Perinatal Hypoxic-ischemic Insult Research Articles

Early changes in cerebral metabolism after perinatal hypoxia-ischemia: a study in normothermic and hypothermic piglets.

Hypoxic ischemic encephalopathy (HIE) after a perinatal insult is a dynamic process that evolves over time. Therapeutic hypothermia (TH) is standard treatment for severe to moderate HIE. There is a lack of evidence on the temporal change and interrelation of the underlying mechanisms that constitute HIE under normal and hypothermic conditions. We aimed to describe early changes in intracerebral metabolism after a hypoxic-ischemic insult in piglets treated with and without TH and in controls. Three devices were installed into the left hemisphere of 24 piglets: a probe measuring intracranial pressure, a probe measuring blood flow and oxygen tension, and a microdialysis catheter measuring lactate, glucose, glycerol, and pyruvate. After a standardized hypoxic ischemic insult, the piglets were randomized to either TH or normothermia. Glycerol, a marker of cell lysis, increased immediately after the insult in both groups. There was a secondary increase in glycerol in normothermic piglets but not in piglets treated with TH. Intracerebral pressure, blood flow, oxygen tension, and extracellular lactate remained stable during the secondary increase in glycerol. This exploratory study depicted the development of the pathophysiological mechanisms in the hours following a perinatal hypoxic-ischemic insult with and without TH and controls.

Early Plasma Magnesium in Near-Term and Term Infants with Neonatal Encephalopathy in the Context of Perinatal Asphyxia.

Magnesium ions are implicated in brain functioning. The disruption of brain metabolism subsequent to a perinatal hypoxic-ischaemic insult may be reflected by plasma magnesium. Infants at 36 weeks after birth or later with neonatal encephalopathy and who were admitted to our neonatal unit from 2011 to 2019 were retrospectively included. The kinetics of plasma magnesium were investigated for the first 72 h of life and correlated to the Barkovich MRI score. Among the 125 infants who met the inclusion criteria, 45 patients (36%) had moderate to severe brain lesions on neonatal MRI. Plasma magnesium values were not strongly associated with the severity of clinical encephalopathy, initial EEG background and brain lesions. Intriguingly, higher plasma magnesium values during the 0–6 h period were linked to the presence of brain injuries that predominated within the white matter (p < 0.001) and to the requirement of cardiac resuscitation in the delivery room (p = 0.001). The occurrence of seizures was associated with a lower mean magnesium value around the 24th hour of life (p = 0.005). This study supports that neonatal encephalopathy is a complex and multifactorial condition. Plasma magnesium could help to better identify the subtypes of neonatal encephalopathy. Further studies are needed to confirm these results in this prospect.

The effect of sulforaphane on perinatal hypoxic-ischemic brain injury in rats.

Perinatal hypoxic-ischemic insult (HII) is one of the main devastating causes of morbidity and mortality in newborns. HII induces brain injury which evolves to neurological sequelae later in life. Hypothermia is the only therapeutic approach available capable of diminishing brain impairment after HII. Finding a novel therapeutic method to reduce the severity of brain injury and its consequences is critical in neonatology. The present paper aimed to evaluate the effect of sulforaphane (SFN) pre-treatment on glucose metabolism, neurodegeneration, and functional outcome at the acute, sub-acute, and sub-chronic time intervals in the experimental model of perinatal hypoxic-ischemic insult in rats. To estimate the effect of SFN on brain glucose uptake we have performed 18F-deoxyglucose (FDG) microCT/PET. The activity of FDG was determined in the hippocampus and sensorimotor cortex. Neurodegeneration was assessed by histological analysis of Nissl-stained brain sections. To investigate functional outcomes a battery of behavioral tests was employed. We have shown that although SFN possesses a protective effect on glucose uptake in the ischemic hippocampus 24 h and 1 week after HII, no effect has been observed in the motor cortex. We have further shown that the ischemic hippocampal formation tends to be thinner in HIE and SFN treatment tends to reverse this pattern. We have observed subtle chronic movement deficit after HII detected by ladder rung walking test with no protective effect of SFN. SFN should be thus considered as a potent neuroprotective drug with the capability to interfere with pathophysiological processes triggered by perinatal hypoxic-ischemic insult.

A case series of neonatal human parecho-virus encephalitis with a seasonality and endemicity

Human parecho viruses are small, non-enveloped, single stranded RNA viruses within parechovirus genus of the large picornaviridae family. In new-born it can cause gastroenteritis, sepsis and encephalitis. We report case series of parecho-virus encephalitis admitted to a tertiary care centre, Perinthalmanna. Parechoviral encephalitis is an endemic disease seasonally present (May-July) in certain regions of Northern part of Kerala. HPeV are viruses that cause CNS infection in the neonatal period, resulting in white matter lesions that can be visualised with MRI. In a retrospective study, 4 newborn babies of neonatal HPeV encephalitis diagnosed on the basis of clinical and radiological findings with a seasonality were assessed. HPeV encephalitis needs to be in differential diagnosis when neonates and young infants present with seizure and sepsis. HPeV infection must be considered in infants with specific pattern of white matter change but no convincing history of a perinatal hypoxic-ischaemic insult.

CARD8 and IL1B Polymorphisms Influence MRI Brain Patterns in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia.

Inflammation and oxidative stress are recognized as important contributors of brain injury in newborns due to a perinatal hypoxic-ischemic (HI) insult. Genetic variability in these pathways could influence the response to HI and the outcome of brain injury. The aim of our study was to evaluate the impact of common single-nucleotide polymorphisms in the genes involved in inflammation and response to oxidative stress on brain injury in newborns after perinatal HI insult based on the severity and pattern of magnetic resonance imaging (MRI) findings. The DNA of 44 subjects was isolated from buccal swabs. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1B rs16944, IL1B rs1143623, IL1B rs1071676, TNF rs1800629, CAT rs1001179, SOD2 rs4880, and GPX1 rs1050450. Polymorphism in CARD8 was found to be protective against HI brain injury detected by MRI overall findings. Polymorphisms in IL1B were associated with posterior limb of internal capsule, basal ganglia, and white matter brain patterns determined by MRI. Our results suggest a possible association between genetic variability in inflammation- and antioxidant-related pathways and the severity of brain injury after HI insult in newborns.

Impact of Education on Hypothermia Delivery during Neonatal Transport

Background: Moderate therapeutic hypothermia (TH) initiated within 6 h of life reduces adverse neurodevelopmental outcomes in infants after perinatal hypoxic ischaemic insult. For infants born in non-tertiary centres, TH may be initiated manually en route to a neonatal intensive care unit (NICU). However, both over- and undercooling is reported with this strategy, precluding some infants from the benefits of TH. Objectives: To evaluate the impact of a region-wide educational programme on the safety and efficacy of manual cooling administered by the Wellington Neonatal Transport Service (NeTS). Methods: Clinical records of infants with hypoxic ischaemic encephalopathy (HIE) retrieved by the Wellington NeTS for TH between January 2012 and June 2017 were reviewed retrospectively. Temperature outcomes of infants retrieved before and after the education programme were compared. Results: A total of 101 infants were cooled manually by Wellington NeTS for TH during the study period. Education and training significantly reduced the rate of overcooling to ≤32.0°C (4/43 [9%] vs. 0/58, p = 0.02). However, there was no difference in the proportion of infants who achieved target rectal temperature within 6 h of life (29/43 [65%] vs. 35/58 [60%], p = 0.57). Conclusions: Introduction of a region-wide educational programme may have improved the safety of manual cooling during neonatal transport but it had a negligible impact on its efficacy. The use of servo-controlled cooling during transport should therefore be considered to improve access to the optimal neuroprotective benefits of TH for outborn infants with HIE.

Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat

BackgroundDespite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. MethodsUnilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O2, 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. ResultsHI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle treatment group. To determine the involvement of microglia in the process of neuronal loss by HI insult, we further examined the influence of hypoxia on rat primary cultured microglia by the quantitative real-time polymerase chain reaction. Hypoxia did not cause the upregulation of interleukin-1beta (IL-1β) mRNA expression, but decreased the microglial intrinsic nitric oxide synthase (iNOS)/arginase1 mRNA expression ratio. NE treatment further decreased the microglial iNOS/arginase1 mRNA expression ratio. In contrast, no significant neuroprotective effect was observed at P14 when atomoxetine was administered at 3 h after HI insult. ConclusionsThese findings suggested that the enhancement of intrinsic neurotransmitter NE signaling by a selective NE reuptake inhibitor, atomoxetine, reduced the perinatal HI insult brain injury. In addition, atomoxetine treatment was associated with changes of TUNEL, pCREB, and BDNF expression levels, and microglial numbers, morphology, and responses.

Prognostic factors of neurological outcomes in late-preterm and term infants with perinatal asphyxia.

PurposeThis study aimed to identify prognostic factors of neurological outcomes, including developmental delay, cerebral palsy and epilepsy in late-preterm and term infants with perinatal asphyxia.MethodsAll late-preterm and term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the neonatal intensive care unit of Inje University Sanggye Paik Hospital between 2006 and 2014 and were followed up for at least 2 years were included in this retrospective study. Abnormal neurological outcomes were defined as cerebral palsy, developmental delay and epilepsy.ResultsOf the 114 infants with perinatal asphyxia, 31 were lost to follow-up. Of the remaining 83 infants, 10 died, 56 had normal outcomes, and 17 had abnormal outcomes: 14 epilepsy (82.4%), 13 cerebral palsy (76.5%), 16 developmental delay (94.1%). Abnormal outcomes were significantly more frequent in infants with later onset seizure, clinical seizure, poor electroencephalography (EEG) background activity, lower Apgar score at 1 and 5 minutes and abnormal brain imaging (P<0.05). Infants with and without epilepsy showed significant differences in EEG background activity, clinical and electrographic seizures on EEG, Apgar score at 5 minutes and brain imaging findings.ConclusionWe should apply with long-term video EEG or amplitude integrated EEG in order to detect and management subtle clinical or electrographic seizures in neonates with perinatal asphyxia. Also, long-term, prospective studies with large number of patients are needed to evaluate more exact prognostic factors in neonates with perinatal asphyxia.

Neonatal parechovirus leucoencephalitis- radiological pattern mimicking hypoxic-ischemic encephalopathy

AimOur objective is to study the MR imaging pattern in neonatal parechoviral leucoencephalitis, a rare cause of neonatal white matter abnormality and to differentiate it from hypoxic-ischemic encephalopathy which is the commonest cause of white matter change in neonates. MethodWe evaluated 25 neonates who presented with features of encephalopathy. Cranial ultrasound and MR imaging was done in all the cases. The pattern of white matter abnormality was analyzed in all cases. ResultsNeonatal leucoencephalitis caused by HPeV has a distinctive clinical presentation and has predilection for the white matter, causing diffusion restricting signal intensity changes involving the periventricular and subcortical white matter, in particular the frontal white matter, also the corpus callosum, internal capsule, external capsule and pyramidal tracts of the supratentorial brain and cerebral peduncle with relative sparing of occipital white matter, thalamus, basal ganglia and the infratentorial regions. Follow up imaging shows disappearance of the lesion without white matter loss. Whereas mild to moderate hypoxic-ischemic injury in a full-term neonate causes lesions in the watershed areas, and subcortical white matter predominantly involving the parietooccipital region and perirolandic region. Thalamus, brainstem, cerebellum, and deep gray matter structures are involved depending on the severity. ConclusionWhite matter changes in the neonatal period are commonly associated with hypoxic-ischemic injuries and metabolic causes, less frequently, infection like parechovirus leucoencephalitis. HPeV infection must be considered in infants with specific pattern of white matter change but no convincing history of a perinatal hypoxic-ischemic insult, thus differentiating it from HIE.

Multicenter programme for the integrated care of newborns with perinatal hypoxic-ischaemic insult (ARAHIP)

Introduction: Newborns with perinatal indicators of a potential hypoxic-ischaemic event require an integrated care in order to control the aggravating factors of brain damage, and the early identification of candidates for hypothermia treatment.

Hyperhomocysteinemia and MTHFR polymorphisms as antenatal risk factors of white matter abnormalities in two cohorts of late preterm and full term newborns.

Higher total homocysteine (tHcy) levels, and C677T and A1298C methylenetetrahydrofolate (MTHFR) polymorphisms, have been reported in preterm or full term newborns with neonatal encephalopathy following perinatal hypoxic-ischemic insult. This study investigated the causal role of tHcy and MTHFR polymorphisms together with other acquired risk factors on the occurrence of brain white matter abnormalities (WMA) detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. A total of 171 newborns (81 M, 47.4%), 45 (26.3%) born <37 wks, and 126 (73.7%) born ≥37 wks were recruited in the study. cUS detected predominant WMA pattern in 36/171 newborns (21.1%) mainly characterized by abnormal periventricular white matter signal and mild-to-moderate periventricular white matter volume loss with ventricular dilatation (6/36, 16.6%). WMA resulted in being depending on tHcy levels (P < 0.014), lower GA (P < 0.000), lower Apgar score at 1 minutes (P < 0.000) and 5 minutes (P < 0.000), and 1298AC and 677CT/1298AC genotypes (P < 0.000 and P < 0.000). In conclusion, both acquired and genetic predisposing antenatal factors were significantly associated with adverse neonatal outcome and WMA. The role of A1298C polymorphism may be taken into account for prenatal assessment and treatment counseling.

PS-108 Urinary Biomarkers May Help Predict Outcome In Neonatal Encephalopathy

Background Following a perinatal hypoxic-is chaemic insult, term infants are at risk of multi-organ injury including AKI. Infants with NE experience up-regulation of urinary cytokines which may reflect severity of brain injury. Objective To investigate the association between novel urinary biomarkers and outcome in a group of term infants with NE compared to controls. Methods Levels of urinary biomarkers [Albumin, B2M, Cystatin-C, EGF, NGAL, Osteopontin, Uromodulin] were serially measured over day 1–11 in a group of term newborns with NE and controls. These values were compared to grade of encephalopathy defined by Sarnat score. Results Ten control and 82 cases had urine samples collected (Grade 0 NE = 7, Grade I NE = 22, Grade II NE = 42, Grade III NE = 11). Thirty-nine infants underwent TH, 4 infants died. Control infants had significantly lower B2M on day 1, NGAL on day 1–2 and significantly higher urinary EGF on day 2–3 and Uromodulin on day 3, compared with cases (p-values Conclusion Infants with NE have elevated urinary biomarkers compared to controls. Abnormal grade of encephalopathy is best predicted by day 2 urinary Cystatin-C and day 3 NGAL. Urinary biomarkers may have a role in long term outcome prediction following NE.

Programa multicéntrico para la atención integral del recién nacido con agresión hipóxico-isquémica perinatal (ARAHIP)

IntroductionNewborns with perinatal indicators of a potential hypoxic-ischemic event require an integrated care in order to control the aggravating factors of brain damage, and the early identification of candidates for hypothermia treatment. Patients and methodsThe application of a prospective, populational program that organizes and systematizes medical care during the first 6hours of life to all newborns over 35 weeks gestational age born with indicators of a perinatal hypoxic-ischemic insult. The program includes 12 hospitals (91,217 m2); two level i centers, five level ii centers, and five level iii hospitals. The program establishes four protocols: a) detection of the newborn with a potential hypoxic-ischemic insult, b) surveillance of the neurological repercussions and other organ involvement, c) control and treatment of complications, d) procedures and monitoring during transport. ResultsFrom June 2011 to June 2013, 213 of 32325 newborns above 35 weeks gestational age met the criteria of a potential hypoxic-ischemic insult (7.4/1000), with 92% of them being cared for following the program specifications. Moderate-severe hypoxic-ischemic encephalopathy was diagnosed in 33 cases (1/1,000), and 31 out of the 33 received treatment with hypothermia (94%). ConclusionsThe program for the Integrated Care of Newborns with Perinatal Hypoxic-Ischemic Insult has led to providing a comprehensive care to the newborns with a suspected perinatal hypoxic-ischemic insult. Aggravators of brain damage have been controlled, and cases of moderate-severe hypoxic-ischemic encephalopathy have been detected, allowing the start of hypothermia treatment within the first six hours of life. Populational programs are fundamental to reducing the mortality and morbidity of hypoxic-ischemic encephalopathy.

Neuroprotective effect of the 3α5β-pregnanolone glutamate treatment in the model of focal cerebral ischemia in immature rats

The perinatal hypoxic-ischemic insult frequently leads to mortality, morbidity and plays a key role in the later pathological consequences. The ischemic insult causes a massive release of glutamate and subsequent excitotoxic damage. The neuroactive steroid 3α5β-pregnanolone glutamate (PG) is a NMDA receptor antagonist acting via use-dependent mechanism and can be used as a neuroprotective agent that may alleviate glutamatergic excitotoxicity in the brain.First, a possible neurotoxic effect of the PG, a novel use-dependent NMDA antagonist, was studied in immature rats. In addition, to compare this effect with a well-described non-competitive NMDA antagonist, the MK-801 (positive control) was used. Animals at postnatal day 12 (P12) were injected intraperitoneally with PG in a doses 1 or 10mg/kg or with MK-801 in a dose 1mg/kg. Effect of PG treatment on the immature brain was evaluated on Fluoro Jade B (FJB) stained sections. Second, a neuroprotective effect of the PG was studied in the model of focal cerebral ischemia in P12. Focal cerebral ischemia was induced by the infusion of the endothelin-1 (ET-1) into the right dorsal hippocampus. PG at the doses 1 or 10mg/kg was administrated intraperitoneally 5min after the end of ET-1 infusion. To evaluate the neuroprotective effect after the PG treatment FJB staining was used. Our results demonstrate a lack of the neurotoxicity of the PG in intact P12. In the second part of the study in the model of the focal ischemia we detected significantly lower occurrence of FJB-positive cells in the afflicted hippocampus in PG treated groups, while animals without PG treatment exhibited massive neurodegeneration. The neuroprotective potential of the PG can serve in the development of therapeutic strategies for brain damage induced by the glutamate excitotoxicity.

Hypoxic-ischemic neonatal encephalopathy: animal experiments for neuroprotective therapies.

Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+)-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult.

Neonatal encephalopathy: An inadequate term for hypoxic–ischemic encephalopathy

This Point of View article addresses neonatal encephalopathy (NE) presumably caused by hypoxia-ischemia and the terminology currently in wide use for this disorder. The nonspecific term NE is commonly utilized for those infants with the clinical and imaging characteristics of neonatal hypoxic-ischemic encephalopathy (HIE). Multiple magnetic resonance imaging studies of term infants with the clinical setting of presumed hypoxia-ischemia near the time of delivery have delineated a topography of lesions highly correlated with that defined by human neuropathology and by animal models, including primate models, of hypoxia-ischemia. These imaging findings, coupled with clinical features consistent with perinatal hypoxic-ischemic insult(s), warrant the specific designation of neonatal HIE.

Late outcome following neonatal hypoxic-ischemic encephalopathy

Finding early biomarkers that can predict the late outcome of neonates who suffer a perinatal hypoxic-ischemic insult has been the subject of numerous studies over the last decade. In this issue of The Journal, Shankaran et al report the ability of a low-cost, low-tech biomarker—the serial neurologic examination—to predict long term outcomes in term infants with hypoxic-ischemic encephalopathy (HIE). The authors performed careful neurologic exams on infants enrolled in the NICHD trial of whole body hypothermia, during the first 72 hours and at neonatal discharge, and examined the ability of the neurologic exams to predict the primary outcome of death or disability at 18 months of age.

Correlation between Periventricular Leukomalacia and Retinopathy of Prematurity

To investigate the correlation between periventricular leukomalacia (PVL) and retinopathy of prematurity (ROP), which are complications of perinatal and postnatal hypoxic-ischemic insults in premature infants. In this retrospective case series study, from 1996 to 2008, after excluding cases with follow-up of less than 3 months, we reviewed medical charts of babies who had gestational age (GA) less than 30 weeks or birthweight (BW) less than 2000 g. A total of 195 patients were diagnosed with ROP and/or PVL and were enrolled in this analysis. We investigated the correlation between ROP and PVL with Pearson chi-square test and evaluated BW, GA, and Apgar scores at 1 minute and 5 minutes after birth as risk factors by independent t test. There were no significant differences in the prevalence of PVL between patients who received ROP treatment and those who did not receive ROP treatment. The BW was significantly lower in patients with PVL than in patients without PVL. Gestational age, BW, and Apgar scores significantly differed between patients who did and did not receive retinal treatment for ROP. Periventricular leukomalacia did not increase the severity of ROP or requirement of ROP treatment. Birthweight, GA, and Apgar scores were the principal factors that determined the necessity of ROP treatment.

Cardiac biomarkers in neonatal hypoxic ischaemia

Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

The prognostic role of evoked potentials in neonatal hypoxic-ischemic insult

Neonatal encephalopathy is a significant cause of infant mortality and morbidity with risk of neurological sequelae in the survivors of neonates admitted to Neonatal (N) Intensive Care Unit (ICU). The EEG and Evoked Potentials (EPs) are very informative in the ICU. In particular, it is known that the SomatoSensory (SS) EPs are the best single indicator of early prognosis in adults and children patients with traumatic and/or hypoxic-ischemic coma compared to the Glasgow Coma Scale (GCS) and CTscan. Most paediatric studies excluded newborns in an attempt to eliminate the age effects, because of the structural and functional immaturity of somatosensory system. In fact, newborns differ from adults and paediatric patients for many aspects: hypoxic-ischemic aetiology, SSEPs normative data, grading and predictive values, timing and techniques recording, clinical scales of evaluation. Recently a diagnostic and predictive role of early SSEPs has been established in perinatal hypoxic-ischemic. We reported a literature review of early diagnostic/prognostic role of SSEPs and our preliminary neurophysiological data of prospective study in mild or severe perinatal hypoxic-ischemic insult.