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Neurovascular coupling refers to the mechanism that links the transient neural activity to the subsequent change in cerebral blood flow, which is regulated by both chemical signals and mechanical effects. Recent studies suggest that neurovascular coupling in neonates and preterm born infants is different compared to adults. The hemodynamic response after a stimulus is later and less pronounced and the stimulus might even result in a negative (hypoxic) signal. In addition, studies both in animals and neonates confirm the presence of a short hypoxic period after a stimulus in preterm infants. In clinical practice, different methodologies exist to study neurovascular coupling. The combination of functional magnetic resonance imaging or functional near-infrared spectroscopy (brain hemodynamics) with EEG (brain function) is most commonly used in neonates. Especially near-infrared spectroscopy is of interest, since it is a non-invasive method that can be integrated easily in clinical care and is able to provide results concerning longer periods of time. Therefore, near-infrared spectroscopy can be used to develop a continuous non-invasive measurement system, that could be used to study neonates in different clinical settings, or neonates with different pathologies. The main challenge for the development of a continuous marker for neurovascular coupling is how the coupling between the signals can be described. In practice, a wide range of signal interaction measures exist. Moreover, biomedical signals often operate on different time scales. In a more general setting, other variables also have to be taken into account, such as oxygen saturation, carbon dioxide and blood pressure in order to describe neurovascular coupling in a concise manner. Recently, new mathematical techniques were developed to give an answer to these questions. This review discusses these recent developments.

Graphs can be used to describe a great variety of real-world situations and have therefore been used extensively in different fields. In the present analysis, we use graphs to study the interaction between cerebral function, brain hemodynamics, and systemic variables in premature neonates. We used data from a propofol dose-finding and pharmacodynamics study as a model in order to evaluate the performance of the graph measures to monitor signal interactions. Concomitant measurements of heart rate, mean arterial blood pressure, arterial oxygen saturation, regional cerebral oxygen saturation-measured by means of near-infrared spectroscopy-and electroencephalography were performed in 22 neonates undergoing INSURE (intubation, surfactant administration, and extubation). The graphs used to study the interaction between these signal modalities were constructed using the RBF kernel. Results indicate that propofol induces a decrease in the signal interaction up to 90 minutes after propofol administration, which is consistent with clinical observations published previously. The clinical recovery phase is mainly determined by the EEG dynamics, which were observed to recover much slower compared to the other modalities. In addition, we found a more pronounced loss in cerebral-systemic interactions with increasing propofol dose.

The microvasculature and macrovasculature undergo extensive, organ-specific perinatal maturation. Multiple studies show associations between low birth weight and subsequent cardiovascular dysfunction in adulthood, suggesting that extreme preterm birth interferes with this maturation process. Therefore, we designed PREMATCH (PREMATurity as predictor of Cardiovascular–renal Health) to phenotype the microcirculation and macrocirculation during childhood in former preterm infants. A well-characterized cohort of former extreme preterm birth survivors and gender- and age-matched controls (aged 8–13 years) will be investigated for microvascular and macrovascular structure and function. In addition to cognitive performance and anthropometrics, we will investigate (i) the microvascular structure and function by endothelial function (photoplethysmography), sublingual capillary glycocalyx function (sidestream dark field imaging) and retinal structure (diameters of arterioles and venules); and (ii) the macrovascular phenotype by cardiac and renal ultrasound, repeated blood pressure measurements and arterial pulse-wave recordings. The PREMATCH study is unique in its design, and ongoing recruitment demonstrates excellent feasibility. The expectation is that the results of this study will identify risk factors during childhood for subsequent cardiovascular–renal disease in the adult life of former preterm infants, while further analysis on mediators in neonatal life of this cardiovascular–renal outcome may provide new information on perinatal risk factors.

Introduction: Cerebral autoregulation (CAR), the ability of the human body to maintain cerebral blood flow (CBF) in a wide range of perfusion pressures, can be calculated by describing the relation between arterial blood pressure (ABP) and cerebral oxygen saturation measured by near-infrared spectroscopy (NIRS). In literature, disturbed CAR is described in different patient groups, using multiple measurement techniques and mathematical models. Furthermore, it is unclear to what extent cerebral pathology and outcome can be explained by impaired CAR.Aim and methods: In order to summarize CAR studies using NIRS in neonates, a systematic review was performed in the PUBMED and EMBASE database. To provide a general overview of the clinical framework used to study CAR, the different preprocessing methods and mathematical models are described and explained. Furthermore, patient characteristics, definition of impaired CAR and the outcome according to this definition is described organized for the different patient groups.Results: Forty-six articles were included in this review. Four patient groups were established: preterm infants during the transitional period, neonates receiving specific medication/treatment, neonates with congenital heart disease and neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Correlation, coherence and transfer function (TF) gain are the mathematical models most frequently used to describe CAR. The definition of impaired CAR is depending on the mathematical model used. The incidence of intraventricular hemorrhage in preterm infants is the outcome variable most frequently correlated with impaired CAR. Hypotension, disease severity, dopamine treatment, injury on magnetic resonance imaging (MRI) and long term outcome are associated with impaired CAR. Prospective interventional studies are lacking in all research areas.Discussion and conclusion: NIRS derived CAR measurement is an important research tool to improve knowledge about central hemodynamic fluctuations during the transitional period, cerebral pharmacodynamics of frequently used medication (sedatives-inotropes) and cerebral effects of specific therapies in neonatology. Uniformity regarding measurement techniques and mathematical models is needed. Multimodal monitoring databases of neonatal intensive care patients of multiple centers, together with identical outcome parameters are needed to compare different techniques and make progress in this field. Real-time bedside monitoring of CAR, together with conventional monitoring, seems a promising technique to improve individual patient care.

Approximately 30 years ago, the myth that nervous system immaturity precluded neonates from pain perception and its negative effects was rejected. Neurobiologists further explored neurodevelopmental nociception. These observations strongly suggest that early pain experience contributes to neurodevelopmental outcome, pain thresholds, pain or stress-related behaviour and physiological responses in later life. Effective management of pain therefore remains an important indicator of the quality of care provided to neonates, not only from an ethical, but also from a short and long-term outcome perspective. Simultaneously, neonatal care itself has changed and data on neuro-apoptosis and impaired synaptogenesis following exposure to analgosedatives emerged. When developmental pharmacology concepts are applied to neonatal analgosedation, this means that this should be based on systematic assessment, followed by titrated administration of the most appropriate analgesic(s) with subsequent re-assessment to adapt treatment. This review will focus on the limitations of the available assessment tools, newly emerging analgosedatives in neonates to illustrate how these compounds can be integrated into the changing concepts of neonatal care.

Drug-related hypotension and decreased cerebral activity after intubation with low propofol doses in preterm neonates were observed, without evidence of cerebral ischemic hypoxia. CAR remained intact during drug-related hypotension in 95.5% of patients. Cerebral monitoring including CAR clarifies the cerebral impact of MABP fluctuations.

CSF-containing cysts at the level of the choroidal fissure may be of the arachnoid or the neuroepithelial type, but pathological confirmation of a CSF-containing cyst at this specific location has never been published. Very infrequently they are symptomatic, and surgical treatment is hardly ever necessary.