Supplementary Material for: Intermittent Hypoxemia and Neurodevelopmental Impairment at 12 and 24 months in Preterm Infants

Background: Neonatal studies have shown a relationship between intermittent hypoxemia (IH) and long-term sequelae although definitions of IH have varied. Employing multiple thresholds of IH and a wider gestational aged cohort of preterm infants, we hypothesized that increased IH exposure during the first month of life was associated with neurodevelopmental impairment (NDI) at 12 and 24 months corrected age.
Methods: IH (<80% or <90%) were documented from day of life 8 to 28 (n=175 infants <31 weeks gestation). Referral for NDI was identified (Ages and Stages questionnaire, ASQ-3) at 12- and 24-months corrected age (>2 SD below the mean for gross motor, communication, fine motor, problem solving, and/or personal-social skills).
Results: Unadjusted models revealed a significant association between increased IH and scores in referral range for gross motor, and communication skills (12 months) and gross motor, communication, fine motor, problem solving, and personal-social skills (24 months). In adjusted models, a greater % time <90% and referral scores for communication skills (p=0.0158) at 12 months remained significant. Subgroup analyses revealed an association between greater % time <80% (12 months, p=0.0311) and longer IH duration <90% (24 months, p=0.0374) and scores in referral range for any domain in infants ≥29 weeks gestation.
Conclusion: There was a limited relationship between IH and ASQ-3 scores in referral range for NDI with an association between IH and ASQ-3 referral at 12 and 24 months in infants ≥29 weeks gestation suggesting IH may be a risk factor for NDI in older infants with less competing morbidities.