Neurodevelopmental Outcomes Following Two Different Treatment Approaches (Early Ligation and Selective Ligation) for Patent Ductus Arteriosus

Department of Pediatrics, University of California San Francisco, San Francisco, CA.
The Journal of pediatrics (Impact Factor: 4.02). 07/2012; 161(6). DOI: 10.1016/j.jpeds.2012.05.062
Source: PubMed

ABSTRACT OBJECTIVE: To examine whether a change in the approach to managing persistent patent ductus arteriosus (PDA) from early ligation to selective ligation is associated with an increased risk of abnormal neurodevelopmental outcomes. STUDY DESIGN: In 2005, we changed our PDA treatment protocol for infants born at ≤27 6/7 weeks' gestation from an early ligation approach, with prompt PDA ligation if the ductus failed to close after indomethacin therapy (period 1: January 1999 to December 2004), to a selective ligation approach, with PDA ligation performed only if specific criteria were met (period 2: January 2005 to May 2009). All infants in both periods received prophylactic indomethacin. Multivariate analysis was used to compare the odds of a composite abnormal neurodevelopmental outcome (Bayley Mental Developmental Index or Cognitive Score <70, cerebral palsy, blindness, and/or deafness) associated with each treatment approach at age 18-36 months (n = 224). RESULTS: During period 1, 23% of the infants in follow-up failed indomethacin treatment, and all underwent surgical ligation. During period 2, 30% of infants failed indomethacin, and 66% underwent ligation after meeting prespecified criteria. Infants treated with the selective ligation strategy demonstrated fewer abnormal outcomes than those treated with the early ligation approach (OR, 0.07; P = .046). Infants who underwent ligation before 10 days of age had an increased incidence of abnormal neurodevelopmental outcome. The significant difference in outcomes between the 2 PDA treatment strategies could be accounted for in part by the earlier age of ligation during period 1. CONCLUSION: A selective ligation approach for PDAs that fail to close with indomethacin therapy is not associated with worse neurodevelopmental outcomes at age 18-36 months.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Observational studies have associated patent ductus arteriosus (PDA) ligation in preterm infants with increased chronic lung disease (CLD), retinopathy of prematurity, and neurodevelopmental impairment at long-term follow-up. Although the biological rationale for this association is incompletely understood, there is an emerging secular trend toward a permissive approach to the PDA. However, insufficient adjustment for postnatal, pre-ligation confounders, such as intraventricular hemorrhage and the duration and intensity of mechanical ventilation, suggests the presence of residual bias due to confounding by indication, and obliges caution in interpreting the ligation-morbidity relationship. A period of conservative management after failure of medical PDA closure may be considered to reduce the number of infants treated with surgery. Increased mortality and CLD in infants with persistent symptomatic PDA suggests that surgical ligation remains an important treatment modality for preterm infants.
    04/2014; 3(2):67-75. DOI:10.4103/2249-4847.134670
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND AND OBJECTIVE Patent ductus arteriosus (PDA) ligation has been variably associated with neonatal morbidities and neurodevelopmental impairment (NDI). The objective was to systematically review and meta-analyze the impact of PDA ligation in preterm infants at <32 weeks' gestation on the risk of mortality, severe neonatal morbidities, and NDI in early childhood. Medline, Embase, Cochrane Central Register of Controlled Trials, Education Resources Information Centre (ERIC), Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Dissertation database were searched (1947 through August 2013). Risk of bias was assessed by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Meta-analyses were performed by using a random-effects model. Unadjusted and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were pooled when appropriate. Thirty-nine cohort studies and 1 randomized controlled trial were included. Nearly all cohort studies had at least moderate risk of bias mainly due to failure to adjust for survival bias and important postnatal preligation confounders such as ventilator dependence, intraventricular hemorrhage, and sepsis. Compared with medical treatment, surgical ligation was associated with increases in NDI (aOR: 1.54; 95% CI: 1.01-2.33), chronic lung disease (aOR: 2.51; 95% CI: 1.98-3.18), and severe retinopathy of prematurity (aOR: 2.23; 95% CI: 1.62-3.08) but with a reduction in mortality (aOR: 0.54; 95% CI: 0.38-0.77). There was no difference in the composite outcome of death or NDI in early childhood (aOR: 0.95; 95% CI: 0.58-1.57). Surgical ligation of PDA is associated with reduced mortality, but surviving infants are at increased risk of NDI. However, there is a lack of studies addressing survival bias and confounding by indication.
    PEDIATRICS 03/2014; 133(4). DOI:10.1542/peds.2013-3431 · 5.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.
    12/2013; 2013:676192. DOI:10.1155/2013/676192
    This article is viewable in ResearchGate's enriched format