Abstract
The identification of an optimal management strategy for the patent ductus arteriosus (PDA) in the context of extreme prematurity remains elusive. Observational studies have reported a persistent association between PDA and neonatal adverse outcomes, but by and large, no clinical trial, to date, has demonstrated that treating a PDA results in a reduction of those morbidities. This discrepancy has led many to assume that the PDA is an innocent bystander in the physiological mechanisms responsible for such complications and a reluctance to actively pursue shunt elimination. It would be remiss to discount the volume of evidence available clearly documenting a strong association between longstanding PDA exposure and negative outcomes. There needs to be a radical change in the design, patient selection and possible outcome assessment in any further trials addressing the PDA. The purpose of this review is to explore the reasons that preclude existing clinical trials from definitively ascribing a causal relationship between PDA patency and adverse outcomes in the context of extreme prematurity, why previous studies have failed to demonstrate significant beneficial effects following PDA treatment and how future research may be conducted to allow us to draw concrete conclusions regarding the potential merits of ductal closure.
Highlights
Despite decades of effort by neonatologists, the identification of an optimal management strategy for the patent ductus arteriosus (PDA) in the context of extreme prematurity remains elusive
Many observational studies have reported a persistent association between PDA and neonatal morbidities, including chronic lung disease (CLD), necrotising enterocolitis (NEC), acute kidney injury (AKI) and intraventricular haemorrhage (IVH), no clinical trial, to date, has demonstrated that treating a PDA results in a reduction of those morbidities [2,3,4]
The purpose of this review is to explore the reasons that preclude existing clinical trials from definitively ascribing a causal relationship between PDA patency and adverse outcomes in the context of extreme prematurity, why previous studies have failed to demonstrate significant beneficial effects following PDA treatment and how future research may be conducted to allow us to draw concrete conclusions regarding the potential merits of ductal closure
Summary
Despite decades of effort by neonatologists, the identification of an optimal management strategy for the patent ductus arteriosus (PDA) in the context of extreme prematurity remains elusive. Many observational studies have reported a persistent association between PDA and neonatal morbidities, including chronic lung disease (CLD), necrotising enterocolitis (NEC), acute kidney injury (AKI) and intraventricular haemorrhage (IVH), no clinical trial, to date, has demonstrated that treating a PDA results in a reduction of those morbidities (with the possible exception of IVH) [2,3,4]. The purpose of this review is to explore the reasons that preclude existing clinical trials from definitively ascribing a causal relationship between PDA patency and adverse outcomes in the context of extreme prematurity, why previous studies have failed to demonstrate significant beneficial effects following PDA treatment and how future research may be conducted to allow us to draw concrete conclusions regarding the potential merits of ductal closure
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