Periodic Reporting for period 2 - PREMADES (Preterm Feeding Maturity Measurement and Evaluation)
Reporting period: 2018-03-01 to 2020-01-31
PREMADES (trademarked as NeoSAFE) is a medical diagnostic device, developed to provide health care practitioners an objective yet noninvasive means for the assessment of feeding maturity. With PREMADES, it is intended to monitor the improvements in the preterms’ feeding maturity and compare evaluations by regular measurements and analysis, and hence improve clinical decisions.
Swallowing oral nutriments is a complex process, in which 26 muscle pairs, 5 cranial nerves as well as nerves stemming from spinal cord that regulates the movements of chest wall for coordination of breathing and swallowing takes role. Sucking muscles, muscles surrounding the mouth generating sucking pressure, opening and closing of the chin, movement of tongue towards the palate and proceeding of the bolus towards the pharynx are responsible for effective sucking.
Most of the term infants, which were born after the regular gestation period of 37 weeks, have coordinated respiration-sucking-swallowing patterns. However, these are underdeveloped in preterm infants. The lack of development of effective feeding in preterms can cause serious complications such as accidentally aspirated food into the respiratory tract and the lungs, respiratory illnesses related problems like brain hypoxia, infections, respiratory arrest and even death. Further, this can also cause preterm infants to get tired very quickly during feeding and thus impact their growth negatively. For these reasons, most of the preterm infants are fed via an orogastric tube in NICU.
Achievement of effective oral feeding after birth is important for ideal growth and for safe discharge. The exact time at which sucking, swallowing, and respiration become coordinated in preterm infants is still unknown; however, integrity of oropharyngeal anatomy and neurological function is essential to complete the maturation. Preterm infants who are discharged before they have acquired effective feeding skills may be at risk for aspiration, breathing difficulties, or severe respiratory and neurological problems.
Given the aforementioned problems, the crucial need to gain knowledge of the time of maturity of effective feeding in newborns and the importance of monitoring their development is obvious. Today in practice, doctors utilize trial-and-error techniques or observational criteria that are, for the most part, subjective, in order to evaluate the feeding effectiveness and safety. Furthermore, our product is appropriate for point of care testing in NICUs, spreadable and marketable globally. Moreover, it is painless for infants and convenient for the medical staff.
At the end of this project PREMADES became ready for the international markets while proving the safeness and effectiveness for preterm infants by conducting multi-site independent clinical trials. During the implementation of the project, it has been validated and verified by the independent test laboratories with respect to related standards and regulations. Additionally, a wide variety of dissemination activities are executed increasing the awareness of key-opinion-leaders, physicians, nurses and general public.
Swallowing oral nutriments is a complex process, in which 26 muscle pairs, 5 cranial nerves as well as nerves stemming from spinal cord that regulates the movements of chest wall for coordination of breathing and swallowing takes role. Sucking muscles, muscles surrounding the mouth generating sucking pressure, opening and closing of the chin, movement of tongue towards the palate and proceeding of the bolus towards the pharynx are responsible for effective sucking.
Most of the term infants, which were born after the regular gestation period of 37 weeks, have coordinated respiration-sucking-swallowing patterns. However, these are underdeveloped in preterm infants. The lack of development of effective feeding in preterms can cause serious complications such as accidentally aspirated food into the respiratory tract and the lungs, respiratory illnesses related problems like brain hypoxia, infections, respiratory arrest and even death. Further, this can also cause preterm infants to get tired very quickly during feeding and thus impact their growth negatively. For these reasons, most of the preterm infants are fed via an orogastric tube in NICU.
Achievement of effective oral feeding after birth is important for ideal growth and for safe discharge. The exact time at which sucking, swallowing, and respiration become coordinated in preterm infants is still unknown; however, integrity of oropharyngeal anatomy and neurological function is essential to complete the maturation. Preterm infants who are discharged before they have acquired effective feeding skills may be at risk for aspiration, breathing difficulties, or severe respiratory and neurological problems.
Given the aforementioned problems, the crucial need to gain knowledge of the time of maturity of effective feeding in newborns and the importance of monitoring their development is obvious. Today in practice, doctors utilize trial-and-error techniques or observational criteria that are, for the most part, subjective, in order to evaluate the feeding effectiveness and safety. Furthermore, our product is appropriate for point of care testing in NICUs, spreadable and marketable globally. Moreover, it is painless for infants and convenient for the medical staff.
At the end of this project PREMADES became ready for the international markets while proving the safeness and effectiveness for preterm infants by conducting multi-site independent clinical trials. During the implementation of the project, it has been validated and verified by the independent test laboratories with respect to related standards and regulations. Additionally, a wide variety of dissemination activities are executed increasing the awareness of key-opinion-leaders, physicians, nurses and general public.
By the work performed, an optimized and renovated product has been developed which is ready for mass production and marketing. Particularly,
- A proprietary main processing electronics and sensors have been developed.
- A new industrial/mechanical design suitable and feasible for manufacturing is achieved.
- Completely innovative probe and corresponding connector pairs are designed and developed including electronical and mechanical components.
- A non-invasive real-time respiration monitoring functionality is added to the product by utilizing chest/diaphragm and belly movement of the infant.
- In parallel to the hardware developments, software stack including BSP is overhauled.
- Signal processing and machine learning algorithms are improved in terms of computational complexity and performance.
- Quality Management System is established.
- A Risk Management System is established.
- Configuration Management System and PLM System is established.
- For mass production, suppliers with backup alternatives are determined.
- Complete Critical Design Review conducted and results are incorporated into the design specifications.
- Necessary design specifications for risk and failure mitigations are determined and incorporated into the product design.
- Multiple International Trade Fair, Conference and Symposium participations are accomplished.
- Participated to multiple pitching events.
- Conformity to relevant electrical and electronics safety standards have been achieved and documented.
- Conformity to relevant biovalidation and biocompatability standards have been achieved and documented.
- Multiple prototypes have been manufactured and demonstrations are conducted for scientific and medical community.
- Multi-site independent clinical trials are successfully conducted with more than 120 patients.
- Pre-orders from multiple researchers is received.
- Research partners for future collaborations are gained.
- Other uses for different patient segments are identified.
- A proprietary main processing electronics and sensors have been developed.
- A new industrial/mechanical design suitable and feasible for manufacturing is achieved.
- Completely innovative probe and corresponding connector pairs are designed and developed including electronical and mechanical components.
- A non-invasive real-time respiration monitoring functionality is added to the product by utilizing chest/diaphragm and belly movement of the infant.
- In parallel to the hardware developments, software stack including BSP is overhauled.
- Signal processing and machine learning algorithms are improved in terms of computational complexity and performance.
- Quality Management System is established.
- A Risk Management System is established.
- Configuration Management System and PLM System is established.
- For mass production, suppliers with backup alternatives are determined.
- Complete Critical Design Review conducted and results are incorporated into the design specifications.
- Necessary design specifications for risk and failure mitigations are determined and incorporated into the product design.
- Multiple International Trade Fair, Conference and Symposium participations are accomplished.
- Participated to multiple pitching events.
- Conformity to relevant electrical and electronics safety standards have been achieved and documented.
- Conformity to relevant biovalidation and biocompatability standards have been achieved and documented.
- Multiple prototypes have been manufactured and demonstrations are conducted for scientific and medical community.
- Multi-site independent clinical trials are successfully conducted with more than 120 patients.
- Pre-orders from multiple researchers is received.
- Research partners for future collaborations are gained.
- Other uses for different patient segments are identified.
As stated in the project proposal, the preterm birth in terms of health and economic issues is still a serious problem for all countries, although the PTB rates are closely related to the socioeconomic statuses of countries. According to the WHO, an estimated 15 million babies are born prematurely every year in the world and it is reported that PTB amount is rising. In developed countries, PTB constitute 6-12% of all births, whereas in developing countries, this ratio is more than 15%. Tremendous effort is being put in action in order to avoid premature births and improving the well-being of preterms. Hence, it can be easily stated that our endeavor is relevant to the patients, their families and other stakeholders as well as to the medical device market rather easily. It should be noted that early discharge of preterm infants with feeding disorders results in serious health problems for newborns and causes emotional and physiological damages to their families. Through our interactions and discussions with fellow neonatologists, physicians and experts the aforementioned problems have become more apparent. Seconding the reasoning that the increase in late preterm birth rates has caused an increase in the number of infant discharges prior to the development of respiration-sucking-swallowing coordination. As a result, it is observed that in the long term, feeding difficulties can cause growth retardations, neurological disorders and recurring readmissions. With our product, preterms’ feeding maturity will be tracked regularly and hence improved clinical decisions will be made. According to our clinical results, NeoSAFE is shown to be a not only noninvasive but also painless and non-irritating for newborns. It has been shown that the observational assessment is not reliable and objective results obtained from NeoSAFE are more conclusive for the correct assessment of feeding maturity compared with healthcare professionals’ subjective assessment. Furthermore, additional medical use possibilities are identified such as the monitorization of adult dysphagia and neuromotor deficiencies. Hence with an effective monitoring method such as PREMADES, the positive impact on the health and treatment of millions who are battling with dysphagia will be remarkable.