Supplementation with Three Different Daily Doses of Vitamin D3 in Healthy Pre-pubertal School Girls: A Cluster Randomized Trial

Objective: To compare the adequacy and efficacy of differentdoses of vitamin D3 in pre-pubertal girls.Design: Cluster Randomized controlled trial.Setting: Public school in Delhi, India, between August 2015 andFebruary 2016.Participants: 216 healthy pre-pubertal girls, aged 6.1-11.8 years.Intervention: Daily supplementation with 600 IU (n=74), 1000 IU(n=67) or 2000 IU (n=75) of vitamin D3 under supervision for 6months.Outcome measures: Primary: Rise in serum 25 hydroxy VitaminD (25(OH)D); Secondary: Change in bone formation andresorption markers.Results: Following 6 months of supplementation, the mean (SD)rise in serum 25(OH)D was maximum with 2000 IU (24.09 (8.28)ng/mL), followed by with 1000 IU (17.96 (6.55) ng/mL) and 600 IU(15.48 (7.00) ng/mL). Serum 25(OH)D levels of ?20 ng/mL wereseen in 91% in 600 IU group , 97% in 1000 IU group and 100% in2000 IU group. The overall mean (SD) rise in urinary calciumcreatinine ratio (0.05 (0.28) to 0.13 (0.12) mg/mg), and serumprocollagen type I N-terminal propeptide (538.9 (199.78) to 655.5(218.24) ng/mL), and reduction in serum carboxy-terminaltelopeptide (0.745 (0.23) to 0.382 (0.23) ng/mL) was significant(P<0.01). The change in the above parameters was comparableamong the three groups after adjustment for age.Conclusion: Daily vitamin D supplementation with 600 IU to 2000IU for 6 months results in Vitamin D sufficiency in >90% of pre-pubertal girls

Vitamin D Deficiency and Parathyroid Response in Critically-ill Children: Association with Illness Severity and Clinical Outcomes.

Objective: To determine the prevalence of vitamin D deficiency in critically ill children, and to study its association with parathyroid response, severity of illness and clinical outcomes. Design: Prospective observational study. Setting: Medical Pediatric Intensive Care Unit of a tertiary care centre of Northern India. Participants: 154 children in-patients: August 2011-January 2013. Main outcome measures: Vitamin D deficient children were (serum 25-hydroxy vitamin D <20 µg/mL) divided into "parathyroid-responder" [serum parathyroid hormone >65 pg/mL with 25(OH)D<20 µg/mL and/or calcium corrected for albumin <8.5 mg/dL] and "non parathyroid-responder.’’ Illness severity was assessed by Pediatric Index of Mortality-2 (PIM-2) score at admission. Biochemical parameters, illness severity scores and clinical outcomes were compared between parathyroid-responders and non-parathyroid-responders. Results: Vitamin D deficiency and hypocalcemia were observed in 125 (83.1%) and 91 (59%) children, respectively at admission. There were no differences in illness severity score at admission, mortality rate and length of stay between vitamin D-deficient children and 19.8% of non-vitamin D-deficient children. Among Vitamin D-deficient children, parathyroid-responders had higher PIM-2 score at admission compared to non-parathyroid-responder [12.8 (7.4,20.6) vs. 6.5 (2.5,12.2), P=0.01]. However, there were no differences in other clinical outcomes between two groups. Conclusion: Critically ill children have high prevalence of vitamin D deficiency. Parathyroid gland response secondary to hypocalcemia or vitamin D defiency is impaired in critical illness.

Age of Onset of Puberty in Apparently Healthy School Girls from Northern India.

Objective: To determine the age of pubertal onset and menarche in school-going girls, and to assess the impact of obesity on pubertal timing. Design: Cross-sectional Setting: Seven schools across Delhi, India. Participants: 2010 school girls, aged 6-17 years Methods: Anthropometric measurement and pubertal staging was performed for all subjects. Menarche was recorded by ‘status quo’ method. Body mass index was used to define overweight/obesity. Serum gonadotropins and serum estradiol were measured in every sixth participant. Main outcome measure: Age at thelarche and menarche—analyzed for entire cohort and stratified based on body mass index. Results: Median (95% CI) ages of thelarche, pubarche and menarche were 10.8 (10.7-10.9) y, 11.0. y (10.8-11.2) y and 12.4 y (12.2-12.5) y. Overweight/obese girls showed six months earlier onset of thelarche and menarche than those with normal BMI (P<0.05). Serum gonadotropins did not vary significantly in overweight/obese subjects. Conclusion: The study provides the normative data for pubertal growth in Indian girls. Pubertal onset occurs earlier in overweight and obese girls.

Vitamin D levels in Indian children with intrathoracic tuberculosis.

Background & objectives: Deficiency of vitamin D, an immunomodulator agent, is associated with increased susceptibility to tuberculosis in adults, but only limited studies are available in the paediatric age group, especially regarding association of vitamin D with type and outcome of tuberculosis. We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis. Methods: Children with intrathoracic tuberculosis, diagnosed on the basis of clinico-radiological criteria, were enrolled as part of a randomized controlled trial on micronutrient supplementation in paediatric tuberculosis patients. Levels of 25-hydroxy vitamin D were measured in serum samples collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology. Results: Two hundred sixty six children (mean age of 106.9 ± 43.7 months; 57.1% girls) were enrolled. Chest X-ray was suggestive of primary pulmonary complex, progressive disease and pleural effusion in 81 (30.5%), 149 (56%) and 36 (13.5%) subjects, respectively. Median serum 25-hydroxy vitamin D level was 8 ng/ml (IQR 5, 12). One hundred and eighty six (69.9%) children were vitamin D deficient (serum 25-hydroxy vitamin D <12 ng/ml), 55 (20.7%) were insufficient (12 to <20 ng/ml) and 25 (9.4%) were vitamin D sufficient (≥ 20 ng/ml). lLevels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis, and in microbiologically confirmed and probable cases. Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease. Children who were deficient or insufficient were less likely to convert (become smear/culture negative) at two months as compared to those who were 25-hydroxy vitamin D sufficient (p<0.05). Interpretation & conclusions: Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children. However, children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did.

Bone mineral density in patients of Graves disease pre- & post-treatment in a predominantly vitamin D deficient population.

Background & objectives: Hyperthyroidism causes bone loss, and its treatment may restore bone mass, however, concomitant vitamin D deficiency may prevent this. We undertook this study to measure the bone mineral density (BMD) 25 (OH) vitamin D levels in patients with Graves disease in our population which is predominently vitamin D deficient and how we change with when patients become euthyroid. Methods: The biochemical, thyroid functions, serum vitamin D levels and BMD were estimated in 80 consecutive patients with Graves and 80 euthyroid controls. Patients were treated and rendered euthyroid. Fifty four completed one year, and 27 completed two years of follow up. Results: Patients had significant reduced BMD during hyperthyroid state compared to normal healthy controls. The mean vitamin D levels at baseline were in the insufficient range both patients (12.67±6.24 ng/ml) and controls (10.99±7.05 ng/ml). The BMD improved at all sites with antithyroid treatment. But, the BMD adjusted for body mass index (BMI) and age at all sites showed significant decrease with time. Interpretation & conclusions: Age and body mass index positively correlated with BMD. There was improvement in absolute BMD of patients at one and two years of follow up. When the BMD was adjusted for age and BMI, there was a decrease in BMD at one year which was less in the second year including that the damage in BMD caused by thyroid hormone excess is not made up even after two years of patient being euthyroid. Whether vitamin D replacement would change this needs to be studied.

Vitamin D deficiency in healthy breastfed term infants at 3 months & their mothers in India: Seasonal variation & determinants.

Background & objectives: Vitamin D deficiency with a resurgence of rickets and tetany are increasingly being reported in young infants from temperate regions, African Americans and also from India. The data on vitamin D status of healthy term breastfed Indian infants and mothers are scant. Therefore, we undertook this study to determine the prevalence of vitamin D deficiency and insufficiency [serum 25 hydroxyvitamin D (25OHD) ≤ 15 ng/ml and 15-20 ng/ml, respectively] among healthy term breastfed 3 month old infants and their mothers, evaluate for clinical and radiological rickets in those infants having 25OHD < 10 ng/ml, and check for seasonal variation and predictors of infants’ vitamin D status. Methods: A total of 98 infants aged 2.5 to 3.5 months, born at term with appropriate weight and their mothers were enrolled; 47 in winter (November- January) and 51 in summer (April-June). Details of infants’ feeding, vitamin D supplementation, sunlight exposure and mothers’ calcium and vitamin D intake were recorded. Serum calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25OHD) and parathormone were estimated. Results: Vitamin D deficiency was found in 66.7 per cent of infants and 81.1 per cent of mothers; and insufficiency in an additional 19.8 per cent of infants and 11.6 per cent of mothers. Radiological rickets was present in 30.3 per cent of infants with 25OHD < 10 ng/ml. 25OHD did not show seasonal variation in infants but maternal concentrations were higher in summer [11.3 (2.5 - 31) ng/ml] compared to winter [5.9 (2.5-25) ng/ml, P=0.003]. Intake of vitamin supplement, sunlight exposure and mother’s 25OHD were predictors of infants’ 25OHD levels. Interpretation & conclusions: Prevalence of vitamin D deficiency and insufficiency was found to be high in breastfed infants and their mothers, with radiological rickets in a third of infants with 25OHD < 10 ng/ml in this study. Studies with large sample need to be done in different parts of the country to confirm these findings.

Presence of 25(OH) D deficiency in a rural North Indian village despite abundant sunshine.

BACKGROUND AND OBJECTIVE: Several studies have shown wide prevalence of vitamin D deficiency with serum 25(OH)D <49.9 nmol/L in urban Indians related to their poor sunshine exposure and skin pigmentation. However, there is limited information in rural Indians. We hypothesized presence of higher 25(OH)D in rural subjects as compared to urban because of farming related abundant sunshine exposure. DESIGN AND METHODS: We assessed serum 25(OH)D levels in residents of a North Indian village with 200 families, located 90 km East of Delhi during February (winter). Fifty seven subjects (32 males and 25 females) from 50 families consented for the study. RESULTS: The mean 25(OH)D values of all subjects in the rural area was 36.4 +/- 22.5 nmol/l/L. Males had significantly higher 25(OH)D values than females. When compared to urban subjects, the mean 25(OH)D value of rural males and females was six and three folds higher, respectively. However even with five hours of daily sunshine exposure only 31.5% had serum 25(OH)D levels > or = 50 nmol/L. CONCLUSIONS: Thus, with longer sunshine exposure subjects residing in rural area had better mean 25(OH)D values than that of urbans. However, 70% of them were still vitamin D deficient. These facts indicate the need for the countrywide vitamin D food fortification program irrespective of rural or urban setting.

Prevalence of multiple micronutrient deficiencies amongst pregnant women in a rural area of Haryana.

Deficiencies of micronutrients (zinc, iron, folic acid and iodine) during pregnancy are known causes of Low Birth Weight (LBW). Studies have documented status of one or two micronutrients amongst pregnant women (PW). However, no attempt has been made to concurrently assess the prevalence of multiple micronutrient deficiencies and the factors associated with them amongst PW. OBJECTIVE: The present study was undertaken to assess the prevalence of multiple micronutrient deficiencies amongst PW in a rural area. METHODS: A community based cross sectional survey was conducted in six villages of a rural area of district Faridabad in Haryana state, India during November 2000 and October 2001. All PW aged 18 years or more, with pregnancy duration of more than 28 weeks were enrolled. Data were collected on socio-economic status and other demographic parameters. Serum zinc, copper and magnesium levels were estimated by utilizing the Atomic absorption spectrophotometry (AAS); serum ferritin and folate was estimated by Enzyme Linked Immuno Sorbent Assay (ELISA) method and the Radio-Immuno Assay (RIA) method, respectively and serum thyroid stimulating hormone (TSH) level was estimated by the Abbot AxSYM System. Serum zinc, copper, magnesium, ferritin, and folate levels less than 70.0 microg/dl, 80.0 microg/dl, 1.80 mg/dl, 15 ng/ml, and 3 ng/ml, respectively were considered as indicative of deficiency for respective micronutrients. The TSH levels of 4.670 and more indicated iodine deficiency status. Dietary intake of micronutrients was assessed utilizing 1-day 24-hour dietary recall methodology. Food consumption pattern was assessed utilizing the food frequency questionnaire methodology. RESULTS: Nearly 73.5, 2.7, 43.6, 73.4, 26.3, and 6.4 percent PW were deficient in zinc, copper, magnesium, iron, folic acid and iodine, respectively. The highest concurrent prevalence of two, three, four and five micronutrient deficiency was of zinc and iron (54.9%); zinc, magnesium and iron (25.6%); zinc, magnesium, iron and folic acid (9.3%) and zinc, magnesium, iron, folic acid and iodine (0.8%), respectively. No pregnant woman was found to have concomitant deficiencies of all the six micronutrients. Dietary intake data revealed an inadequate nutrient intake. Over 19% PW were consuming less than 50% of the recommended calories. Similarly, 99, 86.2, 75.4, 23.6, 3.9 percent of the PW were consuming less than 50% of the recommended folic acid, zinc, iron, copper, and magnesium. The consumption of food groups rich in micronutrients (pulses, vegetables, fruits, nuts and oil seeds, animal foods) was infrequent. Univariate and Multivariate logistic regression analysis revealed that low dietary intake of nutrients, low frequency of consumption of food groups rich in micronutrients and increased reproductive cycles with short interpregnancy intervals were important factors leading to micronutrient deficiencies. CONCLUSION: There was a high prevalence of micronutrient deficiencies amongst the PW of the area, possibly due to the poor dietary intake of food and low frequency of consumption of food groups rich in micronutrients. The concurrent prevalence of two, three, four and five micronutrient deficiencies were common.

Bone mineral parameters in healthy young Indian adults with optimal vitamin D availability.

BACKGROUND: Several recent studies indicate a marked prevalence of vitamin D deficiency in asymptomatic, apparently healthy urban subjects from different socioeconomic groups in north India. METHODS: To further examine this trend, we studied 40 men and 50 women, 20-30 years of age, from the Indian paramilitary forces. These individuals consume a nutritious, high-protein diet, have optimal exposure to sunlight and undertake strenuous outdoor physical exercise. RESULTS: The mean serum calcium, phosphorus and alkaline phosphatase levels were normal in both men and women. The mean (SD) serum intact parathyroid hormone and 25-hydroxyvitamin D3 levels were 19.3 (8.2) pg/ml and 18.4 (5.3) ng/ml in men, and 11.9 (6.6) pg/ml and 25.3 (7.4) ng/ml in women. Bone mineral density estimated in 20 men and 22 women revealed that in comparison with white Caucasians, 35%-50% of men and 14%-32% of women were osteopenic at different sites, while an additional 10% of men had osteoporosis of the lumbar spine. CONCLUSION: We found that with optimal nutrition, good sunlight exposure and regular physical exercise, healthy young individuals have normal bone and mineral biochemical values. The reasons for the abnormalities detected in bone mineral density in them needs further study. The impact of childhood nutrition on accumulation of peak bone mass may contribute to our findings. There is a need for establishing normative bone mineral density data for Indians.