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Diabetes and pregnancy: Risks and opportunities

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Release date: August 1, 2018
Expiration date: July 31, 2018
Estimated time of completion: 1 hour

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ABSTRACT

Diabetes in pregnancy increases the risk of adverse maternal, obstetric, fetal, and neonatal outcomes. Internists can reduce these risks by optimizing glycemic control before conception and providing effective counseling on strategies to reduce the risks associated with pregnancy and diabetes. Routine screening of reproductive-age women with diabetes should include a comprehensive physical examination and laboratory tests to identify at-risk patients and begin strategic management. A review of medications for teratogenic potential is also needed.

KEY POINTS

  • Aim for a hemoglobin A1c of 6.5% or lower, if it is attainable without increasing the risk of hypoglycemia.
  • Avoid teratogenic drugs in sexually active women of childbearing age unless the patient uses effective contraception.
  • Because about half of pregnancies are unplanned, it is important to routinely discuss family planning and provide preconception counseling that includes reducing risks associated with pregnancy.
  • Screen for diabetic end-organ damage, especially retinopathy and nephropathy.


 

References

A 29-year-old nulliparous woman presents for a routine checkup. She has hypertension and type 2 diabetes mellitus. Her current medications are chlorpropamide 500 mg daily, metformin 500 mg twice a day, lisinopril 40 mg daily, simvastatin 40 mg daily, and aspirin 81 mg daily. Her body mass index is 37 kg/m2 and her blood pressure is 130/80 mm Hg. Her hemoglobin A1c level is 7.8% and her low-density lipoprotein cholesterol 90 mg/dL.

She is considering pregnancy. How would you counsel her?

DEFINING DIABETES IN PREGNANCY

Diabetes in pregnant women, both gestational and pregestational, is the most common medical complication associated with pregnancy.1

  • Gestational diabetes is defined as diabetes that is diagnosed during the second or third trimester of pregnancy and that is not clearly pregestational.2
  • Pregestational diabetes exists before pregnancy and can be either type 1 or type 2.

Most cases of diabetes diagnosed during the first trimester reflect pregestational diabetes, as gestational diabetes occurs when insulin resistance increases in the later trimesters.

Type 1 diabetes involves autoimmune destruction of pancreatic islet cells, leading to insulin deficiency and the need for insulin therapy. Type 2 diabetes is characterized by insulin resistance rather than overall insulin deficiency. Type 2 diabetes tends to be associated with comorbidities such as obesity and hypertension, which are independent risk factors for adverse perinatal outcomes.3,4

Gestational diabetes accounts for most cases of diabetes during pregnancy. Although both pregestational and gestational diabetes increase the risk of maternal and fetal complications, pregestational diabetes is associated with significantly greater risks.1

IMPACT OF DIABETES ON THE MOTHER

Pregnancy increases the risk of maternal hypoglycemia, especially during the first trimester in patients with type 1 diabetes, as insulin sensitivity increases in early pregnancy.1 Pregnant women with diabetes may also have an altered counterregulatory response and less hypoglycemic awareness.1 Insulin resistance rises during the second and early third trimesters, increasing the risk of hyperglycemia in women with diabetes.1

Glycemic control during pregnancy is usually easier to achieve in patients with type 2 diabetes than with type 1, but it may require much higher insulin doses.

Because pregnancy is inherently a ketogenic state, women with type 1 diabetes are at higher risk of diabetic ketoacidosis, particularly during the second and third trimesters.1 There are reports of euglycemic diabetic ketoacidosis in pregnant women with either gestational or pregestational diabetes.5

Diabetes is associated with a risk of preeclampsia 4 times higher than in nondiabetic women.6 Other potential pregnancy-related complications include infections, polyhydram­nios, spontaneous abortion, and cesarean delivery.1,7 The risk of pregnancy loss is similar in women with either type 1 or type 2 diabetes (2.6% and 3.7%, respectively), but the causes are different.8 Although preexisting diabetic complications such as retinopathy, nephropathy, and gastroparesis can be exacerbated during pregnancy,1 only severe gastroparesis and advanced renal disease are considered relative contraindications to pregnancy.

IMPACT OF DIABETES ON THE FETUS

Fetal complications of maternal diabetes include embryopathy (fetal malformations) and fetopathy (overgrowth, ie, fetus large for gestational age, and increased risk of fetal death or distress). Maternal hyperglycemia is associated with diabetic embryopathy, resulting in major birth defects in 5% to 25% of pregnancies and spontaneous abortions in 15% to 20%.9,10 There is a 2- to 6-fold increase in risk of congenital malformations.6

The most common diabetes-associated congenital malformations affect the cardiovascular system. Congenital heart disease includes tetralogy of Fallot, transposition of the great vessels, septal defects, and anomalous pulmonary venous return. Other relatively common defects involve the fetal central nervous system, spine, orofacial system, kidneys, urogenital system, gastrointestinal tract, and skeleton.11

The risk of fetopathy is proportional to the degree of maternal hyperglycemia. Excess maternal glucose and fatty acid levels can lead to fetal hyperglycemia and overgrowth, which increases fetal oxygen requirements. Erythro­poietin levels rise, causing an increase in red cell mass, with subsequent hyperviscosity within the placenta and higher risk of fetal death.

Other complications include intrauterine growth restriction, prematurity, and preterm delivery. Fetal macrosomia (birth weight > 90th percentile or 4 kg, approximately 8 lb, 13 oz) occurs in 27% to 62% of children born to mothers with diabetes, a rate 10 times higher than in patients without diabetes. It contributes to shoulder dystocia (risk 2 to 4 times higher in diabetic pregnancies) and cesarean delivery.6 Infants born to mothers with diabetes also have higher risks of neonatal hypoglycemia, erythrocytosis, hyperbilirubinemia, hypocalcemia, respiratory distress, cardiomyopathy, and death, as well as for developing diabetes, obesity, and other adverse cardiometabolic outcomes later in life.11

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