Common anti-inflammatory drug rescues low-growth fetuses in mouse study

Despite advances in prenatal care, about one in twenty babies in the United States are severely underweight at birth -- below the 10th percentile -- resulting in significantly higher rates of infant mortality and childhood disease in that group. Reductions in mental capacities and a vulnerability to heart disease and other difficulties in adult life have been linked to the low-birth weight condition, known as intrauterine growth retardation, or IUGR. While some risk factors have been identified -- most prominently, cigarette smoking, diabetes, and nutritional deprivation of the placenta due to high blood pressure -- the direct cause or causes of IUGR are not known. Prevention and treatment have lagged accordingly.

Now, researchers at the University of Pennsylvania Medical Center report development of a strain of mice in whom pregnancy leads to a condition that closely models IUGR, opening the way for scientists to better understand IUGR and develop interventions to effectively treat it. Indeed, working with the mice, the scientists found they were able to completely rescue underweight fetuses through administration of a drug called indomethacin during what would correspond roughly to the middle trimester of pregnancy. Indomethacin inhibits the action of cyclooxygenase, or COX, a kind of master enzyme involved in such vital processes as inflammation and blood clotting. Well-known members of the COX-inhibitor family of drugs include aspirin and ibuprofen. A report on the new study appears in the February issue of Nature Medicine.

"Intrauterine growth retardation is a relatively common and quite serious complication in pregnancy for which we have very few insights into mechanisms, although we know some of the risk factors," says Garret A. FitzGerald, MD, chairman of pharmacology and senior author on the report. "We now have a mouse that models the condition, including important aspects of what we believe to be the underlying biochemistry of the disorder

Contact: Franklin Hoke
University of Pennsylvania School of Medicine

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