Prognostication in Neurocritical Care.

OBJECTIVE: This article synthesizes the current literature on prognostication in neurocritical care, identifies existing challenges, and proposes future research directions to reduce variability and enhance scientific and patient-centered approaches to neuroprognostication. LATEST DEVELOPMENTS: Patients with severe acute brain injury often lack the capacity to make their own medical decisions, leaving surrogate decision makers responsible for life-or-death choices. These decisions heavily rely on clinicians' prognostication, which is still considered an art because of the previous lack of specific guidelines. Consequently, there is significant variability in neuroprognostication practices. This article examines various aspects of neuroprognostication. It explores the cognitive approach to prognostication, highlights the use of statistical modeling such as Bayesian models and machine learning, emphasizes the importance of clinician-family communication during prognostic disclosures, and proposes shared decision making for more patient-centered care. ESSENTIAL POINTS: This article identifies ongoing challenges in the field and emphasizes the need for future research to ameliorate variability in neuroprognostication. By focusing on scientific methodologies and patient-centered approaches, this research aims to provide guidance and tools that may enhance neuroprognostication in neurocritical care.

Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO.

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100ß, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRß, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.

Association of concussion/brain injury symptoms and diagnosis with mental and social well-being in 2020 National Health Interview Survey (NHIS) children.

BACKGROUND: Population-based data regarding the associations between prior concussion or brain injury symptoms/diagnosis and mental/social well-being is lacking for U.S. children. METHODS: Associations between prior concussion or brain injury symptoms/diagnosis (reported by parents of children ages 5-17 from the 2020 National Health Interview Survey) and current mental/social well-being were determined in multivariable models. RESULTS: Amongst 2020 US children, 8.7% and 5.3% had previous symptoms and diagnosis of concussion/brain injury, respectively. 23% of children with symptoms were never checked for a concussion/brain injury, with younger children at higher risk of not getting checked after symptomatic head trauma. Prior concussion or brain injury symptoms/diagnosis was associated with a higher likelihood of current depressive symptoms (odds ratio [OR] = 1.60; 95% CI = 1.21-2.14; p < 0.001), anxiety (OR = 2.07; 95% CI = 1.52-2.82; p < 0.001), difficulty making friends (OR = 1.57; 95% = 1.06-2.33; p = 0.03), use of medications for mental/social/behavioral issues (OR = 1.69; CI = 1.21-2.36; p = 0.002), and mental health therapy/counseling (OR = 1.52; 95% CI = 1.13-2.04; p = 0.006). CONCLUSION: U.S. children with prior concussion or brain injury symptoms/diagnosis have a higher rate of mental and social disturbances and a more frequent need for mental health services. Nearly one-quarter of children with significant symptoms after head trauma are never checked for a concussion/brain injury; routine concussion evaluation after head trauma should be emphasized especially in younger children.

Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Co-developing 'The CyberABIlity Scale' to assess vulnerability to cyberscams for people with acquired brain injury: Delphi and cognitive interviews with clinicians and people with acquired brain injury.

Background Although individuals with acquired brain injury (ABI) may be vulnerable to cyberscams, the lack of existing measures documenting cybersafety behaviours in people with ABI limits our understanding of ABI-specific risk factors, the frequency of this problem, and the ability to evaluate evidence-based interventions. The CyberABIlity Scale was developed to assess vulnerability in people with ABI via self-rated statements and practical scam-identification tasks. This study aimed to develop and refine The CyberABIlity Scale through feedback from clinicians and people with ABI. Methods Scale feedback was collected via three rounds of clinician surveys (n = 14) using Delphi methods and two rounds of cognitive interviews with participants with ABI (n = 8). Following each round, feedback was quantitatively and qualitatively summarised, and revisions were made accordingly. Results Key revisions included removing 12 items deemed irrelevant. Instructions and rating scales were revised to improve clarity. Cognitive interviews identified 15 comprehension errors, with further revisions made to support response clarity for participants with ABI. Clinicians and participants with ABI endorsed the content and face validities of The CyberABIlity Scale . Conclusions Following further validation, The CyberABIlity Scale has the potential to be an effective screening measure for online vulnerability for people with ABI within clinical and research settings.

Thermography Sensor to Assess Motor and Sensitive Neuromuscular Sequels of Brain Damage.

INTRODUCTION: The aim of this study was to observe the validity, diagnostic capacity, and reliability of the thermographic technique in the analysis of sensitive and motor sequelae in patients with chronic brain damage. METHOD: A longitudinal descriptive observational study was performed. Forty-five people with impairment in at least one anatomical region participated in and completed this study. All patients who had become infected by SARS-CoV-2 in the past year were excluded. Thermographic measurement was conducted, and the Modified Ashworth Scale and Pressure Pain Threshold was analyzed. RESULTS: A high correlation between two times of thermography data was observed. The Spearman correlations obtained between the Ashworth score on each leg and the temperature given by thermography were all significant. DISCUSSION AND CONCLUSIONS: Despite the above, the Spearman correlations obtained between the PPT in each leg and the temperature offered by thermography were not significant in any of the measurements. For this reason, thermography is a potential tool for the diagnosis and assessment of neuromuscular motor sequelae, but not for sensitive sequelae, after brain injury. Nevertheless, for the time being, no statistical relationship has been observed between the data reported by thermography and PPT; thus, future studies are needed to further investigate these results.

Neuromonitoring in the ICU - what, how and why?

PURPOSE OF REVIEW: We selectively review emerging noninvasive neuromonitoring techniques and the evidence that supports their use in the ICU setting. The focus is on neuromonitoring research in patients with acute brain injury. RECENT FINDINGS: Noninvasive intracranial pressure evaluation with optic nerve sheath diameter measurements, transcranial Doppler waveform analysis, or skull mechanical extensometer waveform recordings have potential safety and resource-intensity advantages when compared to standard invasive monitors, however each of these techniques has limitations. Quantitative electroencephalography can be applied for detection of cerebral ischemia and states of covert consciousness. Near-infrared spectroscopy may be leveraged for cerebral oxygenation and autoregulation computation. Automated quantitative pupillometry and heart rate variability analysis have been shown to have diagnostic and/or prognostic significance in selected subtypes of acute brain injury. Finally, artificial intelligence is likely to transform interpretation and deployment of neuromonitoring paradigms individually and when integrated in multimodal paradigms. SUMMARY: The ability to detect brain dysfunction and injury in critically ill patients is being enriched thanks to remarkable advances in neuromonitoring data acquisition and analysis. Studies are needed to validate the accuracy and reliability of these new approaches, and their feasibility and implementation within existing intensive care workflows.

MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study.

Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.

Case identification of non-traumatic brain injury in youth using linked population data.

BACKGROUND: Population-level administrative data provides a cost-effective means of monitoring health outcomes and service needs of clinical populations. This study aimed to present a method for case identification of non-traumatic brain injury in population-level data and to examine the association with sociodemographic factors. METHODS: An estimated resident population of youth aged 0-24 years was constructed using population-level datasets within the New Zealand Integrated Data Infrastructure. A clinical consensus committee reviewed the International Classification of Diseases Ninth and Tenth Editions codes and Read codes for inclusion in a case definition. Cases were those with at least one non-traumatic brain injury code present in the five years up until 30 June 2018 in one of four databases in the Integrated Data Infrastructure. Rates of non-traumatic brain injury were examined, both including and excluding birth injury codes and across age, sex, ethnicity, and socioeconomic deprivation groups. RESULTS: Of the 1 579 089 youth aged 0-24 years on 30 June 2018, 8154 (0.52%) were identified as having one of the brain injury codes in the five-years to 30 June 2018. Rates of non-traumatic brain injury were higher in males, children aged 0-4 years, Maori and Pacific young people, and youth living with high levels of social deprivation. CONCLUSION: This study presents a comprehensive method for case identification of non-traumatic brain injury using national population-level administrative data.

Distance horizontal fusional facility (DFF): A new diagnostic vergence test for the acquired brain injury (ABI) population

Purpose To report the retrospectively-based, clinical diagnostic findings for the horizontal, distance, fusional facility (DFF) test in the non-TBI (traumatic brain inury), ABI (acquired brain injury) population. Methods The DFF test (4 pd base-out/2 pd base-in) was assessed and compared retrospectively in the first author's optometric practice in three clinical populations: (1) post-mTBI, visually-symptomatic (n = 52), (2) post-ABI, non-mTBI, visually-symptomatic (n = 34), and (3) visually-normal, visually asymptomatic (n = 44). Results The DFF values in each group were significantly different from each other (p < 0.05). The mean non-TBI, ABI group value was significantly lower than found in the mTBI group, and both were significantly lower than the mean found in the normal cohort (p < 0.05). There was a significant reduction in DFF with increased age (p < 0.001). ROC values for the AUC ranged from excellent to acceptable (0.94–0.74). Conclusion The DFF test is a new and useful way to assess horizontal, distance, dynamic, fusional facility in those with presumed non-mTBI, ABI neurological conditions to assist in its diagnosis. (AU)

Minimally conscious state plus versus minus: Likelihood of emergence and long-term functional independence.

OBJECTIVE: Severe brain injuries can result in disorders of consciousness, such as the Minimally Conscious State (MCS), where individuals display intermittent yet discernible signs of conscious awareness. The varied levels of responsiveness and awareness observed in this state have spurred the progressive delineation of two subgroups within MCS, termed "plus" (MCS+) and "minus" (MCS-). However, the clinical validity of these classifications remains uncertain. This study aimed to investigate and compare the likelihood of emergence from MCS, as well as the functional independence after emergence, in individuals categorized as in MCS+ and MCS-. METHODS: Demographic and behavioral data of 80 participants, admitted as either in MCS+ (n = 30) or MCS- (n = 50) to a long-term neurorehabilitation unit, were retrospectively analyzed. The neurobehavioral condition of each participant was evaluated weekly until discharge, demise, or emergence from MCS. The functional independence of those participants who emerged from MCS was assessed 6 months after emergence. RESULTS: While only about half of the individuals classified as in MCS- (n = 24) emerged from the MCS, all those admitted as in MCS+ did, and in a shorter postinjury period. Despite these differences, all individuals who emerged from the MCS demonstrated similar high disability and low functional independence 6 months after emergence, regardless of their state at admission. INTERPRETATION: Individuals classified as MCS+ exhibited a higher likelihood of emergence and a shorter time to emergence compared to those in MCS-. However, the level of functional independence 6 months after emergence was found to be unrelated to the initial state at admission.

Covert consciousness.

Covert consciousness is a state of residual awareness following severe brain injury or neurological disorder that evades routine bedside behavioral detection. Patients with covert consciousness have preserved awareness but are incapable of self-expression through ordinary means of behavior or communication. Growing recognition of the limitations of bedside neurobehavioral examination in reliably detecting consciousness, along with advances in neurotechnologies capable of detecting brain states or subtle signs indicative of consciousness not discernible by routine examination, carry promise to transform approaches to classifying, diagnosing, prognosticating and treating disorders of consciousness. Here we describe and critically evaluate the evolving clinical category of covert consciousness, including approaches to its diagnosis through neuroimaging, electrophysiology, and novel behavioral tools, its prognostic relevance, and open questions pertaining to optimal clinical management of patients with covert consciousness recovering from severe brain injury.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Single-pulse transcranial magnetic stimulation for assessment of motor development in infants with early brain injury.

INTRODUCTION: Single-pulse transcranial magnetic stimulation (TMS) has many applications for pediatric clinical populations, including infants with perinatal brain injury. As a noninvasive neuromodulation tool, single-pulse TMS has been used safely in infants and children to assess corticospinal integrity and circuitry patterns. TMS may have important applications in early detection of atypical motor development or cerebral palsy. AREAS COVERED: The authors identified and summarized relevant studies incorporating TMS in infants, including findings related to corticospinal development and circuitry, motor cortex localization and mapping, and safety. This special report also describes methodologies and safety considerations related to TMS assessment in infants, and discusses potential applications related to diagnosis of cerebral palsy and early intervention. EXPERT OPINION: Single-pulse TMS has demonstrated safety and feasibility in infants with perinatal brain injury and may provide insight into neuromotor development and potential cerebral palsy diagnosis. Additional research in larger sample sizes will more fully evaluate the utility of TMS biomarkers in early diagnosis and intervention. Methodological challenges to performing TMS in infants and technical/equipment limitations require additional consideration and innovation toward clinical implementation. Future research may explore use of noninvasive neuromodulation techniques as an intervention in younger children with perinatal brain injury to improve motor outcomes.

Single pulse transcranial magnetic stimulation (TMS) is a safe and noninvasive way to study brain activity in infants and children who have experienced brain injuries around the time of birth. Infants who have had an early brain injury may develop cerebral palsy, a developmental disability that affects movement. TMS uses a device that gives single pulses of energy to activate specific areas of the brain. This can be used to study how the brain connects to the muscles in the body through paths or 'tracts.' TMS helps researchers understand the development of the tracts and the potential need for therapy. This article reviews research studies that used TMS in infants and explains how TMS can be used to assess brain development. It also reviews safety considerations and challenges related to using TMS in infants. TMS could be a valuable tool for early diagnosis of cerebral palsy and could also help guide treatments for infants with brain injuries. However, more research is needed, using larger groups of infants, to potentially expand the use of TMS in clinical practice. Future directions include developing infant-specific research tools and using noninvasive brain stimulation to improve recovery for infants with brain injuries.

Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

Trending Ability of End-Tidal Capnography Monitoring During Mechanical Ventilation to Track Changes in Arterial Partial Pressure of Carbon Dioxide in Critically Ill Patients With Acute Brain Injury: A Monocenter Retrospective Study.

BACKGROUND: Changes in arterial partial pressure of carbon dioxide (Pa co2 ) may alter cerebral perfusion in critically ill patients with acute brain injury. Consequently, international guidelines recommend normocapnia in mechanically ventilated patients with acute brain injury. The measurement of end-tidal capnography (Et co2 ) allows its approximation. Our objective was to report the agreement between trends in Et co2 and Pa co2 during mechanical ventilation in patients with acute brain injury. METHODS: Retrospective monocenter study was conducted for 2 years. Critically ill patients with acute brain injury who required mechanical ventilation with continuous Et co2 monitoring and with 2 or more arterial gas were included. The agreement was evaluated according to the Bland and Altman analysis for repeated measurements with calculation of bias, and upper and lower limits of agreement. The directional concordance rate of changes between Et co2 and Pa co2 was evaluated with a 4-quadrant plot. A polar plot analysis was performed using the Critchley methods. RESULTS: We analyzed the data of 255 patients with a total of 3923 paired ΔEt co2 and ΔPa co2 (9 values per patient in median). Mean bias by Bland and Altman analysis was -8.1 (95 CI, -7.9 to -8.3) mm Hg. The directional concordance rate between Et co2 and Pa co2 was 55.8%. The mean radial bias by polar plot analysis was -4.4° (95% CI, -5.5 to -3.3) with radial limit of agreement (LOA) of ±62.8° with radial LOA 95% CI of ±1.9°. CONCLUSIONS: Our results question the performance of trending ability of Et co2 to track changes in Pa co2 in a population of critically ill patients with acute brain injury. Changes in Et co2 largely failed to follow changes in Pa co2 in both direction (ie, low concordance rate) and magnitude (ie, large radial LOA). These results need to be confirmed in prospective studies to minimize the risk of bias.

Blood Biomarkers in the Fetally Growth Restricted and Small for Gestational Age Neonate: Associations with Brain Injury.

Fetal growth restriction (FGR) and small for gestational age (SGA) infants have increased risk of mortality and morbidity. Although both FGR and SGA infants have low birthweights for gestational age, a diagnosis of FGR also requires assessments of umbilical artery Doppler, physiological determinants, neonatal features of malnutrition, and in utero growth retardation. Both FGR and SGA are associated with adverse neurodevelopmental outcomes ranging from learning and behavioral difficulties to cerebral palsy. Up to 50% of FGR, newborns are not diagnosed until around the time of birth, yet this diagnosis lacks further indication of the risk of brain injury or adverse neurodevelopmental outcomes. Blood biomarkers may be a promising tool. Defining blood biomarkers indicating an infant's risk of brain injury would provide the opportunity for early detection and therefore earlier support. The aim of this review was to summarize the current literature to assist in guiding the future direction for the early detection of adverse brain outcomes in FGR and SGA neonates. The studies investigated potential diagnostic blood biomarkers from cord and neonatal blood or serum from FGR and SGA human neonates. Results were often conflicting with heterogeneity common in the biomarkers examined, timepoints, gestational age, and definitions of FGR and SGA used. Due to these variations, it was difficult to draw strong conclusions from the results. The search for blood biomarkers of brain injury in FGR and SGA neonates should continue as early detection and intervention is critical to improve outcomes for these neonates.

Detecting Asymmetry of Upper Limb Activity with Accelerometry in Infants at Risk for Unilateral Spastic Cerebral Palsy.

AIMS: To examine whether accelerometry can quantitate asymmetry of upper limb activity in infants aged 3-12 months at risk for developing unilateral spastic cerebral palsy (USCP). METHOD: A prospective study was performed in 50 infants with unilateral perinatal brain injury at high risk of developing USCP. Triaxial accelerometers were worn on the ipsilateral and contralesional upper limb during the Hand Assessment for Infants (HAI). Infants were grouped in three age intervals (3-5 months, 5-7.5 months and 7.5 until 12 months). Each age interval group was divided in a group with and without asymmetrical hand function based on HAI cutoff values suggestive of USCP. RESULTS: In a total of 82 assessments, the asymmetry index for mean upper limb activity was higher in infants with asymmetrical hand function compared to infants with symmetrical hand function in all three age groups (ranging from 41 to 51% versus - 2-6%, p < 0.01), while the total activity of both upper limbs did not differ. CONCLUSIONS: Upper limb accelerometry can identify asymmetrical hand function in the upper limbs in infants with unilateral perinatal brain injury from 3 months onwards and is complementary to the Hand Assessment for Infants.