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.

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.

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.

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.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

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 ±â€Š3.0 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.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

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 ±â€Š3.0 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.

Size of testes, ovaries, uterus and breast buds by ultrasound in healthy full-term neonates ages 0-3 days.

BACKGROUND: Hormonally sensitive organs in the neonate can change size within days of birth as circulating maternal estrogen wanes. Although several reports document the size of these organs through infancy, few focus attention on the near-birth period. Clinical and research evaluation of hormonal and genitourinary disorders would benefit from reference size standards. OBJECTIVE: We describe the size of the uterus, ovaries, testes and breast buds in healthy term neonates. MATERIALS AND METHODS: As part of the Infant Feeding and Early Development (IFED) study, we sonographically measured the largest diameter of these organs in sagittal, transverse and anterior-posterior planes for 194 female and 204 male newborns up to 3 days old. We calculated mean, median and percentiles for longest axis length and for volume calculated from measured diameters. We evaluated size differences by laterality, gender and race and compared our observations against published values. RESULTS: Mean length and mean volume were as follows: uterus, 4.2 cm and 10.0 cm3; ovary, 1.0 cm and 0.2 cm3; testis, 1.1 cm and 0.3 cm3 (0.4 cm3 Lambert volume); female breast bud, 1.2 cm and 0.7 cm3; male breast bud, 1.1 cm and 0.6 cm3. Breast buds were larger in females than males. Laterality differences were typically below the precision of clinical measurement. No significant race differences were detected. CONCLUSION: Using data from our large cohort together with published values, we provide guidelines for evaluating the size of reproductive organs within the first 3 days of age. Discrepancies between our results and published values are likely attributable to technique.

Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

Vitamin B(12) status in children with cystic fibrosis and pancreatic insufficiency.

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 ±â€Š3.0 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.

Fat-soluble vitamins in cystic fibrosis and pancreatic insufficiency: efficacy of a nutrition intervention.

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.

Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy.

AIM: The long-term effects of the ketogenic diet, a high fat diet for treating intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of this study was to evaluate the impact of 15 months of ketogenic diet treatment on growth and REE in children with intractable epilepsy. METHOD: Growth, body composition, and REE were assessed at baseline, 3 months and 15 months in 24 children (14 males, 10 females; mean age 5 y 6 mo [SD 26 mo], range 7 mo-6 y 5 mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet responders at 3 months and continued on the ketogenic diet until 15 months. These were compared to 75 healthy children (43 males, 32 females; mean age 6 y 3 mo [SD 21 mo] age range 2-9 y). REE was expressed as percentage predicted, growth as height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free mass (FFM). RESULTS: HAz declined -0.2 and -0.6 from baseline to 3 months and 15 months respectively (p = 0.001), while WAz was unchanged. In ketogenic diet responders, FFM, age and CP diagnosis predicted REE (overall R(2) = 0.76, p<0.001) and REE did not change. REE adjusted for FFM was lower (p<0.01) in children with CP at baseline (mean [standard error], -143[51] kcals/d) and 15 months (-198[53] kcals/d) compared to the healthy children. INTERPRETATION: After 15 months of the ketogenic diet, linear growth status declined while weight status and REE were unchanged. REE remained reduced in children with CP.

Delayed small bowel transit in children with cystic fibrosis and pancreatic insufficiency.

OBJECTIVE: Gastrointestinal disturbances are common in people with cystic fibrosis (CF); however, motility studies in this population have yielded inconsistent results. This study examined gastric emptying (GE) and small bowel transit (SBT) time in children with CF and pancreatic insufficiency compared with a healthy adult reference group. METHODS: Participants consumed an 8-ounce liquid test meal (approximately 550 calories, 32 g of fat) labeled with 300 µCi 99m technetium (Tc) sulfur colloid. Subjects with CF received a standard dose of pancreatic enzymes before consuming the test meal. GE and SBT were measured using a standard nuclear medicine scan. GE was determined after correcting for 99mTc decay in both anterior and posterior images. SBT was determined by following the movement of the tracer from the stomach to the cecum. The percentage arrival of total small bowel activity at the terminal ileum and cecum/ascending colon at 6 hours was used as an index of SBT. A 1-way analysis of covariance was performed for comparisons between groups after adjustment for age, sex, and body mass index. RESULTS: Subjects with CF (n = 16) had similar GE compared with the healthy reference group (n = 12); however, subjects with CF had significantly prolonged SBT time. At 6 hours, 37.2% ± 25.4% (95% CI 23.7-50.7) of the tracer reached the terminal ileum and colon compared with 68.6% ± 13.1% (95% CI 60.2-76.9) for the reference group (P < 0.001). After controlling for sex, age, and body mass index, this difference remained statistically significant (F = 12.06, adjusted R = 0.44, P < 0.002). CONCLUSIONS: Children with CF and pancreatic insufficiency had unaltered GE but delayed SBT time when taking pancreatic enzymes.

Blood lead concentration is not altered by high-dose vitamin D supplementation in children and young adults with HIV.

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.

Diagnosing malabsorption with systemic lipid profiling: pharmacokinetics of pentadecanoic acid and triheptadecanoic acid following oral administration in healthy subjects and subjects with cystic fibrosis.

OBJECTIVE: A Malabsorption Blood Test (MBT) is proposed as an alternative method to the 72-hour stool and dietary collection for assessing the degree of fat malabsorption in people with pancreatic insufficiency. The MBT consists of a simultaneous oral dose of pentadecanoic acid (PA), a free fatty acid, and triheptadecanoic acid (THA), a triglyceride with three heptadecanoic (HA) saturated fatty acids requiring hydrolysis by pancreatic lipase before HA can be intestinally absorbed. The aim of this study is to demonstrate the ability of MBT to detect fat malabsorption in healthy adult subjects using the pancreatic lipase (PL) inhibitor Orlistat (Xenical®), and in subjects with CF and PI while on and off routine pancreatic enzyme doses. MATERIALS AND METHODS: The MBT with the PA and THA were delivered in a breakfast test meal (2.5 g PA and either 5 g or 8 g THA) to healthy adult subjects (ages 18 - 50 years, BMI 21 - 30) and to subjects with CF (> 12 years, FEV1% predicted > 40%), after a 12-hour fast and 24 hours without dairy foods. Serum levels of PA and HA were assessed by gas-liquid chromatography, from blood samples drawn prior to MBT and then hourly for 8 hours. For healthy subjects, the MBT was administered before and after Orlistat treatment, and in subjects with CF, both with subjects receiving routine pancreatic lipase treatment ("on enzyme") and also "off enzyme" treatment. Treatment groups were compared for baseline (C0) and maximum (Cmax) plasma concentrations of PA and HA over 8 hours: area under the curve (AUC) was calculated using linear trapezoid method. The ratio of HA to PA Cmax and AUC was also calculated and compared. RESULTS: For the healthy subjects (n = 15, 60% female, ages 21 - 49 years), absorption of HA was reduced 71% for Cmax (p < 0.001) and 65% for AUC (p = 0.001) after Orlistat treatment, and absorption of PA was unchanged. For subjects with CF (n = 6, 50% female, ages 13 - 19 years), absorption of HA was minimal with subjects "off enzymes" and increased significantly with subjects "on enzymes" while absorption of PA did not differ between groups. Enzyme administration resulted in increased Cmax HA/ PA ratios from 0.02 to 0.92 and from 0.05 to 0.73 in subjects with CF receiving 5.0 g and 8.0 g of THA, respectively. AUC HA/PA ratios showed similar increases. CONCLUSIONS: In this pilot and feasibility proof-of-concept study, the MBT, utilizing the relative absorption of HA to PA, two odd-chained fatty acids, responds to changes in fat absorption in healthy subjects using a lipase inhibitor and in subjects with CF while on or off enzyme therapy. The MBT holds promise to provide a more accurate, specific and acceptable alternative to the 72-hour stool collection to quantify pancreatic-based fat malabsorption in a variety of clinical and research contexts.

Relation between dietary fat intake type and serum fatty acid status in children with cystic fibrosis.

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 ±â€Š1.0 years, 32 girls) and 22 controls (8.5 ±â€Š1.1 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.

Attenuated maximal muscle strength and peak power in children with sickle cell disease.

Dominant hand maximal handgrip strength evaluated with a handgrip dynamometer and peak power evaluated with a force plate, adjusted for body size and composition, were compared in African-American children aged 5 to 13 years, with and without type SS sickle cell disease (SCD-SS). Children with SCD-SS (n = 35; age, 9.0 ± 2.0 y) compared with healthy control children (n = 103; age, 8.6 ± 1.8 y) did not differ by age, sex, or pubertal status, yet had significantly lower Z scores for height, weight, body mass index, upper arm muscle area, upper arm fat area, fat mass-for-height and lean mass-for-height. Children with SCD-SS had significantly lower handgrip strength (12.7 ± 3.3 vs. 15.2 ± 5.1 kg, P < 0.008), peak power (882 ± 298 vs. 1167 ± 384 W, P < 0.001), and growth and body composition adjusted Z scores for handgrip strength (0.6 ± 1.3 standard deviations, P < 0.004) and peak power (male children = 1.0 ± 0.8 standard deviations, P < 0.0002; female children = 1.0 ± 1.7 standard deviations, P < 0.006). Maximal muscle strength and peak power are attenuated in children with SCD-SS compared with healthy control children beyond expectation for growth and body composition deficits suggesting that additional factors contribute to attenuation in anaerobic performance.

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.

Clinical and genetic correlates of exercise performance in young children with cystic fibrosis.

Exercise performance in individuals with cystic fibrosis has been shown to be related to the extent of pulmonary dysfunction and undernutrition and genetic profile. The aim of this study was to examine these relationships in young children with cystic fibrosis. The participants were 64 children ages 8 to 11 years (M = 9.3, SD = 0.9) with cystic fibrosis and pancreatic insufficiency recruited from 13 different U.S. cystic fibrosis centers. Assigned to one of three groups by deltaF508 status: deltaF508/deltaF508 homozygous, deltaF508/Other heterozygous, and Other/Other, growth, nutritional and pulmonary status, and exercise performance were measured. Differences in exercise performance, pulmonary function, and nutritional status were not observed among the three groups. However, undernutrition and decreased pulmonary function were associated with measures of exercise performance. These results imply no effect of deltaF508 status on overall functional capacity during preadolescence in children with cystic fibrosis. Rather, the extent of pulmonary disease and undernutrition were associated with functional performance.

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.