Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm

J Pediatr. 2020 May:220:34-39.e5. doi: 10.1016/j.jpeds.2020.01.069. Epub 2020 Mar 4.


Objectives: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes.

Study design: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio.

Results: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis.

Conclusions: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Keywords: morbidity; mortality; neonatal intensive care; patent ductus arteriosus; preterm infants.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Canada / epidemiology
  • Cardiovascular Surgical Procedures / statistics & numerical data
  • Cerebral Intraventricular Hemorrhage / epidemiology
  • Cohort Studies
  • Ductus Arteriosus, Patent / diagnostic imaging
  • Ductus Arteriosus, Patent / epidemiology
  • Ductus Arteriosus, Patent / therapy*
  • Echocardiography
  • Enterocolitis, Necrotizing / epidemiology
  • Europe / epidemiology
  • Female
  • Humans
  • Ibuprofen / therapeutic use
  • Indomethacin / therapeutic use
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Intensive Care Units, Neonatal*
  • Israel / epidemiology
  • Japan / epidemiology
  • Leukomalacia, Periventricular / epidemiology
  • Linear Models
  • Male
  • Retrospective Studies


  • Anti-Inflammatory Agents, Non-Steroidal
  • Ibuprofen
  • Indomethacin