Deborah A. Kawchak

Total and resting energy expenditure in children with sickle cell disease

OBJECTIVE To investigate energy balance in children with sickle cell disease (SCD) as the possible cause of impaired growth and undernutrition. STUDY DESIGN Growth, resting (REE), total (TEE), and activity-related (AEE) energy expenditure and dietary intake were examined in 36 African American children with SCD (20 girls and 16 boys) and 30 control subjects (15 girls and 15 boys) of similar age (mean, 11.2 years) and ethnicity. TEE was measured by means of the doubly labeled water technique and REE by indirect calorimetry. AEE was calculated as TEE minus REE. Fat free mass (FFM) was calculated from skinfold prediction equations. RESULTS REE was significantly increased (131 kcal/d) in children with SCD (P =.001), after adjusting for sex and FFM. Children with SCD tended to have lower TEE (214 kcal/d) than control subjects, but there was no difference after adjusting for FFM and sex (P =.57). Children with SCD had significantly (P =.025) lower AEE (268 kcal/d) but only marginally (P =.08) lower AEE after adjusting for FFM and sex. CONCLUSIONS The elevated REE and lower AEE, in combination with poor growth status, indicate chronic energy deficiency in children with SCD. Further studies are needed to determine the best approaches to the treatment and prevention of undernutrition in children with SCD.

Prospective Evaluation of Resting Energy Expenditure, Nutritional Status, Pulmonary Function, and Genotype in Children with Cystic Fibrosis

Growth failure and malnutrition are common clinical features in cystic fibrosis (CF), but the relationships among resting energy expenditure (REE), pulmonary function, and nutritional status, are poorly understood. To better understand these relationships, REE, growth, nutritional status, and pulmonary function were measured prospectively in 25 prepubertal children with CF and 26 prepubertal control subjects of similar age and gender over a 3-y period. All subjects with CF had pancreatic insufficiency and mild pulmonary disease. REE was elevated for the CF children compared with control subjects throughout the study. This increased REE was not associated with declining pulmonary function. Longitudinal analyses revealed different patterns of change over time in boys and girls, such that REE significantly increased in the girls with CF and pulmonary function decreased in the boys. Boys with CF experienced a decline in weight Z score and percent ideal body weight, whereas the girls with CF experienced a decline in height Z score. Pulmonary function was not associated with REE, but nutritional status (percent ideal body weight) and genotype (ΔF508 homozygotes versus others) were predictive of changes in pulmonary function over time. Fat free mass and height were found to be the best predictors of REE, and after accounting for these important body size and composition variables, differences in REE between boys and girls and CF and control groups increased over time. These findings identify the importance of investigating gender differences in the course of disease and considering REE as an early indicator of disease severity independent of pulmonary function.

Longitudinal, prospective analysis of dietary intake in children with cystic fibrosis

OBJECTIVES Prospective, 3-year longitudinal dietary intakes of 25 prepubertal, pancreatic-insufficient children with cystic fibrosis (CF) and mild lung disease, and the intakes of 26 control children were compared, and relationships among energy intake, nutritional status, and pulmonary function were determined. STUDY DESIGN Intakes from 3-day weighed food records were compared with CF recommendations, recommended dietary allowances (RDA), and the recommendations of the Third National Health and Nutrition Examination Survey (NHANES III). Energy and nutrient intakes were analyzed by repeated-measures analysis of variance. RESULTS Children with CF consumed more energy than control children (p = 0.025) in terms of calories per day, percentage of RDA by age and by age and weight, energy adjusted for fat malabsorption, and percentage of NHANES III recommendations. Energy intake was similar between boys and girls with CF. The percentage of energy from fat was greater (p = 0.0004) in the CF group (3-year mean, 33%) than in the control group. Height and weight z scores declined in the CF group (p <0.05) with time. Vitamin and mineral intakes were generally adequate in the CF group. CONCLUSIONS The children in this sample did not consume the CF recommended intakes of 120% RDA for energy or a high-fat (40% of energy) diet. Energy intakes may be insufficient in this group to meet requirements for optimal growth.

Energy expenditure and genotype of children with cystic fibrosis

ABSTRACT: Increased energy expenditure, poor dietary intake, and fat malabsorption in patients with cystic fibrosis (CF) frequently lead to growth failure and malnutrition, which are associated with pulmonary failure and decreased survival. The study purpose was to understand better the energy expenditure and requirements in the mild pulmonary disease state in children. Resting and total energy expenditure were measured in 6− to 9-yr-old, pancreatic-insufficient children with CF (n = 25) and control children (n = 25) of similar age, gender, and weight. The effect of the most common genotype, homozygous ΔF508, on energy expenditure was also investigated. Dietary intake, degree of fat malabsorption, body composition, physical activity, and clinical status were determined. The CF group had a 9% increase in resting energy expenditure, which was not related to genotype or severity of lung disease. Both CF genotype subgroups (ΔF508 homozygous and all others) had a similar, modest resting energy expenditure increase. Total energy expenditure was increased by 12% in the entire CF group and by 23% in the ΔF508 homozygous CF subgroup compared with controls. The total energy expenditure increase in ΔF508 homozygous children may be related to increased voluntary physical activity, reflecting no activity reduction associated with lung disease, or to an unidentified genotype-related mechanism. The clinical implication is that a detailed physical activity assessment should be evaluated along with resting energy expenditure, either measured or estimated by equations, when daily energy needs are being determined for children with CF.

Effects of Delayed Pubertal Development, Nutritional Status, and Disease Severity on Longitudinal Patterns of Growth Failure in Children With Sickle Cell Disease

Previous studies of children with sickle cell disease (SCD) reported poor growth and delayed maturation. However, the prevalence, magnitude, and correlates of suboptimal growth remain poorly understood. A prospective longitudinal study was undertaken to determine the effects of disease severity and nutritional status on growth, an indicator of childhood well-being. Children, birth to 18 y of age, with SCD-SS were evaluated annually for 4 y. Growth, nutritional status, skeletal and sexual maturation, disease severity, dietary intake, and maternal education were assessed. In this sample of 148 children (78 females), growth in height, weight, or body mass index declined in 84% of subjects; 38% fell below the 5th percentile in one or more measures. Puberty was delayed 1 to 2 y, and median age at menarche was 13.2 y. Skeletal age was delayed by 0.7 ± 1.4 y overall and by 1.3 ± 1.5 y in children 10 to 15 y old. Height status declined over time and was positively associated with advancing puberty and hematological measures in girls, and nutritional status in girls and boys. Growth failure and maturational delay remain significant chronic problems in children with SCD-SS and are related to potentially modifiable factors such as nutritional status.

Plasma zinc status, growth, and maturation in children with sickle cell disease

OBJECTIVE The objective of this study was to determine the relation of plasma zinc (Zn) status to growth and maturation in children with SS genotype sickle cell disease. STUDY DESIGN A cross-sectional study of 104 subjects who were 50% female and ranged in age from 0.4 to 18 years was performed. Measures included plasma Zn concentration (Znp), height, weight, skinfold thicknesses, elbow breadth, upper arm muscle area, and fat-free mass and fat mass by total body electrical conductivity. Skeletal maturation was assessed by hand-wrist x-ray evaluation and sexual maturation by Tanner stage. RESULTS A total of 44% of the patients had low Znp (<10.7 micromol/L [70 microg/dl]); those with low Znp had significantly lower SD scores for height (p = 0.003), weight (p = 0.003), upper arm muscle area (p = 0.045), fat-free mass (p = 0.025), and elbow breadth (p = 0.017) and greater skeletal maturation delay (p = 0.04). In older children (>9 years) low Znp was associated with decreased Tanner scores for pubic hair (p = 0.001) and breast and genital maturation (p = 0.009). No significant differences were seen in age, sex, or fat stores according to Zn status. CONCLUSIONS Decreased plasma Zn is common in children with SS genotype sickle cell disease and is associated with decreased linear growth, skeletal growth, muscle mass, and sexual and skeletal maturation.

High risk of vitamin D deficiency in children with sickle cell disease.

Vitamin D is a particularly concerning nutrient for children with homozygous SS sickle cell disease (SCD-SS) due to their increased skin melanin concentrations, reduced levels of physical activity, and poor vitamin D intake. The goal of this study was to compare the vitamin D status of children with SCD-SS to healthy African-American children living in the same geographic area. Growth, dietary intake, serum 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone (iPTH) concentrations were measured in 61 African-American subjects with SCD-SS and 89 healthy African-American control subjects age 5 to 18 years from the Philadelphia, PA, region (latitude 39.95 degrees N). Median serum 25(OH)D concentrations were 15 ng/mL (95% confidence interval [CI]: 13, 17) in subjects with SCD-SS and 21 ng/mL (95% CI: 18, 22) in healthy control subjects (P<0.0002). Vitamin D deficiency [25(OH)D<11 mg/mL] was found in 33% of subjects with SCD-SS and 9% of healthy control subjects (P<0.001); 25% of subjects with SCD-SS and 17% of healthy control subjects had elevated iPTH [(>59 rhog/mL), P<0.05]. Ninety-three percent of subjects with SCD-SS and 90% of healthy subjects had vitamin D insufficiency [25(OH)D<30 mg/mL]. The risk of vitamin D deficiency among subjects with SCD-SS was 5.3 (95% CI: 2.5, 8.2) times greater than control subjects, adjusted for season and age. Poor vitamin D status was prevalent in children with SCD-SS and healthy African-American children living in the same geographic area. However, children with SCD-SS were at greater risk for vitamin D deficiency than healthy African-American children.

Bone Area and Bone Mineral Content Deficits in Children With Sickle Cell Disease

Objective. Children with sickle cell disease (SCD) experience poor growth, altered body composition, and delayed maturation. Deficits in bone mineral content (BMC) and bone area (BA) have not been well characterized. The objectives of this study were to assess whole-body BMC (WBBMC) and WBBA in children with SCD, type SS (SCD-SS), compared with healthy control subjects, adjusted for growth and body composition, and to determine the relationships of WBBMC and WBBA to bone age and hematologic parameters in children with SCD-SS. Methods. WBBMC, WBBA, and lean mass were measured by dual-energy x-ray absorptiometry in children who were aged 4 to 19 years. Growth, sexual development, and bone age were assessed. Gender-specific z scores for WBBMC relative to age and height were generated from control data. Results. Ninety children with SCD-SS and 198 healthy control subjects were evaluated. SCD-SS was associated with poor growth. WBBMC was significantly decreased in SCD-SS compared with control subjects, adjusted for age, height, pubertal status, and lean mass. WBBMC relative to age and WBBMC relative to height z scores were −0.95 ± 0.99 and −0.54 ± 0.97, respectively, and were associated with hemoglobin and hematocrit levels and history of delayed bone age. Conclusions. Children with SCD-SS have significant deficits in WBBMC that persist despite adjustment for poor growth and decreased lean mass. These children may be at increased risk for fragility fractures and suboptimal peak bone mass.

Red blood cell folate and serum vitamin B12 status in children with sickle cell disease

Purpose To determine red blood cell (RBC) folate and serum vitamin B12 levels in children with sickle cell disease, SS-type, and to evaluate the associations of these nutrient levels with growth and hematologic parameters. Patients and Methods Subjects enrolled in this prospective, cross-sectional study were recruited from one tertiary care setting. Complete blood counts, measurement of red blood cell (RBC) folate and serum vitamin B12, anthropometric measures (height, weight, skinfold measurements), pubertal status, and 24-hour dietary recalls were obtained from 70 patients ages 1 to 19 years. Results Low RBC folate levels were found in 15% of the children. Fifty-seven percent of the sample had inadequate dietary folate intake. Three percent of the children had low serum vitamin B12 levels. All children and adolescents sampled had adequate dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12 levels (P < 0.01) decreased with increasing age. Conclusions More than half of the subjects had inadequate intake of folate from food, and despite daily folate supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were rare, and dietary vitamin B12 intake was adequate. Additional research is needed to explore the effects of improved folate status, the need for folate supplementation, and the relationship of folate, vitamin B12, and homocysteine levels and the risk for vascular damage and stroke in children with sickle cell disease.

Vitamin B6 status of children with sickle cell disease

Purpose In vitro, vitamin B6 has antisickling properties, but the effect of vitamin B6 status on the health of children with sickle cell disease-SS (SCD-SS) is not well described. The purpose of this study was to assess vitamin B6 status of children with SCD-SS ages 3 to 20 years and determine its relationship to growth, dietary intake, and disease severity. Patients and Methods Vitamin B6 status was assessed by serum pyridoxal 5-phosphate (PLP) concentration in subjects with SCD-SS and by urinary 4-pyridoxic acid (4-PA) concentration in other subjects with SCD-SS and healthy control children. Concentration of PLP was compared with anthropometric measures of growth and nutritional status, dietary intake, hematologic indices, and frequency of SCD-related illness. Results The PLP concentration of subjects with SCD-SS was 15.6 ± 15.2 nmol/L. Seventy-seven percent had a PLP concentration below the deficiency criterion (20 nmol/L) suggested by the Dietary Reference Intakes (1998). Controlling for alkaline phosphatase, age, and gender, PLP concentration was associated positively with weight, body mass index, and arm circumference z-scores and negatively with reticulocyte count. Urinary 4-PA was lower in children with SCD-SS versus controls, although 4-PA/creatinine values did not differ between groups. Conclusions Children with SCD-SS had apparently low serum PLP concentrations in the absence of excess vitamin B6 excretion, suggesting low vitamin B6 status. Low serum PLP concentration was associated with indicators of poor nutritional status and may be related to increased hemolysis in children with SCD-SS.