Risk for Persistent PDA

Chorne N, Jegatheesan P, Lin E, et al. Risk Factors for Persistent Ductus Arteriosus Patency during Indomethacin Treatment. J Pediatr (December 2007);151: 629-634. Full Text | Full-Text PDF (119 KB)

Objective. To test the hypothesis that patent ductus arteriosus that fail to close with prostaglandin inhibition may be regulated by mechanisms that act independently of prostaglandin production.

Study design. We examined a cohort of 446 infants who were treated with indomethacin (within 15 hours of birth) to inhibit prostaglandin production. We used multiple logistic regression modeling to determine which perinatal/neonatal variables were most closely associated with the persistence of ductus patency in the presence of diminished prostaglandin production.

Results. We identified 4 variables (immature gestational age, lack of exposure to antenatal betamethasone, severity of respiratory distress, and Caucasian race) that were significantly and independently associated with the degree of ductus patency.

Conclusion. Gestational age, antenatal glucocorticoid exposure, respiratory distress, and race are independent risk factors that appear to affect ductus closure even when indomethacin has been used to inhibit prostaglandin production. Future studies of these risk factors may identify new potential targets for patent ductus arteriosus treatment.

Comments. The quest to understand the mechanisms that regulate anatomic remodeling and closure of ductus arteriosus continues. This study examined a cohort of 446 infants who were treated with Indomethacin soon after birth, thereby blocking prostaglandin production. 14.7% of the infants did not respond to Indomethacin. The factors that contributed to this lack of response to indomethacin were immature gestational age, lack of antenatal steroids, severe respiratory distress and Caucasian race. Immature gestational age infants have altered sensitivity to the vasodilator nitric oxide and intracellular calcium; antenatal steroids decrease the vasodilator NO and increase vasoconstrictor endothelin and intracellular calcium. In addition increased severity of respiratory distress may lead to increased cytokines contributing to persistent ductal patency; and racial differences can indirectly contribute to lack of response to indomethacin by increasing the severity of lung disease. Identifying the mechanisms underlying ductal patency in this small group of infants may provide potential targets for newer treatment modalities. DB.