“Divergent ancestry” in infants’ DNA associated with increased risk of preterm birth

Higher risk of preterm birth in African-American infants may be explained by distinct ancestry of mitochondrial DNA

TORONTO – Preterm birth is a critical public health problem that may cause a wide range of health issues for the one in ten premature babies born in North America every year.

While ongoing research into various aspects of prematurity has resulted in a better clinical understanding of how to manage the complications that may arise in these babies, the causes of spontaneous preterm birth remain largely unknown. Existing epidemiological evidence has shown that preterm birth rates vary according to ethnic group; according to the National Center for Health Statistics, babies born to African-American mothers have one-and-a-half times the risk of delivery before 37 weeks’ gestation, compared with the general population. Previous research also suggests that maternal heredity may influence the risk of preterm birth, and that good mitochondrial function is important in maintaining pregnancy.

Building upon this existing knowledge base, a new study co-led by The Hospital for Sick Children (SickKids) and the University of Pennsylvania identifies a possible explanation for this phenomenon in some African-American babies: in pregnancies where the mitochondrial DNA and nuclear DNA have highly distinct ancestries, an association with higher rates of prematurity was observed. Divergent ancestry appears to explain up to 20 per cent of the increased risk for preterm birth observed in African-American infants. The research is published in the December 14 online edition of The Journal of Pediatrics.

The research team conducted a re-analysis of three large, publicly available data sets that were previously collected on premature infants. In what is believed to be the first study of its kind, they evaluated how mitochondrial genetics impact common health problems such as preterm birth. Knowing that that mixed nuclear ancestries were more common in women of African ancestry, they decided to study that population in the hopes that differences in mitochondrial and nuclear inheritance may be more apparent.

The re-analysis revealed that the inheritance of mitochondrial and nuclear DNA from distinct ancestral origins is associated with an increased risk for preterm birth.

“This finding will contribute to our collective understanding of genetic influences on prematurity, and may have important clinical implications down the road,” says the study’s principal investigator, Dr. Neal Sondheimer, Staff Physician in Clinical and Metabolic Genetics and Associate Scientist at SickKids. “Testing for divergent ancestry could eventually be used to identify women at elevated risk for spontaneous preterm birth, and to offer enhanced monitoring of their pregnancies.”

Next steps for the research include creating an animal model in which mitochondrial and nuclear ancestries could be controlled, which would enable researchers to confirm the divergence effect and to understand how it impacts the function of the mitochondria.

“Studying an animal model that demonstrates this effect in the lab could help us determine how it could be controlled to prolong pregnancies to full term through the development of new therapies. Ultimately, we hope to help reduce the incidence and severity of preterm birth, and improve outcomes,” says Sondheimer, who is also Assistant Professor in the Department of Paediatrics at the University of Toronto.

This study was funded by March of Dimes Foundation, the Starbucks Clinical Genetics/Genomics Research Studentship Award at SickKids (part of the Starbucks Coffee Company Endowment Fund), and SickKids Foundation. It is an example of how SickKids is contributing to making Ontario Healthier, Wealthier and Smarter. www.healthierwealthiersmarter.ca.

About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized child and family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit www.sickkids.ca. Follow us on Twitter (@SickKidsNews) and Instagram (@SickKidsToronto).