Severe Acute Neurologic Involvement in Children With Hemolytic-Uremic Syndrome

Abstract

Background and objectives: Acute severe neurologic involvement is the most threatening complication in children with hemolytic-uremic syndrome (HUS). Our primary study objectives were to describe the association between acute neurologic manifestations (ANMs) and in-hospital mortality among children with HUS.

Methods: Using the Pediatric Health Information System database, in this retrospective multicenter cohort study, we identified the first HUS-related inpatient visit among children ≤18 years (years 2004-2018). Frequency of selected ANMs and combinations of ANMs, as well as the rate of mortality, was calculated. Multivariate logistic regression was used to identify the association of ANMs and the risk of in-hospital mortality.

Results: Among 3915 patients included in the analysis, an ANM was noted in 10.4% (n = 409) patients. Encephalopathy was the most common ANM (n = 245). Mortality was significantly higher among patients with an ANM compared with patients without an ANM (13.9% vs 1.8%; P < .001). Individuals with any ANM had increased odds of mortality (odds ratio [OR]: 2.25; 95% confidence interval [CI]: 1.29-3.93; P = .004), with greater risk (OR: 2.60; 95% CI: 1.34-5.06; P = .005) among patients with ≥2 manifestations. Brain hemorrhage (OR: 3.09; 95% CI: 1.40-6.82; P = .005), brain infarction (OR: 2.64; 95% CI: 1.10-6.34; P = .03), anoxic brain injury (OR: 3.92; 95% CI: 1.49-10.31; P = .006), and brain edema (OR: 4.81; 95% CI: 1.82-12.71; P = .002) were independently associated with mortality.

Conclusions: In this study, the largest systematic assessment of ANMs among children with HUS to date, we identify differences in in-hospital mortality based on the type of ANM, with increased risk observed for patients with multiple ANMs.

FIGURE 1

Patient outcomes by the number of ANMs (n = 3915). Horizontal lines indicate 95% CIs based on SEs of the means. The number of conditions indicates the number of neurologic manifestations, including meningitis, seizure disorder, brain bleed, brain infarction or hemiplegia, encephalopathy, anoxic brain, and cerebral edema or brain compression.

FIGURE 2

Kaplan-Meier survival estimates by ANM. A, Survival estimate curves stratified by the number of ANMs, including meningitis, seizure disorder, brain bleed, brain infarction or hemiplegia, encephalopathy, anoxic brain, and cerebral edema or brain compression. B, Survival estimate curves for individual ANMs. Note that for panel B, the categories are not mutually exclusive, so a patient may be in >1 category. Graphs were censored at 80 days.