Purpose and Goal: CNEP #2012

  • Understand the effects of maternal diabetes on the fetus.
  • Learn about the effects of cardiomyopathy on the neonate.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for successful completion:

  • Successfully complete the post-test
  • Complete the evaluation form

Date

  • August 2015 – August 2017

Learning Objectives

  • Describe the pathophysiology of maternal diabetes.
  • Describe the effects of maternal diabetes on the neonate.
  • Identify 2 approaches for the treatment of cardiomyopathy.

Introduction

  • Maternal diabetes has many effects on the fetus.
  • Maternal diabetes may be:
    • Pre-gestational
    • Gestational
  • It is associated with ↑ risk of neonatal complications
  • It is associated with ↑ risk of long term complications
  • Neonatal outcomes are related to the severity of disease

Diabetes in Pregnancy

  • Diabetes occurs in 10% of US pregnancies
    • Pre-existing diabetes occurs in 2% of pregnancies
    • Gestational diabetes occurs in 8% of pregnancies
  • Diabetes in pregnancy may be classified as:
    • Type I – insulin dependent
    • Type II – non-insulin dependent
  • Type I diabetes occurs in 35% of US pregnancies
  • Type II diabetes occurs n 65% of US pregnancies
  • There has been a 33% increase in Type II diabetes
  • The highest risk of diabetes has been seen in:
    • African Americans
    • Hispanic Americans
    • Latina Americans
    • Native Americans
    • Asian Americans
    • Native Hawaiians
  • Diabetes can have negative effects on the fetus
  • Outcomes are generally influenced by:
    • Onset of diabetes
    • Duration of diabetes
    • Severity of diabetes
  • Strict glucose control during pregnancy can ↓ risks

Pathophysiology of Maternal Diabetes

  • Normal adaptations during pregnancy include:
    • Alterations in carbohydrate metabolism
    • Acquired insulin resistance due to:
      • ↑ lactogen
      • ↑ progesterone
      • ↑ cortisol
    • Normal “diabetogenic” effect
      • ↑ glucose transfer to fetus
      • ↑ amino acid transfer to fetus
      • ↑ free fatty acids for energy
  • The pattern for diabetic mothers is very different
    • Maladaptation in carbohydrate metabolism
      • Pronounced insulin resistance
      • Decreased numbers of insulin receptors
      • Decreased binding of insulin to target cells
    • This maladaptation leads to:
      • Progressive alteration in glucose tolerance
      • ↑ insulin levels to 2 -3 times normal
  • The diabetic mother experiences:
    • Frequent episodes of hyperglycemia
    • High levels of amino acids
    • Increased transfer of nutrients to the fetus

Effects of Maternal Diabetes on the Fetus

  • The metabolic changes from diabetes
    • Negatively affect the mother
    • Negatively affect the fetus
  • During organogenesis at 3 – 8 weeks gestation
    • Abnormal metabolism is teratogenic
    • Resulting in ↑ risk of malformations
      • Cardiac
      • Musculoskeletal
      • Central nervous system
    • Resulting in 1 - 5% risk of miscarriage
  • Maternal insulin does not cross the placenta
    • Resulting in fetal hyperinsulinemia
  • Maternal hyperglycemia interferes with:
    • Embryonic development
    • Oxygen free radical balance
    • Vascularization of tissues
    • Expression of genetic regulation
  • Maternal hyperglycemia results in:
    • Delivery of ↑ carbohydrates to the fetus
    • Fetal pancreatic hyperplasia
    • Increased fetal insulin levels
    • Increased fetal insulin-like growth factors
  • Increased insulin-like growth factors result in:
    • Increased protein synthesis
    • Increased lipid synthesis
    • Increased glycogen synthesis
    • Increased rate of fetal growth
    • Increased deposition of fetal fat
    • Increased fetal liver and heart growth
    • Generalized fetal macrosomia
  • Fetal hyperinsulinemia results in:
    • Catabolism of ↑ carbohydrates
    • Increased energy use
    • Decreased oxygen stores
  • Decreased oxygen stores result in:
    • Hypoxia
    • Hypertension
    • Cardiac hypertrophy
    • ↑ RBC production
    • Polycythemia

Effects of Maternal Diabetes on the Neonate

  • The metabolic changes from diabetes
    • Negatively affect the neonate
  • Maternal hyperglycemia leads to:
    • Neonatal hypoglycemia
    • ↑ risk of morbidity and mortality
  • Neonatal complications include:
    • Congenital anomalies
      • Caudal regression syndrome
        • Hydronephrosis
        • Renal agenesis
        • Micropenis
        • Cystic kidneys
        • Intestinal atresias
      • Prematurity
      • Perinatal asphyxia
      • Macrosomia
        • ↑ risk of birth injury
      • Respiratory distress
      • Hypocalcemia
      • Hypomagnesemia
      • Polycythemia
      • Low iron stores
      • Hyperbilirubinemia
      • Cardiomyopathy

Cardiomyopathy in Infants of Diabetic Mothers

  • Cardiovascular malformations occur in 3 – 9% of pregnancies
  • Cardiac defects that are frequently seen include:
    • Transposition of the great arteries
    • Double outlet right ventricle
    • Ventricular septal defect
    • Truncus arteriosus
    • Tricuspid atresia
    • Patent ductus arteriosus
  • Hypertrophic cardiomyopathy is also commonly seen
    • Present in up to 49% of neonates
    • It results from fetal hyperinsulinemia
    • Fetal hyperinsulinemia effects myocardial cells
    • Fetal hyperinsulinemia results in:
      • ↑ synthesis of fat and glycogen
      • ↑ deposition of fat and glycogen
      • ↑ cardiac muscle mass
  • Congestive cardiomyopathy can result from:
    • Perinatal asphyxia
    • Neonatal hypoglycemia
    • Neonatal hypocalcemia
  • Several changes occur in cardiomyopathy:
    • Thickened interventricular septum
    • Asymmetrical septal hypertrophy
    • Decreased ventricular chamber size
    • Potentially obstructed left outflow
  • Infants are commonly asymptomatic
    • 5 – 10% have respiratory distress
    • 5 – 10% have poor cardiac output
    • 5 – 10% have signs of heart failure
  • Chest radiographs may show cardiomegaly
  • Cardiomyopathy is best detected by echocardiography
  • Cardiomyopathy is usually transient and reversible
    • It resolves as insulin levels normalize
    • It frequently requires supportive NICU care
  • Symptomatic neonates generally recover in 2 – 3 weeks
  • Echocardiography finding resolve within 6 – 12 months

Management of Hypertrophic Cardiomyopathy

  • Hypertrophic cardiomyopathy usually resolves over time
  • The immediate neonatal period can be complicated
  • Hypertrophic cardiomyopathy leads to:
    • Inadequate ventricular filling
    • Decreased intraventricular volume
    • Left ventricular dysfunction
    • Low cardiac output
  • Infants may present with congestive heart failure:
    • Cyanosis
    • Tachypnea
    • Tachycardia
    • Cardiomegaly
  • Management typically involves the following:
    • Maintenance IV fluids
    • Oxygen as needed
    • Mechanical ventilation as needed
    • Correction of pulmonary hypertension
      • Inhaled nitric oxide
    • Correction of hypoglycemia
    • Correction of hypocalcemia
    • Correction of hypomagnesemia
    • Early diagnostic echocardiography
      • Serial echocardiographs
      • Close cardiology follow up
    • Avoidance of inotrophic agents
      • Digoxin
      • Dopamine
      • Dobutamine
      • Epinephrine
      • Milrinone
    • Avoidance of diuretics
    • Use of Beta-blockers
      • Propranolol
      • Esmolol

Long-Term Outcomes of Infants of Diabetic Mothers

  • Long-term outcome data show increased risks
    • Risk of postnatal metabolic complications
    • Risk of poor neurodevelopmental outcomes
  • Metabolic risks
    • Diabetes
      • Lifelong risk for Type I diabetes is 2%
      • Lifelong risk for Type II diabetes is 45 - 75%
    • Obesity
      • Fetal hyperinsulinemia affects:
        • Development of adipose tissue
        • Development of pancreatic cells
        • Overall ↑ body mass index
        • Overall glucose metabolism
  • Neurodevelopmental outcome
    • Well controlled glucose in pregnancy
      • Similar to normal infants
    • Poorly controlled glucose in pregnancy
      • Developmental abnormalities
        • Decreased head circumference
        • Delayed cognitive development
        • Delayed psychomotor development

Summary

  • Maternal diabetes has negative effects
    • On the mother
    • On the developing fetus
    • On the neonate
  • Neonatal cardiomyopathy is commonly seen
    • Infant may be asymptomatic
    • Infants may present in heart failure
  • The prognosis is generally excellent
  • However, there can be long term complications
  • Optimal glucose control is critical for optimal outcomes

References

  1. Barnes-Powell, L.L. 2007. Infants of Diabetic Mothers: The Effects of Hyperglycemia on the Fetus and Neonate. Neonatal Network, 36 (5), p. 283-290.
  2. Riskin, A. & Garcia-Prats, J.A. 2014. Infant of a Diabetic Mother. Up-To-Date.
  3. Yeh, J. & Berger, S. 2015. Cardiac Finding in Infants of Diabetic Mothers. NeoReviews, 16 (11), P. e624-e631.

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