Neonatal Hypoglycemia

Neonatal Hypoglycemia
(and all of the other neonatal emergencies that Ethan
is making me cover to fulfill the ACGME requirement)
Philippa Augustin, MD
 Review definition, pathophysiology, risk
factors, evaluation and treatment of
neonatal hypoglycemia
 Attempt to cover maybe 1 or 2 others…
Neonatal Emergencies
 Neonatal hypoglycemia
 Neonatal seizures
 Apparent Life Threatening Events
 Neonatal sepsis
 Surgical Emergencies
 Congenital Heart Disease
Neonatal Hypoglycemia
 Common problem, with 10% of neonates
being unable to maintain glucose >30 if
feeding is delayed for 3-6hrs after birth
 Greater risk if SGA or LGA
 No clear consensus about what levels are
• Current definition is <40 for 1st 24hrs, then <50
after that
• Severe is <25
• Neonates are able to tolerate much lower
plasma glucose levels than adults
 Glutamate, aspartate and alanine
• Neonatal brain is also able to use lactate and
ketone bodies
Umbilical venous glucose concentration is 60-80% of
maternal levels
During 1st 2hrs after birth, falls to nadir of 40, then
stabilizes at 4-6hrs to 45-80
• Stabilized by glycogenolysis, stimulated by
epinephrine and glucagon
– Hepatic glycogen depleted after 8-12hrs
• Also supported by gluconeogenesis
– Requires substrate (lactate, amino acids, glycerol)
If either is inadequate, hypoglycemia results
Decreased glucose production
Inadequate stores
• Glycogen stored in liver mostly during the 3rd trimester
– Which infants will be at risk because of this?
• IUGR also have reduced stores
– Chronic intrauterine hypoxia leads to inefficient
glucose metabolism
Metabolic disorders
• Glycogen storage diseases, galactosemia, fructose
intolerance, maple syrup urine disease, propionic
acidemia, methylmalonic acidemia)
 Endocrine disorders
• Deficiency of any of the hormones that
regulate glucose homeostasis (cortisol, GH,
epi, glucagon)
 Other
• Maternal beta blockers
– Interrupts epinephrine stimulating glycogenolysis
• Hypothermia
• Liver failure
Increased Utilization
 Hyperinsulinemia
• Infants of diabetic mothers
– Usually transient, neonate has increased production of
insulin secondary to chronic intrauterine
hyperglycemia (premature maturation of pancreatic
islet cells)
– IDMs also have depressed counterregulatory response
(glucagon and catecholamines)
– Suspect in LGA/macrosomia
• Beckwith-Wiedemann syndrome
– hyperinsulinism
Perinatal asphyxia
Intrapartum glucose infusion
Exogenous insulin
– Given for hyperglycemia, infants must be carefully
monitored after administration
Increased utilization without
Utilization may increase with poor perfusion and poor
• Lower energy produced with anaerobic glycolysis (5%)
• Mechanism unknown
• Increased RBC mass  increased glucose metabolism
• Nml plasma glucose, but def of GLUT1 results in lack of
transport across BBB
– Seizures at 2-3 mos, developmental delay, acquired
 Jitteriness, tremors
 Hypotonia
 Altered LOC (irritable, lethargic, stupor)
 Apnea, bradycardia, cyanosis
 Tachypnea
 Poor feeding/sucking
 Hypothermia
 Seizures
Infants at higher risk
 Preterm
 NICU (sepsis, asphyxia)
 Mother tx’d with Bblockers or oral
hypoglycemic agents
 Start within 1-2 hrs after birth (sooner for
any symptoms)
• Preprandial glucose levels
• Maintain above 50 (40 may be adequate, but
BAEPs are abnormal <45, although this
abnormality reverses with euglycemia)
 Oral breast milk or formula if asymptomatic
and not severe hypoglycemia (<25, which
will result in permanent neuron death)
 IV glucose of 6mg/kg/min if symptomatic,
unable to be fed, or persistently
 Glucocorticoid if persistent hypoglycemia
after 2-3 days of glucose at >12 mg/kg (and
consult pedi endo)
Oral feeds
 ASAP after birth
• Negligible benefit on early hypoglycemia, may
prevent subsequent hypoglycemia
• If screening is <40 in asx term infant, repeat
with blood sample for lab
• Repeat 20-30 min after feeding, feed q2-3hrs
• If preterm with glucose <40, most likely will
need parenteral supplementation
Parenteral Glucose Indications
 Neonate with severe hypoglycemia (20-25)
 Persistent hypoglycemia after feeding
 Neonataes unable to tolerate po
 Unclear if asymptomatic hypoglycemia in
premature infants leads to neurologic
 Symptomatic hypoglycemia leads to
changes in brain MRI
• 33 of 35 neonates had detectable white matter
– 15 mild, 8 mod, 3 with severe impairment
– earlier onset of MRI findings means worse outcome
• transient MRI changes with glucose <46
• injuries usually result in neuro developmental
delay an decreased intellectual fxn
RDS (aka hyaline membrane
 Common cause of respiratory distress,
especially in premature infants
 caused by surfactant deficiency
• surfactant expressed by lung tissue during 3rd
• lipid/protein complex that lowers lung surface
tension preventing alveolar collapse
 Without surfactant, alveoli collapse,
causing decreased lung volum and
decreased lung compliance
• collapsed alveoli lead to V/Q mismatch that
leads to hypoxemia
 low surfactant levels also lead to resp
epithelial injury that causes inflammation
and pulmonary edema
 In animal studies, depletion of neutrophils
prevents pulmonary edema in absence of
 atelectasis --> inflammatory cascade -->
increased cytokine expression -->
increased neutrophil accumulation
• increased protein rich fluid causes
inactivation of any remaining surfactant
Pulmonary edema
 Caused by inflammation, but also caused
by decreased fluid absorption
• epithelial sodium channel (ENaC) expression
occurs during 3rd trimester
 Presents at birth, and if untreated, worsens
over next 48hrs
 nearly always premies
 Symptoms
tachypnea, nasal flaring, grunting, retractions, cyanosis
decreased breath sounds
decreased peripheral pulses
increased peripheral edema
decreased UOP in first 24-48hrs
Disease progression
 If surfactant is not administered, dz will
progress over 24-72 hrs and then improve
neonate produces surfactant
 Diagnosis: neonate with increased WOB,
increased O2 need, and typical x-ray
(ground glass)
 DDx: TTN, penumonia, congenital heart
Neonatal seizures
 Symptomatic vs. neonatal epileptic
• majority are symptomatic seizures (acute
reactive neonatal seizures)
Neonatal epileptic syndromes
 Benign neonatal convulsions
 benign neonatal familial convulsions
 early myoclonic encephalopathy
 early infantile epileptic encephalopathy
Acute reactive neonatal seizures
 Many causes
neonatal hypoxic-ischemia encephalopathy
CNS infection
cerebral infarct
Acute reactive neonatal seizures
 Many causes
neonatal hypoxic-ischemia encephalopathy
CNS infection
cerebral infarct
Acute reactive neonatal seizures
 Many causes
neonatal hypoxic-ischemia encephalopathy
CNS infection
cerebral infarct
Acute reactive neonatal seizures
 Many causes
neonatal hypoxic-ischemia encephalopathy
CNS infection
cerebral infarct
Benign neonatal convulsions
 Idiopathic
 2-7% neonatal seizures
 90% in DOL 4-6
 term/late preterm, no FHx, nml pregnancy
and delivery, nml neuro exam between
 unifocal clonic, occ cuase apnea, lasts 1-3
min and recur for 24-48hrs
 Diagnosis of exclusion
Apgar >7 at 1 min
typical age (4-6 days)
nml neuro exam before and interictally
nml labs/imaging
no FHx
 AEDs, may stop 24-48hrs after
Benign neonatal familial
 14.4/100K live births
 autosomal dominant with 85% penetration
• “channelopathy” of voltage gated K+ channel
 focal or multifocal clonic/tonic seizures
 FHx neonatal seizures
 nml neuro exam
 Onset - days-1wk of life
 Seizures are usually brief and resolve in 2-
3 monts
 Tx: AEDs
• good prognosis, but do have slight increase in
risk of future epilepsy
Early myoclonic encephalopathy
• onset - early neonatal
• occ familial
• usually have inborn errors of metabolism
 Clinical features
• abnml neuro exam - altered LOC at time of
• initially with segmental erratic myoclonic
seizures in 1st few hrs
• partial motor or focal clonic seizures develop
after that
• repetitive tonic spasms at 3-4 months
 Tx: AEDs, but seizures refractory to meds
 Prognosis: poor
• do not develop neurologically
• 50% die in 1st yr
• survivors - persistent vegetative state
 AKA Ohtara’s syndrome
 Onset - infancy (within 1st 3 months)
 frequent tonic spasms and suppression-
burst pattern on EEG
 secondary to structural anomalies
 tonic spasm seizures
 neuro exam abnml even before onset of
 Tx: AEDs
 prognosis: poor; 50% die in infancy,
survivors have severe MR, quadriplegia
 Apparent Life Threatening Events
• some combo of apnea, color change, change in
muscle tone, choking/gagging
• Recovery occurs after
stimulation/rescusitation (being patted or
picked up doesn’t count)
 Unclear if connected to SIDS
5% of SIDS had prior ATLE
ALTE not always fatal
ALTE dx depends on parental observation
80% SIDS 12am-6am, 80% ALTE 8am-8pm
SIDS interventions have not decreased ATLE
different risk factors
 Cause identified in >50%
• 30% GERD
• 15-20% neurologic
– seizures, ventricular hemorrhage, hydrocephalus
• Accidental/intentional poisoning
• no direct association to ATLE
• more likely if gross emesis at time of ALTE,
occur when infant awake and supine, infant
had obstructive apnea
• may use low risk interventions, but also r/o
other causes
 Abuse
• Munchausen’s by proxy vs abusive head
Initial eval
 History and PE (eval for respiratory
 Lbs, CXR, brain imaging, EEG, echo, PSG, CXR
 Consider consulting infant apnea
 Admit for inpt obs if hx suggests
physiologic compromise
Recurrence risk factors
 Idiopathic ALTE
• high incidence of false apnea alarms on home
 immaturity, hx of multiple ALTE prior to
admit, viral URI,
 Caregivers should be given CPR training
 train caregivers in creating safe sleeping
 home monitoring (case by case)
 In premies - good, as lungs mature
 death occurs in <1%
• if have recurrent ATLE requiring CPR, risk of
SIDS is 10-30%
Neonatal Sepsis
 Objectives
Review terminology
Risk factors
Presentations of neonatal sepsis
Most common organisms and treatments
 Rule out sepsis
 Neonate with fever (neonate is 0-28 days)
 Neonatal fever
 Neonatal sepsis
 Serious bacterial infection
 Occult bacteremia
Neonate with fever
 Infant of 0-28 days with rectal temp of
100.4F or higher should automatically be
• Immature immune system
– Cellular immunity
– neonatal PMN deficient in chemotaxis and killing capacity
– Impaired macrophage chemotaxis, with lower absolute numbers in
lung, liver and spleen
– Immature T-cells
– Low numbers of natural killer cells in peripheral blood
– Humoral immunity
– Immunoglobulin transfer from mother occurs in late
gestation, putting premies at risk
– Low IgM levels at birth
– Deficiency of terminal complement cascade necessary
for G- pathogens
• Perinatal pathogen exposure (low barrier function)
• High rate if infections in infants <3 months
– >4% 0-28 days with bacteremia or meningitis
– 10% with UTI
– Higher risk of bacteremia with higher fever
• May appear well and have infxn
 2/1000 live births in US
• 7-13% neonates are evaluated, only 3-8% have
cx proven sepsis
• Aggressive evaluation is indicated as mortality
for untreated sepsis is 50%
 Neonatal meningitis 2-4/1000 live births
How to judge if admission is
 Rochester criteria
 Philadelphia criteria
 Boston criteria
Risk factors
 Prematurity or low birth weight
 Maternal GBS
 Sepsis in previous sibling
 Maternal chorio
 Need for resuscitation
 Male
 Multiple gestation
 Fever/hypothermia
 Poor tone
 Irritability
 Shrill/weak cry
 Skin
- pallor, poor perfusion, mottling,
petechiae, jaundice, cyanosis
 Nonspecific, and are associated with many
other disorders
Poor feeding
Hypo or hyperglycemia
tachypnea and/or retractions
Signs/Sx (cont)
 Low SpO2
 Sunken
or bulging fontanelle
Differential Diagnosis
 Metabolic acidosis
 Bowel obstruction
 Coarctation of aorta
 Congenital diaphragmatic hernia
 Congenital lung malformations
 Congenital pneumonia
DDx (cont)
 Hemolytic disease of the newborn
 Hemorrhagic disease of the newborn
 Hypoglycemia
 Hypoplastic left heart syndrome
 Meconium aspiration syndrome
 Bacterial meningitis
 Necrotizing enterocolitis
DDx (cont)
 Pericarditis
 Pulmonary atresia
 Pulmonary HTN
 Pulmonary hypoplasia
 Single ventricle
 Check everything!
Blood, urine and CSF cultures
CBC with diff
CSF studies
CRP level (which you will get back in 2 wks)
Serum IgM may indicate an intrauterine infxn
HSV PCR if CNS abnormalities, skin vesicles, or
not responding to abx
• May look like RDS in sepsis
 CT or MRI late in course of meningitis
 Head ultrasound may be useful in
What are we treating?
 Early pathogens (1st week)
E coli
Gram neg rods (esp in urine)
Later bugs…
 Late onset sepsis (1-2 wks)
GBS or grp A strep
Enterococcus in urine
Enterovirus, RSV, influenza
 Begin abx as soon as labs done
• IV aminoglycoside and expanded-spectrum
– Usually tx for 7-10 days even if cx neg after 48-72 hrs
• Oxacillin if nosocomial infection is suspected
• Meningitis requires tx for 2wks after
sterilization of CSF
 Term infants usually have no long term
sequelae if treated early
• Residual neuro problems occur in 15-30% with
septic meningitis
 Preterm infants have higher rates of
cognitive defects, CP, and other neuro
Surgical Emergencies
 Pyloric stenosis
 Congenital diaphragmatic hernia
 Tracheoesophageal fistula
 Abdominal wall defects
• Gastroschisis
• Omphalocele
• Necrotizing enterocolitis
Necrotizing enterocolitis
 Intestinal wall inflammation or injury
caused by bacterial invasion or previously
injured or ischemic bowel wall
 Incidence: 5-10% infants <1500 gm
 Mortality: 10-30%
Risk Factors
 PREMATURITY (yes, again…)
 Others…
Bacterial infxn
Enteral feeding
Congenital heart disease
Hyperosmolar formula
Hx umbilical arterial catheter
Hx exchange transfusion
Early Signs
 Temp instability
 Poor feeding
 Bilious vomiting
 Lethargy
 Mucoid or bloody stool
 Apnea
 bradycardia
Late signs
 Hemodynamic instability
 Anemia
 Thrombocytopenia
 Prerenal azotemia
 Metabolic acidosis
 Abdominal x-ray
• Bowel obstruction, edematous bowel, ileus,
intramural air, pneumoperitoneum
Medical Management
 Initial, for 7-10 days; 75% successful
No enteral feeds for 10-14 days
NGT to intermittent suction
Hydration, ‘lyte management
Respiratory support
Blood and platelets if needed
Surgical management
 10-50% mortality
 Indications
• Absolute
– Bowel perforation
– Intestinal gangrene
• Relative
– Metabolic acidosis
– Resp failure
– Oliguria
– Thrombocytopenia
– Leukocytosis
– Air in portal vein
– Bowel wall edema
– Persistent dilated bowel loops