There is currently no consensus for the screening and treatment of patent ductus arteriosus (PDA) in extremely preterm infants. Less pharmacological closure and more supportive management has been observed without evidence to support these changes. In a population-based cohort of extremely preterm infants (EPIPAGE 2), screening echocardiography before day 3 of life was associated with lower in-hospital mortality and likelihood of pulmonary hemorrhage; however this observational study leaves some ambiguity in the interpretation of the results and longer-term evaluation is needed to provide clarity.
Objective: To evaluate the association between screening echocardiography for PDA before day 3 and in-hospital mortality in very preterm newborns.
Method: We compared screened and not screened preterm infants enrolled in a national prospective population-based cohort study including all preterm infants born at less than 29 weeks of gestation and hospitalized in 68 neonatal intensive care units in France from April through December 2011. Two main analyses were performed to adjust for potential selection bias, one using propensity score matching and one using unit preference for early screening echocardiography as an instrumental variable.
The primary outcome was death between day 3 and discharge. The secondary outcomes were major neonatal morbidities: pulmonary hemorrhage, severe bronchopulmonary dysplasia, severe cerebral lesions, and necrotizing enterocolitis.
Results: Among the 1513 preterm infants with data available to determine exposure, 847 were screened for PDA and 666 were not; 605 infants from each group could be paired. Exposed infants were treated for PDA more frequently during their hospitalization (55.1%) than non exposed (43.1%), (Odds Ratio [OR], 1.62; 95% Confidence Interval [CI], 1.31–2.00; Absolute Risk Reduction [ARR] in events per 100 infants, -12.0; 95% CI, -17.3 to -6.7). They had a lower hospital death rate (14.2% versus 18.5% ; OR 0.73 [95% CI, 0.54–0.98]; ARR, 4.3 [95% CI, 0.3 – 8.3]) and a lower rate of pulmonary hemorrhage (5.6% versus 8.9%; OR, 0.60 [95% CI, 0.38–0.95]; ARR, 3.3 [95% CI, 0.4 – 6.3]). No differences in necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions rates were observed. In the overall cohort, Instrumental variable analysis yielded an adjusted OR of in-hospital mortality of 0.62 [95% CI, 0.37-1.04].
Conclusion: In this population-based cohort of extremely preterm infants, screening echocardiography before day 3 of life was associated with lower in-hospital mortality and likelihood of pulmonary hemorrhage but not with differences in necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions. However, results of the instrumental variable analysis leave some ambiguity in the interpretation, and longer-term evaluation is needed to provide clarity.
To learn more:
Rozé JC, Cambonie G, Marchand-Martin L, Gournay V, Durrmeyer X, Durox M, Storme L, Porcher R, Ancel PY, Hemodynamic EPIPAGE 2 Study Group. Association between early screening for patent ductus arteriosus and in-hospital mortality among extremely preterm infants. JAMA 2015;313:2441-8. http://www.ncbi.nlm.nih.gov.gate2.inist.fr/pubmed/26103028