Researchers explore how genetics affects causes and prevalence of preterm birth

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More than 450,000 babies are born too soon each year in the U.S. Preterm birth is a serious health problem that costs the nation more than $26 billion annually, according to the Institute of Medicine, and is the leading cause of newborn death. Babies who survive an early birth are at an increased risk for breathing problems, cerebral palsy, intellectual and developmental disabilities, vision and hearing loss, and other lifelong health problems. In 2012, the U.S. preterm birth rate dropped to 11.5 percent, the lowest in 15 years, but still above the March of Dimes goal of 9.6 percent.

With the help of funding from the March of Dimes, James F. Padbury, MD, pediatrician-in-chief and chief of Neonatal/Perinatal Medicine at Women & Infants Hospital of Rhode Island and the William and Mary Oh-William and Elsa Zopfi Professor of Pediatrics for Perinatal Research at The Warren Alpert Medical School of Brown University, is one of five scientists whose work toward discovering the causes of and reducing the rates of prematurity will be supported by March of Dimes Prematurity Research Initiative (PRI) grants in 2014. The PRI grants, which total nearly $27 million over 10 years, are one of several March of Dimes grant programs available to researchers.

"Prevention is the way to save babies from death and disability caused by preterm birth," says Betsy Akin, RI March of Dimes director. "Research is the key that will provide new insights into the many unknown causes of preterm labor, and help doctors recognize the women and babies most at risk."

Preterm birth not only affects one in eight women but since it "runs in families," it has a strong genetic basis. With prior support from the March of Dimes, Dr. Padbury's laboratory at Women & Infants Hospital has been studying the genetic basis of preterm birth for the past five years. This new, $400,000, three-year Prematurity Research Initiative Program grant will enable Dr. Padbury and his colleagues to continue their work in bioinformatics and targeted sequencing in preterm birth.

"We are so grateful to the March of Dimes for supporting this important work," said Dr. Padbury. "We are using the resources of this grant to sequence the genes we identified in women who delivered preterm, who were preterm themselves, and who have a family history of preterm birth in their relatives. We are sequencing up to 300 women, including 150 we have identified with a strong family history of prematurity at Women & Infants Hospital."

Dr. Padbury and his team have used bioinformatics techniques and "big data" approaches to collect all of the genes known to be involved in preterm birth, reading more than 1,000 scientific articles and pulling data from hundreds of public genetic databases. Their database is now hosted on the Center for Disease Control and Prevention's Genomics in Health Impact website, the University of Florida's Library of Genetic Resources, and Stanford University's Great Placenta Disorders and Preeclampsia Single Nucleotide Resources.

Dr. Padbury continued, "The Human Genome Project revealed that each of us have minor genetic variations, which may, in part, cause preterm birth. In order to identify these minor genetic variations, we will use new DNA sequencing technologies. We will look for minor genetic variations in families with a strong family history of preterm birth and compare genetic sequence to patients of similar background but who delivered full-term children. We hope that, with insights into the cause of prematurity, we can begin to address possible treatment, prevention methods and prediction."

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