Liesbeth Thewissen

Objective: To test the potential utility of applying machine learning methods to regional cerebral (rcSO₂) and peripheral oxygen saturation (SpO₂) signals to detect brain injury in extremely preterm infants. Study design: A subset of infants enrolled in the Management of Hypotension in Preterm infants (HIP) trial were analysed (n = 46). All eligible infants were 2 measurements performed over the first 72 h and cranial ultrasounds performed during the first week after birth. SpO₂ data were available for 32 infants. The rcSO₂ and SpO₂ signals were preprocessed, and prolonged relative desaturations (PRDs; data-driven desaturation in the 2-to-15-min range) were extracted. Numerous quantitative features were extracted from the biosignals before and after the exclusion of the PRDs within the signals. PRDs were also evaluated as a stand-alone feature. A machine learning model was used to detect brain injury (intraventricular haemorrhage-IVH grade II–IV) using a leave-one-out cross-validation approach. Results: The area under the receiver operating characteristic curve (AUC) for the PRD rcSO₂ was 0.846 (95% CI: 0.720–0.948), outperforming the rcSO₂ threshold approach (AUC 0.593 95% CI 0.399–0.775). Neither the clinical model nor any of the SpO₂ models were significantly associated with brain injury. Conclusion: There was a significant association between the data-driven definition of PRDs in rcSO₂ and brain injury. Automated analysis of PRDs of the cerebral NIRS signal in extremely preterm infants may aid in better prediction of IVH compared with a threshold-based approach. Further investigation of the definition of the extracted PRDs and an understanding of the physiology underlying these events are required.

Aim: After preterm birth, supine head midline position is supported for stable cerebral blood flow (CBF) and prevention of intraventricular haemorrhage (IVH), while prone position supports respiratory function and enables skin‐to‐skin care. The prone compared to supine position could lead to a change in near‐infrared derived cerebral tissue oxygen saturation (rScO2), which is a surrogate for cerebral blood flow (CBF). By monitoring rScO2 neonatologists aim to stabilise CBF during intensive care and prevent brain injury. In this systematic review and meta‐analysis, we investigate the effect of the body position on rScO2.Methods: A comprehensive literature search was performed to identify all trials that included preterm infants in the first 2 weeks after birth and compared rScO2 in the prone versus supine head in midline position of the infant. A meta‐analysis, including two subgroup analyses based on postnatal age (PNA) and gestational age (GA), was performed.Results: Six observational cohort studies were included. In the second, but not the first week after birth, a significant higher rScO2 in the prone position was found with a mean difference of 1.97% (95% CI 0.87–3.07). No rScO2 difference was observed between positions in the extremely preterm nor the preterm group.Conclusion: No consistent evidence was found that body position influences rScO2 in the first 2 weeks after preterm birth. Subgroup analysis suggests that in the second week after birth, the prone position might result in higher cerebral rScO2 than the supine position with head in midline. Multiple factors determine the best body position in preterms.

Many neonates undergoing whole body hypothermia (WBH) following moderate to severe perinatal asphyxia may also suffer from renal impairment. While recent data suggest WBH-related reno-protection, differences in serum creatinine (Scr) patterns to reference patterns were not yet reported. We therefore aimed to document Scr trends and patterns in asphyxiated neonates undergoing WBH and compared these to centiles from a reference Scr data set of non-asphyxiated (near)term neonates. Using a systematic review strategy, reports on Scr trends (mean ± SD, median or interquartile range) were collected (day 1–7) in WBH cohorts and compared to centiles of an earlier reported reference cohort of non-asphyxia cases. Based on 13 papers on asphyxia + WBH cases, a pattern of postnatal Scr trends in asphyxia + WBH cases was constructed. Compared to the reference 50th centile Scr values, mean or median Scr values at birth and up to 48 h were higher in asphyxia + WBH cases with a subsequent uncertain declining trend towards, at best, high or high–normal creatinine values afterwards. Such patterns are valuable for anticipating average changes in renal drug clearance but do not yet cover the relevant inter-patient variability observed in WBH cases, as this needs pooling of individual Screa profiles, preferably beyond the first week of life.

Background The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO₂) and autoregulatory capacity (CAR) remains unknown. Methods Prospective cohort study of blinded rScO₂ measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO₂, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. Results In 89 potentially eligible HIP trial patients with rScO₂ measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO₂ was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death. Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. Conclusions Dopamine had no effect on rScO₂ compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. Impact Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Despite increasing use of propofol in neonates, observations on cerebral effects are limited. To investigate cerebral autoregulation (CAR) and activity after propofol for endotracheal intubation in preterm neonates. Twenty-two neonates received propofol before intubation as part of a published dose-finding study. Mean arterial blood pressure (MABP), near-infrared spectroscopy-derived cerebral oxygenation (rScO₂), and amplitude-integrated electroencephalography (aEEG) were analyzed until 180 min after propofol. CAR was expressed as transfer function (TF) gain, indicating % change in rScO₂ per 1 mmHg change in MABP. Values exceeding mean TF gain + 2 standard deviations (SD) defined impaired CAR. After intubation with a median propofol dose of 1 (0.5–4.5) mg/kg, rScO₂ remained stable during decreasing MABP. Mean (±SD) TF gain was 0.8 (±0.3)%/mmHg. Impaired CAR was identified in 1 and 5 patient(s) during drug-related hypotension and normal to raised MABP, respectively. Suppressed aEEG was observed up to 60 min after propofol. 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.

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.

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.

Cardiovascular Journal of Africa: Vol 24 No 3 (April 2013)