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Genetic mutation increases risk of preterm birth

Mutations in immune system gene linked to placental injury common in preterm babies

Genetic mutations in the Toll-like receptor 4 (TLR4) gene appear to have significant association with inflammatory injury to the placenta and developing baby, researchers from the University of Pittsburgh’s department of obstetrics, gynecology and reproductive sciences report at the 28th annual meeting of the Society for Maternal-Fetal Medicine. Scientific sessions continue through Saturday, Feb. 2, at the Dallas Hyatt Regency at Reunion.

“This indicates a possible genetic predisposition to a kind of misfire in immune system response that could contribute to placental inflammation and spontaneous preterm birth,” said Hyagriv Simhan, M.D., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, who is presenting the work. “These injuries are important because they are more common in preterm babies and associated with major health consequences like cerebral palsy.”

TLR4 enables the body to recognize pathogens and activate the immune system. This gene is expressed most abundantly in the placenta and in white blood cells.

For the study, researchers analyzed DNA from placental tissue samples and cord blood from 111 women and their babies, finding that one maternal single nucleotide polymorphism (SNP) in TLR4 (rs1079932) and one fetal SNP (rs1554973) demonstrated “highly significant association with chorionic plate inflammation,” irrespective of adjustment for maternal race, smoking and lower genital tract infection, all of which can contribute to genetic mutation. Women with TLR4 mutation were 5.2 times more likely to exhibit inflammatory injury to placental tissue than those without the mutation, Dr. Simhan noted. Babies with TLR4 mutation were nearly five times more likely to exhibit inflammatory placental injury than those without the mutation.

“Being aware of these genetic mutations may lead to better screening efforts,” Dr. Simhan said.

Defined as any birth prior to 37 weeks gestation, preterm birth affects some 12 percent of pregnancies in the United States. Costs have been estimated at $26 billion, or $52,000 per infant, in medical care and lost productivity as of 2005, according to the Institute of Medicine. A recent study from the U.S. Centers for Disease Control and Prevention found that preterm birth contributed to more than a third of infant deaths – twice as many as previously thought and making it the leading cause of infant deaths – yet the underlying causes of premature birth remain poorly understood.

More than 500,000 babies are born too soon each year nationwide, and the preterm birth rate has increased more than 30 percent since 1981. Babies who do survive face risks of lifelong challenges related to cerebral palsy, mental retardation, chronic lung disease, and vision and hearing loss, as well as other developmental problems.

Michele D. Baum | EurekAlert!
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