Metabolic Disorders

in
the Neonate
Objectives
Hypoglycemia
•Definition**
•Risk factors **
•Clinical features ***
•Prevention ***
•Diagnosis ***
•Prognosis*

Infants of Diabetic Mothers

•Pathophysiology**
•Clinical features ***
•Problems of the infant of diabetic mother :(Maternal problems* & Neonatal
problems***)
•Prognosis*

Treatment of hypoglycemia & infants of diabetic mothers ***

 Hypoglycemia
Hypoglycemia present when serum glucose level are significantly lower
than range among postnatal age-matched normal infant.
Incidence;
- Decreased by early feeding.
- Increased in;
1- Prematurity.
2- Hypothermia.
3- Hypoxia.
4- IUGR.
5- Maternal diabetes.
6- Maternal glucose infusion in labor.

Any plasma glucose level < 35mg/dl at the first 1 - 3 hours of life, or
< 40mg/dl (2.2 mmol/L) during the 3 - 24 hours of life and < 50mg/dl
(2.8 mmol/L) after 24 hours of age, should be viewed as abnormal and
treated.
Infants at risk of hypoglycemia:

1- Hyperinsulinemic state:
a. IDM (infants of mothers with DM or gestational diabetes).

b. Infants with severe erythroblastosis fetalis.

c. Insulinomas or nesidioblastosis (primary hyperplasia of the islets

of
langerhans ).

d. Beckwith- wiedemann syndrome.

e. Maternal drug use: (thiazide diuretics or tocolytics).

Long term use of tocolytics (β agonists) may cause β cell
hyperplasia in fetal pancreas.
2- Intrauterine malnutrition result in reduced
hepatic glycogen storage & total body fat;
a. IUGR.
b. Preterm.
c. Polycythemic infants.
d. Infants of toxemic mother.
e. Infants with placental abnormalities.
3- Increased metabolic need disproportionate to
substrate stores caloric supplied;
a. Very immature or severely ill infants.
b. LBW with RDS.
c. Asphyxia.
d. Hypothermia.
e. Systemic infections.
f. Heart failure with cyanotic CHD.
4- Genetic or primary metabolic defects:
a. Galactosemia.
b. Glycogen storage disease.
C. Tyrosinemia.
d. Fructose intolerance.
5- Others:
a. LGA.
b. Infants of obese mothers.
c. GH deficiency.
d. Maternal medications e.g. high glucose infusion
during labor.
Clinical features :
Usually noted on 1st or 2nd day of life, and vary from
asymptomatic to symptomatic causing CNS, CVS, and pulmonary
disturbances.

1- CNS; Hypotonia, lethargy, poor feeding, jitteriness or tremor,

weak or high-pitched cry, eye rolling, and convulsion are common.

2- CVS; Congestive heart failure, tachycardia, episode of cyanosis,

pallor, sweating & diaphoresis.

3- Respiratory system; Intermittent apneic spells or tachypnea and

hypothermia.

These features are nonspecific and simulate other diseases;

CHD, sepsis, IVH & hypocalcemia.
Prevention:
1- Newborns at risk, but who are asymptomatic and
have no contraindications for feeding should be breast fed or given
formula within 1st hour of life.
A screen glucose test should be performed within 30 minutes
of the first feed.

2- If oral is not possible give 10% glucose IV.

3- All should be monitored with serial blood glucose level during the
1st day of life.

NOTE; Transient hypoglycemia is common during the 1st 2-3 hr

after birth and may be part of normal adaptation to extrauterine
life.
Prognosis:

- For symptomatic hypoglycemia with

convulsion is poor and associated with
abnormal neurointellectual development.

- For other forms of hypoglycemia the

prognosis is better.
Infants of Diabetic Mothers
 Pathophysiology:

1- Maternal hyperglycemia → fetal hyperglycemia and

fetal pancreatic response → fetal hyperinsulinemia.

2- Fetal hyperinsulinemia & hyperglycemia cause

increase hepatic glucose uptake and glycogen synthesis &
accelerate lipogenesis and protein synthesis.

Fetal hyperinsulinism & hyperglycemia → fetal

acidosis which lead to increase the rate of stillbirth.
 At birth, the separation of placenta → suddenly
interrupt glucose infusion without effect on
hyperinsulinism → hypoglycemia and attenuate lipolysis
during 1st hours after birth.

Pathology:
1- Hypertrophy and hyperplasia of the pancreatic islets with ↑
number of β cells.
2- ↑ weight of placenta and infant organs (except the brain).
3- Myocardial hypertrophy.
4- ↑ cytoplasm of liver cells.
5- Extramedullary hematopoiesis.
 Clinical features;

1- IDM and gestational diabetic mother, resemble each other; large

& plump (due to ↑ body fat and large viscera) with puffy & plethoric
facies.

2- These infant may be of normal or LBW (if delivered before term

or if associated with maternal vascular disease).

3- lie on their backs with leg abducted and flexed and with their
hands alongside their heads (like premature posture), tremulous,
and hyperexcitable during the first 3 days of life (but may be
hypotonic, lethargic, and poor sucker).
Notes;
- Early appearance of these sign is related to
hypoglycemia.
- Late appearance of these sign is related to
hypocalcemia.
- These may occur together.
- Perinatal asphyxia & hyperbilirubinemia may produce
similar sign.
- Hypomagnesemia may associated with hypocalcemia.

25-50% of IDM and 15- 25% of infants of mothers

with gestational diabetes develop hypoglycemia but
only a small percentage of these infants become
symptomatic.
 Tachypnea develops in many infants of diabetic
mothers during the 1st 2 days after birth may
be due to;

1- Hypoglycemia.
2- Hypothermia.
3- Polycythemia.
4- Heart failure.
5- Transient tachypnea.
6- Cerebral edema from birth trauma or asphyxia.
7- Respiratory distress syndrome.
Problems of the infant of diabetic mother:
Maternal problems:
1- Ketoacidosis.
2- Hypoglycemia.
3- Pre-eclampsia.
4- Polyhydramnios.
5- Retinopathy.
6- Pyelonephritis.
7- Chronic hypertension.
Neonatal problems:
1- Prematurity.
2- Intrauterine fetal death.
3- Macrosomia.
4- Birth trauma & asphyxia.
5- RDS (antagonistic effect between cortisol and
insulin on surfactant synthesis).
6- TTN.
7- Hypoglycemia & hypocalcemia.
8- Polycythemia.
9- Indirect hyperbilirubinemia.
10-Congenital anomalies
– Cardiac; Cardiomegaly (30%), heart failure (10%),
septal hypertrophy, VSD, ASD, TGA, COA.
– Skeletal; Lumbosacral agenesis is most common.
– CNS; Neural tube defects.
– Renal; Hydronephrosis, renal agenesis & renal vein
thrombosis (flank mass, hematuria and
thrombocytopenia).
– GIT; Duodenal or anorectal atresia & small left
colon syndrome.
Prognosis:

1- Predispose to obesity in childhood and may

extend to adult life.
2- Symptomatic hypoglycemia may ↑ the risk of
impaired intellectual development.
3- Incidence of diabetes mellitus later is higher than
in general population.
 Treatment of
hypoglycemia &
infants of diabetic mothers
Treatment
• Both symptomatic (plasma glucose is <40 mg/dL)
and asymptomatic (plasma glucose is <30 mg/dL)
hypoglycemia should be treated.

NOTE; Hypoglycemia should be treated even in

asymptomatic patient by IV glucose infusion
(8mg/kg/min) to keep blood level well above this
level.
**Treatment of asymptomatic infant with high risk of hypoglycemia:

Blood glucose determination within 1 hour of birth then every 1 hour for next
6-8 hours, then every 4-6 hours till 24 hours. (Depend on oral tolerance & plasma
glucose)

* If oral tolerance (clinically well) & asymptomatic transient

hypoglycemia (plasma glucose is >30 mg/dL) or (normoglycemic high
risk infant), ----- start oral or gavage feeding (breast feeding or
formula) within 1st hours.

* If oral intolerance or asymptomatic transient hypoglycemia (plasma

glucose is <30 mg/dL), ------ start IV glucose infusion at rate of 4-
6mg/kg/min.

Bolus injection and hypertonic glucose should be avoided because it may →

hyperinsulinemia → rebound hypoglycemia.
Summary of asymptomatic infant Rx
Oral feeding
1- Oral tolerance
and
2- Asymptomatic transient hypoglycemia (plasma glucose is >30
mg/dL)
3- Normoglycemic high risk infant

IV glucose infusion
1- Oral intolerance
or
2- Asymptomatic transient hypoglycemia (plasma glucose is <30
mg/dL)
** Treatment of acute symptomatic neonatal hypoglycemia
(plasma glucose is <40 mg/dL) or
** Infants with persistent glucose levels <25 mg/dL during the
1st 4 hr after birth and <35 mg/dL during 4-24 hr after birth.

* Symptom without seizure, IV bolus glucose infusion of 2 mL/kg of D10 W

(200mg/kg).

* Symptom with seizure, IV bolus glucose infusion of 4 mL/kg of D10 W

(400mg/kg).

- Both of them, followed by a maintenance glucose infusion at rate of 6–8

mg/kg/min, adjusting the rate to maintain blood glucose levels in the normal
range.

- If hypoglycemia recurs, repeat the bolus and increase the infusion rate to
maintain physiologic glucose concentration (20% glucose can be used).
Summary of symptomatic infant Rx
1- Acute symptomatic neonatal hypoglycemia
(plasma glucose is <40 mg/dL)
2- Infants with persistent glucose levels <25
mg/dL during the 1st 4hr after birth and <35
mg/dL during 4-24 hr after birth.
-- If ≥ 15 mg/kg/min is inadequate to eliminate
symptoms and maintain constant normal glucose
level, hydrocortisone 2.5mg/kg/6hours or
prednisolone 1mg/kg/day given to enhance
gluconeogenesis

Treatment is usually necessary for few days to

a week.
- If neonatal hyperinsulinism is present, and the infant is
unresponsive to glucose and steroid give diazoxide 10-20
mg/kg/day orally 3 times/day, or long acting somatostatin
(Octreotid) may be used (Diazoxide can suppress insulin
secretion).
- Infant with persistant hyperinsulinemic hypoglycemia
(Nesidioblastoma & islet cell adenoma) --------- subtotal
pancreotectomy.
Glucagon is not as helpful in LBW infant.

Treaement of associated;
* Hypocalcemia (2ml/kg of 10% calcium gluconate.
* Hypomagnesemia (0.25ml/kg of 50% magnesium
sulfate).
* Polycythemia.
* HMD.
Thank you