SYMPOSIUM ON

NEONATAL
HYPOGLYCEMIA

SUBMITTED TO:

LT COL SUNITA
COURSE COORDINATOR
AH R&R

SUBMITTED BY:
CAPT AKANKSHA GAUR
PB DIPLOMA IN NEONATAL
NURSING
AH R & R

NEONATAL HYPOGLYCEMIA

INTRODUCTION
Hypoglycemia is one of the most common metabolic problems seen in sick babies and well babies at-
risk of hypoglycemia. Managing hypoglycemia requires interpretation of blood glucose values within
the clinical context. Blood glucose levels in the first hours of life are typically lower than the normal
values in older children or adults. In healthy infants, blood glucose levels can often be maintained in
the appropriate range by initiating breastfeeding soon after birth. Most cases of neonatal
hypoglycemia are transient, respond readily to treatment, and are associated with an excellent
prognosis. Symptomatic hypoglycemia is associated with high risk of severe neurodisability. Babies
with persistent low sugars must be investigated for underlying causes (hyperinsulinemia is
commonest). Hyperglycemia is very uncommon in the newborn nursery but frequently occurs in very
low-birth-weight (VLBW) infants in the NICU

DEFINITION
Blood glucose level of less than 45 mg/dl or 2.2 mmol/L.

-WHO

OPERATION THRESHOLD
Defined as that concentration of plasma or whole blood glucose at which clinicians should consider
intervention.

- Cornblath

Operational threshold has been defined as blood glucose level of less than 40 mg/dl ( plasma
glucose level less than 45 mg/dl).

CLASSIFICATION
1. Symptomatic infants with blood glucose <40 mg/dL with intravenous (IV)

glucose

2. Asymptomatic infants at risk for hypoglycemia defined as late preterm (34 to

36 weeks of gestation), term SGA, IDM, or LGA

a. First 4 hours of life

i. Initial screen <25 mg/dL (should be done within the first hours after

birth), infants should be fed and rechecked, and if the next level, 1 hour

later, is <25 mg/dL, treatment with IV glucose should be administered.

ii. If the second check is 25 to 40 mg/dL, feeding may be considered as an

alternative to IV glucose.

b. Four to 24 hours of life

i. Glucose <35 mg/dL, infants should be fed and glucose rechecked in 1 hour.

ii. If glucose continues to be <35 mg/dL, IV glucose should be administered.

iii. If recheck after initial feeding is 35 to 45 mg/dL, feeding may be

attempted.

iv. Recommendation is to target glucose >45 mg/dL.

INCIDENCE
The incidence of hypoglycemia varies by population and definition used. Furthermore, blood glucose
levels change markedly within the first hours of life, and it is necessary to know the infant’s exact
age in order to interpret the glucose level and diagnose hypoglycemia.

A recent prospective study of infants at risk for hypoglycemia (defined as a blood glucose
<2.6mosm/L [<46.8 mg/dL])

 Overall incidence = 5-15 /1000 live births

 Normal newborns – 10% if feeding is delayed for 3-6 hours after birth

At Risk infants – 30%

47% of large-for-gestational-age (LGA) infants

52% of small-for-gestational-age (SGA) infants,

48% of infants of diabetic mothers (IDMs)

54% of late preterm infants has low blood sugar levels.

PATHOPHYSIOLOGY
1. Glucose provides approximately 60% to 70% of fetal energy needs. Almost all fetal glucose
derives from the maternal circulation by the process of transplacental facilitated diffusion
that maintains fetal glucose levels at approximately two-thirds of maternal levels.
2. Maternal hepatic glucose production increases by 16% to 30% through gestation to supply
the fetus with energy. The severing of the umbilical cord at birth abruptly interrupts the
source of glucose.
3. Subsequently, the newborn must rapidly respond by glycogenolysis of hepatic stores,
gluconeogenesis, and utilizing exogenous nutrients from feeding to maintain adequate
glucose levels.

4. During this normal transition, newborn glucose levels fall to a low point in the first 1 to 2
hours of life (to as low as 30 mg/dL) and then increase to >45 mg/dL, stabilizing at mean levels of
65 to 70 mg/dL by 3 to 4 hours of age.

ETIOLOGY
1. Hyperinsulinemic hypoglycemia causes persistent, recurrent hypoglycemia in newborns,
and it may be associated with an increased risk of brain injury because it not only decreases
serum glucose levels but also prevents the brain from utilizing secondary fuel sources by
suppressing fatty acid release and ketone body synthesis. Some cases of hyperinsulinemic
hypoglycemia are transient and resolve over the course of several days, whereas others require
more aggressive and prolonged treatment.

a. The most common example of hyperinsulinism is the IDM. Women are screened for
gestational diabetes during pregnancy and blood sugar levels are optimized by diet or
medications. Yet, some women either have mild glucose intolerance that is sub threshold for
diagnosis or develop late-onset glucose intolerance; their infants may be LGA and at risk of
hypoglycemia.

b. Congenital hyperinsulinism. Hyperinsulinism is seen in mutations of genes

encoding the pancreatic beta-cell adenosine triphosphate (ATP)–sensitive

potassium channel, such as ABCC8 and KCNJ11 which encode for SUR1

and Kir6.2. Elevated insulin levels are also associated with loss-of-function

mutations in HNF4A gene. Additional mutations continue to be identified.

c. Secondary to other conditions

i. Perinatal asphyxia

ii. Syndromes such as Beckwith–Wiedemann syndrome (macrosomia,

mild microcephaly, omphalocele, macroglossia, hypoglycemia, and

visceromegaly)

iii. Congenital disorders of glycosylation and other metabolic conditions

iv. Erythroblastosis (hyperplastic islets of Langerhans)

v. Maternal tocolytic therapy with beta-sympathomimetic agents (terbutaline)

vi. Malpositioned umbilical artery catheter used to infuse glucose in high

concentration into the celiac and superior mesenteric arteries T11–

T12, stimulating insulin release from the pancreas

vii. Abrupt cessation of high glucose infusion

viii. After exchange transfusion with blood containing high glucose concentration

ix. Insulin-producing tumors (nesidioblastosis, islet cell adenoma, or islet

cell dysmaturity)

2. Decreased production/stores
a. Prematurity

b. Fetal growth restriction (FGR) or SGA

3. Increased utilization and/or decreased production. Any infant with one

of the following conditions should be evaluated for hypoglycemia; parenteral

glucose may be necessary for the management of these infants.

a.Perinatal stress
i. Sepsis

ii. Shock

iii. Asphyxia

iv. Hypothermia (increased utilization)

v. Respiratory distress

vi. Post-resuscitation

b. Reactive hypoglycemia after exchange transfusion with relatively hyperglycemic citrate-

phosphate-dextrose (CPD) blood

c. Defects in carbohydrate metabolism

i. Glycogen storage disease

ii. Fructose intolerance

iii. Galactosemia

d. Endocrine deficiency
i. Adrenal insufficiency
ii. Hypothalamic deficiency

iii. Congenital hypopituitarism

iv. Glucagon deficiency

v. Epinephrine deficiency

e. Defects in amino acid metabolism

i. Maple syrup urine disease

ii. Propionic acidemia

iii. Methylmalonic acidemia

iv. Tyrosinemia

v. Glutaric acidemia type II

vi. Ethylmalonic-adipic aciduria

f. Polycythemia. Hypoglycemia may be due to higher glucose utilization by the increased mass
of red blood cells. Additionally, decreased amount of serum per drop of blood may cause a
reading consistent with hypoglycemia on whole blood measurements but may yield a normal
glucose level on laboratory analysis of serum.

g. Maternal or infant therapy with beta-blockers (e.g., labetalol or propranolol). Possible

mechanisms include the following: i. Prevention of sympathetic stimulation of glycogenolysis ii.
Prevention of recovery from insulin-induced decreases in free fatty acids and glycerol iii.
Inhibition of epinephrine-induced increases in free fatty acids and lactate after exercise D.

DIAGNOSIS
1. Symptoms that have been attributed to hypoglycemia are nonspecific.

a. Irritability

b. Tremors

c. Jitteriness

d. Exaggerated Moro reflex

e. High-pitched cry

f. Seizures

g. Lethargy

h. Hypotonia

i. Cyanosis

j. Apnea
k. Poor feeding

l. Many infants have no symptoms.

2. Screening. Serial blood glucose levels should be routinely measured in infants

who have risk factors for hypoglycemia and in infants who have symptoms

that could be due to hypoglycemia.

INDICATION FOR ROUTINE EVALUATION

 Birth weight < 2000gm
 Gestational age <35 weeks
 SGA :Birth wt <10th percentile
 LGA: BWt >90th centile
 Infant of diabetic mother
 Neonate with Rh Hemolytic Disease
 Neonate of mother on Beta blockers
 Family history of genetic form of hypoglycemia
 Any sick neonate.
 Congenital syndromes (Beckwith –Wiedmann)
 Neonates on parentral nutrition

SCHEDULE FOR GLUCOSE MONITORING

SN CATEGORY OF INFANTS TIME SCHEDULE
O
1. At risk neonates 2,6,12,24,48 and 72 hrs of life
(72 hrs monitoring can be omitted if feeding has
been established well)

2. Sick neonate ( sepsis, asphyxia, Every 6-8 hrs

polycythemia, shock during acute (Individualize as needed )
phase of illness)

3. Neonates on parenteral nutrition Initial 72 hrs : every 6-8 hrs

After 72 hrs : once a day

3. Reagent strips with reflectance meter.

Although in widespread use as a screening tool, reagent strips are of unproven reliability in
documenting hypoglycemia in neonates.

a. Reagent strips measure whole blood glucose, which is 15% lower than plasma levels.

b. Reagent strips are subject to false-positive and false-negative results as a screen for
hypoglycemia, even when used with a reflectance meter.
4. Laboratory diagnosis
The laboratory sample must be obtained and analyzed promptly to avoid the measurement
being falsely lowered by glycolysis. The glucose level can fall up to 6 mg/dL/hour in a blood
sample that awaits analysis.

5. Subcutaneous (SC) continuous glucose monitors have been shown to be accurate but
have primarily been used in research settings.

6.Critical lab sample.

Diagnosing hyperinsulinemia requires measuring an insulin level that is inappropriately high for a
simultaneous serum glucose. Evaluation requires drawing blood for insulin, cortisol, and amino
acids ata time when the glucose level is <40 mg/dL. The typical critical lab sample includes the
following:

i. Glucose

ii. Insulin

iii. Cortisol. Cortisol levels can be used to screen for the integrity of the

hypothalamic–pituitary–adrenal axis.

iv. Beta-hydroxybutyrate and free fatty acid levels. Measurement of plasma

beta-hydroxybutyrate and free fatty acid levels can be useful because

decreased levels of these substances can indicate excessive insulin action

even if insulin levels are not significantly elevated.

Additional Testing
If the insulin level is normal for the blood glucose level, consider additional testing indicated as
follows to evaluate for other causes of persistent hypoglycemia such as defects in carbohydrate
metabolism,endocrine deficiency and defects in amino acid metabolism

i. Growth hormone

ii. Adrenocorticotropic hormone (ACTH)

iii. Thyroxine (T4) and thyroid-stimulating hormone (TSH)

iv. Glucagon

v. Plasma amino acids

vi. Urine ketones

vii. Urine-reducing substance

viii. Urine amino acids

ix. Urine organic acids

x. Genetic testing for various mutations such as SUR1 and KiR6.

DIFFERENTIAL DIAGNOSIS
The symptoms can be due to many other causes with or without associated hypoglycemia. If
symptoms persist after the glucose concentration is in the normal range, other etiologies should
be considered.

Some of these are as follows:

a. Sepsis

b. Central nervous system (CNS) disease

c. Toxic exposure

d. Metabolic abnormalities : Hypocalcemia ,Hyponatremia or hypernatremia ,

Hypomagnesemia , Pyridoxine deficiency Adrenal insufficiency

f. Heart failure

g. Renal failure

h. Liver failure

MANAGEMENT
Gestation Age >35 Weeks

All infants:

 Skin-to-skin care, keep warm

 Promote breastfeeding within first hour of birth
 Infants should continue breastfeeding on cue
 Not to give water or glucose water or formula may interfere with normal metabolic
compensatory mechanisms

At risk infants:

 Symptomatic and blood glucose < 40 mg/dL: Start intravenous (IV) glucose
 Symptomatic with blood glucose < 25 mg/dL: Give bolus IV dextrose 10% 1–2 mL/kg
followed
 by infusion at the rate of 5–8 mg/kg/min.
 Target glucose > 50 mg/dL
 Continue breastfeeding frequently
 Recheck plasma glucose within 30 minutes

Asymptomatic: <40 mg/dL and <4 hours of age:

 Start breastfeeding within half an hour
 Recheck blood glucose before next feeding
 Continue skin-to-skin care
 Intensify breastfeeding
 Evaluate for other underlying illnesses
 If glucose <35 mg/dL start IV glucose therapy
 Target blood glucose > 50 mg/dL
 Recheck until three normal levels
 Check glucose levels once at 24 hours of age in babies like small for gestational age
(SGA)/low birth weight (LBW)/preterm
 Rate of start of IV fluids: Use graded approach
 IUGR: 5–7 mg/kg/min
 Mother with infants of diabetic mothers (IDM)/LGA infants: 3–5 mg/kg/min
 Infant with other risk group: 4–6 mg/kg/min
 Glucose infusion >12 mg/kg/min: Consider for further interventions
 Maximum dextrose concentration through peripheral IV cannula and central venous
catheter is 12.5% and 25%, respectively
 Infant with persistent hypoglycemia for >72 hours or requiring IV therapy for
symptomatic or asymptomatic low glucose levels should only be discharged if glucose
level maintained above 70 mg/dL through several feed-fast cycles.

GIR (mg/kg/min)= % of Dextrose being infused x rate of infusion (ml/hr)

Body weight (in kg) x 6

For eg: An infant weights 2 kg and is receiving 100ml/kg/day of dextrose 15% solution
GIR = 15% x 8.3
6x2 = 10.3 mg/kg/min
DRUGS USED IN RESISTANT HYPOGLYCEMIA

DRUGS DOSE ROUTE MODE OF SIDE EFFECTS

ACTION
Hydrocortisone 5mg/kg/day BD PO/IV Reduces Hyperglycemia
peripheral Hypertension
glucose
utilisation
Increases
gluconeogenesis,
Increases
glucagon effect

Diazoxide 5-15 PO K channel agonist Fluid retention

mg/kg/day TDS hypertrichosis,
cardiac failure

Octereotide 5-35 SC Somatostatin Cholelithiasis,transient

mg/kg/day analogue inhibits growthimpairement,
TDS/QID insulin secretion tachyphylaxis

Glucagon 0.2 mg/kg SC or IM Glycogenolysis Nausea,

Increased vomiting,
gluconeogenesis skin rash, rebound
hypoglycemia

PREVENTION
 Assess risk factors
 Proper breastfeeding counselling and support
 Proper screening of high risk cases
 Proper assessment of adequacy of breast feed
 Maintain thermoneutral environment.
 Early feeding – as soon as the neonate is ready, preferably within 1 hour of birth.
 Adequate feeding on demand or 2 hrly feed
 Do not feed dextrose as a substitute .It can induce vomiting,decreased glucagon and
rebound hypoglycemia.
 Evaluate symptoms
 No interruption in Iv infusion
NURSING RESPONSIBILITY
ANTENATAL
Asess risk factors ,ensure antenatal screening
Promote proper nutrition
Treat maternal infection
Provide breastfeeding counselling

DURING DELIVERY
Ensure clean delivery

Provide newborn resuscitation

POSTNATAL
Prevent and treat newborn hypothermia by drying and warming
Physical evaluation of symptoms
Prevent and treat newborn hypoglycemia
Encourage immediate and exclusive breastfeeding, prevent and treat underlying causes, Follow up

LONG TERM FOLLOW UP AND EVALUATION

 Newborn babies exposed to hypoglycemia must be followed into late childhood. Recent
systematic review showed no differences in neurodevelopmental impairment in early
childhood, but significant problems were noted in mid childhood.
 Infants and children had visuo-motor problems, poor executive function, low literacy,
and numeracy. Infants with hypoglycemia have been reported to exhibit a typical
pattern of CNS injury particularly in the parieto-occipital cortex and subcortical white
matter.
 However, it is often difficult clinically to separate isolated hypoglycemia from hypoxic-
ischemic encephalopathy plus hypoglycemia. Some clinicians believe that it is useful to
obtain a magnetic resonance imaging (MRI) scan on infants with symptomatic
hypoglycemia, but this is not yet standard of care. Close follow-up of neuro
developmental status is warranted.
 EVALUATION CRITERIA

SN CRITERIA MARKS MARKS

O ALLOTED OBTAINED
1. INTRODUCTION 05

2. ORGANISATION OF CONTENT 10

3. CONTENT MATTER 10

4. NEATNESS AND ELIGIBILITY 05

5. USE OF APPROPRIATE DIAGRAMS 05

6. CONCLUSION AND REFERENCES 10

7. CORRELATING WITH RECENT RESEARCH 05

TOTAL 50