Abnormal Newborn Screens and Acylcarnitines in HIV-exposed and ARV-exposed Infants

Kirmse, Brian; Hobbs, Charlotte V.; Peter, Inga; LaPlante, Bryan; Casini, Michèle; Kloke, Karen M.; Raymond, Kimiyo; Summar, Marshall; Borkowsky, William

doi:10.1097/inf.0b013e31827030a6

Cited by 19 publications

(21 citation statements)

References 30 publications

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“…15,16 To date little is known about the effects of HIV or ARV on fatty acid and acylcarnitine metabolism in neonates, although we recently reported a higher proportion of abnormal ACP in HIV-exposed infants compared to the general population of newborns. 17 In this study we sought to determine the prevalence of abnormal ACP in a large cohort of HIV-exposed, uninfected (HEU) newborns and explore the association of abnormal ACP with clinical laboratory outcomes and in utero ARV exposures.…”

Section: Introductionmentioning

confidence: 99%

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

Kirmse

Yao

Hofherr

et al. 2016

AIDS Research and Human Retroviruses

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We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and to explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated the associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease, and behavioral characteristics. We evaluated the associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP [adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06] with marginal significance while exposure to a nonnucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose, or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PIcontaining as opposed to NNRTI-containing antiretroviral (ARV) regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long-term health implications of abnormal acylcarnitine metabolism at birth in HEU children.

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Section: Introductionmentioning

confidence: 99%

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

Kirmse

Yao

Hofherr

et al. 2016

AIDS Research and Human Retroviruses

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“…One study examined acylcarnitine and amino acid profiles, products of intermediary metabolism, from newborn metabolic screens in the U.S. and found a higher rate of abnormal screens in infants who also screened positive for HIV infection (2.2% vs. 1.2%, p =0.00025). (79) In addition, the rate of abnormal acylcarnitine levels was increased in ARV-exposed infants (43% vs. 0%, p =0.02).…”

Section: Mitochondrial Toxicitymentioning

confidence: 87%

Metabolic Complications of in utero Maternal HIV and Antiretroviral Exposure in HIV-exposed Infants

Jao

Abrams

2014

Pediatric Infectious Disease Journal

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Background Despite a wide body of literature supporting the use of antenatal antiretrovirals (ARV) for the prevention of mother to child transmission, there remains a need for continued monitoring as the intrauterine interval is a critical period during which fetal programming influences the future health and development of the child. Methods We conducted a systematic review of the current literature addressing potential metabolic complications of in utero HIV and ARV exposure. We describe studies evaluating metabolic outcomes such as intrauterine and early postnatal growth, bone health, and mitochondrial toxicity. Results Overall, infants exposed to HIV/ARV do not appear to exhibit vastly compromised intrauterine or early postnatal growth. However, some studies on the effect of combination antiretroviral therapy (cART) on small for gestational age (SGA) and low birth weight (LBW) outcomes in low-middle income countries show a risk for SGA/LBW while those in the U.S. do not. Postnatal growth to 1 year does not appear to be affected by intrauterine tenofovir exposure in African studies, but a U.S. study found statistically significant differences in length for age z scores (LAZ) at 1 year. Little data exists on long term bone health. Mitochondrial toxicity including abnormal mitochondrial morphology and DNA content, as well as neurologic deficits and death have been demonstrated in HIV/ARV–exposed infants. Conclusion Though gross measures of metabolic well-being appear to be reassuring, careful vigilance of even small risks for potential serious adverse effects to infants exposed to intrauterine HIV/ARVs is warranted as intrauterine fetal metabolic programming may substantially impact the future health of the child.

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“…Therefore, to avert the potential for major physical harm such as in the case of diethylstilboestrol exposure, disclosure is necessary in order to properly monitor HEU individuals into adulthood. Second, one could argue that in addition to childhood malignancies [16,17,23,36,37], there are a myriad of concerning data already surrounding malignancies as well as the mitochondrial [38–44], mental [45–47], bone [48–51], cardiovascular [52–54] and metabolic [55–57] health in HEU children as described herein.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, increased risk of elevated cardiac troponin T in abacavir-exposed infants (OR=2.33, 95% CI: 1.03–5.26) and decreased risk of elevated N-terminal pro-brain natriuretic peptide in stavudine-exposed infants (OR=0.13, 95% CI: 0.02–0.99) have been reported [58], the long-term significance of either of which remains unclear. Lastly, studies have shown acylcarnitine and amino acid analytes, products of intermediary metabolism, were increased in ARV-exposed infants (43% vs. 0%, p =0.02) [57] as well as lower insulin levels and abnormal fuel substrate utilization in HEU infants at six weeks of life [56], which may affect the long-term metabolic health of HEU children.…”

Section: Discussionmentioning

confidence: 99%

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Jao

Hazra

Mellins

et al. 2016

Journal of the International AIDS Society

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IntroductionThe tremendous success of antiretroviral therapy has resulted in a diminishing population of perinatally HIV-infected children on the one hand and a mounting number of HIV-exposed uninfected (HEU) children on the other. As the oldest of these HEU children are reaching adolescence, questions have emerged surrounding the implications of HEU status disclosure to these adolescents. This article outlines the arguments for and against disclosure of a child's HEU status.DiscussionDisclosure of a child's HEU status, by definition, requires disclosure of maternal HIV status. It is necessary to weigh the benefits and harms which could occur with disclosure in each of the following domains: psychosocial impact, long-term physical health of the HEU individual and the public health impact. Does disclosure improve or worsen the psychological health of the HEU individual and extended family unit? Do present data on the long-term safety of in utero HIV/ARV exposure reveal potential health risks which merit disclosure to the HEU adolescent? What research and public health programmes or systems need to be in place to afford monitoring of HEU individuals and which, if any, of these require disclosure?ConclusionsAt present, it is not clear that there is sufficient evidence on whether long-term adverse effects are associated with in utero HIV/ARV exposures, making it difficult to mandate universal disclosure. However, as more countries adopt electronic medical record systems, the HEU status of an individual should be an important piece of the health record which follows the infant not only through childhood and adolescence but also adulthood. Clinicians and researchers should continue to approach the dialogue around mother–child disclosure with sensitivity and a cogent consideration of the evolving risks and benefits as new information becomes available while also working to maintain documentation of an individual's perinatal HIV/ARV exposures as a vital part of his/her medical records. As more long-term adult safety data on in utero HIV/ARV exposures become available these decisions may become clearer, but at this time, they remain complex and multi-faceted.

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Abnormal Newborn Screens and Acylcarnitines in HIV-exposed and ARV-exposed Infants

Cited by 19 publications

References 30 publications

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

Metabolic Complications of in utero Maternal HIV and Antiretroviral Exposure in HIV-exposed Infants

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

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