Tailoring treatment for heart defect

The nonsteroidal anti-inflammatory drug indomethacin is routinely used to treat patent ductus arteriosus (PDA), a persistent opening between the aorta and pulmonary artery that is a common complication in preterm infants. Clinical response and toxicity to indomethacin are highly variable. About 1 in 4 infants treated with indomethacin requires subsequent surgical ligation, and adverse effects include kidney and gastrointestinal dysfunction.

Prince Kannankeril, MD, MSCI, a pediatric cardiologist at Monroe Carell Jr. Children’s Hospital at Vanderbilt, and colleagues sought to identify risk factors for indomethacin failure — indomethacin treatment followed by surgical ligation — in preterm infants with PDA. They investigated clinical factors and four candidate genetic variants in a multicenter cohort of 144 preterm infants who received indomethacin to treat PDA.

In the journal Pharmacogenomics, the researchers report that gestational age, surfactant use and a variant in the gene CYP2C9, which encodes a protein that metabolizes indomethacin, were each associated with indomethacin failure.

The study identifies clinical and genetic predictors of indomethacin response, which will help tailor treatment of PDA in preterm infants.

This research was supported in part by grants from the National Institutes of Health (HL132805, HL109199, HL128386, HD084461) and from the Burroughs Wellcome Fund.

– by Leigh MacMillan