IJMEG Copyright © 2010-present. All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Mol Epidemiol Genet 2013;4(2):120-127

Original Article
Maternal blood mitochondrial DNA copy number and placental abrup-tion risk:
results from a preliminary study

Michelle A Williams, Sixto E Sanchez, Cande V Ananth, Karin Hevner, Chunfang Qiu, Daniel A Enquobahrie

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; Sección de Post Grado, Facultad
de Medicina Humana, Universidad San Martín de Porres, Lima, Peru; A.C. PROESA, Lima, Peru; Department of Obstetrics,
Gynecology, College of Physi-cians and Surgeons, Columbia University Medical Center, New York, NY, USA; Center for
Perinatal Studies, Swedish Medical Center, Seattle Washington, USA; Department of Epidemiology, School of Public Health,
University of Washington, Seattle, Washington, USA

Received March 19, 2013; Accepted May 11, 2013; Epub June 25, 2013; Published June 30, 2013

Abstract: Oxidative stress and impaired placental function – pathways implicated in the pathogenesis of placental abruption –
have their origins extending to mitochondrial dysfunction. To the best of our knowledge, there are no published reports of
associations of placental abruption with circulating mitochondrial DNA (mtDNA) copy number – a novel biomarker of systemic
mitochondrial dysfunction. This pilot case-control study was comprised of 233 placental abruption cases and 238 non-
abruption controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of
mtDNA in maternal whole blood samples collected at delivery. Logistic regression procedures were used to estimate adjusted
odds ratios (OR) and 95% confidence intervals (CI). There was some evidence of an increased odds of placental abruption
with the highest quartile of mtDNA copy number (P for trend = 0.09) after controlling for confounders. The odds of placental
abruption was elevated among women with higher mtDNA copy number (≥336.9) as compared with those with lower values
(<336.9) (adjusted OR = 1.60; 95% CI 1.04-2.46). Women diagnosed with preeclampsia and with elevated mtDNA copy
number had a dramatically increased odds of placental abruption as compared with normotensive women without elevated
mtDNA copy number (adjusted OR = 6.66; 95% CI 2.58-17.16). Maternal mitochondrial dysfunction appears to be associated
with placental abruption in the presence of preeclampsia. Replication in other studies, particularly prospective cohort studies
and those that allow for tissue specific assessment of mitochondrial dysfunction (e.g., the placenta) are needed to further
understand cellular and genomic biomarkers of normal and abnormal placental function. (IJMEG1303002).

Keywords: Placental abruption, mitochondrion, mitochondrial DNA, pregnancy, biomarkers

Address correspondence to: Dr. Michelle A Williams, Department of Epidemiology, Harvard School of Public Health, 677
Huntington Ave, Kresge Room 905A, Boston, MA 02115. Tel: 617-432-6477; E-mail: mawilliams@hsph.harvard.edu