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

Abstract

Background: Indomethacin prophylaxis or expectant treatment are common strategies for the prevention or management of symptomatic patent ductus arteriosus (sPDA). Objective:To compare the clinical responses of extremely low birth weight (ELBW) infants to indomethacin prophylaxis with hat of other infants who were managed expectantly by being treated with indomethacin or surgically only after an sPDA was detected.Methods: Retrospective cohort investigation of 167 ELBW infants who received indomethacin prophylaxis (study) and 167 ELBW infants (control) treated expectantly who were matched by year of birth (1999 to 2006), birth weight, gestational age (GA) and gender.Results: Mothers of the two groups of infants were comparable demographically and on the history of preterm labor, pre-eclampsia, antepartum steroids and cesarean delivery. Study and control infants were similar in birth weight, GA, low 5 min Apgar scores, surfactant administration, the need for arterial blood pressure control, bronchopulmonary dysplasia and neonatal mortality. Necrotizing enterocolitis, spontaneous intestinal perforations, intraventricular hemorrhage grade III to IV, periventricular leukomalacia and stage 3 to 5 retinopathy of prematurity occurred also with similar frequency in both groups of infants. In the indomethacin prophylaxis group, 29% of the infants developed sPDA, and of them 38% responded to indomethacin treatment. In the expectantly treated group, 37% developed sPDA, and of them 59% responded to indomethacin treatment. Overall, surgical ligation rate for sPDA was similar between both groups of patients.Conclusion: In our experience, indomethacin prophylaxis does not show any advantages over expectant early treatment on the management of sPDA in ELBW infants. Although no deleterious effects were observed, prophylaxis exposed a significant number of infants who may have never developed sPDA, to potential indomethacin-related complications.

Factors affecting successful closure of hemodynamically significant patent ductus arteriosus with indomethacin in extremely low birth weight infants

“…[1,5,6] However, some studies [7,8] showed that prophylactic pharmacologic or surgical closure of PDA in small premature infants produced only short-term benefi ts like a decrease in later symptomatic PDA or a reduction in the duration of oxygen dependence. In an observational study, [9] a longer duration of indomethacin exposure was associated with less white matter injury in infants Factors affecting successful closure of PDA in ELBW infants Original article delivered before 28 weeks' gestation.…”

Delayed Neonatal Closure of the Ductus Arteriosus Following Early in utero Exposure to Indomethacin in the Rat

“…Prophylactic administration of indomethacin [32,33] administered immediately after birth may inhibit ductal closure further, and is contraindicated, and conservative treatment [34] is indicated. If the pediatrician waits for several days before administering indomethacin, the ductus may recover from the inhibitory effect of in utero exposure to indomethacin and become responsive to the drug.…”

Prophylactic Indomethacin Worsens Short-Term Respiratory Outcomes in Extremely Low-Birth-Weight Infants

“…IVH was diagnosed on head ultrasounds and graded accordingly. 10 We compared baseline demographic and clinical variables between the prophylactic indomethacin and the expectant groups to detect differences in potential confounders at baseline. Baseline characteristics were those that were present prior to onset of prophylactic indomethacin or 24 hours of life, whichever was earlier.…”

“…A few small studies suggest that it may not affect ventilation and oxygen requirements or it may, in fact, increase these requirements. [10][11][12] We conducted this retrospective cohort study to systematically evaluate the effects of prophylactic indomethacin on short-term respiratory outcomes.…”