Pediatric Sickle Cell Disease Linked to Sleep Disorder Complications

Investigators observed that children with sickle cell disease (SCD) may be at an increased risk of comorbid events associated with sleep disordered breathing (SDB).

The findings, from a team of investigators at the University Hospital of Udine in Italy, showed that progression from the common pediatric sickle cell-associated sleep condition could include hypoxemia, obstructive sleep apnea (OSA), and severe cardiovascular or neurological outcomes.

Curating the Research

The study focuses on the epidemiology, clinical presentation, complications, and management of sleep disordered breathing in children with sickle cell disease. Investigators screened a total of 190 research papers on sleep disordered breathing in children with sickle cell disease published between 2000-2020, and narrowed the selection to include 62 studies in their analysis.

Notable Findings

There are 11 studies that reported comparable polysomnography (PSG) results. All selected studies discovered that children with sickle cell disease had significantly lower median oxygen saturation and lower minimal oxygen saturation during sleep when compared with healthy control groups.

Among all the patients with sickle cell disease from the 11 studies, none had any previously known history of OSA (males 470, 45%, WM age of 10.2 years, range, 1-18), calculated WM overnight SpO2 was 95.8% (95% CI, 95.6-95.9), with a WM nadir SpO2 of 88.0% (95% CI, 87.8%-88.2%) and a WM AHI of 3.6 (95% CI, 3.4-3.8).

Pediatric patients with sickle cell disease were found to have more severe and prolonged nocturnal desaturation and hypercapnia compared with non-sickle cell children with OSA. The results of overnight PSG are generally stable or slightly improve over time in the medium-long term.

A single study screened 100 children with sickle cell disease with a specific sleep questionnaire regardless of sleep disordered breathing symptoms and found that 19 children had a positive sleep apnea screening score. A total of 7 patients were diagnosed with OSA and 10 patients underwent PSG.

Interventional Treatments

Investigators found 11 papers that focus on possible treatment options of sleep disordered in children with sickle cell disease. This included 6 studies evaluating clinical effects of tonsillectomy and adenoidectomy (T&A); 2 studies on the Hounsfield unit (HU); and 3 studies on night oxygen.

All interventions showed a significant increase of mean nocturnal SpO2 (MD, 2069; 95% CI, 2.01-3.36; I2 = 0%). Comparatively. oxygen supplementation had a slightly increased performance (MD 2.98; 95% CI, 2.08-3.88).

On nadir SpO2, the effect was even more distinguished (MD, 5.84; 95% CI, 4.41-7.28; I2 = 32%). The reduction of Apnea-hypopnea index (AHI) was significant for all interventions (MD, -6.7; 95% CI, -11.27 to 2.12; I2 = 92%).

Results and Implications

Ultimately, the investigators of this cumulative study found that children with sickle cell disease frequently suffer from sleep disordered breathing, which may correlate with various other complications involving neurological, cognitive, cardiovascular, and pulmonary aspects.

Children with OSA show a higher risk of neurological events such as seizures, but not stroke. The specific relationship between OSA and cerebrovascular complications is undetermined but chronic hypoxemia is associated with a higher incidence of central nervous system event.

The results support the hypothesis that intervention aimed to relieve sleep disordered breathing and nocturnal hypoxemia by T&A and oxygen supplemental therapy, lead to a significant reduction of TCD velocities. However, the clinical implications are still unclear.

Although the evidence is limited, there is no evident impact on the incidence of VOCs and acute coronary syndrome. Nocturnal home oxygen appears to be safe for children with sickle cell and severe overnight hypoxemia but, conclusions can’t be drawn regarding the impact of this measure on long-term clinical outcomes because of the lack of high quality data.

“Prospective and adequately powered studies are needed to further investigate the association between SDB and neurological, cardiovascular and pulmonary complications in children with SCD,” investigators wrote. ”And to evaluate the clinical impact and long‐term safety profile of possible therapeutic interventions.”

The study, “The burden of sleep disordered breathing in children with sickle cell disease” was published in Pediatric Pulmonology.