Background There is emerging evidence of an association between circadian rhythms disruption and pregnancy complications. Preeclampsia is a leading cause of maternal death during pregnancy, and the role of circadian rhythms in predicting preeclampsia is not well understood.

Objective Our aim was to determine whether glucose circadian rhythm disruption is associated with preeclampsia and can be used to predict this pregnancy disorder.

Methods We analyzed a dataset of 92 recruited individuals with Continuous Glucose Monitoring (CGM) data recorded at 24.62 (sd = 4.97) weeks of gestational age. To study rhythmicity, we performed a cosinor analysis using the packages cosinor and cosinor2, and we calculated the non-parametric circadian rhythm variables using the nparACT package in R. Furthermore, we performed multiple component cosinor analysis to detect internal oscillations and identify glucose postprandial peaks using the package CosinorPy in Python.

Results 71 participants (20 women with preeclampsia) had sufficient data for studying glucose circadian rhythmicity and performing cosinor analysis for multiple components to detect the postprandial peaks. We found that all the participants exhibited a significant circadian rhythm in their glucose oscillation. We developed a model including the time difference between the first postprandial peak and the last one, L5 start-time (time at which the five consecutive hours with the lowest average glucose levels start) and age that was predictive for preeclampsia incidence (AUC: 0.80 95%CI: 0.69-0.91, specificity= 0.88, sensitivity = 0.37). Patients diagnoses with preeclampsia from this model had a reduced amplitude (p < 0.05) and less robust (p < 0.05) glucose rhythmicity.

Conclusion We conclude that evaluating glucose circadian rhythm during pregnancy may help to an earlier identification of preeclampsia.

J.A.C. held stocks in Dexcom, Inc at study initiation; however, J.A.C. had relinquished all shares before conducting this research. The remaining authors report no conflict of interest. Study devices were provided by Dexcom, Inc. for the original research. No additional funding was provided. Dexcom, Inc had no role in the study design; conduction of the study; collection, analysis, and interpretation of data; or manuscript writing.

No additional funding was required to perform this research

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The institutional review board approved our protocol at the McGovern Medical School (HSC-MS-18-0774). All participants provided written informed consent to participate in the research study

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