Our group has developed a non-invasive, transabdominal fetal oximeter, to provide worried mothers and obstetricians needed information regarding fetal well-being, namely fetal oxygenation, to reduce the number of unnecessary emergency C-sections. This is done by transmitting light in the near-infrared spectrum through the maternal abdomen and fetus to measure the oxygen saturation in the fetal blood using pulse oximetry. Pulse oximetry is a technique that utilizes the light absorption spectra of oxy- and deoxy- hemoglobin and captures a photoplethysmograph (PPG) from the vascular pulsations of the cardiac cycle. This PPG signal can then be used to calculate the oxygen saturation of the blood based on how much light was detected per heartbeat . In our case, a mixed maternal-fetal PPG is captured since light is traversing both maternal and fetal tissue, to which the fetal contribution can be isolated through Fourier analysis and filtering.
Our device consists of a non-invasive light probe, an embedded system, and custom software for data acquisition, display, and analysis. Our light probe contains the optical components needed to perform deep-tissue pulse oximetry and is encapsulated within poly-dimethylsiloxane (PDMS, or Silicone) for robustness, flexibility, and biocompatibility. Furthermore, PDMS is optically transparent at the wavelengths of interest and has a refractive index similar to human tissue. The embedded system is composed of a microcontroller, optical drivers, and other timing modules which allows us to programmatically control and capture time-synchronized signals from our probe. The custom software works in conjunction with the embedded system to display the real-time PPG measurements and frequency spectra to the user, and allows them to control various optical power and detection settings to get the optimal signal. The raw data can also be exported to allow post-processing for deep-dive analysis.
Cesarean section (C-section) is a major abdominal surgery which introduces significant risks to the mother and can have long-term effects on the respiratory health of the fetus . While the World Health Organization has identified that an ideal C-section rate is between 10-15% to not be under- or overused, many countries report having rates much higher . In 2014, the United States had an unacceptably high-rate of 32.2% . This is in part due to the current paradigm used for monitoring fetal well-being.
Electronic fetal heart rate monitoring (EFM) was adopted in the 1970’s as a means of assessing fetal well-being during labor and delivery and decrease the incidence of cerebral palsy and neonatal death. However, the rates of cerebral palsy, neonatal death, low Apgar scores, and perinatal death remained unchanged with its introduction, while the rate of C-sections rose dramatically . Despite the overwhelming evidence that EFM has not decreased adverse health outcomes, a high-proportion of C-sections are performed partly or fully in response to a non-reassuring EFM trace . Current interpretations of such traces is that it is suggestive of inadequate blood flow to the fetal brain and, if left untreated, can lead to cerebral palsy, fetal acidosis, and other harmful conditions. However, studies have shown that interpretations of EFM traces are unreliable, produce a high rate of false-positives (99.8%), and may be related to a normal chemoreflex response of the fetus . Clearly there is a need for new fetal well-being monitoring techniques. To address this issue and reduce the number of unnecessary emergency C-sections performed, we have developed a device that will non-invasively give physicians information on fetal oxygenation in utero, previously unattainable during critical stages of labor and delivery.
STATUS AND PRELIMINARY RESULTS
Safety calculations were performed to ensure no harm would come to the mother and fetus from our device. After calculating the maximum possible light-emission from our system, we determined that our device is well below the thresholds set forth by the International Electro-technical Commission in the standard IEC 60601-2-57, which is the adopted medical standard for our device classification by the American National Standards Institute, the Association for the Advancement of Medical Innovation, and the Food and Drug Administration which governs medical device regulation. Furthermore, our device also adheres to the International Commission on Non-Ionizing Radiation Protection guidelines on infrared radiation and falls well-below specified exposure limits .
In addition to safety, a large concern is of being able to detect the fetal heart rate at all, since light does not traverse tissue very deeply. On average, the fetus is at a depth of 2.5-cm below the skin of the maternal abdomen. However, to account for a greater size variability between pregnancies we aimed to show device feasibility at a depth of 5-cm. The ability to measure the heart rate (from the PPG) directly correlates to the signal strength and feasibility of calculating oxygen saturation and was the primary focus of our tests. However, as a proof-of-concept several PPG measurements on volunteers were performed and resulted in measured SpO2 values within 2% of those reported by a clinical COTS pulse oximeter.
We have performed Monte Carlo simulations to determine the proportion and strength of the fetal signal to the total mixed PPG with respect to emitter-detector distance and wavelength. Each simulation was performed by sending 10-million photon packets into the tissue model, which included the maternal epidermal/dermal tissue layer, sub-dermal layer, uterine muscle, amniotic fluid, and the fetal head, and generates a resulting photon distribution. For these simulations, the resulting output is the impulse response from an infinitesimally-thin pencil beam. Assuming the steady-state configuration, valid at our measurement time-intervals, a 3-D spatial convolution was performed on the output to match our emitter components with a Gaussian beam-profile. The results helped to guide design decisions towards the optimal selection, placement, and number of components needed for our application.
In addition to the simulation, we designed a 5-cm thick tissue phantom to match the optical properties of the maternal abdomen at appropriate wavelengths, which was then placed upon a volunteer to mimic the fetal PPG signal. The volunteer’s heart rate was simultaneously monitored using a COTS pulse oximeter to validate the signal seen using our device. The signal power of the captured data in the frequency spectrum shows a clear peak at the heart-rate reported by the COTS pulse ox, thereby giving us confidence that our device can capture a fetal signal from 5-cm deep in maternal tissue.
Similarly, this type of a setup was also performed in which the phantom was replaced with a New York strip steak of beef (3-cm thick), which also reported agreeable signals to the validation device.
BURIED ARTERY MEASUREMENTS:
To further show our device’s capability, it was used to measure a volunteer’s PPG signal at the popliteal artery, located behind the knee. This artery was selected because of the absence of other pulsating vascular components near it and its appropriate depth from the surface of the skin. This improves confidence that any signal seen is from that artery. The depth of the popliteal artery on the volunteer, was determined to be around 3.5-cm using ultrasound, and the PPG power spectra captured using our device was validated using a clinical pulse-ox monitor. The matched signal peak of our device and the clinical monitor shows that we are able to capture a PPG signal from 3.5-cm below the surface of actual human tissue.
Some of our planned next steps for our project include performing an animal study using pregnant ewes as a logical step towards approaching clinical trials. We are working with the Surgical Bioengineering Laboratory, run by Dr. Aijun Wang and Dr. Diana Farmer, at the UC Davis Medical Center to develop a plan to take PPG measurements of pregnant sheep using our device in an on-going animal study that they are performing. With positive results from the animal study, and the current results we have from our safety calculations, simulations, optical phantoms, and popliteal arteries an IRB protocol will be drafted and sent for approval to continue making progress towards a clinical trial.
This research is supported by the CITRIS seed funding award 2016-0105 (http://citris-uc.org/).
Many thanks to Dr. Diana Farmer, Dr. Aijun Wang, and Christopher Pivetti, at the Surgical Bioengineering Laboratory (http://www.ucdmc.ucdavis.edu/surgery/research/index.html) for their guidance and continued help with this effort.
UC Davis College of Engineering and the UC Davis Medical Center.
- PI: Dr. Soheil Ghiasi (http://web.ece.ucdavis.edu/~soheil/)
- Co-PI: Dr. Andre Knoesen (http://web.ece.ucdavis.edu/~knoesen/)
- Co-PI: Dr. Neil Ray (http://ucdmc.ucdavis.edu/publish/providerbio/anesthesiology/21812)
- Investigator: Daniel Fong (http://lepsucd.com/?page_id=601)
- Y. Mendelson and B. D. Ochs. Noninvasive pulse oximetry utilizing skin reflectance photo- plethysmography. IEEE Transactions on Biomedical Engineering, 35(10):798–805, Oct 1988.
- Infant and neonatal mortality for primary cesarean and vaginal births to women with “no indicated risk,” United States, 1998-2001 birth cohorts. Birth Sep;33(3):175-82, 2006.
- Hansen AK, Wisborg K, Uldbjerg N, Henriksen TB. Risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study. BMJ 336(7635), 85–87, 2008.
- APPROPRIATE TECHNOLOGY FOR BIRTH. The Lancet, 326(8452):436 – 437, 1985.
- E. Hamilton, J. A. Martin, M. J. Osterman, S. C. Curtin, and T. J. Matthews. Births: final data for 2014. Natl Vital Stat Rep, 64(12):1–64, Dec 2015.
- Alfirevic Z, Devane D, Gyte GML. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD006066. DOI: 10.1002/14651858.CD006066.pub2.
- K. B. Nelson, T. P. Sartwelle, and D. J. Rouse. Electronic fetal monitoring, cerebral palsy, and caesarean section: assumptions versus evidence. BMJ, 355, 2016.
- Sabiani L, Le Dû R, Loundou A, et al. Intra- and interobserver agreement among obstetric experts in court regarding the review of abnormal fetal heart rate tracings and obstetrical management. Am J Obstet Gynecol 2015;213:856.e1-8. doi:10.1016/j.ajog.2015.08. 066 pmid:26348383.
- Nelson KB, Dambrosia JM, Ting TY, Grether JK. Uncertain value of electronic fetal monitoring in predicting cerebral palsy. N Engl J Med 1996;334:613-8. doi:10.1056/ 36 NEJM199603073341001 pmid:8592523.
- G. Ziegelberger. ICNIRP Guidelines on Limits of Exposure to Incoherent Visible and Infrared Radiation. Health Physics, 105(1):74–96, January 2013.