Title: 474: Doppler assessment of the ductus arteriosus with ibuprofen exposure in pregnancy
Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with premature closure of the ductus arteriosus (DA). Ibuprofen is a member of the NSAID class with potential obstetric treatment advantages despite a 40-fold decreased potency compared to indomethacin. We sought to elucidate the effect of ibuprofen treatment in pregnancy on constriction of the DA. A retrospective case-control study was performed of all patients in a perinatology practice receiving Doppler assessment of DA waveforms between March 2014 and February 2019. The incidence of sonographic ductal constriction was quantified in the subset of women exposed to ibuprofen during pregnancy compared to non-exposed pregnancies. During the study period, ibuprofen was utilized as a part of clinical management regimens. DA waveforms were routinely interrogated by measurement of peak systolic velocity (PSV) to assess the risk of ductal constriction. PSV > 140 cm/second indicated increased risk of ductal constriction. All exams were reviewed for any abnormal DA PSV values. When available, subsequent exams were reviewed for persistence of abnormal DA waveforms. Standard statistical methods were used to characterize the effects of ibuprofen exposure. Within the study period, 5062 sonograms were performed with Doppler assessment of the DA. Of these, 547 examinations were performed in 115 patients in the ibuprofen exposure cohort and 4515 examinations in 3692 patients with non-exposed pregnancies. Ibuprofen exposure was associated with an increased incidence of abnormal DA PSV compared to non-exposed subjects (7.83% vs. 1.49%). Relative risk (RR) for abnormal DA PSV with ibuprofen exposure is 5.25 (95% CI 2.66 - 10.37; p< 0.0001). Six of the 9 patients with abnormal DA PSV had follow up exams after cessation of ibuprofen; all demonstrated normal DA PSV. Ibuprofen exposure in pregnancy appears to confer a 5-fold increased risk of abnormal DA PSV, a precursor to fetal ductal constriction. However, correction of PSV values with cessation of ibuprofen suggests that DA waveform changes may be readily reversible.