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

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.

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

Figure 1

Directed acyclic graph depicting the relationship between perinatal and postnatal factors, physiological instability and systemic inflammation, patent ductus arteriosus ligation and neonatal and neurodevelopmental outcomes (ACS – Antenatal corticosteroids, CLD – Chronic lung disease; GA – Gestational age, ROP – Retinopathy of prematurity, PDA – Patent ductus arteriosus)