The Clinical and Hemodynamic Influence on Ductal Closure to Acetaminophen Therapy in High-risk Extreme Low Gestational Age Newborns

Abstract

Aim: To compare clinical and echocardiographic characteristics between infants with successful ductal closure and persistent PDA post-acetaminophen treatment. Design: Single center clinical audit. Patients: Infants born< 28 weeks gestation. Place and Duration of Study: Tertiary NICU, KK Women’s and Children’s Hospital, Singapore from February 1st 2021 until October 31st 2024. Methodology: Infants born at less than 28 weeks gestation requiring treatment for HsPDA and received acetaminophen were included in the study. The clinical audit was conducted retrospectively, with early treatment defined as acetaminophen therapy initiated within the first two weeks of life and late thereafter. Results: Of the 116 infants studied, 70 received early treatment and the rest late therapy (>2 weeks) with acetaminophen, with PDA closure achieved in 30% of both groups. In the early treatment group, successful closures were associated with higher gestational age (27.11 ± 1.44 vs 25.73 ± 1.19 weeks; OR 1.7, 95% CI 1.3–2.3, p=0.001) and small for gestational age infants (38% vs 14%; OR 0.8, 95% CI 0.3–2.8, p=0.02). Echocardiography of infants with closure showed lower ductal diastolic velocity (0.36 ± 0.17 vs 0.51 ± 0.30 m/s, p=0.02), lower left ventricular end-systolic diameter (7.71 ± 1.21 vs 8.39 ± 1.36 mm; OR 1.5, 95% CI 1.08–2.34, p=0.04), and lower Doppler velocities across the main pulmonary  artery (0.66 ± 0.17 vs 0.83 ± 0.26 m/s; OR 0.07, 95% CI 0.01–0.45, p=0.003) and ascending aorta (0.82 ± 0.21 vs 0.95 ± 0.26 m/s, p=0.03). Logistic regression confirmed that higher gestational age and lower MPA systolic Vmax independently predicted ductal closure. In contrast, non-responders in the late therapy group had lower systolic (49.28 ± 6.17 vs 54.50 ± 10.59 mmHg, p=0.04) and mean blood pressures (32.19 ± 6.67 vs 37.71 ± 6.87 mmHg, p=0.01) without significant Doppler differences, and none of the measured variables—including gestational age (OR 0.8, 95% CI 0.54–1.12), SBP (OR 1.10, 95% CI 0.8–1.1), DBP (OR 1.04, 95% CI 0.7–1.08), or MAP (OR 0.87, 95% CI 0.7–1.8)—predicted closure. Conclusions: In infants receiving early acetaminophen therapy, higher gestational age and lower MPA systolic Vmax were significant predictors of PDA closure.