Oxygenation and Echocardiogram Score in First Week Correlates with Outcomes in Newborns with PPHN

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition associated with hypoxemia and increased pulmonary vascular resistance (PVR). Management of PPHN includes supplemental oxygen, mechanical ventilation, pulmonary vasodilators such as inhaled nitric oxide (iNO) and extracorporeal life support (ECLS). Currently, severity of PPHN is primarily assessed by oxygenation index [OI=(mean airway pressure X FIO2 X 100)/PaO2]. However, OI assessment requires arterial access and accounts for hypoxemia but not PVR. We propose to create and validate a reliable assessment tool to evaluate the severity of PPHN by measuring 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 (Table 1).

Methods: We performed a retrospective chart review of infants (0-7 days) admitted to a large academic medical center in 2020 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, and 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. Outcomes included need for and duration of invasive mechanical ventilation (IMV), use of iNO and duration of use, need for ECLS, and survival to discharge. This study received IRB exemption status (ID: 1668854-3).

Results: Eighteen infants were included. The most common mechanism for PPHN was meconium aspiration (44% N=8). HRF/PH scores ranged 3-12 (mean 8.2). HRF/PH scores were categorized into mild (0-5), moderate (6-10) and severe (11-15) of which 11%, 61% and 28% of infants were in each category respectively. Logistic regression demonstrated that a more severe HRF/PH score significantly correlated with increased need for iNO (100% in severe, 73% in moderate, and 0% in mild, p=0.02) and increased need for ECLS (60% in severe vs 0% in both moderate and mild, p<0.01). On linear regression analysis, increasing HRF/PH score significantly correlated with increased duration of iNO (p < 0.01) and increased duration of IMV (p=0.04) among survivors. HRF/PH score did not correlate with death or length of stay.

Conclusion: These findings suggest that the HRF/PH score developed for the purpose of classifying PPHN offers a promising representation of disease severity. Larger, multicenter, longitudinal studies evaluating neurodevelopmental outcomes are needed. These scores are beneficial in epidemiological studies and randomized trials of pulmonary vasodilators in PPHN.