Abstract
Background:
Mitochondrial toxicity related to maternal combined antiretroviral treatment (cART) may have an impact on the heart of HIV-exposed uninfected (HEU) fetuses. Our objective was to evaluate fetal cardiovascular and mitochondrial biomarkers in HIV pregnancies.
Methods:
Prospective cohort including 47 HIV-infected and 47 non HIV-infected pregnancies. Fetal echocardiography was performed at 26-32 weeks of pregnancy. Umbilical cord blood and placental tissue were collected to study mitochondrial DNA content (mtDNA) (ratio 12SrRNA/RNAseP) and mitochondrial function (cytochrome c oxidase, COX, enzymatic activity) normalized by mitochondrial content (citrate synthase, CS).
Results:
HEU fetuses showed hypertrophic hearts (left myocardial wall thickness: HIV mean 3.21 mm (SD 0.81) vs. non-HIV 2.72 (0.42), p = 0.012), with signs of systolic and diastolic dysfunction (isovolumic relaxation time: HIV 52.2 ms (8.85) vs. non-HIV 42.5 ms (7.30); p<0.001). Cord blood mitochondrial content was significantly increased in HIV-exposed fetuses (CS activity: HIV 82.9 nmol/min.mg of protein (SD 40.5) vs. non-HIV 56.7 nmol/min.mg of protein (28.4); p = 0.007), with no differences in mtDNA content and COX activity. Both myocardial and mitochondrial mass parameters were significantly associated with zidovudine exposure.
Conclusions:
HEU fetuses showed signs of increased myocardial and mitochondrial mass associated with maternal zidovudine treatment, suggesting a fetal adaptive response to cART toxicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antiretroviral Therapy, Highly Active*
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Case-Control Studies
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Echocardiography
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Female
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Fetal Blood
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Fetus / drug effects
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Fetus / pathology*
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Fetus / virology
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Gestational Age
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HIV / drug effects*
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HIV / isolation & purification
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HIV Infections / complications*
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HIV Infections / drug therapy
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HIV Infections / virology
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Heart / drug effects
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Heart / physiopathology*
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Heart / virology
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Humans
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Maternal-Fetal Exchange
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Mitochondria / drug effects
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Mitochondria / pathology*
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Mitochondria / virology
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Pregnancy
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Pregnancy Complications, Infectious / epidemiology*
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Pregnancy Complications, Infectious / virology
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Prenatal Exposure Delayed Effects / epidemiology*
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Prenatal Exposure Delayed Effects / virology
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Prospective Studies
Grants and funding
This study was supported by grants from Instituto de Salud Carlos III (grants PI13/01738, PI14/00226, PI15/00130, PI15/00263 and INT16/00168) integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “Otra manera de hacer Europa”, the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2014 SGR grant n° 928, 2016FI_B01184) Spain and European Social Funds, “la Caixa” Foundation (Spain), the Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040) [This publication reflects the views only of the author, and the Commission cannot be held responsible for any use which may be made of the information contained therein]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.