Indomethacin tocolysis increases postnatal patent ductus arteriosus severity

Postnatally, therapeutic indomethacin administration is usually effective in mediating patent ductus arteriosus (PDA) constriction in premature infants. There are infants, however, who remain resistant to indomethacin and require more aggressive surgical intervention to facilitate ductal closure. Indomethacin tocolysis has been reported to increase the incidence of persistent PDA in premature infants. It was our impression that infants exposed to antenatal indomethacin not only suffered from an increased incidence of PDA, but that they were more symptomatic from PDA and that for them, PDA was more resistant to medical closure. It is this observation that we sought to examine in this study.

Medical records of all mothers and premature neonates with birth weight

A total of 105 premature infants met the above criteria. Thirty-six of these 105 infants had echocardiographic signs of a PDA (34.3%). Those with PDA were less mature (gestational age, 28.9 +/- 2.6 vs 30.3 +/- 2.6 weeks, respectively) and tended to be smaller (1060 +/- 270 vs 1166 +/- 261 g). Of the 36 infants with PDA, 15 (42%) resolved spontaneously and 21 (58%) were symptomatic and required treatment with indomethacin. There were no differences in gestational age or birth weight between infants whose PDA resolved spontaneously and those requiring indomethacin therapy. Four of the 21 (19%) treated infants remained unresponsive to indomethacin and required ductal ligation. Of 17 infants with PDA who responded to indomethacin therapy, 1 (6%) was treated with a single course of bolus indomethacin, to which he responded, and 16 (94%) were treated with continuous indomethacin and responded promptly. The differences in therapeutic responsiveness to initial treatment with continuous vs bolus indomethacin were not significant. Of the 105 infants, 29 were exposed to indomethacin tocolysis. Those who were exposed to antenatal indomethacin and those who were not were well-matched with respect to birth weight and gestational age. Fifteen (52%) of the 29 exposed infants versus 18 (24%) of the 76 infants not exposed to antenatal indomethacin developed a PDA postnatally (relative risk = 2.1; 95% confidence interval: 1.22-3.74), and 45% of the antenatally exposed infants versus 12% of the nonexposed infants were symptomatic and required indomethacin (relative risk = 1.9; 95% confidence interval: 1.17-3.20). Four of the exposed infants versus none of the unexposed infants required surgical ligation. (ABSTRACT TRUNCATED)