Dataset Information

High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy.

ABSTRACT:

Background

Vitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function.

Objective

Our objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median).

Methods

Three hundred and six infants were randomly assigned to 50,000 IU vitamin A (VA) or placebo (PL) within 48 h of birth. Primary outcomes were measured at multiple ages and included 1) thymic index (TI) at 1, 6, 10, and 15 wk; 2) T-cell receptor excision circles (TREC), an index of thymic output of naïve T cells; and 3) total/naïve T cells in peripheral blood at 6 wk, 15 wk, and 2 y. A mixed linear model for repeated measures was used to assess group differences at each age and identify interactions with sex and birth weight.

Results

VAS did not significantly (P = 0.21) affect TI overall (i.e., at all ages) but decreased TI by 7.8% (P = 0.029) at 6 wk: adjusted TI means for the PL and VA groups at 1, 6, 10, and 15 wk were 4.09 compared with 3.80 cm2, 7.78 compared with 7.18 cm2, 8.11 compared with 7.84 cm2, and 7.91 compared with 7.97 cm2, respectively. VAS did not significantly (P = 0.25) affect TREC overall but decreased TREC by 19% (P = 0.029) at 15 wk: adjusted TREC means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 13.6 compared with 16.1 copies/pg DNA, 19.4 compared with 15.7 copies/pg DNA, and 11.8 compared with 10.0 copies/pg DNA, respectively. VAS did not significantly affect overall total (P = 0.10) or naïve (P = 0.092) T cells: adjusted naïve T-cell means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 3259 compared with 3109 cells/µL, 3771 compared with 3487 cells/µL, and 1976 compared with 1898 cells/µL, respectively.

Conclusion

In contrast to our hypothesis, VAS decreased thymic function early in infancy but health effects are presumably negligible owing to the transience and small magnitude of this effect. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.

SUBMITTER: Ahmad SM

PROVIDER: S-EPMC6946900 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy.

Ahmad Shaikh M SM Raqib Rubhana R Huda M Nazmul MN Alam Md J MJ Monirujjaman Md M Akhter Taslima T Wagatsuma Yukiko Y Qadri Firdausi F Zerofsky Melissa S MS Stephensen Charles B CB

The Journal of nutrition 20200101 1

<h4>Background</h4>Vitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function.<h4>Objective</h4>Our objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median).<h4>Methods</h4>Three hundred and six infants were random ...[more]

PMID: 31504694

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Project description:BackgroundVitamin A (VA) stores are low in early infancy and may impair development of the immune system.ObjectiveThis study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated.MethodsIn total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight.ResultsVAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y.ConclusionsNeonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.

Project description:BackgroundInfancy is a crucial period for establishing the intestinal microbiome. This process may be influenced by vitamin A (VA) status because VA affects intestinal immunity and epithelial integrity, factors that can, in turn, modulate microbiome development.ObjectivesThe aim of this study was to determine if neonatal VA supplementation (VAS) affected the abundance of Bifidobacterium, a beneficial commensal, or of Proteobacteria, a phylum containing enteric pathogens, in early (6-15 wk) or late (2 y) infancy. Secondary objectives were to determine if VAS affected the abundance of other bacterial taxa, and to determine if VA status assessed by measuring plasma retinol was associated with bacterial abundance.MethodsThree hundred and six Bangladeshi infants were randomized by sex and birthweight status (above/below median) to receive 1 VA dose (50,000 IU) or placebo within 48 h of birth. Relative abundance at the genus level and above was assessed by 16S rRNA gene sequencing. A terminal restriction fragment-length polymorphism assay was used to identify Bifidobacterium species and subspecies at 6 wk.ResultsLinear regression showed that Bifidobacterium abundance in early infancy was lower in boys (median, 1st/3rd quartiles; 0.67, 0.52/0.78) than girls (0.73, 0.60/0.80; P = 0.003) but that boys receiving VAS (0.69, 0.55/0.78) had higher abundance than boys receiving placebo (0.65, 0.44/0.77; P = 0.039). However this difference was not seen in girls (VAS 0.71, 0.54/0.80; placebo 0.75, 0.63/0.81; P = 0.25). VAS did not affect Proteobacteria abundance. Sex-specific associations were also seen for VA status, including positive associations of plasma retinol with Actinobacteria (the phylum containing Bifidobacterium) and Akkermansia, another commensal with possible health benefits, for girls in late infancy.ConclusionsBetter VA status in infancy may influence health both in infancy and later in life by promoting the establishment of a healthy microbiota. This postulated effect of VA may differ between boys and girls. This trial was registered at clinicaltrials.gov as NCT02027610.

Project description:Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo.The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrollment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation.The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.

Project description:Background: Neonatal vitamin A (VA) supplementation is being evaluated as a public health policy for preventing infant mortality, but inconsistencies in mortality trials demand mechanistic work to determine biological plausibility.Objectives: We investigated the absorption, distribution, and storage of single large oral VA doses administered shortly after birth.Methods: Fifty pregnant sows (Sus scrofas domesticas) were fed a VA-free diet. Male and female newborn piglets (n = 313) were orally administered 0, 25,000, 50,000, or 200,000 IU VA in oil within 12 h of birth when mean ± SD weight was 1.56 ± 0.25 kg. Blood was drawn to determine absorption and storage 0.5-240 h after administration. Metabolic and postnatal dose-timing substudies were performed. Liver, lung, kidney, spleen, and adrenal VA concentrations were determined 7-240 h after administration.Results: Serum retinol and retinyl ester concentrations responded to treatment (P < 0.0001); however, differences between groups disappeared by 96 h. Liver VA concentrations responded to treatment (P < 0.0001), which persisted for 240 h. Liver VA for control piglets at 10 d (mean ± SD: 0.05 ± 0.02 μmol/g) was ≤0.1 μmol/g (deficiency), whereas groups that received VA maintained concentrations >0.1 μmol/g. Extrahepatic tissue VA concentrations displayed treatment effects (P ≤ 0.0077); groups that received treatments had higher VA concentrations than controls at early time points. Lung, kidney, and spleen VA did not differ between groups by 96 h, whereas adrenal glands did not differ by 240 h. Body weight was affected by treatment (P = 0.0002); VA-deficient piglets weighed 23-29% more than all treated groups 240 h after administration.Conclusions: A high dose of VA administered to newborn piglets was well absorbed, appeared in serum primarily as retinyl esters, and was taken up dose-dependently in all tissues studied; however, enhancement did not persist in sera, lungs, kidneys, spleens, or adrenal glands. Short-term impacts of retinoid signaling on weight gain remain to be elucidated, and longer follow-up studies are needed.

Project description:BackgroundThymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutritional supplementation.MethodsThe Early Nutrition and Immune Development (ENID) Trial was a randomized 2?×?2?×?2 factorial, partially blinded trial of nutritional supplementation conducted in rural Gambia, West Africa. Pregnant women (N?=?875) were randomized to four intervention groups (iron-folate (standard care), multiple micronutrients, protein energy or protein energy + multiple micronutrients at 'booking' (mean gestational age at enrolment?=?13.6?weeks, range 8-20?weeks) until delivery. The iron-folate and multiple micronutrient arms were administered in tablet form and the protein energy arms as a lipid-based nutritional supplement. All intervention arms contained 60?mg iron and 400??g folic acid per daily dose. From 24 to 52?weeks of age, infants from all groups were randomized to receive a daily lipid-based nutritional supplement, with or without additional micronutrients. Thymic size was assessed by ultrasonography at 1, 8, 24 and 52?weeks of infant age, and a volume-related thymic index calculated. Detailed data on infant growth, feeding status and morbidity were collected.ResultsA total of 724 (82.7%) mother-infant pairs completed the trial to infant age 52?weeks. Thymic size in infancy was not significantly associated with maternal supplement group at any post-natal time point. Infants who received the daily LNS with additional micronutrients had a significantly larger thymic index at 52?weeks of age (equivalent to an 8.0% increase in thymic index [95% CI 2.89, 13.4], P?=?0.002). No interaction was observed between maternal and infant supplement groups.ConclusionsA micronutrient-fortified lipid-based supplement given in the latter half of infancy increased thymic size, a key mediator of immune function. Improving the micronutrient status of infants from populations with marginal micronutrient status may improve immune development and survival.Trial registrationISRCTN registry (controlled-trials.com) Identifier: ISRCTN49285450.

Project description:BACKGROUND:Heightened immune activation and exhaustion drive HIV disease progression and comorbidities. Vitamin D has pleiotropic immunomodulatory effects, but little is known about the effects of supplementation in HIV. Our study investigates changes in immune activation and exhaustion markers after 12 months of supplementation in virologically suppressed HIV-infected youth with vitamin D insufficiency. METHODS:This is a randomized, active-control, double-blind trial investigating with three different vitamin D3 doses (18,000 [standard/active-control dose], 60,000 [moderate dose] and 120,000 IU/month [high dose]) in 8-25-year-old HIV-infected youth on combination antiretroviral therapy with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations ?30 ng/ml. Only subjects (n=51) who maintained an undetectable HIV-1 RNA over the 12-month study period were included in this analysis. RESULTS:Baseline serum 25(OH)D concentrations and immune activation/exhaustion markers were not different between groups. By 12 months, 25(OH)D increased significantly within each dosing group with the greatest increase and most sustained concentrations ?30 ng/ml in the high-dose group. Overall, all measured markers decreased with CD4 activation (CD4+CD38+HLA-DR+), CD8 activation (CD8+CD38+HLA-DR+), CD4 exhaustion (CD4+CD38+HLA-DR+PD1+) and inflammatory monocytes (CD14+CD16+) reaching statistical significance. When analysed separately, there were no significant decreases in the moderate- or standard-dose groups, but CD4 and CD8 activation and inflammatory monocytes decreased significantly in the high-dose group. CONCLUSIONS:Vitamin D supplementation decreased markers of T-cell activation/exhaustion and monocyte activation in HIV-infected youth, with subjects given the highest dose (120,000 IU/month) showing the greatest decreases. These data suggest that high-dose vitamin D supplementation may attenuate immune activation and exhaustion, and serve as adjuvant therapy to antiretroviral therapy in HIV. ClinicalTrials.gov identifier: NCT01523496.

Dataset Information

High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy.

Background

Objective

Methods

Results

Conclusion

Publications

High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy.

Similar Datasets

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