REGULAR ARTICLE The definition of a haemodynamic significant duct in randomized controlled trials: a systematic literature review Inge Zonnenberg (koert.dewaal@hnehealth.nsw.gov.au) 1 , Koert de Waal 2 1.Department of Neonatology, VU Medical Centre, Amsterdam, The Netherlands 2.Department of Neonatology, John Hunter Hospital, Newcastle NSW and University of Newcastle, NSW, Australia Keywords Ductus arteriosus, Newborn, Systematic review Correspondence Koert de Waal, Department of Neonatology, John Hunter Hospital, New Lambton, NSW 2305, Australia. Tel: +61 2 4921 3000 | Fax: +61 2 4921 4969 | Email: koert.dewaal@hnehealth.nsw.gov.au Received 17 May 2011; revised 21 July 2011; accepted 09 September 2011. DOI:10.1111/j.1651-2227.2011.02468.x ABSTRACT Aim: A patent ductus arteriosus (PDA) is associated with morbidity in preterm infants. Treatment is prescribed for a haemodynamically significant duct (HSDA), but its definition varies. We systematically reviewed the clinical and ultrasound criteria used for the definition of an HSDA. Methods: PubMed and the Cochrane library were searched for randomized trials evaluating ductal treatment. The included studies were explored, and we categorized clinical and ultrasound criteria used to define an HSDA. Results: Sixty-seven trials were included in our review. Forty-two were placebo-con- trolled trials, and 25 were comparative trials. The diagnosis of the PDA was made by clinical examination, followed by ultrasound in most trials. Most trials used clinical and ultrasound criteria to define an HSDA, but there was a wide variety in criteria and cut-offs used. Of the clinical criteria, a murmur or hyperdynamic circulation was most used, and of the ultrasound criteria, the left-atrium-to-aorta ratio (LA / Ao ratio) was most used. Conclusion: We found a wide variety in the definition of an HSDA. This finding implies that comparison of studies is difficult. International consensus should be reached on the definition of an HSDA, which will make future studies more comparable. INTRODUCTION A patent ductus arteriosus (PDA) with significant shunting is associated with several important morbidities in prema- ture infants (1). Associated morbidity includes intraventric- ular haemorrhage (IVH), low systemic blood flow, low blood pressure, necrotizing enterocolitis, increased and pro- longed respiratory support and chronic lung disease. The underlying pathophysiology is often described as a steal of blood away from the systemic circulation and, if significant shunting persists, cardiac and pulmonary volume (2). Treatment is commonly prescribed for a haemodynami- cally significant ductus arteriosus (HSDA). Most short- and long-term outcomes have not been shown to be affected by treatment. All Cochrane systematic reviews evaluating pre- vention of or treatment for a PDA with medical or surgical treatment showed a significant reduction in ductal patency with all treatment approaches (3–9). Prophylactic indo- methacin, given in the first 24 h of life, was the only treat- ment approach that could reduce severe IVH, but without the expected improvement in neurodevelopment (4). Surgi- cal ligation as treatment option was often associated with harm (7,10). Benitz proposed that it is time to accept the null hypothesis and questions the necessity to treat the PDA (11). He proposes a trial that compares PDA closure versus treatment not primarily intended to achieve closure in a high-risk population. Although we feel this trial is most needed, we question the available evidence on how the actual diagnosis of a PDA was made and whether shunt severity was taken into account. So, the aim of this study is to systematically review which clinical and / or ultrasound parameters were used to diagnose a PDA and classify the PDA as haemodynamically significant in randomized con- trolled trials evaluating ductal treatment. METHODS We searched PubMed and the Cochrane library to find all randomized controlled trials evaluating PDA treatment using the Mesh terms ‘ductus arteriosus, patent’ and Key notes • A ductus arteriosus is commonly treated when it is deemed haemodynamically significant. • We categorized randomized trials evaluating ductal treatment in which clinical and ultrasound criteria were used to define a haemodynamically significant ductus arteriosus (HSDA). • We found a wide variety in the definition of an HSDA, which implies that comparison of studies is difficult. Acta Pædiatrica ISSN 0803–5253 ª2011 The Author(s)/Acta Pædiatrica ª2011 Foundation Acta Pædiatrica 2012 101, pp. 247–251 247