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.

An unusual case of severe asphyxia with the fetal position unexpectedly inverted in a malformed uterus: a case report.

BACKGROUND: We present a severe neonatal consequence due to the unexpected and crucial inversion of the fetal position after sudden termination of tocolysis during early labor of a woman with congenital uterine anomaly. It has been reported that congenital uterine anomalies latently affect the fetal position. The clinical pitfalls in childbirth with uterine anomalies are discussed here on the basis of clinical evidence. CASE PRESENTATION: At a perinatal medical center in Japan, a 29-year-old Japanese mother who had a history of bicornuate uterus, received tocolysis to prolong her pregnancy for 5 days during the late preterm period after preterm-premature rupture of the membrane. She gave birth to a 2304 g male neonate of the gestational age of 35 weeks and 5 days with severe asphyxia by means of crash cesarean section for fetal sustained bradycardia after sudden termination of tocolysis. We found the fetal position to reverse from cephalic to breech position during early labor. He ended up having severe cerebral palsy after brain cooling against hypoxic-ischemic encephalopathy for 3 days. The mechanism of inversion from cephalic to breech position without amnionic fluid remains unclear, although women with a known diagnosis of a uterine anomaly have higher risk of adverse outcomes such as malpresentation. CONCLUSIONS: When considering the clinical course of this case on the basis of the medical reports, we suspected that uterine anomalies and changes in intrauterine pressure could cause fetal malpresentation and adverse neonatal outcomes.

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.

The effect of hypoxic ischemic encephalopathy towards multi-organ complications and its early outcome at a Malaysian district hospital.

INTRODUCTION: Hypoxic ischemic encephalopathy (HIE) is a clinically defined syndrome of disturbed neurologic function in the newborn with evidence of perinatal asphyxia. Stages of HIE are categorised into mild, moderate or severe based on the Sarnat classification. Neurological dysfunction constitutes a part of the wide spectrum of hypoxic ischemic insult as affected infants can have co-existing multi-organ dysfunction which further contributes to morbidities and mortality. This study aims to determine the relationship between the severity of HIE with multi-organ complications and early clinical outcomes. MATERIALS AND METHODS: All neonates who were admitted to the NICU at Hospital Sultan Abdul Halim between January 2018 to December 2022, who fulfilled the inclusion criteria were included. Demographic data, clinical course and investigation results were retrospectively obtained from the medical records. RESULTS: From a total of 90 infants (n = 90) who fulfilled our inclusion criteria, 31 (34%) were mild, 31 (34%) were moderate and 28 (31%) were severe HIE. The mean maternal age was 27 years. Common antenatal issues include diabetes mellitus (37.8%) and anaemia (22.2%). The Apgar scores at 1 and 5 minutes, initial resuscitation requiring intubation, chest compression and adrenaline were associated with higher severity of HIE (p < 0.05). Coagulation dysfunction was the most common complication (79.7%), followed by respiratory dysfunction (33.3%), cardiac dysfunction (28.9%), renal dysfunction (16.1%), haematological dysfunction (15.6%) and hepatic dysfunction (12%). Respiratory and haematological dysfunctions were significantly associated with higher mortality (p < 0.05). There was a significant longer hospital stay (p = 0.023), longer duration of ventilation (p < 0.001) and increase in frequency of seizures (p < 0.001) when comparing moderate and severe HIE patients to mild HIE patients. With increasing severity of HIE, there was also statistically significant higher mortality (p < 0.001). CONCLUSIONS: There is a significant relationship between multiorgan dysfunction, the severity of HIE and mortality. Early anticipation of multi-organ injury is crucial for optimal early management which would reduce the mortality and improve the neurological outcome of the patients.

Association Between Seizures and Neurodevelopmental Outcome at Two and Five Years in Asphyxiated Newborns With Therapeutic Hypothermia.

OBJECTIVE: To investigate the association between the presence and severity of seizures in asphyxiated newborns and their neurodevelopmental outcome at ages two and five years. METHODS: Retrospective data analysis from a prospectively collected multicenter cohort of 186 term-born asphyxiated newborns undergoing therapeutic hypothermia (TH) in 11 centers in the Netherlands and Belgium. Seizures were diagnosed by amplitude-integrated electroencephalography (EEG) and raw EEG signal reading up to 48 hours after rewarming. Neurodevelopmental outcome was assessed by standardized testing at age two and five years. Primary outcome was death or long-term neurodevelopmental impairment (NDI) including cerebral palsy. Associations were calculated using univariate and multivariate logistic regression analyses adjusting for Thompson score and a validated brain magnetic resonance imaging (MRI) score. RESULTS: Seventy infants (38%) had seizures during TH or rewarming, and 44 (63%) of these needed two or more antiseizure medications (ASMs). Overall mortality was 21%. Follow-up data from 147 survivors were available for 137 infants (93%) at two and for 94 of 116 infants (81%) at five years. NDI was present in 26% at two and five years. Univariate analyses showed a significant association between seizures and death or NDI, but this was no longer significant after adjusting for Thompson and MRI score in the multivariate analysis; this was also true for severe seizures (need for two or more ASMs) or seizures starting during rewarming. CONCLUSION: The presence or severity of seizures in newborns undergoing TH for hypoxic-ischemic encephalopathy was not independently associated with death or NDI up to age five years after adjusting for several confounders.

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.

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.

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

OBJECTIVES: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. METHODS: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. RESULTS: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 µg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. CONCLUSIONS: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.

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.

Hypoxic Ischemic Encephalopathy with Cervical Spinal Cord Injury: A Diagnostic Dilemma.

Perinatal spinal cord injury is a relatively uncommon, but a frequently misdiagnosed disorder. Improvements in obstetric care have certainly led to a decrease in the incidence of birth related spinal cord trauma but unfortunately the incidence of hypoxic-ischemic encephalopathy is still very high. The exact incidence of spinal cord trauma is difficult to determine because the spinal cord is not routinely examined in far and few neonatal autopsies done in India. Here, authors present a neonate who received treatment for birth asphyxia and then had extubation failure which made the clock tick towards cervical cord injury. This baby had a hemorrhagic contusion of cervical spinal cord.

Acute Kidney Injury in Neonatal Hypoxic-Ischemic Encephalopathy Patients Treated with Therapeutic Hypothermia: Incidence and Risk Factors.

Studies in infants with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia have generally focused on neurological outcomes. Although acute kidney injury (AKI) rate decreased in advent of therapeutic hypothermia (TH), it is still a common and important entity. In this retrospective study, we aimed to investigate the risk factors for AKI in HIE patients treated with hypothermia. Infants treated with TH due to HIE were reviewed retrospectively and infants who developed AKI and not were compared. Ninety-six patients were enrolled in the study. AKI developed in 27 (28%) patients and 4 (14.8%) of them were stage III AKI. In the AKI group, gestational age of the patients was significantly higher (p = 0.035), the 1st minute Apgar score was significantly lower (p = 0.042), and convulsions (p = 0.002), amplitude-integrated electroencephalography disorders (p = 0.025), sepsis (p = 0.017), need for inotropic therapy (p = 0.001), need of invasive mechanical ventilation (p = 0.03), and systolic dysfunction in echocardiography (p = 0.022) were significantly higher. In logistic regression tests, Apgar score at the 1st minute was found to be independent risk factor for developing AKI. AKI has the potential to worsen the neurological damage and correlates with morbidities of perinatal asphyxia. It is important to determine the incidence and risk factors for developing AKI in this delicate group of patients to prevent further renal damage.

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.

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.

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.

Placental Histologic Abnormalities and 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: We aimed to examine the association between placental abnormalities and neurodevelopmental outcomes in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) that underwent therapeutic hypothermia. We hypothesized that subjects with acute placental abnormalities would have reduced risk of death or neurodevelopmental impairment (NDI) at 2 years of age after undergoing therapeutic hypothermia compared to subjects without acute placental changes. STUDY DESIGN: Among 500 subjects born at ≥36 weeks gestation with moderate or severe HIE enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, a placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute only, chronic only, or both acute and chronic histologic abnormalities. We calculated adjusted relative risks (aRRs) for associations between placental pathologic abnormalities and death or NDI at age 2 years, adjusting for HIE severity, treatment assignment, and site. RESULT: 321/500 subjects (64%) had available placental pathology reports. Placental abnormalities were characterized as acute only (20%), chronic only (21%), both acute and chronic (43%), and none (15%). The risk of death or NDI was not statistically different between subjects with and without an acute placental abnormality (46 vs. 53%, aRR 1.1, 95% confidence interval (CI): 0.9, 1.4). Subjects with two or more chronic lesions were more likely to have an adverse outcome than subjects with no chronic abnormalities, though this did not reach statistical significance (55 vs. 45%, aRR 1.24, 95% CI: 0.99, 1.56). CONCLUSION: Placental pathologic findings were not independently associated with risk of death or NDI in subjects with HIE. The relationship between multiple chronic placental lesions and HIE outcomes deserves further study.

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.

The PURPOSe cause of death study in stillbirths and neonatal deaths in India and Pakistan: A review.

The PURPOSe study was a prospective, observational study conducted in India and Pakistan to determine the cause of death for stillbirths and preterm neonatal deaths, using clinical data together with minimally invasive tissue sampling (MITS) and the histologic and polymerase chain reaction (PCR) evaluation of fetal/neonatal tissues and the placenta. After evaluating all available data, an independent panel chose a maternal, a placental and a fetal/neonatal cause of death. Here, we summarise the major results. Among the most important findings were that most stillbirths were caused by fetal asphyxia, often preceded by placental malperfusion, and clinically associated with pre-eclampsia, placental abruption and a small-for-gestational-age fetus. The preterm neonatal deaths were primarily caused by birth asphyxia, followed by various infections. An important finding was that many of the preterm neonatal deaths were caused by a nosocomial infection acquired after neonatal intensive care (NICU) admission; the most common organisms were Acinetobacter baumannii, followed by Klebsiella pneumoniae, Escherichia coli/Shigella and Haemophilus influenzae. Group B streptococcus was less commonly present in the placentas or internal organs of the neonatal deaths.

The role of the placenta in perinatal asphyxia, neonatal encephalopathy, and neurodevelopmental outcome: A review.

Perinatal asphyxia contributes significantly to neonatal deaths globally. This may occur due to the effects of various phenomena like uterine rupture, infections, maternal hemodynamic compromise (amniotic fluid embolus), placenta, and umbilical cord (umbilical cord knot, placental abruption, or compression). Perinatal asphyxia is the term used for interrupted blood flow or the exchange of gases in the fetus during the prenatal period. The reduced oxygenation induces a cascade of brain injuries, resulting in long-term damage to the infant's brain. Some infants exposed to perinatal hypoxia-ischemia will make an immediate recovery and have normal survival, while others may suffer from an evolving clinical encephalopathy. This review article focuses on the relationship between the placenta, neonatal encephalopathy, and neurodevelopmental outcome. It also aims to identify possible interventions and drive the focus of policymakers towards issues that evolve around perinatal asphyxia, neonatal encephalopathy, and neonatal care and that have a high impact on infant morbidity in sub-Saharan Africa.