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Biomarkers associated with haemodynamically significant patent ductus arteriosus

Presented at the Neonatal Society 2016 Autumn Meeting (programme).

Kotidis C, Weindling AM, Turner M

Department of Women’s and Children’s Health, University of Liverpool, Liverpool, UK

Background: Patent Ductus Arteriosus (PDA) has significant haemodynamic effects on cardiac and cerebral function. This study assessed established and novel cardiac and cerebral biomarkers during the transitional period. We hypothesised that novel echocardiographic biomarkers were better predictors of cardiac and cerebral haemodynamic status related to PDA patency than those in current use.

Methods: Prospective observational study recruiting infants <29 weeks gestation and without pre-existing significant brain injury. Haemodynamically significant PDA (hsPDA) defined as PDA diameter >1.5mm + left atrial:aortic ratio >1.6. on day 3 of life. Multiple established echocardiographic parameters as described by Sehgal et al (1) were measured in addition to novel biomarkers: MAPSE, TAPSE and tissue Doppler parameters. Cerebral oxygenation was assessed by near infrared spectroscopy (cTOI) and cerebral function by amplitude integrated electroencephalogram [Burdgalov score (2)], cerebral Doppler and heart rate variability metric (HeRO score) as an indicator of autonomic activity. Ethical approval was obtained.

Results: 48 infants were recruited [31 male, median birth weight 0.92 (IQR 0.34) kg, gestation 26.6 (IQR 2.4)] w. HsPDA had a significant effect on cerebral biomarkers: reduced cTOI and Burdjalov score on Day 2 (P=0.03 and 0.033 respectively), increased anterior cerebral artery pulsatility index (aPI) and higher HeRO scores on Days 1, 2 and 3; (P=0.046, 0.069, 0.001 and 0.033, 0.100, 0.004 respectively). Infants with severe intraventricular haemorrhage (>Grade 2) had lower cTOI and Burdjalov score (P=0.000, 0.029 respectively), but no difference in aPI and HeRO scores on Day 3. No novel biomarkers were associated with hsPDA during transition or predictive of brain injury. Tissue Doppler biomarkers were not associated with PDA diameter. Increased peak myocardial systolic velocity on Day 1 and 3 was associated with increased cTOI (P=0.038 and 0.028). MAPSE and TAPSE were not associated with PDA diameter, Burdjalov score or transcranial Doppler. MAPSE was associated with cerebral oxygenation on Day 3 of life (P=0.040). Left ventricular:aortic ratio and transductal velocity were related to hsPDA on a backward regression analysis model including seven components of PDA score.

Conclusion: PDA has significant haemodynamic effect on cerebral oxygenation and function. The most reliable echocardiographic biomarkers for assessing hsPDA (other than PDA size and left atrial:aortic ratio) were the left ventricular:aortic ratio and transductal velocity.

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1. Sehgal, A. et al. Eur J Pediatr, 2013; 172(2): p. 179-84
2. V.F. Burdjalov et al. Pediatrics, 2003; 112: p. 855–861

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