Ductus arteriosus closure and mortality in preterm infants

In the past decades, closure of the patent ductus arteriosus (PDA) has been the standard of care for preterm infants. Closure of the PDA is usually first attempted by the administration of a cyclooxygenase (COX) inhibitor, such as indomethacin or ibuprofen; if pharmacologic closure is unsuccessful, surgery intervention is required in most cases. The primary rationale for this strategy is that left-to-right shunting across the PDA could result in systemic and pulmonary hemodynamic adverse effects, such as hypoperfusion and pulmonary overcirculation. These factors may contribute to the pathogenesis of some major complications of prematurity, such as bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis.
Some clinical studies suggested that indomethacin, the COX inhibitor most commonly used for PDA therapy, is associated with significant short-term and possibly long-term adverse effects. These findings induced some authors to recommend a conservative approach to the treatment of the preterm neonate with a PDA so that pharmacologic and/or surgical closure would be reserved for exceptional cases only. However, since the standard of practice until present has been to close the PDA, there is a paucity of information on the outcome of patients with a persistent PDA.
An American group conducted a single-center, retrospective study on very preterm infants (birth weight ≤ 1500 g and gestational age ≤ 29 weeks) who survived beyond the first 3 postnatal days and did not undergo surgical ligation. Mortality of neonates with a persistent and a closed PDA was compared during the initial hospitalization; the effect of different risk factors on mortality was calculated. The same analysis was repeated after excluding patients who died during the first two postnatal weeks and after including patients who underwent surgical ligation.
Results showed that patients with a persistent patent ductus arteriosus (n=41) had lower birth weight and were less mature than those with a closed ductus (n=260). Unadjusted mortality rate was higher in patients with a persistent (70.7%) than with a closed (11.2%) ductus (p < 0.0001). After adjustment for perinatal factors, level of maturity, disease severity, and morbid pathologies, the hazard for death in neonates with a persistent ductus was eightfold higher than in those with a closed ductus. These results were consistent even after the inclusion of patients who died during the first 2 weeks or the inclusion of those who underwent ductal ligation.
Overall, these findings indicate an higher mortality in mortality in very preterm infants when the ductus arteriosus remained open. These observations do not establish the persistent ductus arteriosus as the cause of the observed increased mortality; however, they strongly raise this possibility. The results observed in this study may be of help in designing future prospective clinical trials, which may clarify this issue.

Top