Sweet path

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The progress in neonatology gives a vast majority of children born prematurely not only a chance to survive, but also the possibility to develop properly and to fulfill their dreams. However, in spite of significant improvement, the development of extremely premature infants born before the 28th week of pregnancy, who often weigh less than 1000 grams, is still at risk.

The risk of impaired development of the central nervous system is highest in prematurely born infants. One of the essential factors influencing the development of a premature infant's brain is the proper glucose concentration in the blood.

Glucose – the golden mean

Glucose is a monosaccharide (simple sugar) whose level of concentration in the blood is strictly regulated by hormones, including insulin and glucagon. Immature hormonal mechanisms and scarce resources of this organic compound accumulated in fetal life often result in fluctuations of the glucose level in premature babies.

Glucose is the main source of energy for nervous cells. Glucose deficits lead to their necrosis and permanent brain damage. However, low glucose concentration in the blood of premature infants often does not give any clinical symptoms although it causes damage to the brain. On the other hand, too high a concentration of glucose may lead to brain haemorrhage or dehydration. Which methods should be applied for the purposes of determining glucose concentration in premature infants? This issue has been discussed for years, but an unambiguous answer to this question has not yet been found.

Research evaluating the influence of glucose concentration on brain development in premature infants is conducted at the Pediatric Clinic of the Jagiellonian University in Kraków Medical College, with the use of a continuous monitoring system that enables measuring the glucose concentration in extracellular fluid. The sensor of the monitoring system is placed in the subcutaneous tissue of the thigh. The sensor is covered with an enzyme, which enables an electrochemical reaction of glucose oxidation. The product of this reaction is an electric signal, and the resulting voltage, proportional to glucose concentration, is recorded in the memory of the monitoring device. Measurements are taken at five-minute intervals, for the first six days of the newborn's life. During this period the risk of glycaemic disorders (i.e., those related to glucose concentration in the blood) is the highest. The application of this method has reduced the number of blood samples collections for analysis. It also enables to start immediate treatment in the cases of excessive increase (hyperglycaemia) or decrease (hypoglycaemia) of glucose concentration.

Tractography showing the course of corticospinal tracts in an infant born prematurely

One test, many possibilities

The development of medical technologies allows for an indepth analysis of the processes occurring in the brains of our youngest patients. The assessment of brain development in premature infants is carried out with use of the most accurate imaging technique – magnetic resonance imaging. This method not only enables us to assess the development of the brain, but also shows the direction and continuity of neural fibers. It enables us to track neural connections, including those responsible for the transmission of signals from the cerebral cortex to the spinal cord. Damage to these pathways is one of the causes of infant cerebral palsy. The determination of the direction of their course does not require the use of contrast, as it is based on the phenomenon of fractional anisotropy. This phenomenon uses the preferential position of water molecules in a strong magnetic field, which is consistent with the course of pathways of white matter, i.e., of one of the elements (along with gray matter) of the central nervous system. Processing of the obtained data enables us to create a spatial map of neural connections in the brain.

Additionally, early detection of brain damage in newborns allows for the implementation of rehabilitation programs, which may significantly improve the child's development, as they are based on the phenomenon of brain plasticity.

Newborns born before the 32nd week of pregnancy, with a birth weight under 1500 grams are eligible for the study. "The study protocol has been approved by the Ethics Committee of the Jagiellonian University, and parents express their consent for the participation of their children in the study after receiving information about the safety of the performed procedures. We are grateful for their trust in us and for their consent to participate in the studies, as it contributes to the development of medicine," emphasized Mateusz Jagła, MD, PhD, a member of the team of scientists working on the issue.

Newborns are randomized to one of two groups differing by the target range of glucose level. A narrower range is maintained in the first group while a wider one is kept in the second one. On the due date of delivery, standard magnetic resonance imaging tests of the brain are performed, along with tractography (the analysis of the course of neural fibers) and an assessment of psychosomatic development. Monitoring of various areas of development of the tested children is also planned. The comparison of results obtained in both study groups will enable us to determine safe levels of glucose concentration in infants born prematurely. In 2013, the first year of the realization of this project, tests were performed on 35 infants born prematurely, which accounts for nearly half of the planned number of participants. The research is supported from the funds of Nutricia Research Foundation, and their results will be analyzed in 2014. Further studies assessing the children's development are scheduled for subsequent years.

Research team: Mateusz Jagła, MD, PhD; Izabella Szymońska, MD; Katarzyna Starzec, MD; Katarzyna Hrnciar, MD