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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 D(3) 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 D(3) 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.

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).

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.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 (JohnsonJohnson-Janssen) at a dose of 5×10Of 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.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.).

BackgroundWhile 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.MethodsIn 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.Results458 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.ConclusionHomologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.(Funded by National Institute of Allergy and Infectious Diseases; Clinical Trials.gov number, NCT04889209)

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)D20 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.

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.

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 &ge, 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.

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 β-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/m2, 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 β-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 β-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.

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.

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.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.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)D20 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.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.

Rickets, the state of vitamin D deficiency, has reemerged as a potential problem in the United States. At the dawn of the 20th century, rickets was pervasive among infants residing in the polluted cities of Europe and the northeastern United States. Important milestones in the history of rickets were the understanding that photosynthesized vitamin D and dietary vitamin D were similar, the discernment of the antirachitic potency of artificial and natural ultraviolet rays, and the discovery that ultraviolet irradiation could render various foods antirachitic. Clinical guidelines were instituted to promote sensible exposure to sunlight and artificial ultraviolet radiation. In addition, irradiated ergosterol from yeast became the major vitamin D source for food fortification and the treatment of rickets, leading to a public health campaign to eradicate rickets by the 1930s. We review the sequence and turn of events pertaining to the discovery of vitamin D and the strategies for the eradication of the reemerging rickets problem.

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-yr-old Pittsburgh-area black and white children enrolled in a randomized, placebo-controlled trial of vitamin D3 1000 IU daily for 6 months with baseline and 2 month 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, 1062, 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 2098 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.

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

To determine the proportion of vitamin D insufficiency in 6- to 10-year-old preadolescent African-American children residing in Pittsburgh, Pennsylvania and to estimate their therapeutic response to vitamin D 400 IU/day for 1-month, an open-label pre- and post-comparison of vitamin D status following vitamin D 400 IU daily for 1 month during winter and early spring was conducted. Outcomes included serum calcium, phosphorus, albumin, 25 hydroxyvitamin D [25 (OH) D], 1, 25 dihydroxyvitamin D [1, 25 (OH)2D], parathyroid hormone (PTH), and markers of bone turnover (serum bone-specific alkaline phosphatase, osteocalcin, and urine n-telopeptide crosslinked collagen type 1 [NTX]). Dietary intake of vitamin D was assessed using a food frequency questionnaire. Forty-one of the 42 enrolled subjects (mean age: 8.9 ± 1.2 yrs [SD]) were analyzed, and 20/41 (49%) were vitamin D insufficient. Vitamin D insufficient group had a suggestive trend of being older (9.2 ± 1.0 years vs. 8.5 ± 1.3 years, p = 0.06) and more pubertally advanced (Tanner II: 7/20 vs. Tanner II: 1/21, p = 0.02). Mean dietary intake of vitamin D was 277 (146 IU/day (n = 41). Adequate intake for vitamin D (200 IU/day) was not met in 16/41 (39%); however, the dietary intake of vitamin D was not significantly different between the vitamin D insufficient and vitamin D sufficient groups.

Rickets, a disease of vitamin D deficiency, is rarely confronted by the practicing pediatrician in the United States today. At the turn of the 20th century, rickets was rampant among the poor children living in the industrialized and polluted northern cities of the United States. With the discovery of vitamin D and the delineation of the anti-rachitic properties of cod-liver oil by the 1930s, it became possible to not only treat but also eradicate rickets in the United States. Rickets was a common disease in 17th century England. Frances Glisson’s treatise on rickets published in 1650, a glorious contribution to English medicine, described the clinical and anatomic features of rickets in great detail. The exact etiology of rickets had been elusive until the 1920s. During the Glissonian era, rickets was a mysterious disease. By the late 19th and early 20th century, faulty diet or faulty environment (poor hygiene, lack of fresh air and sunshine) or lack of exercise was implicated in its etiology. Animal experiments, appreciation of folklore advocating the benefits of cod-liver oil, and the geographical association of rickets to lack of sunshine were all relevant factors in the advancement of knowledge in the conquest of this malady. In this article, the history of rickets pertaining to the discovery of vitamin D, cod-liver oil, and sunlight is reviewed.

HISTORY OF PRESENT ILLNESS This infant presented with a 2-week history of vomiting. Initially, the episodes of vomiting were infrequent and appeared to the parents to be possibly self-induced. They were often associated with tantrums. After 1 week, the episodes of emesis gradually became more frequent and copious. At the time of the initial evaluation, the vomiting was occurring about 4 to 5 times a day. There was no particular time of day or activity in which the vomiting occurred more frequently. There was no relationship with meals. The parents noted a gradual failure to gain weight over the previous 5 months. There was no associated history of fever, diarrhea, or constipation. His activity level was unchanged and he was developmentally appropriate for his age. There was no history of travel or exposure to any pets. He was on no medications.

In a study to compare the clinical diagnostic skills of academic general pediatricians and academic pediatric cardiologists in the evaluation of heart murmurs, a total of 128 patients (aged 1 month to 18 years) newly referred to a university pediatric cardiology clinic were evaluated by one of three general pediatricians and one of four pediatric cardiologists. The murmurs were clinically classified as innocent, pathologic, or possibly pathologic. The classification was revised after the review of electrocardiogram (EKG) and chest radiograph (CXR), if indicated. The definitive diagnosis was ascertained by echocardiography (94 normal, 34 abnormal). The general pediatricians identified as many pathologic heart murmurs as the pediatric cardiologists (27/34 vs. 29/34), with no difference in sensitivity, 79% vs. 85% (p=0.53). The similarity in sensitivity could be because the general pediatricians were more cautious in the classification of heart murmurs and had classified more innocent heart murmurs as pathologic than the pediatric cardiologists (13/39 vs. 3/23), 41% vs. 13% (p=0.02). The pediatric cardiologists correctly identified more innocent murmurs than general pediatricians (52/94 vs.72/94), with a better specificity, 55% vs. 76% (p=0.001); however, the accuracy of prediction of innocence was similar for both groups (52/59 vs. 72/77), 88% vs. 93% (p=0.36). The revision of diagnosis with review of EKG and CXR was more often misleading than helpful for either group. Academic general pediatricians would identify most of the pathologic murmurs and are no more likely than an academic pediatric cardiologist to misclassify a pathologic heart murmur as innocent. Clin Pediatr. 1999;38:511-518

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.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).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; P0.001) and CTx was lower (0.8 ± 0.3 vs 0.9 ± 0.5 ng/mL; P0.001) 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; P0.001). PTH was a significant predictor of serum CTx and OC after adjusting for race, season, Tanner stage, dietary calcium, skin color and BMI.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.

A 3-year 9-month-old child presented unresponsive, dehydrated, and in shock, a consequence, of child neglect, abuse, and starvation. This scenario provides the vehicle for a discussion of three problems which can be precipitated by child neglect, specifically kwashlorkor, central pontine myelinolysis, and intellectual repercussions of malnutrition.

Vitamin D, the “sunshine vitamin,” is back in the limelight.1 Reemergence of rickets among vulnerable infants (dark-skinned and/or breast-fed without vitamin D supplementation) and reports of excessive prevalence of vitamin D deficiency and insufficiency among children have reemphasized the importance of optimal intakes of vitamin D.2–5 The American Academy of Pediatrics (AAP) increased its recommended dietary allowance (RDA) of vitamin D for the prevention of vitamin D deficiency in infants and children from 200 IU to 400 IU in 2008.6–7 Recently, the Institute of Medicine (IOM) revised its RDA for vitamin D from 200 IU to 400 IU in infants (0 to 12 months) and from 200 IU to 600 IU in children (1 to 8 years).8 Without fortification, very few foods are rich in vitamin D. Humans meet their vitamin D needs from sunlight exposure, diet and/or supplements. Of these sources, photosynthesized vitamin D is the major contributor to human vitamin D status.9–11 Vitamin D-fortified milk and infant formula remains the main dietary source of vitamin D. An infant or a child must drink 4 servings (1 liter or 32 ounces) of vitamin D-fortified milk to meet the AAP recommended intake of vitamin D (400 IU/day), which seems to be a tall order for many. Therefore, vitamin D supplements become an important source of dietary vitamin D. In order to meet consumer desires to prevent deficiencies or optimize health benefits related to vitamin D, preparations of higher concentrations of over-the-counter vitamin D supplements have become readily available for the general public, with the potential for inadvertent overdosing in young infants and children.

OBJECTIVE To examine the relationships between plasma 25-hydroxyvitamin D [25(OH)D] and in vivo insulin sensitivity and β-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 HbA1c, 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 ( CONCLUSIONS In healthy youth, plasma 25(OH)D concentrations bear no independent relationship to parameters of glucose homeostasis and in vivo insulin sensitivity and β-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 β-cell function.

In the last few decades, we have witnessed the resurgence of rickets (clinical vitamin D deficiency disorder) in vulnerable populations of infants. Recent National Health and Nutrition Examination surveys also show high rates of biochemical vitamin D insufficiency and deficiency in representative samples of healthy adolescents and adults in the USA. Scientific advances in the vitamin D field have emphasized the relevance of optimal vitamin D status for skeletal and nonskeletal health outcomes. In this context of refocused attention on vitamin D, we have reviewed the history of vitamin D and rickets, and the historical perspectives on vitamin D metabolism.

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.

Objective To assess and compare the attitudes and trust that African American and white parents have toward their children participating in research. Design Self-administered, cross-sectional survey of a convenience sample of parents. Setting Primary Care Center at Children's Hospital of Pittsburgh from August 2004 through April 2005. Participants One hundred ninety parents (140 African American and 50 white parents). Outcome Measure Parental distrust of medical research as measured by a summative score of distrusting responses to 8 questions assessing trust in research. Results African American parents had significantly greater distrust than white parents (67% vs 50%, P = .04). Education was also associated with having significantly greater distrust (74% of those with

Background: Serum 25-hydroxyvitamin D (25(OH)D) is low in obese adults. Objective: To examine serum 25(OH)D in obese (BMI >95th percentile for age) vs. non-obese (BMI = 5th–75th percentile for age) 6–10-year-old African American children and compare their differences in therapeutic response to vitamin D supplementation. Methods and Procedures: In an open label non-randomized pre-post comparison 21 obese (OB) and 20 non-obese (non-OB) subjects matched for age, sex, skin color, and pubertal maturation were treated with 400 IU of vitamin D3 daily for 1 month. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone (PTH), leptin, and markers of bone turnover (serum bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and urine n -telopeptide cross-links of type 1 collagen (urine NTX)) were measured. Vitamin D deficiency was defined as serum 25(OH)D ≤20 ng/ml and insufficiency as 21–29 ng/ml respectively. Results: Vitamin D deficiency occurred in 12/21 (57%) OB vs. 8/20 (40%) non-OB at baseline (P = 0.35) and persisted in 5/21 (24%) OB vs. 2/18 (11%) non-OB (P = 0.42) after treatment. When the cohort was stratified by the baseline levels of 25(OH)D, there were differences in the response to treatment in the obese and non-obese cohorts. Discussion: Vitamin D deficiency was common among OB and non-OB preadolescent African American children, and 400 IU of vitamin D3 (2× the recommended adequate intake) daily for 1 month was inadequate to raise their blood levels of 25(OH)D to ≥30 ng/ml.

Scurvy, a disease of dietary deficiency of vitamin C, is uncommon today. Among diseases, scurvy has a rich history and an ancient past. The Renaissance (14th to 16th centuries) witnessed several epidemics of scurvy among sea voyagers. In 1747, James Lind, a British Naval surgeon, performed a carefully designed clinical trial and concluded that oranges and lemons had the most antiscorbutic effect. Eventually, with the provision of lemon juice to the sea voyagers, scurvy became rare at sea. Infantile scurvy appeared almost as a new disease toward the end of the 19th century. The increased incidence of infantile scurvy during that period was attributed to the usage of heated milk and proprietary foods. Thomas Barlow described the classic clinical and pathologic features of infantile scurvy in 1883. Between 1907 and 1912, Holst and Frolich induced and cured scurvy in guinea pigs by dietary modification. In 1914, Alfred Hess established that pasteurization reduced the antiscorbutic value of milk and recommended supplementation of fresh fruit and vegetable juices to prevent scurvy. Such pioneering efforts led to the eradication of infantile scurvy in the United States. A brief history of infantile scurvy is provided.

Malaria has been in existence since ancient times and for millennia thought to be carried by vapors. Alphonse Laveran made the discovery of the malarial parasite in 1880. The next most important milestone in the history of malaria was the unraveling of the mystery of malaria transmission. Ronald Ross, born in British India and educated as a doctor in England, was working in the Indian Medical Service when he discovered the transmission of malarial parasites by mosquitoes in 1897. The next year, he completed the life cycle of malarial parasites in birds. In celebration of the centennial year of that epic discovery, we reminisce on that event, focusing on the discoverer.

Recent case reports highlight the resurgence of rickets in certain groups of breastfed infants. Infants residing in the North, irrespective of skin color, and dark-skinned African American infants residing anywhere in the United States are most vulnerable to nutritional rickets if they are exclusively breastfed past age 6 months without vitamin D supplementation. At the turn of the 20th century, rickets was nearly universal among African American infants living in the North. The discovery of vitamin D, the initiation of public health campaigns to fortify infant foods with vitamin D, and the supplementation of vitamin D to breastfed infants were responsible for overcoming the rickets scourge. We review a classic nutritional study by Alfred F. Hess, one of the greatest clinical nutritional researchers of the early 20th century, in the context of the resurgence of rickets, especially among dark-skinned infants. The Columbus Hill district, a black community of New York, NY, served as the setting for the study. Sixty-five infants (aged 1-17 months) entered a 6-month open-label trial of daily cod liver oil therapy. Participants were assessed for signs of rickets at recruitment and at 2, 4, and 6 months. Cod liver oil prevented the development of rickets in 34 (92%) of 37 infants treated for 6 months and in 7 (58%) of 12 treated for 4 months. Of the 16 infants who did not take the prescribed treatment, rickets progressed unremittingly in 15. Hess translated his success into a public health campaign leading to the development of the first rickets clinic in 1917. This was the first step in the conquest of the rickets epidemic of the early 20th century.

The Centennial Year of Ronald Ross' Epic Discovery of Malaria Transmission: An Essay and Tribute ♦ 895

COMPARATIVE STUDY OF CLINICAL EVALUATION OF HEART MURMURS BY GENERAL PEDIATRICIANS AND PEDIATRIC CARDIOLOGISTS. † 818