1. Patients who were discharged from a pediatric intensive care unit for respiratory failure were found to have lower IQ scores compared to matched sibling controls, despite no severe cognitive impairments documented at discharge.

2. However, given the small magnitude of the difference, these results should be interpreted with caution.

Evidence Rating Level: 2 (Good)

Study Rundown: It is well-established that significant incidents of hypoxia in the neonatal or early childhood period can impact an individual’s  neurodevelopment well into adulthood. However, little is known about the neurodevelopmental prognosis of children who suffered respiratory distress without a history of perinatal respiratory complications or known cognitive dysfunction. The present study sought to understand the impacts of respiratory distress in children discharged from the pediatric intensive care unit (PICU). It was hypothesized that neurocognitive function would be worse in patients who had visited the PICU for respiratory distress, and that this association would be more pronounced in younger children. 121 sibling pairs were included in this prospective sibling-matched cohort study (242 trial participants in total). Of note, the majority of patients (69%) were younger siblings. The median time of hospitalization in the PICU was 1.0 years and neurocognitive testing was conducted a median of 3.8 years after discharge from the PICU. All patients were being treated for respiratory failure and 72% of patients also had multiple organ dysfunction syndrome. Three to eight years after PICU discharge, patients had a mean IQ score of 101.5, and controls had a mean score of 104.3. Patients with lower IQ scores (i.e., more than one standard deviation below their sibling) tended to be younger at the time of hospitalization. Patients specifically scored lower than their siblings in the following domains: visuospatial skills, fine motor skills and nonverbal memory. This prospective cohort study demonstrated that pediatric patients with a normal cognitive score who are hospitalized in the PICU for respiratory distress may suffer neurocognitive setbacks compared to matched sibling pairs. The magnitude of these findings is clinically small, although this information certainly contributes to our understanding of pediatric brain development and how it may be disrupted. Some strengths of this study include the thorough analysis and standardization of neurocognitive testing. A major weakness is the small sample size, as well as the possibly large variation in the care received (and needed) in the PICU between patients.

Click here to read this study in JAMA

Click to read an accompanying editorial in JAMA

Relevant reading: Intermittent hypoxia in childhood: the harmful consequences versus the potential benefits of its therapeutic use

In-Depth [prospective cohort]: This prospective cohort study derived data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial. Children in this study were 8 years or younger at the time of enrolment, had a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to admission and no worse than 3 at discharge. Patients with significant comorbidities at baseline or known perinatal complications were excluded. Biological siblings (aged 4-16) of enrolled patients were also enrolled as controls, given that they had a PCPC score of 1. Outcomes were assessed using developmentally-appropriate neurocognitive assessment tools beginning when patients were aged 4 or greater. Patients in the experimental group had a lower IQ on average than the control group (101.5 vs 104.3, mean difference -2.8 [95% confidence interval -5.4 to -0.2]). 17% of patients had IQ scores at least 15 points lower than those of their siblings. The difference in IQ between siblings remained statistically significant when the model was adjusted for ages at testing and time span between discharge and outcome assessment. Notably, restriction to the 103 sibling pairs in which the patient’s PCPC was 1 (normal) at the time of outcome assessment demonstrated that there was no statistically significant difference in patient and sibling IQ (102.3 in patients vs 104.2 in siblings; mean difference, –1.9 [95% CI, –4.7 to 0.9]).  Patients with substantially lower IQ scores than their siblings tended to have been hospitalized at younger ages. To illustrate, the median age of hospitalization in those who scored more than 1 standard deviation below their sibling’s IQ score was 0.2 years (interquartile range 0.1-1.1), while patients scoring close to or higher than their siblings had a median age of 1.4 years (0.2-3.9) at admission to the PICU. Secondary outcome analysis demonstrated that patients specifically performed worse than their siblings in the following domains, described with the mean score difference and 95% confidence intervals: visuospatial skills –0.9 (–1.8 to –0.1), nonverbal memory -0.9 (-1.6 to -0.3) and fine motor control -3.1 (-4.9 to -1.4).

Image: PD

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