Neonatal Indirect Hyperbilirubinemia (>35 weeks) (Kutilda, 1/5/2022)

Many thanks to Dr. Pumi Kutilda who is such a dedicated teacher for our residents and gave an excellent detail-packed, graphic-filled presentation on Neonatal Indirect Hyperbilirubinemia this week. 

A recording of her presentation is available HERE.

Abbreviations used below: Total serum bilirubin (TsB), Transcutaneous bilirubin (TcB), gestational age (GA), Red blood cells (RBC), Risk factors (RF)

• Severe hyperbilirubinemia TsB >20 mg/dl (during first 28 days)
• Critical hyperbilirubinemia TsB>25 mg/dl  (during first 28 days)
• Cholestasis is defined as Direct bilirubin >1 mg/dl (need be checked only ONCE)
• RBC lifespan in newborns is 70-80 days (compared to 120 for adults)
• the lower the GA, the lower the RBC lifespan-- which puts preemies at higher risk
• High levels of free unconjugated bilirubin (not bound to albumin) crosses the blood brain barrier (specifically the globus pallidus) and causes neurological effects (i.e. kernicterus)
• this is why babies w/low albumin (<3) are at higher risk for hyperbilirubinemia 
  

History and Physical Exam are essential in diagnosis and management

• Prematurity 
•  <35 weeks GA, be sure to use the Preemie Bili Tool
•  >35 weeks GA use the regular Bili Tool 
• Polycythemia
• Known Hemolysis
• History of dehydration, suboptimal breastfeeding, poor latch, etc
• Constipation

Work up for Neonatal Hyperbilirubinemia

CBC + Diff, reticulocyte count + blood smear (retic count is critical because determines whether or not there is hemolysis, may need to be done serially), albumin, BMP/CMP, Direct bilirubin (just once to rule out conjugated hyperbilirubinemia), CBG/ABG + lactate (if hypoxic), G6PD (if hemolysis identified), Urine Culture (silent infection), thyroid function tests (if persistent jaundice >2 weeks)

See Pumi's excellent graphic for representation of how the peripheral blood smear can determine diagnosis

Where do we go wrong with diagnosing hyperbilirubinemia?

• missed hemolytic disease (e.g. G6PD deficiency)
• not repeating reticulocyte count

Physical Exam

lethargy, s/sx dehydration, hypertonia, "scared" upward gaze, high pitched cry

Screening and Management

1) Promote breastfeeding 

            Should be based on feeding cues

            No forced or supplemental feeding <24 hours (very minimal intake first 24 hours)

            Amount to feed is based on time after birth (H)

                    12-24 hours: 5-10ml q2-3 hour

                    24-48 hours: 10-30ml q2-3 hours

                    48-72 hours: 15-30ml q2-3 hour

                    72-96 hours: >30ml >8 times/day

2) Risk factor assessment 

    MOST important RF: gestation age <38 weeks, sibling who required phototherapy, visible jaundice first 24 hours, maternal coomb's positive

    LESS important RF: male, non-white (esp SE Asian), exclusive breastfeeding, cephalohematoma or significant bruising

Absence of these risk factors means extremely low risk for severe hyperbilirubinemia

    

3) Hour specific TcB screening: @12 hours, 24 hours (plotted on hour specific nomogram)

4) Assess adequate intake via both weight measurements AND stool patterns

                                #stools + # urine             weight loss %

                                    <24 hours 1+1                     <3%

                                    48 hours 2+2                        <7%

                                    72 hours 3+3                        7%

5) Risk factors for phototherapy: GA + hemolytic disease, suspected sepsis, asphyxia, acidosis, serum albumin <3

Added Pearls

• Both ibuprofen and naproxen increase bilirubin so are not used in newborns (indomethacin is used instead, eg PFO closure)
• To avoid degradation and ensure accurate measurements, blood should be carefully handled,  drawn into clouded red tube, and sent to lab to evaluated right away (<2 hours)
• Of note, TcB using one of two specific machines (JM103, JM105-- one of which we have at SSRRH) correlates VERY well with TsB except when TsB gets very high (>17). 
• We should be considering the TcB results as quite accurate as long as TcB is <13. 
• IF TcB>13, TsB indicated right away
• Home phototherapy (via bili blanket) is an option for medically stable patients (no neurotoxicity risk factors, no hemolysis, feeding well and well appearing). Costs about $200 delivery and $85/day. Patients have to pay up front but are generally reimbursed by their insurance
• There are new guidelines from UCSF (Northern California Neonatal Consortium), not active at SSRRH yet but soon will be. Keep your eye out

Therapeutic Neonatal Hypothermia (Spicher, 12/9.2

 A HUGE thank you to Dr. Allison Spicher, who gave an excellent presentation of the assessment of neonates at birth and indications for Therapeutic Neonatal Hypothermia. Cooling compromised babies became standard practice right around the time I graduated from residency-- I really needed this review and update. 

Here are my notes. . .

Therapeutic Neonatal Cooling is a clinical treatment that involves moderately reducing a baby's body temperature to slow disease progression and to improve health. In this case, the goal is to prevent neurological disability in at-risk neonates. Typically a baby is cooled to a core temperature of 33.5 degrees Celsius (92.3 degrees F) for 72 hours. 

Benefits of cooling have been demonstrated repeatedly:

2013 Cochrane Review. 1505 infants, 11 RCTs

• 25% overall relative risk reduction of death or major neurodevelopmental disability at 18-24 months (32% moderate encephalopathy, 17% severe encephalopathy) 
• The NNT to prevent 1 infant from dying or, becoming disabled is 6 for moderate, 7 for severe

Indications for cooling:

• Biochemical (Arterial Blood Gas pH<7 or Base Deficit >16)
• Neurological (moderate to severe encephalopathy)

AND

• >36 weeks of gestational age
• <6 hours of age

The Anatomy of a placenta:

• There are TWO small umbilical arteries, which take waste and carbon dioxide AWAY from the baby (pictured in blue on image below)
• There is ONE large umbilical vein that delivers oxygen and nutrients TO the baby (pictured in red on image below)

Of note, umbilical cord blood gases should be drawn as soon as possible from a preserved segment of the cord (taken at time of birth). Both arterial and venous samples are drawn in order to be able to compare them and be sure you are analyzing the correct information

Studies show that most accurate results come from samples drawn within 20 minutes of birth

Also, of note, Arterial pH and PO2 should always be lower than venous pH and PO2 (and pH should be at least 0.03 lower, or suspect that you have two venous samples)

Errors with umbilical cord blood gases are not uncommon. Reasons for this include:

• mislabeled/mixed up (can tell this by PO2 in arterial sample >> PO2 in venous sample)
• two venous samples (pH should be greater than 0.03 difference)
• air bubbles (tend to increase PO2 and lower PCO2)
• time to collection (PO2 and PCO2 have no major changes within 60 minutes, but BD can increase after 20 minutes-- if unable to draw quickly, put segment on ice)

What is neonatal encephalopathy?

Neonatal encephalopathy can be challenging to diagnose and there is NOT a standardized definition. ACOG and AAP definition appears in the figure here:

Sarnat Staging System

All compromised babies should be scored using the Sarnat Staging System, developed in 1976.  It uses 6 clinical findings to classify severity (1-mild, 2-moderate, 3-severe)

Exclusion Criteria for Cooling at SSRRH

• severe IUGR (<1800gm)
• need for ECMO
• severe coagulopathy with active bleeding
• severe hemodynamic compromise
• severe chromosomal, major congenital anomalies/disorders known to cause severe neurodevelopmental impairment

What kind of follow-up do this babies  get?

Babies who receive therapeutic hypothermia are seen in a high risk infant follow-up clinic at Sutter Santa Rosa at 6 months, 1 year, 2 years for developmental assessment. They also have follow-up with Pediatrics Neurology at CPMC. For more information, contact the coordinator of the high risk infant follow-up clinic: Anne E Parker, parkerae@sutterhealth.org

Trauma Exposure Response

Dr. Spicher ended her Grand Rounds presentation on a reflection on our response to trauma in the work we do. As she reflected during per presentation, participating in the care of an acute ill neonate is always traumatizing, and healthcare providers carry this trauma with us through our professional work and our personal lives.  Dr. Spicher recommended a book for those of you who are interested in delving into this topic and do the work to care for ourselves while caring for others.

RESOURCES:

Good resource for videos of physical exam for neonates with suspected encephalopathy: https://wusthoff.people.stanford.edu/neurologic-exam-neonates-suspected-encephalopathy-0

 Another resource is the FN3 (Florida Neonatological Neurological Network)

 http://hopefn3.org/members/protocols-and-guidelines/

Fetal Acid Base Status and umbilical cord sampling: https://www.mc.vanderbilt.edu/dept/obgyn/High_Risk_Conference/2013/Fetal%20Acid%20Base%20Status%20and%20Umbilical%20Cord%20Sampling-%20D.%20Acker.pdf

Cochrane Review of cooling: https://www.cochrane.org/CD003311/NEONATAL_cooling-for-newborns-with-hypoxic-ischaemic-encephalopathy