Screening for Genetic Mutations Predict Preterm Birth Defects

Genetic mutations in the enzyme methylenetetrahydrofolate reductase (MTHFR) and coagulation protein factor V appear to have significant association with blood clots and tissue injury to the placenta and developing baby.

MTHFR is an enzyme related to amino acid metabolism. Intrauterine growth restriction results in malnutrition of the developing fetus and babies of low birth weight, and can be related to a host of factors usually reflective of the mother's health, including infection, high blood pressure, and use of tobacco, alcohol, or illicit drugs. Factor V is a protein of the coagulation system, sometimes referred to as proaccelerin or labile factor.

Defined as any birth prior to 37 weeks gestation, preterm birth affects some 12% of pregnancies in the United States. A recent study from the U.S. Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) 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. Babies who do survive face risks related to cerebral palsy, mental retardation, chronic lung disease, and vision and hearing loss, as well as other developmental problems.

Scientists from the University of Pittsburgh School of Medicine (Pittsburgh, PA, USA) analyzed DNA from placental tissue samples and cord blood from 111 women and their babies, finding that one fetal single nucleotide polymorphism (SNP) in MTHFR and one fetal SNP in factor V demonstrated "highly significant association with thrombotic and inflammatory lesions,” irrespective of adjustment for maternal race, smoking, and lower genital tract infection, all of which can contribute to genetic mutation. Women and babies with MTHFR mutation were 4.2 times more likely to exhibit blood clots and injury to placental tissue than those without the mutation. For those with factor V mutation, the association was less pronounced, but still elevated.

"This indicates a possible genetic predisposition to a condition of real clinical consequence in terms of intrauterine growth restriction, preeclampsia, 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.

The study was presented at the 28th annual meeting of the Society for Maternal-Fetal Medicine, which was held in Dallas (TX, USA) from January 28 to February 2, 2008.


Related Links:
U.S. Centers for Disease Control and Prevention
University of Pittsburgh School of Medicine