202 - Clinical and Echocardiography predictors of acetaminophen treatment response in preterm infants with hemodynamically significant Patent Ductus Arteriosus.

Poster Number: 202
Publication Number: 202.220

Stephania Cavallaro Moronta, University of Iowa, Coralville, IA, United States; Adrianne Rahde Bischoff, University of Iowa, Iowa city, IA, United States; Kelli K. Ryckman, University of Iowa College of Public Health, Iowa City, IA, United States; Regan E. Giesinger, University of Iowa, Iowa City, IA, United States; John M. Dagle, Univ of Iowa, Iowa City, IA, United States; Patrick J. McNamara, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, United States

Background: Patent ductus arteriosus (PDA) is the most common cardiovascular derangement of prematurity. Medical therapy with Cyclo-oxygenase inhibitors is the usual 1st-line approach; however, treatment is ineffective for 21-40% patients and commonly associated with side effects. Acetaminophen is an emerging therapy and trials have demonstrated its clinical efficacy in mature patients but no studies have characterized predictors of response as a 1st line agent in extremely preterm infants.

Objective: To characterize clinical and echocardiography determinants of response to acetaminophen, as a 1st line agent in preterm infants < 30 weeks with hemodynamically significant PDA (hsPDA).

Design/Methods: Retrospective cohort study of preterm infants born < 30 weeks, admitted to the NICU at the University of Iowa Stead Family Children’s Hospital (Sep 2018 - July 2021) with a targeted neonatal echocardiography (TnECHO) diagnosis of hemodynamically significant PDA and who received 1st line treatment with acetaminophen during the first 2 postnatal weeks was conducted. Modified Iowa PDA score (Table 1) was used to objectively define shunt volume. Acetaminophen response was defined as PDA closure or >50% reduction in PDA score after the last dose of acetaminophen (15mg/kg: 12-28 doses). In cases of borderline change in PDA score (30-50%), response was adjudicated by expert consensus. All TnECHO measurements were performed offline by a single expert operator blinded to the clinical course. Comparative evaluation of neonatal demographics and PDA TnECHO characteristics between responders and non-responders were performed using univariate analysis.

Results: A total of 100 infants were included: 64 responders, 23 (36%) closed after therapy (17 never re-opened) and 41 (64%) had an improved PDA score (16 never required further treatment) and 36 non-responders. Acetaminophen response was associated with ethnicity, intrauterine growth restriction and maternal hypertension (Table 2) but only left ventricular output differentiated the groups on TnECHO evaluation. (Table 3) Non-responders were more likely to require interventional closure and had longer duration of mechanical ventilation.Conclusion(s): First line response to acetaminophen therapy was comparable to ibuprofen and indomethacin in preterm infants < 30 weeks (approximately 60%). Vascular effects of placental insufficiency and other factors may be associated with higher likelihood of response, potentially due to increased ductal muscularization. Further TnECHO modulators such as PDA morphology and genetics warrant further investigation.
Table 1: Modified Iowa patent ductus arteriosus score. Adapted from Rios DR et al, 2020.IVRT = isovolumetric relaxation time, PV = pulmonary vein, LA:Ao = Left atrium to aorta ratio, LVO:RVO = Left ventricular output to right ventricular output ratio.
Table 2: Demographics and baseline characteristics of preterm infants who received acetaminophen as first line therapy for patent ductus arteriosus in the first 2 postnatal weeks.IVH = Intraventricular hemorrhage, ROP = Retinopathy of prematurity, NEC = Necrotizing enterocolitis, SIP = Spontaneous intestinal perforation, PH = Pulmonary hypertension, MV = mechanical ventilation, HF = High frequency, NIV = non-invasive ventilation.