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

International Network for Evaluating Outcomes of Neonates (iNeo) Investigators, Outi Tammela

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)34-39.e5
Publication statusPublished - May 2020
Publication typeA1 Journal article-refereed


  • 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
  • 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

Publication forum classification

  • Publication forum level 2


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