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Porcine epidemic diarrhea virus (PEDV) causes a highly contagious enteric disease with major economic losses to swine production worldwide. Due to the immaturity of the neonatal piglet immune system and given the high virulence of PEDV, improving passive lactogenic immunity is the best approach to protect suckling piglets against the lethal infection. We tested whether oral vitamin A (VA) supplementation and PEDV exposure of gestating and lactating VA-deficient (VAD) sows would enhance their primary immune responses and boost passive lactogenic protection against the PEDV challenge of their piglets. We demonstrated that PEDV inoculation of pregnant VAD sows in the third trimester provided higher levels of lactogenic protection of piglets as demonstrated by >87% survival rates of their litters compared with <10% in mock litters and that VA supplementation to VAD sows further improved the piglets' survival rates to >98%. We observed significantly elevated PEDV IgA and IgG antibody (Ab) titers and Ab-secreting cells (ASCs) in VA-sufficient (VAS)+PEDV and VAD+VA+PEDV sows, with the latter maintaining higher Ab titers in blood prior to parturition and in blood and milk throughout lactation. The litters of VAD+VA+PEDV sows also had the highest serum PEDV-neutralizing Ab titers at piglet post-challenge days (PCD) 0 and 7, coinciding with higher PEDV IgA ASCs and Ab titers in the blood and milk of their sows, suggesting an immunomodulatory role of VA in sows. Thus, sows that delivered sufficient lactogenic immunity to their piglets provided the highest passive protection against the PEDV challenge. Maternal immunization during pregnancy (± VA) and VA sufficiency enhanced the sow primary immune responses, expression of gut-mammary gland trafficking molecules, and passive protection of their offspring. Our findings are relevant to understanding the role of VA in the Ab responses to oral attenuated vaccines that are critical for successful maternal vaccination programs against enteric infections in infants and young animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Amimo, Michael, Chepngeno, Jung, Raev, Paim, Lee, Damtie, Vlasova and Saif.)

Objectives: Vitamin A supplementation (VAS) can protect children from the adverse health consequences of vitamin A deficiency. Granular data on VAS coverage can guide global and national efforts to achieve universal VAS coverage. To provide geographically precise targeting of VAS programs and to monitor progress in reducing geographic disparities, we aimed to create high-resolution (5 × 5 km 2 ) maps of VAS coverage in children under 5 years across VAS priority countries., Study Design: We used cross-sectional data from the Demographic and Health Surveys (DHS) program., Methods: We used data from the DHS program for United Nations Children's Fund -designated VAS priority countries between 2000 and 2017 with data available from 2005 or later. The outcome variable was the proportion of children under 5 years who received a vitamin A dose in each sampled cluster. We applied a Bayesian geostatistical approach incorporating geographic, climatic, and nutritional covariates to estimate VAS coverage for each cell. We estimated and mapped absolute VAS coverage, Bayesian uncertainty intervals, and exceedance probabilities., Results: Our sample included countries from Latin America and the Caribbean, Asia, and Africa. Most countries had estimated VAS coverage levels <70%, and our exceedance probabilities indicated high certainty that our estimates fell below this threshold in most grid cells. International variations were most notable in the Latin America and the Caribbean region and Africa. Intranational variations were greatest in some South Asian and West and Central African countries., Conclusions: These prevalence and exceedance maps, especially used with data on indicators of VAS need, could help to improve equity., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Children in Ethiopia do not receive the recommended dose of vitamin A supplementation (VAS). Objective: This study aimed to explore the barriers to VAS uptake and program implementation among children aged 6-59 months in Ethiopia. Methods: Data were collected qualitatively using focus group discussions and in-depth interviews. The data were audio-recorded, transcribed, and inductively coded. The results were displayed using thematic analysis and the well-spoken verbatim of the respondents. Results: The barriers to VAS uptake were low parental awareness of the program and low interest or motivation, low promotion of the program among health professionals, an excessive workload for health extension workers, and low professional attention to VAS compared to other health services. Conclusion: Both client-side and supply-side issues posed significant obstacles to the uptake of VAS. It is important to educate mothers about VAS. Health workers should receive refresher training to raise their level of concern about VAS's importance and its schedule. It's crucial to initiate outreach programs for remote communities. The departmentalization of health extension packages will improve service and access., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Mulaw, Masresha and Feleke.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vitamin A deficiency is among the leading preventable causes of childhood morbidity and mortality that might be attributable to the low uptake of vitamin A supplementation (VAS). Factors contributing to its low utilization are not researched at the national level and with the appropriate model. Therefore, this study aimed at identifying the magnitude and the individual- and community-level factors associated with vitamin A supplementation among children aged 6-35 months in Ethiopia., Methods: We have used the Ethiopian mini demographic and health survey data, which was conducted from 21 March to 28 June 2019. A weighted sum of 2,362 mothers having children aged 6-35 was extracted. Considering the hierarchical nature of the data, we fitted the multilevel multivariable logistic regression model. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was reported and variables with a p -value of < 0.05 were declared to be significantly associated factors., Results: In this study, 43.4% (95% CI: 41.4-45.4%) of children have taken the VAS. Moreover, the 12-23 age of the child (AOR = 2.64; 95% CI: 1.88-3.72), 30-34 age of the mother (AOR = 3.34; 95% CI: 1.21-9.20), middle household wealth status (AOR = 1.75; 95% CI: 1.06-2.90), and four and above antenatal care (AOR = 2.90; 95% CI: 1.90-4.43) are the individual-level factors associated with VAS whereas being from Amhara (AOR = 2.20; 95% CI: 1.29-3.76) and Tigray (AOR = 2.16; 95% CI: 1.17-3.98) regions is a community-level factor significantly associated with the uptake of VAS., Conclusion: Overall, a low proportion of children have taken the VAS in Ethiopia. The higher age of the child and mother, full antenatal care, and improved wealth status positively influence VAS. Moreover, a child from the Tigray or Amhara regions was more likely to get VAS. Therefore, an intervention has to be designed to address the VAS uptake among young mothers, and working to improve the wealth status of the household would be helpful. Moreover, the advocacy of antenatal care and minimizing the regional disparity through encouraging the uptake in the rest of the regions would help increase the national-level uptake of VAS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Amare, Sime, Legese, Ferede and Alemu.)

Background: Vitamin A is a nutrient that is required in a small amount for normal visual system function, growth and development, epithelia's cellular integrity, immune function, and reproduction. Vitamin A has a significant and clinically important effect since it has been associated with a reduction in all-cause and diarrhea mortality. The aim of this study was to determine factors associated with national vitamin A supplementation among children aged 6-35 months., Method: The data for this study was extracted from the 2019 Ethiopian Mini Demographic and Health Survey. A total weighted sample of 2242 women with children aged 6-35 months was included in the study. The analysis was performed using Stata version 14.2 software. Applying sampling weight for descriptive statistics and complex sample design for inferential statistics, a manual backward stepwise elimination approach was applied. Finally, statistical significance declared at the level of p value < 0.05., Result: The overall coverage of vitamin A supplementation among children aged 6-35 months for the survey included was 44.4 95% CI (40.15, 48.74). In the multivariable analysis, mothers who had four or more antenatal visits [AOR = 2.02 (95% CI: 1.34, 3.04)] were two times more likely to receive vitamin A capsules for their children than mothers who had no antenatal visits. Children from middle-wealth quintiles had higher odds of receiving vitamin A capsules in comparison to children from the poorest wealth quintile [AOR = 1.77 (95% CI: 1.14, 2.73)]. Older children had higher odds of receiving vitamin A capsules than the youngest ones. Other factors that were associated with vitamin A supplementation were mode of delivery and region., Conclusion: The coverage of vitamin A supplementation in Ethiopia remains low and it is strongly associated with antenatal visit, household wealth index and age of child. Expanding maternal health services like antenatal care visits should be prioritized., (© 2022. The Author(s).)

Background: Bi-annual high dose vitamin A supplements administered to children aged 6-59 months can significantly reduce child mortality, but vitamin A supplementation (VAS) coverage is low in Nigeria. The World Health Organization recommends that VAS be integrated into other public health programmes which are aimed at improving child survival. Seasonal malaria chemoprevention (SMC) provides a ready platform for VAS integration to improve health outcomes. This study explored the feasibility and acceptability of integrating VAS with SMC in one local government area in Sokoto State., Methods: A concurrent QUAN-QUAL mixed methods study was used to assess the feasibility and acceptability of co-implementing VAS with SMC in one LGA of Sokoto state. Existing SMC implementation tools and job aids were revised and SMC and VAS were delivered using a door-to-door approach. VAS and SMC coverage were subsequently assessed using questionnaires administered to 188 and 197 households at baseline and endline respectively. The qualitative component involved key informant interviews and focus group discussions with policymakers, programme officials and technical partners to explore feasibility and acceptability. Thematic analysis was carried out on the qualitative data., Results: At endline, the proportion of children who received at least one dose of VAS in the last six months increased significantly from 2 to 59% (p < 0.001). There were no adverse effects on the coverage of SMC delivery with 70% eligible children reached at baseline, increasing to 76% (p = 0.412) at endline. There was no significant change (p = 0.264) in the quality of SMC, measured by proportion of children receiving their first dose as directly observed treatment (DOT), at baseline (54%) compared to endline (68%). The qualitative findings are presented as two overarching themes relating to feasibility and acceptability of the integrated VAS-SMC strategy, and within each, a series of sub-themes describe study participants' views of important considerations in implementing the strategy., Conclusion: This study showed that it is feasible and acceptable to integrate VAS with SMC delivery in areas of high seasonal malaria transmission such as northern Nigeria, where SMC campaigns are implemented. SMC-VAS integrated campaigns can significantly increase vitamin A coverage but more research is required to demonstrate the feasibility of this integration in different settings and on a larger scale., (© 2022. The Author(s).)

Given that combined vitamin A (VA) and retinoic acid (RA) supplementation stimulated the intestinal uptake of plasma retinyl esters in neonatal rats, we administrated an RA dose as a pretreatment before VA supplementation to investigate the distinct effect of RA on intestinal VA kinetics. On postnatal days (P) 2 and 3, half of the pups received an oral dose of RA (RA group), while the remaining received canola oil as the control (CN). On P4, after receiving an oral dose of 3 H-labeled VA, pups were euthanized at selected times ( n = 4-6/treatment/time) and intestine was collected. In both CN and RA groups, intestinal VA mass increased dramatically after VA supplementation; however, RA-pretreated pups had relatively higher VA levels from 10 h and accumulated 30% more VA over the 30-h study. Labeled VA rapidly peaked in the intestine of CN pups and then declined from 13 h, while a continuous increase was observed in the RA group, with a second peak at 10 h and nearly twice the accumulation of 3 H-labeled VA compared to CN. Our findings indicate that RA pretreatment may stimulate the influx of supplemental VA into the intestine, and the increased VA accumulation suggests a potential VA storage capacity in neonatal intestine.

(1) Background: vitamin A deficiency (VAD) is highly prevalent in children living in poor conditions. It has been suggested that vitamin A supplementation (VAS) may reduce the risk of acute respiratory tract infections (ARTI). Our study provides updates on the effects of oral VAS (alone) in children on ARTI and further explores the effect on interesting subgroups. (2) Methods: eight databases were systematically searched from their inception until 5 July 2021. The assessments of inclusion criteria, extraction of data, and data synthesis were carried out independently by two reviewers. (3) Results: a total of 26 randomized trials involving 50,944 participants fulfilled the inclusion criteria. There was no significant association of VAS with the incidence of ARTI compared with the placebo (RR 1.03, 95% CI 0.92 to 1.15). Subgroup analyses showed that VAS higher than WHO recommendations increased the incidence of ARTI by 13% (RR 1.13, 95% CI 1.07 to 1.20), and in the high-dose intervention group, the incidence rate among well-nourished children rose by 66% (RR 1.66, 95% CI 1.30 to 2.11). (4) Conclusions: no more beneficial effects were seen with VAS in children in the prevention or recovery of acute respiratory infections. Excessive VAS may increase the incidence of ARTI in children with normal nutritional status.

Vitamin A supplementation (VAS), started as a short-term strategy pending dietary improvements, has been implemented in Ethiopia for the last 15 years. We aimed to describe the trends in VAS coverage and estimated the associated reductions in child mortality. VAS coverage data obtained from the District Health Information System and the Demographic and Health Surveys were linked to child mortality data from the United Nations Interagency Group for Child Mortality Estimation (UN IGME). The number of child deaths averted was modelled assuming 12% and 24% reductions in all-cause mortality. From 2006 to 2011, VAS was delivered through campaigns, and coverage was above 85%. However, from 2011 onwards, VAS delivery was integrated to the routine health system, and the coverage declined to <60% with significant disparities by wealth quintile and rural-urban residence. VAS has saved between 167,563 to 376,030 child lives (2005-2019), but additional lives (>42,000) could have been saved with a universal coverage (95%). Inconsistent supply of vitamin A capsules, but more importantly, low access to health care, and the limited contact opportunities for children after 24 months may have contributed to the declining VAS coverage. Any changes in target or scale-up should thus consider these spatial and socioeconomic variations. Increasing the coverage of VAS and closing the equity gap in access to nutrition services is critical. However, with alternative programmes like vitamin A fortification being set-up, the benefits and safety of VAS need to be closely monitored, particularly in areas where there will be overlap., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Purpose: Many researchers have reported that vitamin A (VA) deficiency is related to chalazion. The purpose of this article is to clarify the effects of VA supplementation on chalazion in young children with VA deficiency. Methods: Forty-eight young children with VA deficiency suffering from chalazia were enrolled from our previous studies and were followed continuously for 1 year. Serum VA levels and recurrence of chalazion were observed. Results: The mean serum VA levels increased after supplementation ( P  = 2.17E-15). The mean serum VA levels of subjects who experienced recurrence were lower than those without recurrence ( P  = 0.015). The recurrence rate and the mean recurrent frequency after supplementation were lower than before supplementation ( P  = 0.01, P  = 6E-6); the mean time to the first recurrence of subjects without recurrence was longer after supplementation than before supplementation ( P  < 0.01). Conclusions: Oral VA supplementation could reduce the recurrence of chalazion in young children with preexisting VA deficiency.

Since 2006, Sierra Leone has achieved high rates of vitamin A supplementation (VAS) coverage (>88%) during mass campaigns. In 2017, campaigns started transitioning to routine VAS within a six-monthly contact point for integrated reproductive and child health (RCH) services. This contact point included improved counselling and provision of modern contraceptives; throughout this transition high VAS coverage (>85%) has been maintained. VAS programmes have traditionally operated on the assumption that they are gender-neutral, but recent research suggests these programmes should re-examine how they interact with gender. This qualitative study examined intersections between gender and Sierra Leone's integrated VAS programming by conducting 32 individual interviews with parents, district health management and national staff, and six focus group discussions with health workers and community health workers (CHWs) in three pilot program districts. The study found that most senior health positions are held by males, and the lower cadres of majority female health workers often felt unsupported/disrespected by their male superiors and male CHW supervisees, or that their years of experience were overlooked in favour of the academic qualifications of less experienced male colleagues. Gender was not included in program training, and most staff did not have a good understanding of gender intersections; however, health workers actively engaged in awareness raising with male stakeholders to increase male involvement in RCH. Routine delivery requires mothers to invest time and money to access health facilities, where most mothers felt that better qualified staff were able to offer better advice and more services. Health workers felt that outreach services utilizing CHWs could decrease this time/money burden; however, CHWs are unqualified to provide counselling and provision of modern contraception, and there are fewer female CHWs. Records kept in health facilities record VAS by sex, but monthly reports submitted to the district and onwards to the national Health Management Information System are not disaggregated by sex. Programme and policymakers should consider improving the representation by females in senior, decision-making positions, integrating gender information into all trainings, supporting female health workers, training and recruiting more female CHWs, and reporting VAS coverage by sex., (© The Author(s) 2021. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Vitamin A deficiency (VAD) is a prominent and widespread public health problem in developing countries, including Bangladesh. About 2% of all deaths among under-five children are attributable to VAD. Evidence-based information is required to understand the influential factors to increase vitamin A supplementation (VAS) coverage and reduce VAD. We investigated the potential factors affecting VAS coverage and its significant predictors among Bangladeshi children aged 6 to 59 months using the VAS clustered data extracted from the latest Bangladesh Demographic and Health Survey 2014., Methods: Data were analysed using mixed logistic regression (MLR) modelling approach in the generalised linear mixed model framework. The MLR model performs better than logistic regression for analysing the clustered data because of its minimum Akaike information criterion value. The likelihood ratio test showed that the variance component was significant. Therefore, the clustering effect among children was inevitable to use., Results: VAS coverage among under-five children was 63.6%, which is not optimal and below the WHO's recommendation and the country's target of 90%. Children aged 25 to 36 months (AOR = 2.07, 95% CI: 1.711 to 2.513), who had higher educated mothers (AOR = 1.37, p = 0.033, 95% CI: 1.026-1.820) and fathers (AOR = 1.32, p = 0.027, 95% CI: 1.032-1.683), whose mothers had media exposure (AOR = 1.22, p = 0.006, 95% CI: 1.059-1.408) and NGO membership (AOR = 1.24, p = 0.002, 95% CI: 1.089-1.422) were more likely to consume VAS., Conclusion: The relevant authorities should create proactive awareness programs for highly vulnerable local communities, specifically targeted to educate the children's mothers about the necessity and benefits of childhood nutrition.

Background: In low- and middle-income countries routine vitamin A supplementation (VAS) is a key strategy for reducing vitamin A deficiency and mortality and morbidity of preschool children. However, in Ethiopia, there is paucity of evidence regarding the level and determinants of the uptake of the supplement. This study was designed to assess the coverage and predictors of VAS among preschool children in Humbo district, Southern Ethiopia., Methods: A cross-sectional study was conducted in April 2016. A total of 840 mothers/caregivers having children 6-59 months of age were selected using multistage cluster sampling technique from six rural villages implementing routine VAS program. Data were collected using interviewer administered questionnaire. Possible predictors considered in the study include distance from the nearby health facility, household socio-economic status, type of the household (model vs non-model), maternal access to health education on VAS, and knowledge on vitamin A and VAS. Multivariable logistic regression analysis was performed to identify predictors of uptake of VAS. The outputs are presented using adjusted odds ratio (AOR) with the respective 95% confidence interval (CI)., Results: The coverage of VAS was 75.0% (95% CI: 72.1-77.9). Better knowledge of mothers about the importance of the supplement (AOR: 1.49, 1.02-2.17), obtaining VAS related information from frontline community health workers (AOR: 1.51, 1.34-2.72) than health professionals and being from households in the "rich" wealth tertile (AOR: 1.80, 95% CI: 1.07-3.03) were positively associated with uptake VAS., Conclusion: The VAS coverage of the area was approaching the expected national target of 80%. However, the uptake can be enhanced though awareness creation and improving socio-economic status of the community.

In 2017, transition to routine vitamin A supplementation (VAS) commenced as an integrated reproductive and child health service including vaccinations, Albendazole for deworming, complementary feeding demonstrations, 'quality' family planning counselling and provision of modern contraceptives. After 10 months, a lot quality assurance sampling survey evaluated coverage of these interventions. Each of three districts was divided into five supervision areas (lots), and 19 villages were randomly selected in each lot proportional to population size. Households were randomly selected, and a questionnaire was administered to a caregiver of a child 6-11, 12-23 and 24-59 months in each village. Overall, caregivers of 855 children were interviewed, and 19 questionnaires were completed for each age group (6-11, 12-23 and 24-59 months) in each of the five lots in each district. All lots in one district passed the threshold of 80% for VAS and 75% coverage for Albendazole, and two lots failed for either VAS/Albendazole in the other two districts. Overall, weighted VAS coverage for children 6-59 months was 86.9%, and weighted Albendazole coverage for children 12-59 months was 80.9%. Most caregivers (77.2%) knew that complementary feeding should be introduced at 6 months, 44.9% were providing three or more (of six) food groups, 84.9% were aware of family planning and 37.5% were using a modern contraceptive. Integration of reproductive and child health services appears to be a suitable platform for routine VAS and Albendazole whilst improving complementary feeding practices and access to family planning., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons, Ltd.)

Background: Vitamin A supplementation (VAS) in the postpartum period improves the vitamin A concentration of breast milk and vitamin A status is an important predictor of childhood survival. It is also known that Vitamin A Deficiency (VAD) is more prevalent in HIV-infected women. This study investigated the association between vitamin A supplements provided to HIV-positive women in the postpartum period and mortality and morbidity of their breastfed infants in sub-Saharan Africa (SSA) where the prevalence of VAD and HIV is high., Methods: This cross-sectional study was conducted based on the secondary data of 838 HIV-positive women (309 vitamin A supplement and 529 non-supplemented) extracted from the datasets of 43 Demographic and Health Surveys (DHS) conducted in 26 SSA countries between 2003 and 2015. The data of HIV-positive women who gave a live birth in the preceding 6 months of the survey and who were breastfeeding their infants at the time of the survey or who breastfed their deceased infants until the time of death, were included in the analysis. The association of postpartum VAS with early infant mortality (death in the first 6 months of birth) and morbidity secondary to fever, diarrhoea and cough with respiratory difficulties in the preceding 2 weeks was assessed by mixed-effects logistic regression model and interpreted using adjusted odds ratio (AOR) with the 95% confidence intervals (CI)., Results: About one-third (36.9%) of the HIV-positive women received VAS soon after the recent delivery. The early infant mortality rate per 1000 live births in vitamin A supplemented group was 100 (95% CI: 67-133) and the corresponding level for non-supplemented group was 125 (95% CI: 97-154). Yet, in the multivariable model adjusted for seven potential confounders, the association was not significant (AOR = 1.10: 95% CI, 0.57-2.13). Similarly, postpartum VAS was not significantly associated with the occurrence of cough with difficult breathing (AOR = 0.65: 95% CI, 0.39-1.10), diarrhoea (AOR = 0.89: 95% CI, 0.50-1.58) and fever (AOR = 1.19: 95% CI 0.78-1.82) in their breastfed infants., Conclusion: VAS provided to HIV-positive women in the immediate postpartum period does not have significant association with the mortality and morbidity of their breastfed infants.

An ongoing challenge to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance that are safe, efficacious, and avoid unintended consequences. The integration to effective implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the generation, translation, and implementation of evidence to public health guidance/programs. The I-to-I approach was developed under the auspices of the Micronutrient Forum and has been previously applied to the question of safety and effectiveness of interventions to prevent and treat nutritional iron deficiency. The present article applies the I-to-I approach to questions regarding the safety and utility of large-dose vitamin A supplementation programs, and presents the authors' perspective on key aspects of the topic, including coverage of the basic and applied biology of vitamin A nutrition and assessment, clinical implications, and an overview of the extant data with regard to both the justification for and utility of available intervention strategies. The article includes some practical considerations based on specific country experiences regarding the challenges of implementing vitamin A-related programs. This is followed by an overview of some challenges associated with engagement of the enabling communities that play a critical role in the implementation of these types of public health interventions. The article concludes with suggestions for potential approaches to move this important agenda forward., (Copyright © American Society for Nutrition 2019.)

This randomized double-blind placebo-controlled trial evaluated the effects of early postnatal oral vitamin A supplementation (VAS) in 196 inborn very-low birth weight (VLBW) infants requiring respiratory support at 24 h of age. Eligible infants were randomized to receive aqueous syrup of vitamin A (10,000 IU of retinol/dose; n = 98) or placebo (n = 98) on alternate days for 28 days. Primary outcome variable was composite incidence of all-cause mortality and/or oxygen requirement for 28 days. Secondary outcome variables were safety/tolerability of VAS, serum retinol concentration at recruitment and day 28, duration of oxygen requirement and respiratory support and incidences of complications. On intention-to-treat analysis, composite incidence of all-cause mortality and oxygen requirement for 28 days was significantly lower in vitamin A group (relative risk (95% confidence interval), 0.440 (0.229-0.844); p < 0.05, number needed to benefit, 7). Requirement and duration of oxygen supplementation and non-invasive respiratory support, incidences of late-onset sepsis, patent ductus arteriosus, and duration of hospital stay were also significantly lower in vitamin A group. Serum retinol concentration improved significantly after VAS. No major adverse effect was observed.Conclusions: Early postnatal oral VAS was associated with better composite outcome of all-cause mortality and oxygen requirement without any major adverse effects.Clinical Trial Registration: Clinical Trials Registry of India (CTRI/2017/03/008131). What is Known: • Postnatal intramuscular vitamin A supplementation improves the survival, respiratory outcome and other morbidities in very low birth weight neonates without major adverse effects. • Limited studies on oral vitamin A supplementation did not document substantial benefits. What is New: • Early postnatal alternate-day oral vitamin A supplementation at the dose of 10,000 IU/dose for 28 days improves the composite outcome of death and oxygen requirement in very low birth weight neonates with respiratory distress • No major adverse effects were documented.

Background: In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status., Objective: We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification., Methods: After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 μmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography., Results: At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 μmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 μmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007)., Conclusions: In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731., (Copyright © American Society for Nutrition 2019.)

Background: Vitamin A deficiency (VAD) is of major public health significance; it is a risk factor for childhood deaths from diarrhoea and measles in low and middle-income countries and an important cause of preventable childhood blindness in low income countries. Vitamin A supplementation (VAS) is being implemented in many LMICs and high coverage reduces the prevalence of blinding corneal diseases in children. However, national estimates of coverage may not reveal any inequities in intra country coverage. The aim of this study is to assess factors influencing VAS coverage and also assess the relationship between VAS coverage and childhood corneal blindness in Nigeria., Methods: Data were collected from the Nigeria Demographic and Health Survey (NDHS) 2013 and the published literature on population-based childhood blindness surveys in Nigeria. The main outcome measure was the proportion of eligible children who received VAS in the last 6 months preceding the survey. Study factors comprised a range of socioeconomic, and individual factors. Data were analysed using STATA V.12.1 (Statcorp, Texas). To explore the effects of the independent variables on VAS coverage, bivariate and multivariate regression was done. Variables with p < 0.05 in the final multivariable model were considered as independent factors. For the population-based childhood blindness surveys, aggregated and disaggregated data were used. Causes of blindness were stratified into corneal blindness and 'others'. Odds ratios were computed to determine the odds of developing corneal blindness in each geopolitical region. Tests of significance were set at the 95% level., Results: The total VAS coverage in 2013 was 41.5%. VAS coverage was inequitable. Children with very educated mothers (OR 3.27 p < 0.001), from the south-south region (OR 2.38 p < 0.001) or in the highest wealth quintile (OR 2.81 p < 0.001) had higher odds of receiving VAS. The northwest zone had the lowest VAS coverage and the highest prevalence of corneal blindness., Conclusion: Regional and socioeconomic inequities in VAS exist in Nigeria and these may have grave implications for the causes of childhood blindness. The development and implementation of context specific and effective strategies are needed to reduce these inequities in VAS.

Objective: Children from rural households are often deprived of adequate micronutrient intakes either from food or supplementation. The present study examines: (i) the determinants of households' micronutrient-rich food consumption; and (ii) the combined effect of vitamin A supplementation and micronutrient-rich food consumption on child stunting in households with different food allocation patterns., Design: Cross-sectional study. Households' micronutrient-rich food consumption frequency and vitamin A supplementation were used as a proxy measure for child micronutrient intakes. Intra-household food allocation patterns were assessed from caregivers' perception of the disparity in food distribution within the household. Descriptive statistics and logistic regression were employed in analysing the study's objectives., Setting: Rural communities in Kwara State, Nigeria.ParticipantsIncluded 419 children aged 6-59 months and 413 households., Results: Owning small livestock and a refrigerator, knowledge of micronutrient-rich foods and higher parental education had strong associations with households' micronutrient-rich food consumption. Children from households that consumed micronutrient-rich foods and received more diverse diets were less likely to experience stunting. The combined effect of micronutrient-rich food consumption and vitamin A supplementation was stronger on the likelihood of stunting reduction than the separate effect of each., Conclusions: Assets ownership, human capital and knowledge of micronutrient-rich foods improve consumption of micronutrient-rich foods among the study population. Micronutrient supplementation to children with poor access to micronutrient-rich foods may not substantially enhance child growth unless reinforced through consumption of micronutrient-rich foods. Fruit and vegetable gardening, livestock holdings and nutrition education to parents should be integral parts of community nutrition programming.

Background: Vitamin A deficiency (VAD) is one of the most prevalent micronutrient deficiencies in the world. About 2% of all deaths among children under five years of age (U-5) are attributable to VAD. Currently evidence-based knowledge is grossly lacking about the factors associated with low coverage of VAS., Objective: This study aims to determine the factors affecting low coverage of the vitamin A supplementation program among the young children admitted to a diarrheal hospital., Methods: We extracted data from the Diarrhoeal Diseases Surveillance System (DDSS) on children aged 12-59 months admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, from 1996 to 2014. A logistic regression model was constructed to identify the factors that were significantly associated with non-compliance to vitamin A supplementation (VAS). Strength of association was determined by calculating adjusted odds ratios (aORs) and their 95% confidence intervals., Results: A total of 8649 children were enrolled and comprised the analyzable sample. Their mean ± SD age was 25.2 ± 12.8 months and 40% were female. Around 68% of them had received VAS in the previous 6 months. In the logistic regression analysis, older (>24 months) children (aOR: 1.38; 95% CI: 1.24-1.53), having an illiterate mother (aOR: 1.43; 95% CI: 1.27-1.64), having an illiterate father (aOR: 1.3; 95% CI: 1.16-1.50), coming from the two lowest wealth quintiles (aOR:1.13; 95% CI: 1.02-1.27), with an average monthly household income <10,000 BDT, (1 USD = 60 BDT) and children who had not received the measles vaccine (aOR: 1.87; 95% CI: 1.63-2.19) were more likely not to have received VAS in the preceding six months. We also observed an increase in coverage of VAS from 61% to 76% over the last 18 years (p < 0.001)., Conclusions: Non-compliance to VAS was found to be associated with older children, parents without formal schooling, family with greater poverty, low family income, and lack of measles vaccination. Specific programmatic approaches including prioritizing vulnerable children may enhance vitamin A coverage.

Anemia is a worldwide public health problem that can be related to many causes, including vitamin A deficiency. The aim of this study was to assess and estimate the effect of vitamin A supplementation (VAS) on iron status biomarkers and anemia in humans. Six databases, including Cochrane, EMBASE, LILACS, Pubmed, Scopus and Web of Science, were searched for clinical trials and cohort studies that investigated the effect of vitamin A supplementation alone on iron status and anemia, without time-restriction. The search yielded 23 eligible studies, 21 clinical trials and 2 cohort studies, with children, teenagers, pregnant or lactating women. The meta-analysis of the clinical trials showed that VAS reduces the risk of anemia by 26% and raises hemoglobin levels, compared to non-treated group, independent of the life stage. VAS did not alter the prevalence of iron deficiency among the clinical trials conducted with children and teenagers (RR 0.82, 95% CI 0.60 to 1.12, p = 0.204), whereas a significant increase in serum ferritin levels was observed in trials conducted with pregnant and lactating women (WMD 6.61 μg/L; 95% CI 6.00 to 7.21 μg/L; p < 0.001). Therefore, vitamin A supplementation alone may reduce the risk of anemia, by improving hemoglobin and ferritin levels in individuals with low serum retinol levels.

Vitamin A deficiency (VAD) among 1-5 yr old children is reported to be widely prevalent in Southeast Asia and some parts of Africa. It is the leading cause of preventable blindness in young children in the low-income countries in the world. Children even with milder signs of VAD have higher risk of morbidity and mortality. Inadequate dietary intakes of vitamin A with poor bioavailability associated with frequent infections are the primary contributory factors. Currently available approaches to control VAD are ensuring adequate intakes of vitamin A in daily diets, fortification of foods consumed regularly particularly among the low-income communities and periodic administration of massive dose of vitamin A supported by public health interventions and reinforced by behaviour change communication. Under the National Programme in India, six monthly administration of mega dose of vitamin A to 6-59 month old children has been implemented since 1970, to prevent particularly blindness due to VAD and control hypovitaminosis A. Despite inadequate coverage and poor implementation of the programme, blindness due to VAD in children has almost disappeared, though subclinical VAD is still widely prevalent. Based on the results of meta-analysis of eight trials, which indicated that vitamin A supplementation to children aged 6-59 months reduced child mortality rates by about 23 per cent, the World Health Organization made a strong recommendation that in areas with VAD as a public health problem, vitamin A supplementation should be given to infants and children of 6-59 months of age as a public health intervention to reduce child morbidity and improve child survival. At present, in India, there is a need for change in policy with respect to the national programme to opt for targeted instead of universal distribution. However, NITI (National Institution for Transforming India) Aayog, which formulates policies and provides technical support to the Government of India, recommends strengthening of the National Programme for control of VAD through six monthly vitamin A supplementation along with health interventions. Eventually, the goal is to implement food based and horticulture-based interventions harmonizing with public health measures, food fortification and capacity building of functionaries for elimination of VAD., Competing Interests: None

The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.

High-dose vitamin A supplementation (VAS) may affect mortality to infectious diseases in a sex-differential manner. Here, we analysed the long-term immunological effects of neonatal vitamin A supplementation (NVAS) in 247 children, who had been randomly allocated to 50 000 or 25 000 IU vitamin A (15mg and 7·5mg retinol equivalents, respectively) or placebo at birth. At 4-6 months of age, we assessed bacille Calmette-Guérin (BCG) scarification, and we analysed in vitro responses of TNF-α, IL-5, IL-10, IL-13 and IFN-γ in whole blood stimulations to phytohaemagglutinin (PHA), purified protein derivative (PPD), tetanus toxoid and lipopolysaccharide. There were no differences between the two doses of NVAS, and thus they were analysed combined as NVAS (any dose) v. placebo. All analyses were performed unstratified and by sex. NVAS increased the chance of having a scar after BCG vaccination in females (NVAS v. placebo: 96 v. 71 %, proportion ratio: 1·24; 95 % CI 1·09, 1·42), but not in males (P for interaction=0·012). NVAS was associated with significant sex-differential effects on the pro- to anti-inflammatory cytokine ratios (TNF-α:IL-10) to PPD, tetanus toxoid and medium alone, which were increased in females but decreased in males. In addition, IL-17 responses tended to be increased in NVAS v. placebo recipients in males but not in females, significantly so for the PHA stimulation. The study corroborates sex-differential effects of VAS on the immune system, emphasising the importance of analysing VAS effects by sex.

Objective: To compare administrative coverage data with results from household coverage surveys for vitamin A supplementation (VAS) and deworming campaigns conducted during 2010-2015 in 12 African countries., Methods: Paired t-tests examined differences between administrative and survey coverage for 52 VAS and 34 deworming dyads. Independent t-tests measured VAS and deworming coverage differences between data sources for door-to-door and fixed-site delivery strategies and VAS coverage differences between 6- to 11-month and 12- to 59-month age group., Results: For VAS, administrative coverage was higher than survey estimates in 47 of 52 (90%) campaign rounds, with a mean difference of 16.1% (95% CI: 9.5-22.7; P < 0.001). For deworming, administrative coverage exceeded survey estimates in 31 of 34 (91%) comparisons, with a mean difference of 29.8% (95% CI: 16.9-42.6; P < 0.001). Mean ± SD differences in coverage between administrative and survey data were 12.2% ± 22.5% for the door-to-door delivery strategy and 25.9% ± 24.7% for the fixed-site model (P = 0.06). For deworming, mean ± SD differences in coverage between data sources were 28.1% ± 43.5% and 33.1% ± 17.9% for door-to-door and fixed-site distribution, respectively (P = 0.64). VAS administrative coverage was higher than survey estimates in 37 of 49 (76%) comparisons for the 6- to 11-month age group and 45 of 48 (94%) comparisons for the 12- to 59-month age group., Conclusion: Reliance on health facility data alone for calculating VAS and deworming coverage may mask low coverage and prevent measures to improve programmes. Countries should periodically validate administrative coverage estimates with population-based methods., (© 2017 John Wiley & Sons Ltd.)

Background: Vitamin A (VA; retinol) supplementation is used to reduce child mortality in countries with high rates of malnutrition. Existing research suggests that neonates (<1 mo old) may have a limited capacity to store VA in organs other than the liver; however, knowledge about VA distribution and kinetics in individual, nonhepatic organs is limited. Objective: We examined retinol uptake and turnover in nonhepatic organs, including skin, brain, and adipose tissue, in neonatal rats without and after VA supplementation. Design: Sprague-Dawley neonatal rats ( n = 104) were nursed by mothers fed a VA-marginal diet (0.35 mg retinol/kg diet) and treated on postnatal day 4 with an oral dose of either VA (6 μg retinyl palmitate/g body weight) or canola oil (control), both containing 1.8 μCi of [ 3 H]retinol. Subsequently, pups ( n = 4 · group -1 · time -1 ) were killed at 13 different times from 30 min to 24 d after dosing. The fractional and absolute transfer of chylomicron retinyl esters (CM-REs), retinol bound to retinol-binding protein (RBP-ROH), and total retinol were estimated in WinSAAM software. Results: VA supplementation redirected the flow of CM-REs from peripheral to central organs and accumulated mainly in the liver. The RBP-ROH released from the liver was acquired mainly by the peripheral tissues but not retained efficiently, causing repeated recycling of retinol between plasma and tissues (541 compared with 5 times in the supplemented group and control group, respectively) and its rapid turnover in all organs, except the brain and white adipose tissue. Retinol stores in the liver lasted for ∼2 wk before being gradually transferred to other organs. Conclusions: VA supplementation administered in a single high dose during the first month after birth is readily acquired but not retained efficiently in peripheral tissues of neonatal rats, suggesting that a more frequent, lower-dose supplementation may be necessary to maintain steady VA concentrations in rapidly developing neonatal tissues., (© 2017 American Society for Nutrition.)

Objective: Using data from the national micronutrients survey 2011-2012, the present study explored the status of subclinical vitamin A nutrition and the underlying determinants in the Bangladeshi population., Design: A nationwide cross-sectional study. Settings The survey covered 150 clusters; fifty in each of rural, urban and slum strata., Subjects: Three population groups: (i) pre-school age children (6-59 months; PSAC); (ii) school age children (6-14 years; SAC); and (iii) non-pregnant non-lactating women (15-49 years; NPNLW)., Results: National prevalence of subclinical vitamin A deficiency was 20·5, 20·8 and 5·3 % in PSAC, SAC and NPNLW, respectively. Slum populations had higher prevalence compared with urban (PSAC: 38·1 v. 21·2 %, P0·05 for differences in β between <3 months v. 3-6 months, 6-9 months and 9-12 months)., Conclusions: Prevalence of subclinical vitamin A deficiency was high in children in Bangladesh. Intakes of animal-source foods and leafy vegetables were associated with higher and lower retinol status, respectively. Increased food diversity through animal-source foods is required.

Background: Despite evidence for the benefits of vitamin A supplementation (VAS) among children 6 to 59 months of age, the feasibility of introduction and potential benefit of VAS in the neonatal period in public health programmes is uncertain., Objective: The primary objective was to evaluate the feasibility and effectiveness of early neonatal VAS (single dose of 50 000 international units within 48-72 hours after birth) delivered through the public sector Lady Health Worker (LHW) programme in rural Pakistan and to document its association with a reduction in mortality at 6 months of age., Methods: A community-based, cluster randomised, placebo-controlled trial was undertaken in two districts of rural Pakistan. LHWs dispensed vitamin A/placebo in identical capsules to newborn infants within 48-72 hours of birth. Follow-up visits were undertaken at 1 week of age and every 4 weeks thereafter until 6 months of age., Results: Of a total of 15 433 consecutive pregnancies among eligible women of reproductive age, 13 225 pregnancies were registered, 12 218 live births identified and 11 028 newborn infants reached by LHWs. Of these, 5380 (49%) received neonatal VAS and 5648 (51%) placebo. The LHWs successfully delivered the capsules to 79% of newborns within 72 hours of birth with no significant adverse effects. Although the proportion of days observed with symptoms of fever, diarrhoea or rapid breathing were lower with neonatal VAS, these differences were not statistically significant. Mortality rates in the two groups were comparable at 6 months of age., Conclusions: While our study demonstrated that neonatal VAS was safe and could be feasibly delivered by LHWs in Pakistan as part of their early postnatal visits, the overall lack of benefit on neonatal and 6-month morbidity and mortality in our population suggests the need for further evaluation of this intervention in populations at risk., Trial Registration Number: ClinicalTrials.gov NCT00674089., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Vitamin A (VA; retinol) supplementation is recommended for children aged >6 mo in countries with high rates of malnutrition, but the distribution and retention of VA in body tissues have not been extensively explored., Objective: We sought to determine the distribution and retention of VA in tissues of neonatal rats raised under VA-marginal conditions., Methods: Sprague-Dawley neonatal rats (n = 104; 63 males) nursed by mothers fed a VA-marginal diet (0.35 mg retinol equivalents/kg diet) were randomized and treated on postnatal day 4 with an oral dose of either VA (6 μg retinyl palmitate/g body weight) or canola oil as control. Pups (n = 4/group) were killed at 13 time points from 30 min to 24 d after dose administration. The total retinol concentration and mass were determined in all collected organs., Results: In the control group, plasma VA was marginal (0.8 μmol/L), whereas liver VA was deficient (<70 nmol/g). Nonetheless, the liver contained most (∼76%) of the total VA mass in the body, whereas extrahepatic nondigestive organs together contained ∼13%. White adipose tissue (WAT), which was nearly absent before postnatal day 12, contained only ∼1%. In VA-supplemented neonates, the mean total retinol concentrations in all organs were significantly greater than in control pups. However, this increase lasted for only ∼1 d in most extrahepatic tissues, with the exception of WAT, in which it lasted 18 d., Conclusions: Extrahepatic organs in neonatal rats raised under VA-marginal conditions store relatively little VA, and the scarcity of adipose tissue may predispose neonates to a low-VA status. The effect of VA supplementation on VA content in most extrahepatic organs is transient. A more frequent supplementation along with other nutritional interventions may be necessary for maintaining a steady supply of retinol to the rapidly developing extrahepatic organs., Competing Interests: 2 Author disclosures: JK Hodges, L Tan, MH Green, and AC Ross, no conflicts of interest., (© 2016 American Society for Nutrition.)

Unlabelled: Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570)., Conclusion: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.

As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP ≥ 5 mg/l (28 v. 12%; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95% CI 1·44, 10·90) but not in males (GMR 0·44; 95% CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.

Objectives: The aim of this study was to assess the protective effects of vitamin A in a rat model of colitis to elucidate a possible mechanism of action., Methods: Male rats were fed for 21 d with either a normal diet or high vitamin A diet (5000 IU/d). On day 22, colitis was induced with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats were sacrificed after 24 h and colonic tissue was removed for evaluation., Results: Morphologically, in the supplemented group preservation of tissue architecture, no vasculitis or necroses were detected. Biochemically, decreased myeloperoxidase activity and protection of the mitochondria as evaluated by preserving tissue oxygen consumption, mitochondrial DNA, and expression of cytochrome c, was observed. Vitamin A supplementation also increased the levels of nuclear respiratory factor (NFR)-1 and mitochondrial transcription factor-A (TFAM) in normal colon tissue and in colon tissue under inflammatory conditions., Conclusion: The results indicate that tissue damage in colitis is accompanied by the arrest of mitochondrial respiration, loss of mitochondrial DNA, and the expression of mitochondrial proteins. Vitamin A effectively protects colon mitochondria by upregulation of mitochondrial transcription factors, NFR-1 and TFAM, and prevents inflammatory and necrotic changes in colitis. Vitamin A is therefore a potential therapeutic agent in inflammatory bowel disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There is limited data on proportion of Bitot's spots (BS), which could reappear after receiving mega dose of Vitamin A (MDVA), and their complete resolution. A prospective, community-based, cohort study with 12 months follow-up was conducted among children (1-5 years) with BS at a district from North India. On diagnosis, 200,000 IU of vitamin A was administered on the same day, then after 4 weeks and subsequently after 6 months. Out of 262 children with BS, 157 (59.9%, 95% CI: 54.1-65.9) children had shown resolution of BS after the MDVA supplementation. Out of 157 children, 97 (61.8%, 95% CI: 54.2-69.4) had reappearance of BS after complete resolution. Kaplan-Meir analysis found that median duration of reappearance of BS was 5 months (95% CI: 3.8-6.2) after their complete resolution. The reappearance of BS after administration of two MDVA within 12 months suggests that children with possibly adequate serum retinol level status may have reappearance of BS., (© The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A critical role for vitamin A (VA) in development is well established, but still relatively little is known about whole-body VA metabolism in early postnatal life. Recently, methods of mathematical modeling have begun to shed light on retinol kinetics in the postnatal growth period and on the effect of retinoid supplementation on retinol kinetics. Comparison of kinetic parameters from tracer studies in neonatal rats with those previously determined in models of VA metabolism in the adult suggests both similarities and differences in the relative transfer rates of plasma retinol to extrahepatic tissues, resulting in similarities and differences in kinetic parameters and inferences about physiologic processes. Similarities between neonatal and adult models include the capacity for efficient digestion and absorption of VA; characteristics of a high-response system; extensive retinol recycling among liver, plasma, and extrahepatic tissues; and comparable VA disposal rates. Differences between neonatal and adult models include that, in neonates, retinol turnover is faster and retinol recycling is much more extensive; there is a greater role for extrahepatic tissues in the uptake of chylomicron VA; and the intestine plays an important role in chylomicron VA uptake, especially in neonatal rats treated with a supplement containing VA. In summary, retinol kinetic modeling in the neonatal rat has provided a first view of whole-body VA metabolism in this age group and suggests that VA kinetics in neonatal rats differs in many ways from that in adults, perhaps reflecting an adaption to the lower VA concentration found in neonates compared with adults., (© 2015 American Society for Nutrition.)

Background: In May 2012, the twice-yearly Maternal and Child Health Week (MCHW) integrated vitamin A supplementation (VAS) and supplementary measles vaccination to reach all children 6-59 months in Sierra Leone. Following the MCHW, a post event coverage survey was conducted to validate VAS coverage and assess adverse events following immunization., Methods: Using the WHO Expanded Program on Immunization sampling methodology, 30 clusters were randomly selected using population proportionate to size sampling. Fourteen caregivers of children 6-59 months were interviewed per cluster for precision of ±5%. Responses were collected via mobile phones using EpiSurveyor., Results: Overall VAS and measles coverage was 91.9% and 91.6%, respectively, with no significant differences by age group, sex, religion or occupation. Major reasons given for not receiving VAS and measles vaccination were not knowing about the MCHW or being out of the area. Significantly more mild adverse events (fever, pain at injection site) were reported via the post event coverage survey (29.1%) than MCHW (0.01%) (p<0.0001)., Conclusion: The MCHW reached >90% of children in Sierra Leone with equitable coverage. Increased reporting of mild adverse events during the survey may be attributed to delayed onset after measles vaccination and/or direct inquiry from enumerators. Even mild adverse events following immunization requires strengthened reporting during and after vaccination campaigns., (© The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To characterize the coverage of India's national vitamin A supplementation (VAS) programme and document its performance in reaching children in the districts with higher concentration of poor households (2006-2011)., Design: Analysis of VAS programme coverage data collated and collected using standardized bottom-up procedures, data from India's Office of the Registrar General and Census Commissioner, and data from India's District Level Household Survey to compute exposure (poverty) and outcome (full VAS coverage) variables., Setting: Seven Indian states with the highest burden of mortality in children (74 % of all deaths among under-5s in the country in 2006)., Subjects: Children 6-59 months old., Results: Between 2006 and 2011, the mean full VAS coverage (two VAS doses per child per year) in these seven states increased from 44·7 % to 67·3 % while the number of districts with high (≥80 %) full VAS coverage increased from twenty-four (9·4 %) to 131 (51·4 %). The highest increases in full VAS coverage figures were recorded in the districts with the highest concentration of poor households. The estimated number of poor children (i.e. children living in households classified as poor) who did not receive two VAS doses annually decreased from 8·5 million in 2006 to 5·1 million in 2011 (40·3 % decrease); 2·5 million (49·1 %) of these children lived in the districts with the lowest proportion of poor households., Conclusions: Despite significant improvements in VAS, a large number of Indian children are not benefitting yet from this life-protecting intervention, particularly among those who are potentially the most vulnerable. Future programme action needs to give priority to sub-district level units - blocks and villages - with higher concentrations of poor households.

Background: The World Health Organization recommends vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age based on the assumption that it reduces mortality by 24%. The policy has never been evaluated in randomized controlled trials for its effect on overall mortality. We conducted a randomized double-blind trial to evaluate the effect of VAS with vaccines., Methods: We randomized children aged 6 to 23 months 1:1 to VAS (100000 IU if aged 6-11 months, 200000 IU if aged 12-23 months) or placebo at vaccination contacts in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards models overall, and by gender and vaccine., Results: Between August 2007 and November 2010, 7587 children were enrolled. Within 6 months of follow-up 80 nonaccident deaths occurred (VAS: 38; placebo: 42). The mortality rate ratio (MRR) comparing VAS versus placebo recipients was 0.91 (95% confidence interval 0.59-1.41) and differed significantly between boys (MRR 1.92 [0.98-3.75]) and girls (MRR 0.45 [0.24-0.87]) (P = .003 for interaction between VAS and gender). At enrollment, 42% (3161/7587) received live measles vaccine, 29% (2154/7587) received inactivated diphtheria-tetanus-pertussis-containing vaccines, and 21% (1610/7587) received both live and inactivated vaccines. The effect of VAS did not differ by vaccine group., Conclusions: This is the first randomized controlled trial to assess the effect of the policy on overall mortality. VAS had no overall effect, but the effect differed significantly by gender. More trials to ensure an optimal evidence-based vitamin A policy are warranted., (Copyright © 2014 by the American Academy of Pediatrics.)

Background: Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood., Methods: In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy., Results: Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71; 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42; 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88; 1.26-6.58), especially in those who received simultaneous BCG (5.99; 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45; 1.20-4.96)., Conclusions: There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy., Study Registration: Clinicaltrials.gov NCT 01420705., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Vitamin A supplementation (VAS) is recommended to prevent bronchopulmonary dysplasia (BPD). Our objective was to evaluate the effect of VAS on vitamin A (VA) status. We hypothesized that VAS would improve VA status in extremely low birth weight (ELBW) infants., Materials and Methods: Retrospective chart review of infants 1 year before and after initiation of VAS (5000 IU 3 times a week intramuscularly [IM]; total 12 doses). Linear regression was used to model impact of VAS on VA status (retinol level and retinol/retinol binding protein [RBP] ratio). Models were adjusted for time and generalized estimating equations were used to account for intraindividual correlation., Results: Sixty-seven infants (mean gestational age 26 ± 2 weeks; mean body weight 803 ± 142 g) were included; 35 received VAS and 32 did not (no-VAS). Both groups had similar baseline characteristics. Infants who received VAS had mean retinol levels that were 9.0 mcg/dL (95% confidence interval [CI], 4.9-13.2; P < .001) higher and mean retinol/RBP ratios that were 0.21 (95% CI, 0.07-0.36; P = .005) higher than the no-VAS group. Retinol and retinol/RBP ratio increased with time (P < .001). Fewer infants in the VAS group had VA deficiency (retinol/RBP ratios <0.7) compared with the no-VAS group. Culture-positive sepsis was more common in the VAS group (48% vs 12%; P = .002)., Conclusions: VA status in ELBW infants was improved and maintained over the first month of life with IM VAS. Because of concerns for potential risks of repeated injections, further studies are indicated to evaluate the optimal mode of VA delivery in preterm infants.

Abstract Background In low- and middle-income countries routine vitamin A supplementation (VAS) is a key strategy for reducing vitamin A deficiency and mortality and morbidity of preschool children. However, in Ethiopia, there is paucity of evidence regarding the level and determinants of the uptake of the supplement. This study was designed to assess the coverage and predictors of VAS among preschool children in Humbo district, Southern Ethiopia. Methods A cross-sectional study was conducted in April 2016. A total of 840 mothers/caregivers having children 6–59 months of age were selected using multistage cluster sampling technique from six rural villages implementing routine VAS program. Data were collected using interviewer administered questionnaire. Possible predictors considered in the study include distance from the nearby health facility, household socio-economic status, type of the household (model vs non-model), maternal access to health education on VAS, and knowledge on vitamin A and VAS. Multivariable logistic regression analysis was performed to identify predictors of uptake of VAS. The outputs are presented using adjusted odds ratio (AOR) with the respective 95% confidence interval (CI). Results The coverage of VAS was 75.0% (95% CI: 72.1–77.9). Better knowledge of mothers about the importance of the supplement (AOR: 1.49, 1.02–2.17), obtaining VAS related information from frontline community health workers (AOR: 1.51, 1.34–2.72) than health professionals and being from households in the “rich” wealth tertile (AOR: 1.80, 95% CI: 1.07–3.03) were positively associated with uptake VAS. Conclusion The VAS coverage of the area was approaching the expected national target of 80%. However, the uptake can be enhanced though awareness creation and improving socio-economic status of the community.

Given that combined vitamin A (VA) and retinoic acid (RA) supplementation stimulated the intestinal uptake of plasma retinyl esters in neonatal rats, we administrated an RA dose as a pretreatment before VA supplementation to investigate the distinct effect of RA on intestinal VA kinetics. On postnatal days (P) 2 and 3, half of the pups received an oral dose of RA (RA group), while the remaining received canola oil as the control (CN). On P4, after receiving an oral dose of 3H-labeled VA, pups were euthanized at selected times (n = 4–6/treatment/time) and intestine was collected. In both CN and RA groups, intestinal VA mass increased dramatically after VA supplementation; however, RA-pretreated pups had relatively higher VA levels from 10 h and accumulated 30% more VA over the 30-h study. Labeled VA rapidly peaked in the intestine of CN pups and then declined from 13 h, while a continuous increase was observed in the RA group, with a second peak at 10 h and nearly twice the accumulation of 3H-labeled VA compared to CN. Our findings indicate that RA pretreatment may stimulate the influx of supplemental VA into the intestine, and the increased VA accumulation suggests a potential VA storage capacity in neonatal intestine.

Objective: Vitamin A is involved in maintenance of gut mucosal integrity and normal immune function. However, it is unclear whether these functions of vitamin A have any beneficial effects in patients undergoing hematopoietic stem cell transplantation (HSCT). In this study, we aimed to examine the potential protective effect of vitamin A supplementation on gastrointestinal (GI) mucosal integrity in HSCT recipients using plasma citrulline as a surrogate marker of intestinal integrity. Results: We performed a quasi-randomized trial in 30 pediatric patients undergoing HSCT. Half (n = 15) of the patients received a single high dose of vitamin A (200,000 IU) before the conditioning regimen was given, and half (n = 15) did not. Clinical data of patients who developed post-transplant complications were recorded for 60 days after HSCT. There were no significant differences in mean plasma citrulline levels on day 7 after HSCT between the treatment and control groups (5.8 vs. 5.9 µmol/L, respectively). The incidence of mucositis and other complications were not different between the two groups within 60 days of HSCT. Vitamin A supplementation prior to HSCT in pediatric patients had no clinical benefit in protecting GI mucosal integrity. [ABSTRACT FROM AUTHOR]

Background: Randomised trials have shown that early Bacille Calmette-Guérin (BCG) vaccine reduces overall neonatal and infant mortality. However, no study has examined how BCG affects growth. We investigated the effect on infant growth of early BCG vaccine given to low-birth-weight (LBW) infants.Methods: Two-thousand three hundred forty-three LBW infants were randomly allocated 1:1 to "early BCG" (intervention group) or "late BCG" (current practice). Furthermore, a subgroup (N = 1717) were included in a two-by-two randomised trial in which they were additionally randomised 1:1 to vitamin A supplementation (VAS) or placebo. Anthropometric measurements were obtained 2, 6, and 12 months after enrolment.Results: Overall there was no effect of early BCG on growth in the first year of life. The effect of early BCG on weight and mid-upper-arm circumference at 2 months tended to be beneficial among girls but not among boys (interaction between "early BCG" and sex: weight p = 0.03 and MUAC p = 0.04). This beneficial effect among girls was particularly seen among the largest infants weighing 2.0 kg or more at inclusion.Conclusion: Though BCG vaccination is not recommended to be given to LBW infants at birth in Guinea-Bissau, early BCG had no negative effect on infant growth and may have had a beneficial effect for girls.Trial Registration Number: ClinicalTrials.gov (NCT00146302). [ABSTRACT FROM AUTHOR]