Childhood and Adolescent Anemia Burden in India: The Way Forward.

The burden of anemia in Indian children, based on capillary blood sampling, is believed to be profound and worsening (67.1%) according to the successive National Family Health Surveys (NFHS). This might be an overestimate. The recent Comprehensive National Nutrition Survey of Indian children, that used venous blood sampling, found only less than half (30.7%) the NFHS prevalence, of which only one third was due to iron deficiency (ID). Unfortunately, the apparently worsening NFHS anemia burden estimate has been interpreted as an inadequacy of the present iron supplementation policy. This has led to additional iron supply through mandatory rice fortification. However, the lack of efficacy of iron supplementation appears inevitable, if the true prevalence of iron deficiency anemia is only about 10%. Thus, etiology is a critical consideration when devising appropriate and effective prevention policies. Future policies must focus on precision, thoughtfulness, restraint, and community engagement.

Estimated Deficits in Nutrient Intake of ICDS Beneficiaries Who Receive Take Home Ration at Two Districts in Karnataka.

BACKGROUND: The current estimates of energy and protein to bridge nutrient gap in the beneficiaries of the Integrated Child Development Services (ICDS) supplementary nutrition program use sub-optimal methodology for deficit calculation. OBJECTIVE: To estimate the nutrient deficit and the risk of inadequate nutrient intake in beneficiaries of the ICDS, aged 6-36 months, using individual 24-hour diet recalls, from districts of Chitradurga and Davanagere in Karnataka. STUDY DESIGN: Cross-sectional design. PARTICIPANTS: Children (aged 6 to 36 months) registered as beneficiaries of the ICDS in these districts. METHODS: Data were collected on socio-demographic factors, child feeding patterns, perception and usage of take home ration (THR), between August to October, 2019. Three non-consecutive days' 24-hour diet recall data of children were obtained from mothers, and anthropometric measurements were taken. The proportion of children at risk of inadequate nutrient intakes was estimated using the probability approach. Assuming that 50% of a healthy population will be at risk of nutrient inadequacy such that intake and requirement distributions overlap, the proportion at actual risk of nutrient inadequacy (≥50%) was calculated. RESULTS: A combined district analysis showed a median energy deficit of 109 kcal and 161 kcal in children belonging to the age groups of 6-12 month and 13-36 month, respectively. The actual risk of inadequate intake for both age groups ranged between 12-47% for fat and other micronutrient (iron, calcium, zinc, folate, vitamin B12 and vitamin A), despite breastfeeding, complementary feeding and reported THR use. CONCLUSION: Children who receive supplementary nutrition as part of the national program fail to meet their nutrient requirements that are essential for growth and development. The study results may help in strengthening the IYCF counselling and in modification of the existing THR, with quality and cost implications.

Characterisation of anaemia amongst school going adolescent girls in rural Haryana, India.

OBJECTIVE: High burden of anaemia exists amongst rural adolescent girls in India. The objective of this study was to characterise anaemia in school going adolescent girls in rural Haryana, India. DESIGN: Linear and multiple logistic regression analysis of data collected prior to an intervention trial was conducted. Participants were classified into anaemic (haemoglobin <12 g/dl) and non-anaemic group and were further classified into deficiencies of Fe, folate or vitamin B12, mixed, anaemia of other causes and inflammation. SETTING: Three schools in Ballabgarh block of Faridabad District, Haryana, India. PARTICIPANTS: One hundered and ninety-eight non-anaemic and 202 anaemic adolescent girls (12-19 years). RESULTS: Anaemic girls had 29·6 % Fe deficiency, 28·1 % folate or vitamin B12 deficiency, 15·8 % mixed deficiency and 9·7 % acute inflammation. Anaemia of other causes was found in 16·8 % of the anaemic participants. Girls with Fe and isolated folate deficiency had 2·5 times and four times higher odds of developing anaemia, respectively, as compared with non-anaemic girls. Fe deficiency with no anaemia was found amongst 11 % non-anaemic girls. Non-anaemic girls had a high prevalence of combined deficiency of folate or vitamin B12 (29·5 %) and acute inflammation (14·4 %). CONCLUSIONS: The current strategy of Fe and folic acid supplementation alone will not suffice for achieving the desired reduction in the prevalence of anaemia as unknown causes and anaemia of inflammation contribute to a substantial proportion of anaemia. Integrating other nutrition-specific components like improving water, sanitation and hygiene practices with the ongoing micronutrient supplementation program will comprehensively tackle anaemia. Unknown causes of anaemia warrant further research.

World Health Organization and knowledge translation in maternal, newborn, child and adolescent health and nutrition.

The World Health Organization (WHO) has a mandate to promote maternal and child health and welfare through support to governments in the form of technical assistance, standards, epidemiological and statistical services, promoting teaching and training of healthcare professionals and providing direct aid in emergencies. The Strategic and Technical Advisory Group of Experts (STAGE) for maternal, newborn, child and adolescent health and nutrition (MNCAHN) was established in 2020 to advise the Director-General of WHO on issues relating to MNCAHN. STAGE comprises individuals from multiple low-income and middle-income and high-income countries, has representatives from many professional disciplines and with diverse experience and interests.Progress in MNCAHN requires improvements in quality of services, equity of access and the evolution of services as technical guidance, community needs and epidemiology changes. Knowledge translation of WHO guidance and other guidelines is an important part of this. Countries need effective and responsive structures for adaptation and implementation of evidence-based interventions, strategies to improve guideline uptake, education and training and mechanisms to monitor quality and safety. This paper summarises STAGE's recommendations on how to improve knowledge translation in MNCAHN. They include support for national and regional technical advisory groups and subnational committees that coordinate maternal and child health; support for national plans for MNCAHN and their implementation and monitoring; the production of a small number of consolidated MNCAHN guidelines to promote integrated and holistic care; education and quality improvement strategies to support guidelines uptake; monitoring of gaps in knowledge translation and operational research in MNCAHN.

Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis.

BACKGROUND: Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density. METHODS: Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to "Preferred Reporting Items for Systematic reviews and Meta-analysis" guidelines. Search terms were constructed on the basis of the "participants", "intervention", "control", "outcome" and "study type" (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods. RESULTS: Apparently healthy human participants (n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis. CONCLUSIONS: Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D3) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.

Prevalence of Iron Deficiency and its Sociodemographic Patterning in Indian Children and Adolescents: Findings from the Comprehensive National Nutrition Survey 2016-18.

BACKGROUND: Anemia control programs in India focus mainly on the measurement of hemoglobin in response to iron-folic acid supplementation. However, representative national estimates of iron deficiency (ID) are not available. OBJECTIVES: The objective of the present study was to evaluate ID prevalence among children and adolescents (1-19 y) using nationally representative data and to examine the sociodemographic patterning of ID. METHODS: Cross-sectional data from the Comprehensive National Nutrition Survey in children (1-4 y: n = 9635; 5-9 y: n = 11,938) and adolescents (10-19 y; n = 11,507) on serum ferritin (SF) and other biomarkers were analyzed to determine inflammation-adjusted ID prevalence [SF (µg/L): <12 in 1-4 y and <15 in 5-19 y] and its relation to sociodemographic indicators. Multiple-regression analyses were conducted to identify the exposure associations of iron status. In addition, the relation between SF and hemoglobin was assessed as an indicator of iron utilization in different wealth quintiles. RESULTS: ID prevalence was higher in 1- to 4-y-old children (31.9%; 95% CI: 31.0%, 32.8%) and adolescent girls (30.4%; 95% CI: 29.3%, 31.5%) but lower in adolescent boys and 5- to 9-y-old children (11%-15%). In all age groups, ID prevalence was higher in urban than in rural participants (1-4 y: 41% compared with 29%) and in those from richer quintiles (1-4 y: 44% in richest compared with 22% in poorest), despite adjustment for relevant confounders. SF significantly interacted with the wealth index, with declining trends in the strength of association between hemoglobin and SF from the richest to the poorest groups suggesting impaired iron utilization for hemoglobin synthesis in poorer wealth quintiles. CONCLUSIONS: ID prevalence was indicative of moderate (in preschool children and adolescent girls) or mild (in 5- to 9-y-old children and adolescent boys) public health problem with significant variation by state and age. Focusing on increasing iron intake alone, without addressing the multiple environmental constraints related to poverty, may not result in intended benefits.

Haemoglobin thresholds to define anaemia in a national sample of healthy children and adolescents aged 1-19 years in India: a population-based study.

BACKGROUND: WHO's haemoglobin cutoffs to define anemia were based on five studies of predominantly White adult populations, done over 50 years ago. Therefore, a general re-examination of the existing haemoglobin cutoffs is warranted for global application, in representative healthy populations of children and adults. Such data are scarce in low-income and middle-income countries; however, a 2019, large-scale, nationally representative survey of children and adolescents aged 0-19 years in India (Comprehensive National Nutrition Survey [CNNS]) offered an opportunity for this re-examination. Using this survey, we aimed to assess the age-specific and sex-specific percentiles of haemoglobin and cutoffs to define anaemia in the CNNS population. METHODS: For this population-based study, we constructed age-specific and sex-specific haemoglobin percentiles from values reported for a defined healthy population in the CNNS, which used rigorous quality control measures during sample collection and in the laboratory analyses. To obtain a healthy population, we excluded participants with iron, folate, vitamin B12, and retinol deficiencies; inflammation; variant haemoglobins (haemoglobin A2 and haemoglobin S); and history of smoking. We considered age-specific and sex-specific 5th percentiles of haemoglobin derived for this healthy population as the study cutoff to define anaemia. We compared these with existing WHO cutoffs to assess significant differences between them at each year of age and sex for quantifying the prevalence of anaemia in the entire CNNS sample. FINDINGS: Between Feb 24, 2016, and Oct 26, 2018, the CNNS survey collected blood samples from 49 486 individuals. 41 210 participants had a haemoglobin value, 8087 of whom were included in our study and comprised the primary analytical sample. Compared with existing WHO cutoffs, the study cutoffs for haemoglobin were lower at all ages, usually by 1-2 g/dL, but more so in children of both sexes aged 1-2 years and in girls aged 10 years or older. Aanemia prevalence with the study cutoffs was 19·2 percentage points lower than with WHO cutoffs in the entire CNNS sample with valid haemoglobin values across all ages and sexes (10·8% with study cutoffs vs 30·0% with WHO cutoffs). INTERPRETATION: These findings support the re-examination of WHO haemoglobin cutoffs to define anaemia. Our haemoglobin reference percentiles, derived from healthy participants in a large representative Indian survey, are suitable for national use in India. Substantial variations in the 5th percentile of haemoglobin values across the 1-19 years age range and between sexes argue against constructing common cutoffs in stratified age groups for convenience. FUNDING: None. TRANSLATIONS: For the Hindi, Punjabi, Tamil and Kannada translations of the abstract see Supplementary Materials section.

Impact of daily-supervised administration of a package of iron and folic acid and vitamin B12 on hemoglobin levels among adolescent girls (12-19 years): a cluster randomized control trial.

OBJECTIVE: The prevalence of anemia has remained high among Indian adolescent girls over the past decade, despite the ongoing iron and folic acid (IFA) supplementation program. This study was conducted to assess the impact of daily supplementation of a package of IFA with vitamin B12 on hemoglobin levels among adolescent girls. METHODS: A community-based cluster-randomized trial was conducted in the rural block of Faridabad District, Haryana, India in the year 2017. A total of 760 adolescent girls in the age group of 12-19 years with mild and moderate anemia were selected from government schools. Daily-supervised administration of iron and folic acid was conducted for 90 days: experimental group-IFA (iron (60 mg), folic acid (500) mcg), and cyanocobalamin (1000 mcg), control group-IFA and placebo. Hemoglobin, serum ferritin, and vitamin B12 levels were assessed at baseline and endline. RESULTS: Two-hundred adolescent girls completed 90 doses of daily supplementation. The mean hemoglobin (experimental group: 1.3 ± 1.0 g/dL, control group: 1.6 ± 1.2 g/dL, P = 0.004) and ferritin levels (experimental group: 18.6 ± 31.5 ng/mL, control group: 18.8 ± 35.0 ng/mL, P = 0.188) increased in both the control and experiment groups. Serum vitamin B12 deficiency significantly reduced to 2.5% in the experimental group and ferritin deficiency alleviated in more than 96% of the girls post intervention. CONCLUSIONS: Daily supplementation of IFA with/without vitamin B12 for 90 days eliminated iron, vitamin B12 deficiency and reduced the overall proportion of anemia by 53.5%. However, addition of vitamin B12 to IFA supplementation had no impact on improving the hemoglobin levels among adolescent girls. The present study does not recommend provision of vitamin B12 for prevention and treatment of anemia in this population group.

Daily Iron Requirements in Healthy Indian Children and Adolescents.

OBJECTIVE: This study aimed to define the estimated average requirement and the recommended dietary allowance of iron for Indian children and adolescents. Methods: The Estimated average requirement was derived for children aged 1-17y, from the mean bioavailability-adjusted daily physiological iron requirement, which in turn was estimated using a factorial method. This consisted of mean daily iron losses from the body and additional iron required for tissue growth and storage, while also defining the variance of each factor to derive the Recommended dietary allowance. RESULTS: Results: The estimated average requirement of iron for children ranged from 5.6 to 11.0 mg/d in children aged 1-9y. For adolescents aged 10-17y, these ranged from 10.8 to 18.4 mg/d and 15.4 to 18.5 mg/d for adolescent boys and girls, respectively. CONCLUSIONS: New estimates of estimated average requirement for iron in Indian children are presented, and same may be used to inform iron supplementation and food fortification policies.

Zinc Supplementation for Promoting Growth in Children Under 5 years of age in Low- and Middle-income Countries: A Systematic Review.

OBJECTIVE: To study the effect of zinc supplementation in children under 5 years of age rom low- and middle-income countries (LMICs) on anthropometry and prevalence of malnutrition. Design: Systematic review of randomized controlled trials and cluster randomized trials. SETTING: Low- and middle-income countries. PARTICIPANTS: 63 trials with zinc supplementation, incorporating data on 27372 children. Trials conducted exclusively in specifically diseased participants and in children with severe acute malnutrition were excluded. Intervention: Zinc supplementation, provided either as medicinal supplementation or through food fortification. OUTCOME MEASURES: (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference, head circumference; (ii) Prevalence of malnutrition. RESULTS: There was no evidence of effect on height-for-age Z score at the end of supplementation period (25 trials; 9165 participants; MD= 0.00 Z; 95% CI -0.07, 0.07; P=0.98; moderate quality evidence) with significant heterogeneity (I² = 57%; P<0.001) related to dose and duration of zinc between trials. There was little or no effect on change in height-for-age Z score (13 trials; 8852 participants; MD= 0.11 Z; 95% CI -0.00, 0.21; P=0.05), but the heterogeneity was considerable (I²=94%; P<0.001). There was no evidence of effect on length (6303 participants; MD= 1.18 cm; 95% CI -0.63, 2.99 cm, P=0.20; moderate quality evidence; considerable heterogeneity, I²=99%) but a little positive effect on change in length (19 trials; 10783 participants; MD= 0.43 cm; 95% CI 0.16, 0.70, P=0.002; moderate quality evidence; considerable heterogeneity, I²=93%). There was no evidence of effect on weight-for-age Z score or change in weight-for-age Z score but a little positive effect on weight (19 trials; 8851 study participants; MD= 0.23 kg; 95% CI 0.03, 0.42; P=0.02; considerable heterogeneity, I²=91%) and change in weight (kg) (23 trials; 10143 study participants; MD= 0.11 kg; 95% CI 0.05, 0.17, P<0.001, substantial heterogeneity, I²=80%). There was no evidence of effect on weight-for-height Z score, and mid upper arm circumference at the end of supplementation period, but there was a little positive effect on change in MUAC from baseline (8 trials; 1724 participants; MD = 0.09 cm; 95% CI 0.01, 0.16; P=0.03; no heterogeneity, I²=0%). Head circumference in zinc supplemented group was marginally higher compared to control (2966 study participants; MD= 0.39 cm; 95% CI 0.03, 0.75; P=0.03; substantial heterogeneity, I²=67%). There was no evidence of benefit in stunting (10 trials; 11838 study participants; RR= 1.0; 95% CI 0.95, 1.06; P=0.89; Moderate Quality Evidence; no significant heterogeneity, I²=11%), wasting (7 trials; 8988 study participants; RR= 0.94; 95% CI 0.82, 1.06; P=0.31; Moderate Quality Evidence; no significant heterogeneity, I²=13%) or underweight (7 trials; 8677 study participants; RR= 1.08; 95% CI 0.96, 1.21; P=0.19; Moderate Quality Evidence; substantial heterogeneity, I²=73%). CONCLUSION: Available evidence suggests that zinc supplementation probably leads to little or no improvement in anthropometric indices and malnutrition (stunting, underweight and wasting) in children under five years of age in LMICs. Advocating zinc supplementation as a public health measure to improve growth, therefore appears unjustified in these settings with scarce resources.

Maternal antenatal multiple micronutrient supplementation for long-term health benefits in children: a systematic review and meta-analysis.

BACKGROUND: Multiple micronutrient supplementation for pregnant women reduces low birth weight and has been recommended in low- and middle-income countries (LMICs) to improve child survival, growth and health. We aimed to review the evidence from long-term follow-up studies of multiple micronutrient supplementation beginning in the later first or second trimester. METHODS: We searched systematically for follow-up reports from all trials in a 2015 Cochrane review of multiple micronutrient supplementation in pregnancy. The intervention comprised three or more micronutrients and the comparison group received iron (60 mg) and folic acid (400 µg), where possible. Median gestation of commencement varied from 9 to 23 weeks. Primary outcomes were offspring mortality, height, weight and head circumference, presented as unadjusted differences in means or proportions (intervention minus control). Secondary outcomes included other anthropometry, body composition, blood pressure, and cognitive and lung function. RESULTS: We found 20 follow-up reports from nine trials (including 88,057 women recruited), six of which used the UNIMMAP supplement designed to provide recommended daily allowances. The age of follow-up ranged from 0 to 9 years. Data for mortality estimates were available from all trials. Meta-analysis showed no difference in mortality (risk difference -0.05 per 1000 livebirths; 95 % CI, -5.25 to 5.15). Six trials investigated anthropometry and found no difference at follow-up in weight-for-age z score (0.02; 95 % CI, -0.03 to 0.07), height-for-age z score (0.01; 95 % CI, -0.04 to 0.06), or head circumference (0.11 cm; 95 % CI, -0.03 to 0.26). No differences were seen in body composition, blood pressure, or respiratory outcomes. No consistent differences were seen in cognitive function scores. CONCLUSIONS: There is currently no evidence that, compared with iron and folic acid supplementation, routine maternal antenatal multiple micronutrient supplementation improves childhood survival, growth, body composition, blood pressure, respiratory or cognitive outcomes.

Effects of vitamin D supplementation in infancy on growth, bone parameters, body composition and gross motor development at age 3-6 years: follow-up of a randomized controlled trial.

BACKGROUND: The long-term effects of infant vitamin D supplementation and status are unclear since there have been few controlled intervention trials and these have been small and contradictory. The Delhi Infant Vitamin D Supplementation (DIVIDS) trial found that supplementation of low-birthweight term infants with one recommended dietary allowance of vitamin D from 1 week to 6 months of age resulted in increased length and weight at 6 months. In the DIVIDS-2 study we followed up the DIVIDS children, now aged 3-6 years, to determine longer-term effects. METHODS: DIVIDS children, 446 from the vitamin D arm and 466 from the placebo arm, attended the follow-up visit. Data collection included anthropometry, blood pressure, bone structure and strength by quantitative ultrasound (QUS), gross motor tests, deuterium dilution test of body composition on a subset (n = 229) and blood samples for measurement of vitamin D status. RESULTS: Body mass index Z scores (BMIZ) were lower (adjusted P = 0.003)in the vitamin D Group [-1.18 (SD 0.92)] when compared with the placebo [-1.02 (SD 0.91)] group as a result of slightly lower weight and slightly greater height. The vitamin D group also had lower thigh circumference and arm muscle area and borderline lower mid-upper arm circumference. There were no group differences in body fat percentage, bone QUS or blood pressure and few differences in motor development measures. CONCLUSIONS: Vitamin D supplementation of low-birthweight infants in infancy resulted in children being thinner at age 3-6 years but in no differences in functional outcomes.

Effect of iron-fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials.

BACKGROUND: The utility of iron fortification of food to improve iron deficiency, anemia, and biological outcomes is not proven unequivocally. OBJECTIVES: The objectives were to evaluate 1) the effect of iron fortification on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia, 2) the possible predictors of a positive hemoglobin response, 3) the effect of iron fortification on zinc and iron status, and 4) the effect of iron-fortified foods on mental and motor development, anthropometric measures, and infections. DESIGN: Randomized and pseudorandomized controlled trials that included food fortification or biofortification with iron were included. RESULTS: Data from 60 trials showed that iron fortification of foods resulted in a significant increase in hemoglobin (0.42 g/dL; 95% CI: 0.28, 0.56; P < 0.001) and serum ferritin (1.36 µg/L; 95% CI: 1.23, 1.52; P < 0.001), a reduced risk of anemia (RR: 0.59; 95% CI: 0.48, 0.71; P < 0.001) and iron deficiency (RR: 0.48; 95% CI: 0.38, 0.62; P < 0.001), improvement in other indicators of iron nutriture, and no effect on serum zinc concentrations, infections, physical growth, and mental and motor development. Significant heterogeneity was observed for most of the evaluated outcomes. Sensitivity analyses and meta-regression for hemoglobin suggested a higher response with lower trial quality (suboptimal allocation concealment and blinding), use of condiments, and sodium iron edetate and a lower response when adults were included. CONCLUSION: Consumption of iron-fortified foods results in an improvement in hemoglobin, serum ferritin, and iron nutriture and a reduced risk of remaining anemic and iron deficient.

Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trial.

OBJECTIVE: To investigate whether vitamin D supplementation can decrease the mortality and morbidity of low birthweight infants in low income countries. DESIGN: Randomised controlled trial. SETTING: Large government hospital in New Delhi, India. PARTICIPANTS: 2079 low birthweight infants born at term (>37 weeks' gestation). MAIN OUTCOME MEASURES: Primary outcome was admission to hospital or death during the first six months of life. Main secondary outcome was growth. INTERVENTIONS: Weekly vitamin D supplements for six months at a dose of one recommended nutrient intake per day (35 µg/week). Infants were visited weekly at home for observed supplementation and were brought to the clinic monthly for clinical examination and anthropometric measurements. RESULTS: Between group differences were not significant for death or hospital admissions (92 among 1039 infants in the vitamin D group v 99 among 1040 infants in the placebo group; adjusted rate ratio 0.93, 95% confidence interval 0.68 to 1.29; P = 0.68), or referral to the outpatient clinic for moderate morbidity. Vitamin D supplementation resulted in better vitamin D status as assessed by plasma calcidiol levels at six months. In adjusted analyses, vitamin D treatment significantly increased standard deviation (z) scores at six months for weight, length, and arm circumference and decreased the proportion of children with stunted growth (length for age z score ≤ 2) or with arm circumference z scores of 2 or less. CONCLUSION: A weekly dose of vitamin D resulted in better vitamin D status and benefited the classic vitamin D function of bone growth but did not decrease the incidence of severe morbidity or death among young low birthweight infants. Trial registration ClinicalTrials.gov NCT00415402.