469 - The association between hypoxemic respiratory failure treated with rescue inhaled nitric oxide and long-term neurodevelopmental outcomes at 3 years corrected age in ventilated preterm infants.

Publication Number: 4460.469

Alam Randhawa, University of Calgary, Calgary, AB, Canada; Abhay Lodha, University of Calgary,Cumming School of Medicine, Calgary, AB, Canada; Amuchou Soraisham, University of Calgary, Calgary, AB, Canada; Essa Al Awad, University of Calgary, Calgary, AB, Canada; Adel Elsharkawy, Alberta Health services, Calgary, AB, Canada; Selphee Tang, Alberta Health Services, Calgary, AB, Canada; Sue Makarchuk, Alberta Health Services, Calgary, AB, Canada; Heather Kehler, Alberta Health Services, Calgary, AB, Canada; Amina Benlamri, university of calgary, calgary, AB, Canada

Background: Inhaled nitric oxide (iNO) is used for treating hypoxemic respiratory failure (HRF) not responding to standard management in preterm infants. However, the impact of HRF requiring iNO on their neurodevelopmental outcomes at 3 years corrected age (CA) remains unclear.

Objective: To evaluate the association between hypoxemic respiratory failure requiring iNO and long-term neurodevelopmental outcomes at 3 years CA in ventilated preterm infants.

Design/Methods: A retrospective cohort study of ventilated preterm infants ( < 29 weeks gestational age or < 1000 grams) admitted to tertiary NICUs in Southern Alberta between 2009-2016 or 2019-2021 was completed. The exposure was HRF requiring iNO with either clinical or echo confirmed pulmonary hypertension. Study participants were divided into two groups: the no iNO or no HRF group and the HRF requiring iNO group. The primary outcome was severe neurodevelopmental impairment (sNDI) at 3 years CA. Severe NDI was defined as full-scale IQ score < 70 on the Wechsler Preschool and Primary Scale of Intelligence assessment (WPPSI-III/IV), moderate-severe cerebral palsy (Gross Motor Function Classification System level 3-5), bilateral blindness (corrected visual acuity of < 20/200 in the better eye), and/or bilateral sensorineural hearing loss requiring amplification or cochlear implants. Multivariate logistic regression and propensity score-matched analyses were performed.

Results: A total of 947 eligible infants were assessed at 3 years CA in our regional neonatal follow-up clinic. There were 107 infants in the HRF requiring iNO group (66 infants treated in the first 3 days of life) and 840 infants in the no iNO/no HFR group. Infants in the iNO and no iNO groups had mean birth weights of 857 (±220) and 776 (±210) grams and a median GA (IQR) of 26 (2) and 25 (2) weeks respectively (Table 1). After adjusting for confounders in propensity score matched analysis, the odds ratio of sNDI for the iNO group was 1.09 (95% CI: 0.50-2.37) compared to the no iNO group (Table 2). The odds ratio of death for the iNO group in the propensity score matched analysis was 3.30 (95% CI: 1.44-7.57) compared to the no iNO group. Other secondary outcomes with propensity score matched analyses are shown in Table 2.

Conclusion(s): In surviving preterm infants born before 29 weeks gestational age or < 1000 grams who were ventilated, hypoxemic respiratory failure treated with iNO was not associated with a higher risk of sNDI at 36 months of CA.

Figure 1. Patient Flowchart


Table 1. Maternal and Neonatal characteristics
*Chi-squared test for categorical variables; T-test or Wilcoxon rank sum test for continuous variables
a: Dexamethasone or hydrocortisone
ROM, rupture of membrane; SGA, small for gestational age; BPD, bronchopulmonary dysplasia; PDA. Patent ductus arteriosus; NEC, necrotizing enterocolitis; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; ROP, retinopathy of prematurity


Table 2. Outcomes at 36 Months Corrected Age
OR: odds ratio for HRF with iNO vs. No iNO or No HRF; CI: confidence interval; NDI: neurodevelopmental impairment; SD: standard deviation; GMFCS: Gross Motor Function Classification System.
*Chi-square or Fisher's exact test.
†Model not fit due to small number of events.
1Adjusted for: gestational age, SGA, PIH, antenatal steroids, cesarean delivery, chorioamnionitis, inborn, sex, 5-minute APGAR <7.
2Propensity score estimated using a logistic regression model using year of birth, gestational age, SGA, PIH, antenatal steroids, cesarean delivery, chorioamnionitis, inborn, sex, 5-minute APGAR <7. There were 103 matched pairs in each group.