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Neonatal Encephalopathy: Identification, Management, and Outcomes Eric Peeples, M.D. Assistant Professor, Department of Pediatrics
Neonatal Encephalopathy: Identification, Management, and OutcomesEric Peeples, M.D.Assistant Professor, Department of Pediatrics
Nebraska Perinatal Quality Improvement Collaborative
Webinar SeriesNeonatal Encephalopathy: Identification, Management, and Outcomes
Target Audience:Physicians, advanced practice providers, and nurses specializing in family medicine, obstetrics, and pediatricsEducational ObjectivesReview risk factors and presenting signs of neonatal encephalopathyDescribe early management of hypoxic-ischemic encephalopathy and indications for therapeutic hypothermiaDiscuss methods to improve outcomes for these infants, including the development of a regional registry
Requirements for Successful CompletionIn order to receive continuing education credits or contact hours, you must:Sign into ZOOM and attend the entire webinarComplete the online evaluation by signing in to MY Account at www.unmc.edu/cce
Ø Go to Evaluate a course/Print CertificateØ Use CME Activity Code 36552
Save and Print your certificate.Retain certificate for future documentation. Certificates are available up to 60 days post activity upon completion of the evaluation.
CREDITThe University of Nebraska Medical Center, Center for Continuing Education is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The University of Nebraska Medical Center, Center for Continuing Education designates this live activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
The University of Nebraska Medical Center College of Nursing Continuing Nursing Education is accredited with distinction as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. This activity is provided for 1.0 contact hour under ANCC criteria.This activity has been planned and implemented in accordance with the accreditation requirements and policies of the American Nurses Credentialing Center’s Commission on Accreditation (ANCC) through the joint providership of the University of Nebraska Medical Center College of Nursing Continuing Nursing Education (UNMC CON CNE) (provider), University of Nebraska Medical Center, Center for Continuing Education (UNMC CCE), and Nebraska Perinatal Quality Improvement Collaborative (NPQIC).
DISCLOSURE DECLARATIONAs a provider accredited by ACCME, the University of Nebraska Medical Center, Center for Continuing Education, the University of Nebraska Medical Center, College of Nursing Continuing Nursing Education, and the American Nurses Credentialing Center’s Commission on Accreditation must ensure balance, objectivity, independence, and scientific rigor in its educational activities. Faculty are encouraged to provide a balanced view of therapeutic options by utilizing either generic names or the trade names of several to ensure impartiality.All speakers, planning committee members and others in a position to control continuing medical education content participating in a University of Nebraska Medical Center, Center for Continuing Education, University of Nebraska Medical Center, College of Nursing Continuing Nursing Education, and American Nurses Credentialing Center’s Commission on Accreditation activity are required to disclose relationships with commercial interests. A commercial interest is any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. Disclosure of these commitments and/or relationships is included in these course materials so that participants in the activity may formulate their own judgments in interpreting its content and evaluating its recommendations.This activity may include presentations in which faculty may discuss off-label and/or investigational use of pharmaceuticals or instruments not yet FDA-approved. Participants should note that the use of products outside currently FDA-approved labeling should be considered experimental and are advised to consult current prescribing information for FDA-approved indications.All materials are included with the permission of the authors. The opinions expressed are those of the authors and are not to be construed as those of the University of Nebraska Medical Center, Center for Continuing Education, University of Nebraska Medical Center, College of Nursing Continuing Nursing Education, or American Nurses Credentialing Center’s Commission on Accreditation.
FACULTY AND PLANNING COMMITTEE DISCLOSURES
All faculty and planning committee members have no financial relationships to disclose.
§ Ann Anderson-Berry, MD, PhD, FAAP§ Robert Bonebrake, MD, FACOG§ Peggy Brown, DNP, RN, CPHQ (Course Director) § Heidi Keeler, PhD, RN§ Renee Paulin, MSN, RN, CWOCN§ Eric Peeples, MD§ Sara Weber, MSW, CHES, CBE
• Review risk factors and presenting signs of neonatal encephalopathy
• Describe early management of HIE and indications for therapeutic hypothermia
• Discuss methods to improve outcomes in infants with HIE
• Dispel some common misconceptions regarding HIE and hypothermia:
• “The exam was much better after an hour or two, so it’s not HIE”
• “Hypothermia is an experimental therapy”
• “I’ve been by the bed since birth and haven’t seen a seizure, so he/she is not seizing”
Lee, et al. Ped Res, 2013
UNICEF, 2017
Lee, et al. Ped Res, 2013
Hypoxic-Ischemic Encephalopathy
Risk Factors & Pathophysiology
Maternal:• Nulliparity• Eclampsia• Diabetes mellitus• Drug addiction• Cardiac disease
Utero-placental:• Placental abruption• Cord prolapse• Uterine rupture• PROM• Funisitis• Prolonged labor• Forceps delivery
Fetal/Neonatal:• Post-term• Thick meconium• Large for GA• Shoulder dystocia• Feto-maternal
hemorrhage• Genetic factors
Adapted from Hassell, et al. ADC-F&N, 2015
Therapeutic Hypothermia
Hypoxic-Ischemic Encephalopathy
Presentation & Evaluation
• Encephalopathy on exam
• Exam should be:
• >10 min after resuscitation
• Prior to initiation of hypothermia
• First exam within 1 hour; REPEAT!
• Exam evolves
• Mod-severe signs: 70% at 1 hr, 20% at 6 hr
Biselele, et al. Acta Ped, 2014
Mild (Stage 1) Moderate (Stage 2) Severe (Stage 3)Consciousness Hyperalert Lethargic Stupor or coma
Activity Normal Decreased No activity
Seizures None Common Uncommon
Neuromuscular controlPosture Mild distal flexion Strong distal flexion Decerebrate
Tone Normal Hypotonic Flaccid
Stretch Reflex Overactive Overactive Decreased or absent
Primitive reflexesSuck Weak Weak or absent Absent
Moro Strong Weak, incomplete Absent
Autonomic systemPupils Dilated Constricted Variable, min. reactive
Heart rate Tachycardia Bradycardia Variable
Sarnat & Sarnat. Arch Neur, 1976
0 1 2 3Level of Consciousness Normal Hyperalert Lethargic ComatoseTone Normal Hypertonic Hypotonic FlaccidPosture Normal Fisting, cycling Distal flexion DecerebrateFits None <3 per day >2 per dayFontanel Normal Full, not tense TensePrimitive reflexes
Suck Normal Poor AbsentGrasp Normal Poor AbsentMoro Normal Partial
Autonomic systemRespiration Normal Hyperventilation Brief apnea Apnea (PPV)
Thompson, et al. Acta Ped, 1997
Simiyu, et al. BMC Peds, 2017
• Encephalopathy on exam
• Inciting event (cord event, abruption, etc)
• CPR or continued PPV at 10 min of life
• Apgar ≤5 at 10 min of life
• Cord or baby gas (w/in 1 hour) with:
• Base deficit ≥12 or
• pH ≤7.0 (7.1??)
• Encephalopathy on exam
• Inciting event (cord event, abruption, etc)
• CPR or continued PPV at 10 min of life
• Apgar ≤5 at 10 min of life
• Cord or baby gas (w/in 1 hour) with:
• Base deficit ≥12 or
• pH ≤7.0 (7.1??)
• <40% of neonates with HIE have SE
• Cord prolapse – 37%
• Uterine rupture – 29%
• Shoulder dystocia – 20%
• Maternal hemorrhage – 14%
• Higher rate of basal ganglia injury than no SE
• Moderate/severe BG injury 37% vs 22%
• No diff in death or mod/sev disability at 18 mo
Shankaran, et al. J Ped, 2017
Novak, et al. Am J Peri, 2018
• Encephalopathy on exam
• Inciting event (cord event, abruption, etc)
• CPR or continued PPV at 10 min of life
• Apgar ≤5 at 10 min of life
• Cord or baby gas (w/in 1 hour) with:
• Base deficit ≥12 or
• pH ≤7.0 (7.1??)
• Minimal data in term infants
• Increased risk for abnormal neuro outcomes
• Greater if also acidosis
• 89% chance if also cord gas <7.0
• 10% chance if also cord gas >7.0
• 180x increased odds of mortality
Polin, et al. J Peri, 2007Jiang, et al. J Peri 2016
• Encephalopathy on exam
• Inciting event (cord event, abruption, etc)
• CPR or continued PPV at 10 min of life
• Apgar ≤5 at 10 min of life
• Cord or baby gas (w/in 1 hour) with:
• Base deficit ≥12 or
• pH ≤7.0 (7.1??)
• Helps direct need for resuscitative measures
• 5 min Apgar 0-3 correlates with mortality
• 5 min Apgar poor predictor/correlate of:
• Cord pH
• Neurologic outcome
• 90% with 5 min Apgar <4 do not develop CP
• 75-80% with CP had normal 5 min Apgar
Polin, et al. J Peri, 2007
• Encephalopathy on exam
• Inciting event (cord event, abruption, etc)
• CPR or continued PPV at 10 min of life
• Apgar ≤5 at 10 min of life
• Cord or baby gas (w/in 1 hour) with:
• Base deficit ≥12 or
• pH ≤7.0 (7.1??)
• AAP/ACOG statement:
“When a newborn infant has an Apgar score of 5 or less at 5 minutes, umbilical arterial blood gas samples… should be
obtained, if possible. Submitting the placenta for pathologic examination may be valuable.”
• Consider in any infant requiring significant resuscitation
• Baby gas at <1 hour likely as good if not better
AAP/ACOG. Pediatrics, 2015
• Cord pH < 7.0 present in <0.3% of deliveries
• Most do not have neuro sequelae
• 8-17% develop brain injury or seizures
• Respiratory versus metabolic
• pH < 7.0 missed 50% of mod-sev HIE
Polin, et al. J Peri, 2007Vesoulis, et al. ADCF&N, 2017
pH ≤ 7.1 Sensitivity 74% Specificity 99%
pH < 7.0 Sensitivity 30% Specificity 99%
BD Sensitivity 11-30% (depend on cutoff)
Hypoxic-Ischemic Encephalopathy
Management
• 33-34 C for 72 hours
• Initiate within 6 hours of injury
• May start with passive
• Ideally some knowledge of timing
• Whole body cooling
Reduces extent of brain injury by:
• Reducing cerebral metabolism (6-7% per ℃)
• Preventing edema
• Suppressing free radicals and NO
• Inhibiting inflammatory cascades
• Decreasing excitatory amino acids
Shankaran, et al. JAMA, 2014
Death or Major Disability
Cerebral Palsy
• Encephalopathy on exam• ≥35-36 weeks gestation
• Inciting event (cord event, abruption, etc)
• CPR or continued PPV at 10 min of life
• Apgar ≤5 at 10 min of life
• Cord or baby gas (w/in 1 hour) with:
• Base deficit ≥12 or
• pH ≤7.1
• Seizures and/or abnormal aEEG
CoolcapN=235
TOBYN=325
NICHDN=208
EicherN=67
Neo.nEuroN=129
ICEN=204
GA ≥36 ≥36 ≥36 ≥35 ≥36 ≥35Metabolic criteria 1/4 1/4 1/4 1/5 1/4 2/4
10 min Apgar ≤5 ≤5 ≤5 ≤5 ≤5 ≤5pH <7.0 <7.0 <7.0 <7.0/7.1 <7.0 <7.0Base deficit ≥16 ≥16 ≥16 ≥13 ≥16 ≥12PPV/CPR 10 min 10 min 10 min 5 min 10 min 10 min
Neuro criteria 2/4 2/4 3/6 2/5 2/4 2/4ConsciousnessActivityToneAutonomic reflexesPrimitive reflexesSuckPosture
Clinical seizures Any Any Any Any Any AnyAbnormal aEEG
• <35 weeks gestation
• Severe pulmonary hypertension
• Severe hemodynamic compromise
• Underlying fatal disorder/syndrome
• >12 hours after event
• 20-40% develop:
• 22% have abnormal outcomes at 18 months
• In RCTs, abnormal outcome:
• 29% cooled, 37% not cooled DuPont, et al. J Ped, 2013Gagne-Loranger, et al. Am J Peri, 2016
Conway, et al. Early Hum Dev, 2018
No Encephalopathy(n=29)
Mild encephalopathy(n=60)
Abnormal Discharge Exam 1 (3%) 7 (12%)Seizures 0 5 (8%)Abnormal MRI 0 6 (10%)Death 0 1 (2%)
%
Infants with any MRI injury
Adapted from Walsh, et al. J Peds, 2017.
Adapted from Walsh, et al. J Peds, 2017.
%
Infants with moderate/severe MRI injury
• Sinus bradycardia (6x increased risk)
• Thrombocytopenia (1.55x risk)
• No increase in:
• Arrhythmias requiring treatment
• Anemia, leukopenia, coagulopathy
• Hypoglycemia, hypokalemia
• Sepsis
• Seizures
Intervention Prevention NNT
Hypothermia Death or severe NDI 7
Vitamin K Moderate to severe bleeding 140
Phototherapy Bili above exchange threshold 222-3041
Antibiotic ppx Early onset neonatal sepsis 16-9370
Seizure Detection
• 34% of electrographic seizures w/ clinical manifest
• 9% identified and documented by staff
• 27% of “seizures” documented had EEG changes
Murray, et al. ADC F&N, 2008
Hypoxic-Ischemic Encephalopathy
Future Interventions
Dixon, et al. Int J Mol Sci, 2015
Studies in progress:Erythropoiesis-Stimulating Agents
• Completed: DANCE (Utah)
• Completed: NEATO (UCSF)
• Completed: NCT01732146 (Paris)
• Recruiting: HEAL (UCSF)
Melatonin
• Recruiting: NCT02621944 (UF)
Studies in progress:
Stem cells
• Completed: NCT01649648, NCT02890953(Singapore)
• Recruiting: NCT02551003 (Fudan Univ, China)
• Recruiting: NCT02612155 (Duke)
• Not Yet Recruiting: NEOSTEM (Marseille)
”Judge a man by his questions rather than
his answers.”
-Voltaire
Goals:
• Identify regional prevalence and outcomes
• Term & late preterm
• Evaluate epidemiology and antecedents
• Provide outcome dashboards by center
• Potential for targeted QI efforts
≤
≥
Data collection:
• Obstetric/Labor
• Complications, medications, monitoring
• Birth/Admission
• Blood gases, Apgars, need for pressors
• Outcomes
• Seizures, EEG, MRI, status at DC, TIPS
Anticipated opportunities for collaboration:
• Neurological exam documentation
• Identification of infants at risk for HIE
• Pre-transport management for hypothermia
• Regional criteria for hypothermia
Potential early questions:
• Rates of cord blood gases
• Cost/benefit of universal screening
• Outcomes of
• Mild encephalopathy
• Late preterm encephalopathy
• Variation in encephalography monitoring
• UNMC Central IRB Active
• All Omaha delivery/referral centers committed
• Two centers enrolling since Dec ‘17
• Looking to add centers from remainder of NE
• Goal for this year: expand to Colorado, Iowa
• Neonatal encephalopathy
• is a devastating disorder
• can be difficult to diagnose
• can easily be missed during vital time
• If you’re concerned, call your cooling center
• Regional incidence/outcomes unclear
• Lots of room for improvement
• Hope to better define and allow for directed QI
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