Management of unscheduled bleeding on HRT: A joint guideline on behalf of the British Menopause Society, Royal College Obstetricians and Gynaecologists, British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Faculty of Sexual and Reproductive Health, Royal College of General Practitioners and Getting it Right First Time.

Unscheduled bleeding on hormone replacement therapy (HRT) can affect up to 40% of users. In parallel with the increase in HRT prescribing in the UK, there has been an associated increase in referrals to the urgent suspicion of cancer pathway for unscheduled bleeding. On behalf of the British Menopause Society (BMS) an expert review panel was established, including primary and secondary care clinicians with expertise in the management of menopause, with representatives from key related organisations, including the Royal College of Obstetricians & Gynaecologists, the British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Royal College of General Practitioners and Faculty of Sexual and Reproductive Health, and service development partners from NHS England and GIRFT (Getting it Right First Time). For each topic, a focused literature review was completed to develop evidence led recommendations, where available, which were ratified by consensus review within the panel and by guideline groups.

Dietary patterns of Indian school-aged children and associations with markers of chronic disease risk.

There is an increasing burden of noncommunicable diseases (NCDs) in India which may be related to changing dietary patterns. We aimed to assess dietary patterns in children since they have time to change unhealthy patterns before NCDs develop. Participants were 665 children, 9-12 years old, born with low birth weight and 77 similarly aged normal birth weight controls. We collected data on sociodemography, anthropometry, body composition, and markers of risk for NCDs: grip strength, long jump, hemoglobin A1c (HbA1c). A food frequency questionnaire was used to collect dietary data from which dietary patterns were derived using principal component analysis (PCA). Fourteen food groups were included in the PCA analysis, resulting in three components: 'fruits and vegetables', 'protein', and 'sugar and fat'. Higher socioeconomic status and maternal education were associated with lower adherence to the fruit and vegetable pattern and higher adherence to the protein and sugar and fat patterns. Adherence to the fruits and vegetables pattern was associated with lower height-for-age, whereas the fat and sugar pattern was associated with higher indicators of body fat. In linear regression analyses adjusted for age, sex, religion, socioeconomic status, maternal education, and season of data collection, adherence to the 'fruits and vegetables' pattern was associated with lower grip strength, shorter long jump, and lower HbA1c. Adherence to the other patterns was not associated with NCD risk factors. Higher consumption of fruits and vegetables, achievable even by poorer families in the cohort, may lower HbA1c, a risk factor for diabetes.

Longitudinal Growth and Undernutrition Burden Among Term Low Birth Weight Newborns Reared in Adverse Socioeconomic Conditions in Delhi.

BACKGROUND: There is limited data in term low birth weight neonates from urban poor settings on the incidence of and recovery from undernutrition and co-existence of its different forms, under conditions of appropriate health and nutrition care counselling. OBJECTIVES: To determine the longitudinal growth and undernutrition burden among term low birth weight newborns reared in adverse conditions, but with appropriate counselling. METHODS: The study reports follow-up data from DIVIDS trial. 2079 term low birth weight (1800-2499 grams) newborns from an urban poor setting were followed-up for growth from 0 to 26 weeks (n=1282) and at 2.8-6.8 years (n=912). Using Cole LMS approach, age- and sex-specific internal z scores were computed and subsequently adjusted for the effect of a vitamin D intervention and potential bias due to attrition. Back-transformed measurements were then used to compute WHO z scores for height for age (HAZ), weight for age (WAZ), and BMI for age (BMIZ). RESULTS: HAZ remained fairly stable: mean changes from birth till 6 weeks, 26 weeks and 3-7 years were 0.07, 0.04 and 0.2 SD, respectively. BMIZ and WAZ showed considerable catch-up; 0.69 SD, 1.84 SD and 1.38 SD for BMIZ, and 0.25 SD, 0.89 SD and 0.60 SD for WAZ, respectively. 60-92% had at least one form of undernutrition and co-existence was frequent. Half the children remained stunted till 5 years, while underweight and wasting declined considerably from 0-6 months. CONCLUSION: With appropriate counselling of parents, term low birth weight infants reared under adverse socioeconomic conditions show substantial catch-up growth in BMIZ and WAZ but not in HAZ. The long-term consequences of this excess weight over length gain need focused evaluation.

Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids).

OBJECTIVES: To determine whether weekly oral supplementation with 10,000 IU vitamin D3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. METHODS: We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. RESULTS: 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35). CONCLUSION: Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.

Prevalence and Correlates of Vitamin D Deficiency Among Children and Adolescents From a Nationally Representative Survey in India.

OBJECTIVE: To evaluate the prevalence of vitamin D deficiency (VDD) and its correlates among apparently healthy children and adolescents. METHODS: We carried out a secondary analysis of data of Comprehensive National Nutrition Survey 2016-18 to analyze the pre-valence and predictors of VDD among Indian children and adolescents. RESULTS: The over-all prevalence of VDD in preschool children (1-4 years), school age (5-9 years) children, and adolescents (10-19 years) was 13.7%, 18.2%, and 23.9%, respectively. Age, living in urban area, and winter season were significantly associated with VDD. Vegetarian diet and high-income households were the main risk factors observed in 5-19 years age category. Female sex and less than three hour of physical activity/week were independent risk factors among adolescents. CONCLUSION: The prevalence and determinants of VDD across different age-groups are reported, and these should be interpreted and addressed to decrease the burden of VDD in India.

Assessing Menstrual Changes Among Young Indian Females Post-SARS-CoV-2 Vaccination.

Background The rollout of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has significantly enhanced immunity against coronavirus disease 2019 (COVID-19), leading to a reduction in the severity of illness, hospitalizations, and deaths. While various side effects of the vaccine have been reported, its impact on the menstrual cycle remains unclear. Methods We conducted a cross-sectional study involving university students who had received either partial or full vaccination against SARS-CoV-2. Data was gathered through a questionnaire designed to assess the relationship between menstrual changes and the SARS-CoV-2 vaccination. Results A total of 773 participants, with a mean age of 20.6 ± 1.7 years, were included in this study. The participants reported a significant increase in the irregularity of the menstrual cycle. We observed a slight increase in the length of the menstrual cycle, from 30.0 ± 4.0 days (pre-vaccination) to 30.5 ± 5.6 days (post-vaccination), which was statistically significant (p<0.001). The duration of menstruation also increased, from 4.9 ± 1.7 days (pre-vaccination) to 5.0 ± 1.7 days (post-vaccination). However, this increase in menstrual length due to vaccination was not statistically significant (p = 0.898). Notably, there was a significant increase in pain reported by the participants after receiving the SARS-CoV-2 vaccine (p = 0.004). Conclusion The SARS-CoV-2 vaccination significantly impacted the regularity of the menstrual cycle, length of the menstrual cycle, and pain during menstruation, though temporarily. Our study found no significant differences in menstrual changes or the type of vaccine administered (Covishield and Covaxin).

Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol.

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function. Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes. Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.

Effect of energy- and/or protein-dense enteral feeding on postoperative outcomes of infant surgical patients with congenital cardiac disease: A systematic review and meta-analysis.

Infants with congenital heart disease (CHD) are malnourished because of poor dietary intakes and increased requirements. Energy requirements are higher due to increased resting energy expenditure. There are lacunae of nutrition recommendations for these infants. Therefore, this systematic review and meta-analysis was conducted to determine the effect of energy- and/or protein-dense feeds in postoperative CHD infants as compared with the standard feeding. An online literature search was performed on four databases by using different English-language keywords between 2000 and 2020. The inclusion criteria were peer reviewed journals and open access original articles on the feeding practices in infants undergoing congenital heart surgery. Exclusion criteria were editorials, commentaries, discussion papers, conference abstracts, reviews, duplicate studies, and articles on preterm infants and preoperative nutrition. A total of five studies matched the inclusion criteria. The standard mean difference (SMD) of energy intake (SMD = 13.40 kcal, P = 0.001), protein intake (SMD = 2.37 g, P = 0.001), and weight (SMD = 4.99 g, P = 0.001) was significantly higher in the intervention group. The SMD of ventilation duration (SMD = -0.18 h, P = 0.90), intensive care unit (ICU) length of stay (LOS) (SMD = -0.25 d, P = 0.70), and hospital LOS (SMD = -0.20 d, P = 0.67) were not statistically significant between the two groups. Enriched enteral nutrition for the postoperative pediatric patients with cardiac disease helps in achieving energy and protein goals and improves the overall postoperative outcomes (ie, ventilation duration, maintenance of weight, ICU LOS, and hospital LOS).

The Effects of a Single Freeze-Thaw Cycle on Concentrations of Nutritional, Noncommunicable Disease, and Inflammatory Biomarkers in Serum Samples.

Background The stability of biological samples is vital for reliable measurements of biomarkers in large-scale survey settings, which may be affected by freeze-thaw procedures. We examined the effect of a single freeze-thaw cycle on 13 nutritional, noncommunicable diseases (NCD), and inflammatory bioanalytes in serum samples. Method Blood samples were collected from 70 subjects centrifuged after 30 minutes and aliquoted immediately. After a baseline analysis of the analytes, the samples were stored at - 70°C for 1 month and reanalyzed for all the parameters. Mean percentage differences between baseline (fresh blood) and freeze-thaw concentrations were calculated using paired sample t -tests and evaluated according to total allowable error (TEa) limits (desirable bias). Results Freeze-thaw concentrations differed significantly ( p < 0.05) from baseline concentrations for soluble transferrin receptor (sTfR) (- 5.49%), vitamin D (- 12.51%), vitamin B12 (- 3.74%), plasma glucose (1.93%), C-reactive protein (CRP) (3.45%), high-density lipoprotein (HDL) (7.98%), and cholesterol (9.76%), but they were within respective TEa limits. Low-density lipoprotein (LDL) (- 0.67%), creatinine (0.94%), albumin (0.87%), total protein (1.00%), ferritin (- 0.58%), and triglycerides (TAG) (2.82%) concentrations remained stable following the freeze-thaw cycle. In conclusion, single freeze-thaw cycle of the biomarkers in serum/plasma samples after storage at - 70°C for 1 month had minimal effect on stability of the studied analytes, and the changes in concentration were within acceptable limit for all analytes.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Vitamin E status in healthy population in Asia: A review of current literature.

Vitamin E is a lipid soluble antioxidant which mainly circulates as α-tocopherol in the human plasma. Its deficiency is associated with ataxia, neuropathy, anaemia and several other health conditions. Although substantial data on vitamin E status has been published worldwide, there is paucity of data on the extent of deficiency from most Asian countries, including India. Part of the problem is lack of validated biomarkers for vitamin E and no consensus on cut offs for defining deficiency and sufficiency. Thus, interpretation of the data on the vitamin E status is difficult. Limited available data from 31 studies on vitamin E status in healthy people from Asia, the most populated continent, has been collated for the purpose of this review. Broadly, the results suggest inadequate vitamin E status in most age groups, with the prevalence of deficiency reaching 67%, 80%, 56% and 72% in infants, children and adolescents, adults, elderly and pregnant women, respectively, based on varying cut offs. The findings are not surprising as both, vitamin E intakes and its status have not received too much attention in the past. Lack of conclusive data accentuates the need for more research on the vitamin E status across all age groups and to define age, gender and physiological state specific cut offs for vitamin E levels.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed. METHODS: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633). FINDINGS: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test). INTERPRETATION: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. FUNDING: None.

Status of Vitamin B12 among Healthy Adult and Elderly Population in India: A Review.

Vitamin B12 is a water soluble micronutrient found in animal foods. Its deficiency is not uncommon in India owing to vegetarianism but often unrecognized due to diverse clinical manifestations. This review aims to collate the current data on vitamin B12 status in healthy Indian adult and elderly population. Online database Pubmed was searched for articles published in English between 2000 and 2019. Inclusion criteria consisted of original studies conducted on apparently healthy adult and elderly Indian population reporting serum/plasma vitamin B12 levels. Comprehensive literature search identified 14 studies eligible for inclusion. The deficiency prevalence reached 78.5% and 61.7% among adults and elderly, respectively, based on varying cut offs. Higher vitamin B12 levels were reported in women than men. Hyperhomocysteinemia (Hcy >15 µmol/L) was lower in females as compared to males (60% vs 90%, 14.9% vs 57.4% and 3.6% vs 20.9% respectively in three studies). Vitamin B12 deficiency was higher in vegetarians. The results indicate that inadequate vitamin B12 status is a wide spread problem in the Indian population. However, variety of laboratory methods and cut-offs of vitamin B12 deficiency and the heterogeneity in results pose challenges to draw clear conclusions on the extent of vitamin B12 deficiency in India. This review, therefore, highlights the need for more evidence based research to define age and sex specific cut offs for defining vitamin B12 deficiency.

Suboptimal feeding and caring practices among young Indian children ages 12 to 24 mo living in the slums of New Delhi.

OBJECTIVES: Inappropriate infant and young child feeding and caring practices affect nutritional status, increases the risk for growth faltering, and ultimately, affect child survival. The aim of this study was to characterize the feeding and caring practices of disadvantaged urban Indian children 12 to 24 mo of age in relation to the World Health Organization (WHO) and Pan American Health Organization (PAHO) recommendations. METHODS: This cross-sectional study was conducted in self-selected households in a South Delhi slum. A household survey was administered to the mother/primary caregiver of 120 eligible children. We collected child anthropometry, 2-d weighed food records (n = 69), and compliance to WHO and PAHO recommended feeding, caring, food safety, and hygiene practices. RESULTS: Of the children, 39% were stunted, 31% underweight, and 10% wasted; none were overweight. Despite 88% achieving minimum meal frequency (more than three to four meals daily), only 50% consumed at least four food groups (minimum dietary diversity), and 44% a minimum acceptable diet (composite score of minimum meal frequency and minimum dietary diversity). Consumption of iron-rich or iron-fortified foods, vitamin A-rich fruits and vegetables, and eggs was low (<25%) and flesh foods were negligible (1.4%), whereas consumption of both sugary and snack foods was >60%. Reported compliance to responsive feeding indicators was generally ∼50%, but there was a wide range (13-98%) for food safety and hygiene practices, which were not always consistent with home observations. CONCLUSIONS: Complementary feeding and caregiving practices were suboptimal among these disadvantaged young Indian children and education interventions focused on infant and young child feeding, responsive feeding, food safety, and hygiene practices are urgently needed.

Effect of temperature and time delay in centrifugation on stability of select biomarkers of nutrition and non-communicable diseases in blood samples.

INTRODUCTION: Preanalytical conditions are critical for blood sample integrity and poses challenge in surveys involving biochemical measurements. A cross sectional study was conducted to assess the stability of select biomarkers at conditions that mimic field situations in surveys. MATERIAL AND METHODS: Blood from 420 volunteers was exposed to 2 - 8 °C, room temperature (RT), 22 - 30 °C and > 30 °C for 30 min, 6 hours, 12 hours and 24 hours prior to centrifugation. After different exposures, whole blood (N = 35) was used to assess stability of haemoglobin, HbA1c and erythrocyte folate; serum (N = 35) for assessing stability of ferritin, C-reactive protein (CRP), vitamins B12, A and D, zinc, soluble transferrin receptor (sTfR), total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), tryglicerides, albumin, total protein and creatinine; and plasma (N = 35) was used for glucose. The mean % deviation of the analytes was compared with the total change limit (TCL), computed from analytical and intra-individual imprecision. Values that were within the TCL were deemed to be stable. RESULT: Creatinine (mean % deviation 14.6, TCL 5.9), haemoglobin (16.4%, TCL 4.4) and folate (33.6%, TCL 22.6) were unstable after 12 hours at 22-30°C, a temperature at which other analytes were stable. Creatinine was unstable even at RT for 12 hours (mean % deviation: 10.4). Albumin, CRP, glucose, cholesterol, LDL, triglycerides, vitamins B12 and A, sTfR and HbA1c were stable at all studied conditions. CONCLUSION: All analytes other than creatinine, folate and haemoglobin can be reliably estimated in blood samples exposed to 22-30°C for 12 hours in community-based studies.

Steady Growth in Early Infancy Is Associated with Greater Anthropometry in Indian Children Born Low Birth Weight at Term.

BACKGROUND: Patterns of early growth are associated with later body composition and risk of adult noncommunicable disease but information from low-income countries is limited. OBJECTIVES: The aim of this study was to investigate early growth trajectories and later anthropometric and bone density outcomes among children born term low birth weight (LBW: 1.8-2.5 kg). METHODS: We used data from 902 children from the Delhi Infant Vitamin D Supplementation study of LBW term infants (which collected monthly anthropometry from birth to 6 mo) and who had height, weight, midupper arm circumference (MUAC), midupper arm muscle circumference (MUAMC), subscapular and triceps skinfold thicknesses, tibia and radius bone density measured at age 4-6 y. We investigated how growth in the first 6 mo of life, modeled using the SuperImposition by Translation and Rotation (SITAR) growth curve model, was related to these outcomes. SITAR summarizes each infant's weight and length trajectory in terms of a population mean curve and child-specific growth parameters: size, timing, and intensity. These were included as explanatory variables in linear regression models for the childhood outcomes. RESULTS: Considering the infant weight and length SITAR parameters jointly, childhood weight was strongly associated with infant length timing [estimated regression coefficient ß = 0.25 (95% CI: 0.10, 0.39)] and with weight size, timing, and intensity [ß = 9.01 (6.75, 11.27), ß = -0.25 (-0.43, -0.07), ß = 5.03 (3.22, 6.84), respectively]. Childhood height was associated only with the length parameters [ß = 0.97 (0.71, 1.23), ß = -0.43 (-0.77, -0.09), ß = 11.68 (8.60, 14.75), respectively]; childhood MUAC, MUAMC, and skinfolds with all parameters; and bone density with none. Overall, delayed and sustained growth in infant weight and length resulted in higher values of all outcomes except bone density, with the period up to 15 wk of age appearing critical for setting childhood anthropometry in this population. CONCLUSIONS: The explanation for the effects of delayed growth and length of the period in which trajectories are set is unclear; however, sustained and delayed growth in early infancy appears to be beneficial for these LBW children at least in the short-term. The trial was registered at clinicaltrials.gov as BT/PR7489/PID/20/285/2006.

Multiple micronutrient status and predictors of anemia in young children aged 12-23 months living in New Delhi, India.

Anemia has been identified as a severe public health concern among young children in India, however, information on the prevalence of anemia attributed to micronutrient deficiencies is lacking. We aimed to assess multiple micronutrient status (iron, zinc, selenium, vitamin A, vitamin D, folate and vitamin B12) in young Indian children and to investigate the role of these seven micronutrients and other non-nutritional factors on hemoglobin concentrations and anemia. One-hundred and twenty children aged 12 to 23 months were included in a cross-sectional nutritional assessment survey, of which 77 children provided a blood sample. Hemoglobin (Hb), serum ferritin, soluble transferrin receptor (sTfR), total body iron, zinc, selenium, retinol binding protein (RBP), folate, vitamin B12 and 25-hydroxyvitamin D (25(OH)D) were measured, and adjusted for inflammation using C-reactive protein (CRP) and α-1-acid glycoprotein (AGP), where appropriate. Predictors for hemoglobin and anemia were identified in multiple regression models. Most of the children were classified as anemic, of which 86 to 93% was associated with iron deficiency depending on the indicator applied. Deficiencies of folate (37%), and notably vitamin D (74%) were also common; fewer children were classified with deficiencies of vitamin B12 (29%), zinc (25%), and vitamin A (17%) and selenium deficiency was nearly absent. Multiple micronutrient deficiencies were common with over half (57%) deficient in three or more micronutrients, and less than 10% of children were classified with adequate status for all the micronutrients measured. Iron status was found to be the only nutritional factor statistically significantly inversely associated with anemia (P = 0.003) in multivariate analysis after controlling for sex. A coordinated multi-micronutrient program is urgently needed to combat the co-existing micronutrient deficiencies in these young children to improve micronutrient status and reduce the high burden of childhood anemia.

Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis.

BACKGROUND: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. OBJECTIVES: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. STUDY SELECTION: Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. STUDY APPRAISAL: Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. RESULTS: We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. LIMITATIONS: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. CONCLUSIONS: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013953. FUNDING: The National Institute for Health Research Health Technology Assessment programme.