Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest.

Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF's protective mechanisms and optimize its therapeutic application in post-arrest care.

Ischemic Post-Conditioning in a Rat Model of Asphyxial Cardiac Arrest.

BACKGROUND: Ischemic post-conditioning (IPoC) has been shown to improve outcomes in limited pre-clinical models. As down-time is often unknown, this technique needs to be investigated over a range of scenarios. As this tool limits reperfusion injury, there may be limited benefit or even harm after short arrest and limited ischemia-reperfusion injury. METHODS: Eighteen male Wistar rats underwent 7 min of asphyxial arrest. Animals randomized to IPoC received a 20 s pause followed by 20 s of compressions, repeated four times, initiated 40 s into cardiopulmonary resuscitation. If return of spontaneous circulation (ROSC) was achieved, epinephrine was titrated to mean arterial pressure (MAP) of 70 mmHg. Data were analyzed using t-test or Mann-Whitney test. Significance set at p ≤ 0.05. RESULTS: The rate of ROSC was equivalent in both groups, 88%. There was no statistically significant difference in time to ROSC, epinephrine required post ROSC, carotid flow, or peak lactate at any timepoint. There was a significantly elevated MAP with IPoC, 90.7 mmHg (SD 13.9), as compared to standard CPR, 76.7 mmHg (8.5), 2 h after ROSC, p = 0.03. CONCLUSIONS: IPoC demonstrated no harm in a model of short arrest using a new arrest etiology for CPR based IPoC intervention in a rat model.

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.

Risk factors of necrotizing enterocolitis in twin preterm infants.

PURPOSE: This study was aimed to investigate the risk factors of necrotizing enterocolitis (NEC) in twin preterm infants. METHODS: The clinical data of 67 pairs of twin preterm infants admitted to the neonatal department of our hospital from January 2010 to December 2021 were retrospectively collected. One of the twins had NEC (Bell II and above) and the other twin without NEC. They were divided into NEC group and control group according to whether NEC occurred or not. RESULTS: Univariate analysis showed that NEC was associated with congenital heart disease, small for gestational age, mild asphyxia at birth and feeding intolerance (P < 0.05). CONCLUSION: Occurrence of NEC was associated with congenital heart disease, small for gestational age, and asphyxia at birth. For twin preterm infants with congenital heart disease, small for gestational age, or asphyxia at birth, special attention should be paid to the occurrence of NEC to minimize and avoid the occurrence of NEC.

Magnitude of meconium stained amniotic fluid and associated factors among women who gave birth in North Shoa Zone hospitals, Amhara Region, Ethiopia 2022.

BACKGROUND: The presence of meconium-stained amniotic fluid is one of the causes for birth asphyxia. Each year, over five million neonatal deaths occur worldwide because of meconium-stained amniotic fluid and other causes, of which 90% are due to birth asphyxia. The aim of this study was to assess the magnitude of meconium-stained amniotic fluid and associated factors among women who gave birth in North Shoa Zone Hospitals, Amhara Region, Ethiopia, 2022. MATERIALS AND METHODS: An institutional-based cross-sectional study was employed. We used 610 women who gave birth at North Shoa Zone Hospitals, Amhara region, Ethiopia. The study was conducted from June 8 to August 8, 2022. Recruitment for the study was made using a multistage sampling procedure. Fifty percent of the study hospitals were randomly selected, and proportional allocation was done. Participants were selected from the sampling frame, labour and delivery register book, using a systematic random sampling approach. The first person was selected at random, while the remaining individuals were selected at every two "K" intervals across all hospitals. An interview-administered structured questionnaire and chart review checklist were used to gather the data that were entered into Epi-Data Version 4.6 and exported to SPSS. Logistics regression was employed, and a p-value <0.05 was considered statistically significant. RESULT: The magnitude of meconium-stained amniotic fluid was 30.3%. Women with a normal hematocrit level were 83% less likely to develop meconium-stained amniotic fluid. Women whose mid-upper arm circumference value was less than 22.9cm (AOR = 1.9; 95% CI: 1.18-3.20), obstructed labour (AOR = 3.6; 95% CI: 1.48-8.83), prolonged labour ≥ 15 hr (AOR = 7.5; 95% CI: 7.68-13.3), premature rapture of membrane (AOR = 1.7; 95% CI: 3.22-7.40), foetal tachycardia (AOR = 6.2; 95% CI: 2.41-16.3), and Bradycardia (AOR = 3.1; 95% CI: 1.93-5.28) showed a significant association with meconium-stained amniotic fluid. CONCLUSION: The present study revealed that the magnitude of meconium-stained amniotic fluid in North Shoa Zone is nearly one-third. A normal hematocrit level is a preventive factor for meconium-stained amniotic fluid, and a MUAC value <22.9 cm, obstructed and prolonged labour, PROM, bradycardia, and tachycardia are factors associated with meconium-stained amniotic fluid.

Asphyxia, Therapeutic Hypothermia, and Pulmonary Hypertension.

Neonates with a perinatal hypoxic insult and subsequent neonatal encephalopathy are at risk of acute pulmonary hypertension (aPH) in the transitional period. The phenotypic contributors to aPH following perinatal asphyxia include a combination of hypoxic vasoconstriction of the pulmonary vascular bed, right heart dysfunction, and left heart dysfunction. Therapeutic hypothermia is the standard of care for neonates with moderate-to-severe hypoxic ischemic encephalopathy. This review summarizes the underlying risk factors, causes of aPH in neonates with perinatal asphyxia, discusses the unique phenotypical contributors to disease, and explores the impact of the initial insult and subsequent therapeutic hypothermia on aPH.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Association Between Advanced Airway Management With Adrenaline Injection and Prognosis in Adult Patients With Asystole Asphyxia Out-of-hospital Cardiac Arrest.

BACKGROUND: The neurological prognosis of asphyxia is poor and the effect of advanced airway management (AAM) in the prehospital setting remains unclear. This study aimed to evaluate the association between AAM with adrenaline injection and prognosis in adult patients with asystole asphyxia out-of-hospital cardiac arrest (OHCA). METHODS: This study assessed all-Japan Utstein cohort registry data between January 1, 2013 and December 31, 2019. We used propensity score matching analyses before logistic regression analysis to evaluate the effect of AAM on favorable neurological outcome. RESULTS: There were 879,057 OHCA cases, including 70,299 cases of asphyxia OHCAs. We extracted the data of 13,642 cases provided with adrenaline injection by emergency medical service. We divided 7,945 asphyxia OHCA cases in asystole into 5,592 and 2,353 with and without AAM, respectively. After 1:1 propensity score matching, 2,338 asphyxia OHCA cases with AAM were matched with 2,338 cases without AAM. Favorable neurological outcome was not significantly different between the AAM and no AAM groups (adjusted odds ratio [OR] 1.1; 95% confidence interval [CI], 0.5-2.5). However, the return of spontaneous circulation (ROSC) (adjusted OR 1.7; 95% CI, 1.5-1.9) and 1-month survival (adjusted OR 1.5; 95% CI, 1.1-1.9) were improved in the AAM group. CONCLUSION: AAM with adrenaline injection for patients with asphyxia OHCA in asystole was associated with improved ROSC and 1-month survival rate but showed no differences in neurologically favorable outcome. Further prospective studies may comprehensively evaluate the effect of AAM for patients with asphyxia.

Risk-stratified management strategies for intrahepatic cholestasis of pregnancy: A tertiary center population review over nearly 5 years.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes, resulting in a higher risk of perinatal morbidity and mortality. METHODS: The authors conducted a retrospective study of 2385 singletons with ICP who underwent risk-stratified management strategies. To explore the risks of perinatal outcomes of ICP, subgroup analyses were performed using different total bile acid (TBA) levels. RESULTS: In this study, there was only one stillbirth and one neonatal death. Among the study cohort, 2299 patients had ICP with a TBA level ≥10 µmol/L and 86 had ICP with a TBA level <10 µmol/L. The 2299 patients with ICP (TBA level ≥ 10 µmol/L) were divided into three groups: mild ICP (n = 1803), severe ICP (n = 400), and extremely severe ICP (n = 96). Increased TBA concentration was associated with an increased incidence of preterm birth, newborn asphyxia, neonatal intensive care unit hospitalization, meconium-stained amniotic fluid, and low birth weight in the three groups (P < 0.05). Furthermore, severe and extremely severe ICP with hypotonic absonant uterine contraction had a significant effect on neonatal asphyxia (odds ratio, 5.06 [95% confidence interval, 1.09-23.37]; P < 0.05) and meconium-stained amniotic fluid (odds ratio, 2.37 [95% confidence interval, 1.43-3.93]; P < 0.05). CONCLUSIONS: Hypotonic absonant uterine contractions could be high-risk stressors for severe and extremely severe ICP; hence, proper prenatal care is recommended. Risk-stratified management strategies for ICP are critical to obtaining better maternal-fetal outcomes.

Treatments and outcomes of neonatal disseminated intravascular coagulation with and without neonatal asphyxia: A retrospective study using nationwide data in Japan.

BACKGROUND: Although neonatal disseminated intravascular coagulation (DIC) is associated with high mortality and severe complications, few studies have reported its clinical course. We aimed to describe the characteristics, treatments, and outcomes of neonatal DIC by using a national inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified 5533 patients with neonatal DIC who were admitted to neonatal intensive care units between July 2010 and March 2020. We categorized the patients into those with asphyxia (n = 2911) and those without asphyxia (n = 2622). We investigated the patient characteristics, treatments, and outcomes. We further categorized neonates with asphyxia according to its severity. RESULTS: The gestational age of neonates with asphyxia was significantly lower than that of neonates without asphyxia (P < 0.001). Antithrombin was most commonly used for DIC (40%). Neonates with asphyxia were more likely to receive antithrombin (43% vs. 38%; P < 0.001), recombinant human soluble thrombomodulin (28% vs. 20%; P < 0.001), and fresh frozen plasma transfusion (68% vs. 51%; P < 0.001) than those without asphyxia. Neonates with asphyxia had higher in-hospital mortality (17% vs. 10%; P < 0.001), severe bleeding (11% vs. 6.8%; P < 0.001), and hospitalization costs than those without asphyxia. Additionally, neonates with severe asphyxia were more likely to receive several DIC therapies (such as recombinant human soluble thrombomodulin [30% vs. 24%]) and had higher in-hospital mortality (19% vs. 11%) and hospitalization costs than those with mild asphyxia. CONCLUSIONS: In this large retrospective study of neonatal DIC, patients with asphyxia received several treatments and demonstrated unfavorable outcomes when compared to those without asphyxia.

Chest compressions superimposed with sustained inflations during cardiopulmonary resuscitation in asphyxiated pediatric piglets.

BACKGROUND: Pediatric resuscitation guidelines recommend continuous chest compression with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation. We recently described that providing a constant high distending pressure, or sustained inflation (SI) while performing continuous chest compressions (CC = CC + SI) reduces time to return of spontaneous circulation (ROSC) in neonatal and pediatric piglets with asphyxia-induced cardiac arrest. METHODS: To determine if CC + SI compared to CCaV will improve frequency of achieving ROSC and reduce time to ROSC in asphyxiated pediatric piglets. Twenty-eight pediatric piglets (21-24 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to CC + SI or CCaV for resuscitation (n = 14/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: The mean(SD) duration of resuscitation was significantly reduced with CC + SI compared to CCaV with 208(190) vs. 388(258)s, p = 0.045, respectively. The number of piglets achieving ROSC with CC + SI and CCaV were 12/14 vs. 6/14, p = 0.046. Minute ventilation, end-tidal carbon dioxide, ventilation rate, and positive end expiratory pressures were also significantly improved with CC + SI. CONCLUSIONS: CC + SI improves duration of resuscitation and increases number of piglets achieving ROSC secondary to improved minute ventilation. IMPACT: Chest compressions superimposed with sustained inflation resulted in shorter duration of resuscitation Chest compressions superimposed with sustained inflation resulted in higher number of piglets achieving return of spontaneous circulation Further animal studies are needed to examine chest compressions superimposed with sustained inflation.

Perinatal asphyxia does not influence presepsin levels in neonates: A prospective study.

AIM: To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. METHODS: In this prospective study, we enrolled 25 uninfected full-term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. RESULTS: In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut-off but not those of presepsin. CONCLUSION: In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased.

Hearing impairment after asphyxia and neonatal encephalopathy: a Norwegian population-based study.

The purpose of this study is to evaluate the association between perinatal asphyxia, neonatal encephalopathy, and childhood hearing impairment. This is a population-based study including all Norwegian infants born ≥ 36 weeks gestation between 1999 and 2014 and alive at 2 years (n = 866,232). Data was linked from five national health registries with follow-up through 2019. Perinatal asphyxia was defined as need for neonatal intensive care unit (NICU) admission and an Apgar 5-min score of 4-6 (moderate) or 0-3 (severe). We coined infants with seizures and an Apgar 5-min score < 7 as neonatal encephalopathy with seizures. Infants who received therapeutic hypothermia were considered to have moderate-severe hypoxic-ischemic encephalopathy (HIE). The reference group for comparisons were non-admitted infants with Apgar 5-min score ≥ 7. We used logistic regression models and present data as adjusted odds ratios (aORs) with 95% confidence intervals (CI). The aOR for hearing impairment was increased in all infants admitted to NICU: moderate asphyxia aOR 2.2 (95% CI 1.7-2.9), severe asphyxia aOR 5.2 (95% CI 3.6-7.5), neonatal encephalopathy with seizures aOR 7.0 (95% CI 2.6-19.0), and moderate-severe HIE aOR 10.7 (95% CI 5.3-22.0). However, non-admitted infants with Apgar 5-min scores < 7 did not have increased OR of hearing impairment. The aOR for hearing impairment for individual Apgar 5-min scores in NICU infants increased with decreasing Apgar scores and was 13.6 (95% CI 5.9-31.3) when the score was 0.          Conclusions: An Apgar 5-min score < 7 in combination with NICU admission is an independent risk factor for hearing impairment. Children with moderate-severe HIE had the highest risk for hearing impairment. What is Known: • Perinatal asphyxia and neonatal encephalopathy are associated with an increased risk of hearing impairment. • The strength of the association, and how other co-morbidities affect the risk of hearing impairment, is poorly defined. What is New: • Among neonates admitted to a neonatal intensive care unit (NICU), decreased Apgar 5-min scores, and increased severity of neonatal encephalopathy, were associated with a gradual rise in risk of hearing impairment. • Neonates with an Apgar 5-min score 7, but without NICU admission, did not have an increased risk of hearing impairment.

Feasibility and Safety of Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-01): A Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Trial.

OBJECTIVE: To test feasibility and safety of administering sildenafil in neonates with neonatal encephalopathy (NE), developing brain injury despite therapeutic hypothermia (TH). STUDY DESIGN: We performed a randomized, double-blind, placebo-controlled phase Ib clinical trial between 2016 and 2019 in neonates with moderate or severe NE, displaying brain injury on day-2 magnetic resonance imaging (MRI) despite TH. Neonates were randomized (2:1) to 7-day sildenafil or placebo (2 mg/kg/dose enterally every 12 hours, 14 doses). Outcomes included feasibility and safety (primary outcomes), pharmacokinetics (secondary), and day-30 neuroimaging and 18-month neurodevelopment assessments (exploratory). RESULTS: Of the 24 enrolled neonates, 8 were randomized to sildenafil and 3 to placebo. A mild decrease in blood pressure was reported in 2 of the 8 neonates after initial dose, but not with subsequent doses. Sildenafil plasma steady-state concentration was rapidly reached, but decreased after TH discontinuation. Twelve percent of neonates (1/8) neonates died in the sildenafil group and 0% (0/3) in the placebo group. Among surviving neonates, partial recovery of injury, fewer cystic lesions, and less brain volume loss on day-30 magnetic resonance imaging were noted in 71% (5/7) of the sildenafil group and in 0% (0/3) of the placebo group. The rate of death or survival to 18 months with severe neurodevelopmental impairment was 57% (4/7) in the sildenafil group and 100% (3/3) in the placebo group. CONCLUSIONS: Sildenafil was safe and well-absorbed in neonates with NE treated with TH. Optimal dosing needs to be established. Evaluation of a larger number of neonates through subsequent phases II and III trials is required to establish efficacy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT02812433.

Perinatal asphyxia and hypothermic treatment from the endocrine perspective.

Introduction: Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children. Results: Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia. Conclusions: Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.

Associations between maternal metabolic conditions and neurodevelopmental conditions in offspring: the mediating effects of obstetric and neonatal complications.

BACKGROUND: Maternal pre-gestational diabetes (PGDM), gestational diabetes mellitus (GDM), and overweight/obesity have been associated with increased risks of offspring neurodevelopmental conditions (NDCs) including autism, intellectual disability (ID), and attention deficit/hyperactivity disorder (ADHD). Less is known about whether and how obstetric and neonatal complications (e.g., preterm birth, neonatal asphyxia) could mediate these associations. METHODS: In this Swedish register-based cohort study, we examined complications during pregnancy, delivery, and the neonatal period as potential mediators of the relationships between maternal metabolic conditions and offspring NDCs. We quantified the extent to which these obstetric and neonatal factors could mediate the associations of maternal metabolic conditions with offspring NDCs by applying parametric regression models for single mediation analyses and weighting-based methods for multiple mediation analyses under counterfactual frameworks. RESULTS: The study sample included 2,352,969 singleton children born to 1,299,692 mothers from 1987-2010 who were followed up until December 31, 2016, of whom 135,832 children (5.8%) were diagnosed with at least one NDC. A substantial portion of the association between maternal PGDM and children's odds of NDCs could be explained by the combined group of obstetric and neonatal complications in the multiple mediation analysis. For instance, these complications explained 44.4% of the relationship between maternal PGDM and offspring ID risk. The proportion of the relationship between maternal overweight/obesity and children's risk of NDCs that could be explained by obstetric and neonatal complications was considerably smaller, ranging from 1.5 to 8.1%. Some complications considered on their own, including pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities, could explain at least 10% of the associations between maternal PGDM and offspring NDCs. Complications during the neonatal period showed a stronger joint mediating effect for the relationship between PGDM and offspring NDCs than those during pregnancy or delivery. CONCLUSIONS: Obstetric and neonatal complications could explain nearly half of the association between maternal PGDM and offspring risk of NDCs. The mediating effects were more pronounced for complications during the neonatal period and for specific complications such as pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities. Effective preventive strategies for offspring NDCs should holistically address both the primary metabolic issues related to PGDM and the wide array of potential complications, especially those in the neonatal period.

Effect of the smartphone application on caesarean section in women with overweight and obesity: a randomized controlled trial in China.

BACKGROUND: The rate of caesarean section (CS) is increasing worldwide. While a CS can be life-saving when medically indicated, it can cause adverse health effects for both women and children. This trial aims to evaluate the effect of the smartphone application, which aims to control the gestational weight gain, on the rate of CS in overweight and obese women. METHODS: Overweight and obese primiparas (BMI ≥ 24 kg/m2) with age between 20 and 40 years old were recruited at Beijing Obstetrics and Gynecology Hospital, and randomly assigned into the intervention group (143 cases) and the control group (138 cases). The intervention group applied the smartphone application (App) to control gestational weight gain in addition to the usual care, and the control group received the usual care. Primary outcome was cesarean section (CS) rate. Secondary outcomes included gestational hypertension, preeclampsia and eclampsia, gestational diabetes mellitus, postpartum hemorrhage, neonatal asphyxia, and macrosomia. RESULTS: There was a significant difference in CS rate, with 53.3% in the intervention group and 65.4% in the control group (P = 0.044). The difference still exists in the overweight subgroup (32.6% vs. 55.6%, P = 0.04), but disappears in the obesity subgroup (63.0% vs. 69.1%, P = 0.381). The median of gestational weight gain (GWG) of the intervention group is 8.5 kg (IQR 5.5, 11.0), which is significantly less than that of the control group (median 10.0 kg, IQR [6.0, 14.0], P = 0.008). The intervention group has significantly lower rate of postpartum hemorrhage (5.19%) than the control group (12%) (P = 0.045). There were no significant differences between the groups in gestational hypertension, gestational diabetes mellitus, neonatal asphyxia, and macrosomia. CONCLUSION: The smartphone assisted weight control may help reduce CS rate. The effects of the smartphone application might be via the management of gestational weight gain. TRAIL REGISTRATION: This trial was registered at Chinese Clinical Trial Registry. Registration number is ChiCTR2300068845 (retrospectively registered, 01/03/2023).

Effects of season, daytime, sex, and stress on the incidence, latency, frequency, severity, and duration of neonatal seizures in a rat model of birth asphyxia.

Neonatal seizures are common in newborn infants after birth asphyxia. They occur more frequently in male than female neonates, but it is not known whether sex also affects seizure severity or duration. Furthermore, although stress and diurnal, ultradian, circadian, or multidien cycles are known to affect epileptic seizures in adults, their potential impact on neonatal seizures is not understood. This prompted us to examine the effects of season, daytime, sex, and stress on neonatal seizures in a rat model of birth asphyxia. Seizures monitored in 176 rat pups exposed to asphyxia on 40 experimental days performed over 3 years were evaluated. All rat pups exhibited seizures when exposed to asphyxia at postnatal day 11 (P11), which in terms of cortical development corresponds to term human babies. A first examination of these data indicated a seasonal variation, with the highest seizure severity in the spring. Sex and daytime did not affect seizure characteristics. However, when rat pups were subdivided into animals that were exposed to acute (short-term) stress after asphyxia (restraint and i.p. injection of vehicle) and animals that were not exposed to this stress, the seizures in stress-exposed rats were more severe but less frequent. Acute stress induced an increase in hippocampal microglia density in sham-exposed rat pups, which may have an additive effect on microglia activation induced by asphyxia. When seasonal data were separately analyzed for stress-exposed vs. non-stress-exposed rat pups, no significant seasonal variation was observed. This study illustrates that without a detailed analysis of all factors, the data would have erroneously indicated significant seasonal variability in the severity of neonatal seizures. Instead, the study demonstrates that even mild, short-lasting postnatal stress has a profound effect on asphyxia-induced seizures, most likely by increasing the activity of the hypothalamic-pituitary-adrenal axis. It will be interesting to examine how postnatal stress affects the treatment and adverse outcomes of birth asphyxia and neonatal seizures in the rat model used here.

Cardiovascular responses to mild perinatal asphyxia in growth-restricted preterm lambs.

Growth-restricted neonates have worse outcomes after perinatal asphyxia, with more severe metabolic acidosis than appropriately grown neonates. The cardiovascular physiology associated with fetal growth restriction (FGR) may alter their response to asphyxia. However, research on asphyxia in FGR is limited. Here we compared cardiovascular hemodynamics in preterm FGR and control lambs during mild perinatal asphyxia. We induced FGR in one twin at 89 days gestation (term 148 days), while the other served as a control. At 126 days gestation, lambs were instrumented to allow arterial blood pressure and regional blood flow recording, and then mild perinatal asphyxia was induced by umbilical cord clamping, and resuscitation followed neonatal guidelines. FGR lambs maintained carotid blood flow (CBF) for 7 min, while control lambs rapidly decreased CBF (P < 0.05). Fewer growth-restricted lambs needed chest compressions for return of spontaneous circulation (ROSC) (17 vs. 83%, P = 0.02). The extent of blood pressure overshoot after ROSC was similar, but it took longer for MAP to return to baseline in FGR lambs (18.83 ± 0.00 vs. 47.67 ± 0.00 min, P = 0.003). Growth-restricted lambs had higher CBF after ROSC (P < 0.05) and displayed CBF overshoot, unlike control lambs (P < 0.03). In conclusion, preterm growth-restricted lambs show resilience during perinatal asphyxia based on prolonged CBF maintenance and reduced need for chest compressions during resuscitation. However, CBF overshoot after ROSC may increase the risk of cerebrovascular injury in FGR.NEW & NOTEWORTHY Preterm growth-restricted lambs maintain carotid blood flow for longer than control lambs during asphyxia and have a lower requirement for chest compressions than control lambs during resuscitation. Preterm growth-restricted, but not control, lambs displayed an overshoot in carotid blood flow following return of spontaneous circulation.