth in HIV-infected and -exposed children in low- and middle-income countries. OBJECTIVES: To determine the vitamin D status in Batswana HIV-infected mothers and their children, differences among HIV-infected mothers and between HIV-exposed and -infected infants and children, and associations between vitamin D and disease-related outcomes, nutrition, and growth. METHODS: This was a cross-sectional study of HIV+ mothers and HIV-exposed infants and unrelated children (1-7.9 years). Serum 25-hydroxyvitamin D (25(OH)D) was measured, among other nutritional indicators, for mothers, infants and children. Vitamin D status for HIV-infected mothers and children, and an immune panel was assessed. History of HIV anti-retroviral medications and breastfeeding were obtained. Data were collected prior to universal combination antiretroviral therapy in pregnancy. RESULTS: Mothers (n = 36) had a mean serum 25(OH)D of 37.2±12.4ng/mL; 11% had insufficient (<20ng/mL), 17% moderately low (20.0-29.9ng/mL) and 72% sufficient (≥30ng/mL) concentrations. No infants (n = 36) or children (n = 48) were vitamin D insufficient; 22% of HIV- and no HIV+ infants had moderately low concentrations and 78% of HIV- and 100% of HIV+ infants had sufficient status, 8% of HIV- and no HIV+ children had moderately low concentrations and 92% of HIV- and 100% HIV+ children had sufficient concentrations. HIV+ children had significantly lower length/height Z scores compared to HIV- children. Length/height Z score was positively correlated with serum 25(OH)D in all children (r = 0.33, p = 0.023), with a stronger correlation in the HIV+ children (r = 0.47 p = 0.021). In mothers, serum 25(OH)D was positively associated with CD4% (r = 0.40, p = 0.016). CONCLUSIONS: Results showed a low prevalence of vitamin D insufficiency in Botswana. Growth was positively correlated with vitamin D status in HIV-exposed children, and HIV+ children had poorer linear growth than HIV- children.

Vitamin D Supplementation Improves Health-Related Quality of Life and Physical Performance in Children with Sickle Cell Disease and in Healthy Children.

INTRODUCTION: No study determined if vitamin D supplementation improves health-related quality of life (HRQL) using pediatric Patient-Reported Outcomes Measurement Information System or physical functioning in type SS sickle cell disease (HbSS). METHOD: Subjects with HbSS (n = 21) and healthy subjects (n = 23) were randomized to daily oral doses (4,000 vs. 7,000 IU) of cholecalciferol (vitamin D3) and evaluated at 6 and 12 weeks for changes in serum 25 hydroxyvitamin D (25(OH)D), HRQL, and physical functioning. RESULTS: In subjects with HbSS, significant reductions in pain, fatigue, and depressive symptoms and improved upper-extremity function were observed. In healthy subjects, significant reductions in fatigue and improved upper-extremity function were observed. Significant improvements in peak power and dorsiflexion isometric maximal voluntary contraction torques were observed in both groups. In subjects with HbSS, improved plantar flexion isometric maximal voluntary contraction torques were observed. Both groups saw significant improvement in their total Bruininks-Oseretsky Test of Motor Proficiency score. DISCUSSION: Daily high-dose vitamin D supplementation for African American children with and without HbSS improved HRQL and physical performance.

Measures of Dietary Fat and Energy Absorption in Healthy Adults.

OBJECTIVES: Existing reference ranges for stool fat and energy absorption were developed using subjects in controlled environments on precise diets. This study measured energy and fat absorption in healthy, community-dwelling adults eating a moderate-to-high fat American diet via stool- and serum-based methods. METHODS: This was a secondary analysis of healthy subjects recruited as the comparison group in a chronic pancreatitis study. Subjects recorded dietary intake and collected stool over 3-day periods. Stool was analyzed for fat content using the coefficient of fat absorption and for energy content using bomb calorimetry. The malabsorption blood test (MBT) was used to measure dietary fat absorption. RESULTS: Nineteen subjects had mean daily stool measures of 143 g wet weight, 4.1 g of fat, and 178 kcal. The mean coefficients of fat and energy absorption were 96% and 93%, respectively. The mean MBT area under the curve cut-point was greater than 8 mg·h/dL. CONCLUSIONS: This study confirms the historical reference range for the coefficient of fat absorption in contemporary healthy, community-dwelling adults on a moderate-to-high fat diet. The study contributes to the development of reference range values for multiple bomb calorimetry-based outcomes of stool energy losses and to the serum-based MBT as a promising method for measuring fat absorption.

Improved residual fat malabsorption and growth in children with cystic fibrosis treated with a novel oral structured lipid supplement: A randomized controlled trial.

BACKGROUND: In the primary analysis of a 12-month double-blind randomized active placebo-controlled trial, treatment of children with cystic fibrosis (CF) and pancreatic insufficiency (PI) with a readily absorbable structured lipid (Encala™, Envara Health, Wayne, PA) was safe, well-tolerated and improved dietary fat absorption (stool coefficient of fat absorption [CFA]), growth, and plasma fatty acids (FA). OBJECTIVE: To determine if the Encala™ treatment effect varied by severity of baseline fat malabsorption. METHODS: Subjects (n = 66, 10.5±3.0 yrs, 39% female) with baseline CFA who completed a three-month treatment with Encala™ or a calorie and macronutrient-matched placebo were included in this subgroup analysis. Subjects were categorized by median baseline CFA: low CFA (<88%) and high CFA (≥88%). At baseline and 3-month evaluations, CFA (72-hour stool, weighed food record) and height (HAZ), weight (WAZ) and BMI (BMIZ) Z-scores were calculated. Fasting plasma fatty acid (FA) concentrations were also measured. RESULTS: Subjects in the low CFA subgroup had significantly improved CFA (+7.5±7.2%, mean 86.3±6.7, p = 0.002), and reduced stool fat loss (-5.7±7.2 g/24 hours) following three months of EncalaTM treatment. These subjects also had increased plasma linoleic acid (+20%), α-linolenic acid (+56%), and total FA (+20%) (p≤0.005 for all) concentrations and improvements in HAZ (0.06±0.08), WAZ (0.17±0.16), and BMIZ (0.20±0.25) (p≤0.002 for all). CFA and FA were unchanged with placebo in the low CFA group, with some WAZ increases (0.14±0.24, p = 0.02). High CFA subjects (both placebo and Encala™ groups) had improvements in WAZ and some FA. CONCLUSIONS: Subjects with CF, PI and more severe fat malabsorption experienced greater improvements in CFA, FA and growth after three months of Encala™ treatment. Encala™ was safe, well-tolerated and efficacious in patients with CF and PI with residual fat malabsorption and improved dietary energy absorption, weight gain and FA status in this at-risk group.

Effect of High-dose Vitamin A Supplementation in Children With Sickle Cell Disease: A Randomized, Double-blind, Dose-finding Pilot Study.

Suboptimal vitamin A status (serum retinol <30 µg/dL) is associated with poor clinical outcomes in children with the hemoglobin-SS disease (HbSS), and supplementation with the recommended daily allowance of retinol is ineffective in improving vitamin A status. In a single-center randomized blinded dose-finding pilot study, we compared vitamin A and nutritional status in children with HbSS to healthy children and explored the impact of high-dose supplementation on the primary outcome serum vitamin A status. Exploratory outcomes included hematologic, nutritional, immunologic, and muscle function status in children with HbSS. A mixed-effects linear regression model evaluated associations between vitamin A dose, serum retinol, and exploratory outcomes. Twenty healthy children participated, and 22 subjects with HbSS were randomized to oral 3000 or 6000 IU/d retinol for 8 weeks; 21 subjects completed all evaluations. Serum retinol, growth, and nutritional status were all suboptimal in HbSS subjects at baseline, and supplementation did not change vitamin A status. Fetal hemoglobin (Δ=2.5, 95% confidence interval [CI], 0.5-4.3), mean corpuscular volume (Δ=2.7, 95% CI, 0.7-4.7), mean corpuscular hemoglobin (Δ=1.4, 95% CI, 0.5-2.3), and mean corpuscular hemoglobin concentration (Δ=0.5, 95% CI, 0.1-0.9) all improved with supplementation. Mild improvements in erythrocyte indices, growth status, and muscle function occurred independent of hydroxyurea use.

Pancreatic Function in Chronic Pancreatitis: A Cohort Study Comparing 3 Methods of Detecting Fat Malabsorption and the Impact of Short-term Pancreatic Enzyme Replacement Therapy.

OBJECTIVES: Reliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with healthy people and then investigated short-term pancreatic enzyme replacement therapy (PERT) and fat malabsorption, nutritional status, and quality of life (QOL). METHODS: Subjects with CP were evaluated before and after PERT and compared with the healthy cohort using coefficient of fat absorption (CFA), stool bomb calorimetry, and the malabsorption blood test (MBT). Anthropometrics, micronutrients, and QOL data were collected. Group means at baseline and after PERT were analyzed. RESULTS: The 24 subjects with CP had greater stool energy loss (5668 cal/g [standard deviation {SD}, 753] vs 5152 cal/g [SD, 418], P < 0.01), reduced triglyceride absorption (MBT, 8.3 mg·h/dL [SD, 4.3] vs 17.7 mg·h/dL [SD, 10.3], P < 0.001), lower fat intake, and poorer QOL. Differences in CFA were not significant (90.9% [SD, 12.8] vs 95.4% [SD, 9.3]). After PERT, triglyceride absorption (Δ = 1.7 [SD, 3], P < 0.05) and QOL increased. CONCLUSIONS: The MBT detected changes in triglyceride absorption in the absence of CFA changes. The MBT may be helpful in guiding PERT initiation in patients with CP before significant morbidity.

Adherence to Nutritional Supplementation in Cystic Fibrosis.

PURPOSE: The purpose of this study was to examine patterns of adherence to a novel dietary supplement in pediatric cystic fibrosis. Adherence to dietary supplementation in cystic fibrosis is challenging, and examination of patterns of adherence behavior over time is needed to better characterize subgroups of patients who need self-management support. DESIGN AND METHODS: We prospectively examined adherence to Lym-X-Sorb™ (LXS), an organized lipid matrix dietary supplementation for patients with cystic fibrosis (CF) and pancreatic insufficiency (PI), over a 12-month period. Adherence for participants aged 5-17 years with CF and PI (N = 109) was monitored monthly via supplement packet counts. Group-based trajectory modeling was employed to examine patterns in adherence behavior over time. RESULTS: Four distinct trajectories best characterized adherence in this sample, with 18% of participants demonstrating near perfect adherence, 42% demonstrating good adherence (at or above 80%), 16% demonstrating poor adherence that declined over time, and 24% demonstrating significant non-adherence (< 30%). CONCLUSIONS: Some patients with CF and PI who are prescribed nutritional supplements will require intensive, individualized behavioral intervention to enhance adherence. Identifying patients who will have difficulty adhering to dietary interventions may result in better treatment-to-patient matching and improved adherence promotion efforts. PRACTICE IMPLICATIONS: Assessment of adherence to dietary supplementation over time can identify patients at risk for continued difficulty with self-management and provide opportunities for early intervention.

Incidental findings during ultrasound of thyroid, breast, testis, uterus and ovary in healthy term neonates.

Incidental sonographic findings in thyroid and estrogen-responsive organs have been described in children and adults, but no publications describe incidental findings of these organs in infancy. We describe ultrasound features in thyroid, breast buds, testes, uterus, and ovaries in infants up to 32 weeks old that vary from the expected tissue architecture. Infants described in this paper were enrolled as healthy term neonates in a longitudinal study of normal feeding practices. Radiology reports for ultrasound exams in these infants described a range of findings that are similar to those reported in older populations. Knowledge of these asymptomatic variants occurring in infancy may guide radiologists in interpretation of these findings during clinical exams.

Italian and North American dietary intake after ivacaftor treatment for Cystic Fibrosis Gating Mutations.

BACKGROUND: In patients with cystic fibrosis (CF), ivacaftor treatment results in significant weight gain and the impact on diet has not been explored. METHODS: A study in 22 subjects (6.1-61.6 years) compared diet, energy balance, weight gain, and body composition, before and after three months of treatment in Italians and North Americans with CFTR gating mutations. RESULTS: With no differences between groups in energy or macronutrient intake at baseline, fat intake increased in all subjects, and both fat and energy intake increased in Italians. Height, weight, BMI, lean and fat mass, and % body fat increased and resting energy expenditure decreased after treatment. Weight gain was associated with energy and fat intake. CONCLUSIONS: Fat intake increased with treatment, possibly due to the recommendation to take ivacaftor with high fat meals. Increased energy and fat intake correlated with weight gain. Regional dietary patterns differed.

Pediatric Bone Mineral Accrual Z-Score Calculation Equations and Their Application in Childhood Disease.

Annual gains in BMC and areal bone mineral density (aBMD) in children vary with age, pubertal status, height-velocity, and lean body mass accrual (LBM velocity). Evaluating bone accrual in children with bone health-threatening conditions requires consideration of these determinants. The objective of this study was to develop prediction equations for calculating BMC/aBMD velocity SD scores (velocity-Z) and to evaluate bone accrual in youth with health conditions. Bone and body compositions via DXA were obtained for up to six annual intervals in healthy youth (n = 2014) enrolled in the Bone Mineral Density in Childhood Study (BMDCS) . Longitudinal statistical methods were used to develop sex- and pubertal-status-specific reference equations for calculating velocity-Z for total body less head-BMC and lumbar spine (LS), total hip (TotHip), femoral neck, and 1/3-radius aBMD. Equations accounted for (1) height velocity, (2) height velocity and weight velocity, or (3) height velocity and LBM velocity. These equations were then applied to observational, single-center, 12-month longitudinal data from youth with cystic fibrosis (CF; n = 65), acute lymphoblastic leukemia (ALL) survivors (n = 45), or Crohn disease (CD) initiating infliximab (n = 72). Associations between BMC/aBMD-Z change (conventional pediatric bone health monitoring method) and BMC/aBMD velocity-Z were assessed. The BMC/aBMD velocity-Z for CF, ALL, and CD was compared with BMDCS. Annual changes in the BMC/aBMD-Z and the BMC/aBMD velocity-Z were strongly correlated, but not equivalent; LS aBMD-Z = 1 equated with LS aBMD velocity-Z = -3. In CF, BMC/aBMD velocity-Z was normal. In posttherapy ALL, BMC/aBMD velocity-Z was increased, particularly at TotHip (1.01 [-.047; 1.7], p < 0.0001). In CD, BMC/aBMD velocity-Z was increased at all skeletal sites. LBM-velocity adjustment attenuated these increases (eg, TotHip aBMD velocity-Z: 1.13 [0.004; 2.34] versus 1.52 [0.3; 2.85], p < 0.0001). Methods for quantifying the BMC/aBMD velocity that account for maturation and body composition changes provide a framework for evaluating childhood bone accretion and may provide insight into mechanisms contributing to altered accrual in chronic childhood conditions. © 2018 American Society for Bone and Mineral Research.

Type of infant formula increases early weight gain and impacts energy balance: a randomized controlled trial.

Background: Millions of infants are fed breast milk substitutes, and the type of infant formula can impact weight gain patterns. Objective: We conducted a randomized controlled trial to determine the direct impact of 2 types of infant formula (cow milk formula, CMF; extensively protein hydrolyzed formula, EHF) on growth and energy balance. Design: A racially diverse group of formula-fed infants (n = 113) were randomly assigned to either CMF or EHF from the age of 0.75 to 12.5 mo. At each monthly visit, anthropometric measures were obtained to determine growth z scores and weight gain velocity, and to categorize early weight gain patterns as rapid or nonrapid. Also, diet records were collected to determine energy from formula and other sources. Comprehensive assessments of energy balance (intake, expenditure, loss) were made at 0.75, 3.5, and 12.5 mo. Results: Beginning 3 wk after randomization, CMF infants had significantly higher weight, but not length, z scores than did EHF infants, and this persisted after solid foods complemented the formula diet. On average, weight gain velocity from 0.75 to 4.5 mo was within the range of typically growing infants for both groups, yet velocity was 3.9 g/d greater for CMF infants (P = 0.002), who were more likely to be classified as an early rapid weight gainer, than EHF infants (46% compared with 18%; P = 0.007). Early differences in energy intake and fecal loss, yielding greater energy available for deposition among CMF infants, contributed to the differential weight gain patterns. There were no significant differences between the formula treatment groups in total energy expenditure or sleeping energy expenditure. Conclusions: Among healthy infants, the type of formula impacted on early rapid weight gain patterns owing to energy intake and loss mechanisms. Research is needed to identify the macronutrients and other compositional constituents in EHF and breast milk that promote satiation and healthy weight gain during sensitive periods of development. This trial was registered at clinicaltrials.gov as: NCT01700205.

Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations.

OBJECTIVE: To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations. STUDY DESIGN: Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status. RESULTS: There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P < .001) with increased (P < .05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P < .05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P < .01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P = .028) and ΔCFA% (r = 0.47; P = .032) and negatively with ΔREE% (r = -0.50; P = .017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R2 = 0.579; P = .0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI. CONCLUSIONS: Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA). TRIAL REGISTRATION: ClinicalTrials.gov: NCT02141464.

Muscle Strength, Power, and Torque Deficits in Children With Type SS Sickle Cell Disease.

In African-American children aged 5 to 17 years with and without type SS sickle cell disease (SCD-SS), dominant hand maximal handgrip strength, peak power, and plantar flexion isometric maximal voluntary contraction (MVC) torque were compared with adjustments for body size and composition. Children with SCD-SS (n=21; age, 11±1 y) compared with healthy control children (n=23; 10±1 y) did not differ by age, sex, or maturation stage, but had significantly lower Z scores for height, weight, body mass index, arm circumference, upper arm muscle area, and lean mass-for-height. Children with SCD-SS had significantly lower unadjusted handgrip strength (16±2 vs. 23±2 kg, P<0.01), peak power (1054±107 vs. 1488±169 W, P<0.04) and MVC torques at 2 angles (10 degrees: 27±3 vs. 42±5 Nm; 20 degrees: 21±3 vs. 34±4 Nm; all P<0.05). Performance decrements persisted when handgrip strength was adjusted for lean body mass and fat mass explaining 66% of the variance; peak power adjusted for age, lean body mass, fat mass, and height explaining 91% of the variance; and the highest MVC torque (10-degree angle) adjusted for left leg length, lean mass-for-height, and fat mass-for-height Z scores explaining 65% of the variance. This suggests additional factors contribute to the attenuated anaerobic performance.