Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan 28:9:807712.
doi: 10.3389/fped.2021.807712. eCollection 2021.

Randomized Trial on Echocardiography-Guided Ductus Arteriosus Treatment to Reduce Necrotizing Enterocolitis

María Carmen Bravo  1 , Rebeca Sánchez-Salmador  1 , María Teresa Moral-Pumarega  2 , Manuela López-Azorín  3 , Rocío Mosqueda-Peña  2 , Izaskun Dorronsoro  3 , Fernando Cabañas  3 , Adelina Pellicer  1
Affiliations

Randomized Trial on Echocardiography-Guided Ductus Arteriosus Treatment to Reduce Necrotizing Enterocolitis

María Carmen Bravo et al. Front Pediatr. .

Abstract

Objective: Patent ductus arteriosus (PDA) approach remains controversial. We aim to evaluate whether echocardiography-guided (EchoG) PDA closure (to reduce drug exposure) and 24-h continuous ibuprofen infusion (24 h-IB) (to reduce peak concentration), compared with EchoG PDA closure plus conventional bolus (bolus-IB), reduces severe bowel adverse event rate in preterm infants with hemodynamically significant (hs) PDA.

Study design: The study design is a multicenter, blinded, randomized controlled trial. Infants with <28 weeks of gestation underwent routine echocardiographic assessment (18-72 h of birth); infants with 28-33 weeks were screened only in cases where PDA was clinically suspected. HsPDA was considered if ductal diameter >1.5 mm and indicators of pulmonary overflow, systemic hypoperfusion, or both were present. Pharmacodynamic effect of CYP450 genotypes was also analyzed.

Results: One hundred forty-six infants [median gestational age 26 (25-28) weeks; median birth weight 881 (704-1,100) g] were randomized to 24 h-IB (n = 70) or bolus-IB (n = 76) study group at 86 (58-140) h from birth. Groups were comparable regarding perinatal and neonatal clinical data, but higher prevalence of male sex in the bolus-IB group was found. Neither severe bowel adverse event rate [10% (24 h-IB) and 2.6% (bolus-IB), p = 0.1] nor ductal closure rate was different between the study groups. Postnatal age and peripheral SaO2 at treatment start and pulmonary hemorrhage were associated with severe bowel events, independent of treatment group allocation. CYP2C8 genetic polymorphisms were associated with ibuprofen efficacy (p = 0.03).

Conclusions: Ibuprofen intravenous continuous infusion compared with bolus infusion in preterm infants with hsPDA shows similar rates of success and does not reduce the prevalence of severe bowel events.

Keywords: Neonatologist Performed Echocardiography; ductus arteriosus; echocardiographically-guided; ibuprofen; necrotizing enterocolitis; preterm.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Patient flowchart.
See this image and copyright information in PMC

References

    1. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database System Rev. (2018) 9:CD003481. 10.1002/14651858.CD003481.pub7 - DOI - PMC - PubMed
    1. Bravo MC, Cabañas F, Riera J, Pérez-Fernández E, Quero J, Pérez-Rodríguez J, et al. . Randomised controlled clinical trial of standard versus echocardiographically guided ibuprofen treatment for patent ductus arteriosus in preterm infants: a pilot study. J Matern Neonatal Med. (2014) 27:904–9. 10.3109/14767058.2013.846312 - DOI - PubMed
    1. Mitra S, Florez ID, Tamayo ME, Mbuagbaw L, Vanniyasingam T, Veroniki AA, et al. . Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants a systematic review and meta-analysis. J Am Med Assoc. (2018) 319:1221–38. 10.1001/jama.2018.1896 - DOI - PMC - PubMed
    1. El-Mashad AER, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr. (2017) 176:233–40. 10.1007/s00431-016-2830-7 - DOI - PubMed
    1. Lago P, Salvadori S, Opocher F, Ricato S, Chiandetti L, Frigo AC. Continuous infusion of ibuprofen for treatment of patent ductus arteriosus in very low birth weight infants. Neonatology. (2013) 105:46–54. 10.1159/000355679 - DOI - PubMed

LinkOut - more resources