Neonatal hypocalcemia can present with jitteriness, seizures, and other neurological symptoms. It is commonly seen in preterm infants, infants of diabetic mothers, and those with perinatal asphyxia or maternal conditions affecting calcium homeostasis. Diagnosis is made via serum calcium and magnesium levels. Treatment involves calcium gluconate administered intravenously or orally as well as magnesium supplementation if hypomagnesemia is also present. Close monitoring is needed given risks of complications. Late onset hypocalcemia may require increased oral calcium intake and reduced phosphate intake.

1. Neonatal hypoglycemia
Soumya Ranjan Parida

2. DefinitionDefinition
Controversial.Controversial.
RBS< 47mg/dl,(2.6 mmol).RBS< 47mg/dl,(2.6 mmol).
operatinal threshold of 45mg/dloperatinal threshold of 45mg/dl
2011AAP,IAP2011AAP,IAP

3. *Incidence
* 1-5 per 1,000 births
* 8% in LGA
* 15% SGA ( IUGR)
* 30% entire population of high risk infants

4. Clinical types
Early transitional hypoglycemia
• often in LGA babies, diabetic mothers
• within first few hours of life
• resolve with feeding or IV glucose
Secondary associated hypoglycemia
• term/preterm AGA babies in first day of life
• asphyxia, intracranial hemorrhage, congenital heart disease
Due to:
1. Anaerobic glycolysis depleting glucose stores
2. Increased catecholamines and glycogen depletion
3. Insulin hypersecretion
Classic transitional hypoglycemia
• SGA babies with chronic intrauterine malnutrition
• Depleted glycogen and lipid stores
• Usually in latter part of 24 hours of life

5. Clinical types – Severe recurrent hypoglycemia
Least common group and most worrisome, variable onset.
DDx:
Hyperinsulinism
Beta-cell hyperplasia
Nesidioblastosis
Macrosomia
Beckwith-Weidmann Syndrome
Endocrine abnormalities
Panhypopituitarism
Hypothyroidism
Growth hormone deficiency
Cortisol deficiency
Hereditary metabolic disorders
Abnormalities in carbohydrate metabolism
Amino acid disorders (maple syrup urine disease)
Organic acid disorders
Fatty acid oxidation disorders
Glucose transporter defects

6. Risk Factors for Hypoglycemia
Changes in maternal metabolism:
• Intrapartum administration of glucose
• Drug treatment with terbutaline, ritodrine, propanolol, oral hypoglycemics
• Diabetes in pregnancy
Associated neonatal problems:
• Idiopathic condition / failure to adapt
• Perinatal hypoxia-ischemia
• Infection
• Hypothermia
• Hyperviscosity
• Erythroblastosis fetalis, hydrops fetalis
• Iatrogenic causes
• Congenital cardiac malformations
Intrauterine growth restriction
Hyperinsulinism
Endocrine disorders
Inborn errors of metabolism

7. Clinical features
• No pathognomonic signs and symptoms
– Tachypnoea
– Jitteriness,tremors
– Hypotonia
– Changes in cosciousness(lethargy,Apathy ,Irritability)
– Apnea,bradicardia,and/cyanosis
– Poor suck,poorfeeding,
– Weak /high pitched cry
– Hypothermia
– seizure

8. Management
• Goal :
To normalize blood glucose
concentrations as quickly as
possible to avoid further episodes of
hypoglycemia by providing adequate
substrate until normal glucose
homeostasis can be established.

9. Management
• Enteral feeding : term,asymptomatic,mild hypoglycemia
Standard infant formula provide carbohydrate in
the form of lactose plus protein and fats which
are metabolized slowly.
Blood glucose increase by 1.67 mmol/L(30mg/dl)
within the first hour after a feeding of 30-60 ml of
formula

10. Management
• Symptomatic and <40mg/dl—iv glucose
• Give fresh iv canula
• Sample for blood glucose floride
vial,insuline, cortisol

11. Management.......
• asymptomatic
<4hrs of age > 4hrs of age
Initial screen <25 check pre feed
Feed and check 1hr <35mg/dl feed and recheck
<25mg/dl 25-40mg/dl after 1 hr
Iv glucose refeed /iv glucose < ,35mg/dl 35-45mg/dl
iv glu refeed/iv glu

12. Management
• IV therapy
symptomatic infants
unable to tolerate feedings
those in whom disturbance in glucose
homeostasis is severe or is expected to last
more than a few hours.

13. Management
• IV therapy
initial bolus 200 mg/kg of 10% DW (2ml/k D10W)
followed by continous infusion of 5-8 mg/k/min
Blood glucose checked after 15 mins then if stable
every 1-hrly 4hr than 6th hrly
If subsequent value falls , bolus should be repeated
and
infusion rate increased by GIR 2mg/kg/min (12-15
mg/k/min).
Umbilical venous catheter or PICC line is needed

14. Management
When can an infant be weaned from IV
therapy?
Decrease infusion rate by 2mg/kg/min every 6th hrly
if euglycemic range for 2hr,start feeding, increase feed
by 4o ml/kg /day each time
if GIR >12.5mg/dl and hypoglycaemia persist or
hypoglycaemia persist more than 7 days---persistsant
/refractory hypoglycemia---- need further evaluation

15. Additional Management
• Reduce energy needs
• Correct acidosis , avoid cold stress
• Monitor treatment at least every 30 mins
until the infant’s condition is stable
• Consider sepsis for patients with no risk
factor

16. Refractory hypoglycemia

17. Main Disorders with
Hypoglycemia
• Galactosemia
• Tyrosenemia
• FAO
• Hyperinsulinism
• GSD 1
• B Ketothiolase Deficiency
• Ketotic Hypoglycemia
• Endocrine (Hypothyroidism and Hypopitutarism)
• Organic Acidemia

18. • Management
– Avoid iatrogenic hyperinsulinism from
umbilical arterial glucose infusion into
pancreatic artery and rebound hypoglycemia
following rapid IV bolus of hypertonic glucose
– Frequent boluses of D10W will induce a
INSULIN SURGE and REBOUND
HYPOGLYCEMIA.
– Try to use a max of 2 boluses of D10W

19. Main Investigations or
Findings
• Urine reducing substance
• Urine Ketones
• Glucose Insulin Ratio<3;1
• Lactate
• FFA
• Urine Organic Acids
• Plasma Amino acids
• Hepatomegaly
Cortisol >20micg/dl

20. Adjunct Therapies
Therapy Effect Dosage
Corticosteroids Decreased peripheral
utilisation of glucose
Hydrocortisone-5-
15mg/kg/day or
Prednisolone
-2mg/kg/day
Glucagon Stimulates
glycogenolysis
30mcg/kg if normal
insulin and 300 if insulin
increases
Diazoxide Inhibits insulin secretion 15mg/kg/day
Somatostatins[long
acting octreotide]
Inhibits insulin secretion
and growth hormone
release
5-10mcg/kg 6-8hrs

22. Concomitant disorders
Hypoglycemia is more deleterious when superimposed on hypoxia-ischemia
or seizures, according to animal studies.
Vannucci RC, Vannucci SJ. Cerebral carbohydrate metabolism during hypoglycemia and anoxia in newborn rats.
Ann Neurol 1978, 4:73-9.
In newborn rat pups subjected to anoxia, normoglycemic pups survived 10x
longer than hypoglycemic ones.
.

23. Neuropathology in hypoglycemia
Acute changes:
Pathological studies of severely hypoglycemic neonatal brains showed:
• neuronal injury in cerebral cortex, hippocampus, basal ganglia, thalamus,
brainstem, and spinal cord.
• neuronal necrosis occurred more than ischemic injury
• widespread glial cell degeneration
• periventricular leukomalacia in a few cases
Chronic changes:
Pathological studies long after the neonatal period showed:
• significant microcephaly
• diffuse loss of neurons in cortex
• increase in astrocytes and microglia
• calcifications in the necrotic zones
• sparing of the cerebellum
Anderson JM, Milner RDG, Strich SJ. Effects of neonatal hypoglycemia on the nervous system: a pathological study. J Neurol
Neurosurg Psychiatry 1967, 30:295-310.
Banker BQ. The neuropathological effects of anoxia and hypoglycemia in the newborn. Dev Med Child Neurol 1967, 9:544-
550.

24. Neuroimaging in hypoglycemia
Spar et al. (1994) were the first to describe neuroimaging changes in
neonatal hypoglycemia.
Case report of one infant with symptomatic hypoglycemia at 58 hours of
age, with hypoglycemia well-documented at over 15 hours.
MRI at DOL#19 showed:
• bilateral occipital lobe parenchymal tissue loss
• near complete absence of cerebral cortex in posterior parietal and
occipital areas
• generalized thinning of the cerebral cortex
No other factors were found to explain this brain damage, and thus was
attributed to the hypoglycemic insult.
Spar HA, Lewine JD, Orrison WW. Neonatal hypoglycemia: CT and MR findings. AJNR 1994, 15:1477-1478.

25. Neuroimaging in hypoglycemia (cont’d)
Symptomatic hypoglycemia is associated with parieto-occipital white matter
abnormalities, as well as abnormal signals in the deep grey matter structures of the
thalamus and basal ganglia.
CT image source: Yager JY. Hypoglycemic injury to the immature brain. Clinics in Perinatology 2002, 29:651-674.

26. Neuroimaging in hypoglycemia (cont’d)
Kinnala A, Rikalainen H, Lapinleinu H, Parkkola R, Kormano M, Karo P. Cerebral magnetic resonance imaging
and ultrasonography findings after neonatal hypoglycemia. Pediatrics 1999, 103:724-9.
In a study of 18 term infants with symptomatic hypoglycemia:
• 39% showed MRI or ultrasound abnormalities
• 4 showed patchy hyperintense lesions on MRI in occipital periventricular
white matter or thalamus
• 3 of 4 did not show these lesions on follow-up MRI

27. Outcome?
Lucas A, Morley R, Cole TG. Adverse neurodevelopmental outcome of moderate neonatal hypoglycemia. BMH
1988, 297:1304-8.
Multi-center study of 661 preterm infants weighing < 1850 g, with outcomes
determined at 18 months of age.
Reduced mental and motor developmental scores were found to be related
to increasing number of days with glucose levels < 2.6 mmol/L.
Relative risk for neurodevelopmental impairment was 3.5x greater in infants
with blood glucose < 2.6 mmol/L for > 5 days.

28. Outcome long term?
Stenninger E, Flink R, Eriksson B, Sahlen C. Long term neurological dysfunction and neonatal hypoglycemia after
diabetic pregnancy. Arch Dis Child 1998, 79:F174-9
Long-term study of 13 children with neonatal hypoglycemia of < 1.5 mmol/L,
compared to 15 children without neonatal hypoglycemia.
Assessments done at an average of 7.75 years of age showed:
• significantly more difficulties in a screening test for minimal brain dysfunction
• more hyperactivity, impulsivity, and inattentiveness
• lower developmental scores
Compared to controls.

29. Take home masage
• Identify the risk baby
• Unit protocol
• Identify early and treat aggressively
• Close surveillance for rare disorder

30. Neonatal hypocalcemia
&
hypomagnesemia

31. Neonatal hypocalcemia is defined as serum
calcium less than 7.0mg/ dl and an ionized
calcium concentration less than 4.0mg/ dl.

32. Etiology
• Prematurity : seen in all VLBW and 50% of preterms.
• Infant of diabetic mother (25-50%):
• Perinatal asphyxia
• SGA
• Maternal hyperparathyroidism
• In-utero exposure to anticonvulsants

33. Etiology………
• Late onset hypocalcemia.
• Hypoparathyroidism
– Idiopathic, transient
– Hypoplasia, aplasia of parathyroid glands (Di
George’s syndrome)
– Pseudohypoparathroidism
• Maternal hyperparathyroidism

34. • Vitamin D deficiency
– Maternal vitamin D deficiency
– Maternal anticonvulsant therapy
– Hepatobiliary disease
– Renal insufficiency
• Hypomagnesemia
• Hyperphosphatemia
– Cow milk intake

35. • Miscellaneous:
– Bicarbonate therapy
– Exchange transfusion with CPD blood
– Phototherapy
– Hypoalbuminemia
– Furosemide induced
– Lipid infusions

36. Clinical presentation
• Jitteriness
• Irritability
• Seizures ( Generalised or focal clonic)
• Laryngospasm with insipratory stridor
• Vomiting ( Pylorospasm)
• Poor feeding
• Extensor hypertonia
• Apnea

37. • Tachycardia/ Tachypnea
• Tremors
• Increased extensor tone, clonus,
hyperreflexia.
• Carpopedal spasm / Chvostek’s sign are
less common.

38. Screening Schedule :
• Preterms ( < 1.0Kg)= 12, 24, 48 hours of life
• Preterms ( 1.0 Kg –1.5Kg) = 24 , 48 hours of life
• Sick/ stressed infants = 12, 24, 48 hours of life

39. Investigations:
• Normal levels 9-11 mg/dl.
• Serum magnesium 1.6-2.2mg/dl. ( , 1.2 mg/dl-
hypomagnesemia. < 0.8mg/dl suggests primary hypomagnesemia)
• Serum phosphate
• Alkaline phosphatase ( increased in hypoparathyroidism)
• PTH levels
• Urine calcium / creatinine ratio ( > 0.2 suggestive of
hypoparathyroidism)
• Chest X-ray (Absence of thymus shadow in Di George’s
syndrome)
• Maternal phosphate, calcium and alkaline phosphatase
levels

40. Management :
• All asymptomatic VLBW - 2ml/kg every 8hrly till
they are on 60 kcal/kg/day of feeds.Thereafter
calcium is supplemented in the form of syrup or
suspension at 100-150 mg/kg of elemental
calcium per day.

41. • Symptomatic hypocalcemia : 2ml/kg of
10% calcium gluconate diluted with equal
amount of 5% dextrose over 5 mins with
heart rate monitoring. Repeat the dose in
10 mins if there is no response. This
should be followed by maintenance dose
orally or parenterally.

42. • If serum calcium is normal and baby is well after
48 hours, IV Calcium can be tapered off over the
next 48 hours. Decrease by 50% over first 24
hrs,25% over next 24 hrs and then discontinue.
• Hypocalcemia not responding to calcium will
require IM Magnesium sulphate as 50% soln. at
a dose of 0.2 ml/kg. Dose can be repeated every
12 hrly till blood levels are normal.
• Duration of supplemental calcium depends on
the cause of the hypocalcemia.

43. • Late onset hypocalcemia :
• As above
• Reduce the phosphate rich diet
• Increase the Ca : P ratio to 4 : 1 by oral calcium
supplements.
• Precautions to be taken
• ensure that tip of the IV cannula is in the vein
• heart rate should be monitored
• slow infusion over 5-10 mins
• Solution is incompatible with NaHCO3 and Dopamine.