II. Epidemiology

  1. Five million neonatal deaths per year worldwide
    1. Birth Asphyxia accounts for 19% of neonatal deaths
  2. Newborns in United States: 4 million births per year
    1. Newborns requiring respiratory assistance at birth: 10%
    2. Newborns requiring extensive Resuscitation at birth: 1%
    3. Newborns developing severe hypoxic-ischemic encephalopathy: 0.2%
      1. Mortality ranges between 6-30%
      2. Cerebral Palsy and other long-term disabilities in survivors: 20-30%
  3. Early Resuscitation is key (intervene at primary apnea)
    1. Primary apnea (initial) responds to simple measures
      1. See Neonatal Airway Assessment
    2. Secondary apnea requires PPV and other interventions
      1. Does not respond to continued stimulation
      2. Associated with prolonged Resuscitation
      3. Associated with poorer outcomes
      4. Associated with decreased Heart Rate and BP

III. Physiology: Transition from Fetal Circulation at birth

  1. See Fetal Circulation
  2. Alveolar fluid is absorbed by lung
  3. Umbilical vessels are clamped
    1. Increases systemic Blood Pressure
  4. Pulmonary circulation increases
    1. Pulmonary vessel vasodilation
    2. Ductus arteriosus Vasoconstriction

IV. Protocol

  1. Prepare equipment and providers before delivery (see prevention below)
  2. Initial evaluation
    1. Core questions to determine if Resuscitation is indicated
      1. Is this baby consistent with term gestation?
      2. Is the newborn breathing or crying?
      3. Does the newborn have good muscle tone?
    2. Other questions
      1. See Newborn History
      2. Is the newborn clear of meconium?
      3. Is the skin pink centrally?
  3. Consider Neonatal Distress Causes
    1. See THE MISFITS Mnemonic
    2. Fever (or Hypothermia)
      1. Associated with serious Bacterial Infection in 10% of age <2 weeks and 5% of age 2-4 weeks
      2. See Neonatal Sepsis for evaluation and management
    3. Congenital Heart Disease is most likely in a hemodynamically unstable infant with normal Temperature
      1. See Congenital Heart Disease for evaluation and management
      2. Obtain early Echocardiogram
      3. Distinguish ductal dependent pulmonary blood flow from ductal dependent systemic blood flow
    4. References
      1. Sloas, Checchia and Orman in Majoewsky (2013) EM: Rap 13(9): 8
  4. Step by step assessment (timer started at delivery)
    1. Precautions
      1. Only two markers guide Resuscitation
        1. Respiratory status and Heart Rate
      2. Only two medications are used in Neonatal Resuscitation
        1. Epinephrine and volume expanders (NS, Blood)
      3. Ventilations are the single most important measure in Neonatal Resuscitation
        1. Initiate Positive Pressure Ventilations (PPV) promptly within 30 seconds (if indicated)
        2. Coordinate PPV and compressions to ensure adequate ventilation until Advanced Airway placed
    2. Perineum management
      1. Perineal suction (peripartum suction) is no longer recommended
      2. Delay cord clamp for 30-60 seconds in newborn not requiring Resuscitation (term, good tone, breathing)
    3. Neonatal Airway Assessment
      1. Includes general measures performed for all infants
      2. Includes warming, suctioning, drying, stimulation
      3. Endotracheal suctioning is no longer recommended for thick meconium
        1. Regardless whether infant is vigorous
        2. However, intubation may be needed as part of general Resuscitation
    4. Neonatal Breathing Assessment
      1. Positive Pressure Ventilation (PPV)
        1. Indicated at 30 second mark for apnea, gasping or Heart Rate <100/min
        2. Rate of 40-60/min for 30 seconds (one-and-two-and-three-and-breath)
        3. Peak inspiratory pressure (PIP) started at 20-25cm H2O (may require 30-40 cm H2O)
        4. Initial FIO2 set at 21% (room air) for term and 21-30% for Preterm Infants
        5. Consider reasons if inadequate Positive Pressure Ventilation (Mnemonic: MR SOPA)
          1. Mask adjustment, Reposition
          2. Suction, Open mouth, Ppv, Alternate airways
      2. Apply O2 Sat monitor if PPV needed
        1. Apply Oxygen Saturation monitor preductally (e.g. right palm or wrist)
        2. See Oxygen Saturation for normal levels for newborns
        3. Oxygen Saturation is normally 60-65% in the first minute of life (and increases 5% every minute)
        4. Oxygen Saturation does not normally increase to >85% until after 10 minutes of life
      3. Endotracheal Tube intubation or Laryngeal Mask Airway (LMA) if PPV for >2-3 minutes (confirm with etCO2)
      4. Consider CPAP
    5. Neonatal Circulation Assessment
      1. Measure Heart Rate with three lead ekg
        1. Palpation of Umbilicus and chest auscultation are no longer considered reliable
      2. Positive Pressure Ventilation for continued Heart Rate <100/min or apnea
      3. Chest Compressions
        1. Indicated at 60 second mark for Heart Rate <60/min after 30 seconds of PPV
        2. Two thumb wrap-around technique is preferred for Chest Compressions
        3. Rate of 3:1 compressions to breaths (90 compressions and 30 breaths per minute)
          1. Count "one-and-two-and-three-and-breath" with one event every 0.5 seconds
          2. Unless cardiac etiology is suspected and then change to 15:2 compressions to breaths
        4. Reassess 45-60 seconds after starting compressions
      4. Epinephrine
        1. Indicated at 2 min for Heart Rate <60/min after 60 sec of compressions (and 90 seconds of PPV)
        2. Umbilical Venous Catheter: 0.01 to 0.03 mg/kg (0.1 to 0.3 ml/kg) of 1:10,000 Epinephrine
        3. Endotracheal Tube: 0.05 to 0.10 mg/kg (0.5 to 1 ml/kg) of 1:10,000 Epinephrine
    6. Neonatal Perfusion Assessment
      1. Central Cyanosis
        1. Initial FIO2 set at 21% (room air) for term and 21-30% for Preterm Infants
        2. Oxygen free flow starting at 21% or blended and titrate up as needed
      2. Blood loss suspected
        1. Normal Saline 10 cc/kg bolus
        2. Transition to pRBC when available (if indicated)
    7. Post-Resuscitation after extensive efforts for severe event
      1. Intravenous Dextrose infusion (prevent Hypoglycemia)
        1. Indicated after core Resuscitation
        2. Maintenance with D10W at 80 ml/kg/day (3.3 ml/kg/hour)
        3. If hypoglycemic (Serum Glucose <35-45 mg/dl)
          1. Give 2 cc/kg D10W
      2. Developing severe hypoxic-ischemic encephalopathy in newborns >36 weeks
        1. Offer Therapeutic Hypothermia protocol (started within 6 hours of event at NICU)
      3. Portable Chest XRay
        1. Evaluate for Pneumothorax

V. Prevention

  1. Prepare for complicated deliveries
    1. NRP-certified Resuscitation team available at all times
    2. NRP-certified provider present for high-risk deliveries
  2. Hospital delivery rooms stocked with adequate equipment
    1. Pulse Oximeter
    2. Fully working warmer
    3. Oxygen supply with air oxygen blender
    4. Suction device
    5. Positive Pressure Ventilation device (e.g. Anesthesia Bag, ambu-bag, T-piece device)
    6. Endotracheal Tubes, Laryngeal Mask Airway, working Laryngoscope, CO2 Detection device
    7. Resuscitation medications (e.g. Epinephrine, Normal Saline)

VI. Precautions: Major changes in Neonatal Resuscitation

  1. As of 2015
    1. Do not endotracheal suction infants regardless of thick meconium or non-vigorous infant
    2. Delay cord clamping for 30-60 sec in term infants, with normal tone and breathing, not needing Resuscitation
    3. Prevent Hypothermia and keep infant Temperature 36.5 to 37.5 (monitor with Temperature sticker over liver)
    4. Monitor Heart Rate with 3 lead ekg (cord palpation and auscultation are considered unreliable)
    5. Resuscitate with FIO2 21% in term infants and 21-30% in Preterm Infants
  2. As of 2010
    1. Perineal suctioning for meconium is no longer recommended
    2. Monitor Resuscitation efforts with Pulse Oximetry (but do not expect O2 Sat >85% until after 10 min of life)
    3. End Tidal CO2 (etCO2) detector or monitor to confirm proper Endotracheal Tube placement
    4. Laryngeal Mask Airway (LMA) size 1 may be used instead of ET for ventilation in infants >2kg or >34 weeks gestation
    5. Naloxone and Sodium Bicarbonate are no longer recommended in Newborn Resuscitation

VII. Management: Indications to Discontinue Resuscitation Efforts

  1. No detectable Heart Rate (Asystole) with APGAR Score of 0 after 10 minutes of full Resuscitation efforts
  2. Lethal anomalies (Informed Consent with parents if withholding care)
    1. Very premature (Gestational age <22 weeks, NO weight cutoff - previously cited as <400 grams)
    2. Anencephaly
    3. Trisomy 13 Syndrome

VIII. Management: Therapeutic Hypothermia Protocol

  1. Indications
    1. Gestational age >36 weeks AND
    2. High risk of severe hypoxic-ischemic encephalopathy
      1. pH <7 (or pH <7.15 if follows acute perinatal event)
      2. Base Deficit >16 mmol/L (or >10 mmol/L if follows acute perinatal event)
      3. APGAR Score <5
      4. Encephalopathy or Seizures
  2. Protocol
    1. Start within 6 hours of birth
    2. Initiated for 72 hours and then gradual rewarming over 4 hours
    3. Consult with accepting neonatologist
    4. Goal Temperature: 92.3 to 94.1 F (33.5 to 34.5 C)
      1. Turn off the warmer and remove all blankets, hats
  3. References
    1. Olsen (2013) Pediatrics 131(2): e591-603 [PubMed]

IX. Preparations: Medications no longer recommended in Newborn Resuscitation (listed for completeness)

  1. Sodium Bicarbonate (Use only 4.2% solution)
    1. Not recommended as worse outcomes with use
    2. Primary treatment of acidosis is by maximizing ventilation, not with bicarbonate
    3. Dose: 4 ml/kg (2 meq/kg of 4.2%) very slowly via large vessel (Umbilical Vein Catheter)
  2. Naloxone
    1. Not recommended as of 2010 as no evidence for improved outcomes with use
    2. Primary treatment of apnea is with Positive Pressure Ventilation
    3. Dose: 0.1 mg/kg of 1.0 mg/ml IV, ET, IM or SQ
    4. Indications (old)
      1. Respiratory depression despite PPV (with normal Heart Rate and color)
      2. Maternal Narcotic Analgesics within 4 hours

X. References

  1. (1995) World Health Report, WHO
  2. Bhalla (2014) Crit Dec Emerg Med 28(1): 2-11
  3. Claudius, Behar, Nichols in Herbert (2015) EM:Rap 15(1): 3-4
  4. Spangler, Claudius, Behar and Nicholas in Herbert (2016) EM:Rap 16(9): 11-3
  5. Kattwinkel (2000) Neonatal Resuscitation, AAP-AHA
  6. Kattwinkel (2010) Neonatal Resuscitation, AAP-AHA
  7. (2015) Pediatrics 136(suppl 2): 196-218 +PMID:26473001 [PubMed]
  8. Raghuveer (2011) Am Fam Physician 83(8): 911-8 [PubMed]

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Ontology: Neuropilin-1 (C0100804)

Definition (NCI) Encoded by human NRP1 Gene (Neuropilin Family), Neuropilin 1 contains 1 MAM, 2 F5/8 type C, and 2 CUB domains. Found in embryonic nervous system, and adult heart, placenta lung, liver, skeletal muscle, kidney, and pancreas, type I membrane-bound 923-aa 103-kDa (precursor) isoform 1, expressed by blood vessels, acts as a receptor in cardiovascular development, angiogenesis, formation of neuronal circuits, and organogenesis. Binding to semaphorin 3A, PLGF-2, VEGF-165, and VEGF-B, Isoform 1 appears to mediate chemorepulsion by semaphorins, to increase VEGF-165 binding to KDR, and to regulate VEGF-induced angiogenesis. Expressed in hepatocytes and kidney distal/proximal tubules, secreted 644-aa isoform 2 may bind semaphorins and induce apoptosis by sequestering VEGF-165; it has an adverse effect on blood vessel integrity. Expression of isoforms 1 and 2 does not seem to overlap. (NCI)
Definition (MSH) Dimeric cell surface receptor involved in angiogenesis (NEOVASCULARIZATION, PHYSIOLOGICAL) and axonal guidance. Neuropilin-1 is a 140-kDa transmembrane protein that binds CLASS 3 SEMAPHORINS, and several other growth factors. Neuropilin-1 forms complexes with plexins or VEGF RECEPTORS, and binding affinity and specificity are determined by the composition of the neuropilin dimer and the identity of other receptors complexed with it. Neuropilin-1 is expressed in distinct patterns during neural development, complementary to those described for NEUROPILIN-2.
Concepts Receptor (T192) , Amino Acid, Peptide, or Protein (T116)
MSH D039942
Swedish Neuropilin-1
English NEUROPILIN 001, Neuropilin-1 [Chemical/Ingredient], Antigen, A5, NRP1 Protein, Npn 1 Protein, Npn-1 Protein, Receptor, Sema III, Sema III Receptor, Semaphorin III Receptor, A5 Antigen, Neuropilin-1, NRP, Neuropilin 1, NRP1, VEGF165R, Vascular Endothelial Cell Growth Factor 165 Receptor
Czech neuropilin-1
Finnish Neuropiliini-1
Japanese ニューロピリン-1, Npn-1蛋白質, NRP1蛋白質, SemaIII受容体, セマフォリンIII受容体, セマホリンIII受容体
German NEUROPILIN 001, Neuropilin 1
Polish Neuropilina-1
French Neuropiline 1, Neuropiline-1
Italian Neuropilina 1
Portuguese Neuropilina-1
Spanish Neuropilina-1