[Skip to Navigation]
Views 399
Citations 0
Comment & Response
January 19, 2021

Nonintervention Is Not Noninferior to Oral Ibuprofen for Treatment of Patent Ductus Arteriosus—Reply

Author Affiliations
  • 1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • 2Statistics and Data Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
JAMA Pediatr. 2021;175(4):430-431. doi:10.1001/jamapediatrics.2020.5329

In Reply We thank Razak for the comments on our randomized clinical trial comparing nonintervention and oral ibuprofen treatment for patent ductus arteriosus (PDA).1

First, because the PDA might close spontaneously,2 we could avoid unnecessary treatment exposure in 37% (143 of 383) of patients by delaying their enrollment for approximately 1 week.1 In contrast with other trials showing 21% pulmonary hemorrhage, 12.5% of intraventricular hemorrhage, and 40% of backup treatments,3 6% of intraventricular hemorrhage and no pulmonary hemorrhage nor backup treatment were observed in the nonintervention arm of our trial.1 Therefore, nonintervention alone is not enough, but meticulous neonatal intensive care including judicious fluid restriction starting at 67 mL/kg per day is essential for the success of this approach.1,2,4,5 Considering no significantly higher odds of PDA closure (1.63; 95% CI, 0.83-3.25) with high vs standard dose of oral ibuprofen and lowest incidence of bronchopulmonary dysplasia (BPD)/death with standard dose observed in a meta-analysis,6 our data showing significant PDA closure only in infants at the gestational age of 27 to 30 weeks but not at the gestational age of 23 to 26 weeks might thus reflect that it is gestational age rather than dose-dependent variation for PDA closure.1,2 Because only patients with symptomatic PDA requiring respiratory support, with the average PDA size of 2.5 mm and left atrium/aorta ratio of 1.69 and 1.61 in the ibuprofen and nonintervention arm, respectively, were enrolled, our study population was homogenous with moderate to severe clinical and echocardiographic severity in both arms.

Add or change institution
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×