A study to establish a case definition of thiamine responsive disorders (TRD) among infants in Lao PDR
Thiamine (vitamin B1) is an essential micronutrient and thiamine deficiency can lead to a broad spectrum of clinical abnormalities, referred to as thiamine deficiency disorders (TDD), of which the classic forms of beriberi in adults are best known. Because of the broad and non-specific spectrum of clinical symptoms associated with thiamine deficiency, infantile beriberi and TDD often remain unrecognized. The likely progression of thiamine deficiency starts with dietary inadequacy and/or dietary thiamine inhibitors followed by biochemical evidence of deficiency. Interpretation of appropriate cut-offs of biomarkers to determine different degrees of thiamine deficiency requires linking the biomarkers to clinical or functional disorders, and ultimately to the response to thiamine (delivered prophylactically or therapeutically). Thus, we propose to develop a case definition for Thiamine Responsive Disorders (TRD), assess its associations with biochemical biomarkers of thiamine status and explore potential risk factors associated with TRD and biochemical indicators of thiamine deficiency.
We plan to implement a hospital- and community-based study at the Lao Friends Hospital for Children in Luang Prabang, Lao PDR. The proposed study will include a group of hospitalized children 21 days to <12 months of age who are diagnosed with TDD-compatible symptoms. Based on the infants’ response to a thiamine injection, children will be defined as either TRD cases or non-responders. A community-based comparison group of infants in the same age range will be included in the study to serve as a control group for identification of potential risk factors.
Contact: Sonja Y Hess
Collaborating institutions
- Lao Tropical and Public Health Institute
- Lao Friends Hospital for Children
- Global Ultrasound Fellowship, UC Davis Health
- Department of Emergency Medicine, UC Davis Health
- Pediatric Cardiology, Department of Pediatrics, UC Davis Health
- Pediatric Radiology, Department of Radiology, UC Davis Health
- UC Davis Western Human Nutrition Research Center
- NIHR BRC Nutritional Biomarker Laboratory, University of Cambridge
- Lao-Korea Children Hospital, Vientiane, Laos
Financial support
Bill & Melinda Gates Foundation
ClinicalTrials.gov identifier
NCT03626337
Publications
Hess SY, Smith TJ, Fischer PR, et al. Establishing a case definition of thiamine responsive disorders among infants and young children in Lao PDR: protocol for a prospective cohort study. BMJ Open. 2020 Feb 13;10(2):e036539. doi: 10.1136/bmjopen-2019-036539.
Smith TJ, Arnold CD, Fischer PR, et al. A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic. J Pediatr. 2024 May;268:113961. doi: 10.1016/j.jpeds.2024.113961.
Hess SY, Smith TJ, Arnold CD, et al. Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study. Curr Dev Nutr. 2024 May 23;8(6):103786. doi: 10.1016/j.cdnut.2024.103786.
Hess SY, Arnold CD, Smith TJ, et al. Thiamine Concentration in Human Milk Is Correlated With Maternal and Infant Thiamine Status: A Cross-Sectional Analysis of the Lao Thiamine Study. Matern Child Nutr. 2025 Jul;21(3):e70027. doi: 10.1111/mcn.70027.