Fluid restriction for treatment of symptomatic patent ductus arteriosus in preterm infants.

Background: The ductus arteriosus is a blood vessel connecting the main pulmonary artery and the proximal descending aorta. After birth, the ductus arteriosus usually closes completely. However, sometimes it remains patent in the neonate, which is called patent ductus arteriosus (PDA). If a PDA is clinically symptomatic, it can lead to overcirculation in the lungs, and reduced perfusion to the gut and kidneys. Most clinical practice guidelines suggest fluid restriction as a conservative management strategy for the treatment of symptomatic PDA. Restricting fluid has been shown to reduce the incidence of PDA in older preterm infants. However, aggressive restriction of fluids may affect systemic blood flow in extremely preterm infants. Given the potential adverse effects, it is important to systematically evaluate the evidence on the use of fluid restriction to treat symptomatic PDA to inform clinical decisions.

Objectives: To assess the effects of fluid restriction on morbidity and mortality for symptomatic PDA in preterm infants.

Search methods: We searched CENTRAL, MEDLINE, and Embase in October 2023. We also searched Clinicaltrials.gov, ICTRP, ANZCTR, and Epistemonikos. We planned to search the reference list of included studies and relevant systematic reviews for studies not identified by the database searches, but did not identify any.

Selection criteria: We planned to include randomized controlled trials (RCTs), quasi-RCTs, cluster-RCTs, and cross-over RCTs. We planned to include neonates who were born preterm (less than 37 weeks' gestational age), or with low birth weight (less than 2500 g), with a symptomatic PDA, diagnosed either clinically or by echocardiographic criteria, in the neonatal period. We planned to include studies that compared therapeutic restriction of parenteral or enteral fluids, or both, with or without diuretics, with control groups that received standard fluid intake, defined as no parenteral or enteral restriction, with or without diuretic use.

Data collection and analysis: We used standard Cochrane methods. Our primary outcome was closure of PDA. Other relevant outcomes were all-cause mortality by 36 weeks' postmenstrual age, need for interventional closure of the PDA, need for treatment with a cyclooxygenase inhibitor, bronchopulmonary dysplasia, severe intraventricular hemorrhage, and duration of hospitalization. We planned to use GRADE to assess the certainty of evidence for each outcome.

Main results: We did not identify any completed or ongoing RCTs that met our inclusion criteria and explored the effectiveness and safety of fluid restriction to treat symptomatic PDA.

Authors' conclusions: No evidence from RCTs is currently available to evaluate the benefits and harms of fluid restriction for the treatment of symptomatic patent ductus arteriosus in preterm infants. We identified no ongoing studies. Evidence from sufficiently powered RCTs evaluating fluid restriction for treatment of symptomatic PDA in preterm neonates is needed to inform clinical decisions.