Association of Acute Respiratory Failure in Early Childhood With Long-term Neurocognitive Outcomes

R. Scott Watson, Sue R. Beers, Lisa A. Asaro, et al

JAMA. 2022;327(9):836-845. doi:10.1001/jama.2022.1480

Key Points

Question Do children with previously normal neurocognitive function who survive an episode of acute respiratory failure requiring intensive care and invasive mechanical ventilation have worse long-term neurocognitive function than their matched siblings?

Findings In this cohort study that included 121 sibling pairs, children discharged from intensive care hospitalization for respiratory failure without severe cognitive dysfunction compared with their matched siblings had a mean IQ score of 101.5 vs 104.3, a difference that was statistically significant.

Meaning Acute respiratory failure in early childhood was associated with a slightly, but statistically significant, lower subsequent IQ score.Abstract

Importance Approximately 23 700 US children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function.

Objective To evaluate neurocognitive outcomes of children who survive pediatric intensive care unit (PICU) hospitalization for acute respiratory failure compared with their biological siblings.

Design, Setting, and Participants Prospective sibling-matched cohort study conducted at 31 US PICUs and associated neuropsychology testing centers. Patients were 8 years or younger with a Pediatric Cerebral Performance Category score of 1 (normal) before PICU admission and less than or equal to 3 (no worse than moderate neurocognitive dysfunction) at PICU discharge, excluding patients with a history of neurocognitive deficits or who were readmitted and underwent mechanical ventilation. Biological siblings were aged 4 to 16 years at testing, with Pediatric Cerebral Performance Category score of 1 and no history of mechanical ventilation or general anesthesia. A total of 121 sibling pairs were enrolled from September 2, 2014, to December 13, 2017, and underwent neurocognitive testing starting March 14, 2015. The date of the final follow-up was November 6, 2018.

Exposures Critical illness and PICU treatment for acute respiratory failure.

Main Outcomes and Measures The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included measures of attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Evaluations occurred 3 to 8 years after hospital discharge.

Results Patients (n = 121; 55 [45%] female patients) underwent PICU care at a median (IQR) age of 1.0 (0.2-3.2) years, received a median (IQR) of 5.5 (3.1-7.7) days of invasive mechanical ventilation, and were tested at a median (IQR) age of 6.6 (5.4-9.1) years. Matched siblings (n = 121; 72 [60%] female siblings) were tested at a median (IQR) age of 8.4 (7.0-10.2) years. Patients had a lower mean estimated IQ than matched siblings (101.5 vs 104.3; mean difference, –2.8 [95% CI, –5.4 to –0.2]). Among secondary outcomes, patients had significantly lower scores than matched siblings on nonverbal memory (mean difference, –0.9 [95% CI, –1.6 to –0.3]), visuospatial skills (mean difference, –0.9 [95% CI, –1.8 to –0.1]), and fine motor control (mean difference, –3.1 [95% CI, –4.9 to –1.4]) and significantly higher scores on processing speed (mean difference, 4.4 [95% CI, 0.2-8.5]). There were no significant differences in the remaining secondary outcomes, including attention, verbal memory, expressive language, and executive function.

Conclusions and Relevance Among children, survival of PICU hospitalization for respiratory failure and discharge without severe cognitive dysfunction was associated with significantly lower subsequent IQ scores compared with matched siblings. However, the magnitude of the difference was small and of uncertain clinical importance.