Patent Ductus Arteriosus Therapy: Impact on Neonatal and 18-Month Outcome

Patent ductus arteriosus (PDA) occurs in a large percentage of extremely low birth weight (ELBW) infants, and is associated with an increased risk for necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), or intraventricular hemorrhage (IVH). Optimal therapy for PDA is still controversial: the only direct comparison of primary medical versus surgical treatment did not include infants <29 weeks' gestation and was completed before the widespread use of antenatal glucocorticoids and postnatal surfactant. Moreover, the actual benefits of indomethacin therapy still require further confirmation.
An American group has conducted a study to understand if therapy for PDA is a risk factor for death or neurodevelopmental impairment at 18 to 22 months, BPD, or NEC in ELBW infants.
This analysis was conducted on infants included in the National Institute of Child Health and Human Development Neonatal Research Network Generic Data Base. Infants born between 2000 and 2004, with a gestational age from 23 to 28 weeks', a birth weight <1000g and affected by PDA, were included in the study.
In total, 2938 infants were evaluated. Among them, 403 received supportive treatment only, 1525 were treated with indomethacin only, 775 with indomethacin followed by secondary surgical closure, and 135 underwent primary surgery. Statistical analysis showed that patients receiving supportive therapy did not differ from subjects treated with indomethacin only for any outcome. When compared with indomethacin alone, primary surgery was associated with increased risk for neurodevelopmental impairment and BPD. Secondary surgical closure was associated with increased risk for neurodevelopmental impairment and for BPD, but overall decreased the risk for death. Risk of NEC did not differ among treatments.
Overall, these findings suggest that supportive therapy has no difference in terms of neurodevelopmental impairment, death, BPD, or NEC when compared with indomethacin treatment. The risk of neurodevelopmental impairment was higher for surgical ligation, both primary and secondary, than indomethacin therapy. These approaches were also associated to an higher risk of BPD when compared to patients receiving indomethacin treatment. Interestingly, the prophylactic administration of indomethacin did not modify the incidence of different outcomes. This raises the possibility that outcomes with supportive therapy, even in this extremely premature cohort, may be the same as with indomethacin therapy. It must be emphasized, however, that this study was not meant to clarify whether the outcomes of interest were primarily attributable to the PDA therapy, the failure of PDA therapy in some cases, the inherent risks of surgery, or the underlying risks of PDA.
In conclusion, outcome is likely to be better in ELBW infants with a PDA that successfully responds to medical therapy alone, with or without the use of indomethacin, compared with those who undergo surgical ligation of the ductus.

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