The effects of indomethacin tocolysis on the postnatal response of the-ductus arteriosus to indomethacin in extremely low birth weight infants

Background: Antenal indomethacin reportedly, decreases the responses of a symptomatic patent ductus arteriosus (sPDA) to postnatal indomethacin treatment. Whether a similar exposure affects the responses to indomethacin prophylaxis is unknown. Objective: To evaluate the clinical responsiveness of ductus arteriosus to indomethacin prophylaxis and to the treatment of sPDA in extremely low birth weight (ELBW) infants following indomethacin tocolysis. Methods: Retrospective cohort study of 58 ELBW infants whose mothers received indomethacin tocolysis (study) and 58 ELBW infants whose mothers did not (controls), matched by gender, gestational age (GA), birth weight and postnatal sPDA management (prophylaxis or early treatment). Results: Indomethacin was used as a tocolytic at a median dose of 250 mg, for a duration of 2 days, and ending I day before delivery. Study and control mothers were comparable in demographics, antenatal steroid use, cesarean delivery, but were different in the incidence of preeclampsia and preterm labor. Study and control infants were similar in birth weight, GA, indomethacin prophylaxis, early sPDA treatment, mortality, necrotizing enterocolitis, severe intraventricular hemorrhage and stage 3-5 retinopathy of prematurity. Seventeen of 43 study and 16 of 43 control infants who received indomethacin prophylaxis developed sPDA and were combined with early treatment sPDA infants (15 to each group). Two of 32 study and two of 31 control infants underwent surgical ligation whereas the remaining were treated with indomethacin. Sixteen of 30 (53%) and 13 of 29 (45%) were successfully treated and did not require ligation. Study infants were divided according to their mothers' indomethacin total dose (28 infants received <= 225 mg and 30 infants received > 225 mg). Both subgroups were demographically and clinically 1 comparable and their response to indomethacin prophylaxis and treatment were similar. Conclusion: In ELBW infants, exposure to indomethacin tocolysis does not affect the clinical responsiveness of the ductus arteriosus to prophylaxis or that of the sPDA to indomethacin treatment.