Background: Obstructive sleep apnea (OSA) is prevalent in obese women with gestational diabetes (GDM). In non-pregnant population, metabolomics profiles have been shown to differ between those with and without OSA. This study explored associations between OSA severity and metabolites in women with GDM.

Methods: Eighty-two obese women with diet-controlled GDM had OSA assessment by a home monitor (mean gestational age, GA, 28 weeks). OSA severity was assessed by apnea hypopnea index (AHI). Metabolic profile was assayed from fasting serum samples via LC-MS using an untargeted approach. The metabolites were extracted and subjected to an Agilent 1290 UPLC coupled to an Agilent 6545 Q-TOF MS. Data were acquired using electrospray ionization (ESI) in positive and negative ion modes. The raw LC-MS data were processed using the OpenMS toolkit to detect and quantitate features and these LC-MS features were annotated using the Human Metabolite Database (HMDB) as a reference. The feature data were compared with OSA status, AHI, BMI and GA using limma in R. Correlation analyses of the continuous covariates (AHI, BMI, GA) were performed using Kendall’s Tau test. P-values were adjusted for multiple testing using Benjamini-Hochberg’s FDR correction.

Results: Forty-three women (52.4%) had OSA, with a median AHI of 9.4. There were no significant differences in metabolomics profiles between those with and without OSA. However, differential analyses modeling in GA and pre-pregnancy BMI found 12 features that significantly associated with AHI. These features could be annotated to estradiols and phospholipids (e.g., Lysophospholipids, long-chain acyl carnitine, methyl-branched fatty acids) with higher levels related to higher AHI.

Conclusion: Biomarkers including estradiols and phospholipids may be involved in pathogenesis of OSA in pregnant women with GDM. Targeted approach may help further identify these metabolites to better understand their role in OSA in this population.


S. Reutrakul: None. N. Chirakalwasan: None. S. Charoensri: None. S. Amnakkittikul: None. S. Saetung: None. H. Chen: None. G.E. Chlipala: None.


National Center for Advancing Translational Sciences (UL1TR002003); Mahidol University

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