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

Abstract

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 1 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 p225 mg and 30 infants received >225 mg). Both subgroups were demographically and clinically 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.

A novel role for PGE2-EP4 in the developmental programming of the mouse ductus arteriosus: consequences for vessel maturation and function

“…This discrepancy is likely due to variations in the timing, dosage, and length of tocolytic treatments. In general, tocolytic treatments later in pregnancy ( 22 , 87 ), closer to delivery ( 90 ), with a higher dosage ( 92 ), or longer duration ( 91 , 92 ) promote PDA. Incidence aside, tocolysis has also been associated with failed pharmacological treatment and an increased need for ligation ( 22 , 88 , 89 , 91 , 93 ).…”

An interpretable machine-learning model for predicting the efficacy of nonsteroidal anti-inflammatory drugs for closing hemodynamically significant patent ductus arteriosus in preterm infants

“…However, 10%-40% of patients obtain no benefits from such drugs (5). Some cohort studies or studies using regression analysis have discovered various maternal and neonatal clinical features that could be used to predict the likelihood of PDA closure with NSAIDs, such as gestational hypertension, gestational age, twin pregnancy, respiratory distress syndrome, age in days, and prenatal exposure to drugs such as magnesium sulfate and NSAIDs (5,7,(14)(15)(16)(17). Changes in urine volume or pulse pressure before and after NSAIDs treatment are not useful predictors of the responsiveness of preterm infants with PDA to a drug (18,19).…”

Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?

“…13,14 A recent study of 58 ELBW infants whose mothers received indomethacin tocolysis and 58 ELBW control infants showed that neither the incidence of sPDA nor the responses to postnatal indomethacin have been affected by the antenatal pharmacological exposure. 15 Among the multiple factors known to decrease the response of the ductus arteriosus to postnatal indomethacin, GA and postnatal age at the time of treatment are the most relevant. [1][2]12 In humans, the ductus arteriosus constricts as early as 24-week GA, but that constriction is considered to be minimal at least until 31 weeks.…”