The birthing process is a stressful time for both the mother and fetus. As the uterus contracts to expel the fetus out of the birth canal, the placenta and umbilical cord are temporarily unable to deliver vital oxygen to the fetus. Most fetuses tolerate the birthing process, but approximately 1% do not. Clinicians struggle to identify which fetuses are not tolerating the birthing process because the current fetal monitors that are used during labor and delivery have a high false positive rate for predicting fetal distress, thereby resulting in unnecessary C-sections.
Fetal heart rate monitoring was developed in 1968 to identify the distressed fetus during childbirth. This technology has been used for the past 50 years with very little advancement. The technology looks at changes in the fetus’s heart rate that are associated with fetal distress. These heart rate changes, however, are also associated with normal physiological variation, making it difficult for clinicians to identify which fetuses are in distress versus experiencing a normal physiological variation in the heart rate pattern. The technology has been reported to have an 89% false positive rate for detecting fetal distress and 52% positive predictive value for detecting fetal distress. Its accuracy has been deemed a "coin toss." This uncertainty leads to approximately 33% more C-sections than are required. In 1975, C-section rates in the U.S. were 10.4% and have tripled since then.1 The World Health Organization believes that a 10-15% C-section rate is ideal—leading to the most lives saved and avoiding unnecessary complications.2 This problem leads to substantial costs to the healthcare system and unnecessary risks to the mother and baby.
Furthermore, the current technology sometimes fails to identify a fetus that is truly in distress. The sensitivity of fetal heart rate monitoring has been reported to vary between 85% to 97%. While these numbers seem high, they are not good enough. With over four million childbirths annually in the United States, these numbers translate to thousands of babies being born every year in the U.S. with neurological birth injuries that were not identified by the current technology used to monitor fetuses. These situations devastate families and can cost the health care system hundreds of millions of dollars in litigation and subsequent healthcare support. Just this past August, CBS News reported on the maternal mortality crisis in the U.S. Dr. Mary-Ann Etiebet (Executive Director of Merck for Mothers, Merck’s 10-year $500m initiative to create a world where no woman dies while giving birth) said, "The United States is the only industrialized country where the rates of maternal deaths have increased, not decreased. And so, young women actually have a higher risk of dying during pregnancy and childbirth than their mothers did. The United States is ranked 46th when it comes to maternal mortality. That’s behind countries like Saudi Arabia and Kazakhstan." In the U.S., at least two pregnant and/or delivering women die per day. The "near deaths" amount to 60,000 a year.3
There are several factors that have contributed to this public health care issue, such as women waiting longer in life to have babies and often beginning their pregnancies less healthy (i.e., obese, high blood pressure and diabetes). Some medical professionals suggest the primary cause is the mode of delivery. These doctors blame the dramatic rise of C-sections for the increase in deaths and near-deaths. Dr. Neel Shah, Professor of Obstetrics at Harvard Medical School and practicing physician said, "If you have a C-section in 2018, you have a 90% chance of having a C-section the second time. But the second time it’s a more complicated surgery. And the third time it can be like operating on a melted box of crayons. And in those cases, women can bleed to death." Dr. Shah believes more than half of C-sections are not necessary.
Dr. Justin Lavin, Chairman Emeritus at Cleveland Clinic - Akron General and Professor Emeritus at Northeast Ohio College of Medicine, said the currently used algorithm to determine when a C-section is necessary is designed to be overly cautious, leading to more C-sections. There is no technology to sort out which babies are properly oxygenated. A non-invasive device that can report the fetal oxygenation would serve a large unmet clinical need, as it would help doctors know when a C-section is in fact necessary (due to such issues as oxygen loss which can lead to brain damage) and when it is not necessary.
Technological improvements, specifically LEDs and solid-state photo detectors, have made non-invasive fetal pulse monitoring possible with safe, low-cost equipment. Raydiant Oximetry Sensing System (ROSS) is a noninvasive monitor placed on the mother’s abdomen that uses light-based technology to perform a color analysis of the fetus’s blood. The basic premise of the technology is that blood with oxygen is red, while blood without oxygen is blue. A color analysis quantifies the red and blue variations, which correlate to the amount of oxygen in the baby’s blood.
Raydiant has patented three techniques for distinguishing pulse oximetry between the mother and baby. The system performs frequency based filtering and separation from the differences in heart rates of mother and baby, utilizes wavelengths of light that have stronger affinity for fetal hemoglobin vs adult hemoglobin, and takes advantage of the fact that the mother’s oxygen saturation is usually over 95% and a normal fetal oxygen saturation in utero is 50% to 70%.
The normal movement of a mother during labor contraction should not be an issue, as Raydiant uses conventional pulse oximeters that utilize well-known signal processing algorithms for motion artifact. The system performs 500 samples per second per wavelength of light. The initial FDA indication for use will be a singleton pregnancy (a single child as opposed to twins or triplets) with a vertex presentation (the fetus is headdown in the birth canal) at 36 weeks gestation or greater. In the future, Raydiant will expand that indication for use of premature deliveries and monitoring the fetus during the 3rd trimester. In the OA (occiput anterior) position (head first and the body facing the mother’s back), the system will be measuring from the back of the head to the back of the neck while in the OP (occiput posterior) position, it will be measuring from the forehead. The reading can be done anywhere on the baby (through the mother’s abdomen), but the head has the strongest signal as it is closest to the mother’s abdomen. Since ROSS samples 500 times per second per wavelength of light, the slow rotation from OP to OA and slow decent down the birth canal will not interfere with measurements.
The irradiation levels of light being used by ROSS has been deemed safe, and the device received an IDE (Investigation Device Exemption) and a non-significant risk determination for testing in pregnant human subjects from the FDA. A clinical trial has been completed by Raydiant Oximetry where pregnant women in their third trimester were studied to demonstrate the feasibility of the technology. The study was registered with clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03013842).
|Fetal Oxygen Saturation in utero|
|Maternal Oxygen Saturation|
|Maternal Oxygen Saturation|
|Normal Range||45% - 70%||>90%||>94%|
The initial early feasibility study (results above) shows promising human data that trans-abdominal fetal oximetry is possible in pregnant women with BMIs (body mass indexes) less than 50. The ROSS sensor demonstrated the ability to obtain a fetal pulse oximeter signal and calculate oxygen saturations for the fetus with results that are known to be in the normal range of a fetus in-utero. The ROSS sensor was then applied to just the mother to validate the Raydiant Oximetry algorithms with an external maternal pulse oximetry and the results highly correlated. Because it is not possible to deprive a human fetus of oxygen and collect blood samples through a maternal abdomen, the FDA has agreed that validation of fetus oxygen saturations need to be conducted through pregnant animal models
A pregnant sheep model was used for validation of ROSS. The sheep model was deemed an appropriate model because the fetal sheep hemoglobin has similar oxygen binding properties to the fetal human hemoglobin and the depth of the fetal sheep is similar to the depth of the human fetus, which ranges between 3 to 5 cm. The model is common for validation of pulse oximeters
Multiple R : 0.92269544
R Square : 0.85136688
Adjusted R Square : 0.84207731
Standard Error : 0.04602646
Learnings from these sheep studies are as follows:
- Normal fetus oxygen saturation is between 45%-70% (think of it as a "green light"), 30%-45% needs caution (a yellow light) and below 30% is abnormal (a red light), needing immediate attention. ROSS is able to distinguish between these levels of fetal oxygen saturation.
- ROSS’s current accuracy is +/- 4.6%. Nellcor received FDA approval with +/- 4.7%. Raydiant will discuss with the FDA what accuracy level is needed (at a maximum between 3.5-4.7%).
- ROSS technology has some outlier data in the low oxygen saturation environment. Improved system stability is required to improve the reliability of data collection.
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