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Neonatal dysglycemia has been a longstanding interest of research in neonatology. Adverse outcomes from hypoglycemia were recognized early but are still being characterized. Premature infants additionally introduced and led the reflection on the importance of neonatal hyperglycemia. Cohorts of infants following neonatal encephalopathy provided further information about the impacts of hypoglycemia and, more recently, highlighted hyperglycemia as a central concern for this population. Innovative studies exposed the challenges of management of neonatal glycemic levels with a “u-shape” relationship between dysglycemia and adverse neurological outcomes. Lately, glycemic lability has been recognized as a key factor in adverse neurodevelopmental outcomes. Research and new technologies, such as MRI and continuous glucose monitoring, offered novel insight into neonatal dysglycemia. Combining clinical, physiological, and epidemiological data allowed the foundation of safe operational definitions, including initiation of treatment, to delineate neonatal hypoglycemia as ≤47 mg/dL, and >150–180 mg/dL for neonatal hyperglycemia. However, questions remain about the appropriate management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to continue to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes. Impact statement Safe operational definitions guide the initiation of treatment of neonatal hypoglycemia and hyperglycemia. Innovative studies exposed the challenges of neonatal glycemia management with a “u-shaped” relationship between dysglycemia and adverse neurological outcomes. The importance of glycemic lability is also being recognized. However, questions remain about the optimal management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes.

BackgroundThis study aims to compare the longitudinal changes in heart rate variability (HRV) during therapeutic hypothermia in neonates with different subtypes of hypoxic-ischemic brain injury.MethodsHRV was computed from 1 hour time-epochs q6 hours for the first 48 hours. Primary outcome was brain-injury pattern on MRI at 4(3–5) days. We fitted linear mixed-effect regression models with HRV metric, brain injury subtype and postnatal age.ResultsAmong 89 term neonates, 40 neonates had abnormal brain MRI (focal infarct 15 (38%), basal-ganglia predominant 8 (20%), watershed-predominant 5 (13%), and mixed pattern 12 (30%)). There was no significant difference in the HRV metrics between neonates with normal MRI, focal infarcts and basal ganglia pattern. At any given postnatal age, the degree of HRV suppression (HRV measure in the brain-injury subtype group/HRV measure in Normal MRI group) was significant in neonates with watershed pattern (SDNN(0.63, p = 0.08), RMSSD(0.74, p = 0.04)) and mixed pattern injury (SDNN (0.64, p < 0.001), RMSSD (0.75, p = 0.02)). HRV suppression was most profound at the postnatal age of 24–30 h in all brain injury subtypes.ConclusionNeonates with underlying watershed injury with or without basal-ganglia injury demonstrates significant HRV suppression during first 48 hour of hypothermia therapy.ImpactOur study suggests that suppression of heart rate variability in neonates during therapeutic hypothermia varies according to the pattern of underlying hypoxic-ischemic brain injury.Neonates with watershed predominant pattern and mixed pattern of brain injury have the most severe suppression of heart rate variability measures.Heart rate variability monitoring may provide early insights into the pattern of hypoxic-ischemic brain injury in neonates undergoing therapeutic hypothermia earlier than routine clinical MRI

Micronutrient deficiencies continue to be widespread among children under-five in low- and middle-income countries (LMICs), despite the fact that several effective strategies now exist to prevent them. This kind of malnutrition can have several immediate and long-term consequences, including stunted growth, a higher risk of acquiring infections, and poor development outcomes, all of which may lead to a child not achieving his or her full potential. This review systematically synthesizes the available evidence on the strategies used to prevent micronutrient malnutrition among children under-five in LMICs, including single and multiple micronutrient (MMN) supplementation, lipid-based nutrient supplementation (LNS), targeted and large-scale fortification, and point-of-use-fortification with micronutrient powders (MNPs). We searched relevant databases and grey literature, retrieving 35,924 papers. After application of eligibility criteria, we included 197 unique studies. Of note, we examined the efficacy and effectiveness of interventions. We found that certain outcomes, such as anemia, responded to several intervention types. The risk of anemia was reduced with iron alone, iron-folic acid, MMN supplementation, MNPs, targeted fortification, and large-scale fortification. Stunting and underweight, however, were improved only among children who were provided with LNS, though MMN supplementation also slightly increased length-for-age z-scores. Vitamin A supplementation likely reduced all-cause mortality, while zinc supplementation decreased the incidence of diarrhea. Importantly, many effects of LNS and MNPs held when pooling data from effectiveness studies. Taken together, this evidence further supports the importance of these strategies for reducing the burden of micronutrient malnutrition in children. Population and context should be considered when selecting one or more appropriate interventions for programming.

White matter (WM) injury is the most common type of brain injury in preterm infants and is associated with impaired neurodevelopmental outcome (NDO). Currently, there are no treatments for WM injury, but optimal nutrition during early preterm life may support WM development. The main aim of this scoping review was to assess the influence of early postnatal nutrition on WM development in preterm infants. Searches were performed in PubMed, EMBASE, and COCHRANE on September 2022. Inclusion criteria were assessment of preterm infants, nutritional intake before 1 month corrected age, and WM outcome. Methods were congruent with the PRISMA-ScR checklist. Thirty-two articles were included. Negative associations were found between longer parenteral feeding duration and WM development, although likely confounded by illness. Positive associations between macronutrient, energy, and human milk intake and WM development were common, especially when fed enterally. Results on fatty acid and glutamine supplementation remained inconclusive. Significant associations were most often detected at the microstructural level using diffusion magnetic resonance imaging. Optimizing postnatal nutrition can positively influence WM development and subsequent NDO in preterm infants, but more controlled intervention studies using quantitative neuroimaging are needed. IMPACT: White matter brain injury is common in preterm infants and associated with impaired neurodevelopmental outcome. Optimizing postnatal nutrition can positively influence white matter development and subsequent neurodevelopmental outcome in preterm infants. More studies are needed, using quantitative neuroimaging techniques and interventional designs controlling for confounders, to define optimal nutritional intakes in preterm infants.

Background Neonatal neurocritical care (NNCC) is a rapidly advancing field with limited fellowship training available in locally developed, non-accredited programs. A standardized survey aimed to understand the training backgrounds of individuals practicing NNCC, the structure of existing clinical NNCC services/training programs, and suggested clinical competencies for new graduates. Methods We developed an anonymous survey electronically sent to members of societies related to NNCC. Using the survey results as a guide, we discuss a competence by design (CBD) curriculum as a complementary approach to traditional time-based training. Results There were 82 responses to the survey from 30 countries; 95% of respondents were physicians. Thirty-one (42%) institutions reported having an NNCC service, 24 (29%) individuals reported formal NNCC training, 81% reported “significant variability” across NNCC training programs, and 88% were both in favor of standardizing training programs and pursuing formal accreditation for NNCC in the next 5 years. Conclusions The survey results demonstrate international interest in standardizing NNCC training and development of an accreditation or certification process. We propose consideration of a CBD-type curriculum as a training approach to focus on the development of specific NNCC competencies, rather than assuming the acquisition of these competencies based on time as a surrogate. Impact Continued growth and development in the field of NNCC has led to increasing need for training programs suited to meet the diverse needs of trainees from varied backgrounds. We present the results of an international survey that assessed the structure of existing training programs and the priority areas in which graduates must demonstrate competence, highlighting the combination of CBD and time-based training as one approach to address these recommendations. The survey results support interest in translating published training competencies, existing expertise, and infrastructure across centers into a standardized curriculum for NNCC including certification opportunities.

Objective Assess the capacity of brain state of the newborn (BSN) to predict neurodevelopment outcomes in neonatal encephalopathy. Methods Trends of BSN, a deep learning‐based measure translating EEG background to a continuous trend, were studied from a three‐channel montage long‐term EEG monitoring from a prospective cohort of 92 infants with neonatal encephalopathy and neurodevelopmental outcomes assessed by Bayley Scales of Infant Development, 3rd edition (Bayley‐III) at 18 months. Outcome prediction used categories “Severe impairment” (Bayley‐III composite score ≤70 or death) or “Any impairment” (score ≤85 or death). Results “Severe impairment” was predicted best for motor outcomes (24 h area under the curve (AUC) = 0.97), followed by cognitive (36 h AUC = 0.90), overall (24 h AUC = 0.84), and language (24 h AUC = 0.82). “Any impairment” was best predicted for motor outcomes (12 h AUC = 0.95), followed by cognitive (24 h AUC = 0.85), overall (12 h AUC = 0.75), and language (12 and 24 h AUC = 0.68). Optimal BSN cutoffs for outcome predictions evolved with the postnatal age. Low BSN scores reached a 100% positive prediction of poor outcomes at 24 h of age. Interpretation BSN is an excellent predictor of adverse neurodevelopmental outcomes in survivors of neonatal encephalopathy after therapeutic hypothermia, even at 24 h of life. The trend provides a fully automated, objective, quantified, and reliable interpretation of EEG background. The high temporal resolution supports continuous bedside brain assessment and early prognostication during the initial dynamic recovery phase.

Objectives: The current study used a mixed-method design to qualitatively examine parents’ definitions of resilience and factors they believed optimized their child’s early outcome following neonatal brain injury. This was followed by quantitative analyses of early developmental and mental health outcomes and their relation to salient biopsychosocial factors. Methods: Participants were parents of children diagnosed with neonatal brain injury due to stroke or hypoxic-ischemic encephalopathy (N=51; age range of children 18 months to 8 years). The Parent Experiences Questionnaire (PEQ) was used to qualitatively analyze parents’ open-ended responses about their child’s early experiences and outcome. The Child Behavior Checklist (CBCL) and Scales of Independent Behaviour Early Developmental Form (SIB-ED) parent ratings were used to measure child resilience from a quantitative perspective, identifying “at-risk” and “resilient” children using standard cutoffs. “Resilient” and “at-risk” children were compared on biopsychosocial variables using univariate t tests and chi-square analyses. Results: Parents provided five unique definitions of their child’s positive outcomes, and many children demonstrated resilience based on parent perspectives and quantitative definitions. Supporting factors included close medical follow-up, early intervention, and intrinsic factors within the child and parent. Group comparisons of “resilient” and “at-risk” children highlighted the importance of parent mental health across these early developmental and mental health outcomes. Conclusions: Many children were described as resilient during the early years by parents using qualitative and quantitative approaches. Findings highlighted the importance of parent well-being in promoting optimal early outcomes. (JINS, 2019, 25, 390–402.)

To investigate the effect of age and refractive error on changes in the retinal microvascular network. Subjects were recruited from the Doheny Eye Institute. Refractive error and axial length were measured. High myopia was defined as refractive error greater than -6 diopters (D). Optical coherence tomography angiography (OCTA) imaging was performed and images were analyzed using fractal analysis. Primary outcomes were superficial capillary plexus (SCP) vessel density, deep capillary plexus (DCP) vessel density, and foveal avascular zone (FAZ) area. One hundred thirty-eight eyes of 69 subjects were included. Twenty-eight (41%) subjects were male and 41 (59%) subjects were female. Mean age was 42.81 years ± 19.91 years (range: 8 years to 87 years). Mean refractive error was -1.74 D ± 3.18 D (range: -15.78 D to 4.25 D), and mean axial length (AL) was 24.29 mm ± 1.35 mm (range: 21.73 mm to 28.32 mm). SCP and DCP vessel densities were negatively correlated to age (r = -0.22, P = .011; and r = -0.49, P < .001). Controlling for age, patients with high myopia and longer AL had decreased SCP density (P = .021 and P = .027, respectively), but no difference in DCP vessel density was observed (P = .065 and P = .058, respectively). FAZ area was not significantly correlated to age, gender, refraction, or AL. SCP and DCP vessel densities decreased with age. In addition, SCP density but not DCP vessel density was reduced in eyes with high myopia and longer AL. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:925-931.].