Markers of bone turnover are associated with growth and development in young subjects with sickle cell anemia.

Children with sickle cell anemia (SCA) have low bone mass though bone turnover has not been well described. In this study, growth and pubertal development were assessed twice, 1 year apart, in 80 young subjects with type-SS SCA, while whole body bone mineral content (BMC) and density where measured in a subset (n = 46). Markers of bone turnover were measured at the second visit. Bone formation (alkaline phosphatase) was elevated, whereas bone resorption (deoxypyridinoline) was decreased compared to published data in healthy children. Markers of bone turnover correlated with growth velocity and pubertal development but not with changes in bone mass.

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.

Adequacy of dietary intake declines with age in children with sickle cell disease.

Dietary intake (24-hour recall) was evaluated prospectively over four annual visits in 97 children and adolescents (53 female), aged 1.5 to 18.7 years, with sickle cell disease, type SS. Macro- and micronutrient intakes were compared to Dietary Reference Intakes (DRI) and expressed as %DRI. z scores for height, weight, and body mass index were calculated to assess growth status. Both t tests and Mann-Whitney U tests were used for year 1 comparisons, and longitudinal mixed effects analysis was used for the longitudinal data. Intake of vitamins E and D, folate, calcium, and fiber as %DRI was low for children of all ages. Intake of protein, vitamin C, riboflavin, vitamin B-12, and magnesium was lower by at least 28% DRI in the oldest (aged 14 to 18 years) compared to the youngest children (aged 1 to 3 years), and intake of vitamin A, magnesium, and phosphorus was suboptimal in children older than 9 years. After adjusting for initial age and sex, intake of riboflavin, zinc, calcium, magnesium, and phosphorus declined steeply (8% to 16% DRI annually) across the 3 years. Weight and body mass index z scores also declined over time. Dietary intake was particularly poor in adolescents. Efforts are needed to ensure dietary adequacy in children with sickle cell disease, type SS and to understand the etiology of poor dietary intake.

Effect of zinc supplementation on growth and body composition in children with sickle cell disease.

BACKGROUND: Poor growth and delayed maturation in children with sickle cell disease (SCD) may be due, in part, to mild zinc deficiency. OBJECTIVE: The objective was to determine the effects of zinc supplementation on growth and body composition in children with SCD. DESIGN: Forty-two prepubertal children (20 girls and 22 boys) aged 4-10 y with SCD-SS were randomly assigned to receive 10 mg elemental Zn/d in cherry syrup (zinc group) or cherry syrup alone (control group). The 2 groups were stratified by sex and initial height status. Dietary intakes were evaluated and anthropometric, high-precision knee-height, and plasma zinc measurements were made at baseline and at 3, 6, and 12 mo. Body composition was determined every 6 mo with dual-energy X-ray absorptiometry, and z scores for anthropometric variables were computed from national reference data. Longitudinal-mixed-effects analysis was used to test for differences between the groups over the 12-mo observation period. RESULTS: Thirty-eight children completed the study. No significant differences were observed at baseline. After 12 mo, the zinc group had significantly greater mean (+/- SE) increases in height (0.66 +/- 0.29 cm/y), sitting height (0.97 +/- 0.40 cm/y), knee height (3.8 +/- 1.2 mm/y), and arm circumference z scores (0.27 +/- 0.12 cm/y). Height-for-age and weight-for-age z scores decreased significantly by 0.11 +/- 0.04 and 0.13 +/- 0.05, respectively, in the control group but did not change significantly in the zinc group. CONCLUSIONS: Prepubertal children with SCD-SS may have zinc deficiency and may benefit from zinc supplementation to improve linear growth and weight gain.

Body composition in children with sickle cell disease.

BACKGROUND: Impaired growth, poor nutritional status, and delayed skeletal and sexual maturation are common in children with sickle cell disease (SCD), yet the nature of associated body-composition deficits has not been fully described. OBJECTIVE: The objective was to assess growth, nutritional status, and body composition in 36 African American children with type SS SCD (20 females and 16 males) and 30 healthy control children (15 females and 15 males) of similar age (5-18 y) and ethnicity. DESIGN: Height, weight, bone age, pubertal status, skinfold thickness, and arm circumference were assessed. Height and weight were converted to z scores by comparison with national reference data and skinfold-thickness measurements were converted to z scores by comparison with African American- specific reference data. Fat-free mass (FFM) and fat mass (FM) were estimated by using 4 methods. Prepubertal children, pubertal males, and pubertal females were analyzed separately. RESULTS: Relative to the control subjects and to a national sample, children with SCD had significantly lower z scores for weight, height, arm circumference, and upper arm fat and muscle areas. Relative skeletal maturation was significantly delayed. After adjustment for age, children with SCD had significantly lower FM (prepubertal children and pubertal males only) and FFM (all 3 groups). CONCLUSIONS: Children with SCD have impaired growth, delayed puberty, and poor nutritional status. Low z scores for upper arm fat area indicate deficits in fat (energy) stores, and low FFM coupled with low upper arm muscle area indicate muscle wasting and low protein stores. These body-composition abnormalities suggest that the nutritional needs of the African American children with SCD were not being met.

Plasma zinc is an insensitive predictor of zinc status: use of plasma zinc in children with sickle cell disease.

BACKGROUND: This study was designed to explore the use of plasma zinc in determining zinc deficiency in children with sickle cell disease-SS (SCD-SS) as indicated by a growth response to zinc supplementation. METHODS: Fasting plasma zinc was assessed in children with SCD-SS (ages 4 to 10 years) who were randomly assigned to receive 10 mg zinc/d in cherry syrup (zinc) or cherry syrup alone (placebo) for 12 months. Evaluations for growth, dietary intake, and other biochemical parameters were made at baseline and 3, 6, and 12 months. Longitudinal mixed effects analysis evaluated differences between groups over 12 months. RESULTS: A total of 38 prepubertal children (20 male and 18 female; 18 zinc and 20 placebo) completed the study (7.1 +/- 1.7 years old). At baseline, plasma zinc was low (< or = 70 microg/dL) in 7 male subjects. Despite the significant increase in height over 12 months (+0.7 cm) with zinc supplementation (p = .019), plasma zinc did not change over the 12 months of study, and there was no association between plasma zinc and linear growth. Those children with low plasma zinc who received zinc supplementation showed improved linear growth. CONCLUSIONS: These findings suggest that plasma zinc is an insensitive indicator of zinc status in children with SCD-SS. Children with low plasma zinc will benefit from zinc supplementation. However, some children with normal plasma zinc and poor growth may also have growth-limiting zinc deficiency and exhibit a growth response to zinc supplementation. Although this study focused on children with SCD-SS, results may be generalized to other pediatric clinical illnesses where nutrition-related growth failure is investigated.

No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease.

BACKGROUND: Suboptimal vitamin A status is prevalent in children with type SS sickle cell disease (SCD-SS) and is associated with hospitalizations and poor growth and hematologic status. The supplemental vitamin A dose that optimizes suboptimal vitamin A status in this population is unknown. OBJECTIVE: The efficacy of Recommended Dietary Allowance (RDA) doses (based on age and sex) of vitamin A (300, 400, or 600 µg retinyl palmitate/d) or vitamin A + zinc (10 or 20 mg zinc sulfate/d) compared with placebo to optimize vitamin A status was assessed in children aged 2.0-12.9 y with SCD-SS and a suboptimal baseline serum retinol concentration (<30 µg/dL). DESIGN: In this randomized, double-blind, placebo-controlled trial, vitamin A status (serum retinol, prealbumin, retinol-binding protein, and relative-dose-response test) and disease-related illness events were assessed. RESULTS: Twelve months of vitamin A supplementation at the doses recommended for healthy US children (based on age and sex) failed to improve serum retinol values in either group (vitamin A: n = 23; vitamin A + zinc: n = 18) compared with placebo (n = 21). By 12 mo, the increase (±SD) in serum retinol (3.6 ± 2.8 µg/dL) in those taking 600 µg vitamin A/d was significantly different from the decrease (±SD; -2.8 ± 2.4 µg/dL) in those taking 300 µg/d, which possibly suggests a dose-response relation (P < 0.05) with RDA doses. CONCLUSIONS: Compared with placebo, 12 mo of vitamin A supplementation at the RDA for healthy children did not improve serum retinol values in children with SCD-SS, which possibly suggests that higher doses are needed. However, the existence of alternative conclusions emphasizes the need for future research.

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.

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.

Low vitamin D status in children with sickle cell disease.

OBJECTIVES: To examine vitamin D status in children with sickle cell disease (SCD)-SS and its relation to season and dietary intake. STUDY DESIGN: Growth, dietary intake, 25-hydroxyvitamin D (25-OHD), and parathyroid hormone levels were measured. Children with low and normal vitamin D status were compared. Low vitamin D status was defined as a serum concentration of 25-OHD <27.5 nmol/L. Serum 25-OHD and parathyroid hormone levels were compared among children with SCD-SS and healthy children. RESULTS: Children with SCD-SS (n=65), 5 to 18 years of age, were evaluated. Mean (+/-SD) serum 25-OHD concentration was 25.5 +/- 12.8 nmol/L; 65% of subjects had low vitamin D status. Low vitamin D prevalence was highest during spring (100%). Children with SCD-SS were at higher risk for low vitamin D status than healthy children. Vitamin D intake was lower in subjects with SCD-SS and low vitamin D than those with normal serum vitamin D status (P <.05). CONCLUSIONS: Low serum vitamin D status was highly prevalent in black children with SCD-SS. Vitamin D status was associated with season and dietary intake.

Brief report: parent perspectives of nutritional status and mealtime behaviors in children with sickle cell disease.

OBJECTIVE: To qualitatively evaluate parent perspectives of eating problems, nutritional status, and the potential for nutritional intervention in children with sickle cell disease (SCD). METHODS: Twenty parents of children with SCD participated in one of three focus groups to discuss questions related to the study's objectives. Three coders rated transcripts to identify common perceptions and experiences (themes) among participants. RESULTS: Poor appetite and its impact on nutritional and general health were particular concerns for parents. Parents addressed eating challenges with dietary supplementation, limit setting, and compromising at meals, often without consultation from health professionals. An intervention program should include facilitators, such as flexible scheduling and incentives to counter barriers, such as scheduling and child care conflicts. CONCLUSIONS: Parents of children with SCD reported a range of eating behavior challenges. Parents presented ideas on how nutritional intervention could be culturally sensitive and on how to promote participation in such programs.

Vitamin A status, hospitalizations, and other outcomes in young children with sickle cell disease.

OBJECTIVE: To determine the relation of serum vitamin A status to growth, nutritional and hematologic status, and to the number of hospitalizations in children with sickle cell disease-SS (homozygous for the S allele, SCD-SS). STUDY DESIGN: Children (2-9.9 years of age) with SCD-SS were assessed for serum retinol, hemoglobin, hematocrit, reticulocyte count, height, weight, body mass index, and recalled dietary intake. Vitamin A status was defined on the basis of serum retinol concentration as suboptimal (<30 microg/dL) and normal (> or =30 microg/dL). Hospitalizations were determined for 1 year after vitamin A assessment. RESULTS: Mean serum retinol was 26.7 +/- 6.8 microg/dL in 66 subjects (39 girls) and was suboptimal in 66% of children. Compared with those with normal status, children with suboptimal vitamin A had significantly lower body mass index z score (-0.7 +/- 1.0 vs -0.1 +/- 0.6) and hemoglobin (7.9 +/- 1.1 vs 8.5 +/- 1.1), and hematocrit (23.3 +/- 3.0 vs 25.1 +/- 3.8) and significantly more hospitalizations (2.8 +/- 2.0 vs 0.7 +/- 0.8). After adjusting for age and sex, suboptimal vitamin A status was associated with a 10-fold increased risk for hospitalization (OR, 10.5; 95% CI, 2.3, 48.6) and with increased pain (OR,5.3; 95% CI, 1.3, 21.6) and fever episodes (OR, 6.4; 95% CI, 1.7, 24.9) requiring hospitalization. CONCLUSIONS: Suboptimal vitamin A status was prevalent in US children with SCD-SS and was associated with increased hospitalizations and poor growth and hematologic status.

Vitamin B6 status of children with sickle cell disease.

PURPOSE: In vitro, vitamin B(6) has antisickling properties, but the effect of vitamin B 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 B(6) 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 B(6) 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 -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 B(6) excretion, suggesting low vitamin B(6) 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.