Intrauterine inflammation as a risk factor for persistent ductus arteriosus patency after cyclooxygenase inhibition in extremely low birth weight infants.
OBJECTIVE
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.


METHODS
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(1α) 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 F(1α) 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.
Kim
Eun Sun
ES
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kim
Ee-Kyung
EK
Choi
Chang Won
CW
Kim
Han-Suk
HS
Kim
Beyong Il
BI
Choi
Jung-Hwan
JH
Park
Joong Shin
JS
Moon
Kyung Chul
KC
D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005315:Fetal Diseases; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007249:Inflammation / Q000150:complications*; D008297:Male; D010865:Pilot Projects; D012307:Risk Factors; D017211:Treatment Failure
D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin