Intrauterine Inflammation as a Risk Factor for Persistent Ductus Arteriosus Patency after Cyclooxygenase Inhibition in Extremely Low Birth Weight Infants

Objectives To test the hypothesis that intrauterine inflammation increases prostaglandin production and may be a risk factor for persistent ductus arteriosus after therapy with indomethacin, a nonselective cyclooxygenase inhibitor. Study design Indomethacin therapy was started after confirming ductus arteriosus within 24 hours after birth in extremely low birth weight infants. After one cycle of therapy, infants with closed ductus were classified as responders, and those with patent ductus were classified as nonresponders. Multiple logistic regression analysis was used to determine important perinatal factors associated with persistent ductus arteriosus. Immunohistochemistry with cyclooxygenase antibodies and radioimmunoassay by 6-keto prostaglandin F(1 alpha) kit were used to determine the relationship between intrauterine inflammation and ductal patency. Results Forty-one infants were responders, and 37 infants were nonresponders. Responders were frequently small for gestational age; nonresponders frequently had lower gestational age, respiratory distress syndrome, and intrauterine inflammation. By multiple logistic regression analysis, respiratory distress syndrome and intrauterine inflammation were more frequent in nonresponders. Cyclooxygenase-1 expression in the umbilical arteries and plasma 6-keto prostaglandin F1a levels were higher in nonresponders. Conclusions Respiratory distress syndrome and intrauterine inflammation were independent risk factors for persistent ductus arteriosus after indomethacin therapy in extremely low-birth weight infants. Intrauterine inflammation may have a negative influence on ductus arteriosus closure via increased cyclooxygenase-1 activity. (J Pediatr 2010; 157:745-50).Chorne N, 2007, J PEDIATR, V151, P629, DOI 10.1016/j.jpeds.2007.05.007LEE SE, 2007, AM J OBSTET GYNECOL, V197, P294KIM KW, 2007, AM J OBSTET GYNECOL, V197, P292KIM KW, 2007, AM J OBSTET GYNECOL, V197, pE1LEE SE, 2007, AM J OBSTET GYNECOL, V197, pE1Trivedi DB, 2006, PEDIATR RES, V60, P669, DOI 10.1203/01.pdr.0000246480.13170.c0Rheinlaender C, 2006, PEDIATR RES, V60, P270, DOI 10.1203/01.pdr.0000233066.28496.7cWaleh N, 2005, PEDIATR RES, V57, P254, DOI 10.1203/01.PDR.0000148278.64777.EFCoceani F, 2005, PROSTAG LEUKOTR ESS, V72, P71, DOI 10.1016/j.plefa.2004.10.004Bancalari E, 2005, BIOL NEONATE, V88, P192, DOI 10.1159/000087582Shim SS, 2004, AM J OBSTET GYNECOL, V191, P1339, DOI 10.1016/j.ajog.2004.06.085Itabashi K, 2003, J PEDIATR, V143, P203, DOI 10.1067/S0022-3476(03)00303-2Robel-Tillig E, 2003, EARLY HUM DEV, V72, P123, DOI 10.1016/S0378-3782(03)00045-8Park JS, 2001, AM J OBSTET GYNECOL, V185, P1156Coceani F, 2001, BRIT J PHARMACOL, V132, P241Guerguerian AM, 1998, AM J OBSTET GYNECOL, V179, P1618Gonzalez A, 1996, J PEDIATR, V128, P470YOON BH, 1995, AM J OBSTET GYNECOL, V172, P960REMMELE W, 1993, PATHOL RES PRACT, V189, P862ARISHIMA K, 1990, JPN J VET SCI, V52, P807HEYMAN E, 1990, ACTA PAEDIATR SCAND, V79, P698CLYMAN RI, 1989, PEDIATR RES, V25, P136CLYMAN RI, 1981, J PEDIATR, V98, P123COTTON RB, 1981, ACTA PAEDIATR SCAND, V70, P723CLYMAN RI, 1980, J PEDIATR, V97, P455CLYMAN RI, 1980, J PEDIATR, V96, P94FRIEDMAN Z, 1978, PEDIATRICS, V61, P341LUCAS A, 1978, LANCET, V2, P130LUBCHENC.LO, 1966, PEDIATRICS, V37, P403