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: 3.79). 07/2012; 161(6). DOI: 10.1016/j.jpeds.2012.05.062
Source: PubMed


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).

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.

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.

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    • "Studies have reported that strategies avoiding or more selectively administering ductal closure treatments resulted in outcomes that are no worse (and perhaps better) than outcomes where infants were more aggressively treated with medication or surgery.[89909192] Jhaveri et al. reported similar neonatal outcomes with a late, selective ligation strategy compared with an early ligation approach for infants with a persistent PDA after medical therapy failure.[91] "
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    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.
    Full-text · Article · Apr 2014
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    • "A secondary analysis of data from TIPP trial revealed increase risk of neurosensory impairment and cognitive delay at 18 months in infants who were subjected to surgical ligation [64]. Further subsequent studies, in which multivariate analysis of data was done to adjust other potential confounders for abnormal neurodevelopmental outcome, revealed that ligation status itself (ligation versus no ligation) does not appear to be a predictor of neurodevelopmental outcome [58, 176, 178]. However, Wickremasinghe et al. [178] found an increased incidence of abnormal neurodevelopmental outcome in patients who underwent ligation before 10 days of age. "
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    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.
    Full-text · Article · Dec 2013

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