Preterm babies must adapt to the new environment outside the womb to be able to survive, often with increased risk of complications and abnormal neurodevelopmental outcomes in later life. The ductus arteriosus is a vascular structure joining the aorta and pulmonary artery that normally closes soon after birth. A patent ductus arteriosus (PDA) results from failure of the ductus arteriosus to close, and is a frequent cardiovascular complication in preterm infants. Early studies have shown associations between a PDA and neonatal morbidity, hence most preterm infants with a PDA will receive treatment with either medication or surgical ligation. However, meta-analysis of trials including almost 5000 preterm infants showed no improvement in clinical outcomes, even though PDA was reduced. It is possible that the treatment is causing harm in addition to benefit or treatment is being directed at the wrong patient subgroups.
Interpreting the existing data in previous trials on which we base our current treatment is difficult due to poorly chosen eligibility criteria, the lack of a uniform definition of a hemodynamically significant PDA and high rates of open label treatment. Furthermore, if left alone, over 80% of all PDA’s would close spontaneously before discharge from the neonatal intensive care unit. In light of these findings, investigators now advocate an approach not directed at PDA closure thus avoiding possible harmfull treatments. This supportive approach where the hemodynamic effects of a PDA are countered with increased positive airway pressure and careful fluid managment while awaiting spontaneous closure has been reported with variable success.
To date, supportive management of a PDA in preterm infants has not been attempted in a placebo controlled trial. A definitive trial, with primary aim to compare current standard treatment including supportive care versus supportive care alone using a randomized placebo controlled trial design is necessary to resolve doubts regarding the quality or conduct of prior studies. We hypothesise that there will be comparable short and medium term clinical outcomes between the 2 approaches. A secondary aim would be to determine patient subgroups that may benefit from treatment by collecting comprehensive clinical and echocardiography data.
Our team has successfully run trials in preterm infants with a PDA and other cardiovascular problems, and has built substantial experience with novel echocardiography techniques that can increase our understanding of the developing and adapting cardiovascular system. We expect to be able to answer an important question on our approach to PDA treatment which has been troubling neonatologists and pediatric cardiologists now for over 50 years, and significantly contribute to national and international priorities in health care for preterm infants. Supportive care management, if successful, could benefit many preterm infants by reducing the need for expensive pharmacological therapy with potential harm. Reducing harm in preterm infants will reflect in improved outcome throughout childhood and have its merits extended well into adulthood.