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. 2013 Feb;32(2):146-50.
doi: 10.1097/INF.0b013e31827030a6.

Abnormal newborn screens and acylcarnitines in HIV-exposed and ARV-exposed infants

Brian Kirmse  1 , Charlotte V Hobbs, Inga Peter, Bryan Laplante, Michele Caggana, Karen Kloke, Kimiyo Raymond, Marshall Summar, William Borkowsky
Affiliations

Abnormal newborn screens and acylcarnitines in HIV-exposed and ARV-exposed infants

Brian Kirmse et al. Pediatr Infect Dis J. 2013 Feb.

Abstract

Background: Antiretroviral drugs (ARV), specifically nucleoside analogs, are toxic to mitochondrial oxidative phosphorylation. Other metabolic pathways, such as fatty acid oxidation, organic acid metabolism and amino acid metabolism, are dependent on normal oxidative phosphorylation but remain unexamined as potential points of ARV toxicity.

Methods: We analyzed newborn screening data from New York and compared proportions of abnormal newborn metabolic screens in HIV antibody screen-positive and HIV screen-negative neonates. Subsequently, we compared acylcarnitine levels in ARV-exposed (n = 16) and ARV-unexposed (n = 14) HIV-exposed infants to assess for dysfunctional fatty and organic acid metabolism.

Results: : The rate of abnormal newborn metabolic screens in HIV screen-positive infants was higher than that in the general population (2.2% versus 1.2%; P = 0.00025), most of which were for disorders of mitochondria-related metabolism. Abnormal acylcarnitine levels occurred more frequently in ARV-exposed compared with ARV-unexposed infants (43% versus 0%; P = 0.02).

Conclusions: A higher proportion of positive metabolic screens in HIV screen-positive neonates suggests that HIV or ARV exposure is associated with dysfunctional intermediary metabolism in newborns. Abnormal acylcarnitine levels were more frequent in ARV-exposed infants, suggesting that ARV may perturb normal fatty acid oxidation in some infants. Studies designed to validate and determine the clinical significance of these findings are warranted.

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Conflict of interest statement

None of the authors above have any conflicts of interest to declare.

Figures

Figure 1
Figure 1
Acylcarnitine levels in ARV-unexposed (○) and ARV-exposed (●) infants. Each acylcarnitine species (C3 through C18) corresponds to a substrate for a step of either fatty acid oxidation or organic acid catabolism. Group means, standard deviations and p-values for significant differences are listed under corresponding species. Circled measurements represent values of birth sample and/or 2 month sample that were >99th percentile of age-matched references.
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