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

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.

Figure 1.. Flow of Participants in a Study of the Association of Acute Respiratory Failure in Early Childhood With Long-term Neurocognitive Outcomes

PCPC indicates Pediatric Cerebral Performance Category; PICU, pediatric intensive care unit. ^aSixteen patients were unable to undergo testing due to behavioral or other factors on the day of testing.

Figure 2.. Estimated IQ of Patients and Matched Siblings in a Study of the Association of Acute Respiratory Failure in Early Childhood With Long-term Neurocognitive Outcomes

A. Within each box, solid circles represent mean values and horizontal lines denote median values; boxes extend from the 25th to the 75th percentile. Open circles denote individual observations. The horizontal line at an estimated IQ score of 100 indicates the population mean, and the dashed horizontal lines at estimated IQ scores of 85 and 115 indicate cutoffs representing 1 standard deviation below and above this value, between which roughly two-thirds of the population typically scores. E, Each vertical line represents 1 sibling pair; the vertical line plots the difference between the patient estimated IQ (black line) and the sibling estimated IQ (end of vertical line). Vertical lines that extend above the black line represent pairs in which the sibling scored higher than the patient, while vertical lines that extend below the black line represent pairs in which the sibling scored lower than the patient. PICU indicates pediatric intensive care unit.