Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy

Abstract

Background: Obstructive sleep apnea (OSA) is prevalent in pregnancy and it is associated with adverse pregnancy-related outcomes such as gestational diabetes, pre-eclampsia, and low birth weight. Maternal systemic inflammation is proposed to be one of the main intermediate mechanisms. However, the effects of OSA on systemic inflammation are unknown in normal pregnancy. Methods: Women in the 3rd trimester underwent hospital polysomnography to evaluate whether OSA increases systemic inflammation in normal pregnancy and its potential association with adverse fetal outcomes. OSA was defined as an apnea-hypopnea index (AHI) of ≥ 5 h^-1. Plasma cytokines levels (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were determined by multiple immunoassays. Results: We included 11 patients with OSA and 22 women with AHI < 5 h^-1, who were homogeneous in age, and body mass index (BMI). Women with OSA had significant higher levels of TNF-α, IL-1β, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α (r = 0.40), IL-1β (r = 0.36), IL-6 (r = 0.52), IL-8 (r = 0.43), between obstructive apnea index and TNF-α (r = 0.46) and between AHI and IL-1β (r = 0.43). We also found that CT90% was related to IL-8 (r = 0.37). There were no significant differences in neonatal characteristics; however, we found inverse correlations between TNF-α and IL-8 with birth weight (both r = -0.48), while IL-8 showed a significant inverse relationship with neonatal gestational age (r = -0.48). Conclusions: OSA in our normal pregnancy population was associated with higher systemic inflammation, which was related to obstructive events, especially during REM sleep. Moreover, systemic inflammation was inversely correlated with neonatal birth weight and age.

Keywords: Obstructive sleep apnea; REM; apneas-hypopneas index; cytokine; fetal outcomes; hypoxia; inflammation.

Figure 1

Comparison of cytokines levels in OSA and non-OSA pregnant women. Comparison of cytokines levels in OSA and non-OSA pregnant women. Statistical tests: t-Student^¥; U Mann- Whitney^¶. (A) TNF-α^¥; (B) IL-1β^¶; (C) IL-8^¶; (D) IL-10^¶. The bar chart represents mean and standard deviation (TNF-α) and boxplots represent medians and interquartile ranges (IL-1β, IL-8, and IL-10). IL, interleukin; OSA, Obstructive sleep apnea; TNF-α, Tumor necrosis factor alpha.

Figure 2

Inflammatory cytokines levels and sleep study parameters correlations. Pearson^ϕ (TNF-α) and Rho de Spearman^σ (IL-1β, IL-6, IL-8, and IL-10) correlations. (A) Correlation between TNF-α and REM AHI^ϕ; (B) Correlation between IL-1β and REM AHI^σ; (C) Correlation between IL-6 and REM AHI^σ; (D) Correlation between IL-8 and REM AHI^σ; (E) Correlation between TNF-α and the total number of OA^ϕ; (F) Correlation between TNF-α and OAI^ϕ; (G) Correlation between TNF-α and mean duration of OA^ϕ; (H) Correlation between TNF-α and maximum duration of OA^ϕ; (I) Correlation between IL-1β and the total number of AH^σ; (J) Correlation between IL-1β and AHI^σ. AHI, Apneas-hypopneas index; IL, Interleukin; OA, Obstructive apneas; OAI, Obstructive apneas index; p, p-value; r, Correlation coefficient; REM, Rapid eye movement; TNF-α, Tumor necrosis factor alpha.

Figure 3

Inflammatory cytokines levels and neonatal characteristics correlations. Pearson^ϕ (TNF-α) and Rho de Spearman^σ (IL-8) correlations. (A) Correlation between TNF-α and neonatal weight^ϕ; (B) Correlation between IL-8 and neonatal weight^σ; (C) Correlation between IL-8 and neonatal gestational age^σ. IL, Interleukin; p, p-value; r, Correlation coefficient; TNF-α, Tumor necrosis factor alpha.