Factors Associated With Benefit of Treatment of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis

• Main Authors: Esther J. S. Jansen (Author), Tim Hundscheid (Author), Wes Onland (Author), Elisabeth M. W. Kooi (Author), Peter Andriessen (Author), Willem P. de Boode (Author)
• Format: Book
• Published: Frontiers Media S.A., 2021-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2296-2360; 10.3389/fped.2021.626262
• Keywords: ductus botalli; patent ductus arteriosis; premature (babies); ibuprofen; indometacin; acetaminophen; Pediatrics; RJ1-570
• Source: Frontiers in Pediatrics, Vol 9 (2021)

Context: There is an ongoing debate on the optimal management of patent ductus arteriosus (PDA) in preterm infants. Identifying subgroup of infants who would benefit from pharmacological treatment might help.Objective: To investigate the modulating effect of the differences in methodological quality, the rate of open-label treatment, and patient characteristics on relevant outcome measures in randomized controlled trials (RCTs).Data Sources: Electronic database search between 1950 and May 2020.Study Selection: RCTs that assessed pharmacological treatment compared to placebo/no treatment.Data Extraction: Data is extracted following the PRISMA guidelines. Outcome measures were failure to ductal closure, surgical ligation, incidence of necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, periventricular leukomalacia, intraventricular hemorrhage (IVH) grade ≥3, retinopathy of prematurity and mortality.Results: Forty-seven studies were eligible. The incidence of IVH grade ≥3 was lower in the treated infants compared to the placebo/no treatment (RR 0.77, 95% CI 0.64-0.94) and in the subgroups of infants with either a gestational age <28 weeks (RR 0.77, 95% CI 0.61-0.98), a birth weight <1,000 g (RR 0.77, 95% CI 0.61-0.97), or if untargeted treatment with indomethacin was started <24 h after birth (RR 0.70, 95% CI 0.54-0.90).Limitations: Statistical heterogeneity caused by missing data and variable definitions of outcome parameters.Conclusions: Although the quality of evidence is low, this meta-analysis suggests that pharmacological treatment of PDA reduces severe IVH in extremely preterm, extremely low birth weight infants or if treatment with indomethacin was started <24 h after birth. No other beneficial effects of pharmacological treatment were found.