Evidence Of Hypoxic-ischemic Encephalopathy Research Articles

Quantitative Evaluation of Brain Echogenicity in Hypoxic-Ischemic Encephalopathy in Term Neonates Compared with Controls.

Purpose Neurosonography evaluation of neonatal hypoxic-ischemic encephalopathy (HIE) is mainly qualitative. We aimed to quantitatively compare the echogenicity of several brain regions in patients with HIE to healthy controls. Materials and Methods 20 term neonates with clinical/MRI evidence of HIE and 20 term healthy neonates were evaluated. Seven brain regions were assessed [frontal, parietal, occipital, and perirolandic white matter (WM), caudate nucleus head, lentiform nucleus, and thalamus]. The echogenicity of the calvarial bones (bone) and the choroid plexus (CP) was used for ratio calculation. Differences in the ratios were determined between neonates with HIE and controls. Results Ratios were significantly higher for HIE neonates in each region (p<0.05). The differences were greatest for the perirolandic WM, with CP and bone ratios being 0.23 and 0.22 greater, respectively, for the HIE compared to the healthy neonates (p<0.001). The perirolandic WM had a high AUC, at 0.980 for both the CP and bone ratios. The intra-observer reliability for all ratios was high, with the caudate to bone ratio being the lowest at 0.832 and the anterior WM to CP ratio being the highest at 0.992. Conclusion When coupled with internal controls, quantitative neurosonography represents a potential tool to identify early neonatal HIE changes. Larger cohort studies could reveal whether a quantitative approach can discern between degrees of severity of HIE. Future neurosonography protocols should be tailored to evaluate the perirolandic region, which requires posterior coronal scanning.

Prenatal selective serotonin reuptake inhibitors and therapeutic hypothermia for suspected hypoxic ischemic encephalopathy.

To evaluate the association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and postnatal therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. Matched case-control study of singleton deliveries at a tertiary hospital from 2010 to 2016. Cases were infants treated with therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. Controls were noncase infants, matched on gestational age, maternal age, obstetric provider group, and hospital shift. Prenatal SSRI exposure occurred in 18.4% of cases compared with 4.1% of controls (aOR: 5.9, 95% CI: 1.8-19.7). Among all cases, 36.8% had evidence of hypoxic ischemic encephalopathy on postnatal MRI. In addition, 28.6% of SSRI-exposed cases and 38.7% of SSRI-unexposed cases had MRI confirmation of hypoxic ischemic encephalopathy, respectively. Future research to disentangle signs of SSRI exposure from true hypoxic ischemic encephalopathy may facilitate targeting therapeutic hypothermia stewardship toward infants more likely to benefit.

Association of Low Umbilical Cord pH and Hypoglycemia in Healthy Term Newborns: Should it Be a Part of Postnatal Screening?

Hypoglycemia may lead to neurological impairment; therefore, high-risk newborns are screened postnatally. However, hypoglycemia monitoring protocols often do not include cord blood acidosis as a risk factor. The study aimed to find an association between asymptomatic cord blood acidosis and hypoglycemia. All healthy term infants born at McMaster Children Hospital, Hamilton, Canada, between October 2013 and September 2014, who had umbilical cord blood pH <7.0 or base excess <12 mmol/L were studied. Infants with evidence of hypoxic-ischemic encephalopathy, birth weights outside of 10th to 95th percentiles for gestation, mothers with preeclampsia, diabetes or taking a -blockers at the time of the birth were excluded. Hypoglycemia was defined as blood glucose <2.6 mmol/L in the first two hours of life. One hundred sixtysix infants met the cord blood gas criteria, but only 16 had hypoglycemia. Although infants with mild perinatal depression are at risk for hypoglycemia, a significant association could not be proved.

Utility of Rapid Sequence Magnetic Resonance Imaging in Guiding Management of Patients With Neonatal Seizures

ObjectiveTo determine whether the use of rapid sequence magnetic resonance imaging (rsMRI) is associated with improved efficiency of care when managing infants with suspected neonatal onset seizures. MethodsWe conducted a preintervention and postintervention study of the use of rsMRI in term infants with suspected neonatal onset seizures without evidence of hypoxic ischemic encephalopathy. Study patients were collected from a contemporary cohort from 2016 to 2017 and were compared with a historical cohort from 2014. The primary outcome was hospital length of stay. Secondary outcomes included use of other imaging modalities (head ultrasound, computed tomography [CT], and MRI), use of antiseizure medications at the time of discharge, and cost of hospitalization. Continuous variables were compared using the Mann-Whitney U test and categorical variables using the Fisher's exact or χ2 tests. A two-tailed P < 0.05 was considered statistically significant. ResultsNinety-five patients met inclusion criteria, 47 in the preintervention and 48 in the postintervention group. Incorporation of the protocol-guided rsMRI in the evaluation of patients with neonatal seizures was associated with decreased use of CT scans (34% vs 10%, P = 0.007) and full MRIs (85% vs 62%, P = 0.019). Use of head ultrasound, length of stay, and costs were not different between groups. ConclusionsIn patients with neonatal seizures, rsMRI was not associated with a reduced hospital length of stay. The use of rsMRI resulted in fewer neonates receiving CT scans during their hospitalization. rsMRI may hasten the identification of stroke or hemorrhage in neonates with seizures.

SUN-271 Prominent Parietal Lobe Brain Injury in a Neonate with Seizure Due to Hyperinsulinemic Hypoglycemia

Background: Severe hypoglycemia causes brain injury in neonates, which is most commonly described as white matter (WM) changes in the occipital region. These WM changes can extend anteriorly to involve the parietal regions, which can be equally or less severely affected (1, 2). Early visual impairment can be seen in patients with severe occipital involvement. Clinical Case: A male infant born at 39 weeks gestation via C-section after fetal intolerance of induction presented on day of life (DOL) 4 with seizure. Pregnancy was uncomplicated without gestational diabetes, hypertension, or infection. Birth weight was 3.1 kg. He had an unremarkable postnatal course and was discharged on DOL2. At home, he became sleepier with decreased feeding, and developed abnormal extremity movements. Tonic-clonic seizure activity was observed in the ED with serum glucose level of < 10 mg/dL, anion gap of 13 and trace ketonuria. Cerebral spinal fluid studies were not suggestive of infection. Glucose was corrected with intravenous dextrose. Brain CT scan without contrast showed hypodensity involving the distribution of the right posterior cerebral artery with loss of normal gray white differentiation. MRI brain without contrast showed bilateral WM restricted diffusion more prominent in the right parietal lobe than in the occipital lobes. There were also bilateral areas of cortical restricted diffusion in the occipital and parietal lobes, but no evidence of hypoxic ischemic encephalopathy. Proton MR Spectroscopy showed findings consistent with hypoglycemic brain injury. In the setting of hypoglycemia (serum glucose 37 mg/dL), serum beta-hydroxybutyrate was 0.13 mMol/L (0.02-0.27 mMol/L) and serum insulin was 5.7 mU/L (3.0-25.0 mU/L), consistent with hyperinsulinemic hypoglycemia. Growth hormone level (13.18 mg/mL) and ACTH stimulation test were normal. Treatment with diazoxide was initiated with excellent response. He was discharged and continues to work with Early Intervention. Conclusion: We describe a newborn with hyperinsulinemic hypoglycemia and more significant WM changes in the parietal lobe compared to the occipital lobe on brain MRI. Although occipital WM is thought to be most vulnerable to hypoglycemia, our patient’s findings suggest that parietal WM may also be disproportionally susceptible to injury. Neurodevelopmental deficits may be less obvious soon after injury, and long term surveillance of these patients is required.

A randomized controlled trial of the impact of dopamine on outcome of asphyxiated neonates

Background : Vasoactive drugs such as low dosage dopamine are often used in the intensive care of asphyxiated term neonates but there is insufficient evidence to support the practice. Aims : To evaluate the impact of low dose dopamine on the clinical course and outcome of newborns with severe perinatal asphyxia and to determine factors that predict survival. Methods : This was a randomized controlled trial. Term asphyxiated newborns were alternately recruited into ‘dopamine’ and ‘nodopamine’ sub groups. Asphyxia was defined as Apgar score ≤3 at one minute or ≤5 at five minutes, and/or clinical evidence of hypoxic ischemic encephalopathy (HIE). The intervention comprised dopamine infusion at 3.0mcg/kg/minute. Primary outcome was death or survival till discharge while secondary measures were apnoea, oliguria, seizures and other clinical morbidities. The Student t-test was used to compare outcomes between the subgroups. Results : A total of fifty five asphyxiated infants took part in the study: 27 in the intervention group while 28 were in the control group. The subgroups were similar in mean gestational age, Apgar scores, age at admission and modes of delivery (p>0.05). HIE occurred in over a half of the subjects. The frequency of apnoea, oxygen requirement, duration of anticonvulsant treatment and urine outputs were similar between the subgroups(p > 0.05).The mean durations of admission (days) were 5.13±3.0 and 5.3±3.0 for the intervention and non-intervention subgroupsrespectively (t=0.183, p=0.856). Likewise,survival rates were similar (x 2 = 1.261, p = 0.948). Selected perinatal eventsdid not influence outcome (p>0.05). Conclusion : Low-dosedopamine has no impact on the short term outcome of asphyxiated infants. Key words: hypoxic ischemic encephalopathy, clinical course, outcome, dopamine

Outcomes of neonates with perinatal asphyxia at a tertiary academic hospital in Johannesburg, South Africa

Background. Perinatal asphyxia is a significant cause of death and disability. Aim. To determine the outcomes (survival to discharge and morbidity after discharge) of neonates with perinatal asphyxia at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Methods. This was a descriptive retrospective study. We reviewed information obtained from the computerised neonatal database on neonates born at CMJAH or admitted there within 24 hours of birth between 1 January 2006 and 31 December 2011, with a birth weight of >1 800 g and a 5-minute Apgar score <6. Results. Four hundred and fifty infants were included in the study; 185 (41.1%) were females, the mean birth weight (± standard deviation) was 3 034.8±484.9 g, and the mean gestational age was 39.1±2.2 weeks. Most of the infants were born at CMJAH (391/450, 86.9%) and by normal vaginal delivery (270/450, 60.0%). The overall survival rate was 86.7% (390/450). Forty-two infants were admitted to the intensive care unit (ICU). The ICU survival rate was 88.1% (37/42). Significant predictors of survival were place of birth ( p =0.006), mode of delivery ( p =0.007) and bag-mask ventilation at birth ( p =0.040). Duration of hospital stay ( p =0.000) was significantly longer in survivors than in non-survivors (6.5±6.6 days v. 2.8±9.8 days). The remaining factors, namely gender, antenatal care, chest compressions, diagnosis of meconium aspiration syndrome or persistant pulmonary hypertension, did not differ significantly between the two groups. The rate of perinatal asphyxia (5-minute Apgar score <6) was 4.7/1 000 live births, and there was evidence of hypoxic ischaemic encephalopathy (HIE) in 3.6/1 000 live births. Of the 390 babies discharged from CMJAH, 113 (29.0%) had follow-up records to a mean corrected age of 5.9±5.0 months. The majority (90/113, 79.6%) had normal development. Conclusions. ( i ) The high overall survival and survival after ICU admission provides a benchmark for further care; ( ii ) obtaining adequate data for long-term follow-up was not possible with the existing resources – surrogate early markers of outcome and/or more resources to ensure accurate follow-up are needed; and ( iii ) the high incidence of HIE suggests that a therapeutic hypothermia service including a long-term follow-up component would be beneficial.

Prediction of neurodevelopmental outcome in term neonates with hypoxic-ischemic encephalopathy

BackgroundHypoxic ischemic encephalopathy may result in many neurological deficits. It is crucial to make early diagnosis and assess the prognosis correctly. AimsWe aimed to determine the factors to evaluate the prognosis of hypoxic ischemic encephalopathy. MethodsElectroencephalography, neuroimaging, periodic neurological exams and a developmental test at 44–48 months after discharge from the hospital were performed on twenty five term newborn infants with clinical evidence of hypoxic ischemic encephalopathy. ResultsNormal/mildly abnormal neonatal electroencephalography correlated with favorable outcome, particularly if neuroimaging was normal. The cranial MRI sensitivity was 83.3%, while the specificity was 57.9%, the positive predictive value was 38.5%, and the negative predictive value was 91.6%. Moderate/severely abnormal electroencephalography and multifocal/diffuse cortical or deep gray matter lesions correlated with poor outcome. ConclusionsNewborn infants with hypoxic ischemic encephalopathy should be treated in neonatal intensive care units, assessed with periodic neurological examination, electroencephalogram and brain imaging. This would help to initiate early intervention and improve the outcome of patients.

Perinatal Risk Factors and Later Social, Thought, and Attention Problems after Perinatal Stroke

Objective. Survivors of perinatal stroke may be at risk for behavioral problems. Perinatal risk factors that might increase the likelihood of later behavior problems have not been identified. The goal of this study was to explore whether perinatal factors might contribute to behavior problems after perinatal stroke. Methods. 79 children with unilateral perinatal stroke were studied. Perinatal factors included gender, gestational age, neonatal seizures, instrumented delivery, fetal distress, acute birth problems, birth weight, and time of diagnosis. Subjects with evidence of hypoxic ischemic encephalopathy were excluded. Parents completed the Achenbach Child Behavior Checklist (CBCL) (Achenbach 1985). The CBCL yields T-scores in several symptom scales. We focused on Social, Thought, and Attention Problems scates. Results. Gestational age and the presence of uteroplacental insufficiency were associated with significant differences on the Thought Problems scale; Attention Problems scores approached significance for these variables. Fetal distress, neonatal seizures, or neonatal diagnosis was associated with 25–30% incidence of clinically significant T-scores on Social, Thought, and Attention Problems scales. Conclusions. Several perinatal factors were associated with a high incidence of social, thought, and behavior problems in children with perinatal stroke. These findings may be useful in anticipatory guidance to parents and physicians caring for these children.

Serum creatine kinase and lactic dehydrogenase levels as useful markers of perinatal asphyxia

Objectives To determine the usefulness of creatine kinase (CK) alone or in combination with lactic dehydrogenase (LDH) in identifying, those infants at risk of developing hypoxic ischaemic encephalopathy (HIE) or a major handicap following perinatal asphyxia. Design Prospective observational study. Method CK and LDH in serum were measured in 35 asphyxiated infants and in 30 controls within 6 hours of delivery. The asphyxiated newborns were monitored for evidence of HIE. Both groups were followed up in paediatric outpatients clinic and a developmental assessment was done at the end of one year. Results Both the CK and LDH levels were significantly raised in all asphyxiated newborns. 25.7% of asphyxiated babies developed HIE. The CK and LDH values of those who developed HIE were significantly higher than the rest of the asphyxiated newborns. Five babies had developmental delay and their CK values too were significantly higher. The same relationship was not seen with their LDH values. Conclusion Both the CK and LDH values are raised in birth asphyxia. The increase is more marked among those who developed HIE. However, only the raised CK levels correlated with long-term outcome. Babies with CK values above 2860 IU/ L should be closely monitored for both the immediate and longterm sequelae. Sri Lanka Journal of Child Health , 2000; 29 : 49-52 (Key words: creatine kinase, lactic dehydrogenase, markers of perinatal asphyxia) doi: 10.4038/sljch.v29i2.604

Fetal Heart Rate Patterns in Neonatal Hypoxic-Ischemic Encephalopathy: Relationship with Early Cerebral Activity and Neurodevelopmental Outcome

Despite widespread use of fetal heart rate monitoring, the timing of injury in hypoxic-ischemic encephalopathy (HIE) remains unclear. Our aim was to examine fetal heart rate patterns during labor in infants with clinical and electroencephalographic (EEG) evidence of HIE and to relate these findings to neurodevelopmental outcome. Timing of onset of pathological cardiotocographs (CTGs) was determined in each case by two blinded reviewers and related to EEG grade at birth and neurological outcome at 24 months. CTGs were available in 35 infants with HIE (17 mild, 12 moderate, 6 severe on EEG). Admission CTGs were normal in 24/35 (69%), suspicious in 8/35 (23%), and pathological in 3/35 (8%). All CTGs developed nonreassuring features prior to delivery. Three patterns of fetal heart rate abnormalities were seen: group 1, abnormal CTGs on admission in 11/35 (31%); group 2, normal CTGs on admission with gradual deterioration to pathological in 20/35 cases (57%); and group 3, normal CTGs on admission with acute sentinel events in 4/35 (11.5%). The median (interquartile range) duration between the development of pathological CTGs and delivery was 145 (81, 221) minutes in group 2 and 22 (12, 28) minutes in group 3. There was no correlation between duration of pathological CTG trace and grade of encephalopathy (R = 0.09, P = 0.63) or neurological outcome (P = 0.75). However, the grade of encephalopathy was significantly worse in group 3 (P = 0.001), with a trend to worse outcomes. The majority of infants with HIE have normal CTG traces on admission but develop pathological CTG patterns within hours of delivery. More severe encephalopathy was associated with normal admission CTG and acute sentinel events shortly before delivery.

Patterns of Cerebral Injury and Neurodevelopmental Outcomes After Symptomatic Neonatal Hypoglycemia

Symptomatic neonatal hypoglycemia may be associated with later neurodevelopmental impairment. Brain injury patterns identified on early MRI scans and their relationships to the nature of the hypoglycemic insult and neurodevelopmental outcomes are poorly defined. We studied 35 term infants with early brain MRI scans after symptomatic neonatal hypoglycemia (median glucose level: 1 mmol/L) without evidence of hypoxic-ischemic encephalopathy. Perinatal data were compared with equivalent data from 229 term, neurologically normal infants (control subjects), to identify risk factors for hypoglycemia. Neurodevelopmental outcomes were assessed at a minimum of 18 months. White matter abnormalities occurred in 94% of infants with hypoglycemia, being severe in 43%, with a predominantly posterior pattern in 29% of cases. Cortical abnormalities occurred in 51% of infants; 30% had white matter hemorrhage, 40% basal ganglia/thalamic lesions, and 11% an abnormal posterior limb of the internal capsule. Three infants had middle cerebral artery territory infarctions. Twenty-three infants (65%) demonstrated impairments at 18 months, which were related to the severity of white matter injury and involvement of the posterior limb of the internal capsule. Fourteen infants demonstrated growth restriction, 1 had macrosomia, and 2 had mothers with diabetes mellitus. Pregnancy-induced hypertension, a family history of seizures, emergency cesarean section, and the need for resuscitation were more common among case subjects than control subjects. Patterns of injury associated with symptomatic neonatal hypoglycemia were more varied than described previously. White matter injury was not confined to the posterior regions; hemorrhage, middle cerebral artery infarction, and basal ganglia/thalamic abnormalities were seen, and cortical involvement was common. Early MRI findings were more instructive than the severity or duration of hypoglycemia for predicting neurodevelopmental outcomes.

Neurological Complications of Kernicterus

Prevention of bilirubin encephalopathy relies on the detection of newborns who are at risk of developing serious hyperbilirubinemia. The objective of this study was to reassess the clinical syndrome of kernicterus as neurodiagnostic studies have become more readily available and can be used to evaluate these infants. The study population was neonates born at term or near term admitted to The Hospital for Sick Children in Toronto, Ontario, Canada, between January 1990 and May 2000. During the study period, there were 9776 admissions (average number of admissions per year--888 infants). The inclusion criteria were that patients had total serum bilirubin levels of >400 micromol/L at the time of diagnosis and no evidence of hypoxic ischemic encephalopathy. Records were reviewed to establish neurodevelopment outcomes. Twelve neonates (nine males) were identified. Bilirubin levels at the time of diagnosis ranged from 405 to 825 micromol/L. Causes of these elevated levels included glucose-6-phosphate dehydrogenase deficiency (seven patients), dehydration (three patients), sepsis (one patient), and was undetermined in one patient. Abnormal visual evoked potentials were found in three of nine patients and abnormal brainstem auditory evoked potentials in seven of ten patients. Abnormal electroencephalograms were documented in five patients studied. Brain magnetic resonance imaging results were abnormal in three of four patients. Magnetic resonance imaging typically showed an increased signal in the posteromedial aspect of the globus pallidus and was, therefore, useful in the assessment of the structural changes of chronic bilirubin encephalopathy after kernicterus.

Hypoxic-ischemic encephalopathy in term neonates: Perinatal factors and outcome

Ninety-five infants of 37 weeks' gestation or greater with evidence of hypoxic-ischemic encephalopathy following perinatal asphyxia were prospectively identified in the neonatal period. The degree of encephalopathy was graded the staging system of Sarnat and Sarnat. Six infants died, 78 infants were sequentially followed in the Neonatal Follow-up Clinic, and in five additional infants, follow-up information was available. The mean duration of follow-up was 19.3 months. Fifty-eight (65%) of the 89 infants followed were normal or mildly handicapped, six (7%) died, and the remainder had significant handicap. There was no significant relationship between any of over 100 obstetrical antepartum or intrapartum variables and outcome. Infants with five-minute Apgar scores of 0 to 3, seizures within the first day of life, Stage II or III encephalopathy, or a suppressed electroencephalogram had a significantly greater incidence of severe handicap or death. In addition, although there were fewer females, they had a significantly greater incidence of handicap. There appeared to be an improved outcome in the last two years (1977-1978) compared to the first two years (1975-1976), suggesting that improved recognition and neonatal management may lead to a decrease in significant sequelae.