1) Hypoglycemia is common in newborns, affecting 1-3 per 1000 live births, with risk decreasing with increasing gestational age. 2) Significant neurodevelopmental deficits can occur in neonates who experience prolonged hypoglycemia. Studies in monkeys and infants show neuronal injury, particularly in parieto-occipital cortex and other regions. 3) There is no consensus on the definition and threshold for treating hypoglycemia. Guidelines generally recommend treating if blood glucose is less than 50 mg/dL in symptomatic newborns or less than 36 mg/dL in at-risk but asymptomatic newborns.

1. HYPOGLYCEMIA
Dr. C. Niramala
Asso. Professor, Niloufer Hospital

2. INCIDENCE
 1-3/ 1000
live births
 Incidence is
inversely
proportional
to
Gestational
age

3. Why identify hypoglycemia in newborns?
 Hypoglycemia is a common disorder in neonates,
however no clear definition exists.
 The level of blood glucose that warrants treatment
depends much on other factors: Gestational Age,
concomitant risk factors, and conditon of the
newborn
 Significant neurodevelopmental deficits can occur in
neonates who experience days of hypoglyemia.

4.  Adolescent monkeys when exposed to blood glucose of
<20mg/dL for more than 2 hours showed neuronal injury
predominantly in the regions of parieto-occipital cortex. Less
commonly involved regions were hippocampus, caudate nucleus,
& putamen.The injury was most in regions contiguous to
cerebrospinal fluid-superficial cerebral cortical layers
 (Agardh et al., 1980; Auer et al., 1984, 1985;Kalimo et al., 1985;
Siesjo, 1988).
 Similar topographical distribution of neuropathology was observed
in premature infants using autopsy studies, computed
tomography, magnetic resonance imaging and single photon
emission computed tomography blood flow scans
 (Anderson et al., 1967; Spar et al., 1994; Chiu et al., 1998; Volpe,
2008).
Studies based on neurodevelpoment

5.  The hypoglycemic brain injury primarily involves neurons but glia
are also affected
 (Anderson et al., 1967).
 Studies of oligodendrocyte precursor cells and cerebellar slice
cultures showed that hypoglycemia induces apoptotic cell death
and inhibits differentiation and myelination
 (Yan & Rivkees 2006).

6.  At birth, the blood glucose concentration is about 70% of the maternal level.
 It falls rapidly to a nadir by 1 h or so of life to as low as 20 to 25 mg/dl.
 The decrease is a part of the normal adaptation for postnatal life that helps
establish postnatal glucose homeostasis.
 The decrease in glucose concentrations
 essential to stimulate physiological
processes including gluconeogenesis and glycogenolysis.
 enhances oxidative fat metabolism,
stimulates appetite and may help adapt to fast-feed cycles.
 might be the result of mechanisms for
the fetus to allow maternal-to-fetal glucose transport but not reversed after birth.
Neonatal hypoglycemia: is 60 the new 40? The questions remain the same DH Adamkin1 and R Polin2; Journal of Perinatology
(2016) 36, 10–12; doi:10.1038/jp.2015.125

7.  Low blood glucose concentrations (< 2.6 mmol/l) are
commonly found during the initial days in healthy AGA
and SGA term neonates.
 Marked ketogenic response occurs.
 Ketone bodies - provides glucose-sparing fuel to the
brain - protects neurological function.
 No studies have shown that treating transiently low blood glucose
levels results in better short-term or long-term outcomes
compared with no treatment
 There is no evidence that hypoglycemic infants with no clinical
signs benefit from treatment.
 Transient, single, brief periods of hypoglycemia are unlikely to
cause permanent neurologic damage.
ABM Clinical Protocol #1: Guidelines for Blood Glucose Monitoring and Treatment of Hypoglycemia in Term and Late-
Preterm Neonates, Revised 2014 Nancy Wight,1,2 Kathleen A. Marinelli,3,4 and The Academy of Breastfeeding Medicine

8. In some conditions
 preterm delivery
 IUGR
 Perinatal hypoxic–ischaemia
suboptimal control of diabetes in
pregnancy, there is impaired ketone
body production and hypoglycaemia, if
present, must be diagnosed and treated
effectively.

9. Hypoglycemia

10. How low is too low?
4 approaches to the definition of hypoglycemia: “ALL
FLAWED”
1) an approach based on clinical manifestations
2) the epidemiologic approach based on measured
range of glucose value(<5th percentile from
statistical calculations)
3) An approach based on acute changes in
metabolic and endocrine responses and on
neurologic function
4) An approach based on long-term neurologic
outcome.
World Health Organization. Hypoglycaemia of the newborn: review of the literature. Geneva, Switzerland: World Health Organization;
1997. Available at: http://www.who.int/chd/pub/imci/bf/hypoglyc/hypoglyc.htm

11. In general, a plasma glucose level of <50 mg/dL is a
practical, reasonable, and safe threshold for assessing a
newborn for hypoglycemia.
Cornblath M., Mawdon JM, Aynsley-Green A., Ward-Platt MP, Schwartz R, Kalhan Sccontroversies regarding definition of
hypoglycemia: suggested operational thresholds. Pediatrics. May 2000,105(5)
Hussain, 2005. Hussain K.: Congenital hyperinsulinism. Semin Fetal Neonatal Med 2005; 10: pp. 369-376;
Sperling and Menon, 2004. Sperling M.A., and Menon R.K.: Differential diagnosis and management of neonatal hypoglycemia.
Pediatr Clin North Am 2004; 51: pp. 703-723
• <36mg/dlAt-risk
neonates(without
signs/ symptoms)
• <45mg/dlNewborns with
abnormal clinical
signs/ symptoms
• <63mg/dlNewborns with
hyperinsulinemia

12. AAP-PES: hypoglycemia
• <48 hrs:
• > 48 hrs:
SYMPTOMATIC
• <4 hrs:
• 4-24 hrs:
• 24-48hrs:
• >48 hrs:
ASYMPTOMATIC
plasma glu <50 mg/dl
plasma glu <60 mg/dl
plasma glu <25 mg/dl
Pl. glu <35 mg/dl
Pl. glu <50 mg/dl
Pl. glu <60 mg/dl

13. 1-2hrs: < 28mg/dl
3-47hrs: <40mg/dl
48-72hrs: <48mg/dl
Practical threshold <
50mg/dl
The therapeutic objective
(45 mg/dL) is different from
the operational threshold
for intervention (36 mg/dL)
Endocrinological approach
(PES) - 55 to 65mg/dl as a
critical glucose range.
ABM Clinical Protocol #1: Guidelines for Blood Glucose Monitoring and Treatment of Hypoglycemia in Term and Late-
Preterm Neonates, Revised 2014 Nancy Wight,1,2 Kathleen A. Marinelli,3,4 and The Academy of Breastfeeding Medicine
Based on hours of life for
healthy term neonates:

14. ETIOLOGY
HYPERINSULINEMIC
~IDM
~Gene mutations
~Others: Perinatal asphyxia,
syndromes, eryhroblastosis,
maternal tocolytics, abrupt
cessation of high glucose
infusion, tumors
LARGE FOR GA
↓ PRODUCTION OR
STORES
~Prematurity
~IUGR
~Delayed onset of
feeding
~inadequate cal intake
↑ UTILISATION &/OR ↓
PRODUCTION
~perinatal stress
~defects in
Carbohydrate &
Amino acid
metabolism
~Endocrine
deficiencies
~polycythemia
~maternal therapy
with B-blockers

15. CLINICAL MANIFESTATIONS
 Due to AUTONOMIC NERVOUS SYSTEM
 Anxiety
 Perspiration
 Palpitations
 Pallor
 Tremulousness
 Hunger
 Nausea
 emesis

16. d/t CEREBRAL GLUCOPENIA
 Headache
 Dysrathria
 Confusion/inability to concentrate
 Visual disturbances
 Dizziness
 Amnesia
 Refusal to feed
 Somnolence
 Seizures
 Coma
 Stroke, hemiplegia, aphasia
 posturing

17. APPROACH

18. INVESTIGATIONS:
 ABG
 Base line investigation: CBP, Blood culture.
 Free fatty acids
 Ketones
 Lactate
 Uric acid
 Ammonia
 HORMONES:-
 Insulin
 Cortisol
 Growth hormone
 ACTH
 Thyroxine, thyroid-stimulating hormone
 Insulin-like growth factor binding protein
 TMS/GCMS : to rule out IEM

20. Pl.Glu ↑ <30
mg/dl in response
to GLUCAGON
= no hepatic
glycogen not
consistent with HI
No
No
↑↑↑
↑↑
Normal to ↑
Normal
FAO dis.
MCAD-
VLCAD-
No
No
↑↑
Normal
↑↑
↑
Defect in Glycogen
met/gluconeogene
sis
Von gierkes ds.
F1,6BP def.
No
No
↑↑
Normal
↑↑
↑↑
N. FAO, Glycogen
met. Gluconeogen.
Prolonged fasting
Ketotic HG
GSD 0,3,6,9
GH-; Cortisol-

22. FOLLOW UP
MRI
•@ 4-6Weeks
VISION
•@ 4Weeks
NEURODEV.
VISION &
HEARING
assesment
•@ 3,6,9,12 & 18 Mn of
age

23. Thank you