Editor’s Note: Dr. Elif Ozdogan (she/her) is a resident physician in Pediatrics at The Boston Combined Residency Program at Boston Children's Hospital and Boston Medical Center. She is interested in quality improvement and computational research and hopes to pursue further training in Transplant Medicine. -Rachel Y. Moon, MD, Associate Editor, Digital Media, Pediatrics
The fetal ductus arteriosus diverts cardiac blood flow away from the lungs to the systemic circulation. After an infant’s birth, the ductus arteriosus constricts and closes as the resistance in the pulmonary circulation drops. Failure of the ductus arteriosus to close by 3 days of life is termed patent ductus arteriosus (PDA). In extremely preterm infants (<28 weeks’ gestational age), incidence of PDA may exceed 50% and medical treatment is needed for those infants who have PDAs that affect pulmonary circulation (resulting in fluid in the lungs) and systemic circulation (resulting in reduced blood flow to the brain, bowel and kidneys).
In their article entitled “Acetaminophen for Patent Ductus Arteriosus and Risk of Mortality and Pulmonary Morbidity,” being early released this week in Pediatrics (10.1542/peds.2023-065056), Dr. Erik Jensen from Children’s Hospital of Philadelphia and colleagues studied a retrospective cohort of 1,921 extremely preterm infants in the NICHD Neonatal Research Network to compare the morbidity and mortality when acetaminophen or a cyclooxygenase (COX) inhibitor (ibuprofen or indomethacin) is used to treat PDA. The accompanying video abstract effectively illustrates their methodology and findings.
The authors especially focus on lung side effects of acetaminophen, because mouse studies suggest that the developing lung expresses the enzyme responsible for metabolizing acetaminophen into its toxic metabolite. Clinical and large epidemiological studies also raise similar concerns about the potential lung toxicity of acetaminophen.
Here is a summary of the comparison in outcomes between acetaminophen versus COX-inhibitor treatment:
- There was no difference in lung morbidity (defined as grade 2–3 bronchopulmonary dysplasia) or death prior to 36 weeks’ postmenstrual age.
- The infants who received acetaminophen had a higher risk of death prior to hospital discharge, with 2-fold increase in this risk in the subgroup of infants who received single drug therapy (i.e., only acetaminophen) for PDA. However, when late postnatal factors (>7 days) such as late-onset sepsis and systemic corticosteroid use were taken into account, this higher risk of pre-discharge mortality disappears.
- The infants who received acetaminophen had a higher risk of needing catheterized or surgical PDA closure.
As with any retrospective study, it is challenging to definitively determine whether acetaminophen caused or was merely associated with these effects. Large, randomized trials are necessary to tackle this question.
In the meantime, this study provides more data about the potential safety of acetaminophen use in PDA closure in extremely preterm infants.
