Transcript of Perspectives from the ACOG & AAP Revision1. A sentinel \⠀猀椀最渀愀氀尩 hypoxic event...
Neonatal Encephalopathy: Perspectives from the ACOG & AAP Revision
Mary E. D’Alton, M.D.Willard C. Rappleye Professor and
Chair, Department of Obstetrics & GynecologyColumbia University College of Physicians & Surgeons
Objectives
• Identify neonatal signs consistent with an acute peripartum or intrapartum event
• Identify type and timing of contributing factors consistent with an acute peripartum or intrapartum event
• Discuss root cause analysis that will assist teams in the evaluation of newborns with encephalopathy and help define both the cause and timing of NE
• Identify advances in neuroimaging and differences between the 2003 and 2013 documents
Criteria Required to Define an Acute Intrapartum Hypoxic Event as Sufficient to Cause Cerebral Palsy (2003)
Essential criteria:1. Evidence of a metabolic acidosis in fetal,
umbilical cord arterial blood obtained at delivery (pH<7.00 and base deficit >12 mmol/L)
2. Early onset of severe or moderate NE in infants of 34 or more weeks of gestation
3. Cerebral palsy of the spastic quadriplegic or dyskinetic type
4. Exclusion of other identifiable etiologies such as trauma, coagulation disorders, infectious conditions, or genetic disorders
ACOG/AAP
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Presentation Notes
Must meet all four essential criteria.
Criteria That Collectively Suggest an Intrapartum Timing but Are Nonspecific to Asphyxial Insults (2003)
• A sentinel (signal) hypoxic event
• A sudden and sustained fetal bradycardia or category 3* tracing following a previously normal FHR pattern
• Apgar scores of 0-3 beyond 5 minutes
• Evidence of multi-system involvement up to 72 hours
• Early imaging study showing evidence of acute nonfocal cerebral abnormality
ACOG/AAP
* = 2008 definition NICHD
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Presentation Notes
1. A sentinel (signal) hypoxic event occurring immediately before or during labor. 2. A sudden and sustained fetal bradycardia or the absence of fetal heart rate variability in the presence of persistent, late, or variable decelerations, usually after an hypoxic sentinel event when the pattern was previously normal 3. Apgar scores of 0-3 beyond 5 minutes 4. Onset of multisystem involvement within 72 hours of birth 5. Early imaging study showing evidence of acute nonfocal cerebral abnormality
Antepartum Risk Factors for Newborn Encephalopathy: The Western Australian Case-Control Study
• Metropolitan Western Australia June 93-Sept 95• All 164 term infants with moderate/severe encephalopathy
• Controls – 400 randomly selected
• Stats• Birth prevalence of moderate/severe newborn encephalopathy
3.8/1000 term live births
• Neonatal Fatality 9.1%
• Conclusions• Causes of newborn encephalopathy are heterogeneous and many
of the causal pathways start before birth
Badawi N et al. BMJ 1998;317:1549–53
Distribution of Risk Factors for Newborn Encephalopathy
Antepartum risk factors only (69%)
Antepartum risk factors and intrapartum
hypoxia (25%)
Intrapartum hypoxia only (4%)
Unknown (2%)
Badawi N et al. BMJ 1998;317:1549–53
Conclusions of Task Force 2003
“Epidemiological studies suggest that in about 90% of cases of cerebral palsy intrapartum hypoxia could not be the cause of cerebral palsy . . .
and in the remaining 10% intrapartumsigns compatible with damaging hypoxia may have had antenatal or intrapartum origins.”
MRI Findings in 245 Term Infants with Neonatal Encephalopathy and Perinatal Asphyxia
MRI Findings Incidence
Acute Injury Pattern 197/245 (80%)
Normal 40/245 (16%)
Findings not compatible with hypoxia 8/245 ( 3%)
Acute hypoxic damage with other disorders 9/245 ( 4%)
NE defined by abnormal tone pattern, feeding difficulties, altered alertness.
Perinatal Asphyxia defined by at least 3 of the following:
• Late decelerations or MSAF • Apgar <7 at 5 minutes• Delayed onset respirations • Multi organ failure• Arterial cord blood ph < 7.1
Cowan, F., et. al., The Lancet, 2003;vol 361:736-742
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Events in the perinatal period most important in brain injury “Although our results cannot exclude the possibility that antenatal or genetic factors might predispose some infants to perinatal brain injury, our data strongly suggest that events in the immediate perinatal period are most important in neonatal brain injury.” Criticism of Cowen Criteria to define group I Late decels 99% false positive for CP MSAF 14-20% of term gestations Umbilical arterial pH <7ּ1 Pathologic acidemia agreed by most as <7ּ0 Significant number of normal babies can/will have this level of acidemia. Respiratory versus metabolic? Apgar <7 at 5 minutes What is the rate of any of these markers in their general population? From article: Summary Background: The role of intrapartum asphyxia in neonatal encephalopathy and seizures in term infants is not clear, and antenatal factors are being implicated in the causal pathway for these disorders. However, there is no evidence that brain damage occurs before birth. We aimed to test the hypothesis that neonatal encephalopathy, early neonatal seizures, or both result from early antenatal insults. Methods: We used brain MRI or post-mortem examination in 351 fullterm infants with neonatal encephalopathy, early seizures, or both to distinguish between lesions acquired antenatally and those that developed in the intrapartum and early post-partum period. We excluded infants with major congenital malformations or obvious chromosomal disorders. Infants were divided into two groups: those with neonatal encephalopathy (with or without seizures), and evidence of perinatal asphyxia (group 1); and those without other evidence of encephalopathy, but who presented with seizures within 3 days of birth (group 2). Findings: Brain images showed evidence of an acute insult without established injury or atrophy in 197 (80%) of infants in group 1, MRI showed evidence of established injury in only 2 infants (<1%), although tiny foci of established white matter gliosis, in addition to acute injury, were seen in three of 21 on post-mortem examination. In group 2, acute focal damage was noted in 62 (69%) of infants. Two (3%) also had evidence of antenatal injury. Interpretation: Although our results cannot exclude the possibility that antenatal or genetic factors might predispose some infants to perinatal brain injury, our data strongly suggest that events in the immediate perinatal period are most important in neonatal brain injury. Discussion: Our findings show that more than 90% of term infants with neonatal encephalopathy, seizures, or both, but without specific syndromes or major congenital defects, had evidence of perinatally acquired insults, and there was a very low rate of established brain injury acquired before birth. Reasons for injuries of perinatal onset remain poorly understood. The frequency of risk factors in infants with and without established brain abnormality did not differ greatly, but the study was not designed to explore antenatal aspects of perinatal brain injury. Our data do not exclude the possibility that antenatal factors could initiate a causal pathway for perinatal brain injury and that they, possibly together with genetic predispositions to hypoxic-ischaemic injury, might make some infants more susceptible than others to the stresses of labour and delivery.
Clinical Characteristics MRI Pattern in 173 infants with NE
Miller, SP et. al., J Pediatr, April 2005; 453-460
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From Miller article: Objectives: To determine whether the pattern of brain injury in term neonatal encephalopathy is associated with distinct prenatal and perinatal factors and to determine whether the pattern of injury is associated with 30-month neurodevelopmental outcome. Study design: A total of 173 term newborns with neonatal encephalopathy from 2 centers underwent magnetic resonance imaging (MRI) at a median of 6 days of age (range, 1-24 days). Patterns of injury on MRI were defined on the basis of the predominant site of injury:: watershed predominant, basal ganglia/thalamus predominant, and normal. Results: The watershed pattern of injury was seen in 78 newborns (45%), the basal ganglia/thalamus pattern was seen in 44 newborns (25%), and normal MRI studies were seen in 51 newborns (30%). Antenatal conditions such as maternal substance use, gestational diabetes, premature rupture of membranes, pre-eclampsia, and intra-uterine growth restriction did not differ across patterns. The basal ganglia/thalamus pattern was associated with more severe neonatal signs, including more intensive resuscitation at birth (P = .001), more severe encephalopathy (P = .0001), and more severe seizures (P = .0001). The basal ganglia/thalamus pattern was associated with the most impaired motor and cognitive outcome at 30 months. Conclusion: The patterns of brain injury in term neonatal encephalopathy are associated with different clinical presentations and neurodevelopmental outcomes. Measured prenatal risk factors did not predict the pattern of brain injury.
Neurodevelopmental Outcome of Newborns Observed to 30 months of Age by MRI
Normal Watershedpredominant
Basal ganglia / thalamus predominant
P value
Number 20 48 21
Died* 0 3 5 .01
30-month MDI 101(77-121)
84(50-116)
62.5(50-104)
.0007
12-month MDI 93(53-109)
91.5(50-120)
58(50-109)
.006
30-month NMS 0(0-2)
1 (0-5)
5(0-5)
.0001
12-month NMS 0(0-3)
1 (0-5)
5(0-5)
.0008
Miller SP, et. al., J Pediatr, April 2005; 453-460
*All infants died before 12 months of age.MDI = Mental Development Index NMS = Neuromotor score
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Presentation Notes
MR could be used in prediction Motor and cognitive injury QUOTE FROM MILLER ABOUT ACUTE INJURY
Conclusion by Dr. Steven Miller et al. 2005
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“Brain injury in most newborns with encephalopathy
occurs at or near the time of birth . . .”
Miller SP, et. al., J Pediatr, April 2005; 453-460
Process for 2014 Report
• Dr. Richard Waldman’s presidential initiative
• Task Force convened in 2010
• Met 4 times over span of 3 years
• Task Force identified clinicians and scientists from multiple disciplines
• 88 international consultants
• Reviewed and edited draft manuscripts and deliberated to achieve consensus
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Presentation Notes
14 consultants in comparison to the Green Report, all consultants were from the US.
Major Changes Since 2003 Report
• Classification of EFM patterns
• MRI studies conflict with epidemiological data
• Landmark introduction of hypothermia for neonatal treatment
• New chapters on neuroimaging, patient safety, placental pathology, neonatal interventions, and fetal physiology
• Significantly expanded document
Vermont Oxford NE Registry
• 4,171 infants ≥ 36 weeks from 95 centers met encephalopathy criteria in first 3 days of life 2006-2010
• 3,493 infants (84%) underwent some form of neuroimaging evaluation (MRI, HUS, CT)
• Infants who died more commonly had no neuroimaging compared to surviving infants (23.3% vs. 15.5%)
• 15% living term NE infants had NO neuroimaging
Barnette AR, et al. Pediatrics 2014 133; e1508
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It became apparent to us that many infants were not getting the benefit of appropriate imaging. Data made available to us prior to publication.
Imaging Findings
Ultrasound CT Scan MRI
Number of exams 2006/4111(48.8%) 933/4107 (22.7%) 2690/4109
(65.5%)
Day of life at first scan 2 (1-3) 2 (2-3) 6 (4-8)
Abnormal 642 (32.3%) 552 (59.4%) 1798 (67.2%)
DNGM 140 (7%) 65 (7%) 603 (22.6%)
Diffuse WM Injury - - 628 (23.5%)
Diffuse cortical signal abnormality - - 572/2673 (21.4%)
Head to Head Comparison Abnormal = any reported abnormality METHODS: The Vermont Oxford Network Neonatal Encephalopathy Reg-istry enrolled 4171 infants ($36 weeks’ gestation or treated with therapeutic hypothermia) between 2006 and 2010 who were diag-nosed with encephalopathy in the first 3 days of life. Demographic, perinatal, and medical conditions were recorded, along with treat-ments, comorbidities, and outcomes. The modality, timing, and results of neuroimaging were also collected. RESULTS: CT scans were performed on 933 of 4107 (22.7%) infants, and 100 of 921 (10.9%) of those received multiple CT scans. Compared with MRI, CT provided less detailed evaluation of cerebral injury in areas of prognostic significance, but was more sensitive than cranial ultra-sound for hemorrhage and deep brain structural abnormalities. DISCUSSION: Using a large, multicenter database, this study indicates that CT is still commonly used for the evaluation of term and near term infants with suspected brain injury. Our data indicate that CT performs relatively poorly for delineation of the common patterns of brain injury in neonatal encephalopathy, including deep nuclear gray matter and white matter injury. In comparison with MRI, CT detected less than one-third of deep nuclear gray matter injuries and few brainstem or cerebellar lesions. These findings are consistent with previous publications revealing MRI detects brain injuries and malformations in infants that CT misses. Because CT was inferior in detecting pathology in the deep gray matter, white matter, brain-stem, and cerebellum, using CT alone for assessing the prognosis may lead to inaccurate counseling. Because CT scanning has inherent risks, one should consider alternative neuroimaging modalities. Physician groups, government organizations, and the media have voiced concerns about the harmful effects of medical radiation and encourage the use of alternative forms of imaging when possible. Major national and international organizations agree that there is likely no amount of radiation that can be considered absolutely safe.4 Recent data from irradiated children demonstrate small, but significant increases in cancer risk, even at levels of radiation (25–50 milligray; 1.8–3.8 millisievert) comparable with those produced by neonatal and pediatric CT scans. CONCLUSIONS: This study has identified key gaps in the implementation of optimal neuroimaging methods to define the nature of brain injury in newborns with encephalopathy. A significant proportion of infants received no neuroimaging evaluation. Many of the cohort infants were exposed to CT scanning, a modality with less sensitivity for brain injury and greater potential harm due to radiation exposures. For infants with neonatal encephalopathy, we conclude that using cranial ultrasound for screening, followed by MRI is more appropriate than CT at any stage of evaluation. Our data support the superiority of MRI in identifying injuries to the deep nu-clear gray matter, brainstem, and cerebellum, and perinatal strokes. These lesions are consistent with but not di-agnostic of hypoxic-ischemic injury as the major etiology for encephalopathy.
Efficacy of Hypothermia: Cochrane Analysis
11 randomized clinical trials including 1505 patients counted in analysis
Jacobs et al., Cochrane Database Syst Rev. 2013 Jan 31;1:CD003311.
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CONFIRMED – This is the most recent reference from Cochrane. Outcomes at 2 years. Infants w/ NE will die or have major disability MAIN RESULTS We included 11 randomized controlled trials in this updated review, comprising 1505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia. Therapeutic hypothermia resulted in a statistically significant and clinically important reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (typical RR 0.75 (95% CI 0.68 to 0.83); typical RD -0.15, 95% CI -0.20 to -0.10); number needed to treat for an additional beneficial outcome (NNTB) 7 (95% CI 5 to 10) (8 studies, 1344 infants). Cooling also resulted in statistically significant reductions in mortality (typical RR 0.75 (95% CI 0.64 to 0.88), typical RD -0.09 (95% CI -0.13 to -0.04); NNTB 11 (95% CI 8 to 25) (11 studies, 1468 infants) and in neurodevelopmental disability in survivors (typical RR 0.77 (95% CI 0.63 to 0.94), typical RD -0.13 (95% CI -0.19 to -0.07); NNTB 8 (95% CI 5 to 14) (8 studies, 917 infants). Some adverse effects of hypothermia included an increase sinus bradycardia and a significant increase in thrombocytopenia. AUTHOR’S CONCLUSION There is evidence from the 11 randomized controlled trials included in this systematic review (N = 1505 infants) that therapeutic hypothermia is beneficial in term and late preterm newborns with hypoxic ischaemic encephalopathy. Cooling reduces mortality without increasing major disability in survivors. The benefits of cooling on survival and neurodevelopment outweigh the short-term adverse effects. Hypothermia should be instituted in term and late preterm infants with moderate-to-severe hypoxic ischaemic encephalopathy if identified before six hours of age. Further trials to determine the appropriate techniques of cooling, including refinement of patient selection, duration of cooling and method of providing therapeutic hypothermia, will refine our understanding of this intervention. PLAIN LANGUAGE SUMMARY There is evidence that induced hypothermia (cooling) of newborn babies who may have suffered from a lack of oxygen at birth reduces death or disability, without increasing disability in survivors. This means that parents should expect that cooling will decrease their baby’s chance of dying, and that if their baby survives, cooling will decrease his/her chance of major disability. A lack of oxygen before and during birth can destroy cells in a newborn baby’s brain. The damage caused by the lack of oxygen continues for some time afterwards. One way to try to stop this damage is to induce hypothermia - cooling the baby or just the baby’s head for hours to days. This treatment may reduce the amount of damage to brain cells. This review found that there is evidence from trials to show that induced hypothermia helps to improve survival and development at 18 to 24 months for term and late preterm newborn babies at risk of brain damage. More research is needed to understand which infants need cooling and the best way of cooling, including duration of treatment and method of cooling. NNT 6 Death or major disability in survivors assessed Five trials reported the effect of hypothermia on death of major dis-ability by severity of baseline encephalopathy (Gunn 1998; Cool Cap Study 2005; NICHD Study 2005; Zhou 2010; ICE Study 2011). There were 472 infants with moderate encephalopathy, of whom 212 died or survived with major neurodevelopmental dis-ability. Meta-analysis of the five trials demonstrated a significant effect on death or major disability in survivors who had moderate encephalopathy (typical RR 0.68 (95% CI 0.56 to 0.84), typical RD -0.17 (95% CI -0.26 to -0.08), NNTB 6 (95% CI 4 to 13)). There was no significant heterogeneity of treatment effect (I2 = 0%). There were 283 infants with severe encephalopathy, of whom 220 died or survived with major neurodevelopmental disability. Meta-analysis of the five trials found a significant reduction in death or major neurodevelopmental disability in survivors (typical RR 0.82 (95% CI 0.72 to 0.93), typical RD -0.16 (95% CI -0.25 to -0.06), NNTB 6 (95% CI 4 to 17)). There was no significant heterogeneity of treatment effect (I2 = 0%)
Cool Cap
How to cool?
Whole Body CoolingImages courtesy of Terrie Inder, MD
34.5
33
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Presentation Notes
Cool Cap All of the fetal lamb studies documenting benefit for cooling were done with the cool cap which circulates cold water at 10C and the baby’s body temperature drops 34.5C whereas in the body cooling devices the body temperature is dropped to 33.%C. No head to head trial has been done but people have moved away from the cool cap because of continuous EEG monitoring which is challenging under a cool cap. Whole Body Cooling Criticool blanket –the parents can hold the baby Black&White Photo is from the Blanketrol NICHD trials
Reduction in cerebral lesions on MRI with therapeutic hypothermia (TOBY trial)
Lesion Site Adjusted odds ratio (95% confidence intervals)
Basal ganglia and thalami 0.36 (0.15-0.84) P=0.02
Posterior limb of internal capsule 0.38 (0.17-0.85) P=0.02
White matter 0.30 (0.12-0.77) P=0.01
Cortex 0.62 (0.27-1.41) P=0.25
Rutherford M, et al. Lancet Neurol. Jan 2010; 9(1): 39–45.
131 of 325 had MRI
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Findings 325 infants were recruited in the TOBY trial between 2002 and 2006. Images were available for analysis from 131 infants. Therapeutic hypothermia was associated with a reduction in lesions in the basal ganglia or thalamus (OR 0·36, 95% CI 0·15–0·84; p=0·02), white matter (0·30, 0·12–0·77; p=0·01), and abnormal posterior limb of the internal capsule (0·38, 0·17–0·85; p=0·02). Compared with non-cooled infants, cooled infants had fewer scans that were predictive of later neuromotor abnormalities (0·41, 0·18–0·91; p=0·03) and were more likely to have normal scans (2·81, 1·13–6·93; p=0·03). The accuracy of prediction by MRI of death or disability to 18 months of age was 0·84 (0·74–0·94) in the cooled group and 0·81 (0·71–0·91) in the non-cooled group. Interpretation Therapeutic hypothermia decreases brain tissue injury in infants with hypoxic–ischaemic encephalopathy. The predictive value of MRI for subsequent neurological impairment is not affected by therapeutic hypothermia.
2014 Report
• AAP - Co-Author• ACOG - Co-Author• CREOG• RCOG• SMFM• SOGC• Federal agencies can no
longer endorse but were represented• CDC• NICHD
Neonatal Encephalopathy and Neurologic Outcome
• Task Force prefers term “neonatal encephalopathy” [NE] to “hypoxic ischemic encephalopathy” [HIE]
• HIE is a cause-specific subset of NE
• Continued absence of precise terminology in the literature since 2003 document
• An array of developmental outcomes may arise following NE in addition to CP
ACOG/AAP 2014
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In the first edition of this report, the Task Force on Neonatal Encephalopathy and Cerebral Palsy out-lined criteria deemed essential to establish a causal link between intrapartum hypoxic events and cerebral palsy. The title of this report has been changed from Neonatal Encephalopathy and Cerebral Palsy: Defining the Pathogenesis and Pathophysiology to Neonatal Encephalopathy and Neurologic Outcome to indicate that an array of developmental outcomes arise after neonatal encephalopathy in addition to cerebral palsy.
Pre- and Perinatal Causal Pathways to CP in Term Infants
A B C D E
Conception ± DRF ± DRF ± DRF ± DRF
Antepartum ± DRF PRF PRF ± DRF
Intrapartum PRF PRF PRF ± DRF
Neonatal NE NE ± NE NE PRF NE
Childhood CP CP CP CP CP
DRF= distal risk factor PRF= proximal risk factor = Time of irreversible brain damage/anomaly
ACOG/AAP 2014
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Presentation Notes
It is now known that there are multiple potential causal pathways that lead to cerebral palsy in term infants, and the signs and symptoms of neonatal encephalopathy may range from mild to severe, depending on the nature and timing of the brain injury. Prenatal and perinatal causal pathways to cerebral palsy in term infants. Distal risk factors exert a pathogenic effect on fetal brain development starting at a time that is remote from the onset of irreversible brain injury. Examples include genetic abnormalities, environmental and socio-demographic factors, and some placental abnormalities. Proximal risk factors exert pathogenic effects on fetal brain development at a time that closely predates or coincides with the onset of irreversible brain injury. Examples include abruptio placentae, chorioamnionitis, and twin–twin transfusion. There are multiple potential causal pathways that lead to cerebral palsy in term infants, and the signs and symptoms of neonatal encephalopathy may range from mild to severe, depending on the nature and timing of the brain injury. Intrapartum brain injury that is due to a proximal risk factor may lead to neonatal encephalopathy and subsequent cerebral palsy. Intrapartum brain injury may be the result of both distal and proximal risk factors that predispose the fetus to brain injury and cerebral palsy. . Brain injury or anomaly may occur in the antepartum period as a result of distal and proximal risk factors. When brain injury or anomaly occurs at a time that is remote from the delivery process, neonatal encephalopathy may or may not be seen after birth. Brain injury may occur at multiple points during gestation. Proximal risk factor and brain injury may occur in the neonatal period following predisposing distal risk factors. Note that postneonatal causes of cerebral palsy are not addressed in this diagram. Abbreviations: DRF, distal risk factor; PRF, proximal risk factor.
that accurately identifies with high sensitivity and specificity, an infant whose NE is attributable to an acute intrapartum event
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Presentation Notes
Thus, for the current edition, the task force determined that a broader perspective may be more fruitful. This conclusion reflects the sober recognition that knowledge gaps still preclude a definitive test or set of markers that accurately identifies, with high sensitivity and specificity, an infant with whom NE is attributable to an acute intrapartum event. The information necessary for assessment of likelihood can be derived from a comprehensive evaluation of all potential contributing factors in cases of neonatal encephalopathy. This is the broader perspective championed in the current report. If a comprehensive etiologic evaluation is not possible, the term hypoxic–ischemic encephalopathy should best be replaced by neonatal encephalopathy, because neither hypoxia nor ischemia can be assumed to have been the unique initiating causal mechanism. The title of this report has been changed from Neonatal Encephalopathy and Cerebral Palsy: Defining the Pathogenesis and Pathophysiology to Neonatal Encephalopathy and Neurologic Outcome to indicate that an array of developmental outcomes may arise after neonatal encephalopathy in addition to cerebral palsy.
Piecing it together…
Comprehensive Evaluation of NE
• Maternal medical history
• Obstetric antecedents
• Intrapartum factors
• Placental pathology
• Newborn course
• Labs
• EEG
• Neuroimaging
Ob and Neonatal Checklist examples provided in the publication appendix.
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Presentation Notes
To determine the likelihood that an acute hypoxic-ischemia event occurring within close temporal proximity to delivery contributed to neonatal encephalopathy, it is recommended that a comprehensive multidimensional assessment be performed of neonatal status and all potential contributing factors, including maternal medical history, obstetric antecedents, intrapartum factors (including fetal heart rate monitoring results and issues relating to the delivery itself ), and placental pathology. The items to be included in the assessment are described as follows…
Purpose of identifying the cause(s) which have contributed to NE
Guide treatment
Judge prognosis
Appropriate family counseling
Improving clinical practice
Guide research efforts
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Presentation Notes
To set the framework for this perspective, we pose the following question: What is the purpose of identifying an acute intrapartum hypoxic–ischemic event as a contributory factor to neonatal encephalopathy? The answers highlight potential benefits for patients in terms of guiding treatment, judging prognosis, providing appropriate family counseling, improving clinical practice, as well as fostering advances in research to investigate the complex heterogeneous processes leading to neonatal encephalopathy. TREATMENT One of the aims of thorough assessment of the contributing events in neonatal encephalopathy is to identify neonates who are more likely to benefit from treatment. Different therapeutic interventions may be appropriate for different etiologic features or physiologic responses to harm. For example, oxygen deprivation as an instigator of neonatal encephalopathy would likely lead to different intervention strategies than cases caused by thrombosis or inflammation. More accurate and timely identification of the salient factors for intervention in each individual case will improve accuracy of the assignment of optimal treatment for a given patient and may improve the outcome of all the treated neonates. The fact that more than 40% of neonates undergoing hypothermia treatment still develop adverse neurologic outcomes underscores the research need to further understand the underlying processes in neonatal encephalopathy, which ideally will yield more effective clinical criteria for matching each patient with tailored treatment options. The current emphasis is on identification of the optimal criteria for the identification of cases in which there is a hypoxic or ischemic contribution to a neonatal encephalopathy of recent onset, which inevitably will be much less stringent than defining essential criteria. PROGNOSIS Another aim of assessing the contributing events and medical profile of a neonate with neonatal encephalopathy is to compile a prognostic profile that sets reliable short-term and long-term expectations for the neonate’s clinical course, treatment needs, and outcome. Current prognostic indicators, such as the Sarnat classification system or electroencephalography to stratify the severity of neonatal encephalopathy, are useful but insufficient as stand-alone tests. It is likely that a battery of markers in conjunction with clinical findings and brain imaging will be most predictive, rather than any one feature alone. Thus, better understanding of the processes leading to neonatal encephalopathy and their associated outcomes may help develop more accurate and reliable tools for prognostic forecasting. FAMILY COUNSELING Refinement of the eligibility protocols for specific interventions that improve efficacy of treatment, as well as development of better prognostic indicators, will enhance the quality of information provided to families about the care and expected outcome for their infant. More accurate information gathering regarding the contributors to the encephalopathy will also more quickly address family concerns over potential sources of harm. IMPROVING CLINICAL PRACTICE AND SYSTEMS A comprehensive evaluation of contributing events in neonatal encephalopathy also should include assessment of the delivery of clinical care with the aim of identifying existing strengths, weaknesses, and opportunities for improvement (see appendix a). Medical errors are frequently the result of inadequate or inaccurate communication, and a cornerstone of patient safety programs is error reporting. Root-cause analysis can serve as a powerful tool to identify the contributing causes that underlie variations in performance associated with adverse events. Institutions can use root cause analysis both to explain why an adverse event occurred and to design systems to prevent or reduce the frequency of recurrence. RESEARCH Clinical practice and research have a direct relationship. Recognition of the limitations in current clinical assessment and data collection practices inform the research questions that need to be addressed and the corresponding data collection needs. In turn, results from laboratory, clinical, and epidemiologic research on the heterogeneous processes leading to neonatal encephalopathy and associated outcomes will have a significant effect on shaping the relevant data content needed for clinical assessment to determine the processes leading to neonatal encephalopathy in individual cases. As emphasized throughout this guideline, future research in this area requires detailed, in-depth data gathering on the complex causal mechanisms underlying neonatal encephalopathy and testing of novel hypotheses to provide new opportunities for intervention. (EPO NO)
I. Case Definition
II. Neonatal Signs Consistent with an Acute Peripartum or Intrapartum Event
III. Type & Timing of Contributing Factors
IV. Developmental Outcome Is Spastic Quadriplegia or Dyskinetic Cerebral Palsy
Comprehensive Evaluation of NE
Presenter
Presentation Notes
(Clinical Definition) Definition and criteria in 2003 report is as follows: “A clinically defined syndrome of disturbed neurologic function in the earliest days of life in the term infant, manifested by difficulty with initiating and maintaining respiration, depression of tone and reflexes, subnormal level of consciousness, and often by seizures.” Criteria to Define an Acute Intrapartum Hypoxic Event as Sufficient to Cause Cerebral Palsy Evidence of a metabolic acidosis in fetal, umbilical cord arterial blood obtained at delivery (pH<7.00 and base deficit >12 mmol/L) Early onset of severe or moderate NE in infants of 34 or more weeks of gestation Cerebral palsy of the spastic quadriplegic or dyskinetic type Exclusion of other identifiable etiologies such as trauma, coagulation disorders, infectious conditions, or genetic disorders From 2014 report, pg 208: This expanded clinical definition must be put into use based on measures that can be reliably and accurately implemented by trained staff. The first mandatory step in an assessment of neonatal encephalopathy is to confirm whether a specific patient meets the case definition. In confirmed cases of neonatal encephalopathy, the following assessment items will determine the likelihood that an acute peripartum or intrapartum event was a contributor. This list is based on the premise that neonatal encephalopathy that is due to acute hypoxia–ischemia will be accompanied by abnormal neonatal signs and be associated with contributing events in close temporal proximity to labor and delivery. The goal of the assessment is to compile a constellation of markers concerning neonatal status, contributing events, and developmental outcome to determine if they are consistent with acute hypoxia–ischemia and may not be explained by other etiologies. Thus, when more of the elements from each of the item categories are met, it becomes increasingly more likely that peripartum or intrapartum hypoxia–ischemia played a role in the pathogenesis of neonatal encephalopathy.
I. Case Definition
Neonatal Encephalopathy• “A syndrome of disturbed neurological
function • in the earliest days of life in the infant at or
beyond 35 weeks gestation, • manifested by subnormal levels of
consciousness or seizures, • and often accompanied by difficulty with
initiating and maintaining respirations and depression of tone and reflexes.”
ACOG/AAP 2014
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Presentation Notes
2003 Definition: A clinically defined syndrome of disturbed neurologic function in the earliest days of life in the term infant, manifested by difficulty with initiating and maintaining respiration, depression of tone and reflexes, subnormal level of consciousness, and often by seizures.
I. Case Definition
II. Neonatal Signs Consistent with an Acute Peripartum or Intrapartum Event
III.Type & Timing of Contributing Factors
IV.Developmental Outcome Is Spastic Quadriplegia or Dyskinetic Cerebral Palsy
Comprehensive Evaluation of NE5, 10 min Apgar <5Fetal UA AcidemiaClinical EvaluationNeuroimagingMultisystem organ failure
II. Neonatal Signs Consistent with an Acute Peripartum or Intrapartum Event
Apgar Score of <5 at 5 and 10 Minutes
• Low Apgar scores at 5 and 10 minutes significantly increase the risk of long-term neurologic impairment
• Degree of Apgar abnormality at 5 and 10 minutes correlates with the risk of CP
• If the Apgar score at 5 minutes is ≥ 7, it is unlikely that peripartum hypoxia–ischemia played a major role in causing NE
ACOG/AAP 2014
Presenter
Presentation Notes
Apgar Score of Less Than 5 at 5 and 10 Minutes Low Apgar scores at 5 and 10 minutes significantly increase the risk of long-term neurologic impairment The degree of Apgar abnormality at 5 and 10 minutes correlates with the risk of CP. However, the vast majority of infants with low Apgar scores will not develop CP There are many potential causes for a low Apgar score. If the Apgar score at 5 minutes is greater than or equal to 7, it is unlikely that peripartum hypoxia–ischemia played a major role in causing NE.
II. Neonatal Signs
Fetal Umbilical Artery Acidemia
pH less than < 7 or BD ≥12mmol/L
• Commonly accepted as indicative of pathologic fetal acidemia
• Continuum of increasing risk of NE with worsening acidemia
• Even in the presence of significant acidemia, the majority of newborns will be neurologically normal
• If the cord arterial gas pH levels are 7.20 or greater, it is unlikely that peripartum hypoxia played a role in causing NE
• The presence of metabolic acidemia does not define the timing of the onset of a hypoxic–ischemic event
ACOG/AAP 2014
Presenter
Presentation Notes
Although the thresholds of pH less than 7 or base deficit greater than or equal to 12mmol/L are commonly accepted as indicative of pathologic fetal acidemia, there is a continuum of increasing risk of NE with worsening acidemia It is important to remember that even in the presence of significant acidemia, the majority of newborns will be neurologically normal The presence of metabolic acidemia does not define the timing of the onset of a hypoxic–ischemic event
II. Neuroimaging Evidence of Acute Brain Injury
• MRI is the neuroimaging modality of choice
• Distinct patterns of neuroimaging abnormalities recognized in HIE injury in infants
• Have prognostic value for predicting neurodevelopmental impairment
• A normal MRI/MRS obtained after the first 24 hours of life makes intrapartum hypoxia unlikely
ACOG/AAP 2014
Presenter
Presentation Notes
From 2014 report, pg. 209: Magnetic resonance imaging (MRI) is the neuroimaging modality that best defines the nature and extent of cerebral injury in neonatal encephalopathy. Cranial ultrasonography and computed tomography lack sensitivity for the evaluation of the nature and extent of brain injury in the term encephalopathic infant. Distinct patterns of neuroimaging abnormalities are recognized in hypoxic–ischemic cerebral injury in the infant born at or beyond 35 weeks of gestation and have prognostic value for predicting later neurodevelopmental impairments. If the results of the MRI or magnetic resonance spectroscopy, obtained after the first 24 hours of life, are interpreted by a trained neuroradiologist and no areas of injury are noted, then it is unlikely that significant peripartum or intra-partum hypoxic–ischemic brain injury was a significant factor in neonatal encephalopathy. It is important to note that the full extent of injury may not be evident on MRI until after the first week of life. Early MRI between 24 hours and 96 hours of life may be more sensitive for the delineation of the timing of perinatal cerebral injury, whereas an MRI undertaken optimally at 10 days of life (with an acceptable window between 7 days and 21 days of life) will best delineate the full extent of cerebral injury.
Intrapartum Hypoxic-Ischemic Brain Injury
- Sentinel Event Identified
- Cord pH < 7.00 - Resuscitation
- Low Apgar scores - More Severe
Encephalopathy and Seizures
- Mechanism frequently not as clear
- Cord pH < 7.00- Variable Resuscitation
requirement - Apgar scores usually
higher- Milder or Delayed Onset
Encephalopathy - Neuroimaging +
Patterns of “Acute” Cerebral Injury
Sarkar A, et al. J Pediatr 2011; 159:726-30. Shalak L, et al. Early Hum Dev. 2004 Nov;80(2):125-41.
Images courtesy of Terrie Inder, MD
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Presentation Notes
2014 report, pg. 210, #4: There are several well-defined patterns of brain injury and their evolution on MRI that are typical of hypoxic–ischemic cerebral injury in the newborn, including deep nuclear gray matter or watershed cortical injury. If a different pat-tern of brain injury or evolution of injury exists on MRI, then alternative diagnoses should be actively pursued (e.g., metabolic and genetic investigations). Shalak paper: MR techniques have become very important in delineating evolving structural, metabolic and functional changes following intrapartum hypoxia–ischemia. Thus, using conventional MR, three patterns of signal abnormalities can be identified including injury to the thalami and/or posterior–lateral putamen with involvement of the subcortical white matter in the most severe cases; injury to the parasagittal gray matter and subcortical white matter, posterior usually more than anterior; and focal or multifocal injury. The initial step in management is early identification of those infants at greatest risk for evolving to the syndrome of hypoxic–ischemic encephalopathy (HIE). This is a highly relevant issue because the therapeutic window, i.e., the time interval following hypoxia–ischemia during which interventions might be efficacious in reducing the severity of ultimate brain injury, is likely to be short. Based on experimental studies, it is estimated to vary from 2 to 6 h. Given this presumed short window of opportunity, infants must be identified as soon as possible following delivery in order to facilitate the implementation of early interventions. There are increasing data to indicate that the highest risk infant can be identified shortly after birth by a constellation of findings. These include evidence of a sentinel event during labor, i.e., fetal heart rate abnormality, a severely depressed infant (low extended Apgar score), the need for resuscitation in the delivery room (i.e., intubation, chest compression Fepinephrine administration), evidence of severe fetal acidemia (cord umbilical artery pHb7.00 and/or base deficit N16 mEq/l), followed by evidence of an early abnormal neurologic examination and/or abnormal assessment of cerebral function, i.e., integrated EEG. Thus, in a prospective study of 50 infants who had evidence of intrapartum distress, Apgar score 5 at 5 min, or cord arterial pH 7.00 and underwent an early neurologic examination using a modified Sarnat staging system (stages 2 and 3 were regarded as abnormal) and a blinded simultaneous a-EEG measurement, predictive values were calculated for a short-term abnormal outcome defined as persistent moderate to severe encephalopathy beyond 5 days. An abnormal outcome evolved in 14 (28%) of the 50 infants. A combination of abnormalities had the highest specificity (94%) and positive predictive value (85%). Thus, a combination of the a-EEG and the neurologic examination shortly after birth enhances the ability to identify high-risk infants and limits the number of infants who would be falsely identified compared with either evaluation alone.
Posterior Limb of the Internal Capsule (PLIC)
Rutherford MA, et el. Pediatrics 1998; 102;323.
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Presentation Notes
Imaging helps to determine the prognosis. Left image shows bright signal in myelinated PLIC (like a railroad) in contrast right image shows high signal in the thalamus and lentiform with absent rail road so looks black instead of bright white. Methods. We have examined 73 term neonates with HIE between 1 and 17 days after birth with cranial magnetic resonance imaging and related the magnetic resonance imaging findings to neurodevelopmental outcome at 1 year of age. Results. All infants with an abnormal signal intensity in the PLIC developed neurodevelopmental impairment although in 4 infants with very early scans the abnormal signal was not apparent until up to 4 days after birth. A normal signal intensity was associated with a normal outcome in all but 4 cases; 3 of these infants had minor impairments and all had persistent imaging changes within the white matter. The 4th infant with a normal signal intensity on day 2 died before a further image could be obtained. The absence of normal signal predicted abnormal outcome in term infants with HIE with a sensitivity of 0.90, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.87. The test correctly predicted outcome in 93% of infants with grade II HIE, according to the Sarnat system. Applying a Bayesian approach, the predictive probability of the test (the probability that the test would predict an outcome correctly) was distributed with a mean of 0.94 and 95% confidence limits of 0.89 to 1.0. Conclusion. Abnormal signal intensity in the PLIC is an accurate predictor of neurodevelopmental outcome in term infants suffering HIE.
Deep Nuclear Gray Matter Injury
Martinez-Biarge M, et al. Early Hum Dev. 2010 Nov;86(11):675-82.
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Presentation Notes
There are three severities of DNGM injury – mild with minimal high signal in the lentiform (left image arrow) but with an intact PLIC – high signal (lower image arrow) due to the myelination in the posterior limb of the internal capsule which is the major pathway for the corticospinal tract from the motor cortex to the spinal cord. The middle image shows moderate injury with more definitive high signal in the thalamus and lentiform and equivocal PLIC in the lower image. The right image shows severe thalamic and lentiform high signal with sparing of the caudate and absent PLIC signal. Basal ganglia and thalami Abnormal signal intensities in the BGT, the posterior limb of the internal capsule (PLIC) and the brainstem are typical of neonates with encephalopathy after an acute hypoxic–ischaemic event. This pattern of injury, particularly when moderate or severe, is usually accompa-nied by some damage to the cortex and sub-cortical white matter, but the periventricular and deep white matter may also be involved, usually when there is no history of a sentinel event. We have classified BGT lesions into mild, moderate and severe (Fig. 1, top row). Mild lesions are defined as focal and subtle abnormalities, usually in the ventrolateral nuclei of the thalami and/or the posterior putamen. Moderate lesions appear as either multifocal discrete areas of damage or more diffuse abnormal signal intensities (usually on the T2-weighted images) involving different regions in the BGT. Severe injury refers to the widespread abnormal signal intensity involving the whole BGT area (sometimes the caudate nuclei are preserved). Posterior limb of the internal capsule The appearance of the PLIC is very important and is usually connected with the severity of the BGT lesions. It can be described as: normal, equivocal and abnormal. A normal PLIC is myelinating at term age and is of high signal intensity on T1-weighted or inversion recovery sequences (extending forward about halfway towards the genu of the internal capsule) and of low signal intensity on T2-weighted sequences (not to the same degree as seen on the T1-weighted image and with a more ovoid shape). An equivocal PLIC is one with reduced or asymmetrical signal intensity and an abnormal PLIC has loss, reversed or abnormal signal intensity on T1 and/or T2-weighted sequences (Fig. 1, bottom row). Most infants with mild BGT injury have a normally appearing PLIC and almost all infants with severe BGT injury have an abnormal PLIC; however infants with moderate lesions may have equivocal or abnormal signal intensity in the PLIC. In a normal brain the whole of the PLIC should be myelinated on a T1-weighted image by 46 weeks post-menstrual age; when inter-preting scans done in the later neonatal period it is important to note any delay in this normal maturation process. Cortex Most children with BGT injury have cortical injury and many have some accompanying white matter injury. Cortical changes are usually seen in specific regions, most commonly around the central sulcus, the interhemispheric fissure and the insula. During the first week cortical abnormalities are seen as a loss of markings (loss of grey/white matter differentiation), whereas cortical highlighting is more commonly seen after the first week. Cortical injury can be classified as mild when only 1–2 sites are involved; moderate when 3–4 sites are involved and severe when the involvement is widespread. Death 20–30% of infants with HIE die during the neonatal period, usually after withdrawal of intensive care. The decision to withdraw life support is generally based on the clinical state with further information being provided by sequential cranial ultrasound imaging and Doppler measurements of cerebral blood flow velocity, early amplitude integrated and/or conventional EEG, and MR imaging and spectroscopy, confirming the expected poor prognosis. Another 15–20% of children will die within the first 2–3 years. In almost all children who die after the neonatal period, death is preceded not only by motor abnormality but also by severe feeding problems and epilepsy. Perinatal variables (Apgar scores, cord pH and need for resuscitation), are predictive of neonatal death in infants with HIE. In our cohort, infants with Apgar scores of b3 at 1 and b5 at 5 min., with apHb7.0 and who required intubation, cardiac compressions and drugs for resuscitation were four times more likely to die in the neonatal period than those who were not so severe as this at birth. MRI scans of infants who die usually show severe BGT lesions and not infrequently, significant damage to the cortex and the white matter, but the best predictor of death both in the neonatal period and later is the presence and severity of the brainstem lesions. Our data shows that infants with a normal looking brainstem had a very low risk of dying, whereas 50% of infants with severe brainstem injury died neonatally or during infancy. Infants with a moderately abnormal looking brainstem were at an intermediate (~25%) risk of dying.
Severe: 19%Martinez-Biarge M, et al. Early Hum Dev. 2010 Nov;86(11):675-82.
Presenter
Presentation Notes
Miriam Martinez-Biarge et al , Outcomes after central grey matter injury in term perinatal hypoxic-ischaemic encephalopathy. Early Human Development, Volume 86, Issue 11, 2010, 675 - 682 ABSTRACT: Central grey matter damage following perinatal hypoxia–ischaemia frequently leads to death or motor abnormality often with deficits in other developmental domains. Predicting these different outcomes is difficult yet very important for early management, planning and providing for needs on discharge and later and not least for parents to know how their children will be affected. The best single predictor of the pattern of outcomes for an individual infant is an early MRI scan. We present a guide for predicting outcome at 2 years in different developmental domains based on the severity of injury seen in the basal ganglia and thalami (BGT) on neonatal MRI. CHILDREN WITH MILD BGT We found that most of these infants had a normal PLIC, a small percentage having an equivocal PLIC. Only 10–15% of infants in this group developed cerebral palsy and most had only mild or moderate motor impairment (maximum GMFCS level III). Infants with mild BGT and a normal PLIC were able to walk independently by 2 years; in the small subgroup of infants with an equivocal PLIC, most were walking by 2 years, although some not before 18 months. The prevalence of co-morbidities in this group was also low. In our cohort almost 80% had a developmental quotient (DQ) N85 and 12%had a DQ between 70 and 84. We found that only infants with moderate or severe cortical injury were at increased risk of developing seizures in infancy. This group that appears to be making good developmental progress still needs longer term follow-up. Info from full chart: Feeding: 10% may have some mild feeding problems. No need for gastrostomy. Speech & language: 25% may have some speech problems; in most cases mild-moderate Vision: The probability of visual impairment is very low, unless there is more extensive white matter injury. Developmental Quotient (DQ): >84 in 80% and >70 in 90%, especially if PLIC is normal
Moderate Basal Ganglia/Thalamic
Equivocal PLIC
Look at the PLIC
SeizuresDQ
Cerebral palsy 60%Mostly mild (75%)
2/3 will be walking, may start late
VisionFeeding
Abnormal PLIC
Cerebral palsy 75%Moderate (50%) or Severe (40%)
70-80% will not walk at 2 yrs
Speech & language
40-50%Most, with
severe in 25% 20-55% 50-75% assessable35% DQ <70
Look in the cortex
Normal/Mild: 3-6%Moderate: 11%
Severe: 19%Martinez-Biarge M, et al. Early Hum Dev. 2010 Nov;86(11):675-82.
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CHILDREN WITH MODERATE BGT This is the most difficult group in terms of prediction (Fig. 5). The risk of cerebral palsy in this group varied according to the involvement of the PLIC: 60% of infants with an equivocal PLIC and 75% with an abnormal PLIC developed CP, whereas most of the infants with an equivocal PLIC had the mildest form of motor impairment (GMFCS I), the majority of infants with an abnormal PLIC had moderate or severe motor impairment and most were not be able to walk by the age of 2 years. Feeding and speech problems were relatively common in this group, especially the latter. Although half of the infants in this group showed some grade of oromotor dysfunction in infancy, only a minority had severe problems later and needed a gastrostomy. The grade of visual impairment was variable and seemed to depend on the accompanying white matter and brainstem injury: when the white matter damage was extensive and there was brainstem involvement, especially at the level of the mesencephalon, over 50% of infants had some visual impairment.
Martinez-Biarge M, et al. Early Hum Dev. 2010 Nov;86(11):675-82.
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Presentation Notes
CHILDREN WITH SEVERE BGT Almost all infants in this group developed cerebral palsy and the functional impairment was severe (GMFCS IV/V) in the majority, making it very unlikely that they would be able to walk at the age of 2 or later. Feeding and communication problems were very common. Assessing the brainstem added important information to the prediction of the most severe feeding problems: when it was severely affected the probability of needing a gastrostomy in infancy was higher than 90%. Visual impairment was frequent, especially with significant white matter or mesencephalic injury. The probability of having seizures was high in general and related to the severity of the cortical injury. As most children had significant motor impairment and communication difficulties, the assessment of their cognitive abilities was challenging. Even in cases where a child could be tested using a developmental test the score obtained may not reflect the child's real abilities. Info from chart: Feeding: 90% will have some feeding problems Speech & language: 95% will have some speech problems; severe in most Vision: 50-75% will have some grade of visual impairment, especially with moderate-severe white matter and brainstem injury Developmental Quotient (DQ): Children are in general difficult to assess because of their motor impairment at this age
II. Neuroimaging Evidence of Acute Brain Injury Summary
• MRI is the neuroimaging modality of choice
• Distinct patterns of neuroimaging abnormalities recognized in HIE injury in infants
• These patterns have prognostic value for predicting neurodevelopmental impairment
ACOG/AAP 2014Images courtesy of Terrie Inder, MD
II. Presence of Multisystem Involvement Consistent With HIE
• Multisystem involvement includes:
• renal, hepatic, cardiac, gastrointestinal injury, or hematologic abnormalities
• Although presence of organ dysfunction increases the chance of HIE in the setting of NE, severity of brain injury seen on imaging does not always correlate with injuries to other organ systems
Presenter
Presentation Notes
or a combination of these
I. Case Definition
II. Neonatal Signs Consistent with an Acute Peripartum or Intrapartum Event
III. Type & Timing of Contributing Factors
IV. Developmental Outcome Is Spastic Quadriplegia or Dyskinetic Cerebral Palsy
Comprehensive Evaluation of NE
• Was there a sentinel event?• What was interpretation of fetal heart rate
strips?• Timing of and findings on neuroimaging?• Other contributing events
Presenter
Presentation Notes
Is there a sentinel event What is happening with the fetal heart rate strips Imaging Multi system involvement Other contributing events
III. Type and Timing of Contributing Factors Consistent with an Acute Peripartum or Intrapartum Event
• A sentinel hypoxic or ischemic event occurring immediately before or during labor and delivery
Uterine rupture
Placental abruption
Umbilical cord prolapse
Amniotic fluid embolus
Maternal cardiac arrest
ACOG/AAP 2014
III. Fetal Heart Rate Patterns
• Fetal heart rate monitor patterns consistent with an acute peripartum or intrapartum event
• A category 1 or category 2 FHR tracing associated with • Apgar scores ≥7 at 5 minutes
• Normal arterial cord gases [+/- 1 standard deviation (SD)]
is not consistent with an acute hypoxic–ischemic event
• Great distinction needs to be made between • a patient who initially presents with an abnormal fetal heart rate pattern
• one who presents with a normal pattern and develops an abnormal fetal heart rate pattern during labor
ACOG/AAP 2014
III. Fetal Heart Rate Patterns
• An FHR pattern in a fetus who presents with • persistent minimal or absent variability and no accels• lasting ≥ 60 minutes (even in the absence of decels)
is suggestive of a previously compromised or injured fetus
• Patient presenting with a Category I FHR pattern that converts to Category III is suggestive of intrapartum hypoxia
• Other patterns that develop following a Category I FHR pattern that may suggest intrapartum timing of HIE: • tachycardia with recurrent decelerations • persistent minimal variability with recurrent decelerations
ACOG/AAP 2014
Presenter
Presentation Notes
Other patterns that develop following a Category I FHR pattern that may suggest intrapartum timing of HIE include.
III. Timing and Type of Brain Injury Patterns Consistent with an Acute Event• Cranial ultrasound lacks sensitivity for common forms of brain injury
in term NE
• Echodensity seen 48 hours or longer following hypoxic-ischemic injury
• U/S may be the only neuroimaging modality available in a very unstable infant
• CT lacks sensitivity for brain injury
• MRI and MRS most sensitive (24-96 hours) to assist with the timing of a cerebral injury
• Using conventional MRI, cerebral abnormalities become most evident after 7 days following a cerebral injury
ACOG/AAP 2014
Presenter
Presentation Notes
If Echodensity is detected on ultra sound it is seen 48 hours or longer following hypoxic ischemic injury. 2014 report, pg 210: Magnetic resonance imaging and magnetic resonance spectroscopy are the most sensitive neuroimaging modalities to assist with the timing of cerebral injury. Magnetic resonance imaging – combining conventional, diffusion, and spectroscopy - between 24 hours and 96 hours of life provides the most useful guide on the potential timing of cerebral insult.
III. Timing and Type of Brain Injury Patterns Consistent with an Acute Event• Diffusion abnormalities are most prominent between 24
and 96 hours of life
• Two MRI/MRS scans
• First between 24 and 96 hours of life with emphasis on the evaluation of diffusion and spectroscopic abnormalities to assist in clinical management and evaluation of the timing of cerebral injury
• Second at day 10 or later with an acceptable window of 7 to 21 days —will assist with full delineation of the nature and extent of cerebral injury
ACOG/AAP 2014
Presenter
Presentation Notes
2014 report, pg. 210: Diffusion abnormalities are most prominent between 24 hours and 96 hours of life. With conventional qualitative MRI, cerebral abnormalities will become most evident after 7 days from a cerebral injury. Two MRI or magnetic resonance spectroscopy scans—the first between 24 hours and 96 hours of life with emphasis on the evaluation of diffusion and spectroscopic abnormalities to assist in clinical management and evaluation of the timing of cerebral injury, and a second at day 10 of life or later—will assist with full delineation of the nature and extent of cerebral injury.
McKinstry RC, et al. Neurology. 2002 Sep 24;59(6):824-33.
Presenter
Presentation Notes
The evolution of imaging findings demonstrating that on the left hand images day 1 Dav = ADC there is minor abnormality on day 1 which becomes more obvious on day 3 and then disappears on day 8 whereas the T1 and FLAIR have abnormality that becomes visible on day 8 – T1 day 1 is questionable and T2 day 3 is also looking swollen but you would not call on that alone. This demonstrates the evolution in non-TH babies (non cooled). The right hand images are mild DNGM – principally isolated thalamic injury alone – with ADC low on day 1.9 and then negative after but T1 present on day 7.8.
III. Timing and Type of Brain Injury Patterns Consistent with an Acute Event
If different patterns pursue an alternative diagnosis
suggest intrapartum hypoxia did NOT play a role in NE
Typical of HIE injury in newborn
Deep Nuclear Grey Matter Watershed Cortical Injury
ACOG/AAP 2014
• Focal arterial infarction • Venous infarction• Intraparenchymal or
Intraventricular hemorrhage• Porencephaly
III. Timing and Type of Brain Injury Patterns Consistent with an Acute Event
• Accurate interpretation of neuroimaging is key
• If limited expertise, an expert opinion is recommended
• Despite advances in neuroimaging ability to precisely time the occurrence of HIE is still limited (days rather than hours or minutes)
ACOG/AAP 2014
III. No Evidence of Other Contributing Factors
• In the presence of other significant risk factors: • abnormal fetal growth • maternal infection • fetomaternal hemorrhage• neonatal sepsis• chronic placental lesions
• An acute intrapartum event as the sole underlying cause of NE becomes much less likely.
ACOG/AAP 2014
I. Case Definition
II. Neonatal Signs Consistent with an Acute Peripartum or Intrapartum Event
III. Type & Timing of Contributing Factors
IV. Developmental Outcome Is Spastic Quadriplegia or Dyskinetic Cerebral Palsy
Comprehensive Evaluation of NE
IV. Developmental Outcome After HIE Due to Intrapartum Events• Developmental Outcome is
• Spastic Quadriplegia or Dyskinetic Cerebral Palsy
• Other subtypes of cerebral palsy less likely to be associated with acute intrapartum hypoxia
• Other developmental abnormalities may occur
• Not specific to acute intrapartum HIE
• May arise from a variety of other causes
ACOG/AAP 2014
In the decade since the 2003 “Green Book” was first published, considerable advances have been made in our
knowledge and understanding of NE and long-term neurodevelopmental outcome.
Presenter
Presentation Notes
In the decade since the 2003 “Green Book” was first published, considerable advances have been made in our knowledge and understanding of the processes contributing to NE and long-term neurodevelopmental outcome.
• Reflects the current state of scientific knowledge
• Acknowledges limitations in definitively distinguishing HIE from other forms of NE
• No one strategy to identify HIE at present is infallible
• No single strategy will achieve 100% certainty of determining the cause of NE in all cases
This comprehensive assessment is key to recognizing: