Association Between Early Screening for Patent Ductus Arteriosus and In-Hospital Mortality Among Extremely Preterm Infants

Abstract

for the Hemodynamic EPIPAGE 2 Study Group IMPORTANCE 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 have been observed without evidence to support these changes.OBJECTIVE To evaluate the association between early screening echocardiography for PDA and in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTSComparison of screened and not screened preterm infants enrolled in the EPIPAGE 2 national prospective population-based cohort study that included 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 neonatal unit preference for early screening echocardiography as an instrumental variable.EXPOSURES Early screening echocardiography before day 3 of life. MAIN OUTCOMES AND MEASURESThe 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 than nonexposed infants (55.1% vs 43.1%; odds ratio [OR], 1.62 [95% CI, 1.31 to 2.00]; absolute risk reduction [ARR] in events per 100 infants, −12.0 [95% CI, −17.3 to −6.7). Exposed infants had a lower hospital death rate (14.2% vs 18.5% ; OR, 0.73 [95% CI, 0.54 to 0.98]; ARR, 4.3 [95% CI, 0.3 to 8.3]) and a lower rate of pulmonary hemorrhage (5.6% vs 8.9%; OR, 0.60 [95% CI, 0.38 to 0.95]; ARR, 3.3 [95% CI, 0.4 to 6.3]). No differences in rates of necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions were observed. In the overall cohort, instrumental variable analysis yielded an adjusted OR for in-hospital mortality of 0.62 [95% CI, 0.37 to 1.04]. CONCLUSIONS AND RELEVANCEIn this national 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.

Cerebral oxygenation and echocardiographic parameters in preterm neonates with a patent ductus arteriosus: an observational study

“…This is presumably why extremely low values of cerebral oxygenation were not observed during the first 6 days after birth. The reasoning behind early treatment is underlined by a recent study by Rozé et al , who reported that early screening and treatment for a hsPDA was associated with lower in-hospital mortality and likelihood of pulmonary haemorrhage 37. In our study, infants with a non-sPDA show slightly lower cerebral oxygenation after 6 days and a sharper decline over time compared with infants with a closed duct.…”

Abstention or intervention for isolated hypotension in the first 3 days of life in extremely preterm infants: association with short-term outcomes in the EPIPAGE 2 cohort study

“…The wide variability of bedside practices and our statistical results support the validity of our propensity score. Here, as for other clinical policies, such as PDA screening strategies,28 our analysis can provide results otherwise difficult to identify in randomised trials 29. Finally, this study is the first to our knowledge that has the ability to distinguish, among hypotensive infants who received antihypotensive treatments, those who had only isolated low BP values from those who had additional signs of haemodynamic compromise.…”

Morbidity and mortality with early pulmonary haemorrhage in preterm neonates

“…The significant PDA results in large volume ductal shunting,10 excessive pulmonary blood flow9 and haemorrhagic pulmonary oedema 11. Early PDA screening,12 early PDA therapy13 and indomethacin prophylaxis6 have all been found to reduce the incidence of pulmonary haemorrhage in very preterm infants but not overall survival. However, interpretation of clinical trials in this area has often been complicated by open-label rescue therapy available to the placebo groups 13 14…”