Neonatal Neurodevelopmental Outcome Research Articles

Continuous Electroencephalogram (cEEG) Findings and Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease (CHD) at 12-24 Months of Age.

This study aims to assess the role of continuous EEG (cEEG) background patterns and duration of cross-clamp time and cardiopulmonary bypass (CPB) in children with congenital heart disease (CHD) undergoing cardiac surgery and its correlation with abnormal neurodevelopmental outcomes at 12-24 months on Bayley Scales of Infant and Toddler Development (BSID-III). This retrospective cohort study included infants with CHD and cEEG monitoring, who underwent surgery by 44 weeks gestational age. 34 patients were included, who were operated at median age - 7 days. Longer duration of cross- camp time was associated with poor language composite scores (LCS) (p value = 0.036). A significant association existed between severity of encephalopathy in 24-hour post-operative period and poor LCS (p value = 0.026). Majority of neonates with CHD have below average cognitive, language and motor composite scores on BSID-III. Longer duration of cross-clamp time and severity of encephalopathy during 24-hour post-operative EEG monitoring are associated with poor LCS.

Brain development in newborns and infants after ECMO.

Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies. A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature. About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%-23% of neonates within the first 24hours, and bleeding events occur in 27%-60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects. The impact of ECMO on an infant's nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants.

Predictors of poor neurodevelopmental outcomes in neonates with clinically observed seizures: A prospective observational study in a tertiary care hospital of Bangladesh

Neonatal seizures can lead to long-term neurodevelopmental problems. This study aims to identify predictors of poor developmental outcomes in neonates with seizures to aid in early intervention and referral for follow-up and rehabilitation.This observational study was conducted in the Department of Neonatology and Institute of Paediatric Neurodisorder and Autism, Bangabandhu Sheikh Mujib Medical University. Among 75 study cases of neonatal seizure, 23 died, and 46 were followed-up at 6 and 9 months after discharge. EEGs were performed on every patient. A comprehensive neurological examination and developmental evaluation were performed using Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III).Three-fourths of neonates were born at term (76.1 %), and over half were male (56.5 %). The majority were appropriate for gestational age (79.7 %) and had an average birth weight of 2607 ± 696 g (±SD). Over half of the neonates (52.2 %) had adverse neurodevelopmental outcomes, with global developmental delay being the most common. Recurrent seizures, the number of anticonvulsants needed to control seizures, and abnormal Electroencephalograms were identified as independent predictors of adverse neurodevelopmental outcomes.The study highlights the need for early referral for follow-up and rehabilitation of neonates with seizures having abnormal electroencephalograms, recurrent seizures and requiring more anticonvulsants to control seizures.

Perinatal Morbidity, Mortality, and Neurodevelopmental Outcomes of Neonates with Fetal Growth Restriction

Perinatal Morbidity, Mortality, and Neurodevelopmental Outcomes of Neonates with Fetal Growth Restriction

Impacts of Integrating Family-Centered Care and Developmental Care Principles on Neonatal Neurodevelopmental Outcomes among High-Risk Neonates.

Integrating family-centered care (FCC) and developmental care (DC) principles in neonatal care settings may improve neurodevelopmental outcomes for high-risk neonates. However, the combined impact of FCC and DC has been underexplored. This study aimed to investigate the effects of integrated FCC and DC on neurodevelopment and length of hospital stay in high-risk neonates. A quasi-experimental pre-post study was conducted among 200 high-risk neonates (<32 weeks gestation or <1500 g) admitted to neonatal intensive care units (NICU) in Saudi Arabia. The intervention group (n = 100) received integrated FCC and DC for 6 months. The control group (n = 100) received standard care. Neurodevelopment was assessed using the Bayley Scales of Infant Development-III. Length of stay and readmissions were extracted from medical records. The intervention group showed significant improvements in cognitive, motor, and language scores compared to controls (p < 0.05). The intervention group had a 4.3-day reduction in the mean length of stay versus a 1.4-day reduction in controls (p = 0.02). Integrated care independently predicted higher cognitive scores (p = 0.001) and shorter stays (p = 0.006) in regression models. Integrating FCC and DC in neonatal care enhances neurodevelopmental outcomes and reduces hospitalization for high-risk neonates compared to standard care. Implementing relationship-based, developmentally supportive models is critical for optimizing outcomes in this vulnerable population.

Association of EEG Background and Neurodevelopmental Outcome in Neonates With Hypoxic-Ischemic Encephalopathy Receiving Hypothermia.

Predicting neurodevelopmental outcome for neonates with hypoxic-ischemic encephalopathy (HIE) is important for clinical decision-making, care planning, and parent communication. We examined the relationship between EEG background and neurodevelopmental outcome among children enrolled in a trial of erythropoietin or placebo for neonates with HIE treated with therapeutic hypothermia. Participants had EEG recorded throughout hypothermia. EEG background was classified as normal, discontinuous, or severely abnormal (defined as burst suppression, low voltage suppressed, or status epilepticus) at 5 1-hour epochs: onset of recording, 24, 36, 48, and 72 hours after birth. The predominant background pattern during the entire continuous video EEG monitoring recording was calculated using the arithmetic mean of the 5 EEG background ratings (normal = 0; discontinuous = 1; severely abnormal = 2) as follows: "predominantly normal" (mean = 0), "normal/discontinuous" (0 < mean<1), "predominantly discontinuous" (mean = 1), "discontinuous/severely abnormal" (1 < mean<2), or "predominantly severely abnormal" (mean = 2). Primary outcome was death or neurodevelopmental impairment (NDI) defined as cerebral palsy, Gross Motor Function Classification Score ≥1, or cognitive score <90 on Bayley Scales of Infant Toddler Development, third edition at age 2 years. Neurodevelopment was also categorized into a 5-level ordinal measure: no, mild, moderate, severe NDI, or death for secondary analysis. We used generalized linear regression models with robust standard errors to assess the relative risk of death or NDI by EEG background in both unadjusted and adjusted analyses controlling for the effects of treatment group, sex, HIE severity, and study recruitment site. Among 142 neonates, the predominant background EEG pattern was predominantly normal in 35 (25%), normal/discontinuous in 68 (48%), predominantly discontinuous in 11 (7.7%), discontinuous/severely abnormal in 16 (11%), and predominantly severely abnormal in 12 (8.5%). Increasing severity of background across monitoring epochs was associated with increasingly worse clinical outcomes. Children with severe EEG background abnormality at any time point (n = 36, 25%) were significantly more likely to die or have severe NDI at 2 years (adjusted relative risk: 7.95, 95% CI 3.49-18.12). EEG background is strongly associated with NDI at age 2 years. These results can be used to assist health care providers to plan follow-up care and counsel families for decision-making related to goals of care.

Neurodevelopmental outcome of babies with moderate to severe birth asphyxia with hypoxic ischemic encephalopathy treated with and without therapeutic hypothermia followed up till 6-24 month of age at tertiary care hospital of Southern Rajasthan

hypoxic ischemic encephalopathy. There are very few studies comparing the neurodevelopmental outcomes in neonates with moderate to severe HIE who received and not received TH. Objective was assessment of neurodevelopmental outcome between TH and non-TH group till last follow-up. Methods: Hospital Based Prospective study. All term neonates with Moderate to severe birth asphyxia with HIE who received TH and not received TH, admitted in NICU of BalChikitsalay, RNTMC, Udaipur, consenting for the study were followed up at age 3-6 month, 6-12 month, 12-18 month and 18-24 month from September 2018 to February 2021 and neurodevelopment outcome was assessed. Results: 70 neonates with birth asphyxia HIE II / III were included in the study, 35 in TH group and 35 in non-TH group. Out of 70 babies enrolled 46 (65.7%) were having normal development and 24 (34.3%) were having development delay. Out of 46 who were having development delay 6 (17.4%) were of TH group and 18 (51.4%) were of non-TH group. Most of the babies of TH group i.e., 30 (85.7%) were neurodevelopmentally normal and 5 (14.3%) were having some neurodevelopmental abnormality. In non-TH group 15 (42.8%) were normal and 20 (57.2%) were having some neurodevelopmental abnormality. Conclusions: Results of the study showed significantly better outcome in infant who received therapeutic hypothermia than those who did not.

Correlating Quantitative MRI-based Apparent Diffusion Coefficient Metrics with 24-month Neurodevelopmental Outcomes in Neonates from the HEAL Trial.

Background Multiple qualitative scoring systems have been created to capture the imaging severity of hypoxic ischemic brain injury. Purpose To evaluate quantitative volumes of acute brain injury at MRI in neonates with hypoxic ischemic brain injury and correlate these findings with 24-month neurodevelopmental outcomes and qualitative brain injury scoring by radiologists. Materials and Methods In this secondary analysis, brain diffusion-weighted MRI data from neonates in the High-dose Erythropoietin for Asphyxia and Encephalopathy trial, which recruited participants between January 2017 and October 2019, were analyzed. Volume of acute brain injury, defined as brain with apparent diffusion coefficient (ADC) less than 800 × 10-6 mm2/sec, was automatically computed across the whole brain and within the thalami and white matter. Outcomes of death and neurodevelopmental impairment (NDI) were recorded at 24-month follow-up. Associations between the presence and volume (in milliliters) of acute brain injury with 24-month outcomes were evaluated using multiple logistic regression. The correlation between quantitative acute brain injury volume and qualitative MRI scores was assessed using the Kendall tau-b test. Results A total of 416 neonates had available MRI data (mean gestational age, 39.1 weeks ± 1.4 [SD]; 235 male) and 113 (27%) showed evidence of acute brain injury at MRI. Of the 387 participants with 24-month follow-up data, 185 (48%) died or had any NDI. Volume of acute injury greater than 1 mL (odds ratio [OR], 13.9 [95% CI: 5.93, 32.45]; P < .001) and presence of any acute injury in the brain (OR, 4.5 [95% CI: 2.6, 7.8]; P < .001) were associated with increased odds of death or any NDI. Quantitative whole-brain acute injury volume was strongly associated with radiologists' qualitative scoring of diffusion-weighted images (Kendall tau-b = 0.56; P < .001). Conclusion Automated quantitative volume of brain injury is associated with death, moderate to severe NDI, and cerebral palsy in neonates with hypoxic ischemic encephalopathy and correlated well with qualitative MRI scoring of acute brain injury. Clinical trial registration no. NCT02811263 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Huisman in this issue.

Association of Hospital Resource Utilization With Neurodevelopmental Outcomes in Neonates With Hypoxic-Ischemic Encephalopathy

Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes. To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE. Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children's hospitals participating in the Children's Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022. Infants who survived to 4 days of age and had neurodevelopmental outcomes assessed at greater than 11 months of age were divided into 2 groups: (1) death or NDI and (2) survived without NDI. Resource utilization was defined as costs of hospitalization including neonatal neurocritical care (NNCC). Data were linked with Pediatric Health Information Systems to quantify standardized costs by terciles. The main outcome was death or NDI. Characteristics, outcomes, hospitalization, and NNCC costs were compared. Among the 381 patients who were included, median (IQR) gestational age was 39 (38-40) weeks; maternal race included 79 (20.7%) Black mothers, 237 (62.2%) White mothers, and 58 (15.2%) mothers with other race; 80 (21%) died, 64 (17%) survived with NDI (combined death or NDI group: 144 patients [38%]), and 237 (62%) survived without NDI. The combined death or NDI group had a higher rate of infants with Apgar score at 10 minutes less than or equal to 5 (65.3% [94 of 144] vs 39.7% [94 of 237]; P < .001) and a lower rate of infants with mild or moderate HIE (36.1% [52 of 144] vs 82.3% [195 of 237]; P < .001) compared with the survived without NDI group. Compared with low-cost centers, there was no association between high- or medium-hospitalization cost centers and death or NDI. High- and medium-EEG cost centers had lower odds of death or NDI compared with low-cost centers (high vs low: OR, 0.30 [95% CI, 0.16-0.57]; medium vs low: OR, 0.29 [95% CI, 0.13-0.62]). High- and medium-laboratory cost centers had higher odds of death or NDI compared with low-cost centers (high vs low: OR, 2.35 [95% CI, 1.19-4.66]; medium vs low: OR, 1.93 [95% CI, 1.07-3.47]). High-antiseizure medication cost centers had higher odds of death or NDI compared with low-cost centers (high vs. low: OR, 3.72 [95% CI, 1.51-9.18]; medium vs low: OR, 1.56 [95% CI, 0.71-3.42]). Hospitalization costs during the first 4 days of age in neonates with HIE treated with TH were not associated with neurodevelopmental outcomes. Higher EEG costs were associated with lower odds of death or NDI yet higher laboratory and antiseizure medication costs were not. These findings serve as first steps toward identifying aspects of NNCC that are associated with outcomes.

Effects of 1.5-T versus 3-T magnetic resonance imaging in fetuses: is there a difference in postnatal neurodevelopmental outcome? Evaluation in a fetal population with left-sided congenital diaphragmatic hernia.

The utilization of 3-T magnetic field strength in obstetric imaging is increasingly common. It is important to ensure that magnetic resonance (MR) imaging with higher magnetic field strength is safe for the fetus. Comparison of neurodevelopmental outcome in neonates undergoing prenatal MR imaging with 1.5-T versus 3-T is of interest but has not yet been examined. We hypothesized no clinically meaningful difference in neurodevelopmental outcome between fetuses undergoing 1.5-T versus 3-T fetal MR imaging. As imaging a normal fetus for research purposes is illegal in Pennsylvania, this study was conducted in a population of fetuses with left congenital diaphragmatic hernia (left-CDH). A retrospective review of neurodevelopmental outcome of fetuses with left-CDH scanned at 1.5-T (n=75) versus 3-T (n=25) magnetic field strength between July of 2012 and December of 2019 was performed. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development, 3rd Edition (BSID-III). There were no statistical differences in median age of assessment (1.5-T: 18 [12, 25] versus 3-T: 21 [11, 26], P=0.79), in mean BSID-III cognitive (1.5-T: 91 ± 14 versus 3-T: 90 ± 16, P=0.82), language (1.5-T: 92 ± 20 versus 3-T: 91 ± 20, P=0.91), and motor composite (1.5-T: 89 ± 15 versus 3-T: 87 ± 18, P=0.59) scores, subscales scores (for all, P>0.50), or in risk of abnormal neuromuscular exam (P=0.29) between neonates with left-CDH undergoing a 1.5-T versus 3-T MR imaging during fetal life. Additionally, the distribution of patients with average, mildly delayed, and severely delayed BSID-III scores was similar between the two groups (for all, P>0.50). The overall distribution of the composite scores in this CDH population was similar to the general population independent of exposure to 1.5-T or 3-T fetal MR imaging. Two 3-T patients (8%) and five 1.5-T patients (7%) scored within the significant delayed range for all BSID-III domains. Subjects with lower observed-to-expected fetal lung volume (O/E FLV) and postnatal need for ECMO had lower cognitive, language, motor, and subscales scores (for all, P<0.03) regardless of being imaged at 1.5-T versus 3-T. This preliminary study suggests that, compared to 1.5-T MR imaging, fetal exposure to 3-T MR imaging does not increase the risk of neurodevelopmental impairment in fetuses with left-CDH. Additional MR imaging studies in larger CDH cohorts and other fetal populations are needed to replicate and extend the present findings.

EBNEO Commentary: Safety and efficacy of erythropoietin in neonates with hypoxic-ischaemic encephalopathy.

EBNEO Commentary: Safety and efficacy of erythropoietin in neonates with hypoxic-ischaemic encephalopathy.

Impact of Cerebral Oxygen Saturation Monitoring on Short-term Neurodevelopmental Outcomes in Neonates with Encephalopathy - A Prospective Cohort Study.

Near-infrared spectroscopy (NIRS) has been used for monitoring cerebral oxygen saturation (rSO2) in neonates. There is a lack of data from low-middle income countries (LMIC) setting of cerebral rSO2 in neonates with encephalopathy of diverse etiologies. This study aimed to monitor cerebral rSO2 using NIRS in encephalopathic neonates to maintain the rSO2 between 55 to 85 % in the first 72 hours of admission to improve short-term neurodevelopmental outcomes (NDO). This prospective cohort study enrolled encephalopathic neonates with hypoxic- ischemic encephalopathy (HIE) and non-HIE etiologies into 8 clinical categories. The cerebral rSO2 was monitored and targeted to be between 55 to 85 %, with predefined actions and management alterations over 72 hours. The neurodevelopmental assessment was conducted at 3, 6, and 9-12 months corrected age. Moreover, the motor and mental developmental quotients (MoDQ) (MeDQ) were recorded and compared to historical control. A total of 120 neonates were enrolled and assessed for NDO. The MoDQ (mean ± SD) was 92.55 ± 14.85, 93.80 ± 13.20, 91.02 ± 12.69 and MeDQ (mean ± SD) was 91.80 ± 12.98, 91.80 ± 13.69, 88.41 ± 11.60 at 3, 6 and 9-12 months. The MoDQ and MeDQ scores of the historic cohort at 12 months were 86.35 ± 20.34 and 86.58 ± 18.27. The mean difference [MD (95 %CI)] for MoDQ was - 4.670 (- 8.48 to - 0.85) (p=0.0165) and for MeDQ was - 1.83 (- 5.26 to 1.6) (p=0.29). There was a negative correlation between the composite developmental quotient (CoDQ) with mean rSO2 and a positive correlation with cerebral fractional tissue oxygen extraction (CFTOE). Neonates with HIE and neonatal encephalopathy (NE) (n=37/120) had the lowest motor and mental DQ on neurodevelopmental assessment. Clinical categories, neonatal meningitis (NM), and intraventricular hemorrhage (IVH) improved in DQ scores over the study period. Monitoring and maintaining cerebral rSO2 between 55-85 % through appropriate management changes improved neurodevelopmental scores at the 12-month follow-up in neonates with encephalopathy caused by varied etiologies.

Optimizing Neurodevelopmental Outcomes in Neonates With Congenital Heart Disease.

Neurodevelopmental impairment is a common and important long-term morbidity among infants with congenital heart disease (CHD). More than half of those with complex CHD will demonstrate some form of neurodevelopmental, neurocognitive, and/or psychosocial dysfunction requiring specialized care and impacting long-term quality of life. Preventing brain injury and treating long-term neurologic sequelae in this high-risk clinical population is imperative for improving neurodevelopmental and psychosocial outcomes. Thus, cardiac neurodevelopmental care is now at the forefront of clinical and research efforts. Initial research primarily focused on neurocritical care and operative strategies to mitigate brain injury. As the field has evolved, investigations have shifted to understanding the prenatal, genetic, and environmental contributions to impaired neurodevelopment. This article summarizes the recent literature detailing the brain abnormalities affecting neurodevelopment in children with CHD, the impact of genetics on neurodevelopmental outcomes, and the best practices for neonatal neurocritical care, focusing on developmental care and parental support as new areas of importance. A framework is also provided for the infrastructure and resources needed to support CHD families across the continuum of care settings.

Neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections during pregnancy: a national prospective study in Kuwait

BackgroundAn increasing proportion of women are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study was to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy.MethodsIn this prospective cohort study, the neurodevelopmental status of infants (N = 298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10–12 months post-discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff scores ≤ 2 standard deviations (SDs) below the population mean) and no delays (scores > 2 SDs above the population mean).ResultsThe majority (90%) of the infants born to mothers with SARS-CoV-2 infections during pregnancy had favorable outcomes and only 10% showed developmental delays. Two of the 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infections during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P = 0.039) and second trimesters (P = 0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester.ConclusionThe neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections seem favorable. However, more studies with larger sample sizes and longer follow-up periods are required.

Serum neuron-specific enolase, magnetic resonance imaging, and electrophysiology for predicting neurodevelopmental outcomes of neonates with hypoxic-ischemic encephalopathy: a prospective study

BackgroundNeonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity. Effective indicators for the early diagnosis of brain injury after HIE and prognosis are lacking. This study aimed to examine the predictive value of serum neuron-specific enolase (NSE), amplitude-integrated electroencephalography (aEEG), and magnetic resonance imaging (MRI), alone and in combination, for the neurological outcomes in neonates with HIE.MethodsNewborns with HIE born and treated at the Third Affiliated Hospital of An-Hui Medical University were consecutively included in this prospective cohort study (June 2013 to December 2020). Encephalopathy was classified as mild, moderate or severe according to Samat and Sarnat. All patients were assessed serum 1-day NSE and 3-day NSE levels after birth. The children were classified by neurological examination and Bayley Scales of Infant Development II at 18 months of age. ROC analysis was used to evaluate the predictive accuracy of the neurodevelopment outcomes.ResultsA total of 50 HIE neonates were enrolled (normal group: 32 (64.0%), moderate delay: 5 (10.0%), severe delay: 30(26.0%)) according to Bayley II scores. Serum 3-day NSE levels increased with worsening neurodevelopment outcomes (normal: 20.52 ± 6.42 μg/L vs. moderate: 39.82 ± 5.92 μg/L vs. severe: 44.60 ± 9.01 μg/L, P < 0.001). The MRI findings at 4–7 days after birth were significantly different among the three groups (P < 0.001). Forty-two (84.0%) children had abnormal aEEG. The combination of the three abnormalities combined together had 100% sensitivity, 97.70% specificity, 98.25% PPV, and 99.98% NPV.ConclusionsMRI, aEEG, and 3-day NSE can predict the neurological prognosis of newborns with HIE without hypothermia treatment. Their combination can improve the predictive ability for long-term neurobehavioral prognosis.

Therapeutic Hypothermia on Transport: The Quest for Efficiency: Results of a Quality Improvement Project.

Introduction:Therapeutic hypothermia (TH) within 6 hours after birth is known to improve both survival and neurodevelopmental outcomes in neonates with hypoxic ischemic encephalopathy (HIE). Meeting this recommended target temperature for neonates who require transport for TH treatment can be complex for various reasons. This study aimed to reduce the time from birth to the initiation of TH and target temperature, thereby increasing the proportion of transported neonates reaching target temperature within 6 hours to >50%.Methods:We evaluated the effect of three quality improvement interventions, including revised transport team processes, outreach education/resources, and the use of a servo-controlled cooling device on land transports. We compared key outcome TH metrics for cohorts before and after implementation.Results:The study team compared baseline data for 77 to 102 neonates born between 2009 and April 2015 (preintervention) and September 2015 and September 2020 (postintervention(s)). We observed reductions in both the time from birth to the initiation of passive cooling (38%) and time to reach target TH temperature (23%), with an increase in the proportion of neonates reaching target temperature by 6 hours of age from 50% to 71%.Conclusions:We used quality improvement methodology to identify key areas for intervention(s) and improvement. Targeted interventions have successfully and consistently improved the timing and delivery of TH to neonates with hypoxic ischemic encephalopathy within the transport environment, with a 20% increase in neonates reaching target temperature by 6 hours of age.

Longitudinal Analysis of Amplitude-Integrated Electroencephalography for Outcome Prediction in Hypoxic-Ischemic Encephalopathy

To investigate the prognostic accuracy of longitudinal analysis of amplitude-integrated electroencephalography (aEEG) background activity to predict long-term neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. This single-center observational study included 149 neonates for derivation and 55 neonates for validation with moderate-severe HIE and of gestational age ≥35weeks at a tertiary neonatal intensive care unit. Single-channel aEEG background pattern, sleep-wake cycling, and seizure activity were monitored over 84hours during therapeutic hypothermia and rewarming, then scored for each 6-hour interval. Neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition. Favorable outcome was defined as having both a Mental Development Index (MDI) score and Psychomotor Development Index (PDI) score ≥70, and adverse outcome was defined as either an MDI or a PDI <70 or death. Regression modeling for longitudinal analysis of repeatedly measured data was applied, and area under the receiver operating characteristic curve (AUC) was calculated. Longitudinal aEEG background analysis combined with sleep-wake cycling score had excellent predictive value (AUC, 0.90; 95% CI, 0.85-0.95), better than single aEEG scores at any individual time point. The model performed well in the independent validation cohort (AUC, 0.87; 95% CI, 0.62-1.00). The reclassification rate of this model compared with the conventional analysis of aEEG background at 48hours was 18% (24 patients); 14% (18 patients) were reclassified correctly. Our results were used to develop a user-friendly online outcome prediction tool. Longitudinal analysis of aEEG background activity and sleep-wake cycling is a valuable and accurate prognostic tool.

Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult

Perinatal hypoxic/ischemic (HI) brain injury is a major clinical problem with devastating neurodevelopmental outcomes in neonates. During HI brain injury, dysregulated factor production contributes to microvascular impairment. Glycolysis-derived lactate accumulated during ischemia has been proposed to protect against ischemic injury, but its mechanism of action is poorly understood. Herein, we hypothesize that lactate via its G-protein coupled receptor (GPR81) controls postnatal brain angiogenesis and plays a protective role after HI injury. We show that GPR81 is predominantly expressed in neurons of the cerebral cortex and hippocampus. GPR81-null mice displayed a delay in cerebral microvascular development linked to reduced levels of various major angiogenic factors and augmented expression of anti-angiogenic Thrombospondin-1 (TSP-1) in comparison to their WT littermates. Coherently, lactate stimulation induced an increase in growth factors (VEGF, Ang1 and 2, PDGF) and reduced TSP-1 expression in neurons, which contributed to accelerating angiogenesis. HI injury in GPR81-null animals curtailed vascular density and consequently increased infarct size compared to changes seen in WT mice; conversely intracerebroventricular lactate injection increased vascular density and diminished infarct size in WT but not in GPR81-null mice. Collectively, we show that lactate acting via GPR81 participates in developmental brain angiogenesis, and attenuates HI injury by restoring compromised microvasculature.

A predictive value of early clinical parameters for abnormal brain MRI scan in neonates treated with therapeutic hypothermia

Introduction:Brain MRI scans can predict neurodevelopmental outcomes in neonates treated with therapeutic hypothermia. It is a common clinical practice to perform brain MRI before discharge, but brain MRI scans performed at around four months of age have a better prognostic value for a long-term neurological outcome in asphyxiated neonates. Aim: To identify which of three selected clinical parameters (oral feeding ability, muscle tone, history of seizure) evaluated 10 days after therapeutic hypothermia could predict the primary outcome of an abnormal brain MRI. Methods: We reviewed the medical records of neonates ≥ 36 completed weeks of gestation consecutively treated with therapeutic hypothermia who underwent brain MRI. Clinical parameters on day 10 after therapeutic hypothermia were correlated with brain MRI findings in the first 7-14 days of life. Logic regression analysis was performed using all three covariates of the clinical status, with an abnormal MRI as the primary outcome. Results: Brain MRI was abnormal in 42 (51.85 %) neonates with the following distribution of brain injury patterns: abnormal signal in the basal nuclei in 6, an abnormal signal in the cortex in 16, an abnormal signal both in the cortex and basal nuclei in 20 neonates. Out of three analyzed clinical parameters, feeding difficulty (P &lt; 0.001, OR 8.3, 95% CI 2.9 - 28.9) and a history of seizures (P &lt; 0.001, OR 11.95, 95% CI 3 - 44.5) were significantly associated with an abnormal MRI. Conclusion: Neonates who were capable of full oral feeding by day 10 after therapeutic hypothermia and had no history of seizures were unlikely to have an abnormal MRI. This may be used in selective planning of pre-discharge MRI in asphyxiated neonates.

Multisystem Inflammatory Syndrome-Neonate: Biochemical Parameters as Early Marker of Adverse Neurodevelopmental Outcome

Background: Pregnant women and newborns are highly susceptible to Covid-19, manifesting as multisystem inflammatory syndrome-New-born (MISC-N) in many babies born to Covid positive mothers. The relationship between Covid-19 infection during pregnancy and neonatal neurodevelopmental outcome, if any, is unclear necessitating a follow-up study in this aspect. Methods: 16 babies with MIS-N, born to symptomatic Covid antibody positive mothers were enrolled. Demographic profile, treatment details and biochemical parameters were analyzed with neurodevelopmental follow-up. Results: 25% mothers received 2 doses of Covid vaccine; 50% had oligohydramnios and 75% received antenatal steroids. 87.5% were preterm of which 62.5% required surfactant with ventilator support and 75% required ionotropic support. Significant association was found between the antibody level and D-dimer levels with the ferritin and LDH levels of the baby (p 0.05); gestational age with LDH and D-dimer levels (p 0.05) and Covid antibody level of the baby vs the duration of ventilator requirement (P-value-0.0009). D-dimer values of babies were positively associated with both maternal antibody and D-dimer levels. Neurodevelopmental follow-up done at 6 months of corrected gestational age showed 37.5% were normal, 37.5% hypertonic and 25% hypotonic. HINE score was below 60 in 62.5%. Development assessment using Bayley-III showed a delay in the motor domain (62.5%), cognitive domain (56.25%) and language domain (62.5%). Conclusion: Neurodevelopmental problems occur in babies born to Covid positive mothers and should be stratified as “high risk”. Anticipatory guidance to prospective mothers for preterm care should be given. Covid antibody titre and D-dimer levels may help to predict the NICU stay, ventilator requirement and the adverse neurodevelopmental outcomes in these babies.