A predictive model for thiamine responsive disorders among infants and young children: results from a prospective cohort study in Lao People's Democratic Republic

Authors: SMITH, TARYN - University Of California, Davis; ARNOLD, CHARLES - University Of California, Davis; FISCHER, PHILIP - Mayo Clinic; TREHAN, INDI - University Of Washington; HIFFLER, LAURENT - Non ARS Employee; SITTHIDETH, DALAPHONE - Lao Tropical And Public Health Institute(LAO TPHI); STEIN-WEXLER, REBECCA - University Of California, Davis; YEH, JAY - University Of California, Davis; JONES, KERRY - University Of Cambridge; HAMPEL, DANIELA - University Of California, Davis; TANCREDI, DANIEL - University Of California, Davis; SCHICK, MICHAEL - University Of California, Davis; MCBETH, CHRISTINE - University Of California, Davis; TAN, XIUPING - University Of California, Davis; Allen, Lindsay - A; SAYASONE, SOMPHOU - Lao Tropical And Public Health Institute(LAO TPHI); KOUNNAVONG, SENGCHANH - Lao Tropical And Public Health Institute(LAO TPHI); HESS, SONJA - University Of California, Davis

Submitted to: Journal of Pediatrics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/13/2024
Publication Date: 2/17/2024
Citation: Smith, T.J., Arnold, C.D., Fischer, P.R., Trehan, I., Hiffler, L., Sitthideth, D., Stein-Wexler, R., Yeh, J., Jones, K.S., Hampel, D., Tancredi, D.J., Schick, M.A., Mcbeth, C.N., Tan, X., Allen, L.H., Sayasone, S., Kounnavong, S., Hess, S.Y. 2024. A predictive model for thiamine responsive disorders among infants and young children: results from a prospective cohort study in Lao People's Democratic Republic. Journal of Pediatrics. 268. Article 113961. https://doi.org/10.1016/j.jpeds.2024.113961.
DOI: https://doi.org/10.1016/j.jpeds.2024.113961

Interpretive Summary: We developed a predictive model for thiamine responsive disorders (TRD) among hospitalized infants and young children with possibly thiamine deficiency disorders (TDD), in order to identify those who positively respond to therapeutic thiamine in a high-burden setting. Therefore, children aged 21 days – <18 months with signs/symptoms suggestive of TDD in northern Lao PDR were treated with parenteral thiamine (100mg daily) for =3 days in addition to routine care. Physical examinations, including evaluating the recovery, were carried out frequently for 72 hours after thiamine treatment was initiated. Every case report was independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which was then used to develop the model. We found that in 449 children (median [IQR] 2.9 [1.7, 5.7] months; 70.3% exclusively/predominantly breastfed) 60.8% had a TRD. Those most predictive factors of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. Here, the majority of symptomatic children responded favorably to thiamine. While five factors were identified as most predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to infants and children presenting with any signs/symptoms consistent with TDD in similar high-risk settings.

Technical Abstract: Objective: To develop a predictive model for thiamine responsive disorders (TRD) among infants and young children hospitalized with signs and symptoms suggestive of thiamine deficiency disorders (TDD) to identify those who positively respond to therapeutic thiamine in a high-burden setting. Study design: Children aged 21 days – <18 months hospitalized with signs/symptoms suggestive of TDD in northern Lao PDR were treated with parenteral thiamine (100mg daily) for =3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve (AUROC). Results: 449 children (median [IQR] 2.9 [1.7, 5.7] months; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. The AUROC (95% CI) was 0.82 (0.78, 0.86). Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact and no diarrhea in the previous 2 weeks. Conclusions: In this study in Lao PDR, the majority of children with signs/symptoms of TDD responded favorably to thiamine. While five specific features were identified as most predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to infants and children presenting with any signs/symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. Trial registration Clinicaltrials.gov NCT03626337