Neonatal Hypoglycemia:
Neonatal Hypoglycemia:
Evidences and Practice
Evidences and Practice
Prof. Pushpa Raj Sharma
Department of Child Health




•
Inability to breast feed and weight <2500 g were
independently associated with hypoglycaemia. Mortality
was 45.2% compared to 19.6% in normoglycaemic neonates
(p < 0.001).
Osier FH, Berkley JA, Ross A, Sanderson F, Mohammed S, Newton CR.
Abnormal blood glucose concentrations on admission to a rural Kenyan district
hospital: prevalence and outcome.
Arch Dis Child. 2003 Jul;88(7):621-5.
•
41% newborn infants had mild (less than 2.6 mmol/l) and
11% had moderate hypoglycaemia: Hospital based study.
Pal DK, Manandhar DS, Rajbhandari S, Land JM, Patel N, de L Costello AM.
Arch Dis Child Fetal Neonatal Ed. 2000 Jan;82(1):F46-51.
Why This Topic is Important?
Why This Topic is Important?

Koivisto M, Blaco-Sequeiros M, Krause U. Neonatal
Koivisto M, Blaco-Sequeiros M, Krause U. Neonatal
symptomatic hypoglycaemia: a follow-up study of 151
symptomatic hypoglycaemia: a follow-up study of 151
children. Dev Med. Child Neurol 1972; 14:603-14
children. Dev Med. Child Neurol 1972; 14:603-14

Their conclusions? TIME is most important factor
affecting onset of sx and SYMPTOMATIC hypoglycemia with convulsions has
poor prognosis for permanent CNS damage, while asymptomatic
hypoglycemia without convulsions appears to have no influence on CNS
pathology




Long term neurological outcomes

Lucus A, Morley R, Cole TJ. Adverse
neurodevelopmental outcome of moderate
neonatal hypoglycemia. British Medical Journal
1988; 297:1304-1308

661 preterm infants (BW <1850 g) surviving >48hrs

Weekly glucose level taken; reagent strips q6h for first
48-72 hours (if <1.5 or 2 low values below 2.5  blood

test)

Treated by feeds/iv or bolus if less than 1 mmol/l or sx

At 18 months  92% assessed with Bayley motor and
development scale

Results examined by statistical adjustment for
differences between infants with and without
hypoglycemia




Lucus A, Morley R, Cole TJ.
Lucus A, Morley R, Cole TJ.

Their findings?
<2.6 on 3 to 30 separate days  associated with reductions in Bayley
motor ad mental development scores even after adjusting for
confounding factors
<2.6 on 5 or more consecutive days  increased risk (3.5 fold) of CP




Kinnala et al. Cerebral magnetic resonance
Kinnala et al. Cerebral magnetic resonance
imaging and ultrasonography findings after
imaging and ultrasonography findings after

neonatal hypoglycemia. Pediatrics 103; 1999
neonatal hypoglycemia. Pediatrics 103; 1999

Investigated neuroradiologic changes in the
brains of infants after transient neonatal
hypoglycemia via MRI and U/S

Def’n of hypoglycemia: <2.5 mM WITH symptoms

Treatment included feeds, IV, hydrocortisone

MRI and US at fullterm and at 2m in 18 symptomatic
fullterms (6 babies with SGA, 2 infants of diabetic
mom) without any other pathology and 19 term
controls




Kinnala et al. Cerebral magnetic resonance
Kinnala et al. Cerebral magnetic resonance
imaging andultrasonography findings after
imaging andultrasonography findings after
neonatal hypoglycemia. Pediatrics 103; 1999
neonatal hypoglycemia. Pediatrics 103; 1999
Results?

39% of hypoglycemic infants had abnormalities detected on
MRI  4 showed patchy hyperintensity lesions in occipital
periventricular white matter of the thalamus; lesions

recovered by 2 months with only 1 neurologically affected

Controls  10% had caudothalamic cysts

Relative risk of hypoglycemic child compared with
normoglycemic child to have ay abnormality detected in
the brain was 3.7 (4x more often)

Developmental assessment at 11 months  94% normal; 1
infant had rightsided hemiplegia ad tremors




Glucose Physiology in a Nutshell!
Glucose Physiology in a Nutshell!
FETUS:

Energy as glucose, lactate, FFAs, ketones,
surplus amino acids

Gluconeogenesis & ketogenesis virtually
absent

Energy stored at rapid rate (100 cal of
fat/day in 9
th
month!)
AT DELIVERY:


Adaptive response  surge in plasma
glucagon & decrease in plasma insulin 
mobilizes glucose & fatty acids from
glycogen & triglyceride depots




Glucose Physiology II….
Glucose Physiology II….
NEONATE:

Stores become insufficient so must rely
on gluconeogenesis

Glucose is main oxidative fuel, but
neonates can oxidize ketone bodies,
lactate & amino acids

Glucose requirements exceed those of
adults mainly b/c of increased ratio of
brain to body mass

Low blood glucose values are usually NOT
related to any significant problem but are
2
0
to normal process of metabolic
adaptation to extrauterine life





Definition of neonatal
Definition of neonatal
hypoglycemia
hypoglycemia
•
The definition of clinically significant
hypoglycemia remains one of the most
confused and contentious issues in
contemporary neonatology.
Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-
Platt MP, Schwartz R, Kalhan SC. Controversies regarding
definition of neonatal hypoglycemia: suggested operational
thresholds.
Pediatrics. 2000 May;105(5):1141-5.




Approaches to defining neonatal
Approaches to defining neonatal
hypoglycemia!
hypoglycemia!
Clinical Manifestations

Must fulfill Whipple’s Triad
a) Low glucose
b) S&S consistent with hypoglycemia

(eg. Jitteriness, tremors, lethargy, seizures,
apnea, cyanotic spells, hypotonia, difficulty
feeding, hypothermia, coma)
c) Resolution of S&S after restoring glucose




Serum level?
Serum level?
Epidemiological Approach

Def’n based on statistical definition of glucose
values < or = to 2 SD below the mean in the
population of well full term & LBW infants
“in neonates any value below 40 mg/dL (2.8
mM) be viewed with suspicion”:
Sperling MA. in Hypoglycemia; Chapter 77,
page 420. Nelson’s Textbook of Paediatrics, 15
th
ed.




Operational Threshold
Operational Threshold
•
Indication for intervention


Based on evidence currently available in the
literature
Concentration of glucose in the blood or plasma at which
the individual demonstrates a unique response to the
abnormal milieu caused by the inadequate delivery of
glucose to a target organ
Cornblath et al. Controversies regarding definition of neonatal
hypoglycemia: suggested operational thresholds. Pediatrics 105:
153-157, 2000

Provides large margin of safety by designating
the lower level of glucose that a neonate can
safely tolerate based on physical maturity and
influence of pathology




Proposed Operational Thresholds
Proposed Operational Thresholds
1
st
24 hours of life:
Healthy preterm*/full term neonate:
a) NO clinical signs: <2.0 mM
b) Abnormal clinical signs: <2.5 mM
Sick, Hypoxic, LBW, Infant of
diabetic mom or premature neonate:
<2.5 mM
* >34 weeks





Proposed Operational Thresholds
Proposed Operational Thresholds
>24 hours of life: Others:
2.2  2.8 mM TPN: <2.5 mM
Note: Level can be  in asymptomatic breast fed
neonates because of concentrations of ketones
(<1.7 or <2.0 mM  but there is controversy!!)




Operational Thresholds: How to use
Operational Thresholds: How to use
them?
them?

Remember: INDICATION FOR ACTION!
But, what is your goal?

THERAPEUTIC OBJECTIVE
Raise glucose to > 2.6 mmol/l
IF Recurrent, profound, sick
or symptomatic neonates: > 2.8  3.3
Why is your Therapeutic Objective different
from your Operational Threshold?


Higher therapeutic goal is chosen to include a
significant margin of safety

Note: Response to Rx is NOT necessary




Who’s at Risk? What could be the
Who’s at Risk? What could be the
cause?
cause?
At Risk Groups:
A. Increased Insulin
•
Intrapartum glucose
•
Drug Treatment (eg. Propranolol)
•
Infant of Diabetic Mother
•
Asphyxia ,SGA
•
Insulinomas
•
Beckwidth’s syndrome
•
Familial or sporadic hyperinsulinemia
•
Familial or sporadic hyperammonemic hyperinsulinemia

•
Severe erythroblastosis fetalis
•
Panhypopituitarism




At Risk Infants/Causes II…
At Risk Infants/Causes II…
B. Decreased Stores
•
Placental abnormalities
•
IUGR
•
Preterms <32 weeks, <1500g
•
Smaller of discordant twins (especially if discordant by
>25% with wt <2kg)
C. Increased Needs
•
Very immature, SGA (high brain:liver ratio)
•
Severely ill (RDS, Septic)
•
Brain injury  meningitis, trauma, hemorrhage,
hypoxia-ischemia (increased brain glucose needs)
•
Hypothermia

•
Cyanotic heart disease
•
Drug withdrawal, CNS irritability




At Risk Infants/Causes III…
At Risk Infants/Causes III…
D. Inadequate production or substrate delivery
•
Delayed/ inadequate feedings
•
Transient developmental immaturity of critical
metabolic pathways
•
Deficient brain glucose transporters: posthypoxia-
ischemia, inherited glucose transporter defects
•
Galactosemia
•
Glycogen storage disease
•
Fructose intolerance
•
Maple syrup urine disease
•
Long- or medium-chain acyl-CoA dehydrogenase
deficiency

To name a few!!! Many more …………………… !!




When do you screen these “at risk”
When do you screen these “at risk”
babies?
babies?
FIRST OF ALL in ANY BABY:
If symptomatic: SCREEN IMMEDIATELY
If asymptomatic but AT HIGH RISK including infant of diabetic mom,
septic, premature (<32 wks), <1500g: Screen at 30-60 min of life
If asymptomatic but AT RISK:
Screen baby at 3-4 hrs of life
ALWAYS CHECK VALUE WITH LAB TEST!!
ONE VALUE IS SUFFICIENT FOR ACTION!




Practical Points for Blood
Practical Points for Blood
Glucose Estimation
Glucose Estimation
•
Can it be used for neonate? Dextrostix.
•
False positive: hematocrit <35%, contamination with
isopropylalcohal.

•
False negative: hematocrit >55%.
•
Glucose level can fall by 14-18 mg/dl/hr.
•
False results if done < 18degree C or >35 degree C.




So……
So……
you’ve got a low
glucose,
Now WHAT DO YOU DO???