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Prenatal and childhood exposures are associated with thymulin concentrations in young adolescent children in rural Nepal

Part of: DOHaD on International Women's Day 2020

Published online by Cambridge University Press:  02 September 2019

Amanda C. Palmer Open the ORCID record for Amanda C. Palmer [Opens in a new window] ,
Kerry J. Schulze ,
Subarna K. Khatry  and
Keith P. West Jr.
Amanda C. Palmer*
Affiliation:
Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Kerry J. Schulze
Affiliation:
Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Subarna K. Khatry
Affiliation:
Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA Nepal Nutrition Intervention Project-Sarlahi, Sarlahi, Nepal National Society for the Prevention of Blindness, Kathmandu, Nepal
Keith P. West Jr.
Affiliation:
Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
*
Address for correspondence: Amanda C. Palmer, Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Email: acpalmer@jhu.edu
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Abstract

The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n = 290; aged 9–13 years) born to participants in a cluster-randomized trial of maternal vitamin A or β-carotene supplementation in rural Nepal (1994–1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (β = 0.02; P = 0.05) and higher concentrations among children born to β-carotene-supplemented mothers (β = 0.19; P < 0.05). At ∼9–12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (β = 0.02; P < 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (β = −0.13; P = 0.15), during the monsoon (β = −0.22; P = 0.04), and pre-harvest (β = −0.34; P = 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.

Keywords

Thymusplasticityimmune developmentneuroendocrineseasonality
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 2 , April 2020 , pp. 127 - 135
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019

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