J E S S I CA MI L L E R , MD P GY 3

J U L Y 1 4 , 2 0 1 3
MORNING REPORT
THE CASE:
39 week male infant brought to the well baby nursery
from L&D at approximately 3 hours of life. Assessed by
nurse at time of arrival as very jittery. Bedside glucose
measured at < 30. Confirmation is sent to the lab and
returns at < 5.
PAST MEDICAL HISTORY
Birth history:
Membranes ruptured 6 hours prior to delivery. Born by
NSVD. APGARS 8, 9. Pediatrics was not called. Baby
received warm, dry, stimulation by L&D nurse, midwife.
Delayed cord clamping.


Maternal history: Pregnancy complicated by mild
thrombocytopenia.
PAST MEDICAL HISTORY
Maternal labs:
AB+, coombs negative
Rubella: immune
RPR: nonreactive
Hep B: nonreactive
HIV: negative
GBS: negative
Chlamydia: negative
Gonorrhea: negative

Maternal medications: prenatal vitamins
FAMILY AND SOCIAL HISTORY
Family History: No known medical problems in
parents. No chronic childhood illnesses, congenital
heart disease, seizure disorders, renal disorders, history
of jaundice or sudden infant death in other family
members.

Social History: Mother and father live in downtown Salt
Lake. Moved to Utah from Colorado 10 months prior
to delivery. No pets at home. No smoking at home.
PHYSICAL EXAM
Temp 36.5 HR 128 RR 42

General: well developed, strong cry, quivering lip
HEENT: conjunctiva clear, pupils reactive bilaterally, red reflex
bilaterally. Moist mucus membranes. Chin is notably small.
Neck: normal range of motion, clavicles intact
CV: regular rate, rhythm. No murmur. Palpable pulses.
RESP: Normal rate. No nasal flaring or retractions. Lung sounds clear
bilaterally.
ABD: Soft, non-distended and non-tender. No hepatomegaly or
splenomegaly.
GEN: Penis normal, testicles descended.
MSK: Normal tone. Full range of motion.
NEURO: Alert, normal strength. Suck normal. Moro exaggerated
SKIN: Warm, pink. Cap refill < 3 seconds.
DIFFERENTIAL DIAGNOSIS
3 hour old term infant with symptomatic
hypoglycemia
DIFFERENTIAL DIAGNOSIS
Sepsis
LGA
Infant of diabetic mother
Preterm (inaccurate dating)
IUGR
Post-term infants
Multiple gestations
Birth asphyxia
Hypothermia
Exposure to B-agonist tocinolytics
(Terbutaline)
Erythroblastosis fetalis
Polycythemia
Congenital hyperinsulinemia
Beckwith-Weideman (pancreatic
hyperplasia)
Pancreatic adenoma
Metabolic
Glycogen storage diseases
Galactosemia
Fatty acid oxidation defects
Carnitine deficiency
Amino acidemias
Hereditary fructose intolerance
Endocrine
Hypopituitarism
Cortisol deficiency


INITIAL WORK-UP AND MANAGEMENT
Baby was immediately transferred to NYI for IV
placement. While waiting to place IV, baby was fed,
and took 25 mL of Similac Advance.

CBC w/ diff, CMP, blood culture were obtained.

Birth weight: 3185g (AGA)

Baby was given a D10W bolus at 2 mL/kg, and started
on D10W drip at 60 mL/kg/day
INITIAL WORKUP AND MANAGEMENT
BCBC (heelstick):
WBC- 22.65 (76% PMNs, 7% bands, 13%
lymphocytes, 3 % monocytes, 1%
eosinophils)
Hgb: 23.8
Hct: 75
Platelets: 405
I:T- 0.08

CBC (venous):
WBC- 17.76 (79% PMNs, 2% bands, 12%
lymphocytes, 6% monocytes, 0%
eosinophils)
Hgb- 21.4
Hct- 65.1
Platelets: 155
I:T- 0.02



CMP: initial clotted, repeated
Na- 133
K- 5.0
Cl- 102
CO2- 21
BUN-7
Cr-0.66
Protein- 5.9, Albumin- 3.5
Total Bilirubin- 4.3
Alkaline Phosphatase- 249
AST-73
ALT -21

Random Insulin-17 (normal)

Blood culture: pending
INITIAL WORKUP AND MANAGEMENT
Glucose 30 minutes after feed, prior to D10W bolus: 37.
Glucose- repeated after D10W bolus: 45.

Baby continued on D10W drip x 48 hours. Did not
tolerate initial wean after 24 hours, but later was able
to wean, and demonstrated euglycemia > 12 hours
off drip.

CBC repeated after 12 hours of IV fluid hydration, Hct
had trended down to 60
INITIAL WORKUP AND MANAGEMENT
Hypoglycemia was thought to be most likely due to a
combination of polycythemia, possibly unrecognized
insulin resistance in mother.
NEONATAL GLUCOSE HOMEOSTASIS
Glucose concentration in umbilical vein at birth is
60-80% of maternal glucose level
Decline in glucose concentration over the first 2
hours, steady state is usually reached by 2-3 hours
after birth
Establishment of steady state is associated with
hepatic glucose release
HEPATIC GLUCOSE RELEASE

BIRTH increased catecholamines
1) glucagon secretion release of glycogen from hepatic
stores
Term infants have estimated hepatic glycogen stores to maintain
glucose supply for 10 hours

2) release of free fatty acids which allows for gluconeogenesis
by 4-6 hours of life


Infants who have low hepatic glycogen stores, or low levels
of fatty acids are more likely to experience disordered
glucose homeostasis
ALTERNATIVE FUELS
Fetal and neonatal brains can also use ketones,
lactate and possibly amino acids as fuel
Breastfed infants have lower concentrations of
glucose, but higher concentrations of ketone
bodies than formula-fed infants
HOW DO WE DEFINE NEONATAL
HYPOGLYCEMIA?
There is debate

No consensus on what level requires intervention in
the asymptomatic infant
Generally adopted plasma glucose concentration
of neonatal hypoglycemia is < 47 mg/dL, and
without rigorous scientific justification (Pediatrics,
2011)
In symptomatic infants, generally accepted that
intervention should be taken with glucose < 40
mg/dL



WHAT ARE THE SYMPTOMS OF
HYPOGLYCEMIA?
Jitteriness
Cyanosis
Apneic episodes
Tachypnea
High-pitched cry
Low tone, lethargy
Poor feeding
Seizures

WHO IS AT RISK?
Infants with low glycogen stores
Infants with higher levels of insulin
Infants with increased glucose utilization
LOW GLYCOGEN STORES
Premature
limited hepatic glycogen stores due to missing period of
glucose accumulation
IUGR
Head size tends to be preserved leading to increased
demand on already low glycogen stores
Post-term infants, infants of multiple gestation
Relative placental insufficiency
SGA
Inadequate substrate available for glycogen synthesis
ELEVATED INSULIN LEVELS
Infants of Diabetic Mothers, LGA infants
Consistent exposure to increased maternal glucose levels in
utero up-regulation of fetal insulin secretion
After birth, glucose supply drops, but insulin secretion
remains high increased glucose utilization, decreased
hepatic glucose production
May take 24-72 hours for insulin secretion patterns to
normalize
ELEVATED INSULIN LEVELS
Congenital hyperinsulinemia
Most common cause of hypoglycemia persisting beyond
1st week of life
Autosomal dominant and autosomal recessive forms
described
Pancreatic hyperplasia
May occur in Beckwith-Weidemann syndrome
Islet cell adenoma
Rare cause

ELEVATED INSULIN LEVELS
Erythroblastosis fetalis
Increased insulin and increased number of pancreatic B-
cells
Glutathione released in RBC hemolysis may inactivate
insulin in circulation, lead to increased insulin production
Tocolytic agents (Terbutaline)
Associated with elevated insulin levels, decreased
glycogen stores if used for more than 2 weeks, discontinued
less than 1 week prior to delivery
INCREASED GLUCOSE UTILIZATION
Sepsis
Hypoxia
Increased reliance on anaerobic metabolism
Respiratory distress
Hypothermia
Increased metabolic demands
WHO DO WE SCREEN?
Late pre-term
Small for Gestational Age (SGA)
Intrauterine Growth Restriction (IUGR)
Large for Gestational Age (LGA)
Infants of Diabetic Mothers (IDM)




RARE CAUSES TO KEEP IN MIND IF
HYPOGLYCEMIA PERSISTS
Inborn errors of metabolism
Glycogen storage diseases
Galactosemia
Fatty acid oxidation defects
Carnitine deficiency
Amino acidemias
Hereditary fructose intolerance
Endocrine
Hypopituitarism
Adrenal failure

FURTHER WORKUP TO CONSIDER:
At time of hypoglycemia:
Insulin
Cortisol
Growth Hormone
Amino Acids
IGFBP-3 level (decreased in hyperinsulinemia)
Urine Ketones, reducing substances and organic acids
NEUROLOGIC CONSEQUENCES
The level or duration of hypoglycemia that is
harmful to the developing infants brain is unknown

Review article in Pediatrics from 2006 identified 45
potentially relevant articles, only defined 3 as high
quality

NEUROLOGIC CONSEQUENCES
Effect of transient hypoglycemia on fist postnatal day in
75 healthy term LGA infants on neurodevelopmental
outcome at 4 years age
No difference in total IQ on Denver Developmental Scale and
Child Behavior Checklist scores between normoglycemic and
hypoglycemic infants
(Brand 2005)

Effect of hypoglycemia in 661 premature infants on
neurodevelopmental outcome at 18 months of age
Reduced mental and motor scores on Bayley developmental
scale in infants with hypoglycemia recorded on > 5 days
Incidence of Cerebral Palsy/Developmental Delay increased
by factor 3.5
(Lucas et al., 1988)
CHANGES ON MRI
18 symptomatic term infants with hypoglycemia,
glucose < 45 mg/dL (range of 12-43 mg/dL)
compared to control group of 19 normoglycemic
infants
MRI and ultrasound performed at 40 weeks and 2
months
MRI abnormality identified on 33% of hypoglycemic infants
at 40 weeks, 4/7 had resolved by 2 month MRI
Development assessed clinically between 5-12 months, 94%
of hypoglycemic infants had normal development
(Kinnala, Pediatrics, 1999)


CHANGES ON MRI
35 term infants with early brain MRI after
symptomatic hypoglycemia (mean level 18 mg/dL)
and developmental assessment at 18 months
94% of infants had white matter abnormalities
29% had posterior pattern
51% had cortical abnormalities
40% basal ganglia/ thalamic lesions
65% had impairments at 18 months which was related to
severity of white matter injury and basal ganglia
involvement
(Burns, Pediatrics, 2008)
RESOURCES
Neurodevelopment After Neonatal Hypoglycemia: A Systematic Review and Design
of an Optimal Future Study. Boluyt, Nicole. Anne can Kempen and Martin Offringa.
Pediatrics. 2006; 117;2231.

Neonatal Hypoglycemia. McGowan, Jane. Pediatrics in Review. 1999; 20;e6.

Postnatal Glucose Homeostasis in Late-Preterm and Term Infants. Committee on
Fetus and Newborn. Pediatrics. 2011; 127;575.

Controversies Regarding Definition of Neonatal Hypoglycemia: Suggested
Operational Thresholds. Marvin Cornblath, Jame Hawdon, Anthony Williams, Albert
Aynsley-Green, Martin P. Ward, Robert Schwartz and Satish C. Kalhan. Pediatrics. 2000;
105; 1141.

Cerebral Magnetic Resonance Imaging and Ultrasonography Findings After Neonatal
Hypoglycemia. Kinnala, Anna et al. Pediatrics. 1999; 103; 724.

Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic
neonatal hypoglycemia. Burns, Rutherford, Boardman, Cowan. Pediatrics. 2008;
122(1): 65.