A case control study of patent ductus arteriosus in preterm infants treated with acetaminophen and platelet-rich plasma

Abstract

Objective To study the possible mechanisms, efficacy and safety of acetaminophen and platelet-rich plasma (PRP) on promoting the closure of ductus arteriosus in preterm infants. Method From January 2016 to May 2018, preterm infants (gestational age<34 weeks) with symptomatic patent ductus arteriosus (sPDA) admitted to our neonatal intensive care unit were enrolled prospectively. 15 mg/kg of acetaminophen was orally given every 6 hours for three days (acetaminophen group). If acetaminophen was contraindicated (PRP group) or acetaminophen therapy failed (PRP rescue group), PRP transfusion was given at a single dose of 20 ml/kg. Echocardiogram, platelet-derived growth factors (PDGF) and urinary prostaglandin E2 (PGE2) were examined before and 72 hours after treatment. The data were analyzed using ANOVA, student′s t test, Kruskal-Wallis H method and chi-square test. Result A total of 70 cases were enrolled. 61 cases were treated with acetaminophen. The success rate (67.2%, 41/61) was similar to PRP group (6/9) (P=1.000), and significantly higher than PRP rescue group (6/17) (P=0.017). The complications in acetaminophen group included 22 cases of hyperbilirubinemia (36.1%), 5 cases of upper gastrointestinal hemorrhage (8.2%), 4 cases of positive fecal occult blood test (6.6%), 3 cases of oliguria (4.9%), 1 case of Grade Ⅲ~Ⅳ intraventricular hemorrhage (IVH) (1.6%), and 1 case of ≥Ⅱ stage necrotizing enterocolitis (NEC) (1.6%). A total of 3 cases of hyperbilirubinemia were in PRP group. One case of hyperbilirubinemia, one oliguria, one Grade Ⅲ~Ⅳ IVH and one ≥Ⅱ stage NEC were in PRP rescue group. The urinary PGE2 level in post-treatment was lower than pre-treatment in acetaminophen group (t=6.878, P<0.001). The blood platelet count and PDGF level in post-treatment were higher than pre-treatment in PRP group (t=-2.496, -8.906; P=0.037,<0.001) and PRP rescue group (t=-3.374, -2.503; P=0.004, 0.024). Conclusion Oral acetaminophen and PRP transfusion had similar efficacy in promoting the closure of ductus arteriosus in preterm infants. If oral acetaminophen was contraindicated or failed, PRP transfusion could be one of the candidates for rescue therapy to promote the closure of ductus arteriosus in preterm infants. Key words: Acetaminophen; Blood Platelets; Ductus arteriosus, patent; Platelet-derived growth factor; Infant, premature