Intermittent episodes of hypoxemia lasting more than 1 minute during the first 2-3 months after extremely preterm birth are associated with severe disability at age 18 months, according to a report published online Aug. 11 in JAMA.
Almost all extremely preterm infants experience intermittent hypoxemia during their NICU stay, but the relationship between this hypoxemia and later neurodevelopmental problems is uncertain. To examine this issue, researchers performed a post-hoc analysis of data gathered in the multicenter Canadian Oxygen Trial, which compared the effects of lower (85%-89%) vs. higher (91%-95%) oxygen saturation targets in preterm infants. The post-hoc study focused on 1,019 infants born at 23-27 weeks’ gestation who survived to 36 weeks’ postmenstrual age, said Dr. Christian F. Poets of the department of neonatology at Tuebingen (Germany) University Hospital and his associates.
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The investigators assessed whether hypoxemia correlated with the composite outcome of death after 36 weeks’ postmenstrual age or disability – motor impairment, cognitive or language delay, severe hearing loss requiring hearing aids or cochlear implants, bilateral blindness, or severe retinopathy of prematurity – assessed at a corrected age of 18 months. These adverse outcomes occurred in 43% of the study population.
The mean percentage of time with hypoxemia ranged from 0.4% in the lowest decile to 13.5% in the highest. The probability of each adverse outcome increased significantly as the percentage of time in hypoxemia increased. For the primary outcome of late death or disability, the relative risk was 1.53 among infants in the highest vs. the lowest decile. Stated another way, hypoxemic episodes were associated with death or severe disability in 56.5% of infants in the highest decile of hypoxemia exposure, compared with only 36.9% of those in the lowest decile. Each individual adverse outcome also followed this pattern of risk, the investigators said (JAMA. 2015;314(6):595-603. doi: 10.1001/jama.2015.8841). Only prolonged episodes of hypoxemia lasting more than 1 minute were found to correlate with adverse outcomes; shorter episodes did not. The risk of adverse outcomes increased as age at the time of hypoxemia episodes increased, so that the greatest risk was observed in infants whose hypoxemia occurred 9-10 weeks after birth.
The post-hoc design of this study can only generate hypotheses for future research rather than determine definitive conclusions, so it is not yet known whether prolonged intermittent hypoxemia contributes to neurodevelopmental impairment or is just a feature that denotes which infants are destined to develop impairments. If future studies determine that hypoxemia is a cause of adverse outcomes, it may be a preventable cause – perhaps with caffeine therapy, specific ventilator strategies, or doxapram administration, Dr. Poets and his associates said.
This study was funded exclusively by the Canadian Institutes of Health Research. Dr. Poets reported receiving research grants from Chiesi Farmaceurici SpA and Masimo.