Signs Of Hypoxic-ischemic Encephalopathy Research Articles

Brain injury markers in blood predict signs of hypoxic ischaemic encephalopathy on head computed tomography after cardiac arrest

Background/AimSigns of hypoxic ischaemic encephalopathy (HIE) on head computed tomography (CT) predicts poor neurological outcome after cardiac arrest. We explore whether levels of brain injury markers in blood could predict the likelihood of HIE on CT. MethodsRetrospective analysis of CT performed at 24–168 h post cardiac arrest on clinical indication within the Target Temperature Management after out-of-hospital cardiac arrest-trial. Biomarkers prospectively collected at 24- and 48 h post-arrest were analysed for neuron specific enolase (NSE), neurofilament light (NFL), total-tau and glial fibrillary acidic protein (GFAP). HIE was assessed through visual evaluation and quantitative grey-white-matter ratio (GWR) was retrospectively calculated on Swedish subjects with original images available. ResultsIn total, 95 patients were included. The performance to predict HIE on CT (performed at IQR 73–116 h) at 48 h was similar for all biomarkers, assessed as area under the receiving operating characteristic curve (AUC) NSE 0.82 (0.71–0.94), NFL 0.79 (0.67–0.91), total-tau 0.84 (0.74–0.95), GFAP 0.79 (0.67–0.90). The predictive performance of biomarker levels at 24 h was AUC 0.72–0.81. At 48 h biomarker levels below Youden Index accurately excluded HIE in 77.3–91.7% (negative predictive value) and levels above Youden Index correctly predicted HIE in 73.3–83.7% (positive predictive value). NSE cut-off at 48 h was 48 ng/ml. Elevated biomarker levels irrespective of timepoint significantly correlated with lower GWR. ConclusionBiomarker levels can assess the likelihood of a patient presenting with HIE on CT and could be used to select suitable patients for CT-examination during neurological prognostication in unconscious cardiac arrest patients.

Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study

SummaryBackgroundTherapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes.MethodsWe did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit.Findings6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2–0·9] in the fed group vs 1·1% [0·7–1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference −11·6% [95% CI −14·0 to −9·3]; p<0·0001), higher survival to discharge (5·2% [3·9–6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1–10·8]; p<0·0001), and shorter neonatal unit stays (−2·2 [–3·0 to −1·2] days; p<0·0001) compared with the unfed group.InterpretationNecrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia.FundingUK National Institute for Health Research Health Technology Assessment programme 16/79/13.

Detection of myocardial injury in perinatal asphyxia by echocardiography and cardiac biomarkers

Perinatal hypoxia can induces cardiac (Cd) injury in the newborn and requires an early diagnosis. Cd troponin I (cTnI) is correlated to hypoxic myocardial lesion-may be a useful marker of it Objectives: to evaluate the utility of echocardiography(echo) and research of cTnI values for diagnosis of myocardial injury. Patients: 98 newborns (0–14 days), with perinatal hypoxia, without major Cd anomalies, to wich were performed: clinical exam, ECG, Rx.CT, echo, research of cTnT values. The patients had mainly signs of neurological post hypoxic suffering without signs of Cd distress. The Cd exam: tachycardia, systolic murmur (64 pts); RxCT: cardiomegaly (35); ECG: LV repolarization disturbances (37);. Echo at 2–7 days of life: the absence of severe Cd malformations; myocardial LV hypertrophy (42 pts); normal LV systolic function(all); LV diastolic dysfunction (45 pts).The importance of Cd involvement were correlated with signs of hypoxic ischemic encephalopathy. The pts received spironolactone 1 mg/kg/day for 1 month, then 1 mg/Kg at 2 days (the alternating pattern) for 2–3 months. Evolution: absence of new myocardial suffering signs, is maintains systolic murmur (2/3 pts); reevaluation of echo at 6 months: the reduction of the myocardial hypertrophy, normal LV diastolic function; elevated cTnT values (> 0.12 μg/l): 56% pts with perinatal hypoxic suffering. The perinatal hypoxia can induce the apparition of post hypoxic hypertrophic cardiomyopathy(HCMP)(69% pts), LV diastolic function disturbancies and normal systolic LV function, even if the signs of Cd suffering missing often; echo is the main method for diagnosis and follow up of perinatal hypoxic HCMP and is necessary from the first week of life; increased values of cTnT(> 0.12 μg/l) in perinatal asphyxia prove hypoxi c myocardial damage; traitement with spironolactone for 2–3 months induced improving of HCMP and normalising of LV diastolic disfunction and cTnI values.

Wavelet Spectral Deep-training of Convolutional Neural Networks for Accurate Identification of High-Frequency Micro-Scale Spike Transients in the Post-Hypoxic-Ischemic EEG of Preterm Sheep.

Early diagnosis and prognosis of babies with signs of hypoxic-ischemic encephalopathy (HIE) is currently limited and requires reliable prognostic biomarkers to identify at risk infants. Using our pre-clinical fetal sheep models, we have demonstrated that micro-scale patterns evolve over a profoundly suppressed EEG background within the first 6 hours of recovery, post HI insult. In particular, we have shown that high-frequency micro-scale spike transients (in the gamma frequency band, 80-120Hz) emerge immediately after an HI event, with much higher numbers around 2-2.5 h of the insult, with numbers gradually declining thereafter. We have also shown that the automatically quantified sharp waves in this phase are predictive of neural outcome. Initiation of some neuroprotective treatments within this limited window of opportunity, such as therapeutic hypothermia, optimally reduces neural injury. In clinical practice, it is hard to determine the exact timing of the injury, therefore, reliable automatic identification of EEG transients could be beneficial to help specify the phases of injury. Our team has previously developed successful machine- and deep-learning strategies for the identification of post-HI EEG patterns in an HI preterm fetal sheep model.This paper introduces, for the first time, a novel online fusion approach to train an 11-layers deep convolutional neural network (CNN) classifier using Wavelet-Fourier (WF) spectral features of EEG segments for accurate identification of high-frequency micro-scale spike transients in 1024Hz EEG recordings in our preterm fetal sheep. Sets of robust features were extracted using reverse biorthogonal wavelet (rbio2.8 at scale 7) and considering an 80-120Hz spectral frequency range. The WF-CNN classifier was able to accurately identify spike transients with a reliable high-performance of 99.03±0.86%.Clinical relevance-Results confirm the expertise of the method for the identification of similar patterns in the EEG of neonates in the early hours after birth.

Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study

BackgroundIdentification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE.MethodsA retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors.ResultsMRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect.ConclusionHIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.

Factors associated with neonatal hypoxic ischemic encephalopathy in infants with an umbilical artery pH less than 7.00

ObjectiveOur objective was to identify factors associated with hypoxic-ischemic encephalopathy (HIE) among newborns with an umbilical pH < 7.00. Study designCase-control study during a four-year study period in a single academic tertiary-center, including all neonates ≥35 weeks with an umbilical pH < 7.00. Cases were neonates with HIE, regardless of Sarnat classification, and controls were neonates without signs of HIE. We used univariate and multivariate analysis to compare the maternal, obstetric, and neonatal characteristics of cases and controls. ResultsAmong 21,211 births, 179 neonates≥35 weeks (0.84%) had an umbilical pH < 7.00. One hundred and forty-seven(82.1%) newborns had severe asphyxia without HIE, 32(17.9%) had HIE and 21(11.7%) needed therapeutic hypothermia. Neonates with HIE were significantly more likely to have 5-minute Apgar score<7(75% versus 15.7% P < 0.01), together with a lower mean umbilical arterial pH (6.84 versus 6.95, P < 0.01) and lower mean base deficits (-17.0 versus -12.7, P < 0.01). Factors significantly associated with HIE were the mother being overweight(28.1% for cases versus 14.3% for controls, adjusted OR=4.6[1.4–15.2]) or obese(25.0% versus 13.6%, aOR=15.5[1.1–12.5]), smoking(18.7% versus 5.4%, aOR=5.8[1.6–21.2]), a sentinel event as cord prolaps or placenta abruption (34.4% versus 13.6%, aOR=2.7[1.1–7.2]), and decreased fetal heart rate variability(68.7% versus 44.2%, aOR=2.8[1.1–6.9]). ConclusionAmong neonates with an umbilical cord pH < 7.00, those with HIE had a more severe metabolic acidosis. Maternal factors associated with HIE among newborns with an umbilical pH < 7.00, were being overweight or obese, and smoking, and the associated obstetric factors were a sentinel event and decreased fetal heart rate variability.

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study

Purpose: To investigate the feasibility of a study based on treatment with topiramate (TPM) added to moderate hypothermia in newborns with hypoxic ischemic encephalopathy (HIE). Materials and methods: Multicenter randomized controlled trial. Term newborns with precocious metabolic, clinical and electroencephalographic (EEG) signs of HIE were selected according to their amplified integrated EEG pattern and randomized to receive either TPM (10 mg/kg once a day for the first three days of life) plus moderate hypothermia or hypothermia alone. Safety was assessed by monitoring cardiorespiratory parameters and blood samples collected to check renal, liver, metabolic balance and TPM pharmacokinetics. Efficacy was evaluated by the combined frequency of mortality and severe neurological disability as primary outcome. Incidence of magnetic resonance injury, epilepsy, blindness, hearing loss, neurodevelopment at 18–24 months of life was assessed as secondary outcomes. Results: Forty-four asphyxiated newborns were enrolled in the study. Twenty one newborns (10 with moderate and 11 with severe HIE) were allocated to hypothermia plus TPM and 23 (12 moderate and 11 severe HIE) to hypothermia. No statistically or clinically significant differences were observed for safety, primary or secondary outcomes. However, a reduction in the prevalence of epilepsy was observed in newborns co-treated with TPM. Conclusions: Results of this pilot trial suggest that administration of TPM in newborns with HIE is safe but does not reduce the combined frequency of mortality and severe neurological disability. The role of TPM co-treatment in preventing subsequent epilepsy deserves further studies.

Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns

Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.

Outcome After Therapeutic Hypothermia in Term Neonates With Encephalopathy and a Syndromic Diagnosis.

The large randomized, controlled trials of therapeutic hypothermia for hypoxic-ischemic encephalopathy excluded neonates with congenital disorders. The objective of this study was to report our experience using hypothermia in neonates with signs of hypoxic-ischemic encephalopathy and a syndromic disorder or brain anomaly. Subjects were identified from a database of neonates admitted to the Neuro-Intensive Care Nursery at University of California, San Francisco. Of 169 patients fulfilling criteria for hypothermia, 8 (5%) had a syndromic disorder and were cooled per guidelines for nonsyndromic neonates. Perinatal characteristics of infants with and without syndromic disorder were not significantly different. Overall outcome was poor: 38% had evidence of acute hypoxic-ischemic injury, 3 subjects died, and 2 survivors had low developmental quotient (ie, 25). The risk versus benefit of therapeutic hypothermia for hypoxic-ischemic encephalopathy among neonates with congenital brain malformations or syndromic diagnoses is uncertain.

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

BackgroundDespite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment.Methods/DesignTerm newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests.DiscussionThis pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns.Trial registrationCurrent Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25

Selective cerebral hypothermia for post-hypoxic neuroprotection in neonates using a solid ice cap.

The main objective of this study was to study the safety and efficacy of a simple, cost-effective method of selective head cooling with mild systemic hypothermia in newborn infants with hypoxic ischaemic encephalopathy. Ethical approval was obtained for a randomized controlled study in which 20 asphyxiated neonates with clinical signs of hypoxic ischaemic encephalopathy would be randomised into cooled and non-cooled groups. However, after cooling the first 4 babies, it was clear that repeated revisions to the cooling technique had to be made which was inappropriate in the context of a randomised controlled trial. The study was therefore stopped and the data for the 4 cooled infants are presented here in the form of a technical report. Hypothermia was achieved by applying an insulated ice cap to the heads of the infants and replacing it at 2-3-hourly intervals, aiming to achieve a target rectal temperature of 35-35.5 degrees C and a target scalp temperature of 10-28 degrees C. This study was carried out between July 2000 and September 2001 in the neonatal units of Groote Schuur Hospital and Mowbray Maternity Hospital, Cape Town. Term infants with signs of encephalopathy were recruited within the first 8 hours of life if they had required resuscitation at birth and had significant acidosis within the first hour of life. Target rectal temperature was achieved in all infants, but large variations in incubator and scalp temperatures occurred in 3 of the 4 infants. Reducing the target core temperature in a stepwise manner did not prevent excessive temperature variation and resulted in a longer time to reach target temperature. There was least variation in scalp temperature when the ice pack was covered in two layers of mutton cloth before application, but the resulting scalp temperatures were above the target temperature. The maximum scalp temperature variation was reduced from 22 degrees C to 12 degrees C using this method. Nasopharyngeal temperatures varied excessively within less than a minute, suggesting that air cooling via mouth breathing was occurring. The surface site that correlated best with deep rectal temperature was the back, with the infant supine. During cooling, the respiratory rate and heart rate dropped while the mean arterial blood pressure was elevated. There were no irreversible adverse events due to cooling, but infants did become agitated and exhibited shivering which required sedation and analgesia. Nasopharyngeal temperature monitoring was not reliable as an acute clinical indicator of brain temperature in these spontaneously breathing infants, and the back temperature in supine infants correlated better with deep rectal temperature than did exposed skin temperature. This method of cooling achieved systemic cooling but there were large variations in regional temperatures in 3 of the 4 infants. The variations in temperature were probably due to the excessive cooling effect of the ice cap, coupled with the use of external heating to maintain systemic temperature at 35-35.5 degrees C. Variation in temperature was reduced when additional insulation was provided. However, the additional insulation resulted in the loss of the selective cerebral cooling effect. This cooling technique was therefore not an appropriate method of selective head cooling, but did successfully induce systemic hypothermia. This method of insulating an ice cap could therefore be used to induce whole-body cooling but the use of lower core temperatures of 33-34 degrees C is recommended as this will probably result in fewer regional temperature fluctuations. Ideally a more uniform method of cooling should be used.

Distortion product otoacoustic emissions in term infants with a low Apgar score

Conclusion. Term infants with a low Apgar score have cochlear impairment, mainly at the frequencies 1–3 kHz. Compared with infants with both a low Apgar score and hypoxic-ischaemic encephalopathy we reported before, the impairment is less severe. Objective. To detect any peripheral impairment of cochlear origin in infants with a low Apgar score. Subjects and methods. Fifty-four term infants with a low Apgar score at 1 and/or 5 min but without clinical signs of hypoxic-ischaemic encephalopathy were recruited. Distortion product otoacoustic emissions (DPOAEs) were recorded with the f2 primary tone at 10 frequencies (0.5–10 kHz) on days 3–5 and 1 month after birth. Results. On days 3–5 DPOAE pass rates at most frequencies tended to be decreased, and were significant lower than those in normal term controls at 1, 2, 3, 5, 6 and 10 kHz (χ2=4.49–40.31, p<0.05–0.005). The greatest difference occurred at 1 kHz; 18.5% failed the DPOAE test and this was significantly higher than in the controls (4.3%, χ2=7.65, p<0.01). At 1 month the DPOAE pass rate at most frequencies did not show any significant improvement. The overall failure rate (14.8%) did not differ significantly from that on days 3–5.

Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy

The aim of this study was to evaluate serum concentrations of neuron-specific enolase (NSE) as a marker of the severity of hypoxic ischemic encephalopathy (HIE) and to elucidate the relation among the concentrations of NSE, grade of HIE and short-term outcome. Forty-three asphyxiated full-term newborn infants who developed symptoms and signs of HIE (Group 1) and 29 full-term newborn infants with meconium-stained amniotic fluid but with normal physical examination (Group 2) were studied with serial neurological examination, Denver developmental screening test (DDST), electroencephalogram and computerized cerebral tomography (CT) for neurological follow-up. Thirty healthy infants were selected as the control group. In the patient groups, two blood samples were taken to measure NSE levels, one between 4 and 48 h and the other 5–7 days after birth. Serum NSE levels were significantly higher in infants with HIE compared to those infants in Group 2 and control group. The mean serum concentrations of the second samples decreased in all groups studied but they were significantly higher in Group 1 compared to those in Group 2. Serum NSE concentrations of initial samples were significantly higher in patients with stage III HIE than in those with stages II and I. The sensitivity and specificity values of serum NSE as a predictor of HIE of moderate or severe degree (cut-off value 40.0 μg/l) were 79 and 70%, respectively, and as a predictor of poor outcome (cut-off value 45.4 μg/l) were calculated as 84 and 70%, respectively. The predictive capacity of serum NSE concentrations for poor outcome seems to be better than predicting HIE of moderate or severe degree. However, earlier and/or CSF samples may be required to establish serum NSE as an early marker for the application of neuroprotective strategies.

Evaluation of Protein S‐100 serum concentrations in healthy newborns and seven newborns with perinatal acidosis

We measured Protein S‐100 serum levels in 66 healthy newborns during the first week of life and in 7 newborns with perinatal acidosis. Normal values (n= 66) constantly ranged between 0.66 and 3.33 ug/1 (2.5 and 97.5 percentiles) during the evaluation period. Conclusions: Newborns with signs of hypoxic‐ischaemic encephalopathy (HIE) after perinatal acidosis showed elevated Protein S‐100 serum levels, whereas newborns without these signs had normal concentrations. S‐100 might thus be a marker of central nervous system damage in newborns.

Evaluation of protein S-100 serum concentrations in healthy newborns and seven newborns with perinatal acidosis.

We measured Protein S-100 serum levels in 66 healthy newborns during the first week of life and in 7 newborns with perinatal acidosis. Normal values (n = 66) constantly ranged between 0.66 and 3.33 microg/l (2.5 and 97.5 percentiles) during the evaluation period. Newborns with signs of hypoxic-ischaemic encephalopathy (HIE) after perinatal acidosis showed elevated Protein S-100 serum levels, whereas newborns without these signs had normal concentrations. S-100 might thus be a marker of central nervous system damage in newborns. Key words: Asphyxia, brain damage, neonate

Proton spectroscopy of the neonatal brain following hypoxic-ischaemic injury.

Proton magnetic resonance spectroscopy was used to examine, within the first month of life, the brains of 11 infants born at term--10 with signs of hypoxic-ischaemic encephalopathy (HIE) and one who was neurologically normal at birth. All the infants had peak resonances on their spectra which could be assigned to N-acetyl-aspartase (NAA), choline-containing compounds (Cho) and creatine plus phosphocreatine (Cr). When neurodevelopmental outcome at one year was correlated with initial spectroscopy findings, the NAA/Cho and NAA/Cr ratios reflected clinical outcome. This study suggests that proton spectroscopy not only provides new information about biochemical changes occurring in the brains of infants with HIE, but also may help to predict outcome within the first month of life.

Bedeutung der intrapartalen Asphyxie für die Entstehung von kindlichen Hirnschäden

The prevalence of cerebral palsy is around 0.2% and has remained constant during the last 30 years. Retrospective case-control studies do not show a clear correlation between perinatal asphyxia and the development of cerebral palsy. Less than 10% of all cerebral palsy cases show signs of severe asphyxia during labour and delivery as the major pathological and likely cause for the brain damage. Severe cases of birth asphyxia with multiorgan defects and signs of hypoxic-ischaemic encephalopathy have a high mortality and the risk of permanent brain damage is increased by a factor of 10 to 30. Inspite of this, 90% of the survivors show normal development. The association between perinatal asphyxia and neuromotor developmental disturbances does not provide proof of a causal connection. Intrapartal abnormalities of foetal heart rate monitoring are not specific for foetal asphyxia and show only a limited correlation with the apgar and the cord blood pH. Foetal heart rate recording with pathological changes does not imply an elevated risk of later problems with neuromotor development and the widespread use of foetal heart rate monitoring during labour and delivery did not result in a significant reduction in the frequency of cerebral palsy. In addition to malformations, various forms of antinatal pathology like prematurity, intrauterine growth retardation and congenital infections are related to the development of brain damage. In each case of birth asphyxia, additional pathology like congenital infections or malformations in addition to changes in brain structure as a result of asphyxia must be ruled out using specific diagnostic methods like ultrasound, computed tomography and magnetic resonance. Furthermore, a careful documentation of the developmental phases is of fundamental importance for a final evaluation. In otherwise unremarkable deliveries at term, four conditions must be fulfilled to postulate a causal relationship between asphyxia and the development of cerebral palsy: The asphyxia must be severe. During the early neonatal period, clinical symptoms of moderate to severe hypoxic-ischaemic encephalopathy with functional impairment of other organs must be present. The neurological symptoms must be typical for intrapartal asphyxia. Documentation of diagnostic evaluation to rule out other forms of pathology must be complete (21).

POWER SPECTRAL ANALYSIS OF THE EEG OF TERM INFANTS FOLLOWING BIRTH ASPHYXIA

The aim of this pilot study was to perform power spectral analysis of the EEGs of term infants following birth asphyxia, to establish its value as a prognostic indicator. 16 term infants were studied over an 18-month period. Power spectral analysis was performed on the EEGs of babies with signs of hypoxic-ischaemic encephalopathy at regular intervals during the first five days of life. It showed distinct changes following birth asphyxia, which were related to the eventual outcome of the babies. Absolute power was significantly reduced in the babies with poor outcome compared with those with good outcome, particularly in the delta bands.

Neonatology in the developing world. Part 1.

With proper nursing care and procedures, small hospitals in rural areas of developing countries can provide good neonatal care and achieve perinatal mortality rates comparable to those found at teaching hospitals. The 1st ingredient of adequate neonatology is the establishment of proper regimens for feeding, observation, and resuscitation of newborns. Even in areas where the majority of births take place at home, good neonatal care is possible as long as local risk factors are identified, all newborns are screened for these factors, and at-risk infants are referred for treatment. Factors that place infants at risk include birthweight under 2 kg or above 4 kg, delivery before 34 weeks' gestation, respiratory distress, severe birth asphyxia or trauma, jaundice, prolonged rupture of the membranes, infant not sucking or febrile, convulsions, congenital malformations, and maternal disease. 4 areas require special knowledge on the part of health personnel: the asphyxiated infant, hypothermia, hypoglycemia, and neonatal sepsis. Health workers must be familiar with proper resuscitation techniques, especially avoidance of excessive suctioning of the pharynx, and be alert to signs of hypoxic ischemic encephalopathy. Premature, small, asphyxiated, and sick infants are at greatest risk of hypothermia, a condition that can be prevented by drying and wrapping newborns immediately. Providers should be alert to signs of hypoglycemia in infants of diabetic mothers, large-for-gestational-age babies, the low- birthweight infant, and sick babies. To prevent sudden infant deaths, all sick newborns should be treated for neonatal sepsis.

Birth Complications and Risk of Cerebral Palsy

Statisticians at the National Institutes of Health (NINCDS), Bethesda, MD have compared the follow-up neurologic status of full-term infants whose birth was complicated but who were free of signs of hypoxic-ischemic encephalopathy (HIE) in the nursery period with asymptomatic infants whose births were uncomplicated.