PC1049: Validation of Novel Hypoxic Respiratory Failure/pulmonary Hypertension Score in Neonates with PPHN

Background: Randomized controlled trials evaluating hypoxic respiratory failure (HRF) and persistent pulmonary hypertension of the newborn (PPHN) have relied on oxygenation index [OI=(mean airway pressure * FIO2 * 100)/PaO2] as the main criteria to dictate enrollment and/or as a primary outcome. However, OI does not take into account the severity of pulmonary hypertension. We propose to create and validate a reliable assessment tool to evaluate the severity of PPHN by measuring pulmonary vascular resistance (PVR) and hypoxemia without need for invasive arterial access. In a collaborative effort with neonatologists, pediatric cardiologists, and pediatric intensivists at our institution, a hypoxic respiratory failure/pulmonary hypertension (HRF/PH) score was developed. It combines the level of respiratory support and oxygenation (measured by arterial gas or pulse oximetry) at the time of echocardiographic assessment of PVR to create a severity score that ranges from 0-15 (Figure 1).

Methods: We performed a retrospective chart review of infants (0-7 days) admitted to an academic Children’s Hospital from 2016-2021 with a documented diagnosis of PPHN, gestational age > 34 weeks, and complete echocardiograms in the first 7 days after birth. Those with congenital diaphragmatic hernia (CDH), Trisomy 21, and HIE on therapeutic hypothermia were included; those with congenital heart disease other than ASD/PFO, PDA, or VSD < 2 mm were excluded. The correlation between HRF/PH score and outcomes of hospitalization were assessed. Primary outcomes included need for and duration of invasive mechanical ventilation (IMV), iNO, and ECLS, as well as length of stay and survival to discharge. Secondary outcomes included need for vasoactive infusions and vasoactive-isotropic score (VIS). This study received IRB exemption status (ID: 1668854-3).

Results: Eighty-three infants were included. The most common mechanism for PPHN was meconium aspiration (36% #=30). HRF/PH scores ranged 2-12 (mean 8.5). HRF/PH scores were categorized into mild (0-5), moderate (6-10) and severe (11-15) of which 6%, 78% and 16% of infants were in each category respectively. Logistic regression demonstrated that HRF/PH score category significantly correlated (p < 0.05) with death before discharge, as well as need for iNO, IMV, high frequency oscillatory ventilation (HFOV), ECLS, and vasoactive infusions. On linear regression analysis, total HRF/PH score correlated with duration of iNO use and duration of IMV among survivors, as well as VIS score. HRF/PH score did not correlate with length of stay.

Conclusion: These findings suggest that the HRF/PH score developed for the purpose of assessing PPHN offers a promising representation of combined disease severity of hypoxemia and pulmonary hypertension and may offer an alternate criterion for inclusion and/or primary outcome in trials evaluating PPHN. Larger, multicenter, longitudinal studies evaluating both short-term and long-term outcomes are needed to further validate this score.