This article summarizes the current evidence regarding inflammatory biomarkers (placental and postnatal) and provides a comprehensive understanding of their roles: (1) diagnostic accuracy to predict the severity of hypoxic-ischemia encephalopathy (HIE), (2) value in assessing treatment responses, and (3) prediction of both short- and long-term neurodevelopmental outcomes. In the early critical stages of perinatal asphyxia, inflammatory biomarkers may guide clinical decision-making. Additional research is required to increase our understanding of the optimal utility of biomarkers to predict the severity, evolution, and developmental outcomes after exposure to HIE.

BACKGROUND: 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.
METHODS: 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.

BACKGROUND: 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.
CONCLUSIONS: 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.

OBJECTIVE: To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE).
METHODS: This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability).
RESULTS: Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53-0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58-0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34-1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86-10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14-1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision.
CONCLUSIONS: Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.

Asphyxiated newborns often require both therapeutic hypothermia (TH) and mechanical ventilation (MV) and the complex interrelationship between these two therapeutic interventions is very interesting, which could not only have several synergistic positive effects but also some risks. Perinatal asphyxia is the leading cause of neonatal hypoxic-ischemic encephalopathy (HIE) and TH is the only approved neuroprotective treatment to limit brain injury, improving the mortality rate and long-term neurological outcomes. HIE is often associated with severe respiratory failure, requiring MV, due to different lung diseases or an impairment of the respiratory drive. The respiratory support management of asphyxiated newborns is very difficult, considering (a) various pathophysiological contexts, (b) the strong impact of TH on gas metabolism and (c) on lung mechanics, and (d) complex TH-MV interactions. Therefore, it is necessary to evaluate the real indications of MV for cooled newborns, considering the risks of respiratory overassistance (hypocapnia/hyperoxia), as well as the adequate monitoring systems. To date, specific randomized studies about the optimal respiratory approach for cooled newborns are lacking, and strategies for MV support vary from center to center. Moreover, there are many open questions about the real effects of cooling on lung mechanics and on surfactant, most appropriate method of blood gas analysis, and clear indications for pharmacological sedation. The aim of this review is to propose a reasoned approach for respiratory management of cooled newborns, considering the pathophysiological context, multiple actions of TH, and consequences of TH-MV matched action and its related risks.

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.

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.

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BACKGROUND: Despite evidence on the prenatal pathogenesis of Cerebral Palsy (CP), there are many instances where obstetricians face litigation for malpractice.
OBJECTIVE: A scoping review of research on the association of CP with \"difficult\" delivery in term neonates.
METHODS: For the purposes of this review an internet search was performed using credible electronic databases.
RESULTS: There are more than 32,500 citations under the keyword cerebral palsy, the majority of which, focus on diagnosis and treatment. Only 451 citations were included in the final review, associated with perinatal asphyxia, birth trauma, difficult delivery and obstetric litigations. Additionally, 139 medical books from various specialties were included in the research.
CONCLUSIONS: The sequence of events is hereby presented, through which the original connection between CP and delivery, has gradually been cut off. Meanwhile, all contributing factors of difficult delivery are evaluated. Persistent abnormal fetal attitude seems to be strongly connected to the difficult birth in affected term neonates. Vaginal delivery is accomplished only after sufficient passive flexion of the fetal head, achieved by additional expulsive efforts by both the mother and the assisting personnel. This additional force is perceived by the parents to be as the principal etiology of CP in their infant. In the past decades, there has been increasing evidence pertaining fetal perceptual abilities and cognitive functions.
CONCLUSIONS: Difficult birth may be the first, amongst the early manifestations of neonatal encephalopathy.

Current diagnostic criteria for hypoxic-ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610).
Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle-Ottawa Scale. The search and data extraction were verified by two authors separately.
From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic-ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult.
Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.