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

Christopher Chua, Kaohsiung Medical University College of Pharmacy

Patent ductus arteriosus (PDA) is considered a vascular structure that connects the proximal descending aorta to the roof of the main pulmonary artery near the origin of the left branch pulmonary artery.  This essential fetal structure normally closes spontaneously after birth.  After the first few weeks of life, persistence of ductal patency is said to be abnormal.  The physiological impact and clinical significance of the PDA depend largely on its size and the underlying cardiovascular status of the patient.1  The PDA may be “silent” (not evident clinically but diagnosed incidentally by echocardiography done for a different reason), small, moderate, or large.  Regardless of the size, complications may arise, and it is suggested for both pediatric and adult cardiologists to have an understanding of the pathophysiology, clinical implications, and management of PDA.2

Title: Association Between Early Screening for Patent Ductus Arteriosus and In-Hospital Mortality Among Extremely Preterm Infants3

Design Prospective population-based cohort study; N=1,513
Objective To evaluate the association between early screening echocardiography for PDA and in-hospital mortality
Study Groups Preterm infants that included all preterm infants born at less than 29 weeks of gestation and hospitalized in 68 neonatal intensive care units were placed into two groups:

Non-exposed group: Subjects who had not undergone early PDA screening

Methods Information was collected about ductus arteriosus diagnosis, including PDA markers from the echocardiography (ductus arteriosus diameter >1.5 mm), high-velocity flow in the left pulmonary artery (mean velocity >0.4 m/s or end-diastolic velocity >0.2m/s), diastolic aortic flow reversal or low superior vena cava flow (<40 mL/kg/min), pulsatile ductus shunt flow pattern.
Duration April 2011 through December 2011
Primary Outcome Measure Death between day 3 and discharge
Baseline Characteristics Overall cohort Matched cohort
Characteristic Nonexposed Exposed Nonexposed Exposed
Gestational age median, week 27 26 27 27
Time of first echocardiographic evaluation
Evaluation before day 3 16.0% 100% 17.0% 100%
Evaluation at day 3 or after 64.2% 0% 65.3% 0%
Observed PDA markers during echocardiographic evaluation
Ductus arteriosus diameter >1.5 mm/kg 59.0% 62.5% 62.0% 63.3%
Pulsatile ductus shunt flow pattern 17.6% 21.7% 18.9% 22.1%
High-velocity flow in left pulmonary artery 26.5% 30.9% 27.5% 30.7%
Diastolic aortic flow reversal or low superior vena cava flow 10.3% 9.7% 10.0% 9.3%
Results Exposed infants Nonexposed infants 95% CI
Treated for PDA  during their hospitalization 55.1% 43.1% 1.31 to 2.00
Hospital death rate 14.2% 18.5% 0.54 to 0.98
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].
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions In this national population-based cohort of extremely preterm infants, screening echocardiography for PDA 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.

Early screening echocardiography was associated with lower rates of in-hospital mortality and pulmonary hemorrhage, a well-recognized life-threatening complication of PDA.  The higher mortality in the non-exposed group was mainly observed in untreated infants who were in higher proportion in that group.  No relationship was observed between the characteristics of a NICU and its PDA screening strategy, suggesting the lack of performance bias.

 

References

  1. Aboulhosn JA, Child JS.Congenital Heart Disease in the Adult. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J.  Harrison’s Principles of Internal Medicine, 19eNew York, NY: McGraw-Hill; 2015.http://accesspharmacy.mhmedical.com/content.aspx?bookid=1130&Sectionid=79742703. Accessed July 06, 2015.
  2. Schneider DJ, Moore JW. Patent ductus arteriosus. Circulation. 2006;114(17):1873-82.
  3. Rozé J, Cambonie G, Marchand-Martin L, et al. Association Between Early Screening for Patent Ductus Arteriosus and In-Hospital Mortality Among Extremely Preterm Infants.2015;313(24):2441-2448. doi:10.1001/jama.2015.6734.
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