Age-dependent closure of the patent ductus arteriosus by indomethacin

Indomethacin has been shown to be effective in closing a patent ductus arteriosus (PDA) in small premature infants. However, the age range over which this therapy is effective remains undetermined. Eighteen infants ranging in age from 4 to 45 days were studied. All had auscultatory and clinical findings indicative of PDA. Seventeen had roentgenographic evidence of cardiomegaly and/or increased pulmonary vascular markings, and eight had ECG evidence of ventricular hypertrophy. Indomethacin was administered to most patients in two doses of 0.1 to 0.3 mg/kg 24 hr apart. In eight of 12 patients, 3 wk of age or younger, the PDA closed after indomethacin therapy. Two patients had a decrease in the intensity of murmur and improvement of congestive heart failure after treatment, but the PDA did not close completely. Only patients 33 wk of age (actual age) or younger responded to indomethacin therapy with complete ductal closure. The condition of patients 34 to 36 wk of age improved but there was not complete closure; in patients older than 36 wk there was no response. The data suggest an age-related mechanism for PDA closure and that treatment with indomethacin before 33 wk of age is probably required. A role for prostaglandin in ductal patency is postulated.