Supplementation of red palm olein-enriched biscuits improves levels of provitamin A carotenes, iron, and erythropoiesis in vitamin A-deficient primary schoolchildren: a double-blinded randomised controlled trial.

PURPOSE: Vitamin A deficiency (VAD) remains a significant contributor to childhood morbidity and mortality in developing countries; therefore, the implementation of sustainable and cost-effective approaches to control VAD is of utmost pertinence. This study aims to investigate the efficacy of red palm olein (RPO)-enriched biscuit supplementation in improving vitamin A, haematological, iron, and inflammatory status among vitamin A-deficient schoolchildren. METHODS: We conducted a double-blinded, randomised controlled trial involving 651 rural primary schoolchildren (8-12 years) with VAD in Malaysia. The schoolchildren were randomised to receive either RPO-enriched biscuits (experimental group, n = 334) or palm olein-enriched biscuits (control group, n = 317) for 6-month duration. RESULTS: Significant improvements in retinol and retinol-binding protein 4 levels were observed in both groups after supplementation (P < 0.001). The improvement in retinol levels were similar across groups among subjects with confirmed VAD (P = 0.40). Among those with marginal VAD, greater improvement in retinol levels was recorded in the control group (P < 0.001) but lacked clinical significance. The levels of α- and ß-carotenes, haematological parameters (haemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin) and iron enhanced more significantly in the experimental group (P < 0.05). The significant reduction in the prevalence of microcytic anaemia (- 21.8%) and high inflammation (- 8.1%) was only observed in the experimental group. CONCLUSION: The supplementation of RPO-enriched biscuits enhanced levels of provitamin A carotenes, iron, and erythropoiesis, and exhibited anti-inflammatory effects. Therefore, the incorporation of RPO into National Nutritional Intervention Programs may be a potential measure to improve the health status of vitamin A-deficient children, among various other interventions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03256123).

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Effect of vitamin A on maternal, fetal, and neonatal outcomes: An overview of deficiency, excessive intake, and intake recommendations.

Vitamin A imbalance during pregnancy and lactation is a global public health concern with potentially negative consequences for fetuses and neonates. Inadequate vitamin A intake during this critical period can lead to anemia, weakened immune function, night blindness, and increased susceptibility to infections. Conversely, excessive intake of vitamin A can result in birth defects, hypercalcemia, and psychiatric symptoms. This review aims to identify risk factors contributing to vitamin A deficiency in pregnant women and its impact on maternal, fetal, and neonatal outcomes. It also examines the effects of high-dose vitamin A supplementation during pregnancy on offspring health. By analyzing existing literature and recommendations, the review emphasizes the significance of vitamin A in the development of various body systems and organs. It provides a comprehensive overview of the effects of vitamin A during pregnancy and lactation, encompassing deficiencies, excessive intake, and supplementation guidelines. The need for further research in this field is highlighted. In conclusion, maintaining a balanced vitamin A status is crucial during pregnancy to promote better outcomes for fetuses and newborns. Effective monitoring and intervention strategies are essential to address vitamin A deficiency and excess in pregnant women, thereby improving fetal and neonatal health.

Benefits and Harms of Edible Vegetable Oils and Fats Fortified with Vitamins A and D as a Public Health Intervention in the General Population: A Systematic Review of Interventions.

This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and ameliorating deficiency states in the general population. In November 2022, we systematically searched MEDLINE, Cochrane CENTRAL, Scopus, Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP (International Clinical Trials Registry Platform) for randomized controlled trials (RCT) and non-randomized studies of interventions (NRSI) investigating the fortification of edible vegetable oils and fats with either vitamin A or vitamin D or both as compared to the same vegetable oils and/or fats without vitamin A and D fortification or no interventions, in the general population, without age restriction. We assessed the methodological quality of included RCTs using Cochrane's risk of bias tool 2.0 and of NRSIs using ROBINS-I tool. We performed random-effects meta-analysis and assessed certainty of evidence using GRADE. We included eight studies. Available evidence showed no significant effect of fortification with vitamin A on serum retinol levels (RCTs: MD 0.35 µmol/L, 95% CI -0.43 to 1.12; two trials; 514 participants; low-certainty evidence; CCTs: MD 0.31 µmol/L, 95% CI -0.18 to 0.80; two trials; 205 participants; very low-certainty evidence) and on subclinical vitamin A deficiency. Low-certainty evidence showed no effect of vitamin D fortification on serum 25-hydroxy vitamin D concentration (MD 6.59 nmol/L, 95% CI -6.89 to 20.07; one trial; 62 participants). In conclusion, vitamin A-fortified vegetable oils and fats may result in little to no difference in serum retinol levels in general populations. The dose of vitamin A used in the trials may be safe but may not be sufficient to reduce subclinical vitamin A deficiency. Further, the evidence suggests that vitamin D fortification results in little to no difference in serum 25-hydroxy vitamin D concentration. Several aspects of providing fortified oils and fats to the general population as a public health intervention should be further investigated, including optimal fortification dose, effects on vitamin D deficiency and its clinical symptoms and potential adverse effects.

Potential blindness from nutritional xerophthalmia in autistic patients.

BACKGROUND: Vitamin A is vital to retinal rod function and epithelial cell differentiation. Although uncommon in the developed world, vitamin A deficiency (VAD) secondary to poor diets or gastrointestinal disease has been reported and can lead to xerophthalmia, which is characterized by night blindness and a spectrum of ocular surface changes. Patients with autism spectrum disorder have been shown to have restrictive diets secondary to sensory issues leading to rejection of foods except for those of certain color or texture. METHODS: We present a case series of 6 pediatric patients with autism who developed varying degrees of xerophthalmia due to VAD, which resulted from restrictive eating. RESULTS: All patients presented with a history of eye irritation that was not relieved by antibiotic or allergy eye drops. Further questioning revealed they had restrictive diets consisting of only or mostly white and tan foods, and serum vitamin A testing confirmed severe VAD. Most stages of xerophthalmia were completely reversed with vitamin A supplementation, but in 2 patients more advanced xerophthalmia resulted in irreversible blindness and ocular damage. CONCLUSIONS: Both pediatricians and pediatric eye care providers must be vigilant for VAD as an etiology of eye irritation, photophobia, or new-onset visual impairment in autistic children. A review of the child's diet must be implemented as a standard part of routine history taken in this vulnerable population. Early identification and vitamin A supplementation can prevent irreversible ocular compromise and vision loss.

Shifts in Social Determinants of Vitamin A Supplementation Among Children Under Five in Kenya, 2003-2014.

OBJECTIVES: In Africa and Asia, 190 million preschoolers are vitamin A deficient. This study examined the social determinants of intake of vitamin A supplementation (VAS) among children aged 6-59 months during three different time periods in Kenya to identify those most vulnerable to vitamin A deficiency and highlight the varied targeting and outreach efforts; before the onset of a national restructuring and targeted distribution of VAS in children below 5 years through a twice-yearly door-to-door campaign called Child Health Weeks, during the implementation period, and several years later. METHODS: The cross-sectional, national Demographic and Health Surveys were administered in Kenya in 2003, 2008-09, and 2014. Bivariate and multivariable logistic regression analyses were used to assess variables associated with VAS among children (n = 28,239). RESULTS: An overall two-fold increase in VAS was recorded between 2003 (31.8%) and 2014 (67.5%). In 2008-09, children aged 6-11 months were the most likely to receive VAS. In 2003 and 2014, geographical regions and settings, birth order of the child, educational level of the mother, religion, wealth index, number of antenatal visits, and access to a radio were identified as being significantly associated with VAS, in at least one of the years. These determinants were not significant in 2008-09 during the initial Child Health Weeks promotion campaign. The determinants of VAS varied during the three study periods, particularly in 2008-09 when the Child Health Weeks was first implemented. CONCLUSION: As efforts to increase VAS continue, addressing child-specific determinants will be essential to reduce health disparities.

Vitamin A supplementation coverage and its associated factors among children aged 6-59 months in West Azernet Berbere Woreda, South West Ethiopia.

BACKGROUND: Vitamin A deficiency is one of the major public health problems in low and middle-income countries including Ethiopia. Despite this fact, little attention was given to routine vitamin A supplementation in hard-to-reach rural areas and districts. Therefore, this study aimed to assess vitamin A supplementation coverage and its associated factors among children aged 6-59 months in West Azernet Berbere woreda, southern Ethiopia, 2021. METHODS: A community-based cross-sectional study was conducted from April to May 2021. A total sample size of 471 study participants was involved in the study area. A simple random sampling technique was used to recruit the study subject. A pretested structured interviewer-administered questionnaire was used. Bivariable and multivariable logistic regression analyses were done to identify variables having a significant association with vitamin A supplementation. The variables having a p-value ≤ 0.05 with 95% CI were used to declare an association between factors and a dependent variable. RESULTS: In this study, a total of 471 respondents were successfully interviewed with a response rate of 97.3%. The coverage of vitamin A supplementation was found to be 58.0%. Family monthly income [AOR = 2.565, 95% CI(1.631,4.032)], having PNC visit [AOR = 1.801, 95% CI (1.158, 2.801)], husbands disapproval about vitamin A supplementation [AOR = 0.324, 95% CI (0.129, 0.813)], information about vitamin A supplementation [AOR = 2.932, 95% CI (1.893, 4,542)] and ANC follow-up [AOR = 1.882, 95% CI (1.084, 3.266)] were factors significantly associated to vitamin A supplementation. CONCLUSION: Vitamin A supplementation was found to be low and it is strongly associated with family monthly income, postnatal care, husband's disapproval of vitamin A supplementation, antenatal care follow-up, and information about vitamin A supplementation. Based on our findings, it is recommended to improve the monthly income of the household by actively engaging in various income-generating activities, enhance health information dissemination among mothers, particularly those who are underprivileged by using different strategies like local health campaigns, and mass media, advocacy of antenatal, and postnatal follow-up and promote the involvement of males/husband in childhood immunization service.

Evaluating equity dimensions of infant and child vitamin A supplementation programmes using Demographic and Health Surveys from 49 countries.

OBJECTIVES: Vitamin A deficiency affects an estimated 29% of all children under 5 years of age in low/middle-income countries, contributing to child mortality and exacerbating severity of infections. Biannual vitamin A supplementation (VAS) for children aged 6-59 months can be a low-cost intervention to meet vitamin A needs. This study aimed to present a framework for evaluating the equity dimensions of national VAS programmes according to determinants known to affect child nutrition and assist programming by highlighting geographical variation in coverage. METHODS: We used open-source data from the Demographic and Health Survey for 49 countries to identify differences in VAS coverage between subpopulations characterised by various immediate, underlying and enabling determinants of vitamin A status and geographically. This included recent consumption of vitamin A-rich foods, access to health systems and services, administrative region of the country, place of residence (rural vs urban), socioeconomic position, caregiver educational attainment and caregiver empowerment. RESULTS: Children who did not recently consume vitamin A-rich foods and who had poorer access to health systems and services were less likely to receive VAS in most countries despite potentially having a greater vitamin A need. Differences in coverage were also observed when disaggregated by administrative regions (88% of countries) and urban versus rural residence (35% of countries). Differences in vitamin A coverage between subpopulations characterised by other determinants of vitamin A status varied considerably between countries. CONCLUSION: VAS programmes are unable to reach all eligible infants and children, and subpopulation differences in VAS coverage characterised by various determinants of vitamin A status suggest that VAS programmes may not be operating equitably in many countries.

Comparison of Total Body Vitamin A Stores Using Individual versus Population 13C-Natural Abundance of Serum Retinol in Preschool Children and Women Residing in 6 Diverse African Countries.

BACKGROUND: Stable isotope techniques using 13C to assess vitamin A (VA) dietary sources, absorption, and total body VA stores (TBSs) require determination of baseline 13C abundance. 13C-natural abundance is approximately 1.1% total carbon, but varies with foods consumed, supplements taken, and food fortification with synthetic retinyl palmitate. OBJECTIVES: We determined 13C variation from purified serum retinol and the resulting impact on TBSs using pooled data from preschool children in Burkina Faso, Cameroon, Ethiopia, South Africa, Tanzania, and Zambia and Zambian women. METHODS: Seven studies included children (n = 639; 56 ± 25 mo; 48% female) and one in women (n = 138; 29 ± 8.5 y). Serum retinol 13C-natural abundance was determined using GC-C-IRMS. TBSs were available in 7 studies that employed retinol isotope dilution (RID). Serum CRP and α1-acid-glycoprotein (AGP) were available from 6 studies in children. Multivariate mixed models assessed the impact of covariates on retinol 13C. Spearman correlations and Bland-Altman analysis compared serum and milk retinol 13C and evaluated the impact of using study- or global-retinol 13C estimates on calculated TBSs. RESULTS: 13C-natural abundance (%, median [Q1, Q3]) differed among countries (low: Zambia, 1.0744 [1.0736, 1.0753]; high: South Africa, 1.0773 [1.0769, 1.0779]) and was associated with TBSs, CRP, and AGP in children and with TBSs in women. 13C-enrichment from serum and milk retinol were correlated (r = 0.52; P = 0.0001). RID in children and women using study and global estimates had low mean bias (range, -3.7% to 2.2%), but larger 95% limits of agreement (range, -23% to 37%). CONCLUSIONS: 13C-natural abundance is different among human cohorts in Africa. Collecting this information in subgroups is recommended for surveys using RID. When TBSs are needed on individuals in clinical applications, baseline 13C measures are important and should be measured in all enrolled subjects.

Vitamin A deficiency and associated risk factors in children aged 12-59 months living in poorest municipalities in the South Region of Brazil.

OBJECTIVE: To estimate the prevalence of vitamin A deficiency (VAD) in children and associated risk factors. DESIGN: Analysis of data from a cross-sectional multicentre study performed in the primary care units of the municipalities from January to June 2015. The children's legal guardians answered a socio-economic questionnaire, and the children's blood samples were obtained by venipuncture. Plasma retinol was determined by HPLC. Plasma retinol values of <0·70 µmol/l were considered VDA. Poisson multiple regression with robust variance was used. Values of P < 0·05 were considered significant. The data were analysed in the SPSS software, 21.0. SETTING: Forty-eight poorest municipalities in the South Region of Brazil. PARTICIPANTS: Children (n 1503) aged 12-59 months. RESULTS: The prevalence of VAD in the sample was 1·9 % (95 % CI (0·5, 6·8)). The following risk factors were associated with the outcome in the final explanatory model: family received Bolsa Familia program benefits (PR = 3·19; 95 % CI (1·69, 6·02)), child was not being breastfed (PR = 5·22; 95 % CI (1·68, 16·18)) and stunting (PR = 4·75; 95 % CI (2·10, 10·73)). CONCLUSIONS: VAD did not represent a public health problem for children living in socio-economically vulnerable municipalities in the South Region of Brazil, suggesting a new panorama of this nutritional deficiency even in regions of low socio-economic conditions in these three states. Thus, in view of the current nutritional transition scenario, it is necessary to continuously monitor and improve public policies related to vitamin A supplementation in the country.

Total Liver Vitamin A Reserves, Determined With 13C2-Retinol Isotope Dilution, are Similar Among Tanzanian Preschool Children in Areas With Low and High Vitamin A Exposure.

BACKGROUND: In Tanzania, some districts have single vitamin A (VA) interventions and others have multiple interventions. There is limited information on total liver VA reserves (TLRs) among preschool children (PSC) in Tanzania. OBJECTIVES: We assessed total body VA stores (TBSs) and TLRs among PSC living in 2 districts with low and high exposures to VA interventions using 13C-retinol isotope dilution. METHODS: A cross-sectional, health facility-based study was conducted in 2 districts with access to VA supplementation only (low exposure to VA interventions) or multiple interventions (high exposure to VA interventions) to determine TLRs in 120 PSC aged 36-59 months. A questionnaire was used to collect data. Height and weight were measured, and the prevalence of undernutrition was based on z-scores. Blood samples were collected for measurement of TBSs, TLRs, retinol, biomarkers of infection and inflammation, and hemoglobin. 13C2-retinyl acetate (1.0 µmol) was administered to each child after blood collection, and the second sample was taken 14 days later. Serum was analyzed with HPLC and gas chromatography-combustion-isotope ratio mass spectrometry. Mann-Whitney U test was used to compare medians of nonnormally distributed variables. Pearson χ2 test was used to assess associations between 2 categorical variables. RESULTS: Median TBSs differed between PSC from low-exposure (196 µmol; IQR, 120 µmol) and high-exposure (231 µmol; IQR, 162 µmol) intervention areas (P = 0.015). Median TLRs were 0.23 µmol/g liver (IQR, 0.14 µmol/g liver) and 0.26 µmol/g liver (IQR, 0.16 µmol/g liver) from low- and high-exposure areas, respectively, which did not significantly differ (P = 0.12). Prevalences of VA deficiency (VAD; ≤0.1 µmol/g liver) were 6.3% and 1.7% for PSC from low- and high-exposure areas, respectively. There was no significant difference in VAD (P = 0.25). No child had hypervitaminosis A (≥1.0 µmol/g liver). CONCLUSIONS: TLRs in Tanzanian PSC from 2 districts did not differ between low and high exposures to VA interventions. The majority had adequate VA stores. VAD in the study area presented a mild public health problem.

A Review of Vitamin A Supplementation in South Sudan: Successes, Challenges, and Opportunities for the Way Forward.

AIM: To identify vitamin A supplementation (VAS) trends in South Sudan and provide insights to refocus VAS programming vis a vis polio eradication campaigns recently phased out while access to health care, land, food, and markets remain challenging. METHOD: Review of data from survey and coverage reports; review of policy and program documents; key informant responses; general literature search. RESULTS: Vitamin A deficiency (VAD) is likely a severe public health problem among preschool-aged children in South Sudan based on a high under-5 mortality rate (96.2 deaths/1,000 live births) and high levels of undernutrition, infections, and food insecurity. Vitamin A capsules, with deworming tablets (VASD), have been delivered to preschool-aged children during national immunization days (NIDs) for the past decade. Although areas of South Sudan and certain populations continue to have low VAS coverage, when comparing national VAS coverage (reported in the last 6 months) between 2010 and August 2019, a large improvement is noted from 4% to 76%. In 2021, VAS coverage was more than 90% at the national level during 2 stand-alone distribution campaigns. Deworming coverage trends generally mimicked VAS coverage. VAS is provided to postpartum mothers who deliver at health facilities (approximately 12%-25%), but coverage data are not available. CONCLUSION: Twice-yearly VAS should remain a key lifesaving intervention to address VAD, but alternative delivery strategies will be needed. Conducting events, such as child health days, supported by promotional activities or community-based VASD distribution activities for the youngest children and those missed during campaigns, should be considered. For the long term, a hybrid approach targeting underserved areas with mass distribution events while integrating VASD into community-based programs such as quarterly screening for wasting should be tested further and gradually scaled up everywhere as this has the potential to sustainably reach all vulnerable children twice yearly.

Vitamin A supplementation among 9-59 month old children in India: geospatial perspectives and implications for targeted coverage.

INTRODUCTION: Vitamin A supplementation (VAS) is yet to reach all Indian children aged 9-59 months, despite guidelines for universal coverage. This study mapped geospatial patterns underlying VAS coverage across two policy-relevant administrative unit levels (states and districts) in India. The relationship between spatial distribution of VAS coverage and vitamin A deficiency (VAD) prevalence was also investigated. METHODS: The study draws on nationally representative cross-sectional data collected during National Family and Health Survey 4 (NFHS-4) and Comprehensive National Nutritional Survey (CNNS). VAS coverage was estimated using information obtained during NFHS-4 from mothers about whether their children (n=204 645) had received VAS within 6 months of the survey. VAD prevalence estimates were based on serum retinol measurements during CNNS in under-five children (n=9563). State-level and district-level choropleth maps of VAS coverage were constructed. Spatial patterns were probed using Moran's statistics, scatter plots and local indicators of spatial association (LISA). Relationship between VAS coverage (as an explanatory variable) and VAD prevalence was explored using spatial autoregressive models. RESULTS: VAS coverage in India (overall 60.5%) ranged from 29.5% (Nagaland) to 89.5% (Goa) across the various states/union territories. Among districts, it ranged from 12.8% (Longleng district, Nagaland) to 94.5% (Kolar district, Karnataka). The coverage exhibited positive spatial autocorrelation, more prominently at the district-level (univariate Moran's I=0.638, z-value=25.614, pseudo p value=0.001). LISA maps identified spatial clusters of high coverage and low coverage districts. No significant spatial association was observed between VAS coverage and VAD prevalence in the states during spatial error (R2=0.07, λ=0.30, p value=0.14) and spatial lag (R2=0.05, ρ=0.25, p value=0.23) regression. CONCLUSION: Two out of every five eligible Indian children were not supplemented with vitamin A. The coverage was geographically heterogeneous with discernible spatial patterns. Their consequences on vitamin A status and associated health effects in the community deserve close monitoring.

Prevalence of vitamin A and vitamin D deficiency in hospitalized neonates in Xi'an, China.

BACKGROUND AND OBJECTIVES: To investigate the prevalence of vitamin A and vitamin D deficiency and the associated factors in hospitalized neonates in Xi'an, China. METHODS AND STUDY DESIGN: A total of 524 hospitalized neonates were collected in this study. Serum vitamin A and D concentrations were detected in neonates within two weeks of birth. RESULTS: Serum vitamin A and D concentrations of hospitalized neonates were 0.55±0.21 µmol/L and 42.0±20.6 nmol/L, respectively. They were greater in full-term neonates than in preterm neonates, greater in rural neonates than in urban, and greater in single than in twin (all p<0.001). The prevalence of vitamin A and D deficiency were 14.9% and 33.0%, the prevalence of marginal vitamin A deficiency was 64.7%, and vitamin D insufficiency was 35.1%. Neonatal serum vitamin A and D concentrations were all positively correlated with birth weight and gestational age. Neonatal serum vitamin D concentration was also positively correlated with maternal serum vitamin D concentration. Additionally, neonatal vitamin A concentration was positively correlated with neonatal serum vitamin D concentration. CONCLUSIONS: Vitamin A and vitamin D statuses are compromised in hospitalized neonates in Xi'an, especially in premature neonates, low birth weight neonates, twins, and those born in urban areas. Individualized supplementation with vitamin A and vitamin D in neonates should be a clinical consideration.

Is routine Vitamin A supplementation still justified for children in Nepal? Trial synthesis findings applied to Nepal national mortality estimates.

BACKGROUND: The World Health Organization has recommended Vitamin A supplementation for children in low- and middle-income countries for many years to reduce child mortality. Nepal still practices routine Vitamin A supplementation. We examined the potential current impact of these programs using national data in Nepal combined with an update of the mortality effect estimate from a meta-analysis of randomized controlled trials. METHODS: We used the 2017 Cochrane review as a template for an updated meta-analysis. We conducted fresh searches, re-applied the inclusion criteria, re-extracted the data for mortality and constructed a summary of findings table using GRADE. We applied the best estimate of the effect obtained from the trials to the national statistics of the country to estimate the impact of supplementation on under-five mortality in Nepal. RESULTS: The effect estimates from well-concealed trials gave a 9% reduction in mortality (Risk Ratio: 0.91, 95% CI 0.85 to 0.97, 6 trials; 1,046,829 participants; low certainty evidence). The funnel plot suggested publication bias, and a meta-analysis of trials published since 2000 gave a smaller effect estimate (Risk Ratio: 0.96, 95% CI 0.89 to 1.03, 2 trials, 1,007,587 participants), with the DEVTA trial contributing 55.1 per cent to this estimate. Applying the estimate from well-concealed trials to Nepal's under-five mortality rate, there may be a reduction in mortality, and this is small from 28 to 25 per 1000 live births; 3 fewer deaths (95% CI 1 to 4 fewer) for every 1000 children supplemented. CONCLUSIONS: Vitamin A supplementation may only result in a quantitatively unimportant reduction in child mortality. Stopping blanket supplementation seems reasonable given these data.

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age.

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation (VAS) for children aged 6 to 59 months. The last version of this review was published in 2017, and this is an updated version of that review. OBJECTIVES: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers up to March 2021. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently assessed studies for inclusion resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: The updated search identified no new RCTs. We identified 47 studies, involving approximately 1,223,856 children. Studies were set in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most studies included equal numbers of girls and boys and lasted about one year. The mean age of the children was about 33 months. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for VAS compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-certainty evidence). Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 children; high-certainty evidence). There was no evidence of a difference for VAS on mortality due to measles (RR 0.88, 95% CI 0.69 to 1.11; 6 studies, 1,088,261 children; low-certainty evidence), respiratory disease (RR 0.98, 95% CI 0.86 to 1.12; 9 studies, 1,098,538 children; low-certainty evidence), and meningitis. VAS reduced the incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies, 77,946 children; low-certainty evidence), measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies, 19,566 children; moderate-certainty evidence), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 studies, 1,063,278 children; moderate-certainty evidence), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 studies, 22,972 children; moderate-certainty evidence), and VAD (RR 0.71, 95% CI 0.65 to 0.78; 4 studies, 2262 children, moderate-certainty evidence). However, there was no evidence of a difference on incidence of respiratory disease (RR 0.99, 95% CI 0.92 to 1.06; 11 studies, 27,540 children; low-certainty evidence) or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies, 10,541 children; moderate-certainty evidence). AUTHORS' CONCLUSIONS: This update identified no new eligible studies and the conclusions remain the same. VAS is associated with a clinically meaningful reduction in morbidity and mortality in children. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented VAD, it would be unethical to conduct placebo-controlled trials.

Recognizing vitamin A deficiency: special considerations in low-prevalence areas.

PURPOSE OF REVIEW: Although vitamin A deficiency (VAD) is rare in well resourced countries, there is a growing trend of VAD in at-risk pediatric populations. Early diagnosis is critically important to prevent its associated morbidity and mortality. This review highlights key lessons for evaluation, diagnosis, and management of children with xerophthalmia in the United States. It synthesizes the latest findings from the literature on the pathophysiology, epidemiology, risk factors, evaluation, and management of VAD in low-prevalence areas. RECENT FINDINGS: Vitamin A is crucial for maintaining the functional integrity of the eye, immune system, skin, and mucous membranes. Despite the scarcity of VAD in developed countries, there are increasing reports of VAD in at-risk children, including those with autism spectrum disorder and gastrointestinal conditions. There is a broad range of manifestations of VAD, posing a diagnostic challenge. Familiarity with the variable presentations of VAD and having a high index of suspicion in at-risk populations can aid in its early diagnosis. Systemic vitamin A supplementation and a multidisciplinary approach are important components of the management of VAD. SUMMARY: Even in well resourced countries, VAD should remain on the differential in patients with risk factors who present with relevant signs and symptoms. Early diagnosis and appropriate involvement of a multidisciplinary care team can help prevent morbidity and mortality associated with VAD.