Diabetes mellitus (DM) is present in nearly 10% of women of childbearing age, and about 1% of all pregnancies are complicated by the disease.1 Uncontrolled DM during pregnancy increases the risks for maternal, fetal, and neonatal complications, including pre-eclampsia, miscarriage, fetal demise, congenital defects, and neonatal hypoglycemia and hyperbilirubinemia.2 Therefore, preconception care should be a routine part of healthcare for reproductive-aged women with DM who have the potential to become pregnant.1-3

Reproductive life planning

Women with DM are at increased risk for adverse health outcomes as a result of pregnancy, especially when pregnancy is unintended. DM increases the risk for cardiovascular disease (CVD) and renal disease, which may be exacerbated by pregnancy. Many drugs used in the treatment of DM and its complications are teratogenic, and prolonged hyperglycemia further increases the risk for fetal developmental abnormalities.1 Therefore, effective contraception is essential to prevent unintended pregnancy or to delay conception while treatment of DM is optimized to improve pregnancy outcomes.1,2 Women who express concern about the safety of contraceptives should be advised that the risks of unplanned pregnancy outweigh those of any contraceptive method.2,4

Until they are ready to become pregnant, women with DM who are of childbearing age and sexually active should use the most reliable form of contraception that is acceptable to and appropriate for them.1,2,4 Long-acting reversible contraceptives (LARC), including subdermal implants and intrauterine contraceptives, are the most effective forms of reversible contraception available. These methods do not rely on user compliance and are appropriate for most females, including adolescents and nulliparous women.4 Depot medroxyprogesterone acetate (DMPA); contraceptive pills, patches, and vaginal rings; and diaphragms are effective when used consistently and correctly but have higher typical-use failure rates than LARC.4 Condoms, spermicides, withdrawal, and fertility awareness methods are the least reliable forms of contraception, but condoms should be used in addition to a more reliable method to reduce the risk of acquiring a sexually transmitted infection.4

Long-acting reversible contraceptive methods and progestin-only pills are safe and appropriate for use in women with DM regardless of disease duration or presence of cardiovascular or other complications.4 Combined hormonal contraceptives (CHCs) and DMPA are safe for use in women with DM of less than 20 years’ duration without retinopathy, nephropathy, neuropathy, or other vascular disease.4 CHCs and DMPA must be avoided in women with any of these conditions or DM of greater than 20 years’ duration.4 Healthcare providers (HCPs) prescribing contraceptives for women with DM should refer to the U.S. Medical Eligibility Criteria for Contraceptive Use, 2016 for specific information about the efficacy and safety of each method.4

These recommendations apply to sexually active adolescents with DM, who may be unaware of the risks of DM during pregnancy.5 Under ideal circumstances, parents of female adolescents with DM, who are instrumental in guiding their daughters in self-care, should participate in preconception counseling sessions.5

Preconception counseling and evaluation

Preconception counseling improves DM knowledge, enhances patient engagement and self-efficacy, and improves pregnancy outcomes.6 HCPs should explain to patients the benefits of a team approach, and offer referral to a certified diabetes educator, registered dietician (RD), or others who can address their particular needs and concerns.6 Specific goals of preconception counseling include education about the risks of poorly controlled DM during pregnancy and about strategies to achieve and maintain glycemic control prior to conception and throughout pregnancy.3

When pregnancy is desired or anticipated, every effort should be made to achieve hemoglobin A1C values as close to normal as is safely possible.1,2 In addition, HCPs need to assess for women’s use of teratogenic medications, and change or discontinue these agents prior to discontinuing contraception.2 Preconception evaluation for women with DM also includes assessment for nephropathy, retinopathy, and neuropathy, which may progress during pregnancy; CVD or CVD risk; and thyroid disease.2,3

Preconception management

Medical nutrition therapy (MNT) is a cornerstone of DM management.3 In the preconception period, MNT goals are to meet women’s nutritional needs and to achieve and maintain glycemic control and a healthy body weight.2 Referral should be made to an RD with expertise in MNT in women with DM, both before and during pregnancy.3 The U.S. Preventive Services Task Force recommends that all women planning or capable of pregnancy take a daily supplement containing 400-800 mcg of folic acid to prevent neural tube defects (NTDs) in infants.7 Presence of DM increases NTD risk.7 The American Diabetes Association (ADA) recommends that women with DM who are planning a pregnancy take a prenatal vitamin containing at least 400 mcg of folic acid.2

Glycemic control

An elevated glucose level increases the risk for fetal developmental abnormalities in the first trimester.1 For women who maintain good glycemic control prior to and throughout the first trimester of pregnancy, the risk for complications is similar to that of women without DM.3 Glycemic targets are individualized based on health status and risk for hypoglycemia.2 The ADA recommends achieving an A1C <6.5%, or as low as can be safely achieved without hypoglycemia, prior to conception.2

Insulin

Insulin is the preferred medication for managing type 1 or type 2 diabetes mellitus during pregnancy; HCPs may consider initiating insulin prior to conception when indicated.2,3 Data from human studies indicate that most insulins are safe to use in pregnancy.2,8 Glulisine and degludec have not been studied in humans, however8; HCPs should consider switching women using either of these agents to an insulin that has been studied in humans prior to conception.2

Metformin

Human data suggest that metformin is safe for use in pregnancy and is less likely than insulin or some other oral antidiabetics to cause hypoglycemia.2,8 Women using metformin before conception may continue the drug but should understand that it may be insufficient to maintain glycemic control during pregnancy.2 Metformin crosses the placenta; although no fetal adverse effects have been found, no long-term studies of its safety during pregnancy have been reported.2

Sulfonylureas

Some studies support the use of sulfonylureas in pregnancy, but the FDA has not approved these drugs for use during pregnancy.3 Glipizide has not been studied in humans in terms of its potential teratogenic effects. Animal studies show a low risk of fetal harm from glipizide, but the drug can cause prolonged fetal hypoglycemia and is not recommended for use late in pregnancy. Glyburide has shown minimal risk of fetal hypoglycemia in human studies, as well as no teratogenicity.8 Women taking sulfonylureas who are contemplating or attempting pregnancy should consider changing to insulin in the preconception period. Other classes of oral antidiabetics are not well studied in pregnancy and are not recommended.3

Hypertension

Hypertension (HTN), common in patients with DM, increases the risk for CVD and microvascular disease.6 Chronic HTN in pregnancy increases the risk of poor pregnancy outcomes and maternal end-organ damage.1 DM increases the risks for pre-eclampsia and the development and/or progression of retinopathy and nephropathy, which may be exacerbated by HTN.6 The goal of hypertensive management before and during pregnancy is to optimize blood pressure (BP) control—target BP goals of 110-129/65-79 mmHg are reasonable—using medications with good safety profiles for mother and fetus.2 Unsafe antihypertensives should be avoided in women at risk for pregnancy and discontinued in those contemplating pregnancy.1,2

Antihypertensives contraindicated in pregnancy include angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, which have been linked to fetal renal dysplasia, oligohydramnios, and intrauterine growth restriction.2 Chronic diuretic use may decrease maternal plasma volume and inhibit uteroplacental circulation.2 Antihypertensives that are safe for use in pregnancy include labetalol, methyldopa, diltiazem, clonidine, and prazosin.2

Dyslipidemia

Dyslipidemia, another common co-morbidity in DM, contributes to CVD risk. Although many women with DM take antihyperlipidemics, most of these medications should not be used during pregnancy. Statins are contraindicated in pregnancy; other antihyperlipidemics, including ezetimibe, bile acid sequestrants, fibrates, and niacin, are not recommended because of insufficient data evaluating risk.9 Women using antihyperlipidemics should be counseled about fetal risks and discontinue these agents prior to conception.2 Omega-3 fatty acids are the only pharmacologic treatment for dyslipidemia known to be safe during pregnancy.9

Overweight/obesity

Overweight/obesity (OW/O) is associated with adverse maternal and fetal outcomes, including pre-eclampsia, macrosomia, and cesarean delivery, and has adverse effects on BP, lipid profile, and glycemic control. Diet and exercise are the cornerstones of weight management; women with DM and OW/O can benefit from referral to an RD. Women should strive to follow a healthful diet that includes monounsaturated fats, fruits, vegetables, and whole grains and limits refined sugar, and engage in ≥150 minutes of moderate-intensity exercise each week.2 Currently available medications for treatment of obesity are contraindicated in pregnancy; if medications are prescribed for weight loss, they must be discontinued before pregnancy is attempted.8 Women who attempt weight loss through bariatric surgery should delay conception for 12-18 months following surgery to minimize the adverse effects of postsurgical nutritional deficiencies.10

Nephropathy

Healthcare providers should assess patients’ renal function prior to conception and advise them that nephropathy may progress during pregnancy.2 HCPs and patients should aim to optimize control of risk factors for nephropathy, including elevated BP and elevated blood glucose.2

Retinopathy

Retinopathy may occur or progress during pregnancy.2 Women with DM who are contemplating pregnancy should be referred for a dilated retinal examination prior to conception and should undergo follow-up eye exams every trimester and as indicated during the first postpartum year.2 Optimization of blood glucose control may decrease the risk for progression of retinopathy.2

Conclusion

Nearly half of all pregnancies are unplanned.1 For women with DM, unplanned pregnancy carries a significant risk for poor maternal, fetal, and neonatal outcomes. HCPs should address reproductive life planning and preconception care components with all reproductive-aged patients with the potential to become pregnant. For those with DM, an additional focus on the unique preconception considerations to reduce risks related to DM and promote healthy pregnancy outcomes is important. Optimization of glycemic control; discontinuation of teratogenic medications; management of cardiovascular, renal, and ophthalmic risks; and patient education are essential components of preconception care that can reduce the risks for adverse maternal and fetal effects and optimize pregnancy outcomes.

Cynthia S. Watson and Janis R. Guilbeau are nursing faculty at the University of Louisiana at Lafayette. The authors state that they do not have a financial interest in or other relationship with any commercial product named in this article.

References

References

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  2. American Diabetes Association. Management of diabetes in pregnancy. Diabetes Care. 2016;39(suppl 1):S94-S98.
  3. American Academy of Clinical Endocrinologists. AACE Diabetes Resource Center. Management of Pregnancy Complicated by Diabetes.
  4. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. July 29, 2016.
  5. Charron-Prochownik D, Fischl AR, Choi J, et al. Mother-daughter dyadic approach for starting preconception counseling at puberty in girls with diabetes. Res J Womens Health. 2014;1.
  6. American Diabetes Association. Foundations of care and comprehensive medical evaluation. Diabetes Care. 2016;39(suppl 1):S23-S35.
  7. U.S. Preventive Services Task Force. Folic acid supplementation for the prevention of neural tube defects. U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2017;317(2):183-189.
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  9. Mukherjee M. Dyslipidemia in pregnancy. Am Coll Cardiology. 2014.
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