Beyond Legal Boundaries: Public and Clinician Perspectives on Treatment Withdrawal in Infants With Poor Neurological Prognosis.

BACKGROUND: Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. METHODS: We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. RESULTS: Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. CONCLUSION: The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.

Risk factors for neonatal hypoxic ischemic encephalopathy and therapeutic hypothermia: a matched case-control study.

BACKGROUND: Peripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonates, therapeutic cooling can be used to prevent or reduce permanent brain damage. The aim of this study was to assess the significance of different antenatal and delivery related risk factors for moderate and severe HIE and the need for therapeutic hypothermia. METHODS: We conducted a retrospective matched case-control study in Helsinki University area hospitals during 2013-2017. Newborn singletons with moderate or severe HIE and the need for therapeutic hypothermia were included. They were identified from the hospital database using ICD-codes P91.00, P91.01 and P91.02. For every newborn with the need for therapeutic hypothermia the consecutive term singleton newborn matched by gender, fetal presentation, delivery hospital, and the mode of delivery was selected as a control. Odds ratios (OR) between obstetric and delivery risk factors and the development of HIE were calculated. RESULTS: Eighty-eight cases with matched controls met the inclusion criteria during the study period. Maternal and infant characteristics among cases and controls were similar, but smoking was more common among cases (aOR 1.46, CI 1.14-1.64, p = 0.003). The incidence of preeclampsia, diabetes and intrauterine growth restriction in groups was equal. Induction of labour (aOR 3.08, CI 1.18-8.05, p = 0.02) and obstetric emergencies (aOR 3.51, CI 1.28-9.60, p = 0.015) were more common in the case group. No difference was detected in the duration of the second stage of labour or the delivery analgesia. CONCLUSIONS: Smoking, induction of labour and any obstetric emergency, especially shoulder dystocia, increase the risk for HIE and need for therapeutic hypothermia. The decisions upon induction of labour need to be carefully weighed, since maternal smoking and obstetric emergencies can hardly be controlled by the clinician.

Drug Disposition in Neonatal Göttingen Minipigs: Exploring Effects of Perinatal Asphyxia and Therapeutic Hypothermia.

Asphyxiated neonates often undergo therapeutic hypothermia (TH) to reduce morbidity and mortality. Since both perinatal asphyxia (PA) and TH influence physiology, altered pharmacokinetics (PK) and pharmacodynamics (PD) are expected. Given that TH is the standard of care for PA with moderate to severe hypoxic-ischemic encephalopathy, disentangling the effect of PA versus TH on PK/PD is not possible in clinical settings. However, animal models can provide insights into this matter. The (neonatal) Göttingen Minipig, the recommended strain for nonclinical drug development, was selected as translational model. Four drugs-midazolam (MDZ), fentanyl (FNT), phenobarbital (PHB), and topiramate (TPM)-were intravenously administered under four conditions: control (C), therapeutic hypothermia (TH), hypoxia (H), and hypoxia plus TH (H+TH). Each group included six healthy male neonatal Göttingen Minipigs anesthetized for 24 hours. Blood samples were drawn at 0 (predose) and 0.5, 2, 2.5, 3, 4, 4.5, 6, 8, 12, and 24 hours post drug administration. Drug plasma concentrations were determined using validated bioanalytical assays. The PK parameters were estimated through compartmental and noncompartmental PK analysis. The study showed a statistically significant decrease in FNT clearance (CL; 66% decrease), with an approximately threefold longer half-life (t1/2) in the TH group. The H+TH group showed a 17% reduction in FNT CL, with a 62% longer t1/2 compared with the C group; however, it was not statistically significant. Although not statistically significant, trends toward lower CL and longer t1/2 were observed in the TH and H+TH groups for MDZ and PHB. Additionally, TPM demonstrated a 28% decrease in CL in the H group compared with controls. SIGNIFICANCE STATEMENT: The overarching goal of this study using the neonatal Göttingen Minipig model was to disentangle the effects of systemic hypoxia and TH on PK using four model drugs. Such insights can subsequently be used to inform and develop a physiologically based pharmacokinetic model, which is useful for drug exposure prediction in human neonates.

The benefit of active management in true knot of the umbilical cord: a retrospective study.

PURPOSE: To compare perinatal outcomes between active and routine management in true knot of the umbilical cord (TKUC). METHODS: A retrospective study of singletons born beyond 22 6/7 weeks with TKUC. Active management included weekly fetal heart rate monitoring(FHRM) ≥ 30 weeks and labor induction at 36-37 weeks. Outcomes in active and routine management were compared, including composite asphyxia-related adverse outcome, fetal death, labor induction, Cesarean section (CS) or Instrumental delivery due to non-reassuring fetal heart rate (NRFHR), Apgar5 score < 7, cord Ph < 7, neonatal intensive care unit (NICU) admission and more. RESULTS: The Active (n = 59) and Routine (n = 1091) Management groups demonstrated similar rates of composite asphyxia-related adverse outcome (16.9% vs 16.8%, p = 0.97). Active Management resulted in higher rates of labor induction < 37 weeks (22% vs 1.7%, p < 0.001), CS (37.3% vs 19.2%, p = 0.003) and NICU admissions (13.6% vs 3%, p < 0.001). Fetal death occurred exclusively in the Routine Management group (1.8% vs 0%, p = 0.6). CONCLUSION: Compared with routine management, weekly FHRM and labor induction between 36 and 37 weeks in TKUC do not appear to reduce neonatal asphyxia. In its current form, active management is associated with higher rates of CS, induced prematurity and NICU admissions. Labor induction before 37 weeks should be avoided.

Neonatal Resuscitation Online Registry in Shenzhen: protocol for a prospective, multicentre, open, observational cohort study.

INTRODUCTION: Preterm birth complications and neonatal asphyxia are the leading causes of neonatal mortality worldwide. Surviving preterm and asphyxiated newborns can develop neurological sequelae; therefore, timely and appropriate neonatal resuscitation is important to decrease neonatal mortality and disability rates. There are very few systematic studies on neonatal resuscitation in China, and its prognosis remains unclear. We established an online registry for neonatal resuscitation in Shenzhen based on Utstein's model and designed a prospective, multicentre, open, observational cohort study to address many of the limitations of existing studies. The aim of this study is to explore the implementation and management, risk factors and outcomes of neonatal resuscitation in Shenzhen. METHODS AND ANALYSIS: This prospective, multicentre, open, observational cohort study will be conducted between January 2024 and December 2026 and will include >1500 newborns resuscitated at birth by positive pressure ventilation at five hospitals in Shenzhen, located in the south-central coastal area of Guangdong province, China. Maternal and infant information, resuscitation information, hospitalisation information and follow-up information will be collected. Maternal and infant information, resuscitation information and hospitalisation information will be collected from the clinical records of the patients. Follow-up information will include the results of follow-up examinations and outcomes, which will be recorded using the WeChat applet 'Resuscitation Follow-up'. These data will be provided by the neonatal guardians through the applet on their mobile phones. This study will provide a more comprehensive understanding of the implementation and management, risk factors and outcomes of neonatal resuscitation in Shenzhen; the findings will ultimately contribute to the reduction of neonatal mortality and disability rates in Shenzhen. ETHICS AND DISSEMINATION: Our protocol has been approved by the Medical Ethics Committee of Shenzhen Luohu People's Hospital (2023-LHQRMYY-KYLL-048). We will present the study results at academic conferences and peer-reviewed paediatrics journals. TRIAL REGISTRATION NUMBER: ChiCTR2300077368.

Effect of continuous workshop training of the helping babies breathe program on the retention of midwives' knowledge and skills: A clinical trial study.

AIM: To investigate the impact of ongoing workshop training of the "Helping Babies Breathe" program on the durability of midwives' knowledge and skills. BACKGROUND: Implementing the Helping Babies Breathe (HBB) program is crucial as a simple protocol for neonatal resuscitation in low-resource healthcare settings to decrease the rate of asphyxia and perinatal mortality by the initial healthcare providers. In addition to training in this program, it is also essential to guarantee the retention of the acquired knowledge and skills. DESIGN: A quasi-experimental clinical trial study with a single-group, pre-test-and-post-test design. METHODS: This study was conducted throughout the year 2022, with a sample size of 61 midwives selected through a census sampling from those working in the delivery and operating rooms of X Hospital in x City. The midwives participated in 3-hour workshops. This study was performed in two stages: intervention and follow-up. The evaluation Instruments included the HBB educational package, which consisted of a questionnaire and 3 Objective Structured Clinical Exams. During the intervention phase, the HBB program training was conducted through a series of workshops held at four different time points over a span of six months. In the follow-up stage, the learners were not provided with any further training. The evaluation was done immediately after the initial training workshop of the HBB program, at the end of the final workshop in the sixth month and at the end of the follow-up period. RESULTS: The mean knowledge score of the baseline, at six months and at twelve months after the initial workshop were documented as (17 SD1.2), (17.79 SD 0.4) and (17.73 SD 0.5), respectively. There was a statistically significant difference in the mean knowledge scores between the baseline and the six and twelve months (P<0.05), but no statistically significant difference was observed between six and twelve months (P>0.05). The mean skill scores showed a significant improvement and were maintained after six months compared with the initial assessment (P<0.05); however, there was a significant decrease in skill score twelve months later, in comparison to both the initial assessment and the first six months (P<0.05). CONCLUSIONS: Healthcare workers can maintain their knowledge and skills by participating in ongoing training workshops. However, without continuous training, their skills may diminish. Therefore, it is essential to implement training programs that emphasize regular practice and repetition to ensure knowledge and skills retention. REGISTRATION NUMBER: The present research was a part of the research work with the ethics ID IR.IRSHUMS.REC.1400.019.

Volumetric apparent diffusion coefficient histogram analysis in term neonatal asphyxia treated with hypothermia.

OBJECTIVES: Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). METHODS: Brain MRI studies of 83 term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) fourth and sixth days were retrospectively re-evaluated by 2 radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major, and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. RESULTS: With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (P = .02 and P = .03, respectively) and ADCmin (P = .03 and P = .04, respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (P = .04) and normal development (P = .04) via cytotoxic oedema of the thalamus, corpus striatum, and diffuse cerebral cortical. CONCLUSION: The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimated similarly with volumetric ADC-HA and the conventional assessment of the ADC map. ADVANCES IN KNOWLEDGE: This study compares early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We could not find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.

Quality assessment of clinical practice guidelines on hypoxic-ischaemic encephalopathy in newborns using the AGREE II tool: a systematic review.

INTRODUCTION: Hypoxic-ischaemic encephalopathy is a clinical syndrome of neurological dysfunction that occurs immediately after birth following an episode of perinatal asphyxia. We conducted a scoping review to assess the methodological quality of clinical practice guidelines that address this condition. METHODOLOGY: We conducted the evaluation using the AGREE II tool. High methodological quality was defined as a score greater than 70% in every domain. RESULTS: The analysis included three clinical practice guidelines; the highest scores were in the scope and purpose domain (84.26%; SD, 14.25%) and the clarity of presentation domain (84.26%; SD, 17.86%), while the lowest score corresponded to the applicability domain (62.50%; SD, 36.62%). Two guidelines were classified as high quality and one guideline as low-quality. CONCLUSIONS: Two of the assessed guidelines were classified as being of high quality; however, the analysis identified shortcomings in the applicability domain, in addition to methodological variation between guidelines developed in middle- or low-income countries versus high-income countries. Efforts are needed to make high-quality guidelines available to approach the management of hypoxic-ischaemic encephalopathy in newborns.

Stakeholders' Perspectives on the "Helping Babies Breathe" Program Situation in Nepal Following the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic impacted healthcare systems, including resuscitation training programs such as Helping Babies Breathe (HBB). Nepal, a country with limited healthcare resources, faces challenges in delivering effective HBB training, managing deliveries, and providing neonatal care, particularly in remote areas. AIMS: This study assessed HBB skills and knowledge postpandemic through interviews with key stakeholders in Nepal. It aimed to identify strategies, adaptations, and innovations to address training gaps and scale-up HBB. METHODS: A qualitative approach was used, employing semistructured interviews about HBB program effectiveness, pandemic challenges, stakeholder engagement, and suggestions for improvement. RESULTS: The study encompassed interviews with 23 participants, including HBB trainers, birth attendants, officials, and providers. Thematic analysis employed a systematic approach by deducing themes from study aims and theory. Data underwent iterative coding and refinement to synthesize content yielding following 5 themes: (1) pandemic's impact on HBB training; (2) resource accessibility for training postpandemic; (3) reviving HBB training; (4) impacts on the neonatal workforce; and (5) elements influencing HBB training progress. CONCLUSION: Postpandemic, healthcare workers in Nepal encounter challenges accessing essential resources and delivering HBB training, especially in remote areas. Adequate budgeting and strong commitment from healthcare policy levels are essential to reduce neonatal mortality in the future.

Qualitative Insights Into Enhancing Neonatal Resuscitation in Post-Pandemic Vietnam: A Stakeholder Perspective on the Helping Babies Breathe Program.

BACKGROUND: The neonatal phase is vital for child survival, with a substantial portion of deaths occurring in the first month. Neonatal mortality rates differ significantly between Vietnam (10.52/1000 live births) and the United States (3.27/1000). In response to these challenges, interventions such as the Helping Babies Breathe (HBB) program have emerged, aiming to enhance the quality of care provided during childbirth, and the postpartum period in low-resource settings. PURPOSE: The purpose of this study was to explore stakeholder perceptions of the HBB program in Vietnam postpandemic, aiming to identify requisites for resuming training. METHODS: Utilizing qualitative content analysis, 19 in-person semistructured interviews were conducted with diverse stakeholders in 2 provinces of Central Vietnam. RESULTS: The content analysis revealed following 5 main themes: (1) the pandemic's impact on HBB training; (2) resource needs for scaling up HBB training as the pandemic abates; (3) participants' perceptions of the pandemic's effect on HBB skills and knowledge; (4) the pandemic's influence on a skilled neonatal resuscitation workforce; and (5) future prospects and challenges for HBB training in a postpandemic era. IMPLICATIONS FOR PRACTICE AND RESEARCH: This research highlights the importance of sustainable post-HBB training competencies, including skill assessment, innovative knowledge retention strategies, community-based initiatives, and evidence-based interventions for improved healthcare decision-making and patient outcomes. Healthcare institutions should prioritize skill assessments, refresher training, and collaborative efforts among hospitals, authorities, non-government organizations, and community organizations for evidence-based education and HBB implementation.

Enteral plasma supports brain repair in newborn pigs after birth asphyxia.

Newborns exposed to birth asphyxia transiently experience deficient blood flow and a lack of oxygen, potentially inducing hypoxic-ischaemic encephalopathy and subsequent neurological damage. Immunomodulatory components in plasma may dampen these responses. Using caesarean-delivered pigs as a model, we hypothesized that dietary plasma supplementation improves brain outcomes in pigs exposed to birth asphyxia. Mild birth asphyxia was induced by temporary occlusion of the umbilical cord prior to caesarean delivery. Motor development was assessed in asphyxiated (ASP) and control (CON) piglets using neonatal arousal, physical activity and gait test parameters before euthanasia on Day 4. The ASP pigs exhibited increased plasma lactate at birth, deficient motor skills and increased glial fibrillary acidic protein levels in CSF and astrogliosis in the putamen. The expression of genes related to oxidative stress, inflammation and synaptic functions was transiently altered in the motor cortex and caudate nucleus. The number of apoptotic cells among CTIP2-positive neurons in the motor cortex and striatal medium spiny neurons was increased, and maturation of preoligodendrocytes in the internal capsule was delayed. Plasma supplementation improved gait performance in the beam test, attenuated neuronal apoptosis and affected gene expression related to neuroinflammation, neurotransmission and antioxidants (motor cortex, caudate). We present a new clinically relevant animal model of moderate birth asphyxia inducing structural and functional brain damage. The components in plasma that support brain repair remain to be identified but may represent a therapeutic potential for infants and animals after birth asphyxia.

Cerebral rScO2 Measured by Near-Infrared Spectroscopy (NIRS) During Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review.

INTRODUCTION: Perinatal asphyxia, a leading cause of neonatal mortality and neurological sequelae, necessitates early detection of pathophysiological neurologic changes during hypoxic-ischaemic encephalopathy (HIE). This study aimed to review published data on rScO2 monitoring during hypothermia treatment in neonates with perinatal asphyxia to predict short- and long-term neurological injury. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Study identification was performed through a search between November and December 2021 in the electronic databases PubMed, Embase, Lilacs, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). The main outcome was short-term (Changes in brain magnetic resonating imaging) and long-term (In neurodevelopment) neurological injury. The study protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews) with CRD42023395438. RESULTS: 380 articles were collected from databases in the initial search. Finally, 15 articles were selected for extraction and analysis of the information. An increase in rScO2 measured by NIRS (Near-infrared spectroscopy) at different moments of treatment predicts neurological injury. However, there exists a wide variability in the methods and outcomes of the studies. CONCLUSION: High rScO2 values were found to predict negative outcomes, with substantial discord among studies. NIRS is proposed as a real-time bedside tool for predicting brain injury in neonates with moderate to severe HIE.

Clinical-functional correlation with brain volumetry in severe perinatal asphyxia: a case report.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) appears in neurological conditions where some brain areas are likely to be injured, such as deep grey matter, basal ganglia area, and white matter subcortical periventricular áreas. Moreover, modeling these brain areas in a newborn is challenging due to significant variability in the intensities associated with HIE conditions. This paper aims to evaluate functional measurements and 3D machine learning models of a given HIE case by correlating the affected brain areas with the pathophysiology and clinical neurodevelopmental. CASE PRESENTATION: A comprehensive analysis of a term infant with perinatal asphyxia using longitudinal 3D brain information from Machine Learning Models is presented. The clinical analysis revealed the perinatal asphyxia diagnosis with APGAR <5 at 5 and 10 minutes, umbilical arterial pH of 7.0 BE of -21.2 mmol / L), neonatal seizures, and invasive ventilation mechanics. Therapeutic interventions: physical, occupational, and language neurodevelopmental therapies. Epilepsy treatment: vagus nerve stimulation, levetiracetam, and phenobarbital. Furthermore, the 3D analysis showed how the volume decreases due to age, exhibiting an increasing asymmetry between hemispheres. The results of the basal ganglia area showed that thalamus asymmetry, caudate, and putamen increase over time while globus pallidus decreases. CLINICAL OUTCOMES: spastic cerebral palsy, microcephaly, treatment-refractory epilepsy. CONCLUSIONS: Slight changes in the basal ganglia and cerebellum require 3D volumetry for detection, as standard MRI examinations cannot fully reveal their complex shape variations. Quantifying these subtle neurodevelopmental changes helps in understanding their clinical implications. Besides, neurophysiological evaluations can boost neuroplasticity in children with neurological sequelae by stimulating new neuronal connections.

General movement assessment efficacy for assessment of nervous system integrity in children after hypoxic-ischemic encephalopathy in middle income countries.

BACKGROUND: Many infants who survive hypoxic-ischemic encephalopathy (HIE) face long-term complications like epilepsy, cerebral palsy, and developmental delays. Detecting and forecasting developmental issues in high-risk infants is critical. AIM: This study aims to assess the effectiveness of standardized General Movements Assessment (GMA) and Hammersmith Infant Neurological Examinations (HINE) in identifying nervous system damage and predicting neurological outcomes in infants with HIE. DESIGN: Prospective. SUBJECTS AND MEASURES: We examined full-term newborns with perinatal asphyxia, classifying them as Grade 2 HIE according to Sarnat and Sarnat. The study included 31 infants, with 14 (45.2 %) receiving therapeutic hypothermia (Group 1) and 17 (54.8 %) not (Group 2). We evaluated general movements during writhing and fidgety phases and conducted neurological assessments using the HINE. RESULTS: All infants exhibited cramped-synchronized - like movements, leading to cerebral palsy (CP) diagnosis. Three children in Group 1 and four in Group 2 lacked fidgety movements. During active movements, HINE and GMA showed high sensitivity and specificity, reaching 96 % and 100 % for all children. The ROC curve's area under the curve (AUC) was 0.978. CONCLUSION: Our study affirms HINE and GMA as effective tools for predicting CP in HIE-affected children. GMA exhibits higher sensitivity and specificity during fidgety movements. However, study limitations include a small sample size and data from a single medical institution, necessitating further research.

Population pharmacokinetics of vancomycin in term neonates with perinatal asphyxia treated with therapeutic hypothermia.

AIMS: Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48 h of treatment with pharmacokinetic/pharmacodynamic target attainment. METHODS: Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study. A vancomycin PPK model was constructed using nonlinear mixed-effects modelling. The model was used to evaluate published dosing guidelines with regard to pharmacokinetic/pharmacodynamic target attainment. The area under the curve/minimal inhibitory concentration ratio of 400-600 mg*h/L was used as target range. RESULTS: Sixteen patients received vancomycin (median gestational age: 41 [range: 38-42] weeks, postnatal age: 4.4 [2.5-5.5] days, birth weight: 3.5 [2.3-4.7] kg), and 112 vancomycin plasma concentrations were available. Most samples (79%) were collected during the rewarming and normothermic phase, as vancomycin was rarely initiated during the hypothermic phase due to its nonempirical use. An allometrically scaled 1-compartment model showed the best fit. Vancomycin clearance was 0.17 L/h, lower than literature values for term neonates of 3.5 kg without perinatal asphyxia (range: 0.20-0.32 L/h). Volume of distribution was similar. Published dosing regimens led to overexposure within 24 h of treatment. A loading dose of 10 mg/kg followed by 24 mg/kg/day in 4 doses resulted in target attainment. CONCLUSION: Results of this study suggest that vancomycin clearance is reduced in term neonates with perinatal asphyxia treated with TH. Lower dosing regimens should be considered followed by model-informed precision dosing.

Initial lactate levels linked to oliguria in term neonates with perinatal asphyxia.

BACKGROUND: Oliguria is a sign of impaired kidney function and has been shown to be an early predictor of adverse prognoses in patients with acute kidney injury. The relationship between urine output (UOP) and early lactate levels in neonates with perinatal asphyxia (PA) has not been extensively explored. This study aimed to investigate the link between oliguria during the first 24 h of life and early lactate levels in neonates with PA. METHODS: The medical records of 293 term neonates with asphyxia from 9216 hospitalized newborns were retrospectively analyzed, including 127 cases designated as the oliguria group and 166 cases as controls. Peripheral arterial blood gas after PA and UOP within 24 h after birth were analyzed. Logistic regression analyses and receiver operating characteristic curve analysis were conducted. RESULTS: Oliguria occurred in 43.34% of neonates with PA. The median UOP of the oliguria and control groups were 0.65 and 1.46 mL/kg/h, respectively. Elevated lactate levels after PA are an independent risk factor for oliguria in the following 24 h (p = 0.01; OR: 1.19; 95%CI: 1.04-1.35) and show a moderate discriminatory power for oliguria (AUC = 0.62). Using a cut off value of 8.15 mmol/L, the positive and negative predictive values and the specificity were 59.34%, 63.86%, and 78.30%, respectively. CONCLUSION: Neonates with elevated lactate levels after PA face a risk of oliguria in the following 24 h. Based on early elevated lactate levels after resuscitation, especially ≥ 8.15 mmol/L, meticulously monitoring UOP will allow this vulnerable population to receive early, tailored fluid management and medical intervention.

Therapeutic hypothermia after perinatal asphyxia in Vietnam: medium-term outcomes at 18 months - a prospective cohort study.

AIM: To determine neurodevelopmental outcome at 18 months after therapeutic hypothermia for hypoxic-ischaemic encephalopathy (HIE) infants in Vietnam, a low-middle-income country. METHOD: Prospective cohort study investigating outcomes at 18 months in severely asphyxiated outborn infants who underwent therapeutic hypothermia for HIE in Hanoi, Vietnam, during the time period 2016-2019. Survivors were examined at discharge and at 6 and 18 months by a neonatologist, a neurologist and a rehabilitation physician, who were blinded to the infants' clinical severity during hospitalisation using two assessment tools: the Ages and Stages Questionnaire (ASQ) and the Hammersmith Infant Neurological Examination (HINE), to detect impairments and promote early interventions for those who require it. RESULTS: In total, 130 neonates, 85 (65%) with moderate and 45 (35%) with severe HIE, underwent therapeutic hypothermia treatment using phase change material. Forty-three infants (33%) died during hospitalisation and in infancy. Among the 87 survivors, 69 (79%) completed follow-up until 18 months. Nineteen children developed cerebral palsy (8 diplegia, 3 hemiplegia, 8 dyskinetic), and 11 had delayed neurodevelopment. At each time point, infants with a normal or delayed neurodevelopment had significantly higher ASQ and HINE scores (p<0.05) than those with cerebral palsy. CONCLUSION: The rates of mortality and adverse neurodevelopment rate were high and comparable to recently published data from other low-middle-income settings. The ASQ and HINE were useful tools for screening and evaluation of neurodevelopment and neurological function.