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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Immunity and Disease Prevention Research » Research » Publications at this Location » Publication #348598
Title: High-Dose, neonatal vitamin A supplementation transiently decreases thymic function in early infancy

Author
item AHMAD, SHAIKH - International Centre For Diarrhoeal Disease Research
item RAQIB, RUBHANA - International Centre For Diarrhoeal Disease Research
item HUDA, NAZMUL - University Of California, Davis
item ALAM, MOHAMMAD - International Centre For Diarrhoeal Disease Research
item MONIRUJJAMAN, MOHAMMAD - International Centre For Diarrhoeal Disease Research
item AKHTER, TASLIMA - International Centre For Diarrhoeal Disease Research
item WAGATSUMA, YUKIKO - University Of Tsukuba
item QADRI, FIRDAUSI - International Centre For Diarrhoeal Disease Research
item TANUMIHARDJO, SHERRY - University Of Wisconsin
item ZEROFSKY, MELISSA - University Of San Francisco
item Stephensen, Charles

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2019
Publication Date: 1/1/2020
Citation: Ahmad, S., Raqib, R., Huda, N.M., Alam, M.J., Monirujjaman, M., Akhter, T., Wagatsuma, Y., Qadri, F., Tanumihardjo, S., Zerofsky, M.S., Stephensen, C.B. 2020. High-Dose, neonatal vitamin A supplementation transiently decreases thymic function in early infancy. Journal of Nutrition. Volume 150, Issue 1, January 2020, Pages 176–183. https://doi.org/10.1093/jn/nxz193.
DOI: https://doi.org/10.1093/jn/nxz193

Interpretive Summary: Infants above 6 m of age in regions with a public health-level risk of vitamin A deficiency benefit from high-dose vitamin A supplementation. Such supplements reduce mortality from common infectious diseases, presumably by preventing immune-deficiency that results from vitamin A deficiency. In the present study, ARS scientists working with colleagues in Bangladesh conducted a randomized, controlled intervention trial. Infants were randomized to receive a single, 50,000 IU dose of vitamin A (VA) or placebo (PL) within 48 h of birth. This study tested the hypothesis that VA supplementation of infants at risk of VA deficiency would improve thymic function as the thymus is the source of T-cells, which are key components of the adaptive immune response to infection or to vaccination. Outcomes included (1) thymic index (TI), a measure of thymus size; (2) CD4 T-helper cell concentrations in peripheral blood; and (3) T-cell receptor excision circle (TREC) levels. TREC levels in peripheral blood are an index T-cells recently released from the thymus. The study was conducted at a public maternity hospital in Dhaka, Bangladesh. A total of 306 infants (50% male) were enrolled. Study visits occurred between birth and 15 w of age, and again at 2 y of age. VA treatment had a transient, negative effect on thymic index, decreasing the average size in the VA group relative to the PL by 8.3% at 6 w of age. VA treatment also decreased CD4 T-cell concentrations in a subgroup of infants, girls below the median birthweight; concentrations were 11.2% lower at 6 w, 8.4% lower at 15 w and 19% lower at 2y. VA did not significantly affect TREC concentrations. Additionally, independent of treatment, sex differences were seen in these measures of thymic function, with girls having a smaller TI at all ages, higher CD4 T-cell concentrations early in infancy, and higher TREC levels at 6 w, but lower levels at 2 y. In summary, this study found that VA supplementation at birth had a modest, negative effect on thymic function, which does not support the use of VA supplementation to newborn infants to improve immune function in order to decrease mortality from infectious diseases.

Technical Abstract: Intervention: Infants were randomized to receive a single, 50,000 IU dose of vitamin A (VA) or placebo (PL) within 48 h of birth. Main Outcomes and Measures: This study tested the hypothesis that VA supplementation of infants at risk of VA deficiency would improve thymic function. Outcomes included (1) thymic index (TI); (2) CD4 T-cell concentrations; and (3) T-cell receptor excision circle (TREC) levels. Results: The study was conducted at a public maternity hospital in Dhaka, Bangladesh. A total of 306 infants (50% male) were enrolled. Study visits occurred between birth and 15 w and at 2 y of age (n = 265). VA had a transient, negative effect on TI, decreasing the VA mean (7.45 ± 2.33 cm2, n = 142) relative to the PL (8.12 ± 2.86 cm2, n = 147) by 8.3% at 6 w of age (p = 0.0497). VA treatment interacted with sex and birthweight (p = 0.034) to decrease CD4 T-cell concentrations in girls below the median birthweight (p = 0.020); 11.2% lower at 6 w (VA, 2,490 ± 750 cells/µL, n = 36; PL, 2,695 ± 700 cells/µL, n = 34), 8.4% lower at 15 w (VA, 2,653 ± 813 cells/µL, n = 34; PL, 3,105 ± 870 cells/µL, n = 37) and 19% lower at 2y (VA, 1,411 ± 737 cells/µL, n = 31; PL, 1,807 ± 1,012 cells/µL, n = 35). VA did not significantly affect TREC concentrations. Additionally, independent of treatment, sex differences were seen in these measures of thymic function, with girls having a smaller TI at all ages, higher CD4 T-cell concentrations early in infancy, and higher TREC levels at 6 w, but lower levels at 2 y. Conclusions and Relevance: High-dose VA treatment from 6-59 m of age is recommended to decrease mortality for infants at risk of VA deficiency. The same strategy has been evaluated at birth but survival benefits are inconsistent. This study found that VA supplementation at birth had a modest, negative effect on thymic function, which does not support this approach to improve infant survival. Trial Registration: ClinicalTrials.gov Identifiers NCT01583972 and NCT02027610.