Infant of the Diabetic Mother
Sunhwa Kim, MD
Loma Linda University
Children Hospital
Diabetes … Obesity
Not every high blood sugar
is
Diabetes
Obesity
Diabetes
Obesity…Diabetes

Metabolic abnormalities associated with obesity
– Hyperglycemia, dyslipidemia, alterations in
growth factors, hyperinsulinism etc.

Excessive abdominal fat independently associated
with diseases: cardiovascular, cancer,
osteoarthritis, gall bladder, diabetes, etc

Excess body fat leads to type 2 diabetes within 20
years

Undiagnosed diabetes
Obesity…
Pregnancy Complications
Adjusted* Odds Ratios for Pregnancy Complications by Maternal BMI
Adjusted Odds Ratio
5
4
Normal
(BMI 20.0-24.9)
3
Overweight
(BMI 25.0-29.9)
2
Obese
(BMI >= 30.0)
1
0
Gestational
diabetes
Preeclampsia
Eclampsia
*Adjusted for maternal age, smoking, education, marital status,
trimester prenatal care began, payer, and weight gain during
pregnancy; BMI<20.0 (lean) reference group.
Baeten et al., Am J Public Health 91;436, 2001
Maternal Complications of Diabetes







Unstable maternal BG
Cardiovascular
conditions
Sepsis
Birth Difficulties
PP recovery issues
Psychosocial issues
Delivering an
affected infant
Infant of the Diabetic
Mother
 First described: 1880

Insulin isolated in 1921
maternal mortality
decreased from 50 to 9 %

Stillbirhts decreased from
>20% to 2% in the 1980’s
Perinatal mortality
decreased after 1970NICU
is still higher than controls
(17 vs. 6/1000 in Europe
22 vs. 10/1000 in CA)


Congenital malformations
remain high
IDM - Definitions
 Any
offspring of a gestational or insulin
dependent diabetic woman
– Type 1-insulin dependent
– Type 2
– Gestation Diabetes Mellitus
– Impaired Glucose Tolerance
Diabetes complicating Pregnancy
 0.5-1.0%
of all pregnancies are
complicated by pre-existing diabetes
 0.1
% are insulin dependent diabetes
 1-5%
gestational diabetes
IDM -Incidence
 50-150,000
 Perinatal
 5%
IDMs born annually
mortality: 20/1000 total births
of all NICU admissions
IDM - Outcome
 Outcome
is largely dependent on
consistent blood glucose control from the
preconception period through embryonic
and fetal life.
 Lack
of control in early or late
pregnancy leads to different problems in
the offspring
IDM -Early Pregnancy
Diabetic Embryopathy
 Poor
early control (Hyperglycemic embryo)
 Risk for Congenital Malformations
Glucose Control and Malformations
MALFORMATION RATES BY LEVEL Of
MATERNAL HEMOGLOBIN A1c
6.9 or less
7.0-8.5
8.6 or greater
0%
5.1 %
22.4 %
Miller et al. N Engl J Med 304:1331-1333, 1988
Glucose Control and Malformations
HbA1c*
% Malformations
<6
6.1-9.0
9.1-12.0
12.1-15.0
>15.0
3.0%
5.2%
4.3%
38.9%
40.0%
RR (95% CI)
1.0
1.7 (0.4-1.7)
1.4 (0.3-8.3)
12.8 (4.7-35.0)
13.2 (4.3-40.4)
*1st trimester HbA1c in 303 insulin-requiring diabetics
(Green et al. Teratology 39:224-231, 1989)
Embryopathy
Gestational Diabetic Women’s Risk

Becerra JE et al., 1990
– Relative risk for major malformations among IDM was
7.9 compared to infants of non-diabetic mothers
– Gestational diabetics who require insulin in 3rd trimester
were 20.6 times more likely to have a child with a
cardiovascular defect

Kouseff BG, 1999
– 152 infants of women with gestational DM, 87 had
anomalies compatible with diabetic embryopathy
Embryopathy
Gestational Diabetic Women’s Risk

Schaefer-Graf et al., Am J Obstet Gynecol 182:313-320, 2000
– 4,180 consecutive pregnancies complicated by gestational diabetes
(3,764) or type 2 diabetes (416) diagnosed after 20 weeks gestation
(County USC).
» Initial fasting glucose < 120 mg/dL
2.1% malfs
» Initial fasting glucose 121-200 mg/dL
5.9% malfs
» Initial fasting glucose > 200 mg/dL
12.9% malfs

Watkins et al., Pediatrics 111:1152-1158, 2003
– Prepregnancy obesity (with no known diabetes) associated with
increased risks for spina bifida, omphalocele, heart defects, and
multiple anomalies.
Diabetic Embryopathy -Incidence
2
to 4-fold Increased Risk for Malformations (48%)
7
to 10-fold Increased Risk for Major Anomalies
that are fatal or require surgery
 Central
nervous system
 Cardiac malformations
 Renal / urinary and GI tract anomalies
 Skeletal anomalies
Diabetic Embryopathy -CNS anomalies
 Central
nervous system

Neural tube defects
– Anencephaly
– Meningomyelocele

Hydrocephaly

Holoprosencephaly
Diabetic Embryopathy

Midline facial defects
 Facial
microsomia and
microtia/anotia:
Diabetes in 10.3% of 155 case mothers
versus 1.4% of 854 control mothers
Multivariate-adjusted odds ratios (CI):
Diabetes
6.3 (2.7 -1 4.9)
(Werler et al., Birth Defects Research 70:258, 2004)
Diabetic Embryopathy – Cardiac anomalies
Transposition of great vessels
 Coarctation of the aorta
 Atrial & Ventricular septal
defects
 Dextrocardia
 Single ventricle, hypoplastic
right heart
 Patent ductus arteriosus
 Pulmonary hypoplasia /
atresia
 DiGeorge sequence

Diabetic Embryopathy, GI anomalies

GI: Small Left Colon Syndrome
 Bowel

atresia
Bowel dysmotility
(feeding intolerance)
Diabetic Embryopathy –
Skeletal Anomalies
 Caudal
Dysplasia or Regression SD
– Rare disorder (1/25000)
– The most specific malformation related to
diabetes 200-400 times more often in
IDMs
– Sacral agenesis with hypoplastic pelvis and
spinopelvic instability
– Usually with other malformations like:
femoral hypoplasia, extrophy of the
bladder, and club foot
Diabetic Embryopathy Pathophysiology




Hyperglycemia + Genetic background
Teratogenic period (3-6 weeks)
Disturbances in maternal-fetal circulatory transport
systems
Concentrations of metabolites
–
–
–
–
Hyperglycemia
Hyperketonemia
Elevated intracellular levels of free oxygen radicals
Disturbances in arachadonic acid and prostaglandin/prostacyclin
metabolism affecting intracellular signaling and circulation
– Somatomedin inhibitors
– Genotoxicity as a result of aberrant fuels
(Reece et al., Teratology 54:171-182, 1997)
Diabetic Embryopathy



PREVENTION BEFORE CONCEPTION
Good Glycemic control
Folic Acid/ Vitamin intake
IDM - Late Pregnancy
Fetal and Neonatal Complications
 Poor
late control (Hyperglycemic fetus)
 Risk for Hyperinsulinemia (growth factor)
IDM -Late Pregnancy
Fetal
and Neonatal Complications of
Hyperinsulinemia
– Macrosomia growth of insulin-sensitive tissues plus
glycogen and fat deposition
–
–
–
–
–
Hypoglycemia
Polycythemia/hyperbilirubinemia
Renal vein thrombosis
Cardiomyopathy
RDS
Fetal & Neonatal Complications
Macrosomia
 LGA
– Birth weight > 4 kg or
above the 90th percentile
for gestational age
 Occurs
in 20-60% IDM
 Physical findings
– Increased adipose tissue
– Disproportionate
head/shoulder ratio
– Plethoric
– Large placenta & cord
IDM may also be SGA
in advanced diabetes complicated
with renal and cardiac disease
Fetal & Neonatal Complications
Macrosomia
Complications associated with delivery

Birth trauma
–
–
–
–

Shoulder dystocia
Brachial plexus injury
Fractured clavicle
Visceral hemorrhage
CPD
– Risks associated with C/Section and
operative vaginal deliveries (vacuum
extraction, forceps, etc.)
– Fetal distress
– Meconium aspiration
– Birth Asphyxia
Hypoglycemia
Symptoms
 Jitteriness
81%
 Seizures 58%
 Apnea/cyanosis 47%
 Irritability 41 %
 Hypotonia 26%
 Poor feeding
 Hypothermia
 None
Defintition: Blood glucose <40 mg/dL
Usually presents at ½-2 hours of life
Incidence: up to 40% of IDM
Hypoglycemia
Treatment
If
stable give early feedings
If
not able to feed:
D10%W
2mL/kg (slow IVP) plus
Continuous
IV infusion of D10%W
at 80-100 mL/kg/day
Use
Follow
glucagon in extreme cases
blood glucose with
frequent Chemstrips
Hyperbilirubinemia

Definitions: Elevated indirect
(unconjugated) bilirubin >10mg/dL in
term infant, lower levels for preterms
Incidence in IDM 20-40%

Pathophysiology
– Increased bilirubin production
» Polycythemia
» Heme turnover (ineffective
erythropoeitin. and trauma)
– Decrease in bilirubin binding and
excretion
» Liver immaturity
Hyperbilirubinemia

Prevention
– Early, adequate breastfeeding
– Good hydration and stooling

Diagnosis
– Transcutaneous or serum bilirubin
at 24 hours of age, and at signs of
increasing jaundice

Treatment:
– Adequate hydration and nutrition
– Phototherapy
– Exchange transfusion
– Medications (agar)
– Family teaching
– Appropriate follow-up after
discharge
Polycythemia








Due to bone marrow stimulation (high erythropoietin levels)
Elevated venous hematocrit of > 65%
Caused by chronic hypoxia and increased O2 requirements in utero
Placental insufficiency during fetal life
May be worsened by placental transfusion at birth
Incidence in IDM 35%
Signs and symptoms
– Plethora
– Jitteriness
– Tachypnea
– Cyanosis (general or circumoral)
– Oliguria
– Poor feeding
– Lethargy/seizures
Screening: obtain hematocrit at 24 hrs of life or if symptoms noted
Polycythemia

Treatment
– Treat underlying symptoms
– Hydration
– Hyperbilirubinemia treatment
– Partial exchange transfusion

Common complications
–
–
–
–
–
Respiratory Distress
Hyperbilirubinemia
Respiratory distress
Renal vein thrombosis
Hypertension
IDM -Cardiomyopathy
 Cardiomegaly
present in 30%
 Septal hypertrophy
 Myocardial dysfunction
– Glycogen stores
– Hypoxia
 CHF
in 5%
– Treatment: supportive therapy and beta blockers
Other Fetal & Neonatal Complications

Perinatal hypoxia/asphyxia

Respiratory Distress

Metabolic abnormalities:
– Hypocalcemia
– Hypomagnesemia

Small left colon Syn.

Neurologic dysfunction
Perinatal Hypoxia
 May
lead to fetal demise or neonatal asphyxia
 May result from complicated labor and
delivery
–
–
–
–
–
–
–
Placental insufficiency (vascular disease, pre eclampsia)
Maternal ketoacidosis
CPD/ Prolonged labor due to Macrosomia
Meconium Aspiration
Intra-abdominal hematoma/hemorrhage
Polycythemia
Increased oxygen utilization from hyperinsulinism and
increased metabolism
Respiratory Distress
 Transient
Tachypnea of Newborn (delayed
lung fluid clearance)
 Aspiration of meconium or amniotic fluid
 Prematurity
Diagnosis
Tachypnea/Retractions
 Grunting
 Cyanosis
 Apnea
 Hypoxemia
 Chest X-Ray

Respiratory Distress Syndrome
RDS
(delayed lung maturity), higher risk than non IDMs.
Respiratory Distress Syndrome

surfactant from
decreased steroids due to
insulin

Prevention: Check for lung maturity with
presence of PG and L:S ratio >2
Treatment:

– Surfactant
– Assisted support and ventilation
– Supplemental oxygen
Hypocalcemia/Hypomagnesemia

Incidence: 25%

Secondary to hypoparathyroid function due to
maternal-fetal hypomagnesemia


Related to severity of maternal diabetes
Develops in first 3 days
Hypocalcemia/Hypomagnesemia

Symptoms:
– Irritability
– Jitteriness
– Apnea
– Lip smacking
– Tongue thrusting

Laboratory Tests
– Calcium
– Ionized CA
– Magnesium

Treatment
– Transfer to Neonatal Intensive Care Unit
– Calcium gluconate
– Magnesium sulfate
IDM - Neurologic Dysfunction
 Due
Jitteriness
 Irritability
 Increased or Decreased
tone
 Seizures

to:
– Chronic and/or acute
hypoxia
– Immaturity
– Hypoglycemia
– Hypocalcemia
– Polycythemia/strokes
– Delivery trauma
– Iron deficiency
Oral Feedings
 Significant
feeding difficulties
Severe uncoordination
 Assess
oral-motor coordination
 Assess adequacy of feeding
 Monitor
pre feeding
blood glucose
IDM and Breastfeeding





Offer breast as soon as possible
within 1 hour of delivery
Encourage feedings whenever
oral cues noted or at least every
3 hours
Formulas: only when medically
indicated or mother has given
informed consent
Keep mother and infant
together continuously
Support mothers to nurse often
(10-12 times per day)
IDM- Long Term Prognosis
Metabolic Syndrome
(identifiable early precursor to adult chronic
diseases including diabetes, heart disease,
certain cancers, and others)
• Obesity
• Glucose Intolerance
• Dyslipidemia
• Hypertension
Predisposing factors
. Infant of a diabetic mother
. Infant of an obese mother
. Large for gestational age infant
Long Term Prognosis
Growth / Development
Childhood obesity
(50%, 5 fold higher at adolescence)
Risk of Developing Insulin Dependent DM
. Diabetic mother 2%
. Diabetic father 7%
Risk for delayed motor and cognitive development
Neurological development indefinite
IDM
Neurodevelopmental Outcome

The IDM needs to be supported since conception

If we are to help the mothers to achieve