Towards the early detection of pregnancy complications
Maretha Bester defended her PhD thesis at the department of Electrical Engineering on June 30th.
Every year, over 100 million women become pregnant. Approximately 15% of these women will develop a pregnancy complication like high blood pressure or diabetes. Such complications negatively impact the health of the mother and fetus during pregnancy, increase the risk for both of future diseases, and burden healthcare systems. This negative impact can be reduced if complications are detected early enough to allow for the use of existing interventions, such as lifestyle changes or pharmaceutical regimens. A promising option for early detection is the assessment of autonomic nervous system (ANS) activity, as differences between the ANS of pregnant women who develop complications and those who stay healthy are already evident in early pregnancy. Moreover, wearable devices which assess ANS activity are already available. However, while the necessary technology already exists, the necessary research on maternal ANS activity during pregnancy does not. In her PhD research Maretha Bester focused on filling multiple research gaps to move us closer to implementing such monitoring solutions for the early detection of pregnancy complications.
Since the ANS is responsible for regulating involuntary processes such as heart rate (HR), we can non-invasively assess ANS activity by studying heart rate variability (HRV). Therefore, first, she acquired a comprehensive understanding of maternal HRV (mHRV) during healthy pregnancy by assessing the largest group of pregnant women available in the literature. She found that pregnancy has a large, significant impact on mHRV. In some cases, the differences in HRV between pregnant and non-pregnant women were larger than those between women and men. Moreover, she found that the results from the non-invasive analysis matched those from invasive analyses available in the literature.
Smartwatch most suitable
Thereafter, she considered the practical implementation of the proposed solution. Assuming it is known what constitutes healthy mHRV, if it’s detected that a woman has abnormal maternal HRV, does this necessarily indicate a complication? To answer this question, Maretha investigated which other factors may be influencing mHRV in a healthy pregnancy and found that not only do factors such as maternal age impact mHRV, but mHRV also changes as pregnancy progresses. Consequently, it was concluded using mHRV to track maternal health would necessitate that each woman serves as her own baseline. This means that the focus should be on tracking trends in mHRV rather than comparing spot measurements against a normative range.
Based on these conclusions, it was evident that the most suitable device to implement the proposed solution would be a smartwatch, which can be worn continuously to facilitate long-term monitoring. These watches typically work with photoplethysmography (PPG), which is an optical sensor that tracks blood flow from which HRV can be determined. Subsequently, the additional advantages of using PPG data were explored. First, in addition to HRV, information concerning the blood vessels can be extracted from PPG data. It was demonstrated that using this information alongside mHRV provides additional value in assessing maternal health. Second, sleep information can also be derived from PPG data. Using this information, it was further demonstrated that assessing maternal ANS activity only during periods of deep sleep holds advantages over assessing these metrics averaged across an entire night.
Unknown effect of corticosteroids
Furthermore, a common obstacle in assessing mHRV is the unknown effect of corticosteroids, a medication that is commonly administered to women with pregnancy complications. Understanding this effect is necessary for understanding the changes in mHRV that mark pregnancy complications. Therefore a study was set up and executed at the Máxima Medical Center what led to the discovery that administering corticosteroids alter maternal HRV and increases maternal HR. And because of that, it was concluded that mHRV cannot be reliably assessed in the four days following corticosteroid administration.
Evaluating coupling relationships useful
Finally, while mHRV is presently the most practical method for assessing maternal health, Maretha also looked to future options. She researched physiological coupling relationships – i.e., reciprocal interactions between organ systems – in pregnancy, as these relationships are in part facilitated by the ANS. Specifically, the coupling between the heart and lungs was examined, finding that while this coupling still exists in pregnancy, it is weaker than in non-pregnant women. Furthermore, the theory that coupling exists between the hearts of the mother and fetus was investigated, concluding that this coupling indeed exists and may be useful for tracking the development of the fetus. Ultimately, we believe that evaluating such coupling relationships may in future be useful for assessing maternal health.
Title of PhD-thesis: Towards the early detection of pregnancy complications using non-invasive assessments of autonomic regulation. Supervisors: prof. dr. ir. Massimo Mischi, TU/e; dr. ir. Rik Vullings, TU/e; dr. Judith O.E.H. van Laar, Máxima Medical Center; dr. ir. Rohan Joshi, Philips Research. Other main parties involved: e/MTIC (Eindhoven MedTech Innovation Center)