Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial.

Importance: The large overlap between symptoms of acute sinusitis and viral upper respiratory tract infection suggests that certain subgroups of children being diagnosed with acute sinusitis, and subsequently treated with antibiotics, derive little benefit from antibiotic use. Objective: To assess if antibiotic therapy could be appropriately withheld in prespecified subgroups. Design, Setting, and Participants: Randomized clinical trial including 515 children aged 2 to 11 years diagnosed with acute sinusitis based on clinical criteria. The trial was conducted between February 2016 and April 2022 at primary care offices affiliated with 6 US institutions and was designed to evaluate whether symptom burden differed in subgroups defined by nasopharyngeal Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis on bacterial culture and by the presence of colored nasal discharge. Interventions: Oral amoxicillin (90 mg/kg/d) and clavulanate (6.4 mg/kg/d) (n = 254) or placebo (n = 256) for 10 days. Main Outcomes and Measures: The primary outcome was symptom burden based on daily symptom scores on a validated scale (range, 0-40) during the 10 days after diagnosis. Secondary outcomes included treatment failure, adverse events including clinically significant diarrhea, and resource use by families. Results: Most of the 510 included children were aged 2 to 5 years (64%), male (54%), White (52%), and not Hispanic (89%). The mean symptom scores were significantly lower in children in the amoxicillin and clavulanate group (9.04 [95% CI, 8.71 to 9.37]) compared with those in the placebo group (10.60 [95% CI, 10.27 to 10.93]) (between-group difference, -1.69 [95% CI, -2.07 to -1.31]). The length of time to symptom resolution was significantly lower for children in the antibiotic group (7.0 days) than in the placebo group (9.0 days) (P = .003). Children without nasopharyngeal pathogens detected did not benefit from antibiotic treatment as much as those with pathogens detected; the between-group difference in mean symptom scores was -0.88 (95% CI, -1.63 to -0.12) in those without pathogens detected compared with -1.95 (95% CI, -2.40 to -1.51) in those with pathogens detected. Efficacy did not differ significantly according to whether colored nasal discharge was present (the between-group difference was -1.62 [95% CI, -2.09 to -1.16] for colored nasal discharge vs -1.70 [95% CI, -2.38 to -1.03] for clear nasal discharge; P = .52 for the interaction between treatment group and the presence of colored nasal discharge). Conclusions: In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens on presentation, and its effects did not depend on the color of nasal discharge. Testing for specific bacteria on presentation may represent a strategy to reduce antibiotic use in this condition. Trial Registration: ClinicalTrials.gov Identifier: NCT02554383.

Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants.

As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

Homologous and Heterologous Covid-19 Booster Vaccinations.

BACKGROUND: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. METHODS: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 µg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. RESULTS: Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. CONCLUSIONS: Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

CONTEXT AND PURPOSE: There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. METHODS: IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. RESULTS: To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. CONCLUSIONS: Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. TRAIL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

Heterologous SARS-CoV-2 Booster Vaccinations - Preliminary Report.

Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-µg, Janssen Ad26.COV2.S 5×1010 virus particles, or Pfizer-BioNTech BNT162b2 30-µg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 153 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

Effect of vitamin D3 supplementation on vascular and metabolic health of vitamin D-deficient overweight and obese children: a randomized clinical trial.

BACKGROUND: Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health. OBJECTIVES: The aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects. METHODS: We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome. RESULTS: Dose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group. CONCLUSIONS: Correction of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.

Gene Expression and Cardiometabolic Phenotypes of Vitamin D-Deficient Overweight and Obese Black Children.

Associations between whole blood transcriptome and clinical phenotypes in vitamin D-deficient overweight and obese children can provide insight into the biological effects of vitamin D and obesity. We determined differentially expressed genes (DEGs) in relation to body mass index (BMI) in vitamin D-deficient black children with a BMI ≥ 85th percentile and ascertained the cardiometabolic phenotypes associated with the DEGs. We examined whole-blood transcriptome gene expression by RNA sequencing and cardiometabolic profiling in 41, 10- to 18-year-old children. We found 296 DEGs in association with BMI after adjusting for age, race, sex, and pubertal status. Cardiometabolic phenotypes associated with the BMI-related DEGs, after adjusting for age, sex, pubertal status, and %total body fat, were (i) flow-mediated dilation (marker of endothelial function), (ii) c-reactive protein (marker of inflammation), and (iii) leptin (adipocytokine). Canonical pathways of relevance for childhood obesity and its phenotypes that were significantly associated with the BMI-related DEGs affected immune cell function/inflammation, vascular health, metabolic function, and cell survival/death; several immune and inflammatory pathways overlapped across the three phenotypes. We have identified transcriptome-based biomarkers associated with BMI in vitamin D-deficient, overweight and obese black children. Modulating effects of vitamin D supplementation on these biomarkers and their related phenotypes need further exploration.

Utility of sun-reactive skin typing and melanin index for discerning vitamin D deficiency.

BackgroundSkin color, a vitamin D status determinant, can be assessed subjectively by Fitzpatrick sun-reactive skin typing (FST) and objectively by melanin index (MI). FST was validated against MI for discerning vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) <20 ng/ml) in children.MethodsWe measured FST, MI, and serum 25(OH)D in healthy, 8- to 18-year-old children from one of two vitamin D trials. MI from forehead, hand, and upper arm split at the median of the more racially balanced study cohort and FST (I-III vs. IV-V) were used for discriminating vitamin D deficiency.ResultsA total of 296 participants (mean age, 12.3±2.3 years; black, 208; FST IV-V, 209; 25(OH)D <20 ng/ml, 159) were studied. MI and FST had a strong positive association. Serum 25(OH)D was negatively associated with MI and FST. Sensitivity, specificity, and predictive values were similar for discriminating vitamin D deficiency between higher vs. lower MI and between FST I-III vs. IV-V. ROC area under the curves for FST (0.59) and MI (forehead (0.63); hand (0.62); and arm (0.64)) were similar.ConclusionsFST is comparable to MI for discerning vitamin D deficiency and can be deemed as an inexpensive, useful surrogate measure of skin color in the context of vitamin D research.

Estimations of dietary vitamin D requirements in black and white children.

BACKGROUND: The Institute of Medicine (IOM) dietary guidelines for vitamin D are based on limited pediatric data. Our objective was to estimate the dietary vitamin D requirements for maintaining serum 25-hydroxyvitamin D [25(OH)D] concentrations at the various IOM-considered thresholds of vitamin D status (12, 16, and 20 ng/ml) during fall and winter in children. METHODS: Ninety-six healthy 8- to 14-y-old Pittsburgh-area black and white children enrolled in a randomized, placebo-controlled trial of vitamin D3 1,000 IU daily for 6 mo with baseline and 2-mo follow-up assessments completed during October through April were studied. Vitamin D intake from diet and study supplement adjusted for adherence and serum 25(OH)D were measured. RESULTS: The vitamin D intakes needed to maintain serum 25(OH)D concentrations at 12, 16, and 20 ng/ml in 90% of the children were 581, 1,062, and 1543 IU/day, respectively. The estimated vitamin D intakes needed to maintain serum 25(OH)D concentrations at 20 ng/ml in 97.5% of the children was 2,098 IU/day. CONCLUSION: Our data suggest that the current vitamin D recommended dietary allowance (RDA) (600 IU/day) is insufficient to cover the skeletal health needs of at least 50% of black and white children.

Determinants of 25-Hydroxyvitamin D Concentrations in Infants and Toddlers.

BACKGROUND: Resurgence of rickets and recognition of excessive prevalence of hypovitaminosis D among all age groups in the western hemisphere have refocused attention on vitamin D nutrition. OBJECTIVE: To examine the prevalence of hypovitaminosis D [25-hydroxyvitamin D [25(OH)D] <30ng/mL] and characterize the determinants of 25(OH)D concentrations in 8- to 24-month-old healthy infants and toddlers living in Pittsburgh, Pennsylvania. METHODS: Serum 25(OH)D concentrations were measured and dietary intake of vitamin D, mode of feeding, summertime sun exposure characteristics, and skin color (sun-reactive skin type and melanin index) were assessed. RESULTS: A total of 111 healthy 8- to 24-month-old children (mean age [±SD] 14.4 [±3.5] months; male, 51%; black, 67%) were studied. Serum 25(OH)D concentration was <30 ng/mL in 16% (n=18) of the children. Median (interquartile) 25(OH)D concentration was lower in children who were ≥ 13 months vs. <13 months of age [35 (31, 40.5) vs. 40 (35.8, 44.3) ng/mL, p=0.013]; with sun-reactive skin type IV and V vs. I, II, and III [36 (31, 41) vs. 44 (36.5, 48.5) ng/mL, p=0.001]; and examined during fall/winter vs. spring/summer [35.5 (32.5, 38.5) vs. 39 (32.5, 44) ng/mL, p=0.05]. Age and skin type were significant independent predictors of 25(OH)D. CONCLUSIONS: Concentrations of 25(OH)D tend to be lower in infants and toddlers during fall/winter, and in children who are older (≥13 months vs. <13 months of age) and have darker skin tone. Benefits of enhancement of 25(OH)D concentrations during fall/winter and in children with higher sun-reactive skin type need further exploration.

Effect of Vitamin D3 Supplementation in Black and in White Children: A Randomized, Placebo-Controlled Trial.

CONTEXT: Dosages of vitamin D necessary to prevent or treat vitamin D deficiency in children remain to be clarified. OBJECTIVE: To determine the effects of vitamin D3 1000 IU/d on serum 25-hydroxyvitamin D [25(OH)D], PTH, and markers of bone turnover (osteocalcin and collagen type 1 cross-linked C-telopeptide) in black children and white children, and to explore whether there is a threshold level of 25(OH)D associated with maximal suppression of serum PTH concentration. DESIGN: Healthy 8- to 14-year-old Pittsburgh-area black (n = 84) and white (n = 73) children not receiving vitamin supplements, enrolled from October through March from 2008 through 2011, were randomized to vitamin D3 1000 IU or placebo daily for 6 months. RESULTS: The mean baseline concentration of 25(OH)D was <20 ng/mL in both the vitamin D-supplemented group and the placebo group (19.8 ± 7.6 and 18.8 ± 6.9 ng/mL, respectively). The mean concentration was higher in the supplemented group than in the placebo group at 2 months (26.4 ± 8.1 vs 18.9 ± 8.1 ng/mL; P < .0001) and also at 6 months (26.7 ± 7.6 vs 22.4 ± 7.3; P = .003), after adjusting for baseline 25(OH)D, race, gender, pubertal status, dietary vitamin D intake, body mass index, and sunlight exposure. Increases were only significant in black children, when examined by race. The association between 25(OH)D and PTH concentrations was inverse and linear, without evidence of a plateau. Overall, vitamin D supplementation had no effect on PTH and bone turnover. CONCLUSIONS: Vitamin D3 supplementation with 1000 IU/d in children with mean baseline 25(OH)D concentration <20 ng/mL effectively raised their mean 25(OH)D concentration to ≥20 ng/mL but failed to reach 30 ng/mL. Vitamin D supplementation had no effect on PTH concentrations.

Impact of seasonal flux on 25-hydroxyvitamin D and bone turnover in pre- and early pubertal youth.

BACKGROUND: Seasonal fluxes in 25-hydroxyvitamin D (25(OH)D) in children can affect bone turnover, and in turn potentially affect bone accrual and peak bone mass. The aim of this study was to examine the effect of seasonal flux on the association among 25(OH)D, parathyroid hormone (PTH) and markers of bone turnover in pre- and early pubertal black children and white children. METHODS: Data were collected during summer (June-September) and winter (December-March) in 6-12-year-old children. Measurements included serum 25(OH)D, PTH, osteocalcin (OC), collagen type 1 cross-linked C-telopeptide (CTx), dietary intake of vitamin D and calcium, skin color, sunlight exposure, and body mass index (BMI). RESULTS: A total of 138 children (mean age, 9.1 ± 1.7 years; black, n = 94; male, n = 81) were studied. 25(OH)D was higher (41.2 ± 13 vs 34.5 ± 11.1 ng/mL; P < 0.001) and CTx was lower (0.8 ± 0.3 vs 0.9 ± 0.5 ng/mL; P < 0.001) in all participants during summer when compared to winter. Furthermore, seasonal differences in CTx were more pronounced in black children (summer, 0.7 ± 0.3 vs winter, 1.0 ± 0.5 ng/mL; P < 0.001). PTH was a significant predictor of serum CTx and OC after adjusting for race, season, Tanner stage, dietary calcium, skin color and BMI. CONCLUSION: 25(OH)D declined significantly in both black children and white children during winter. CTx significantly increased during winter in black children compared to white children, suggesting increased rates of resorption in black children during winter. Benefits of enhancement of wintertime vitamin D status on bone health need further exploration.

25-Hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes.

OBJECTIVE: To 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and ß-cell function in this cohort. RESEARCH DESIGN AND METHODS: Plasma 25(OH)D concentrations were examined in banked specimens in 9- to 20-year-old obese youth (n = 175; male 42.3%, black 46.3%) (NGT, n = 105; impaired glucose tolerance [IGT], n = 43; type 2 diabetes, n = 27) who had in vivo insulin sensitivity and secretion measured by hyperinsulinemic-euglycemic and hyperglycemic clamp techniques and had an assessment of total body composition and abdominal adiposity. RESULTS: The mean age and BMI of the subjects were 14.3 ± 2.1 years and 35.7 ± 5.6 kg/m(2), respectively. BMI, plasma 25(OH)D, and the proportion of vitamin D-deficient and -insufficient children did not differ across the three groups. Furthermore, there was no association between 25(OH)D and in vivo insulin sensitivity or ß-cell function relative to insulin sensitivity (disposition index) in all groups combined or in each group separately. CONCLUSIONS: Our data in obese youth show 1) no differences in plasma 25(OH)D concentrations across the glucose tolerance groups and 2) no relationship between 25(OH)D and in vivo insulin sensitivity and ß-cell function relative to insulin sensitivity in any of the groups. It remains uncertain if enhancement of the vitamin D status could improve pathophysiological mechanisms of prediabetes and type 2 diabetes in obese youth.

The effectiveness of a short food frequency questionnaire in determining vitamin D intake in children.

Previous studies have found a high prevalence of vitamin D deficiency in children, yet few validated dietary vitamin D assessment tools are available for use in children. Our objective was to determine whether a short food frequency questionnaire (SFFQ) can effectively assess vitamin D intake in children. Vitamin D intake ascertained by a SFFQ was compared with assessments by a previously validated long food frequency questionnaire (LFFQ) in a population of 296 healthy 6- to 14-y-old children (54% male, 60% African American) from Pittsburgh, PA. The questionnaires were completed at two points 6 mo apart. Median reported daily vitamin D intake from the SFFQ (baseline: 380 IU, follow-up: 363 IU) was higher than the LFFQ (255 IU and 254 IU, respectively). Reported median dairy intake, including milk, cheese, and yogurt, was 3.7 cups/day, which meets the USDA recommendation for children. Vitamin D intake reported by the 2 questionnaires was modestly correlated at baseline and follow-up (r = 0.35 and r = 0.37, respectively; p < 0.001). These associations were stronger in Caucasians (r = 0.48 and r = 0.49, p < 0.001) than in African Americans (r = 0.27 and r = 0.31; p = 0.001). The sensitivity of the SFFQ for predicting daily vitamin D intake, defined as intake of ≥ 400 IU on both the SFFQ and LFFQ, was 65%. Specificity, defined as intake of < 400 IU on both questionnaires, was 42%. Vitamin D requirements may not be met despite adequate consumption of dairy products. The SFFQ was found to be a modestly valid and sensitive tool for dietary assessment of vitamin D intake in children.

25-hydroxyvitamin D concentrations and in vivo insulin sensitivity and ß-cell function relative to insulin sensitivity in black and white youth.

OBJECTIVE: To examine the relationships between plasma 25-hydroxyvitamin D [25(OH)D] and in vivo insulin sensitivity and ß-cell function relative to insulin sensitivity, disposition index (DI), in black and white youth. RESEARCH DESIGN AND METHODS: Plasma 25(OH)D concentrations were analyzed in banked specimens in healthy youth aged 8 to 18 years who had existing data on hyperinsulinemic-euglycemic and hyperglycemic clamp to assess insulin sensitivity and secretion, and measurements of body composition, and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). RESULTS: A total of 183 research volunteers (mean ± SD; age, 12.6 ± 2.2 years; 98 white, 98 male, 92 obese) were studied. Analysis of HbA(1c), fasting glucose and insulin, insulin sensitivity, and DI across quartiles of plasma 25(OH)D revealed no differences among whites. In blacks, the observed significance of higher insulin sensitivity and DI in the highest quartile of 25(OH)D disappeared after adjusting for any of the adiposity measures (BMI or fat mass or VAT or SAT). The difference in insulin sensitivity (9.4 ± 1.2 vs. 5.6 ± 0.5 mg/kg/min per µU/mL; P = 0.006) between 25(OH)D nondeficient (≥20 ng/mL) versus deficient (<20 ng/mL) black youth also was negated when adjusted for adiposity. CONCLUSIONS: In healthy youth, plasma 25(OH)D concentrations bear no independent relationship to parameters of glucose homeostasis and in vivo insulin sensitivity and ß-cell function relative to insulin sensitivity. It remains to be determined whether in youth with dysglycemia the relationships are different and whether vitamin D optimization enhances insulin sensitivity and ß-cell function.

Impact of season and diet on vitamin D status of African American and Caucasian children.

Seasonal variation of vitamin D status and adequacy of dietary vitamin D and impact of race on maintaining vitamin D sufficiency was assessed in 140 healthy 6- to 12-year-old African American (AA) and Caucasian (C) children residing in Pittsburgh, Pennsylvania during summer and winter. Vitamin D insufficiency was not rare in either group (AA vs C, summer, 17.2% vs 14.3%, nonsignificant; winter, 34.1% vs 32.5%, nonsignificant) despite a mean dietary intake of vitamin D above the American Academy of Pediatrics (AAP) recommended intake (400 IU/d; AA vs C, summer, 421 vs 456 IU/d, nonsignificant; winter, 507 vs 432 IU/d, nonsignificant). Race/season and dietary vitamin D were predictors of serum 25-hydroxyvitamin D [25(OH)D] concentrations. However, dietary vitamin D influenced 25(OH)D only in Caucasians during winter. Current AAP recommended daily intake for vitamin D is inadequate for maintaining vitamin D sufficiency in children.

Vitamin D status, adiposity, and lipids in black American and Caucasian children.

OBJECTIVE: The aim of the study was to examine the relationship between vitamin D status, total and abdominal adiposity, and lipids in black and white children. METHODS: Plasma 25-hydroxyvitamin D [25(OH)D], adiposity [body mass index (BMI), percentage of total body fat, visceral adipose tissue (VAT), sc adipose tissue (SAT)], and fasting lipids were assessed in healthy obese and nonobese 8- to 18-yr-old black and white children. RESULTS: We studied 237 children (mean ± sd age, 12.7 ± 2.2 yr; 47% black, 47% obese, and 43% male). Mean 25(OH)D concentration for the entire cohort was 19.4 ± 7.4 ng/ml. The majority of the children were vitamin D deficient [25(OH)D < 20 ng/ml; 73% blacks, 40% whites]. Plasma 25(OH)D was associated inversely with BMI, BMI percentile, percentage of total body fat, VAT, and SAT and positively with HDL cholesterol in the entire cohort. VAT was higher in vitamin D-deficient whites, and SAT was higher in vitamin D-deficient blacks compared with their respective vitamin D-nondeficient counterparts. Race, season, pubertal status, and VAT were independent significant predictors of 25(OH)D status. CONCLUSIONS: In black and white youth examined together, lower levels of 25(OH)D are associated with higher adiposity measures and lower HDL. Furthermore, vitamin D deficiency is associated with higher VAT in whites and greater SAT in blacks. Besides therapeutic interventions to correct the high rates of vitamin D deficiency in youth, benefits of vitamin D optimization on adiposity measures and lipid profile need to be explored.