Treatment of Patent Ductus Arteriosus and Neonatal Mortality/Morbidities: Adjustment for Treatment Selection Bias

Abstract

To examine the association between treatment for patent ductus arteriosus (PDA) and neonatal outcomes in preterm infants, after adjustment for treatment selection bias. Secondary analyses were conducted using data collected by the Canadian Neonatal Network for neonates born at a gestational age ≤ 32 weeks and admitted to neonatal intensive care units in Canada between 2004 and 2008. Infants who had PDA and survived beyond 72 hours were included in multivariable logistic regression analyses that compared mortality or any severe neonatal morbidity (intraventricular hemorrhage grades ≥ 3, retinopathy of prematurity stages ≥ 3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥ 2) between treatment groups (conservative management, indomethacin only, surgical ligation only, or both indomethacin and ligation). Propensity scores (PS) were estimated for each pair of treatment comparisons, and used in PS-adjusted and PS-matched analyses. Among 3556 eligible infants with a diagnosis of PDA, 577 (16%) were conservatively managed, 2026 (57%) received indomethacin only, 327 (9%) underwent ligation only, and 626 (18%) were treated with both indomethacin and ligation. All multivariable and PS-based analyses detected significantly higher mortality/morbidities for surgically ligated infants, irrespective of prior indomethacin treatment (OR ranged from 1.25-2.35) compared with infants managed conservatively or those who received only indomethacin. No significant differences were detected between infants treated with only indomethacin and those managed conservatively. Surgical ligation of PDA in preterm neonates was associated with increased neonatal mortality/morbidity in all analyses adjusted for measured confounders that attempt to account for treatment selection bias.