Vitamins E and A increase the passing of the P-gp substrate ivermectin into the brain in mice.

This study aimed to determine the effect of administration of oral vitamins A and E at different doses on plasma and brain concentrations of ivermectin in mice. The study was carried out on 174 Swiss Albino male mice aged 8-10 weeks. After leaving six mice for method validation, the remaining mice were randomly divided into seven groups with equal numbers of animals. Mice received ivermectin (0.2 mg/kg, subcutaneous) alone and in combination with low (vitamin A: 4000 IU/kg; vitamin E: 35 mg/kg) and high (vitamin A: 30 000 IU/kg; vitamin E: 500 mg/kg) oral doses of vitamins A and E. The plasma and brain concentrations of ivermectin were measured using high-performance liquid chromatography-fluorescence detector. We determined that high doses of vitamins A and E and their combinations increased the passing ratio of ivermectin into the brain significantly. The high-dose vitamin E and the combination of high-concentration vitamins E and A significantly increased the plasma concentration of ivermectin (P < 0.05). The high-dose vitamins E and A and their high-dose combination increased the brain concentration of ivermectin by 3, 2, and 2.7 times, respectively. This research is the first in vivo study to determine the interaction between P-gp substrates and vitamins E and A.

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.

Might Routine Vitamin A Monitoring in Cystic Fibrosis Patients Reduce Virus-Mediated Lung Pathology?

Cystic fibrosis (CF) is an autosomal recessive gene disorder that affects tens of thousands of patients worldwide. Individuals with CF often succumb to progressive lung disease and respiratory failure following recurrent infections with bacteria. Viral infections can also damage the lungs and heighten the CF patient's susceptibility to bacterial infections and long-term sequelae. Vitamin A is a key nutrient important for immune health and epithelial cell integrity, but there is currently no consensus as to whether vitamin A should be monitored in CF patients. Here we evaluate previous literature and present results from a CF mouse model, showing that oral vitamin A supplements significantly reduce lung lesions that would otherwise persist for 5-6 weeks post-virus exposure. Based on these results, we encourage continued research and suggest that programs for the routine monitoring and regulation of vitamin A levels may help reduce virus-induced lung pathology in CF patients.

Excessive Vitamin A Supplementation Increased the Incidence of Acute Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

(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.

Effect of a dietary supplement on the reduction of lymphedema-progression in mouse tail-cut model.

OBJECTIVE: The aim of our study was to evaluate in vivo, in a mouse tail model of lymphedema, the effects of a dietary supplement, Garlive®, based on hydroxytyrosol from olive leaves, spermidine from rice seeds, hesperidin from citrus fruits and vitamin A. Hydroxytyrosol has anti-inflammatory, antioxidant and antimicrobial activities and inhibits leukotriene B4 generation; spermidine is able to inhibit the production of pro-inflammatory cytokines and mediators; hesperidin inhibits the secretion of pro-inflammatory cytokines: IFN-γ, IL-2, IL-4, IL-10; vitamin A deficiency was shown to induce inflammation and aggravate existing inflammatory states, whereas supplementation with vitamin A could ameliorate inflammation. MATERIALS AND METHODS: The active compounds were included in tablets: 250 mg of olive leaf extract titrated in 10% hydroxytyrosol, 200 mg of citrus fruits extract titrated in 60% hesperidin, 10 mg of rice (Oryza sativa) seeds extract titrated in 1% spermidine and 0.8 mg of vitamin A. Mice of an inbred group were randomly selected and divided in the control group and drug-treated group. The wound necessary for lymphedema generation was made on the tail of each mice 1 cm below the base of the trunk. RESULTS: After surgical intervention, there was a gradual increase in the circumference of both ends of the wound. The control group showed higher increase of tail volume than the drug-treated group. The differences in tail swelling between the control group and the drug-treated group were significantly different. The peak of swelling was anticipated to the 6th day in the drug-treated group, whereas in the control group the peak was reached later on. CONCLUSIONS: The tested drug prevented the induction of swelling from day 5th of wound creation and decreased the duration of swelling, favoring the wound healing.

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of ß-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

Cardio-protective and Anti-atherosclerosis Effect of Crocetin on Vitamin D3 and HFD-induced Atherosclerosis in Rats.

Cardiovascular disease (CVD) is a chronic disease and causes the highest rate of death globally. CVD-related deaths account for 80% of all deaths in low and middle-income countries, such as China. Crocetin (CT), a carotenoid phytoconstituent already confirm their anti-inflammatory and antioxidant effects in various diseases animal models. In the study, we make effort to access the cardio-protective effect of Crocetin against vitamin D3 and high fat induced atherosclerosis in rats and scrutinize the underlying mechanism. Sprague Dawley (SD) rats were used in this study and rats were divided into different groups and high fat diet and vitamin D was used for induction the atherosclerosis. The rats were received oral administration of crocetin (5, 10 and 15 mg/kg) and simvastatin (0.5 mg/kg) until 30 days. At the end of the experimental period, lipid, cardiac markers, anti-inflammatory, antioxidant, pro-inflammatory cytokines and atherogenic index were estimated. The mRNA expression of Intercellular adhesion molecule-1 (ICAM-1), Monocyte Chemoattractant Protein-1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) in aortic tissue of the atherosclerotic rats. Crocetin significantly reduced the aortic membrane thickness and platelet aggregation rates. Crocetin also dose-dependently reduced total cholesterol (TC), very low-density lipoprotein (VLDL), triacylglycerol (TG), low-density lipoprotein (LDL) and augmented the level of high-density lipoprotein (HDL) level. Additionally, Crocetin significantly (p < 0.001) abridged the level of malonaldehyde (MDA) and augmented the level of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione peroxidase (GPx). Furthermore, Crocetin significantly (p < 0.001) dose-dependently reduced the levels of pro-inflammatory cytokines and inflammatory mediators. Crocetin attenuated mRNA expression of VCAM-1, ICAM-1 and MCP-1. Crocetin had anti-atherosclerosis and cardio-protective effects on vitamin D3 and high fat induced atherosclerosis in rats through anti-inflammatory and antioxidant mechanisms.

Functional Cupcake for Preventing Vitamin A Deficiency and Correlated Anemia and Oxidative Stress.

<b>Background and Objective:</b> Vitamin A Deficiency (VAD) is a critical public health problem that affects the health of kids worldwide and may induce anemia and oxidative stress. The current study aimed to pre-clinically assess the effect of a cupcake, prepared to be served for primary school children, on vitamin A deficiency and related anemia and oxidative stress in rats. <b>Materials and Methods:</b> Flour of flash orange sweet potatoes, as a rich source of pro-vitamin A, was used to prepare the cupcake. The chemical composition, amino acids and sensory evaluation of the cupcake were done. The biological evaluation was carried out using 18 weaning rats in three groups (control group, vitamin A-deficient group and vitamin A-deficient group fed on a diet fortified with 20% of the prepared cupcake for two months). <b>Results:</b> The results indicated the high value of vitamin A in the prepared cupcake. Excellent sensory characteristics were noticed. Feeding on the VDA diet fortified with the prepared cupcake suppressed the reduction in Retinol-Binding Protein (RBP), hemoglobin and iron. Total Iron Binding Capacity (TIBC) increased in the VAD group. Also, feeding on the prepared cupcake suppressed the reduction in Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) and the elevation of Malondialdehyde (MDA). <b>Conclusion:</b> It can be suggested that the prepared cupcake is promising in preventing of vitamin A deficiency and related anemia and oxidative stress. Thus, the prepared cupcake may be efficient for children to prevent vitamin A deficiency.

Methodologies to measure the coverage of vitamin A supplementation: a systematic review.

Countries are increasingly transitioning from event-based vitamin A supplementation (VAS) distribution to delivery through routine health system contacts, shifting also to administrative, electronic-based monitoring tools, a process that brings certain limitations affecting the quality of administrative VAS coverage. At present, there is no standardised methodology for measuring the coverage of VAS delivered through routine health services. To address this gap, we conducted a systematic review of the literature to identify and recommend methods to measure VAS coverage, with the aim of providing guidance to countries on the collection of consistent data for planning, monitoring and evaluating VAS programmes integrated into routine health systems. We searched the PubMed®, Embase®, Scopus, Google Scholar and World Health Organization (WHO) Global Index Medicus databases for studies published from 1 January 2000 to 1 January 2021, reporting original data on VAS coverage and methodologies used for measurement. We screened 2371 original titles and abstracts, assessed twenty-seven full-text articles and ultimately included eighteen studies. All but two studies used a coverage cluster survey (CCS) design to measure VAS coverage, adapting the WHO Vaccination Coverage Cluster Surveys methodology, by modifying sample size and sampling parameters. Annual two-dose VAS coverage was reported from only four studies. Until electronic-based systems to collect and analyse VAS data are equipped to measure routine two-dose VAS coverage using administrative data, CCSs that comply with the 2018 WHO Vaccination Coverage Cluster Surveys Reference Manual represent the gold-standard method for effective VAS programme monitoring.

Assessment of Micronutrient Situation among Reproductive-Age Women (15-49) and Under-Five Children in Sudan.

BACKGROUND: Micronutrient malnutrition is a form of undernutrition that causes diseases, and this is mainly due to insufficient intake of nutrients in daily foods. The status of micronutrients for people in Sudan remains scarce, and information is limited. The aim of this study is to highlight the status of micronutrients among women of reproductive age (15-49 years of age) and their children in Sudan. METHODS: This manuscript is a quantitative descriptive study, based on the data from Sudan Micronutrient Survey (SMS); it is part of the second round of the Simple Spatial Survey Method (S3M II) in Sudan (a total of 93,882 households). RESULTS: The level of consumption of vitamin A-rich foods was found to be moderate at 67.36% for reproductive-age women and low at 23.44% for under-five children. Similarly, consumption rate of vitamin B-rich foods among reproductive-age women was 62.13%, and low for children at 11.02%. The consumption of iron-, calcium-, and zinc-rich foods was moderate among women (66.75%, 47.69%, 69.72%, respectively) and very low in children (12.28%, 17.62%, 14.99%, respectively). The iron deficiency prevalence was 47% in non-pregnant women, 58% in pregnant women, and 54% in children. The prevalence of anemia was 30% in non-pregnant women, 37% in pregnant women, and 48% in children. Generally, urinary iodine concentration was inadequate in lactating and non-pregnant women as well as in pregnant women. Most indicators of micronutrients in Sudan for children and women of reproductive age were highly significant. Sudan needs more efforts to create an enabling environment through legislation, policies, and strategies to strengthen the nutrition-sensitive and specific interventions and improving status of micronutrients among women and children, focusing on food fortification, food supplements, and counseling on micronutrients intake for mothers during antenatal and postnatal services as well as raising community awareness.

Impact of Maternal Daily Oral Low-Dose Vitamin A Supplementation on the Mother-Infant Pair: A Randomised Placebo-Controlled Trial in China.

BACKGROUND: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. METHODS: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D2), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. RESULTS: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. CONCLUSIONS: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.

Vitamin A in Children Hospitalized for Measles in a High-income Country.

BACKGROUND: Worldwide medical authorities recommend vitamin A supplementation for severe measles requiring hospitalization; however, evidence supporting its use in high-income countries is lacking. A nationwide vitamin A shortage reported in concomitance with a recent measles outbreak in Italy provided an opportunity to test the effectiveness of vitamin A in a high-income setting, approximating an unbiased allocation. METHODS: We conducted a prospective controlled cohort study involving children admitted for measles to a tertiary-care hospital in Southern Italy. The primary outcome was the duration of fever. Secondary outcomes included the length of hospitalization, rate of complications, need for antibiotic treatment and body temperature. RESULTS: A total of 108 inpatient children (36% female, median age 16.3 months) were enrolled; 36 received 2 doses of oil-based vitamin A according to age, and 72 matched controls received standard care. There were no significant differences between the study groups in the duration of fever (7.03 ± 2.67 vs. 6.82 ± 3.27, P = 0.72), length of hospitalization (median, 5.0 vs. 5.0 days, P = 0.50), maximum body temperature (median, 39°C in both groups, P = 0.23), rate of organ (69.4% vs. 63.9%, P = 0.72) and hematologic complications (41.7% vs. 59.7%, P = 0.12), or need for antibiotic treatment (66.7% vs. 61.1%, P = 0.72). Overall, vitamin A supplementation did not reduce the risk of any complications (relative risk, 1.33; 95% confidence intervals: 0.59-2.96). CONCLUSION: Vitamin A does not change the clinical course of measles infection or the rate of complications in children hospitalized in a high-income country. STUDY REGISTRATION NUMBER: EU PAS 31805.

Vitamin A and retinoic acid accelerate the attenuation of intestinal adaptability upon feeding induced by high-fat diet in mice.

With its unique cellular plasticity, the small intestinal mucosa exhibits efficient adaptability upon feeding. However, little is known about the effect of high-fat diet (HFD) feeding on this adaption and its underlying mechanism. Herein, we demonstrated that the cell proliferation ability, mitochondrial morphology, and global transcriptomic profile of the small intestine exhibited a prominent discrepancy between the fasted and refed state in mice, which were markedly attenuated by long-term HFD feeding. The retinol (Vitamin A, VA) metabolism pathway was dramatically affected by HFD feeding in the small intestine. Both VA and its active metabolite retinoic acid (RA), with the administration of lipid micelles, promoted the expression of genes involved in lipid absorption and suppressed the expression of genes involved in the cell proliferation of intestinal organoids. Via chip-qPCR and RT-qPCR, genes involved in lipid metabolism and cell proliferation were target genes of RARα/RXRα in small intestinal organoids treated with RA and lipid micelles. The role of VA in the in vivo attenuation of intestinal adaptability, in response to HFD, was evaluated. Mice were fed a normal chow diet, HFD, or HFD diet supplemented with additional 1.5-fold VA for 12 weeks. VA supplementation in HFD accelerated the attenuation of intestinal adaptability upon feeding induced by HFD, promoted lipid absorption gene expression, and increased body weight and serum cholesterol levels. In conclusion, the discrepancy of the small intestine between the fasted and refed state was dramatically attenuated by HFD feeding, in which VA and RA might play important roles.

Vitamin A supplementation ameliorates motor incoordination via modulating RORα in the cerebellum in a valproic acid-treated rat autism model with vitamin A deficiency.

Motor dysfunctions are common comorbidities among autism spectrum disorder (ASD) patients. Abnormal cerebellar development throughout critical periods may have an effect on motor functions and result in motor impairments. Vitamin A (VA) plays a crucial role in the developing process of the nervous system. The correlation of VA deficiency (VAD) and ASD with motor dysfunctions, however, is not clear. Therefore, we built rat models with different VA levels based on the valproic acid (VPA)-treated autism model. ASD rats with VAD showed aggravated motor coordination abnormalities, Purkinje cell loss and impaired dendritic arborization of Purkinje cells compared to ASD rats with normal VA levels (VA normal, VAN). Additionally, the expression levels of retinoid-related orphan receptor α (RORα) and retinoic acid receptor α (RARα) were lower in the cerebellum of ASD rats with VAD than in those of ASD rats with VAN. VA supplementation (VAS) effectively improved motor coordination and cerebellar Purkinje cell abnormalities in ASD rats with VAD. Furthermore, the results of chromatin immunoprecipitation (ChIP) assays confirmed that the enrichment of RARα was detected on the RORα promoter in the cerebellum and that VAS could upregulate the binding capacity of RARα for RORα promoters. These results showed that VAD in autism might result in cerebellar impairments and be a factor aggravating a subtype of ASD with motor comorbidities. The therapeutic effect of VAS on motor deficits and Purkinje neuron impairments in autism might be due to the regulation of RORα by RARα.

The Effect of Oral Vitamin A Supplementation on Chalazion in Young Children with Vitamin A Deficiency: A Pilot Study.

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.

Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial.

OBJECTIVE: To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk. STUDY DESIGN: We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant. RESULTS: As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups. CONCLUSIONS: Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01203488.

Vitamin A Fortification Quality Is High for Packaged and Branded Edible Oil but Low for Oil Sold in Unbranded, Loose Form: Findings from a Market Assessment in Bangladesh.

Although mandatory fortification of oil with vitamin A is efficacious, its effectiveness can be compromised by suboptimal compliance to standards. In this study, we assessed (1) the availability of oil brands across the eight divisions of Bangladesh, (2) fortification quality (the extent to which vitamin A content is aligned with fortification standards) of oil brands and producers and (3) the market volume represented by available edible oil types. We visited different retail outlets in rural and urban market hubs to ascertain available oil brands and bulk oil types and collected samples. We used high-performance liquid chromatography to quantify average vitamin A content and compared them to the national oil fortification standards. Among the 66 packaged brands analyzed, 26 (39%) were not fortified, and 40 (61%) were fortified, with 28 (42%) fortified above the standard vitamin A minimum. Among the 41 bulk oil type composites analyzed, 24 (59%) were not fortified, and 17 (41%) were fortified, with 14 (34%) fortified below and 3 (7%) fortified above the standard minimum. Vitamin A fortification is high for packaged and branded edible oil but low for oil sold in unbranded, loose form. As bulk oil makes up a large proportion of the oil market volume, this means the majority of the oil volume available to the population is either not (25%) or fortified below the standard requirement (39%). Regulatory inspections of producers selling bulk oil should be prioritized to support and incentivize the industry to make all oil traceable and fortified to standard.

Risk factors for measles deaths among children during a Nationwide measles outbreak - Romania, 2016-2018.

BACKGROUND: Case fatality ratio (CFR) among all age groups during the 2016-2018 measles outbreak in Romania was increased compared with previous outbreaks. To identify risk factors for measles death, we conducted a case-control study among infants and children hospitalized for measles. METHODS: National surveillance data were used to identify hospitalized cases of laboratory-confirmed or epidemiologically linked measles in infants and children aged < 59 months with rash onset from January 2016 to July 2018. We abstracted medical records of 50 fatal cases ("cases") and 250 non-fatal cases ("controls") matched by age, sex, district of residence, and urban/rural place of residence. We calculated univariable and multivariable matched odds ratios (OR) and 95% confidence intervals (CIs) for risk factors. RESULTS: Ninety-three percent of case-patients and controls had not received a valid dose of a measles-containing vaccine; only 5 % received Vitamin A supplementation once diagnosed with measles. In the univariable analysis, cases were more likely than controls to have had a healthcare-related exposure to measles manifesting as inpatient admission for pneumonia during the 7 to 21 day measles incubation period (OR: 3.0; 95% CI [1.2, 7.2]), to have had a history of malnutrition (OR: 3.4; 95% CI [1.1, 9.9]), and to have had pneumonia as a complication of measles (OR:7.1; 95% CI [2.0-24.8]). In the multivariable analysis, pneumonia as a measles complication remained a risk for death (OR: 7.1; 95% CI [1.4-35.3]). CONCLUSIONS: Implementing infection prevention and control practices, ensuring immunization of healthcare workers, and hospitalizing only severe measles cases may minimize the risk of nosocomial measles transmission. Implementing World Health Organization (WHO) recommendations for Vitamin A supplementation, improving immunization of children to prevent influenza, pneumococcal, and other bacterial respiratory diseases may decrease complications and deaths due to measles in Romania.

Vitamin A deficiency has declined in Malawi, but with evidence of elevated vitamin A in children.

BACKGROUND: Reduction of vitamin A deficiency (VAD) in Malawi coincided with introduction of vitamin A-fortified staple foods, alongside continued biannual high-dose vitamin A supplementation (VAS). OBJECTIVE: We describe coverage of vitamin A interventions and vitamin A status in the 2015-2016 Malawi Micronutrient Survey. METHODS: Food samples and biospecimens were collected within a representative household survey across 105 clusters. Retinol was measured using ultraviolet excitation fluorescence (sugar) and photometric determination (oil). Preschool children (PSC, aged 6-59 mo, n = 1102), school-age children (SAC, aged 5-14 y, n = 758), nonpregnant women (n = 752), and men (n = 219) were initially assessed for vitamin A status using retinol binding protein (RBP) and modified relative dose response (MRDR). Randomly selected fasted MRDR participants (n = 247) and nonfasted women and children (n = 293) were later assessed for serum retinol, retinyl esters, and carotenoids. Analyses accounted for complex survey design. RESULTS: We tested sugar and oil samples from 71.8% and 70.5% of the households (n = 2,112), respectively. All of the oil samples and all but one of the sugar samples had detectable vitamin A. National mean retinol sugar and oil contents were 6.1 ± 0.7 mg/kg and 6.6 ± 1.4 mg/kg, respectively. Receipt of VAS in the previous 6 mo was reported by 68.0% of PSC. VAD prevalence (RBP equivalent to <0.7µmol retinol/L) was 3.6% in PSC, and <1% in other groups. One woman and no children had MRDR ≥0.060 indicating VAD. Among fasted PSC and SAC, 18.0% (95% CI: 6.4, 29.6) and 18.8% (7.2, 30.5) had >5% of total serum vitamin A as retinyl esters, and 1.7% (0.0, 4.1) and 4.9% (0.0, 10.2) had >10% of total serum vitamin A as retinyl esters. Serum carotenoids indicated recent intake of vitamin A-rich fruits and vegetables. CONCLUSIONS: Near elimination of VAD in Malawi is a public health success story, but elevated levels of vitamin A among children suggests that vitamin A interventions may need modification.

Biofortified and fortified maize consumption reduces prevalence of low milk retinol, but does not increase vitamin A stores of breastfeeding Zambian infants with adequate reserves: a randomized controlled trial.

BACKGROUND: Replacement of conventional staples with biofortified or industrially fortified staples in household diets may increase maternal breast milk retinol content and vitamin A intakes from complementary foods, improving infant total body stores (TBS) of vitamin A. OBJECTIVES: To determine whether biofortified or industrially fortified maize consumption by Zambian women and their breastfeeding infants could improve milk retinol concentration and infant TBS. METHODS: We randomly assigned 255 lactating women and their 9-mo-old infants to a 90-d intervention providing 0 µg retinol equivalents (RE)/d as conventional maize or ∼315 µg RE/d to mothers and ∼55 µg RE/d to infants as provitamin A carotenoid-biofortified maize or retinyl palmitate-fortified maize. Outcomes were TBS, measured by retinol isotope dilution in infants (primary), and breast milk retinol, measured by HPLC in women (secondary). RESULTS: The intervention groups were comparable at baseline. Loss to follow-up was 10% (n = 230 mother-infant pairs). Women consumed 92% of the intended 287 g/d and infants consumed 82% of the intended 50 g/d maize. The baseline geometric mean (GM) milk retinol concentration was 1.57 µmol/L (95% CI: 1.45, 1.69 µmol/L), and 24% of women had milk retinol <1.05 µmol/L. While mean milk retinol did not change in the biofortified arm (ß: 0.11; 95% CI: -0.02, 0.24), the intervention reduced low milk retinol (RR: 0.42; 95% CI: 0.21, 0.85). Fortified maize increased mean milk retinol (ß: 0.17; 95% CI: 0.04, 0.30) and reduced the prevalence of low milk retinol (RR: 0.46; 95% CI: 0.25, 0.82). The baseline GM TBS was 178 µmol (95% CI: 166, 191 µmol). This increased by 24 µmol (± 136) over the 90-d intervention period, irrespective of treatment group. CONCLUSIONS: Both biofortified and fortified maize consumption improved milk retinol concentration. This did not translate into greater infant TBS, most likely due to adequate TBS at baseline. This trial was registered at clinicaltrials.gov as NCT02804490.