380 - Investigating the Potential Pulmonary Toxicity of Acetaminophen in Preterm Infants Treated for Patent Ductus Arteriosus

Publication Number: 380.5946

Swathi U. Ariyapadi, CHOC Children's Hospital of Orange County, Irvine, CA, United States; Rhucha Joshi, CHOC Children's Hospital of Orange County, Orange, CA, United States; Tricia Morphew, CHOC Children's Hospital of Orange County, Bothell, WA, United States; Michel Mikhael, CHOC Children's Hospital of Orange County, Orange, CA, United States

Background: Hemodynamically significant patent ductus arteriosus (PDA) frequently requires treatment in extremely preterm infants. Options for medical treatment include nonsteroidal anti-inflammatory drugs and recently acetaminophen, with rising popularity. Less is known about the effects of acetaminophen on pulmonary morbidity. Animal models suggest preterm lungs are vulnerable to its toxic metabolites. Clinical studies have shown an association between acetaminophen exposure and risk for asthma and bronchopulmonary dysplasia (BPD). No prior studies have investigated the temporal short-term effects of acetaminophen on respiratory illness.

Objective: Evaluate potential pulmonary adverse effects of acetaminophen compared to ibuprofen for treatment of PDA in preterm infants through assessment of short-term and hospitalization respiratory outcomes.

Design/Methods: A single-center retrospective study included infants born ≤ 28 wk. gestational age (GA) between 2018-2023 who received acetaminophen or ibuprofen as the first line treatment for PDA in the first 4 weeks of life. The primary outcome was the effect of either drug on respiratory severity score (RSS) through three days of treatment. RSS is the product of mean airway pressure and fraction of inspired oxygen. It has been previously validated as a proxy of pulmonary illness severity and a predictor of respiratory outcomes in preterm infants. Secondary outcomes included ventilator days, BPD severity, and home oxygen at discharge. T-test and chi-square testing were used for continuous and categorical variables.

Results: Sixty-three infants were included with an average of 25.2 wk. GA and 747 g birthweight. Out of whom 24 received ibuprofen and 39 received acetaminophen for PDA treatment. Infants who received acetaminophen had less exposure to antenatal steroids (62% vs. 91%, p=0.013) and more severe intraventricular hemorrhage (34% vs. 8%, p=0.032). There were no other statistically significant differences in perinatal and clinical characteristics (Table 1). Figure 1 displays RSS at baseline and after initiation of PDA treatment and shows no differences between the groups. Mechanical ventilator days, BPD and home oxygen therapy were comparable for the study cohort (Table 2).

Conclusion(s): First line treatment for PDA with acetaminophen or ibuprofen has similar effects on preterm infants’ pulmonary health in our cohort. Larger studies are needed to further investigate the impact of crossover treatment, repeated courses and other potential confounding variables that might contribute to respiratory outcomes.

Figure 1. Boxplot displays the distribution of Respiratory Severity Score (RSS) at baseline (Day 0) prior to starting treatment and over the subsequent three days.
A generalized linear mixed model with a gamma distribution assessed average RSS between treatment groups, adjusting for repeated measures across days and shows no statistical differences.

Table 1. Comparison of the perinatal and baseline clinical characteristics for the study cohort.
a Race listed among non-Hispanic patients: Asian (n=6), Black (n=6), White (n=8), Other (n=5)
* p<.05, P-value based on Chi-square test for categorical variables, independent t-test for continuous factors (Mann-Whitney U test when departures from normality apparent and median [IQR] reported]

Table 2. Comparison of hospitalization outcomes by treatment group.
* p<.05, P-value based on Chi-square test for categorical variables (Fisher’s exact test when expected cell count <5), independent t-test for continuous factors (Mann-Whitney U test when departures from normality apparent and median [IQR] reported]