Association of Vitamin A and D Deficiencies with Infectious Outcomes in Children Undergoing Intensive Induction Therapy for Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy. STUDY DESIGN: We conducted an institutional review board-approved, retrospective cohort study of children with newly diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models. RESULTS: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17%, respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR], 1.7; P = .0072), clinically documented infection (aHR, 1.73; P = .025), and likely bacterial infection (aHR, 1.86; P = .008). Conversely, vitamin A deficiency was associated solely with a lower risk of sepsis (aHR, 0.19; P = .027). CONCLUSIONS: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect.

Vitamin A Deficiency Disturbs Ret Expression and Induces Urinary Tract Developmental Abnormalities in Mice.

INTRODUCTION: Moderate vitamin A levels during pregnancy are strongly related to normal embryonic development in both animal models and population studies. Abnormal development of urinary tract system is linked to either an excess or a shortage of vitamin A. The relationships among maternal vitamin A deficiency prior to conception, moderate vitamin A supplementation during pregnancy, and abnormal urinary system development in offspring are unclear. METHODS: By creating preconception and preconception + pregnancy vitamin A insufficiency mouse models, we investigated whether moderate vitamin A treatment during pregnancy may reduce the prevalence of CAKUT and increase distant vitamin A levels in offspring, as well as any potential pathways involved. RESULTS: We effectively established a prepregnancy vitamin A-deficient mouse model by providing a particular diet with or without vitamin A for 4 weeks. The offspring of the hypovitaminosis A model group presented a greater proportion of neonatal urinary tract developmental malformations. Abnormalities in ureteral bud emergence and key molecules during renal development, such as p-Plcγ and Ret, may be the primary causes of offspring development of CAKUT as a result of mothers' hypovitaminosis A. Normal vitamin A diets, on the other hand, may help mitigate the teratogenic consequences of prepregnancy hypovitaminosis A, as well as defects produced by ureteral budding and major molecular changes. CONCLUSION: In contrast, the administration of normal vitamin A feeds during pregnancy may ameliorate the teratogenic effects of prepregnancy hypovitaminosis A to a certain extent and may also ameliorate the abnormalities associated with ureteral budding and key molecular changes.

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

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

Case of persistent corneal epithelial damage after cataract surgery leading to diagnosis of vitamin A deficiency.

PURPOSE: To report our findings of reduced full-field electroretinograms (ff-ERGs) and abnormal optical coherence tomographic (OCT) images in a patient with poor visual acuity after cataract surgery who was eventually diagnosed with vitamin A deficiency (VAD). METHODS: This was a clinical study of a patient who complained of blurred vision after cataract surgery. To determine the cause of the reduced vision, we recorded full-field electroretinograms (ff-ERGs) to determine the scotopic and photopic status of the retina. We also performed optical coherence tomography to assess the changes in the retinal structure. Serological tests were performed. RESULTS: A 74-year-old man presented with persistent corneal epithelial damages and reduced vision that developed after conventional cataract surgery. OCT showed an interrupted ellipsoid zone, and fundus autofluorescence (FAF) showed a severe hypofluorescence in the retina of the left eye. The scotopic ff-ERGs were severely reduced, and the photopic ff-ERGs were mildly reduced. Serological examinations revealed a vitamin A concentration < 7 IU/dL (normal, 97-316 IU/dL). Based on these findings, we diagnosed the patient with VAD and started treatment with oral vitamin A supplements. After three months, his visual acuity, ff-ERGs, and OCT findings recovered to normal levels. The amplitudes and implicit times of the RETeval flicker ERGs increased to be within the normal range, and the hypofluorescence of the left eye disappeared. The length of the photoreceptor outer segments increased after the vitamin A supplementation. CONCLUSION: Our findings indicate that the ERGs are helpful for diagnosing patients with VAD associated with persistent corneal epithelial damages.

Gut microbiota, vitamin A deficiency and autism spectrum disorder: an interconnected trio - a systematic review.

Accumulating evidence proves that children with autism have gastrointestinal problems. However, a significant difference in gut microbiota (GM) exists between autistic and non-autistic children. These changes in the GM may stem from several factors. Recently, researchers focused on nutritional factors, especially vitamin deficiency. Thus, our systematic review investigates the connections among autism, GM alterations, and vitamin A deficiency (VAD), by analyzing studies sourced from PubMed and Embase databases spanning from 2010 to 2022. Adhering to PRISMA guidelines, we meticulously selected 19 pertinent studies that established links between autism and GM changes or between autism and VAD. Our findings uniformly point to significant alterations in the GM of individuals with autism, indicating these changes as promising biomarkers for the disorder. Despite the consistent association of GM alterations with autism, our analysis revealed no notable differences in GM composition between individuals with autism and those experiencing VAD. This suggests that VAD, especially when encountered early in life, might play a role in the onset of autism. Furthermore, our review underscores a distinct correlation between reduced levels of retinoic acid in children with autism, a disparity that could relate to the severity of autism symptoms. The implications of our findings are twofold: they not only reinforce the significance of GM alterations as potential diagnostic markers but also spotlight the critical need for further research into nutritional interventions. Specifically, vitamin A supplementation emerges as a promising avenue for alleviating autism symptoms, warranting deeper investigation into its therapeutic potential.

Urethral keratosis caused by vitamin A deficiency: two case reports.

BACKGROUND: Dysuria in children can have various etiologies, including ureteric stones, phimosis, congenital obstructive posterior urethral membrane, and neurogenic bladders. However, there have been no reports of vitamin A deficiency (VAD) causing dysuria due to urethral keratosis. Here, we report two cases of urethral keratosis caused by a VAD. CASE PRESENTATION: An 8-year-old boy (Patient 1) and a 6-year-old boy (Patient 2) presented with multiple episodes of dysuria and epididymitis. Both patients had intellectual disabilities and autism, which prevented voiding cystourethrography. Therefore, the patient was admitted for cystoscopy under general anesthesia. Cystoscopy revealed urethral diastolic dysfunction and a large amount of desquamated epithelium obstructing the urethra in both patients, causing urinary obstruction and dysuria. Catheterization was repeated; however, the symptoms recurred after catheter removal. Although the cause of recurrent urinary obstruction could not be initially identified, an ophthalmologist found Bitot's spots and suggested the possibility of a VAD. Serum vitamin A levels were extremely low in both patients, leading to the diagnosis of urethral keratosis due to VAD. VAD can be attributed to an unbalanced diet resulting from intellectual disabilities or autism. Vitamin A replacement therapy improved both the urethral symptoms and cystoscopic findings. CONCLUSION: Dysuria due to VAD is extremely rare, and urethral keratosis as a cause of dysuria is likely the first report of its kind worldwide. VAD may develop due to an unbalanced diet in patients with intellectual disabilities or autism. Therefore, it is essential to consider VAD as a potential cause of dysuria in patients with intellectual disabilities and autism.

Pre- and Postnatal Vitamin A Deficiency Impairs Motor Skills without a Consistent Effect on Trace Mineral Status in Young Mice.

Pregnant women and children are vulnerable to vitamin A deficiency (VAD), which is often compounded by concurrent deficiencies in other micronutrients, particularly iron and zinc, in developing countries. The study investigated the effects of early-life VAD on motor and cognitive development and trace mineral status in a mouse model. C57BL/6J dams were fed either a vitamin A-adequate (VR) or -deficient (VD) diet across two consecutive gestations and lactations. Offspring from both gestations (G1 and G2) continued the same diets until 6 or 9 weeks of age. Behavioral assays were conducted to evaluate motor coordination, grip strength, spatial cognition, and anxiety. Hepatic trace minerals were analyzed. A VD diet depleted hepatic retinoids and reduced plasma retinol across all ages and gestations. Retracted rear legs and abnormal gait were the most common clinical manifestations observed in VD offspring from both gestations at 9 weeks. Poor performance on the Rotarod test further confirmed their motor dysfunction. VAD didn't affect hemoglobin levels and had no consistent effect on hepatic trace mineral concentrations. These findings highlight the critical role of vitamin A in motor development. There was no clear evidence that VAD alters the risk of iron deficiency anemia or trace minerals.

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

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

Integrated analysis of murine cornea identifies JAK/STAT signaling pathway upregulated specifically in female Vitamin A Deficient mice.

The Keratoconus (KC) is a corneal ectatic disease with unclear etiology. There are increasing studies that reported its association with a variety of inflammatory mechanisms. Vitamin A(VA) is an important nutrient related to inflammation regulation, and its deficiency may cause abnormalities of the ocular surface. However, the proportion of Vitamin A deficiency(VAD) was found surprisingly high among KC patients in our clinic practice. The aim of this study is to explore the effects of VAD on the transcriptome of corneas with the help of the VAD murine model and transcriptomics techniques. Blood samples of KC patients and non-KC controls (NC) were collected and the serum VA concentrations were measured and analyzed. A total of 52 NC and 39 KC were enrolled and the comparison of serum VA showed that the proportion of VAD in KC patients was 48.7% versus 1.9% in NC group. The further analysis of gender differences showed the proportion of VAD in female KC was 88.9% versus 36.7% in KC male patients. To explore the influence of VAD on cornea, the VAD mice fed with VAD diets were used. The RNA sequencing was employed to compare the corneal transcriptomic characteristics between the VAD female mice, NC female mice, VAD male mice and NC male mice. The transcriptome analysis revealed that the upregulated differential genes were mainly enriched in the immune response related pathways in VAD female mice versus NC female mice, especially the genes of JAK-STAT signaling pathway. The downstream molecules of JAK-STAT pathway were also significant after corneal mechanical scratching in female VAD mice. While, the differential genes between VAD male mice and NC male mice were estrogen signaling pathway instead of JAK-STAT pathway. This study indicates that VAD affects the transcriptomics of murine cornea with gender differences, which specifically affects the inflammatory status of the female murine cornea.

High prevalence of malnutrition and vitamin A deficiency among schoolchildren of rural areas in Malaysia using a multi-school assessment approach.

Childhood malnutrition is known as a public health concern globally. The present study aims to assess the anthropometry and blood biochemical status of rural primary schoolchildren in Malaysia. A total of 776 children (7-11 years old) from ten rural primary schools from five states were included in this study. Nutritional outcomes were assessed based on sex, age group and school categories among the children (median age: 9 years (P25:8, P75:10)). The overall prevalence of malnutrition was 53·4 %. Vitamin A deficiency (VAD) was recorded at 20·6 and 39·8 % based on retinol and retinol-binding protein (RBP) levels, respectively. Anaemia, iron deficiency (ID), iron-deficiency anaemia (IDA) and elevated inflammation were found at 14·9, 17·9, 9·1 and 11·5 %, respectively. Malnutrition, VAD, anaemia, ID, IDA and elevated inflammation were more prevalent among Orang Asli (OA) schoolchildren compared with Non-Orang Asli schoolchildren. Higher occurrences of VAD and anaemia were also found among children aged <10 years. Retinol, RBP, α-carotene, ferritin and haemoglobin levels were lower among undernourished children. Besides, overweight/obese children exhibited a higher level of high-sensitivity C-reactive protein. Multivariate analysis demonstrated that OA school children (adjusted OR (AOR): 6·1; 95 % CI 4·1, 9·0) and IDA (AOR: 3·6; 95 % CI 1·9, 6·6) were associated with stunting among this population. The present study revealed that malnutrition, micronutrient deficiencies and anaemia are prevalent among rural primary schoolchildren in Malaysia, especially those from OA schools and younger age children (<10 years). Hence, more appropriate and targeted measures are needed to improve the nutritional status of these children.

Prevalence of vitamin A deficiency in women of childbearing age in Brazil: a systematic review and meta-analysis.

Vitamin A is an essential micronutrient, especially during pregnancy. We aimed to assess the prevalence of vitamin A deficiency in Brazilian women of childbearing age. We conducted a systematic review with meta-analysis of studies that assessed vitamin A deficiency in women of childbearing age following the registered protocol (CRD42020171856). Independent peer researchers selected the studies retrieved from MEDLINE, Embase, Scopus and other sources. Data from the eligible studies were extracted in pairs and assessed for methodological quality. The prevalence of vitamin A deficiency (< 0·70 µmol/l or <0·20 µg/dl) and 95 % CI was combined by meta-analysis, and heterogeneity was estimated by I2. Out of 3610 screened records, thirty-two studies were included, which assessed 12 577 women from 1965 to 2017, mostly in maternity hospitals. Main limitations of the studies were in sample frame (30/32) and sampling method (29/32). Deficiency occurred in 13 % (95 % CI 9·4, 17·2 %; I² = 97 %) of all women and was higher in pregnant women (16·1 %; 95 % CI 5·6, 30·6 %; I² = 98 %) than non-pregnant women (12·3 %; 95 % CI 8·4, 16·8 %; I² = 96 %). The prevalence increased according to the decade, from 9·5 % (95 % CI 1·9­21·6 %; I² = 98 %) up to 1990, 10·8 % (95 % CI 7·9, 14·2 %; I² = 86 %) in the 2000s and 17·8 % (95 % CI 8·7, 29·0 %; I² = 98 %) in the 2010s. Over 10 % of Brazilian women in childbearing age were deficient in vitamin A. Higher prevalence was observed in pregnant women, and deficiency seemed to be increasing over the decades. Low representativeness of the studies, mainly based on convenience sampling that included pregnant, postpartum, lactating and non-pregnant women, as well as high heterogeneity, limits the findings.

Electrophysiological assessment of nutritional optic neuropathy: a case report.

PURPOSE: To report an unexpectedly asymmetric, progressive nutritional optic neuropathy associated with vitamin A deficient optic canal hyperostosis in a 15-year-old female with a long history of a restricted diet. METHODS: We performed comprehensive ophthalmic assessments in a fifteen-year-old female with a long history of restricted eating who presented with suspected nutritional optic neuropathy, predominantly affecting the right eye vision. RESULTS: A review of computerised tomography and magnetic resonance imaging revealed bilateral optic canal hyperostosis likely associated with vitamin A deficiency. Electrodiagnostic tests and optical coherence tomography provided structure-function evidence of bilateral retinal ganglion cell dysfunction and notably revealed severe loss of temporal fibres in the left eye which showed cecocentral scotoma but normal visual acuity. Although selective damage of the papillomacular bundle has been well-documented in nutritional and toxic optic neuropathies, compressive optic canal hyperostosis secondary to nutritional deficiency has been rarely reported. CONCLUSIONS: Nutritional deficiencies are increasing in high-income countries and may be linked to the rise of gastrointestinal disorders, strict vegan and vegetarian diets and avoidant restrictive food intake disorder (ARFID) associated with conditions such as depression and autism spectrum syndrome (ASD). Our findings highlight the value of electrodiagnostic testing alongside imaging in complex nutritional optic neuropathies to help monitor, guide treatment and preserve remaining sight in a child.

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

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

Vitamin A Deficiency, COVID-19, and Rhino-Orbital Mucormycosis (Black Fungus): An Analytical Perspective.

Mucormycosis is a rare but serious opportunistic fungal disease characterized by rhino-orbito-cerebral and pulmonary involvement. It is mainly seen in people with secondary immunosuppression, isolated vitamin A deficiency, measles, and AIDS patients. It showed a rise during the second wave of the COVID-19 epidemic in the spring of 2021 in India, especially in diabetic COVID-19 patients. Vitamin A deficiency is known to cause nutritional immunodeficiency and hence leading the way to increased opportunistic fungal, bacterial, and viral infections. In the eye, it causes keratitis, night blindness, xerophthalmia, conjunctivitis, Bitot spots, keratomalacia, and retinopathy. It also causes decreased tear secretion and deterioration of the anatomical/physiological defense barrier of the eye. The negative impact of vitamin A deficiency has been previously demonstrated in measles, AIDS, and COVID-19. We think that mucormycosis in COVID-19 might be rendered by vitamin A deficiency and that vitamin A supplementation may have preventive and therapeutic values against mucormycosis and other ocular symptoms associated with COVID-19. However, any vitamin A treatment regimen needs to be based on laboratory and clinical data and supervised by medical professionals.

Kinetics of thermal degradation of carotenoids related to potential of mixture of wheat, cassava and sweet potato flours in baking products.

BACKGROUND: The consumption of foods such as sweet potato and cassava with high levels of carotenoids is a possible solution to reduce vitamin A deficiency. In this study, we evaluated the kinetics of thermal degradation of carotenoids. The content of carotenoids was quantified by high-performance liquid chromatography, first in fresh material, then in flour and finally in bakery products using mixtures of wheat, sweet potato and cassava. The degree of acceptance of the bakery products by children was also assessed through a sensory acceptance test. RESULTS: The study found that the degradation of carotenoid compounds in sweet potato followed first-order kinetics and fitted the Arrhenius equation with correlations of R2 > 0.9. The retention rates of all-trans-ß-carotene were 77%, 56% and 48% at cooking temperatures of 75, 85 and 95 °C respectively, during a cooking time of 20 min. The concentrations of all-trans-ß-carotene, after baking, for bread, cookies and cake were 15, 19 and 14 µg g-1 db, respectively. In a sensory acceptance test carried out in a school, 47.6% of the boys and 79.2% of the girls rated the cookies made from a mixture of cassava, sweet potato and wheat flour with the indicator I like it a lot. CONCLUSION: The content of carotenoid compounds was reduced by exposure to high temperatures and long cooking times. The combinations of cooking time and temperature which minimized degradation of all-trans-ß-carotene occurred at 75 °C-20 min and 95 °C-10 min. All-trans-ß-carotene retentions for bread, cookies and cake were 25%, 15% and 11% respectively. The mixture of wheat, sweet potato and cassava flour can be considered in the development of cookies with positive contributions of all-trans-ß-carotenes and with a good acceptance by children between 9 and 13 years old. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Vitamin a supplementation during pregnancy in shaping child growth outcomes: A meta-analysis.

Abnormal fetal growth increases risks of childhood health complications. Vitamin A supplementation (VAS) is highly accessible, but literature inconsistency regarding effects of maternal VAS on fetal and childhood growth outcomes exists, deterring pregnant women from VAS during pregnancy. This meta-analysis aimed to analyze effects of vitamin A only or vitamin A + co-intervention during pregnancy in healthy mothers (MH) or with complications (MC, night blindness and HIV positive) on perinatal growth outcomes, also assess VAS dose impacts. The Cochrane Library, PubMed, ScienceDirect, Scopus, Embase and Web of Science databases were searched from inception to July 15, 2021. We covered subgroup analyses, including VAS in MH or MC within randomized controlled trial (RCT) or observational studies (OS). Fifty-five studies were included in this meta-analysis (426,098 pregnancies). Vitamin A decreased risk of preterm birth by 9% in MH-RCT (P < 0.001), by 62% in MH-OS (P = 0.029), by 10% in MC-RCT (P = 0.089); decreased LBW by 24% in MC-RCT (P = 0.032); increased neonatal weight in MC-RCT (SMD 0.96; P = 0.051). Besides, vitamin A + co-intervention decreased risks of preterm by 18% in MH-OS (P = 0.021); LBW by 25% in MH-OS (P < 0.001); by 32% in MC-RCT (P = 0.006); decreased neonatal defects by 33% in MH-OS (P = 0.064); decreased anemia by 25% in MH-OS (P = 0.0003); increased neonatal weight in MH-OS (SMD 0.51; P = 0.014); and increased neonatal length in MH-OS (SMD 1.83; P = 0.013). Meta-regression of VAS dose with individual outcomes was not significant, and no side effects were observed for VAS doses up to 4000 mcg (RAE/d). Regardless of maternal health conditions, VAS during pregnancy can safely and effectively improve fetal development and neonatal health even in mothers without VAD.

Prevalence of vitamin A deficiency and dietary inadequacy in Indian school-age children and adolescents.

PURPOSE: There are no representative estimates of vitamin A deficiency (VAD) and risk of vitamin A (VA) dietary inadequacy in Indian children and adolescents. To evaluate, from national surveys, the prevalence of VAD measured by serum retinol concentrations (< 0.7 µmol/L or < 20 µg/dL), and the risk of VA dietary inadequacy and excess intake beyond the tolerable upper limit (TUL). METHODS: National and state-level VAD prevalence adjusted for inflammation was estimated in school-age children (5-9 years: 10,298) and adolescents (10-19 years: 9824) from the Comprehensive National Nutrition Survey (CNNS 2016-18). The risk of dietary inadequacy against age-specific average VA requirements, and excess intake against the TUL, was assessed from the National Sample Survey Office (NSSO 2014) data. RESULTS: Serum retinol concentrations increased with age (5-19 years) in both genders and were significantly lower in school-age children (1.02 µmol/L, CI: 1.01-1.03) compared to adolescents (1.13 µmol/L, CI 1.12-1.15). The inflammation-adjusted prevalence of VAD in school-age children and adolescents was 19.3% (CI 18.8-19.9) and 14.4% (CI 13.9-14.9) respectively, and this was > 20% in seven and four states for children and adolescents, respectively. The prevalence of VAD was significantly higher among children with lower socio-economic status. The risk of dietary VA inadequacy, from the NSSO survey, was 69 and 78% in children and adolescents, respectively. This risk reduced to 6 and 17% with VA fortified oil and milk intake, while the proportion of intakes exceeding the TUL became 6 and 0.5% in children and adolescents, respectively. CONCLUSIONS: The national prevalence of VAD in school-age children and adolescents in India was just less than 20%. The risk of dietary VA deficiency is likely to decline substantially with VA fortified food intake, but a risk of excessive intake also begins to appear; therefore, a careful assessment of the risk of hypervitaminosis A is required at these ages.

Documentation of recovery from vitamin A deficiency-related retinopathy via multimodal imaging and electroretinogram testing.

PURPOSE: To describe vitamin A deficiency using multimodal functional visual assessments and imaging. METHODS/CASE: A 50-year-old female with past medical history significant for Roux-en-Y gastric bypass surgery complained of nyctalopia and "yellowing" of vision. RESULTS: Vitamin A levels were noted to be < 0.06 mg/L (normal 0.3-0.12 mg/L). Fundus examination was notable for peripheral yellow punctate lesions, superior arcuate defects on HVF 30-2 testing, an indistinct ellipsoid zone on SD-OCT, and absent rod responses and severely reduced amplitudes for the cone photoreceptors on full-field ERG. These findings resolved with initiation of parenteral vitamin A supplementation. CONCLUSION: This report documents an example of vitamin A deficiency in the developed world. We aim to provide a comprehensive description of clinical examination and multimodal imaging findings before and after vitamin supplementation for vitamin A deficiency.

Triad of hypovitaminosis A, hyperostosis, and optic neuropathy in males with autism spectrum disorders.

BACKGROUND: Persons with autism spectrum disorder (ASD) can have restrictive diets due to stereotyped behaviors. These restrictive diets can manifest with nutritional deficiencies, such as Vitamin A deficiency. The most frequent manifestation of hypovitaminosis A is vision loss secondary to xerophthalmia. Here the authors report six cases of males with a clinical triad of hypovitaminosis A, cranial hyperostosis, and optic neuropathy. METHODS: A retrospective case series of six males (ages 5-17 years old) with ASD who presented with several weeks of vision loss and nyctalopia were reviewed. RESULTS: All six subjects were found to have a barely detectable Vitamin A level (<10 mcg/dL). Three of the six cases had elevated protein (45.9-74.0 mg/dL) in their CSF. MRI imaging demonstrated mild T2 enhancement of bilateral optic nerve sheaths and CT showed diffuse skull hypertrophy. Upon further history collection, all subjects had a very limited food repertoire with major nutritional deficiencies. Subjects were prescribed high doses of vitamin A and most were noted to have improved vision at follow-up, and all had resolution of imaging abnormalities on repeat scans. No common genetic variant was identified in patients with expanded genetic sequencing. CONCLUSIONS: We present a clinical triad of hypovitaminosis A, cranial hyperostosis, and optic neuropathy in six males with ASD. Skull abnormalities and xeropthalmia likely contributed to the development of vision loss.

Development and evaluating the biopotency of ready to eat liver meat balls in fighting anaemia and vitamin A deficiency, improving selected nutritional biochemical indicators and promoting the cognitive function among mildly anaemic Egyptian children aged 3-9 years.

OBJECTIVE: Ready to eat fried liver meat balls (LMB) were developed to fight anaemia and vitamin A deficiency and promote cognitive function. DESIGN: Randomised controlled trial consisting of two arms: control group with no supplement and LMB group receiving LMB supplement three times a week for 90 d. Criteria of evaluations included dietary assessment, anthropometric measurements, laboratory investigations and cognitive function by Wechsler test. SETTING: Kinder Garten and primary school in Urban Giza. PARTICIPANTS: Sixty boys and girls aging 3-9 years. RESULTS: The LMB supplement contributed to significant increases in the intakes of high bioavailable Fe and vitamin A in the diets of all children. Initial overall prevalence of mild and moderate anaemia was 43 %, which disappeared completely from all children aging < 72 months and from 88 % of children ≥ 72 months after the 90 d dietary intervention with the LMB. Faecal systemic immune globulin A, urinary hydroxyproline index and urinary iodine excretion increased significantly (P < 0·05) only after the dietary intervention with the LMB supplement for 90 d. The standard scores of verbal and non-verbal cognitive function tests (Δ day 90-day 0) increased significantly (P < 0·05) among the LMB group compared with the respective changes observed among the control group. The increase in height-for-age Z score and blood Hb were good predictors for improvement in cognitive function. CONCLUSION: LMB supplement is effective sustainable nutritious biotherapeutic food in fighting hidden hunger and promoting the cognitive function.