Effect of Obstructive Sleep Apnea during Pregnancy on Fetal Development: Gene Expression Profile of Cord Blood.

Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood (WCB). Ten women in the third trimester of pregnancy were included, five OSA and five non-OSA cases. WCB RNA expression was analyzed by microarray technology to identify differentially expressed genes (DEGs) under OSA conditions. After data normalization, 3238 genes showed significant differential expression under OSA conditions, with 2690 upregulated genes and 548 downregulated genes. Functional enrichment was conducted using gene set enrichment analysis (GSEA) applied to Gene Ontology annotations. Key biological processes involved in OSA were identified, including response to oxidative stress and hypoxia, apoptosis, insulin response and secretion, and placental development. Moreover, DEGs were confirmed through qPCR analyses in additional WCB samples (7 with OSA and 13 without OSA). This highlighted differential expression of several genes in OSA (EGR1, PFN1 and PRKAR1A), with distinct gene expression profiles observed during rapid eye movement (REM)-OSA in pregnancy (PFN1, UBA52, EGR1, STX4, MYC, JUNB, and MAPKAP). These findings suggest that OSA, particularly during REM sleep, may negatively impact various biological processes during fetal development.

Impact of Obstructive Sleep Apnea on Gestational Diabetes Mellitus.

INTRODUCTION: Obstructive sleep apnea (OSA) increases the risk of type 2 diabetes, and hyperinsulinemia. Pregnancy increases the risk of OSA; however, the relationship between OSA and gestational diabetes mellitus (GDM) is unclear. We aimed (1) to evaluate OSA prevalence in GDM patients; (2) to assess the association between OSA and GDM; and (3) to determine the relationships between sleep parameters with insulin resistance (IR). METHODS: A total of 177 consecutive women (89 with GDM, 88 controls) in the third trimester of pregnancy underwent a hospital polysomnography. OSA was defined when the apnea-hypopnea index (AHI) was ≥5h-1. RESULTS: Patients with GDM had higher pregestational body mass index (BMI) and neck circumference than controls, but no differences in snoring or OSA-symptoms, or AHI (3.2±6.0 vs. 1.9±2.7h-1, p=.069). OSA prevalence was not significantly different in both groups. We did not identify OSA as a GDM risk factor in the crude analysis 1.65 (95%CI: 0.73-3.77; p=.232). Multiple regression showed that total sleep time (TST), TST spent with oxygen saturation<90% (T90), and maximum duration of respiratory events as independent factors related with homeostasis model assessment of IR, while T90 was the only independent determinant of quantitative insulin sensitivity check index. CONCLUSION: OSA prevalence during the third trimester of pregnancy was not significantly different in patients with GDM than without GDM, and no associations between OSA and GDM determinants were found. We identified T90 and obstructive respiratory events length positive-related to IR, while TST showed an inverse relationship with IR in pregnant women.

Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy.

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-1ß, 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-1ß, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α (r = 0.40), IL-1ß (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-1ß (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.

Impact of Obstructive Sleep Apnea on Gestational Diabetes Mellitus.

INTRODUCTION: Obstructive sleep apnea (OSA) increases the risk of type 2 diabetes, and hyperinsulinemia. Pregnancy increases the risk of OSA; however, the relationship between OSA and gestational diabetes mellitus (GDM) is unclear. We aimed (1) to evaluate OSA prevalence in GDM patients; (2) to assess the association between OSA and GDM; and (3) to determine the relationships between sleep parameters with insulin resistance (IR). METHODS: A total of 177 consecutive women (89 with GDM, 88 controls) in the third trimester of pregnancy underwent a hospital polysomnography. OSA was defined when the apnea-hypopnea index (AHI) was ≥5h-1. RESULTS: Patients with GDM had higher pregestational body mass index (BMI) and neck circumference than controls, but no differences in snoring or OSA-symptoms, or AHI (3.2±6.0 vs. 1.9±2.7h-1, p=.069). OSA prevalence was not significantly different in both groups. We did not identify OSA as a GDM risk factor in the crude analysis 1.65 (95%CI: 0.73-3.77; p=.232). Multiple regression showed that total sleep time (TST), TST spent with oxygen saturation<90% (T90), and maximum duration of respiratory events as independent factors related with homeostasis model assessment of IR, while T90 was the only independent determinant of quantitative insulin sensitivity check index. CONCLUSION: OSA prevalence during the third trimester of pregnancy was not significantly different in patients with GDM than without GDM, and no associations between OSA and GDM determinants were found. We identified T90 and obstructive respiratory events length positive-related to IR, while TST showed an inverse relationship with IR in pregnant women.