Bone mass in newborns and its predictors.

OBJECTIVE: Optimal bone mass (a function of foetal programming and adequate intrauterine bone mineral accrual) is essential for prevention of osteoporosis. The present study was planned with the objectives to describe newborn bone mass (NBBM) and study the associated factors. DESIGN: Observational study Patients: Singleton pregnant women ≤16 weeks gestation. MEASUREMENTS: Maternal factors and antenatal events: Dietary assessment (3 days-24-h diet recalls at ≤16 and 32-34 weeks), fetal femoral volume (FFV) assessment at 19 and 34 weeks, serum 25 hydroxyvitamin D (S.25OHD) and placental weight. Newborn anthropometric parameters, cord S.25OHD & IGF-1 level and NBBM by DXA (whole-body bone mineral content (BMC), bone mineral density (BMD) and bone area). RESULTS: Total 224 subjects were studied: 198 full-term and 26 preterm. The mean BMC, BMD and bone area for term newborns was 46.5 g (95% confidence interval [CI]: 45.35-47.66), 0.209 g/cm2 (95% CI: 0.206-0.212) and 221.6 cm2 (95% CI: 218.52-224.62), respectively. The mean placental weight was 403.2 ± 75.01 g (n = 72) while FFV was 0.71 ± 0.28 ml (19 weeks; n = 59) and 4.4 ± 1.17 ml (34 weeks; n = 33). Factors significantly associated with NBBM -gestational age at delivery, gestational weight gain, FFV at 19 weeks, placental weight, third-trimester maternal serum albumin and newborn anthropometric parameters (univariable analysis) and newborn birth weight, placental weight and FFV at 19 weeks (multivariable analysis). CONCLUSION: This study described NBBM among term newborns and birth weight, second-trimester FFV and placental weight were the associated factors.

Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

Introduction: To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. Methods: It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. Results: A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Conclusion: Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

Efficacy of vitamin D loading doses on serum 25-hydroxy vitamin D levels in school going adolescents: an open label non-randomized prospective trial.

AIM: Vitamin D deficiency (VDD) among adolescents is a major health problem in India. The aim of this study was to assess the efficacy of therapeutic/loading doses of vitamin D supplementation on serum 25-hydroxy vitamin D (25OHD) levels in vitamin D deficient adolescents. METHODS: A total of 482 out of the 511 subjects recruited for the study were divided into three groups, each group receiving 60,000 IU of vitamin D3 weekly for 4, 6 and 8 weeks followed by 600 IU daily for 12 weeks, respectively. Clinical evaluation was followed by estimation of biochemical markers and serum 25OHD levels. RESULTS: VDD was observed in 94.8% of adolescents. All three vitamin D loading doses were equally efficacious in achieving vitamin D sufficiency >75 nmol/L (>30 ng/mL) in more than 90% subjects in the three groups. Mean 25OHD levels in groups 2 and 3 following maintenance therapy were 67.5±16.5 nmol/L (27.0±6.6 ng/mL) and 70.0±21.8 nmol/L (28.0±8.7 ng/mL), respectively. CONCLUSION: Supplementing 60,000 IU of vitamin D3 per week for 4-8 weeks, followed by 600 IU daily through fortified milk, is an effective strategy for achieving vitamin D sufficiency in Indian adolescents.

Effect of Maternal Supplementation With Two Different Doses of Vitamin D During Lactation on Vitamin D Status, Anthropometry and Bone Mass of Infants: A Randomized Controlled Trial.

BACKGROUND: There is a high prevalence of vitamin D deficiency (VDD) in exclusively breast-fed infants in the absence of appropriate vitamin D supplementation. OBJECTIVE: To evaluate the efficacy of two doses of maternal vitamin D supplementation on vitamin D levels of mother-infant pairs and to assess its effect on growth parameters (weight, length and head circumference) and bone mass of infants. STUDY DESIGN: Randomized controlled trial. PARTICIPANTS: Lactating mother-infant pairs (n=220). INTERVENTION: Maternal oral vitamin D supplementation in two doses (group 1: 1,20,000 IU/month and group 2: 12,000 IU/month) for 12 months. MAIN OUTCOMES: Main outcomes: Maternal and infant serum 25OHD levels, and infants' growth and bone mass. RESULTS: There was high prevalence of VDD at baseline in mothers (94%) as well as infants (98.5%), which was reduced to 43.1% in (mothers) and 46.5% in infants after 12 months. Significantly higher median (IQR) serum 25OHD levels (ng/mL) were observed among mothers in group 1 compared to group 2 [46 (17-159) vs 18 (6-64); P<0.01] and in infants [36.5 (15-160) vs 17 (7-32); P<0.01]. No significant association was observed between growth parameters or bone mass and serum 25OHD levels of mother or infant between the two groups. Four mothers (3.6%) and two infants (1.8%) in group I had serum 25OHD>100 ng/mL, but without hypercalciuria or hypercalcemia. CONCLUSION: Bolus vitamin D supplementation in the dose of 1,20,000 IU/month was more efficacious in improving maternal and infant vitamin D status at 12 months, as compared to 12,000 IU/month.

Bone Mass in Newborns Assessed by DXA - A Systematic Review and Meta-analysis.

PURPOSE: Peak bone mass - a key determinant of osteoporotic fractures result from bone accretion starting form intrauterine life to early adulthood. Optimal skeletal growth in-utero and infancy may offer protection against osteoporosis in adult life. We attempted to pool the data from available literature to get a consensus on average bone mass among healthy newborns (age ≤30 days after birth). METHODS: Systematic review was conducted (PRISMA guidelines) to generate pooled estimates of bone mass parameters at whole body (WB) and lumbar spine (LS), based on both fixed and random effect models of meta-analyses. Two investigators independently carried out a comprehensive literature search using PubMed, Google Scholar and Embase. Meta-regression was applied to further explore causes of heterogeneity. RESULTS: Out of a total 2703 studies, 2682 was excluded leaving 21 studies for final analysis. Thirteen studies reported bone mass by Hologic® and eight by Lunar®. The pooled WBBMC was 66.2g (95% CI 65.4 to 67.05 by fixed effect model, while the corresponding parameter for LS was 2.3g (95% CI 2.2 to 2.4). The subgroup and meta-regression analyses done for controlling potential confounders did not significantly affect heterogeneity. CONCLUSION: We generated the pooled estimate of bone mass (WBBMC) among healthy newborn subjects. There was high degree of heterogeneity among studies.

Height Velocity in Apparently Healthy North Indian School Children.

OBJECTIVE: Linear growth is best estimated by serial anthropometric data or height velocity (HV). In the absence of recent data on growth velocity, we undertook to establish normative data in apparently healthy North Indian children. MATERIALS AND METHODS: Prospective longitudinal study in a representative sample of 7710 apparently healthy children, aged 3-17 years from different regions of Delhi. Height was measured at baseline and at 12 months while pubertal examination was performed at baseline in a subset of children. RESULTS: The data on HV and puberty were available in 5635 participants (73.08%; 2341 boys and 3294 girls) and 1553 participants (622 boys; and 931 girls), respectively. The mean peak height velocity (PHV) was 7.82 ± 2.60 cm in boys seen at 12-12.9 years and 6.63 ± 1.81 cm in girls at 10-10.9 years Although late maturing boys had a greater HV than early or normal maturers, it did not vary with the age of pubertal maturation in girls. HV correlated with parental height in prepubertal boys, girls, and pubertal boys (P < 0.01) while no correlation was seen in girls. CONCLUSIONS: The study presents normal height velocities in North Indian children. A secular trend was observed in achieving PHV in both boys and girls.

Effect of vitamin D supplementation on insulin kinetics and cardiovascular risk factors in polycystic ovarian syndrome: a pilot study.

To assess the effect of vitamin D supplementation on parameters of insulin sensitivity/resistance (IS/IR) and insulin secretion in subjects with polycystic ovarian syndrome (PCOS). A prospective double-blind randomized control trial was conducted to assess the effect of vitamin D on insulin kinetics in women with PCOS. The trial was conducted in a tertiary care research hospital. A total of 36 subjects with PCOS, aged 18-35 years, were included in this study. Vitamin D3 4000 IU/day versus placebo was given once a month for 6 months and both groups received metformin. IS (by whole-body IS index or Matsuda index), IR (by homeostasis model assessment IR (HOMA-IR)), and insulin secretion (by insulinogenic index; II30) were the main outcome measures. Secondary outcome included blood pressure (BP), lipid profile, disposition index (DI), and vascular stiffness. Out of 36 subjects who consented, 32 completed the study. Subjects were randomized into two groups: group A (n=15; metformin and vitamin D 4000 IU/day) or group B (n=17; metformin and placebo). Oral glucose tolerance tests with 75 g glucose were carried out at baseline and 6 months after supplementation. Hypovitaminosis D was observed in 93.8% of all subjects with mean serum 25 hydroxy vitamin D level of 7.30±4.45 ng/ml. After 6 months of vitamin D supplementation, there was no significant difference in any of the parameters of IS/IR (area under curve (AUC)-glucose, AUC-insulin, insulin:glucose ratio, HOMA-IR, Matsuda index, insulinogenic index, and DI), II30, and cardiovascular risk factors between the two groups. Supplementation of vitamin D, at a dose of 4000 IU/day for 6 months, did not have any significant effect on parameters of IS/IR and insulin secretion in subjects with PCOS.

Disparity in cholecalciferol content of commercial preparations available in India.

BACKGROUND: High prevalence of vitamin D deficiency (VDD) has been reported throughout the India for all age groups. Increased awareness about VDD among treating physicians has led to increased prescriptions of vitamin D preparations. Based on our experience of varied clinical and radiological response with different vitamin D formulations, we decided to assess cholecalciferol content of commonly available vitamin D formulations. MATERIALS AND METHODS: We measured cholecalciferol content of 14 commercial preparations (two in the form of tablets and 12 as sachet) available in Indian market. Lab analysis was carried out in Shriram Institute for Industrial Research by high-performance liquid chromatography. RESULTS: Of the total 14 samples analyzed only 4 (28.57%) were found to be within the acceptable ranges from -90 to +125% as defined by Indian Pharmacopia while 5 (35.7%) had higher and 5 (35.7%) had lower than the acceptable range. The percentage variation in cholecalciferol content as observed from the printed ranged widely from -91% to +65%. CONCLUSIONS: Our study shows a high degree of variability in cholecalciferol content of commercial preparations available in the Indian pharmaceutical market. This variation has many clinical implications as it may lead both, under treatment as well as vitamin D toxicity.