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. 2024 Feb:265:113816.
doi: 10.1016/j.jpeds.2023.113816. Epub 2023 Nov 4.

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death

Priya M Gupta  1 , Zachary J Madewell  2 , Bryan M Gannon  3 , Michael Grahn  3 , Victor Akelo  4 , Dickens Onyango  5 , Sana Mahtab  6 , Shabir A Madhi  6 , Judith Giri  1 , Dianna M Blau  2 , Usha Ramakrishnan  1 , Aryeh D Stein  1 , Cynthia G Whitney  1 , Melissa F Young  1 , Sherry A Tanumihardjo  3 , Parminder S Suchdev  7
Affiliations

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death

Priya M Gupta et al. J Pediatr. 2024 Feb.

Abstract

Objectives: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD).

Study design: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 μmol/g, >0.1 to <0.7 μmol/g, ≥0.7 to <1.0 μmol/g, and ≥1.0 μmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review.

Results: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013).

Conclusions: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Keywords: malnutrition; pediatric infections; under-5-mortality; vitamin A.

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Conflict of interest statement

Declaration of Competing Interest This work was funded by grant OPP1126780 from the Bill & Melinda Gates Foundation and a seed grant from the Global Health Institute at University of Wisconsin-Madison. The funders participated in discussions of study design and data collection. They did not participate in the conduct of the study; the management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study profile of children under 5 years with analyzed liver specimens from CHAMPS Kenya and South Africa Sites.
Figure 2
Figure 2
Crude and adjusted models of the association between vitamin A deficiency and odds of dying of infectious causes of death among children under 5 years with analyzed liver specimens from CHAMPS Kenya and South Africa Sites, n = 312 children. The crude model depicts the unadjusted relationship between vitamin A deficiency and infectious causes of death. Adjusted models depict the relationship between vitamin A deficiency and infectious causes of death controlling for site, age, and sex. Box A. All causes of infectious deaths defined as deaths due to diarrheal diseases, congenital infections, HIV, lower respiratory infection, malaria, measles, meningitis/encephalitis, sepsis, other infections, rabies, syphilis, tuberculosis, or upper respiratory infection in the causal chain. Box B. Sub-analysis of the most common causes of infectious disease mortality which have an established relationship with vitamin A deficiency. These conditions included lower respiratory infection, sepsis, and diarrheal diseases.
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