Diabetes - Loma Linda University Medical Center
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Transcript Diabetes - Loma Linda University Medical Center
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 1970NICU
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