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J Clin Neonatol. 2014 Apr;3(2):67-75. doi: 10.4103/2249-4847.134670.

Patent ductus arteriosus ligation and adverse outcomes: causality or bias?

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Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, Toronto, Canada.
Department of Paediatrics, Division of Neonatology, University of Toronto, Toronto, Canada ; Department of Physiology, University of Toronto, Toronto, Canada ; Department of Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Canada.


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.


Chronic lung disease; confounding by indication; conservative; mortality; neurodevelopmental impairment; neurosensory impairment; preterm; retinopathy of prematurity

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