Pain-free treatment for premature infants
Approximately 6,000 babies are born prematurely in Austria each year. The definition of premature refers to babies born before the 37th week of pregnancy. Many of these babies require intensive medical care – and some also need medication for pain management or sedation. Vito Giordano, a neuroscientist at the Medical University of Vienna, wants such procedures, including intubation, the insertion of a central line, or postoperative care, to be as pain-free as possible for these tiny patients. Giordano specializes in the brain development of premature and newborn infants.
On average, premature infants are exposed to about 3,000 painful stimuli during their hospital stay: “Infants born too early are subjected to a considerable number of diagnostic, therapeutic, and routine examinations. It is therefore extremely important to strike a balance between avoiding pain and excessive sedation.” According to Giordano, current methods make it difficult to strike a precise balance, as they ultimately rely on subjective decisions.
Subjective assessment
Unlike adults, infants cannot verbally express or rate pain, which is why medical staff must rely on indirect signs. In this context, clinical observation scales are used particularly often . One of them is the “N-PASS” (short for “Neonatal Pain, Agitation, and Sedation Scale”), a scoring system that evaluates five categories by means of a point system. These categories take into account both behavioral responses, such as crying, and physiologically measurable parameters, such as heart rate. The calculated score then reflects the estimated level of pain. This is intended to help the treatment team assess the effect of analgesics and sedatives and identify over- or under-treatment early on.
There is a problem, though. Clinical scores do not allow for continuous monitoring of the patient’s condition. Changes are often documented only after they become clinically apparent and a reassessment has been conducted. Moreover, individual parameters are not specific to pain or sedation – a rapid heart rate could also be caused by hunger or stress. According to Giordano, established scales are important clinical tools but they should be supplemented by continuously available and physiologically reliable metrics. “For this reason, we are continuously striving to develop more objective parameters that can detect changes in clinical status as early and continuously as possible.”
Research for premature infants
Neuroscientist Vito Giordano investigates how clinical and environmental factors influence brain development in premature infants. In his Weiss project, he is developing new methods using brain measurements and AI to better support care teams in managing pain in infants born too early.
Brain waves instead of scales
In order to permit even more reliable pain-free treatment for babies in the future, Giordano and his team set out to develop a new approach with funding from the Austrian Science Fund FWF. To do so, they measure the baby’s brain waves using electroencephalography, or EEG for short. In this process, the researchers measure electrical signals triggered by nerve cells in the brain, since sedatives and analgesics alter human brain activity. This said, a baby’s EEG differs significantly from that of an adult.
In order to correctly interpret brain activity in infants, it is crucial to determine the brain’s stage of development. “Especially in premature infants, the functional maturity of the brain as recorded by EEG can deviate from the pattern expected for their age under certain clinical conditions. Sedatives can also cause characteristic changes in EEG activity,” explains Giordano. Ergo, the EEG of preterm infants undergoes profound maturation-related changes, which is why accurate interpretation requires approaches specifically developed for the brain of a newborn.
Machine learning can help
In concrete terms, this means that a reliable assessment requires assembling sufficient EEG reference data from infants to identify recurring patterns. This is precisely what the research group set out to achieve in their FWF-funded project. In the process, they were able to demonstrate that brain activity in sedated newborns changes in a characteristic way: in case of irregular EEG patterns, for instance, the phases of reduced background activity can become longer. These changes can provide clues as to how strongly medications influence the activity of the immature brain.
Such changes in the EEG are, however, not always unambiguously discernible to the human eye. Rather than assessing brain waves purely visually, the researchers now also use quantitative metrics. In recent years, there has been rapid progress in the development of algorithms capable of automatically identifying EEG patterns – a development facilitated by the use of artificial intelligence. “The increasing availability of large EEG datasets from newborns enable us to train and validate increasingly robust machine learning algorithms,” notes Giordano.
More data required
In the long run, an algorithm could automatically detect changes in brain activity and, in an ideal case, display in real time how deeply the baby is sedated. In any case, the initial analysis of the collected data shows a lot of promise: using the machine learning model, the researchers were able to reliably identify different background EEG patterns and detect changes. The objective is to use these data to derive more objective information about a newborn’s level of sedation in the future.
Giordano emphasizes, however, that practical application in everyday clinical practice will require further measurements and validation. For this purpose, the research team plans to combine the EEG with other measurement methods in the future – including monitoring cerebral oxygenation, heart rate variability, or skin conductance. Standardized protocols for brief medical procedures are also intended to help better compare the effects of different medications. The goal is to provide as comprehensive an assessment of the young patients’ condition as possible. Premature infants should experience as little pain as possible – but they also should not be sedated more than necessary.
About the researcher
Vito Giordano studied psychology in Rome and subsequently specialized in cognitive neuroscience with a focus on neurophysiology. He acquired his Ph.D. in clinical neuroscience at the Medical University of Vienna and earned his venia docendi in neuroscience. Today, his research focuses particularly on the functional brain development of premature and newborn infants – ranging from neurophysiological changes in the immature brain to their significance for long-term neurological development. His research project “Sedation Monitoring in Premature Infants” (2022–2026), received funding from the privately endowed Weiss Award of the Austrian Science Fund FWF.
Recent Publications
Automated estimation of EEG maturity in preterm neonates and its association with long-term outcome, in: Clinical Neurophysiology 2026
Adaptive threshold algorithm for detecting EEG-interburst intervals in extremely preterm neonates, in: Physiological Measurement 2024