Drug exposure for PDA closure in France: a prospective, cohort-based, analysis

Eur J Clin Pharmacol. 2020 Dec;76(12):1765-1772. doi: 10.1007/s00228-020-02974-1. Epub 2020 Aug 1.


Purpose: To describe the exposure to drugs used for the treatment of patent ductus arteriosus (PDA) in a large cohort of preterm infants born before 32 weeks of gestation.

Methods: A prospective observational cohort analysis was conducted during 2 years in 28 French level 3 NICU using the same computerized order-entry system. The main outcome was "a medically treated PDA," defined as exposure to ibuprofen, indomethacin, or paracetamol prescribed with the indication of PDA closure. Secondary outcomes were as follows: time of the first treatment administration; total exposure to furosemide during hospitalization; and rate of PDA refractory to pharmacological closure.

Results: The study cohort consisted of 2614 infants. Among them, 474 (18.1%) received a medical treatment for PDA, with a mean postnatal age at treatment of 4.3 ± 6.6 days. The drug used as a first-line treatment was ibuprofen in 89.5% and paracetamol in 10.5%. One hundred and ninety-five infants (7.4%) had a PDA refractory to pharmacological closure. At the multivariate analysis, factors associated with PDA refractory to pharmacological closure (OR; 95% CI) were as follows: gestational age (GA) (0.81; 0.72-0.90), paracetamol as the first-line treatment (0.32; 0.15-0.68), and pharmacological treatment before 48 h of life (0.63; 0.43-0.94). 24.6% of the study cohort was exposed to furosemide (cumulative dose 6.5 ± 12.6 mg/kg). Variables significantly associated with higher cumulative doses of furosemide were lower GA and ibuprofen treatment (both p < 0.0001).

Conclusion: Drug utilization patterns in infants with PDA vary among centers. Pharmacoepidemiology studies can provide new information on factors associated with PDA refractory to medical treatment.

Keywords: Drug utilization; Neonatal diuretics; Neonatal intensive care unit; Non-steroidal anti-inflammatory drugs; Very-low-birth-weight-infants.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Acetaminophen / therapeutic use*
  • Administration, Oral
  • Drug Resistance
  • Drug Utilization / statistics & numerical data
  • Ductus Arteriosus, Patent / drug therapy*
  • Female
  • France
  • Furosemide / therapeutic use*
  • Hospitalization
  • Humans
  • Ibuprofen / therapeutic use*
  • Indomethacin / therapeutic use*
  • Infant, Newborn
  • Infant, Premature
  • Intensive Care Units, Neonatal / statistics & numerical data
  • Male
  • Practice Patterns, Physicians' / statistics & numerical data
  • Prospective Studies
  • Treatment Outcome


  • Acetaminophen
  • Furosemide
  • Ibuprofen
  • Indomethacin