Flexible monitoring devices among other new technologies can assist with detection and prevention of maternal and infant morbidity
Despite spending more on health care, the United States has the highest infant and maternal mortality rates of any high-income country, according to a recent report by the Commonwealth Fund [1]. In 2020, U.S. maternal mortality was over three times the rate in most other high-income countries, at 23.8 maternal deaths for every 100,000 live births. And troublingly, these numbers are rising, with 32.9 maternal deaths for every 100,000 live births reported in 2021 [2]. In addition, rates of maternal morbidity—short- and long-term health problems related to pregnancy or giving birth—are increasing [3].
“I feel like we owe it to pregnant people, their families, and their fetuses to incorporate new technologies to improve maternal and infant health,” says Yalda Afshar, a physician-scientist at the David Geffen School of Medicine at the University of California, Los Angeles (Figure 1). “A good understanding of women’s health has been lacking and technology is just catching up to our field.”
Figure 1. Yalda Afshar, a physician-scientist at the David Geffen School of Medicine at the University of California, Los Angeles, is part of a team that developed a nanotech device capable of detecting placenta accreta spectrum disorder with a blood sample. (Photo courtesy of Afshar.)
Early warnings
Afshar is a high-risk pregnancy physician. Much of her research focuses on the early detection of health issues in pregnancy, including diseases of the heart and placenta. “Pregnancy is not a disease, it’s a normal physiologic state,” she says. “It is so common, yet we really don’t understand the basic underlying biology, let alone when there is disease as well.”
For instance, heart disease is a health risk for pregnant people, but many of its symptoms (such as shortness of breath and a fast heart rate) also commonly occur in pregnancy. Here, Afshar says, care might be improved with better biomarkers for heart disease, as well as better use of electronic medical records for patient education and communication.
In cases of congenital heart disease in the fetus, knowledge of the disease before birth is associated with improved survival and long-term outcomes. While standard prenatal echocardiography can detect most congenital heart disease, it has limited diagnostic accuracy for certain heart abnormalities [4]. Afshar says that for some fetuses at increased risk, prenatal cardiac magnetic resonance imaging (MRI) may provide more information and improve diagnostics.
“Cardiac MRI is now well established and utilized with babies outside of the womb,” she says. “It’s able to look at the structure of the heart and elucidate hemodynamics. But we are lagging in using cardiac MRI when the baby is in utero.”
Prenatal MRI has often been technically challenging and underused, but Afshar and others have made advances in imaging technology to overcome these issues [4]. As the technology continues to develop and evolve, Afshar sees a vital role for it as a complementary diagnostic tool to echocardiography.
Detection and prevention
Early detection is also key for a life-threatening pregnancy condition called placenta accreta spectrum disorder. This condition occurs when the placenta grows too deeply into the uterine wall and fails to separate from the uterus after birth. It can cause significant blood loss and even death. “When placenta accreta is unknown until the time of birth, it can become catastrophic,” says Afshar. “One area that our group is working on is how to detect it very early in pregnancy.”
Currently, placenta accreta spectrum disorder is diagnosed through a combination of ultrasound imaging and assessment of medical history (for example, previous cesarean births may increase risk). But these screening methods are not reliable enough to detect all cases, nor are they available in all health care settings.
Afshar is part of a team that developed a nanotech device capable of detecting placenta accreta spectrum disorder with a blood sample. The approach uses a technology called the NanoVelcro Chip, originally designed to detect tumor cells in individuals with cancer. To detect placenta accreta spectrum disorder, researchers adapted the chip to recognize specific placenta cells in the mother’s blood called trophoblasts. Abnormally elevated numbers of trophoblasts, or clusters of the cells, indicate a risk for the disorder. The blood test, which can be performed as early as the first trimester of pregnancy, was 79% accurate in diagnosing placenta accreta and 93% accurate in ruling it out [5].
In addition to early detection, Afshar is working to understand the biology of placenta accreta. “If we understand the underlying mechanisms, we can move toward therapeutics to prevent placenta accreta,” she says. “We want to make sure we can detect it. Then we need to understand why it happens to subsequently prevent it.”
Pregnancy monitoring for the 21st century
Another issue is that monitoring technology for laboring mothers and newborns has remained relatively unchanged for decades. Mothers are often tethered to their beds with fetal-monitoring belts and an array of other wires, limiting their ability to move freely. Premature babies also require intensive monitoring, which is typically achieved with a cumbersome web of wires and electrodes taped to their fragile skin. The setup is restrictive for both the baby and its caretakers, complicating basic aspects of clinical care and limiting physical bonding between parents and child.
“Pregnancy monitoring has not improved much in the last 50 years,” says Steve Xu, a physician-engineer at Northwestern University (Figure 2). “Monitoring in neonatal intensive care units looks largely the same today as it did in the 1980s.”
Figure 2. Steve Xu, a physician-engineer at Northwestern University, works with a team to develop flexible monitoring systems for premature babies. (Photo courtesy of Xu.)
This need inspired John Rogers, a biomedical engineer at Northwestern University (Figure 3). “We had become comfortable in developing soft, skin-like, stretchable electronic devices and decided that premature babies were the class of patient that could benefit the most from this type of wireless technology,” he says.
Figure 3. John Rogers, an engineer at Northwestern University, is part of team developing wireless, battery-free, flexible sensors for babies and mothers. (Photo courtesy of Rogers.)
In 2019, Rogers, Xu, and colleagues published a validation study of their wireless, battery-free, flexible sensors on premature babies in local Chicago hospitals [6]. The team demonstrated that these new sensors are as precise and accurate as traditional wire-based monitoring devices in measuring babies’ heart rate, body temperature, and other key vitals, and can even gather more data than previous methods. In addition to being gentle on newborns’ skin and enabling more skin-to-skin contact with parents, the sensors are transparent and can be worn during X-rays, MRIs, and computed tomography (CT) scans. The data gathered by the sensors can be wirelessly transmitted via radio frequencies to nurses’ station displays and tablets [6].
Following the publication, the Bill & Melinda Gates Foundation and the Save the Children organization expressed interest in deploying the new sensors in low- and middle-income countries where monitoring technology is lacking. Rogers, Xu, and colleagues launched Sibel Health to develop and scale the sensors. Led by Xu, Sibel is working to commercialize their technology for use around the globe. Already, the sensors have been deployed in hospitals in Ghana, India, Kenya, and Zambia. To improve the wireless operating range and imbue the devices with stable, reliable power, the team added a small, rechargeable battery. They also added extra sensing capabilities to provide information beyond traditional vital signs, including crying, movement, body orientation, and heart sounds [7].
Improving pregnancy and birth outcomes
Building on its work with premature infants, Sibel has also developed wireless sensors to monitor both mother and baby in the ante-, intra-, and postpartum periods. The devices measure vital signs as well as provide new data, such as information about the mother’s physical movements and laboring positions. In tests, the wireless sensors outperformed current monitoring technology in precision and accuracy [8].
In addition to their clinical use, these sensors present an opportunity to collect new kinds of data continuously and unobtrusively, says Jessica Walter, a reproductive endocrinologist and assistant professor at Northwestern University (Figure 4). “The hope is that we can use artificial intelligence and develop algorithms to help identify people who are at risk for adverse outcomes and intervene earlier to prevent morbidity and mortality.”
Figure 4. Jessica Walter is a reproductive endocrinologist and assistant professor at Northwestern University. (Photo courtesy of Walter.)
Sibel is “moving forward on all fronts,” according to Xu. “We have four [U.S. Food and Drug Administration] FDA clearances, and we are in dozens of hospitals worldwide. In 2024, we will be ramping up commercially with partners in the U.S. and Europe and continuing to work with the Gates Foundation and other organizations in low- and middle-income countries.”
With these sensors, Rogers sees an opportunity to improve pregnancy and birth care in all types of settings, from high-resource urban hospitals to remote health clinics or patients’ homes. “Our hope is that it will become a ubiquitous technology for these vulnerable patient populations, which are poorly served by the technologies that exist today,” he says.
Walter agrees that better care for pregnant people and their babies is needed. “The vast majority of maternal mortality is preventable,” she says. “I think tools like these sensors, used correctly and judiciously, have real potential to help providers identify patients at serious risk.”
References
- M. Z. Gunja, E. D. Gumas, and R. D. Williams II, “U.S. health care from a global perspective, 2022: Accelerating spending, worsening outcomes,” Issue Brief (Commonwealth Fund), Jan. 31, 2023, doi:10.26099/8ejy-yc74.
- D. L. Hoyert, “Maternal mortality rates in the United States, 2021,” NCHS Health E-Stats, Mar. 16, 2023, doi: https://dx.doi.org/10.15620/cdc:124678.
- National Institutes of Health Maternal Morbidity & Mortality Web Portal. Accessed: Nov. 8, 2023. [Online]. Available: https://orwh.od.nih.gov/mmm-portal/what-mmm
- A. Desmond et al., “Integration of prenatal cardiovascular magnetic resonance imaging in congenital heart disease,” J. Amer. Heart Assoc., vol. 22, p. e030640, Nov. 2023, doi: 10.1161/JAHA.123.030640.
- Y. Afshar et al., “Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders,” Nature Commun., vol. 12, no. 1, p. 4408, 2021, doi: 10.1038/s41467-021-24627-2.
- H. U. Chung et al., “Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care,” Science, vol. 363, no. 6430, p. eaau0780, Mar. 2019, doi: 10.1126/science.aau0780.
- H. U. Chung et al., “Skin-interfaced biosensors for advanced wireless physiological monitoring in neonatal and pediatric intensive-care units,” Nature Med., vol. 26, no. 3, pp. 418–29, Mar. 2020, doi: 10.1038/s41591-020-0792-9.
- D. Ryu et al., “Comprehensive pregnancy monitoring with a network of wireless, soft, and flexible sensors in high- and low-resource health settings,” Proc. Nat. Acad. Sci. USA, vol. 118, no. 20, p. e2100466118, May 2021, doi: 10.1073/pnas.2100466118.