43 Pulmonary Artery dopplers for early prediction of Bronchopulmonary Dysplasia (BPD) in Extremely Low Birth Weight babies (ELBW): A forgotten tale
Authors: Lalitha Renjini , Bitar Eyad , Hyderi Abbas , Hicks Matthew , Kumaran Kumar 
Published: August 2020

Abstract

Introduction/Background
BPD is a chronic lung disease that affects ELBW babies and contributes significantly to their morbidity and mortality. The early abnormal vasoreactivity observed in babies at risk of BPD increases the pulmonary vascular resistance and can be assessed non-invasively using Time to Peak Velocity: Right Ventricular Ejection Time ratio (TPV: RVET) that is calculated from pulmonary artery doppler waveform. We postulate that screening for this condition early may be useful to predict BPD in this cohort, which may provide prognostic information as well as early clinical management of the ELBW at risk of developing BPD and therefore can potentially present a window of opportunity for therapeutic intervention.

Objectives
1. To determine utility of TPV/RVET ratio in predicting the risk for BPD in ELBW babies in a tertiary center.
2. To determine utility of TPV/RVET(c) ratio in predicting the risk for BPD in ELBW babies in a tertiary center.

Design/Methods
This is a retrospective cohort study of ELBW babies &lt;29 weeks admitted to the Neonatal Intensive Care Unit at Stollery Children Hospital (SCH) over a 4 year time period and had early echocardiograms performed between 7-21 days of life. These babies were further identified to have BPD or no BPD at 36 weeks CGA. TPV/RVET ratios were measured by two reviewers from pulmonary artery doppler waveforms and were corrected for heart rate. The predictive ability of TPV/RVET and TPV/RVET(c) for subsequent development of BPD were analyzed using ROC curve. Inter observer agreement was evaluated. Logistic regression analysis was performed to derive a model that can be used in the 2nd to 3rd weeks of life, to predict the subsequent development of BPD at 36 weeks CGA. Infants with congenital heart disease (other than PDA, persistent foramen ovale/atrial septal defect and Ventricular Septal Defects), congenital lung malformations, multiple congenital anomalies and chromosomal anomalies were excluded.

Results
Out of 589 ELBW babies &lt;29 weeks admitted to SCH NICU, 207 infants were eligible with early echocardiograms done at a mean age of 12.6 days (SD 4.1). One-hundred-and-twenty-five babies (60.4%) were found to have BPD. Babies with BPD were of lower gestational age (25.6 Vs 26.4, p-0.0001), sicker at birth (SNAPPE II 42.3 Vs 33.2, p-0.0024), had higher incidence of PDA needing surgical ligation (18.4% Vs 4.9%, p-0.005) and had spent more days on mechanical ventilation (39.8 Vs 12.5, p&lt;0.0001) than those without BPD. Both TPV, TPV/RVET and its corrected ratios were significantly lower in ELBW babies with BPD compared to non-BPD babies (p&lt;0.0001). The TPV/RVET ratio (cut off 0.34) and TPV/RVET(c) (cut off 0.54) had Sensitivities [76.8% (95%CI 68.4-83.9) and 72% (95%CI 63.3-79.7)], Specificities [85.4% (95%CI 75.8- 92.2) and 84.1% (95%CI 74.4-91.3)], Positive Predictive Values [88.9% (95%CI 81.4-94.1) and 87.4% (95%CI 79.4-93.1)], Negative Predictive values [70.7% (95%CI 60.7- 79) and 66.3% (95%CI 56.4-75.3)] and ROC area [0.811 (95% CI 0.757-0.864) and 0.781 (95% CI 0.725-0.837)] respectively. Multi variant logistic regression analysis showed Odds Ratio(OR) for having BPD at TPV/RVET cut off 0.34 and TPV/RVET(c) cut off 0.54 to be 19.9(95%CI 8.19-48.34) and 16.3(95% 6.78-39.33) respectively and the OR increased by 1.07(95%CI 1.05-1.09) and 1.08(95% CI 1.05-1.10) with every additional days of mechanical ventilation respectively. TPV/RVET ratio had 92.75% inter-observer agreement with kappa 0.83.

Conclusion
TPV/RVET and its corrected ratio are good and reliable early screening tools for subsequent development of BPD in ELBW babies with substantial inter-observer agreement.
Two variable model namely TPV/RVET&lt;0.34 and mechanical ventilation or TPV/RVET(c) &lt;0.54 and mechanical ventilation can be used in the 2nd to 3rd week of life to predict subsequent development of BPD at 36 weeks CGA in ELBW babies.