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

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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 1/49-12 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.

Original languageEnglish (US)
JournalJournal of Developmental Origins of Health and Disease
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Circulating Thymic Factor
Nepal
Carotenoids
Thymus Gland
Mothers
Pregnancy
Proxy
Thymocytes
Nutritional Status
Vitamin A
Growth and Development
Malnutrition
Gestational Age
Confidence Intervals
Inflammation
Phenotype

Keywords

  • immune development
  • neuroendocrine
  • plasticity
  • seasonality
  • Thymus

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

@article{cfbbb33d6bd74fe48c4a90258ac9c22f,
title = "Prenatal and childhood exposures are associated with thymulin concentrations in young adolescent children in rural Nepal",
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 1/49-12 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 = "immune development, neuroendocrine, plasticity, seasonality, Thymus",
author = "Palmer, {Amanda C} and Schulze, {Kerry J} and Khatry, {Subarna K.} and Keith West",
year = "2019",
month = "1",
day = "1",
doi = "10.1017/S2040174419000485",
language = "English (US)",
journal = "Journal of Developmental Origins of Health and Disease",
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TY - JOUR

T1 - Prenatal and childhood exposures are associated with thymulin concentrations in young adolescent children in rural Nepal

AU - Palmer, Amanda C

AU - Schulze, Kerry J

AU - Khatry, Subarna K.

AU - West, Keith

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 1/49-12 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.

AB - 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 1/49-12 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.

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KW - neuroendocrine

KW - plasticity

KW - seasonality

KW - Thymus

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U2 - 10.1017/S2040174419000485

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M3 - Article

JO - Journal of Developmental Origins of Health and Disease

JF - Journal of Developmental Origins of Health and Disease

SN - 2040-1744

ER -