Genetic factors in mothers and fetuses increase risk of premature labor and preterm birthFebruary 4, 2010
A revolutionary discovery by a team of physicians and researchers led by a Wayne State University School of Medicine professor has found that genetics plays a significant role in some preterm births and may explain why some women who do everything right still give birth too soon. The finding has been recognized by the March of Dimes with its prestigious award for Best Research in Prematurity.
Research presented Feb. 4 at the 30th annual Society for Maternal-Fetal Medicine (SMFM) meeting - "The Pregnancy Meeting" -- in Chicago showed that genes of both the mother and fetus can make them susceptible to an inflammatory response that increases the risk of a premature birth.
"Inflammation is a major risk factor for preterm birth," said Roberto Romero, M.D., chief of the National Institute of Child Health and Human Development's Perinatology Research Branch, located at the Wayne State University School of Medicine. "One out of every three preterm births is associated with inflammation or infection. However, numerous studies have shown that treating bacterial infections in pregnant women does not prevent preterm labor."
Dr. Romero, an SMFM member and one of the world's leading experts in the study of complications of pregnancy, led the team investigating genes that control maternal and fetal inflammation that could help explain the process that triggers preterm birth. The research found that variations in the DNA of the pregnant woman and the fetus involved in fighting infection are associated with an increased risk of premature birth.
"The central concept is that there are genetic factors in the maternal and fetal genome that predispose to preterm labor," said Dr. Romero, a professor of Molecular Obstetrics and Genetics with the Wayne State University Center for Molecular Medicine and Genetics.
Preterm birth is a leading cause of infant death worldwide, with more than 540,000 such births in the United States. Prematurity is the most important risk factor for long-term disability including cerebral palsy, chronic lung disease, blindness and deafness. The March of Dimes estimates that preterm births cost the United States $26 billion annually.
Patients in the case-control study - Hispanic mothers who reside in Chile -- had at least one previous preterm birth. The researchers extracted DNA from the cord blood of 822 pregnant women and 807 fetuses, then genotyped single nucleotide polymorphisms (SNP) in candidate genes that predispose to preterm birth. An SNP involved in the control of fetal inflammation (IL6R) doubled the risk of preterm birth among study subjects. DNA variants in maternal genes also increased the risk of preterm birth. Combined, these factors provide new evidence that genetic predisposition to preterm birth can depend on the DNA of both mother and fetus.
The next step in the research, Dr. Romero said, is replication and sequencing of the IL-6 and Il-6 receptor genes. That process should begin soon, he said.
Recognizing the significance of the breakthrough, the March of Dimes gave the study, "Identification of Fetal and Maternal Single Nucleotide Polymorphisms in Candidate Genes That Predispose to Spontaneous Preterm Labor with Intact Membranes," its award for Best Research in Prematurity. This is the seventh study by SMFM members to receive the honor.
The March of Dimes is conducting a national Prematurity Campaign aimed at research and awareness to reduce the growing rate of premature birth.
"The March of Dimes is the organization that was determined to find a cure for polio and did so by supporting the development of the vaccine that is used now worldwide, Dr. Romero said. "Having accomplished this, the March of Dimes has identified the prevention of premature birth as a major health care problem. We are honored by the recognition of the March of Dimes of the work done by the Perinatology Research Branch, Wayne State University, the Detroit Medical Center and its partners."
"This research gives us even more evidence as to the relationship between genetics and preterm birth and is a step toward personalized medicine," said Alan R. Fleischman, M.D., medical director of the March of Dimes. "This has the potential to allow us to identify a woman who is at risk for delivering early and provide her specialized, individualized care so that she may carry her baby to term, and help give more babies a healthy start in life."
Valerie Parisi, M.D., M.P.H., M.B.A, interim dean of the WSU School of Medicine and a past president of the SMFM, said, "As someone who has an extensive background in the field of maternal-fetal medicine and who has worked with Dr. Romero for many years, I am very proud of the accomplishments of his team. Recognition of the work done at the Perinatology Research Branch here at Wayne State is well deserved."
Other institutions collaborating in the research include the University of Miami, Emory University, Vanderbilt University, Genaissance Pharmaceuticals and Sotero del Rio Hospital and Pontifica Universidad Catolica de Childe in Santiago, Chile.
Founded in 1868, the Wayne State University School of Medicine is the largest single-campus medical school in the nation with more than 1,000 medical students. In addition to undergraduate medical education, the school offers master's degree, Ph.D. and M.D.-Ph.D. programs in 14 areas of basic science to about 400 students annually. For more information, visit http://home.med.wayne.edu/
The Society for Maternal-Fetal Medicine, established in 1977, is a nonprofit membership group for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine. The society is devoted to reducing high-risk pregnancy complications by educating its 2,000 members on the latest pregnancy assessment and treatment methods. It serves as an advocate for improving public policy and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual scientific meeting in which new ideas and research in the area of maternal-fetal medicine are unveiled and discussed. For more information, visit www.smfm.org.
The March of Dimes is the leading nonprofit organization for pregnancy and baby health. With chapters nationwide and its premier event, March for BabiesSM, the March of Dimes works to improve the health of babies by preventing birth defects, premature birth and infant mortality. For the latest resources and information, visit marchofdimes.com or nacersano.org.
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