Sunlight Exposure vs Oral Vitamin D Supplementation for Prevention of Vitamin D Deficiency in Infancy: ARandomized Controlled Trial

Objective: To compare the efficacy of sunlight exposure and oral vitamin D3 supplementation to achieve vitamin D sufficiency in infants at 6 months of age. Design: Open-label randomized controlled trial. Setting: Public hospital in Northern India (28.7°N). Participant: Breastfed infants at 6-8 weeks of age. Intervention: Randomized to receive sunlight exposure (40% body surface area for a minimum of 30 minutes/week) or oral vitamin D3 supplementation (400 IU/day) till 6 months of age. Outcome: Primary - proportion of infants having vitamin D sufficiency (>20 ng/mL). Secondary - proportion of infants developing vitamin D deficiency (<12ng/mL) and rickets in both the groups at 6 months of age. Results: Eighty (40 in each group) infants with mean (SD) age 47.8 (4.5) days were enrolled. The proportion of infants with vitamin D sufficiency increased after intervention in the vitamin D group from 10.8% to 35.1% (P=0.01) but remained the same in sunlight group (13.9%) and was significant on comparison between both groups (P=0.037). The mean (SD) compliance rate was 72.9 (3.4)% and 59.7 (23.6)% in the vitamin D and sunlight group, respectively (P=0.01). The geometric mean (95% CI) serum 25(OH) D levels in the vitamin D and sunlight group were 16.23 (13.58-19.40) and 11.89 (9.93-14.23) ng/mL, respectively; (P=0.02), after adjusting baseline serum 25(OH)D with a geometric mean ratio of 1.36 (1.06-1.76). Two infants in sunlight group developed rickets. Conclusion: Oral vitamin D3 supplementation is more efficacious than sunlight in achieving vitamin D sufficiency in breastfed infants during the first 6 months of life due to better compliance.

Impact of Using Different Growth References on Interpretation of Anthropometric Parameters of Children Aged 8-15 Years

Objective: To compare the effect of the application of threegrowth references (Agarwal, 1992; Indian Academy ofPaediatrics (IAP), 2015; and World Health Organisation (WHO),2007) on interpretation of anthropometric parameters inschoolchildren.Setting: Cross-sectional school-based study.Participants: Children 8-15 years studying in one governmentschool and one private school of Delhi.Procedure: The age- and gender-specific standard deviationscores of height-for-age and BMI-for-age were estimated foreach student enrolled, using the three growth referencesindependently.Main outcome measure: The proportion of children withshort stature, thinness and overweight/ obesity determined byeach growth reference were compared.Results: A total of 1237 students participated in the study. Asignificantly higher proportion of children (both sexes) wereclassified to have short stature using WHO 2007 reference(8.8%) as compared to the Agarwal (3.3%) charts and IAP, 2015references (3.6%). The combined prevalence of overweight andobesity was highest (34.8%) by the IAP, 2015 reference asagainst 32% by Agarwal charts and 29.1% by WHO, 2007reference. Good agreement existed between the IAP, 2015reference and Agarwal charts in classifying subjects intodifferent BMI categories (Kappa=0.82) and short stature(Kappa=0.99).Conclusions: In view of differences noted, use of nationalpopulation derived reference data is suggested to correctlydefine growth trajectories in children.

Seasonal Variation in Serum 25-hydroxy Vitamin D and its Association with Clinical Morbidity in Healthy Infants from Northern India

Objective: To evaluate the seasonal change in serum 25-hydroxyvitamin D (25-OHD) level inhealthy infants and to relate it to common childhood morbidities. Methods: 72 healthybreastfed infants residing in Delhi were enrolled at the end of summer and followed till the endof winter [mean (SD) duration 200 (10) d]. Serum 25-OHD was estimated at baseline andfollow-up. Infants were monitored for common childhood diseases. Results: Mean (SD)serum 25-OHD level was lower at the end of winter (20.7 (8.02) ng/mL) than summer (22.9(8.70) ng/mL) [mean difference (95% CI) –2.14 ng/mL (–3.36, –1.06), P<0.001). Theseasonal distribution of children according to vitamin D status in summer and winter -Deficient(15.3%, 12.5%), Insufficient (19.4%, 30.6%) and Sufficient(65.3%, 56.9%),respectively was comparable P=0.17). The morbidity profile remained unaffected by changein vitamin D status from summer to winter. Conclusions: Seasonal changes in vitamin Dlevels do not have significant clinical effect or effect on overall vitamin D status in apparentlyhealthy infants from North India. This may have implications for results of population surveysfor vitamin D status, irrespective of the season when they are conducted.

300,000 IU or 600,000 IU of Oral Vitamin D3 for Treatment of Nutritional Rickets: A Randomized Controlled Trial.

Objective: To evaluate the non-inferiority of a lower therapeutic dose (300,000 IU) in comparison to standard dose (600,000) IU of Vitamin D for increasing serum 25(OH) D levels and achieving radiological recovery in nutritional rickets. Design: Randomized, open-labeled, controlled trial. Setting: Tertiary care hospital. Participants: 76 children (median age 12 mo) with clinical and radiologically confirmed rickets. Intervention: Oral vitamin D3 as 300,000 IU (Group 1; n=38) or 600,000 IU (Group 2; n=38) in a single day. Outcome variables: Primary: Serum 25(OH)D, 12 weeks after administration of vitamin D3; Secondary: Radiological healing and serum parathormone at 12 weeks; and clinical and biochemical adverse effects. Results: Serum 25(OH)D levels [geometric mean (95% CI)] increased significantly from baseline to 12 weeks after therapy in both the groups [Group 1: 7.58 (5.50–10.44) to 16.06 (12.71– 20.29) ng/mL, P<0.001]; Group 2: 6.57 (4.66–9.25) to 17.60 (13.71–22.60, P<0.001]. The adjusted ratio of geometric mean serum 25(OH)D levels at 12 weeks between the groups (taking baseline value as co-variate) was 0.91 (95% CI: 0.65–1.29). Radiological healing occurred in all children by 12 weeks. Both groups demonstrated significant (P<0.05) and comparable fall in the serum parathormone and alkaline phosphatase levels at 12 weeks. Relative change [ratio of geometric mean (95% CI)] in serum PTH and alkaline phosphatase, 12 weeks after therapy, were 0.98 (0.7–1.47) and 0.92 (0.72–1.19), respectively. The serum 25(OH)D levels were deficient (<20 ng/mL) in 63% (38/60) children after 12 weeks of intervention [Group 1: 20/32 (62.5%); Group 2: 18/28 (64.3%)]. No major clinical adverse effects were noticed in any of the children. Hypercalcemia was documented in 2 children at 4 weeks (1 in each Group) and 3 children at 12 weeks (1 in Group 1 and 2 in Group 2). None of the participants had hypercalciuria or hypervitaminosis D. Conclusion: A dose of 300,000 IU of vitamin D3 is comparable to 600,000 IU, administered orally, over a single day, for treating rickets in under-five children although there is an unacceptably high risk of hypercalcemia in both groups. None of the regime is effective in normalization of vitamin D status in majority of patients, 3 months after administering the therapeutic dose.

A simple nomogram for sample size for estimating sensitivity and specificity of medical tests.

Sensitivity and specificity measure inherent validity of a diagnostic test against a gold standard. Researchers develop new diagnostic methods to reduce the cost, risk, invasiveness, and time. Adequate sample size is a must to precisely estimate the validity of a diagnostic test. In practice, researchers generally decide about the sample size arbitrarily either at their convenience, or from the previous literature. We have devised a simple nomogram that yields statistically valid sample size for anticipated sensitivity or anticipated specificity. MS Excel version 2007 was used to derive the values required to plot the nomogram using varying absolute precision, known prevalence of disease, and 95% confidence level using the formula already available in the literature. The nomogram plot was obtained by suitably arranging the lines and distances to conform to this formula. This nomogram could be easily used to determine the sample size for estimating the sensitivity or specificity of a diagnostic test with required precision and 95% confidence level. Sample size at 90% and 99% confidence level, respectively, can also be obtained by just multiplying 0.70 and 1.75 with the number obtained for the 95% confidence level. A nomogram instantly provides the required number of subjects by just moving the ruler and can be repeatedly used without redoing the calculations. This can also be applied for reverse calculations. This nomogram is not applicable for testing of the hypothesis set-up and is applicable only when both diagnostic test and gold standard results have a dichotomous category.