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

Neurodevelopmental Outcomes of Premature Infants Treated for Patent Ductus Arteriosus: A Population-Based Cohort Study

“…Although composite outcome (ie, mortality or severe morbidity, including severe IVH, ROP, NEC, PVL [periventricular leukomalacia], or BPD) was not statistically different between indomethacin-treated infants and those receiving supportive therapy alone, "any surgical ligation" irrespective of other treatments was an independent predictor of adverse composite outcome. 38 The higher risk of adverse neurodevelopmental outcomes seen in our PDASurg group may be related in part to the significantly higher rate of NEC. The association between NEC and subsequent neurodevelopmental impairment at age 18-22 months has been documented in a large multicenter study in ELBW infants.…”

“…This disparity may reflect, in part, the difference in control groups (ie, PDANoneTreat infants vs infants with PDA receiving supportive therapy only), but also may be related to treatment selection bias derived from nonindependent baseline prognostic factors. 38 When considering long-term outcomes, it is important to recognize that neurodevelopment is influenced not only by type of treatment, but also by the details of that treatment. For example, timing of treatment appears to play a major role in long-term outcomes of surgical ligation.…”

PDA Ligation and Health Outcomes: A Meta-analysis

“…Six authors provided additional data or analyses not included in their original publication. 8,[30][31][32][33][34] Baseline characteristics of the 40 studies included 8,10,11, (39 cohort studies and 1 RCT), encompassing 32 345 preterm infants, are reported in Table 1.…”

“…Eleven cohort studies performed multivariate analyses. Data from 9 of these studies 8,10,11,30,33,51,58,63,64 and the RCT 35 were combined in meta-analyses of multivariate results. Data from 2 cohort studies 32,34 could not be pooled because of insufficient information to interpret the adjusted results.…”

“…7 Several investigators have studied PDA ligation and its association with neonatal mortality, short-term morbidity, and neurodevelopmental impairment (NDI) in early childhood. Mirea et al 8 and Clyman et al 9 found increased retinopathy of prematurity (ROP) and CLD in infants treated with ligation compared with non-surgically treated infants. Two large studies found that extremely preterm infants who were treated with surgical ligation had significantly higher odds of NDI at 2-year follow-up, 10,11 although a third study showed no increased risk.…”