Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD".

Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.

Invasive fungal infections in neonates: a review.

Invasive fungal infections remain the leading causes of morbidity and mortality in neonates, especially preterm and very low birth weight infants. Most invasive fungal infections are due to Candida or Aspergillus species, and other fungi are increasingly reported and described. Appropriate identification and treatment are required to augment activity and reduce the toxicity of antifungal drugs. Successful use of antifungals in the vulnerable neonatal population is important for both prevention and treatment of infection. Strategies for prevention, including prophylactic antifungal therapy as well as reducing exposure to modifiable risk factors, like limiting antibiotic exposure, discontinuation of central catheters, and hand hygiene are key techniques to prevent and decrease rates of invasive fungal infections. In conclusion, this is a review of the most common causes, prevention strategies, prophylaxis, and treatment of invasive fungal infections in neonates.

Visual attention and dietary supplementation in children with perinatal brain injury.

AIM: To investigate whether children with perinatal brain injury have impairments in specific components of visual attention, and whether early dietary supplementation can reduce any deficits. METHOD: Children participating in the Dolphin neonatal trial of dietary supplementation were tested at age 6 months with the Infant Fixation Shift Attention Test, and at 4 to 5 years with four subtests of the Early Childhood Attention Battery (ECAB) assessing different components of attention (selective, sustained, and executive function), and the Fluid Crystallized Intelligence Index of the Kaufman Assessment Battery for Children, Second Edition (KABC-II). From 59 children originally assigned to trial groups, 33 were available for testing at 4 to 5 years (18 treatment group of whom seven, six, and five showed mild, moderate, or severe neonatal brain injury; 15 controls with one, seven, and seven in the neonatal brain injury categories respectively). Given the imbalance in numbers with mild brain injury, analysis of trial group differences is restricted to moderate and severe brain injury severities (n=25). RESULTS: Children with perinatal brain injury showed poorer attention across all components relative to age norms (mean standard scores 75-87; p<0.001 for three of the four subtests), with the greatest impairment in sustained attention. These impairments remained when compared with cognitive age assessed using the Fluid Crystallized Intelligence Index. Impairment was reduced in the treatment compared to the control group (p=0.04 for flanker test, p=0.002 for counterpointing, and p=0.027 for the overall ECAB score). INTERPRETATION: Perinatal brain injury is associated with later impaired attention, beyond that predicted from any general cognitive disability. Impairment varies across attention components, being most severe for sustained attention. The effects on flanker and counterpointing suggest that dietary supplementation from 0 to 2 years of age may reduce attention problems. Measuring the different components of attention is important when considering assessment and interventions for children with perinatal brain injury.

A review of the role of extracellular vesicles in neonatal physiology and pathology.

Extracellular vesicles (EVs) are cell-derived membrane-bound particles, extensively investigated across many fields to improve the understanding of pathophysiological processes, as biomarkers of disease and as therapeutic targets for pharmacological intervention. We aim to describe the current knowledge of EVs detected in the body fluids of human neonates, both term and preterm, from birth to 4 weeks of age. To date, EVs have been described in several neonatal body fluids, including cerebrospinal fluid, umbilical cord blood, neonatal blood, tracheal aspirates and urine. These studies demonstrate some important roles of EVs in the neonatal population, particularly in haemostasis. Moreover, some studies have demonstrated the pathophysiological mechanisms and the identification of potential biomarkers of neonatal disease. We must continue to build on this knowledge, evaluating the role of EVs in neonatal pathology, particularly in prematurity and during the perinatal adaption period. Future studies should use larger numbers, robust EV characterisation techniques and always correlate the findings to clinical outcomes. IMPACT: This article summarises the current knowledge of the effect of EVs in neonates. It describes the potential compensatory role of EVs in neonatal haemostasis. It also describes the role of EVs as mediators of pathology and as potential biomarkers of perinatal and neonatal disease.

Later cooling within 6 h and temperatures outside 33-34 °C are not associated with dysfunctional autoregulation during hypothermia for neonatal encephalopathy.

BACKGROUND: Cooling delays, temperature outside 33-34 °C, and blood pressure below the mean arterial blood pressure with optimal cerebral autoregulation (MAPOPT) might diminish neuroprotection from therapeutic hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized that longer time to reach temperature <34 °C and having temperature outside 33-34 °C would be associated with worse autoregulation and greater brain injury. METHODS: Neonates with HIE had rectal temperature and near-infrared spectroscopy autoregulation monitoring during hypothermia (n = 63) and rewarming (n = 58). All underwent brain MRI, and a subset received diffusion tensor imaging MRI before day 10 (n = 41). RESULTS: Most neonates reached <34 °C at 3-6 h of life. MAPOPT was identified in 54/63 (86%) during hypothermia and in 53/58 (91%) during rewarming. Cooling time was not related to blood pressure deviation from MAPOPT. Later cooling was associated with lower ADC scalar in unilateral posterior centrum semiovale but not in other regions. Temperatures >34 °C were associated with blood pressure above MAPOPT but not with brain injury. CONCLUSIONS: In neonates who were predominantly cooled after 3 h, cooling time was not associated with autoregulation or overall brain injury. Blood pressure deviation above MAPOPT was associated with temperature >34 °C. Additional studies are needed in a more heterogeneous population. IMPACT: Cooling time to reach target hypothermia temperature within 6 h of birth did not affect cerebral autoregulation measured by NIRS in neonates with hypoxic-ischemic encephalopathy (HIE). Temperature fluctuations >33-34 °C were associated with blood pressures that exceeded the range of optimal autoregulatory vasoreactivity. Cooling time within 6 h of birth and temperatures >33-34 °C were not associated with qualitative brain injury on MRI. Regional apparent diffusion coefficient scalars on diffusion tensor imaging MRI were not appreciably affected by cooling time or temperature >33-34 °C. Additional research in a larger and more heterogeneous population is needed to determine how delayed cooling and temperatures beyond the target hypothermia range affect autoregulation and brain injury.

Perspectives from the Society for Pediatric Research. Neonatal encephalopathy clinical trials: developing the future.

The next phase of clinical trials in neonatal encephalopathy (NE) focuses on hypothermia adjuvant therapies targeting alternative recovery mechanisms during the process of hypoxic brain injury. Identifying infants eligible for neuroprotective therapies begins with the clinical detection of brain injury and classification of severity. Combining a variety of biomarkers (serum, clinical exam, EEG, movement patterns) with innovative clinical trial design and analyses will help target infants with the most appropriate and timely treatments. The timing of magnetic resonance imaging (MRI) and MR spectroscopy after NE both assists in identifying the acute perinatal nature of the injury (days 3-7) and evaluates the full extent and evolution of the injury (days 10-21). Early, intermediate outcome of neuroprotective interventions may be best defined by the 21-day neuroimaging, with recognition that the full neurodevelopmental trajectory is not yet defined. An initial evaluation of each new therapy at this time point may allow higher-throughput selection of promising therapies for more extensive investigation. Functional recovery can be assessed using a trajectory of neurodevelopmental evaluations targeted to a prespecified and mechanistically derived hypothesis of drug action. As precision medicine revolutionizes healthcare, it should also include the redesign of NE clinical trials to allow safe, efficient, and targeted therapeutics. IMPACT: As precision medicine revolutionizes healthcare, it should also include the redesign of NE clinical trials to allow faster development of safe, effective, and targeted therapeutics. This article provides a multidisciplinary perspective on the future of clinical trials in NE; novel trial design; study management and oversight; biostatistical methods; and a combination of serum, imaging, and neurodevelopmental biomarkers can advance the field and improve outcomes for infants affected by NE. Innovative clinical trial designs, new intermediate trial end points, and a trajectory of neurodevelopmental evaluations targeted to a prespecified and mechanistically derived hypothesis of drug action can help address common challenges in NE clinical trials and allow for faster selection and validation of promising therapies for more extensive investigation.

Subpial Hemorrhage in Neonates: What Radiologists Need to Know.

OBJECTIVE. Subpial hemorrhages, typically seen in neonates, are rare but can harm the adjacent brain parenchyma. The purpose of this review is to summarize the anatomy and pathophysiology of subpial hemorrhage and highlight its characteristic neuro-imaging pattern. CONCLUSION. The distinctive neuroimaging pattern of subpial hemorrhage is best appreciated on brain MRI, which shows the morphology over the cortex and injury to adjacent cortex and subcortical white matter. These findings do not occur in subarachnoid and subdural hemorrhages. Recognizing the pattern of subpial hemorrhages should guide prognostic precision, prognostication, and counseling.

Cardiac Magnetic Resonance Imaging Evaluation of Neonatal Bronchopulmonary Dysplasia-associated Pulmonary Hypertension.

Rationale: Patients with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) have increased morbidity and mortality. Noninvasive assessment relies on echocardiograms (echos), which are technically challenging in this population. Improved assessment could augment decisions regarding PH therapies.Objectives: We hypothesized that neonatal cardiac magnetic resonance imaging (MRI) will correlate with BPD severity and predict short-term clinical outcomes, including need for PH therapies for infants with BPD.Methods: A total of 52 infants (31 severe BPD, 9 moderate BPD, and 12 with either mild or no BPD) were imaged between 39 and 47 weeks postmenstrual age on a neonatal-sized, neonatal ICU-sited 1.5-T magnetic resonance (MR) scanner. MR left ventricular eccentricity index (EI), main pulmonary artery-to-aorta (PA/AO) diameter ratio, and pulmonary arterial blood flow were determined. Echos obtained for clinical indications were reviewed. MRI and echo indices were compared with BPD severity and clinical outcomes, including length of stay (LOS), duration of respiratory support, respiratory support at discharge, and PH therapy.Measurements and Main Results: PA/AO ratio increased with BPD severity. Increased PA/AO ratio, MR-EI, and echo-EIs were associated with increased LOS and duration of respiratory support. No correlation was seen between pulmonary arterial blood flow and BPD outcomes. Controlling for gestational age, birth weight, and BPD severity, MR-EI was associated with LOS and duration of respiratory support. Increased PA/AO ratio and MR-EI were associated with PH therapy during hospitalization and at discharge.Conclusions: MRI can provide important image-based measures of cardiac morphology that relate to disease severity and clinical outcomes in neonates with BPD.

Presumptive Neonatal Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019.

OBJECTIVE: The study aimed to alert the neonatal community to the possibility of multisystem inflammatory syndrome in children (MIS-C) like disease in critically ill neonates born to mothers with coronavirus disease 2019 (COVID-19). STUDY DESIGN: Diagnosis of MIS-C like disease was pursued after echocardiography showed severely depressed ventricular function and pathological coronary artery dilation in the setting of medically refractory multisystem organ failure and maternal COVID-19 infection. The neonate did not respond to standard medical therapy, and there was no alternative disease that could explain the clinical course. High index of clinical suspicion coupled with low risk of intravenous immunoglobulin (IVIG) prompted us to pursue IVIG administration even though the neonate did not meet classic criteria for MIS-C. RESULT: Following treatment with IVIG, there was rapid clinical improvement. Ventricular function improved within 15 hours and coronary artery dilation resolved in 8 days. There was no recurrence of disease during follow-up. CONCLUSION: COVID-19 associated MIS-C like disease has not been well described in neonates. As typical features may be conspicuously absent, a high index of suspicion is warranted in critically ill neonates born to mothers with COVID-19. Echocardiography may provide critical diagnostic information and narrow the differential diagnosis. KEY POINTS: · COVID-19 associated MIS-C can present in neonates.. · Echocardiography is helpful in raising suspicion for MIS-C in neonates.. · Consider MIS-C in the differential diagnosis of ill neonates born to mothers with COVID-19..

Emerging technologies in pediatrics: the paradigm of neonatal diabetes mellitus.

In the era of precision medicine, the tremendous progress in next-generation sequencing technologies has allowed the identification of an ever-increasing number of genes associated with known Mendelian disorders. Neonatal diabetes mellitus is a rare, genetically heterogeneous endocrine disorder diagnosed before 6 months of age. It may occur alone or in the context of genetic syndromes. Neonatal diabetes mellitus has been linked with genetic defects in at least 26 genes to date. Novel mutations in these disease-causing genes are being reported, giving us a better knowledge of the molecular events that occur upon insulin biosynthesis and secretion from the pancreatic ß-cell. Of great importance, some of the identified genes encode proteins that can be therapeutically targeted by drugs per os, leading to transitioning from insulin to sulfonylureas. In this review, we provide an overview of pancreatic ß-cell physiology, present the clinical manifestations and the genetic causes of the different forms of neonatal diabetes, and discuss the application of next-generation sequencing methods in the diagnosis and therapeutic management of neonatal diabetes and on research in this area.

The development of pain circuits and unique effects of neonatal injury.

Pain is a necessary sensation that prevents further tissue damage, but can be debilitating and detrimental in daily life under chronic conditions. Neuronal activity strongly regulates the maturation of the somatosensory system, and aberrant sensory input caused by injury or inflammation during critical periods of early postnatal development can have prolonged, detrimental effects on pain processing. This review will outline the maturation of neuronal circuits responsible for the transmission of nociceptive signals and the generation of pain sensation-involving peripheral sensory neurons, the spinal cord dorsal horn, and brain-in addition to the influences of the neuroimmune system on somatosensation. This summary will also highlight the unique effects of neonatal tissue injury on the maturation of these systems and subsequent consequences for adult somatosensation. Ultimately, this review emphasizes the need to account for age as an independent variable in basic and clinical pain research, and importantly, to consider the distinct qualities of the pediatric population when designing novel strategies for pain management.

Continuous vital sign analysis for predicting and preventing neonatal diseases in the twenty-first century: big data to the forefront.

In the neonatal intensive care unit (NICU), heart rate, respiratory rate, and oxygen saturation are vital signs (VS) that are continuously monitored in infants, while blood pressure is often monitored continuously immediately after birth, or during critical illness. Although changes in VS can reflect infant physiology or circadian rhythms, persistent deviations in absolute values or complex changes in variability can indicate acute or chronic pathology. Recent studies demonstrate that analysis of continuous VS trends can predict sepsis, necrotizing enterocolitis, brain injury, bronchopulmonary dysplasia, cardiorespiratory decompensation, and mortality. Subtle changes in continuous VS patterns may not be discerned even by experienced clinicians reviewing spot VS data or VS trends captured in the monitor. In contrast, objective analysis of continuous VS data can improve neonatal outcomes by allowing heightened vigilance or preemptive interventions. In this review, we provide an overview of the studies that have used continuous analysis of single or multiple VS, their interactions, and combined VS and clinical analytic tools, to predict or detect neonatal pathophysiology. We make the case that big-data analytics are promising, and with continued improvements, can become a powerful tool to mitigate neonatal diseases in the twenty-first century.

Eye-tracking during simulation-based neonatal airway management.

BACKGROUND: Eye-tracking devices help to understand provider behavior during medical tasks. The aim of this study was to assess participants' gaze behavior and usability of eye-tracking glasses during airway management in a simulated neonatal resuscitation. METHODS: This study was an observational simulation-based study. The team member assigned to airway management wore head-mounted eye-tracking glasses. Main outcome measures were airway providers' gaze, dwell time (total amount of time a participant fixates certain areas of interest), and usability of eye-tracking glasses. RESULTS: Data from 13 participants were included. There were significant differences in dwell time during the scenario (p < 0.001), with participants spending twice as much time on the newborn and instruments as on the monitor and other staff. Participants spent about 25% more time focusing on another provider while the provider was inserting the umbilical vein catheter than in all other times of interest (intervals of time with meaningful events) (p = 0.04). The use of the glasses was perceived easy and not disturbing. CONCLUSIONS: Eye-tracking glasses enhance our understanding of providers' gaze and perspective during simulated neonatal airway management. Future studies will better characterize the ideal use in real situations.

NeoDoppler: New ultrasound technology for continous cerebral circulation monitoring in neonates.

BACKGROUND: There is a strong need for continuous cerebral circulation monitoring in neonatal care, since suboptimal cerebral blood flow may lead to brain injuries in preterm infants and other critically ill neonates. NeoDoppler is a novel ultrasound system, which can be gently fixed to the anterior fontanel and measure cerebral blood flow velocity continuously in different depths of the brain simultaneously. We aimed to study the feasibility, accuracy, and potential clinical applications of NeoDoppler in preterm infants and sick neonates. METHOD: Twenty-five infants born at different gestational ages with a variety of diagnoses on admission were included. The probe was placed over the anterior fontanel, and blood flow velocity data were continuously recorded. To validate NeoDoppler, we compared the measurements with conventional ultrasound; agreement was assessed using Bland-Altman plots. RESULTS: NeoDoppler can provide accurate and continuous data on cerebral blood flow velocity in several depths simultaneously. Limits of agreement between the measurements obtained with the two methods were acceptable. CONCLUSION: By monitoring the cerebral circulation continuously, increased knowledge of cerebral hemodynamics in preterm infants and sick neonates may be acquired. Improved monitoring of these vulnerable brains during a very sensitive period of brain development may contribute toward preventing brain injuries.

Pseudo-sawtooth pattern on amplitude-integrated electroencephalography in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: The objective of this study was to describe a novel amplitude-integrated electroencephalography (aEEG) pattern in infants with hypoxic-ischemic encephalopathy (HIE) and to assess the clinical significance. METHODS: The aEEG traces of infants with HIE who were treated with therapeutic hypothermia (TH) from 2012 to 2017 were analyzed. A pseudo-sawtooth (PST) pattern was defined as a periodic increase of the upper and/or lower margin of the trace on aEEG without showing seizure activities on conventional EEG (CEEG). RESULTS: Of the 46 infants, 6 (13%) had the PST pattern. The PST pattern appeared following a flat trace or a continuous low-voltage pattern and was followed by a burst-suppression pattern. On CEEG, the PST pattern consists of alternating cycles of low-voltage irregular activities and almost flat tracing. The PST pattern was associated with neuroimaging abnormalities and with various degrees of neurodevelopmental outcomes. Positive predictive values of the PST or worse pattern for adverse outcomes were high at 12 h after birth. CONCLUSION: A novel aEEG background pattern in infants with HIE was reported. The PST pattern likely indicates a suppressed background pattern and may be linked to unfavorable outcomes. Further multicenter validation study is needed to clarify its clinical significance.

Predicting intestinal recovery after necrotizing enterocolitis in preterm infants.

BACKGROUND: Intestinal recovery after NEC is difficult to predict in individuals. We evaluated whether several biomarkers predict intestinal recovery after NEC in preterm infants. METHODS: We measured intestinal tissue oxygen saturation (rintSO2) and collected urinary intestinal-fatty acid binding protein (I-FABPu) levels 0-24 h and 24-48 h after NEC onset, and before and after the first re-feed. We assessed intestinal recovery in two ways: time to full enteral feeding (FEFt; below or equal/above group's median) and development of post-NEC complications (recurrent NEC/post-NEC stricture). We determined whether the rintSO2, its range, and I-FABPu differed between groups. RESULTS: We included 27 preterm infants who survived NEC (Bell's stage ≥ 2). Median FEFt was 14 [IQR: 12-23] days. Biomarkers only predicted intestinal recovery after the first re-feed. Mean rintSO2 ≥ 53% combined with mean rintSO2range ≥ 50% predicted FEFt < 14 days with OR 16.7 (CI: 2.3-122.2). The rintSO2range was smaller (33% vs. 51%, p < 0.01) and I-FABPu was higher (92.4 vs. 25.5 ng/mL, p = 0.03) in case of post-NEC stricture, but not different in case of recurrent NEC, compared with infants without complications. CONCLUSION: The rintSO2, its range, and I-FABPu after the first re-feed after NEC predicted intestinal recovery. These biomarkers have potential value in individualizing feeding regimens after NEC.

Stress as tool or toxin: physiologic markers and subjective report in neonatal simulation.

BACKGROUND: Cognitive appraisal of stress can influence performance. Increased awareness could facilitate titration to optimal stress levels. This study's primary aim was to investigate whether physiologic variables change with increasingly stressful simulations. Secondary aims include effect of stress on procedural competency and whether individuals recognize their experienced stress. METHODS: This was a single-center, mixed-method, simulation-based study. Participants completed three scenarios requiring resuscitation under increasingly stressful conditions. Wearable biometric devices recorded physiologic parameters. Subjects completed surveys assessing knowledge and perceived stress. Intubation success or failure was noted. Heart rate variability (HRV) analysis was used as a proxy for stress. RESULTS: Twelve participants completed the study. Survey analysis revealed progressive amplification of endorsement of affective states associated with stress. Median low frequency (LF)/high frequency (HF) ratio from scenario 1 (median = 2.29, IQR = 1.97, 3.91) was significantly lower than scenario 2 (median = 4.7, IQR = 2.32, 8.35, p = 0.04) and scenario 3 (median = 4.63, IQR = 2.2, 7.43, p = 0.04). Changes in HRV were noted during all scenarios irrespective of subjective self-assessment of stress. Procedural proficiency suffered during more stressful scenarios. CONCLUSIONS: This study demonstrates alterations in subjective assessment and objective physiologic data in simulations with increasing stress. HRV is useful as a proxy for stress response and does not always correlate with perception.

Neonatal encephalopathy therapy optimization for better neuroprotection with inhalation of CO2: the HENRIC feasibility and safety trial.

BACKGROUND: There is an association between hypocapnia and adverse neurodevelopmental outcome in infants with neonatal encephalopathy (NE). Our aim was to test the safety and feasibility of 5% CO2 and 95% air inhalation to correct hypocapnia in mechanically ventilated infants with NE undergoing therapeutic hypothermia. METHODS: Ten infants were assigned to this open-label, single-center trial. The gas mixture of 5% CO2 and 95% air was administered through patient circuits if the temperature-corrected PCO2 ≤40 mm Hg. The CO2 inhalation was continued for 12 h or was stopped earlier if the base deficit (BD) level decreased <5 mmol/L. Follow-up was performed using Bayley Scales of Infant Development II. RESULTS: The patients spent a median 95.1% (range 44.6-98.5%) of time in the desired PCO2 range (40-60 mm Hg) during the inhalation. All PCO2 values were >40 mm Hg, the lower value of the target range. Regression modeling revealed that BD and lactate had a tendency to decrease during the intervention (by 0.61 and 0.55 mmol/L/h, respectively), whereas pH remained stable. The rate of moderate disabilities and normal outcome was 50%. CONCLUSIONS: Our results suggest that inhaled 5% CO2 administration is a feasible and safe intervention for correcting hypocapnia.

Psychosocial and medical adversity associated with neonatal neurobehavior in infants born before 30 weeks gestation.

BACKGROUND: Psychosocial adversity escalates medical risk for poor outcomes in infants born <30 weeks gestation. Neonatal neurobehavior and maternal psychological and socioenvironmental assessments may identify the earliest specific intervention needs. We hypothesized that maternal prenatal anxiety, depression, and adverse medical and socioenvironmental conditions would be associated with less optimal neonatal neurobehavior at neonatal intensive care unit (NICU) discharge. METHODS: We studied 665 infants at 9 university NICUs. Risk indices of socioenvironmental, maternal, and neonatal medical factors were obtained from standardized, structured maternal interviews and medical record reviews. Brain injuries were classified by consensus ultrasonogram readings. NICU Network Neurobehavioral Scale (NNNS) exams were conducted at NICU discharge. RESULTS: On the NNNS, generalized estimating equations indicated infants of mothers with prenatal anxiety had less optimal attention, and those born to mothers with prenatal depression had increased lethargy. Maternal medical complications predicted suboptimal reflexes. Socioenvironmental risk predicted lower self-regulation and movement quality. Infants with more severe neonatal medical complications had lower attention, increased lethargy, and suboptimal reflexes. CONCLUSIONS: Combined information from the observed associations among adverse prenatal maternal medical and psychosocial conditions, and neonatal complications may assist in the early identification of infants at elevated neurobehavioral risk.

EEG Monitoring of the Epileptic Newborn.

PURPOSE OF REVIEW: Although differentiating neonatal-onset epilepsies from acute symptomatic neonatal seizures has been increasingly recognized as crucial, existing guidelines, and recommendations on EEG monitoring are mainly based on acute symptomatic seizures, especially secondary to hypoxic-ischemic encephalopathy. We aimed to narratively review current knowledge on neonatal-onset epilepsies of genetic, metabolic, and structural non-acquired origin, with special emphasis on EEG features and monitoring. RECENT FINDINGS: A wide range of rare conditions are increasingly described, reducing undiagnosed cases. Although distinguishing features are identifiable in some, how to best monitor and detect less described etiologies is still an issue. A comprehensive approach considering onset, seizure evolution, ictal semiology, clinical, laboratory, EEG, and neuroimaging data is key to diagnosis. Phenotypic variability prevents precise recommendations, but a solid, consistent method moving from existing published guidelines helps in correctly assessing these newborns in order to provide better care, especially in view of expanding precision therapies.