Perinatal outcomes, mitochondrial toxicity and apoptosis in HIV-treated pregnant women and in-utero-exposed newborn

Materno-Fetal Medicine Department, Clinical Institute of Gynaecology, Obstetrics and Neonatology, Barcelona, Spain.
AIDS (London, England) (Impact Factor: 5.55). 12/2011; 26(4):419-28. DOI: 10.1097/QAD.0b013e32834f3232
Source: PubMed


Highly active antiretroviral therapy (HAART) has decreased the risk of HIV mother-to-child transmission. However, HIV and HAART have been associated with adverse perinatal outcome. HAART has been associated with mitochondrial dysfunction in nonpregnant adults, and HIV, additionally, to apoptosis. We determined whether mitochondrial toxicity and apoptosis are present in HIV-pregnant women and their newborns and could be the basis of adverse pregnancy outcome.
Single-site, cross-sectional, controlled observational study without intervention.
We studied mitochondrial and apoptotic parameters in mononuclear cells from maternal peripheral blood and infant cord blood at delivery in 27 HIV-infected and treated pregnant women, and 35 uninfected controls and their infants, to correlate clinical outcome with experimental findings: mitochondrial number (CS), mtDNA content (ND2/18SrRNA), mitochondrial protein synthesis (COX-II/V-DAC), mitochondrial function (enzymatic activities) and apoptotic rate (caspase-3/β-actin).
Global adverse perinatal outcome, preterm births and small newborn for gestational age were significantly increased in HIV pregnancies [odds ratio (OR) 7.33, 5.77 and 9.71]. Mitochondrial number was unaltered. The remaining mitochondrial parameters were reduced in HIV mothers and their newborn; especially newborn mtDNA levels, maternal and fetal mitochondrial protein synthesis and maternal glycerol-3-phosphate + complex III function (38.6, 25.8, 13.6 and 31.2% reduced, respectively, P < 0.05). All materno-fetal mitochondrial parameters significantly correlated, except mtDNA content. Apoptosis was exclusively increased in infected pregnant women, but not in their newborn. However, adverse perinatal outcome did not correlate mitochondrial or apoptotic findings.
Transplacental HAART toxicity may cause subclinical mitochondrial damage in HIV-pregnant women and their newborn. Trends to increased maternal apoptosis may be due to maternal-restricted HIV infection. However, we could not demonstrate mitochondrial or apoptotic implication in adverse perinatal outcome.

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Available from: Òscar Miró, Jul 10, 2014
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