447 - Racial and Ethnic Differences in Patent Ductus Arteriosus Treatment Response to Indomethacin and Ibuprofen in Very-Low-Birthweight Infants: A 12-Year Longitudinal Cohort Study

Publication Number: 3432.447

Priya R. Gupta, University of Connecticut School of Medicine, Farmington, CT, United States; Mariann Pappagallo, University of Connecticut School of Medicine, Farmington, CT, United States; Ted S. Rosenkrantz, University of Connecticut School of Medicine, Farmington, CT, United States; Naveed Hussain, Connecticut Children's Medical Center, Farmington, CT, United States

Background: Variability in the efficacy of indomethacin (INDO) and ibuprofen (IBU) for pharmacologic PDA closure in very-low-birthweight (VLBW) infants is well-recognized. Racial and ethnic variations in cytochrome P450 enzyme alleles (CYP2C8 and CYP2C9) affecting NSAID metabolism may underlie interindividual differences in response. However, race-based differences in INDO vs. IBU efficacy for PDA closure have not been systematically examined.

Objective: To determine whether infant race or ethnicity are associated with the success of INDO or IBU treatment for PDA in VLBW infants.

Design/Methods: We conducted a 12-year retrospective cohort study of VLBW infants (≤ 32 weeks gestational age) admitted to Connecticut Children's NICUs in Hartford, CT and Farmington, CT in 2011-2023. PDA treatment failure, defined as need for repeat medical therapy or surgical closure, was compared by race and ethnicity and treatment type (INDO vs. IBU). Race and ethnicity were classified using maternal self-identification. Analyses were done by race, white vs. non-white, and Hispanic vs. non-Hispanic. Associations between race, treatment type, and treatment failure were analyzed with Fisher's exact tests and multivariable logistic regression models including treatment, race, and interaction terms.

Results: Among 2,003 admitted infants, 726 (36%) were diagnosed with PDA, of which 378 (52%) received pharmacologic treatment (INDO=183, IBU=195). Treatment failure was 46% (172/378) with no differences in treatment failure across racial groups for either drug (p ≥ 0.27). Between-treatment comparisons within racial groups were also not significant (p ≥ 0.61). Logistic regression revealed no significant race × treatment interaction (LRT p = 0.67). The Cochran-Mantel-Haenszel common odds ratio for 'Race | Treatment' was 1.10 (95% CI 0.57-2.11; p = 0.77). Birthweight was inversely associated with treatment failure (OR 0.75 per 100g increase; p = 0.004). After controlling for birthweight, sex, and antenatal steroid exposure, there was no evidence that treatment failure differed by race. There were no differences in overall treatment failure or treatment failure with INDO or IBU in Hispanic vs. non-Hispanic infants (p = 0.06).

Conclusion(s): PDA treatment response to indomethacin or ibuprofen did not differ by race or ethnicity among VLBW infants. These results suggest that genetic polymorphisms rather than race likely drive interindividual variability in NSAID response. Prospective studies incorporating pharmacogenomic profiling are warranted to guide personalized PDA therapy.

Race and Ethnicity of Study Cohort
Figure 1: Race and ethnicity of study cohort. (A) Breakdown of population by race using US census criteria; (B) Distribution of Hispanic and non-Hispanic infants.

PDA Treatment Failure Rates by Race and Treatment
Figure 2: PDA treatment failure rates by race and treatment. No significant differences were seen in response to PDA treatment with indomethacin, ibuprofen, or either medication by race categories. Categories with total sample size < 5 were excluded. Error bars indicate 95% Wilson confidence intervals.

Results of Multiple Logistic Regression
Table 1: Results of multiple logistic regression - adjusted model (with interaction). Results reported as odds ratios (ORs) with 95% confidence intervals (CIs).