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.