Sleep-Associated Hypoxemia Is Common during Pregnancy in Sickle Cell Disease (SCD): A Retrospective Review

INTRODUCTION

Pregnancy in sickle cell disease (SCD) is associated with increased morbidity and mortality for mother and baby. There is a need to identify modifiable risk factors for adverse pregnancy outcomes. In SCD, polymerization of deoxy-hemoglobin is an important driver of disease activity. Thus, the identification of occult hypoxemia (low blood oxygen levels) during pregnancy may present a therapeutic opportunity in this high-risk group. At our institution, we have offered sleep-associated hypoxemia screening to all pregnant patients since 2021.

OBJECTIVE

This retrospective cohort study assessed the cumulative incidence, over 3 years, of sleep-associated hypoxemia during pregnancy in SCD. It also explored the relationship between hypoxemia and clinical characteristics.

METHODS

After obtaining IRB approval, we reviewed the medical records of pregnant adults with SCD between 1/1/2019- 12/31/2023. We identified participants who underwent sleep-associated oximetry while at clinical baseline, but not during inpatient admissions involving acute hypoxemia.

Sleep-associated hypoxemia was defined as SpO₂≤ 88% for at least 5 minutes of sleep time, based on contemporary CMS guidelines for prescribing oxygen. We collected demographics, clinical history, and labs at the time of testing. We described the incidence and duration of sleep-associated hypoxemia and explored relationships between hypoxemia and clinical characteristics using bivariable analysis.

RESULTS

Over 3 years, we identified 36 unique pregnant patients with SCD. 17 participants completed sleep-associated oximetry testing during pregnancy, 2 completed testing but did not meet eligibility, and 17 did not complete testing.

Of the 17 that completed testing, the most common sickle cell genotype was Hb SS (10/17) and Hb SC (3/17). The median age at testing was 27 years old, and most (9/17) tests were completed in the 2^nd trimester. Most participants had no history of smoking (12/17), obstructive sleep apnea (0/17), pulmonary hypertension (0/17), or opioid use disorder (1/17) at the time of testing. The most common pregnancy complication noted was preterm delivery (6/17). Of note, those that did not complete testing had similar demographics- median age at pregnancy of 27 years old, most common genotypes were Hb SS (9/17) and Hb SC (6/17).

Seven of 17 (41.2%) tested participants had night-time hypoxemia. The median duration of hypoxemia was 18.9 minutes, with a range of 6.06- 30.47 minutes. Those who tested positive for hypoxemia tended to have sickle cell anemia (SCA; 7/7 vs 6/10), to be older (median age 30 years old vs 25 years old). They were more anemic (median Hg 7.7g/dL vs 9.9 g/dL) and had higher hemoglobin S (HbS)% (85% vs 47.6%). The duration of hypoxemia had moderate-to-strong correlations with HbS% (r = 0.598, p=0.04), total hemoglobin (r = -0.509, p=0.05), total bilirubin (r = 0.464, p= 0.07), and LDH (r = 0.435, p=0.1). There were no significant differences in pregnancy outcomes by hypoxemia result.

CONCLUSIONS

We have described the presence of sleep-associated hypoxemia during pregnancy in people with SCD that underwent testing. In the absence of other relevant clinical factors, 41.2% participants tested positive for hypoxemia. If untested patients were assumed negative or positive, the cumulative incidence would fall between 20.6% to 70.6%. Similar to other studies of occult hypoxemia in SCD, increased levels of hemolysis, anemia, and inflammation appeared to associate with the presence and duration of hypoxemia during pregnancy.

This study is limited by its retrospective nature and sample size. In addition, structural barriers to completing such testing may contribute to selection bias. These barriers- including denials or delays in scheduling overnight testing, patient adherence, and patient discomfort- can be addressed with the use of innovative, user-friendly sleep trackers. Further studies will be needed to evaluate access to testing, and to clarify the risk factors for hypoxemia, and its relationship with adverse pregnancy outcomes in SCD.

Little:Novo-Nordisk: Other: Adjusications Committee; Novartis: Other: Research support directly and indirectly (through NASCC); Beam: Other: Research support directly and indirectly (through NASCC); Pfizer: Other: Research support directly and indirectly (through NASCC); NASCC: Membership on an entity's Board of Directors or advisory committees; ASH: Research Funding; NHLBI: Honoraria, Research Funding.