Sleep Architecture in Children with Sickle Cell Disease and Nocturnal Hypoxemia
Authors: Pyfer Lauren , Rani Seema , DiVirgilio Nicole , Miller Robin E , Strang Abigail , Chidekel Aaron , Hossain Jobayer 
Published: December 2024

Background:

Children with sickle cell disease (SCD) are at an increased risk for sleep-related issues, both respiratory and non-respiratory. These include sleep disordered breathing, increased sleep latency, frequent nocturnal awakenings, as well as nocturnal hypoxemia. The sleep architecture especially N3 and REM sleep are important for overall functioning, immune response, hormonal regulation, academic performance, learning, and restoration. Reduced deep sleep contributes to preexisting inflammation and has an intricate relationship with pain.

Despite this, few studies have evaluated sleep architecture in children with SCD, and how it is altered in those with nocturnal hypoxemia (NH).

Aim: To evaluate differences in sleep architecture in children with SCD with NH compared to those without NH.

Methods: An IRB approved retrospective chart review was conducted to evaluate the sleep architecture in children with SCD, by examining health metrics and polysomnogram (PSG) reports of 75 children with SCD. We collected demographic data, hematologic laboratory values and PSG variables. Continuous variables were summarized as mean (SD) or median (IQR) and categorical variables were summarized using frequencies and percentages. Distribution of categorical variables were compared using chi-square or Fisher exact test as appropriate

Results: Children analyzed were ages 2-20 years, with a mean age of 10. The population was 50.7% female and 97% of the cohort identified as Black/African American. The mean BMI z-score was 0.773. To analyze data, the cohort was separated to differentiate those with NH (7/75) and those without NH (68/75). Nocturnal hypoxemia was defined as present if oxygen saturations recorded during the sleep study were below 90% for more than 5% of the entire study.

Results: The SS genotype was significantly associated with NH compared to other SCD genotypes. Among laboratory parameters, those with NH had significantly lower Hemoglobin (Hb), higher reticulocyte count, and elevated bilirubin levels. Among the respiratory sleep variables, O2 nadir (lowest recorded oxygen saturation during PSG) was significantly lower in the NH group (Mean 80.3, SD 6.7) compared to the non-NH group (M=88.7, SD=7.5), p value 0.01. There was no difference in apnea-hypopnea indices between these two groups. Among the non-respiratory variables, there was no significant difference in the N1, N2 and REM sleep percentages, however the percent N3 sleep was significantly reduced in children with NH (M=21.3%, SD 8.3) compared to those without NH (M=32.8 %, SD 16), p 0.009. Periodic limb movements (PLM) during sleep were significantly increased in the NH group compared to non-NH group. Interestingly, children with obstructive sleep apnea (OSA) were not more likely to have NH compared to those without OSA. Additionally, we analyzed the entire cohort categorizing as presence (43/75) or absence of OSA (32/75). Presence of OSA was based on apnea hypopnea index per hour of sleep and as diagnosed by sleep certified physician interpreting the PSG. The percent of time spent in each sleep stage (N1, N2, N3, and REM) was not significantly different between those with and without OSA.

Conclusions: We found reduced N3 (deep) sleep and increased PLM to be associated with NH, even in the absence acute illness in children with SCD. This study demonstrates the importance of identifying children with SCD who may have NH, not only due to their increased risk for SCD related complications, but also because of the risk for higher cognitive and learning deficits. Reduced N3 sleep in NH may play additional role in the presence of preexisting inflammation.