Efficacy of pharmacologic closure of patent ductus arteriosus in small-for-gestational-age extremely preterm infants

Early Hum Dev. 2017 Oct;113:10-17. doi: 10.1016/j.earlhumdev.2017.07.011. Epub 2017 Jul 8.


Background: Optimal management of the patent ductus arteriosus (PDA) in preterm infants remains controversial. Therefore, studies identifying infants who are most likely to benefit from PDA treatment are needed.

Aim: We sought to examine if significant intrauterine growth restriction, defined by birth weight z-score, reduces the efficacy of PDA closure with indomethacin or ibuprofen and thereby increases the need for surgical closure of PDA after pharmacologic treatment.

Study design, subjects, and outcome measures: We studied infants 23-28weeks' gestation born 2006-2013 at NICHD Neonatal Research Network centers. We examined the responses to PDA treatment with indomethacin and/or ibuprofen and whether the PDA was subsequently closed surgically. Logistic regression generated adjusted odds ratios (ORs) for the associations between the z-score groups (<-2, -2 to -0.5, and >-0.5) and PDA surgery following pharmacologic treatment.

Results: 5606 infants were diagnosed with PDA; 3587 (64.0%) received indomethacin or ibuprofen or both, and 909 (25.3%) underwent PDA surgery. Mothers of infants with PDA non-closure were less likely to have hypertension (19% vs. 28%). Infants with non-closure were more likely to be female (53% vs. 49%), have lower gestational age and birth weight and to develop sepsis (42% vs. 31%). Compared to infants with z-score>-0.5, PDA surgery was increased among infants with z-score -2 to -0.5 (OR=1.23; 95% CI 1.02-1.47) but not among infants with z-score<-2.

Conclusion: Infants with birth weight z-score -2 to -0.5 are more likely than normally grown infants to require PDA surgery following pharmacologic treatment.

Trial registration: ClinicalTrials.gov NCT00063063 NCT00009633.

Keywords: Ibuprofen; Indomethacin; Morbidity; Mortality; Premature infants.

Publication types

  • Clinical Trial

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Ductus Arteriosus, Patent / drug therapy*
  • Ductus Arteriosus, Patent / epidemiology
  • Ductus Arteriosus, Patent / surgery
  • Female
  • Humans
  • Ibuprofen / adverse effects*
  • Ibuprofen / therapeutic use
  • Indomethacin / adverse effects*
  • Indomethacin / therapeutic use
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Infant, Small for Gestational Age*
  • Male


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

Associated data

  • ClinicalTrials.gov/NCT00063063
  • ClinicalTrials.gov/NCT00009633