University of Toronto - Faculty of Medicine

 

Author
The revision of this chapter was prepared by Denice S. Feig, MD, MSc, FRCPC

 

• Prepregnancy planning is essential to achieve a healthy baby and avoid maternal morbidity such as adverse pregnancy outcomes, and progression of chronic diabetes complications.
• All women of child-bearing age (including adolescents) should be counseled with regard to the need for good glucose control before pregnancy and the use of birth control.
• Ideally, women with preexisting diabetes should be referred to a high risk or special pregnancy team for optimal care.

Glycemic Control & Risk of Congenital Anomalies

• Poor glycemic control in the first weeks of gestation has been associated with an increased risk of congenital anomalies in babies of women with diabetes.
• The most common congenital anomalies are cardiac, central nervous system (anencephaly, spina bifida), skeletal (sacral agenesis) and genitourinary.
• This risk increases with increasing A1C above normal at conception.
• These anomalies are thought to be the cause of the increased rate of spontaneous abortions seen in women with diabetes.
• Organogenesis occurs in the first 8 weeks of gestation therefore excellent glycemic control must be achieved PRIOR to conception, otherwise, by the time pregnancy is discovered, organogenesis will have already begun.
• Patients seeking pregnancy should take 1-5 mg folic acid daily at least 3 months preconception and continuing until at least 12 weeks postconception, as it has been shown to decrease the risk of neural tube defects in normal as well as high risk populations.

 

Glycemic Control

• Excellent glycemic control is achieved by intense diabetes management (i.e. a multiple dose insulin regimen or subcutaneous insulin pump, knowledge about exercise, diet, insulin adjustment. See Section 4.5 Intensive Insulin Regimens). This should involve, whenever possible, a multi-disciplinary team of nurse educators, dieticians, and endocrinologists.
• Treatment Goals:
  • Fasting and AC meal BS of 4-6 mmol/L , 2 hour PC BS of ≤ 7.8 mmol/L
  • Aim for an A1C of <7.0% (<6% if safely achievable), prior to conception.
• Women with type 2 diabetes who are on oral hypoglycemic agents should preferably be changed to insulin prior to conception, except in the setting of PCOS, where metformin can be safely used for ovulation induction.
• Once excellent glycemic control is achieved, A1C's are done monthly to every 2 months while attempting to conceive.

Drugs

• Discontinue medications considered to be potentially teratogenic including
  • ACE inhibitors and ARB's. For hypertension replace with labetolol, methyldopa, or Adalat
  • Statins

 

Retinopathy

• Diabetic retinopathy can progress in pregnancy. With minimal or no retinopathy, there is a 10% chance of progression. With severe preproliferative or proliferative retinopathy there is a 50% chance of progression. Those with proliferative retinopathy who receive laser therapy prior to pregnancy have a better outcome.
• Factors associated with progression of retinopathy during pregnancy:
  1. Poor glycemic control
  2. Uncontrolled hypertension
  3. Baseline retinopathy at onset of pregnancy (the more severe the retinopathy at baseline, the higher the risk of progression)
  4. Rapid institution of tight glycemic control
• Refer all women to an ophthalmologist (preferably a retinal specialist) for assessment.
• Institute laser therapy, if clinically indicated, prior to pregnancy.
• In those with poor glycemic control and moderate to severe retinopathy, lower blood glucose gradually over 1-2 months in the prepregnancy period.

Nephropathy

• The extent of renal dysfunction has implications for the pregnancy and for the woman's renal function postpartum.
• Factors associated with progression of nephropathy during pregnancy:
  1. Poor glycemic control
  2. Uncontrolled hypertension
  3. Baseline nephropathy at onset of pregnancy (the more severe the nephropathy at baseline, the higher the risk of progression)

Effect of Diabetic Nephropathy on Pregnancy

• Proteinuria >190 mg/day before or during early pregnancy is associated with a tripling of risk of hypertensive disorders including worsening of chronic hypertension, development of pregnancy-induced hypertension and preeclampsia.
• Women with established diabetic nephropathy with overt proteinuria (>0.4 g/day) are at increased risk of intrauterine growth retardation and premature delivery, the latter often secondary to preeclampsia.

Effect of Pregnancy on Long Term Renal Function

• Proteinuria increases in pregnancy but returns to baseline by 6 months postpartum.
• Renal function, as measured by creatinine clearance, does not show a permanent worsening postpartum, except in a small subset of women with incipient renal failure.
• Pregnancy may lead to a permanent worsening of renal function in >40% of those with a serum creatinine of 250 umol/L or greater or creatinine clearance 0.85 ml/s or less.

Before Pregnancy

• Measure baseline serum creatinine, 24 hour urine protein and creatinine clearance.
• If serum creatinine over 250 umol/L or creatinine clearance <0.85 ml/s, the woman should be advised that renal function is likely to deteriorate and that pregnancy would not be recommended. Renal dysfunction that is not as severe is not generally considered a contraindication to pregnancy.
• ACE inhibitors should be discontinued prior to conception or as soon as pregnancy is detected. ACE inhibitors have been associated with fetal teratogenicity in some studies. Renal dysfunction and oligohydramnios have been reported when ACE inhibitors were used in the second and third trimester. If they are being used for hypertension, methyldopa or labetolol may be substituted.

Cardiovascular Disease

• There are only a few case reports in the literature of pregnancy in women with diabetes and cardiovascular disease. These show an increase in maternal and fetal mortality.
• Look for evidence of CAD in any woman with diabetes for > 20 years or in those women with established complications.
• Severe CAD should be adequately treated before conception, and women should be advised of the significant risks associated with pregnancy in the setting of coronary disease.

 

• Methods of birth control should be discussed so that timing of pregnancy can be planned.
• Alternatives include a low-dose estrogen birth control pill, progesterone only birth control pill, progesterone injections, condom and foam, and an IUD. Contraindications to the IUD are similar to women who are non-diabetic. Women with significant vascular complications should use progestin-only pills or non-hormonal methods of contraception.
• Women should be counseled about birth control so that pregnancy can be appropriately planned.

 

Maternal & Fetal Risks

• The woman with diabetes is at increased risk of polyhydramnios, pregnancy-induced hypertension, worsening chronic hypertension, pre-eclampsia, and C-section in association with a macrosomic infant.
• The risk of preeclampsia is 22-31% which can lead to premature delivery in 15-30%.
• The fetus is at increased risk of macrosomia, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress syndrome, and stillbirth.
• The fetus of a woman with diabetic nephropathy is at increased risk of IUGR (intrauterine growth retardation) by 11-20%.
• These complications can be reduced with excellent glycemic control and careful blood pressure control.

Glycemic Control

• Glycemic control has an impact on maternal and fetal complications, therefore excellent glycemic control should be continued throughout pregnancy.
• Tight glycemic control leads to an increase in episodes of severe hypoglycemia (those requiring assistance from another person) especially seen in the first and early second trimester. Worsening hypoglycemia unawareness is also seen, which increases the risk of severe hypoglycemia.
• Teach patients to be aware of subtle signs of hypoglycemia, to treat hypoglycemia promptly, and teach partners proper treatment of severe hypoglycemia (i.e. glucagon).
• Targets may have to be adjusted for patients with episodes of severe hypoglycemia and hypoglycemia unawareness.
• Women should perform self-blood glucose monitoring pre and postprandially, and occasionally between 2-4am, to achieve glycemic targets.
• Nutrition counseling should be provided from a registered dietician. Weight gain goals should be based on prepregnancy BMI (Institute of Medicine guidelines http://www.iom.edu/CMS/3788/48191/68004.aspx).
• Maintain A1C < 7.0% (<6% if safely achievable), FBS <5.3, 2 hr. PC < 6.7
• Perform A1C monthly during pregnancy

Monitoring Maternal Diabetic Complications

• Eyes should be checked by an ophthalmologist in the first trimester and thereafter as advised by the ophthalmologist.
• Renal function should be followed with a microalbumin to creatinine ratio and if positive, a 24 hr urine protein, creatinine clearance and serum creatinine each trimester.
• Maintain blood pressure at <140/90, especially in those with pre-existing renal dysfunction.
• Carpel tunnel syndrome is more common in women with diabetes, and can be exacerbated in pregnancy. Treat symptomatically (i.e. splints).

References

1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes 2008;32(suppl 1):S168-S180.
2. American Diabetes Association. Preconception care of women with diabetes. Diabetes Care 2004; 27 (suppl 1):S76-78.
3. Kitzmiller JL, Block JM, Brown FM et al. Managing preexisting diabetes for pregnancy; Summary of evidence and consensus recommendations for care. Diabetes Care 2008;31:1060-1079.