344 - Early Hyperoxemia and Mortality in Infants with Persistent Pulmonary Hypertension of the Newborn (PPHN) Treated with Inhaled Nitric Oxide (iNO)

Publication Number: 344.4834

Marina Santos Oren, University of Texas Southwestern Medical School, Dallas, TX, United States; Kikelomo Babata, University of Texas Southwestern Medical School, Dallas, TX, United States; June Hu, University of Texas Southwestern Medical School, Dallas, TX, United States; Venkatakrishna Kakkilaya, UT Southwestern Medical Center, Dallas, TX, United States; Patti J. Burchfield, University of Texas Southwestern Medical School, Dallas, TX, United States; Michelle Hagans, Texas Health Presbyterian Hospital of Dallas, Dallas, TX, United States; L. Steven Brown, Parkland Health, Dallas, TX, United States; Satyan Lakshminrusimha, UC Davis, Sacramento, CA, United States; Vishal Kapadia, University of Texas Southwestern Medical School, Dallas, TX, United States

Background: While oxygen acts as a pulmonary vasodilator, early hyperoxemia diminishes inhaled nitric oxide responsiveness and exacerbates pulmonary arterial contractility to vasoconstrictors in animal models of PPHN. Early hyperoxemia is also associated with increased mortality and major disability in term infants with perinatal asphyxia. Iatrogenic exposure to hyperoxia has been reported in as high as 80% of infants treated with iNO for PPHN. Impact of early hyperoxemia exposure in this population is unknown.

Objective: Determine if early hyperoxemia exposure is associated with death in infants ≥ 35 weeks with PPHN.

Design/Methods: Retrospective review of infants ≥ 35 weeks born from 2016 to 2022 in three level 3 hospitals in Dallas, TX.
Inclusion criteria: Neonates with a clinical diagnosis of PPHN or ECHO evidence of PPHN treated with iNO in the first week of life.
Exclusion criteria: Severe congenital malformations.
Based on maximum PaO2 measurements during the first 12 hours of life, the cohort was divided into infants with no hyperoxemia (PaO2 < 100 mmHg), mild - moderate hyperoxemia (PaO2 100-199 mmHg) and severe hyperoxemia (PaO2 ≥ 200 mmHg).
Baseline maternal and neonatal characteristics, oxygenation parameters and clinical outcomes were compared between these three groups. Primary outcome was death during hospitalization. Data were compared using χ2 or Fisher exact test for categorical data and median was compared with Mann-Whitney U-test. Multivariable logistic regression was conducted, adjusting for baseline characteristics and confounding variables.

Results: Overall, 118 infants met inclusion criteria and had arterial PaO2 measurements in the first 12 hours of life. 523 blood gases were analyzed. Mild-moderate hyperoxemia was present in 32% and severe hyperoxemia in 17% of infants (Figure 1a). Table 1 shows baseline characteristics and outcomes. There was a significant association between early hyperoxemia and mortality (OR 2.5, 95% CI 1.1-5.3). There was six times higher odds of death with severe hyperoxemia compared to normoxemia. (OR 6, 95% CI 1.5-24) A J shaped curve was noted with mortality higher in low ( < 50 mmHg) and high PaO2 (Figure 1b). Max PaO2 remains statistically significant for higher odds of death even after controlling for birth weight, gender, gestational age, C-section, 5-min APGAR, hypoxic ischemic encephalopathy and meconium aspiration syndrome.

Conclusion(s): Early hyperoxemia is common and associated with mortality in infants ≥35 weeks with PPHN. Carefully weaning FiO2 to appropriate preductal SpO2 may minimize hyperoxia and improve outcomes.

Table 1: Baseline Characteristics and Outcomes of 118 Infants with PPHN Born 2016-2022 in Three Level III Hospitals in Dallas, Texas
*n (%) compared with Chi-square or Fisher exact test; Median compared with Mann-Whitney U-test
**P < 0.05, statistically significant
Abbreviations: HTN = hypertension; DM = Diabetes Mellitus; GA = Gestational Age; BW = Birth Weight; DR = Delivery Room; HFNC = High Flow Nasal Cannula; CPAP = Continuous Positive Airway Pressure; RSS (Respiratory Severity Score) = Mean Airway Pressure (MAP) x FiO2; MAS = Meconium Aspiration Syndrome; HIE = Hypoxic Ischemic Encephalopathy; TTN = Transient Tachypnea of Newborn; RDS = Respiratory Distress Syndrome; UAC = Umbilical Arterial Line; PAL = Peripheral Arterial Line; OI (Oxygen Index) = MAP x FiO2 / PaO2; ECMO = Extracorporeal Membrane Oxygenation

Table 2: Odds Ratio for Mortality by exposure in 118 Infants ≥35 Weeks Gestation with PPHN Born 2016–2022 in Three Level III Hospitals in Dallas, Texas
*Bivariate and Multivariate Logistic Regression Analysis
Abbreviations: OR = Odds Ratio; aOR = Adjusted Odds Ratio; HIE = Hypoxic-Ischemic Encephalopathy; MAS = Meconium Aspiration Syndrome
* = p < 0.05, statistically significant

Figure 1ab: Figure 1a: Study Flow Diagram; Figure 1b: Relationship between PaO2 levels and Mortality
Abbreviation: CDH= Congenital Diaphragmatic Hernia; ECMO= Extracorporeal Membrane Oxygenation