Neurodevelopmental Outcomes (NDO) in Premature Infants Receiving Medical Management for Hemodynamically Significant Patent Ductus Arteriosus (hsPDA)

Background: Hemodynamically significant PDA (hsPDA) in preterm infants is associated with morbidities like bronchopulmonary dysplasia (BPD), poor growth and necrotizing enterocolitis (NEC). Medical management to close hsPDA is variable and sometimes controversial. Short and long term outcomes have been studied well with Indomethacin and Ibuprofen. Acetaminophen is being increasingly used for closure of hsPDA in infants with renal or platelet dysfunction and intraventricular hemorrhage. There is a paucity of literature regarding the long term outcomes for infants treated with acetaminophen. The aim of the study was to compare the NDO of premature infants who received acetaminophen for closure of hsPDA with those who received indomethacin or ibuprofen

Methods: Retrospective cohort study of preterm infants < 32 weeks gestation receiving medications for closure of hsPDA from 2014 to 2018. Infants who died before hospital discharge were excluded. Maternal and infant characteristics were compiled. The infants are followed and assessed by Bayley Scale of Infant Development (BSID) III at 1 and 2 yr corrected gestational age (CGA). The composite scores for cognition (CCS), language (LCS) and motor (MCS) were noted. P values were obtained with appropriate statistical tests.

Results: Eighty one infants were included. Forty four (44 %) were treated with acetaminophen and 56% received indomethacin or ibuprofen. Acetaminophen use is more common in years 2017 & 2018. There were no differences in GA, BW, gender and race between the two groups (Table 1). There were no significant differences in rates of BPD, severe IVH, hypotension requiring inotropes, length of stay, duration ventilation between the two groups. Table 2 shows the BSID scores at one and two-year CGA for the two groups. There was no difference in CCS, LCS and MCS at 1 year CGA between the two groups. At 2 years CGA, median CCS (min, max) were 100 (55, 125) and 95 (55, 115) respectively for acetaminophen and indomethacin/ibuprofen treated infants ( p 0.61). The median LCS (min, max) were 91.5 (43, 110) and 89 (50, 109) respectively for acetaminophen and indomethacin/ibuprofen treated infants ( p=0.55). There was no significant difference in MCS between the groups ( 91 (46, 112) vs 94 (45, 115) p=0.63). There was no significant difference in CCS between the groups (100(55,125) vs 100(75,120) p=0.61).

Conclusion: Acetaminophen is being more commonly used medication in recent years for the management of hsPDA in this cohort of preterm infants. There was no significant difference in long term NDO between the preterm infants treated with acetaminophen compared to indomethacin or ibuprofen for closure of hsPDA.
Further prospective trials with larger number of infants are needed to study long term outcomes of infants treated with acetaminophen for closure of hsPDA.