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Last Updated: 1/17/2014  

Diabetes in Pregnancy

  • Counsel all diabetic women of childbearing potential on the need for pregnancy planning.

  • Optimize glycemic control and stop teratogenic medications (including ACE inhibitors and angiotensin-receptor blockers) before conception.

  • Screen all pregnant nondiabetic women for gestational diabetes at 24 to 28 weeks gestation using a 75g 2-hour OGTT.

  • Use laboratory testing to evaluate diabetic control (using HbA1C) in diabetic women who become pregnant and follow HbA1C every 2 to 3 months during pregnancy.

  • Use metformin, glyburide, or insulin in pregnant patients with diabetes to achieve optimal glycemic control, with the goal of fasting glucose levels of ≤95 mg/dL and 2-hour postprandial glucose levels of ≤140 mg/dL.

Counsel all diabetic women of childbearing potential on the need for pregnancy planning and optimize diabetic control before pregnancy. 
  • Ensure effective birth control at all times, unless the patient is trying to conceive and is in good diabetic control.

  • Counsel women with type 1 or 2 diabetes on the risks of fetal malformation associated with unplanned pregnancies and poor metabolic control.

  • In diabetic women planning pregnancy:

    • Achieve fasting whole-blood glucose levels of 70 to 100 mg/dL and 2-hour postprandial levels of <140 mg/dL

    • Achieve HbA1C of <7%

Evidence
  • The 2014 Standards of Medical Care in Diabetes from the American Diabetes Association recommended that preconception counseling be done in all women of childbearing age with diabetes. Before conception the guideline recommended tight control of end-organ complications, stopping potentially toxic medications such as ACE inhibitors, angiotensin-receptor blockers, statins, and some oral medication for diabetes. The guideline recommended that pregnant women with diabetes achieve an HbA1C of 7% (1).

  • In a meta-analysis of 14 cohort studies, the pooled rates of major and minor fetal anomalies were lower in diabetic women who had received pre-conception care (2.1%) compared with those who had not (6.5%; RR 0.36 [CI, 0.22 to 0.59]) (2).

  • Population-based cohort studies have found an association between adverse fetal outcomes and maternal hyperglycemia even in the absence of frank diabetes (3; 4; 5; 6).

  • A nested case-control study of 209 Canadian women within a cohort of nulliparous women with type 1 diabetes mellitus found that among the 115 women who underwent a trial of labor, 54 (47%) had a cesarean delivery. A prepregnancy BMI greater than 25 (84% compared with 39%; OR, 7.5 [CI, 1.9 to 29.4]) was independently associated with cesarean delivery (7).

Rationale
  • There is an association between elevated maternal glucose or glycohemoglobin levels during embryogenesis and high rates of pregnancy loss and major congenital malformations.

Comments
  • Pre-conception counseling also should include advice on folic acid intake, vaccinations for rubella and varicella, weight control, and a review of current diseases and medications in addition to an assessment of diabetes management.

Counsel all obese women of childbearing age on the need for diet and exercise to decrease the risk of gestational diabetes. 
  • Provide nutritional counseling to obese women of childbearing age.

  • Consider recommending to obese women planning pregnancy or already pregnant:

    • A 30% to 33% calorie restriction if BMI >30

    • Limiting fat intake to <30% of calories

    • Increasing physical activity, as recommended outside pregnancy, or a program of moderate exercise if the woman is already pregnant

Evidence
  • A prospective cohort study of nondiabetic women revealed an adjusted OR of 1.11 (CI, 1.06 to 1.15) for primary cesarean delivery associated with an increase in a fasting plasma glucose level of 1 SD (6.9 mg/dL [0.4 mmol/L]), an adjusted OR of 1.10 (CI, 1.06 to 1.15) for an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg/dL [1.7 mmol/L]), and an adjusted OR of 1.08 (CI, 1.03 to 1.12) for an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg/dL [1.3 mmol/L]). There were no obvious thresholds at which risks increased (5).

  • A prospective observational study found that women diagnosed with gestational diabetes were on average 11.7 kg heavier before pregnancy than women who remained nondiabetic throughout pregnancy, and that the percentage of body fat, LDL cholesterol, and fasting glucose levels in women with gestational diabetes remained elevated 3 months after pregnancy in comparison to the nondiabetic postpartum women (8).

  • Higher maternal prepregnancy BMI and weight gain during pregnancy are associated with macrosomia and an increased risk of fetal malformations (9).

  • A study on 1698 women enrolled in the Pregnancy, Infection, and Nutrition Study found that the predicted probability of gestational diabetes was reduced by one half with a 10% decrease in dietary fat and a 10% increase in carbohydrate (10).

  • In a prospective study of 909 women in Washington, those who participated in any physical activity during the previous year experienced a 56% risk reduction in the incidence of gestational diabetes compared with inactive women (RR, 0.44 [CI, 0.17 to 0.70]). The greatest reduction in the risk for gestational diabetes was seen among women who exercised both before and during pregnancy (adjusted RR, 0.31 [CI, 0.12 to 0.79) (11).

  • Among 21,765 women participating in the Nurses' Health Study II, total and vigorous activity scores before pregnancy were associated with a significantly lower risk of developing gestational diabetes during the next pregnancy (RR, 0.77 [CI, 0.69 to 0.94], P<0.02 for trend) when comparing the highest vs. the lowest quintile of physical activity during the period before pregnancy. Women who spent 20 hours per week or more watching television but did not perform vigorous physical activity had a significantly higher risk of developing gestational diabetes than those who spent less than 2 hours per week watching television and were physically active (multivariate RR, 2.30 [CI, 1.06 to 4.97]) (12).

Rationale
  • Pre-pregnant obesity increases the risk of gestational diabetes.

  • Maternal pre-pregnant obesity, hyperglycemia, or both are associated with fetal malformations and macrosomia.

  • Dietary fat restriction during pregnancy is associated with a reduced risk of gestational diabetes.

  • Increased physical activity is associated with a reduced risk of gestational diabetes.

Stop ACE inhibitor therapy and certain diabetes medications before conception. 
  • Stop all ACE inhibitors and angiotensin-receptor blockers and replace with other medications.

    • Note that labetolol and nifedipine are commonly used to treat hypertension during pregnancy

  • Stop cholesterol-lowering drugs.

  • Stop aspirin therapy.

  • Switch oral hypoglycemic agents to:

    • Metformin, or glyburide in patients with good glycemic control

    • Insulin in patients with poor glycemic control for rapid titration

  • Review other medications and stop any potential teratogens.

Evidence
  • The 2014 Standards of Medical Care in Diabetes from the American Diabetes Association recommended that preconception counseling be done in all women of childbearing age with diabetes. Before conception the guideline recommended tight control of end-organ complications, stopping potentially toxic medications such as ACE inhibitors, angiotensin-receptor blockers, statins, and some oral medications for diabetes. The guideline recommended that pregnant women with diabetes achieve an HbA1C of 7% (1).

  • A 2013 guideline from the Endocrine Society on diabetes and pregnancy recommended that women with diabetes on insulin who are planning to become pregnant be switched to multiple daily injections of insulin or an insulin pump (13).

  • Two 2010 meta-analyses of trials comparing either metformin or glyburide to insulin therapy found no difference between oral agents and insulin in either glycemic control or pregnancy outcomes (14; 15).

  • A 2010 systematic review of continuous subcutaneous insulin infusion (insulin pump) found no evidence that continuous subcutaneous insulin infusion is superior to analogue-based multiple daily injections in pregnancy (16).

  • A 2012 systematic review of pregnancy outcomes after exposure to ACE inhibitors and angiotensin-receptor blockers included 72 studies. Overall, 48% of newborns exposed to ACE inhibitors and 87% of those exposed to angiotensin-receptor blockers had complications (P<0.0001). Complications included death, respiratory distress syndrome, renal failure, limb defects, cerebral complications, oligohydramnios, and intrauterine growth retardation (17).

  • In a surveillance study of lovastatin exposures during pregnancy, the overall rate of normal outcomes was 85%, and the following rates of occurrence were found: congenital anomalies, 4%; spontaneous abortions, 8%; fetal deaths or stillbirths, 1%; and miscellaneous adverse outcomes, 2% (18).

  • In one case-controlled study, 3 of 14 newborns exposed to aspirin within 1 week of delivery had minor hemorrhaging compared with 1 of 17 controls (19). In two retrospective studies, mothers of 1291 malformed infants were found to have consumed aspirin during pregnancy more frequently than mothers of normal infants (20; 21).

Rationale
  • ACE inhibitors and angiotensin-receptor blockers have been associated with fetal malformations.

  • No adverse maternal effects are likely to occur with a 9-month hiatus from cholesterol-lowering agents and they are possible teratogens.

  • Daily aspirin therapy may lead to maternal and newborn hemorrhage, increased perinatal mortality, intrauterine growth retardation, and teratogenic effects.

Comments
  • Many diabetic women take a variety of medications; therefore, pre-conception planning should include a review of all drugs and their potential for teratogenesis.

Screen all pregnant women for gestational diabetes at 24 to 28 weeks' gestation using a 75-gram 2-hour OGTT. 
  • Screen high-risk women at the first prenatal visit to detect prepregnancy diabetes.

  • Screen nondiabetic pregnant women for gestational diabetes between 24 and 28 weeks' gestation using a 2-hour 75-g OGTT.

    • Define overt diabetes as FPG >126 mg/dL

    • Diagnose gestational diabetes if 1-hour glucose is >180 mg/dL or 2-hour glucose is >153 mg/dL

Evidence
  • A 2014 guideline from the U.S. Preventive Services Task Force recommended screening for gestational diabetes in pregnant women after 24 weeks' gestation.

  • A 2013 systematic review for the U.S. Preventive Services Task Force of the accuracy of screening tests for gestational diabetes included 51 studies comparing diagnostic tests to various reference standards. Oral glucose tolerance tests had sensitivity of 70% to 88% and specificity of 69% to 89% at a threshold of 140 mg/dL, and sensitivity of 88% to 99% and specificity of 66% to 77% at a threshold of 130 mg/dL. Fasting plasma glucose had sensitivity of 87% and specificity of 52% at a threshold of 85 mg/dL. Hemoglobin A1c had poorer diagnostic performance and highly variable accuracy across studies (22).

  • The HAPO study, a large observational study of pregnant women, found an association between adverse fetal outcomes and maternal hyperglycemia even in the absence of frank diabetes (5; 6).

  • A randomized trial of 3152 women tested with either a 3-hour, 100-gram oral glucose tolerance test at 32 weeks if any risk factor for gestational diabetes was present, or a universal screening with a 50-gram glucose challenge test. Universal screening detected a prevalence of gestational diabetes of 2.7%, versus 1.45% detected in the risk factor screened group (P<0.03). Universally screened patients had higher rates of spontaneous vaginal delivery at term and lower rates of macrosomia, caesarean section, prematurity, preeclampsia, and neonatal admission to the neonatal intensive care unit (23).

Rationale
  • The identification of prepregnancy diabetes allows for early treatment and avoidance of complications.

  • Rates of adverse outcomes are related to maternal glycemia even at values in the high-normal range.

Evaluate women with pre-gestational diabetes for diabetic complications before conception and review issues of diabetic control and symptoms of hyperglycemia in all pregnant women. 
  • Screen pregnant patients with no previous history of diabetes for hyperglycemic symptoms.

  • Assess history of acute diabetic complications.

  • Review history of retinopathy, nephropathy, hypertension, atherosclerotic disease, and neuropathy.

  • Review duration and type of diabetes and current diabetes management.

  • Document other concomitant medical conditions, including thyroid disease, and drugs.

  • Review basic pregnancy issues, such as past pregnancy history, menstrual history, and support system for the patient.

  • Obtain dilated retinal exam before pregnancy.

  • Measure blood pressure and test for orthostatic changes.

  • Perform cardiovascular exam to look for evidence of cardiac or peripheral vascular disease.

Evidence
  • A randomized trial of 3152 women tested with either a 3-hour, 100-gram oral glucose tolerance test at 32 weeks if any risk factor for gestational diabetes was present, or a universal screening with a 50-gram glucose challenge test, found that universal screening detected a prevalence of gestational diabetes of 2.7%, versus 1.45% detected in the risk-factor screened group (P<0.03). Universally screened patients had higher rates of spontaneous vaginal delivery at term and lower rates of macrosomia, cesarean section, prematurity, preeclampsia, and neonatal admission to the neonatal intensive care unit (23).

  • The term ‘gestational diabetes' has traditionally included all diabetes diagnosed during pregnancy resulting in heterogeneity among patients with this diagnosis. Patients with elevated glucose levels before the second trimester of pregnancy, acute complications, such as diabetic ketoacidosis, and elevated postprandial glucose levels will likely have type 1 or 2 diabetes newly diagnosed during pregnancy (24).

  • Expert opinion suggests screening for history of acute diabetic complications and notes the need for social support in patients with pre-gestational diabetes (25).

  • In a study of 31 continuous diabetic pregnancies, 71% developed nephrotic range proteinuria. In all of these patients, proteinuria reverted to previous levels after delivery (26).

  • In a prospective study to determine the effects of pregnancy on diabetic retinopathy, pregnancy was associated with progression after adjustment for glycosylated hemoglobin measurements (P<0.005; adjusted OR, 2.3) (27).

  • One case series review found a high mortality rate in pregnant, diabetic women with known ischemic heart disease (28).

Rationale
  • Women may be diagnosed with diabetes during pregnancy, which may be a self-limited condition or may indicate chronic diabetes mellitus.

  • Women with a history of acute diabetic complications may be more likely to have recurrences during pregnancy.

  • Conditions such as retinopathy and nephropathy may worsen during pregnancy.

  • Hypertension complicates many diabetic pregnancies.

  • Maternal cardiovascular disease is associated with a high mortality rate during pregnancy.

  • Diabetic pregnancies require management of the pregnancy, management of diabetes and its complications, and involvement of the patient's social support structure.

Use laboratory testing to evaluate diabetic control and to screen for related medical conditions. 
  • Obtain the following in women with pre-gestational diabetes before conception:

    • Hemoglobin A1c level

    • 24-hour urine test for protein and creatinine levels

    • ECG

  • Obtain blood glucose level in all pregnant women:

    • In the first trimester or at the first prenatal visit in those who are at increased risk of pre-gestational diabetes

    • With symptoms of hyperglycemia, to monitor for the development of diabetes

  • Check thyroid levels with the first set of antepartum labs in patients with type 1 diabetes.

  • See table Laboratory and Other Studies for Diabetes in Pregnancy.

Evidence
  • In a review of 14 cohort studies, the pooled rates of major and minor fetal anomalies were lower in diabetic women who had received pre-conception care (2.1%) compared with those who had not (6.5%; RR 0.36 [CI, 0.22 to 0.59]) (2). Population-based cohort studies have found an association between adverse fetal outcomes and maternal hyperglycemia (3; 4; 5).

  • Professional consensus exists on a goal of <6% in pregnancy (29).

  • In a case study of 311 diabetic pregnant women with proteinuria, 31% to 58% of the women developed preeclampsia. The increased risk persisted after controlling for parity, chronic hypertension, retinopathy, and glycemic control (30).

  • In a study of 31 continuous diabetic pregnancies of diabetic women with nephropathy before the pregnancy, 71% of the women developed nephrotic range proteinuria during gestation. In all of these patients, proteinuria reverted to previous levels after delivery (26).

  • A retrospective observational study demonstrated lower IQ scores in children of pregnant women with subclinical hypothyroidism (31). An increased prevalence of subclinical hypothyroidism has been reported in pregnant diabetic patients (32).

  • A 50-year series of diabetic patients showed increased maternal mortality in women with ischemic heart disease (28). Consensus opinion recommends an ECG (33).

Rationale
  • New onset diabetes mellitus may be discovered during pregnancy, and hyperglycemia may adversely affect the fetus.

  • Euglycemia before conception reduces fetal cardiac and neurologic anomalies.

  • Patients with urinary protein excretion >190 mg per 24 hours are at risk of hypertensive disorders during later pregnancy.

  • There is a 5% to 10% coincidence of hyperthyroidism or hypothyroidism and type 1 diabetes; thyroid disease can affect the fetus.

  • All diabetes discovered during pregnancy is termed ‘gestational diabetes.’ Controversy exists surrounding universal screening for the condition in late pregnancy, although most organizations recommend screening.

  • Diabetic women with coronary artery disease have increased mortality rates during pregnancy.

Comments
  • Nephropathy may worsen transiently during diabetic pregnancies, but permanent worsening occurs at rates no higher than the rates for nonpregnant diabetics.

  • In one series of diabetic patients being evaluated for renal transplantation, the authors found virtually no significant coronary disease by angiography if the patient was younger than 45 years, the diabetes duration was <25 years, and there were no ST-T wave changes on ECG (34).

  • The U.S. Preventive Services Task Force concluded that no randomized, controlled clinical trial provides evidence for the benefits of screening for gestational diabetes (35). Most obstetricians screen all women for gestational diabetes mellitus in late pregnancy, but this remains controversial.

Consult appropriate subspecialists for help in defining the status of diabetic complications before conception. 
  • Refer women with pre-gestational diabetes to an ophthalmologist for dilated retinal exam before conception, or at least early in pregnancy.

  • Consider referral of women with pre-gestational diabetes and proteinuria to a nephrologist if proteinuria is noted before conception or early in pregnancy.

  • Consider referral to a cardiologist for the diagnosis of coronary artery disease for those women with pre-gestational diabetes who:

    • Are older than 45 years

    • Have had diabetes for >25 years

    • Show ST-T wave changes on ECG

    • Have symptoms of coronary artery disease

  • Consider referral of women with pre-gestational diabetes and signs or symptoms of neuropathy to a neurologist before pregnancy.

Evidence
  • There is consensus opinion on subspecialist consultation in the American Diabetes Association guidelines on pre-conception care of women with diabetes (33).

  • In a prospective study to determine the effects of pregnancy on diabetic retinopathy, pregnancy was associated with progression after adjustment for glycosylated hemoglobin measurements (P<0.005; adjusted OR, 2.3) (27).

  • In a study of 31 continuous diabetic pregnancies, 71% of the patients developed nephrotic range proteinuria. In all of these patients, proteinuria reverted to previous levels after delivery (26).

  • In a case study of 311 diabetic pregnant women with proteinuria, 31% to 58% of the patients developed preeclampsia. The increased risk persisted after controlling for parity, chronic hypertension, retinopathy, and glycemic control (30).

  • A 50-year series of diabetic patients showed increased maternal mortality in women with ischemic heart disease (28).

  • In one series of diabetic patients being evaluated for renal transplantation, the authors found virtually no significant coronary disease if the patient was younger than 45 years, the diabetes duration was <25 years, and there were no ST-T wave changes on ECG (34).

Rationale
  • Retinopathy and nephropathy may worsen during pregnancy.

  • Diabetic women with coronary artery disease have increased mortality rates during pregnancy.

  • Neuropathy, particularly autonomic neuropathy, may complicate the management of diabetes in pregnancy and should be identified and treated before pregnancy.

Consider consultation with an endocrinologist for help in classifying gestational diabetes. 
  • Consider consultation with an endocrinologist or high-risk obstetrician to further classify gestational diabetes as type 1, type 2, or transient diabetes of pregnancy.

Evidence
Rationale
  • Patients with type 1 or type 2 diabetes diagnosed during pregnancy may be at higher risk for acute and chronic diabetic complications than patients diagnosed with hyperglycemia late in pregnancy, because those diagnosed earlier in pregnancy probably had unrecognized underlying diabetes.

Ensure specialized obstetric care for diabetic women who are pregnant or planning pregnancies. 
  • Refer all women with pre-gestational diabetes to an obstetrician, or a high-risk obstetrician if available, as soon as pregnancy is diagnosed.

  • Consider referral to a high-risk obstetrician for:

    • Fetal and maternal risk determination as part of pregnancy planning

    • Ongoing management if pre-conception fasting whole-blood glucose levels of 70 to 100 mg/dL and 2-hour postprandial levels of <140 mg/dL cannot be achieved before conception

Evidence
  • Consensus.

Rationale
  • Obstetricians will be the primary caregivers for pregnant women who are diabetic, and general internists, family physicians, and/or other specialists may be consulted to assist with management.

Consider consultation with an endocrinologist and other professionals to ensure ideal glucose levels before and during pregnancy in diabetic women. 
  • Consider referral to an endocrinologist if the diabetic woman cannot achieve ideal glucose levels during pregnancy or before conception.

  • Refer all women with diabetes during pregnancy, or women with diabetes considering pregnancy, to a:

    • Nutritionist for instruction on the American Diabetes Association diet

    • Certified diabetic educator for instruction in self-management of diabetes

Evidence
  • In a meta-analysis of 14 cohort studies, the pooled rates of major and minor fetal anomalies were lower in diabetic women who had received pre-conception care (2.1%) compared with those who had not (6.5%; RR, 0.36 [CI, 0.22 to 0.59]) (2).

  • Population-based cohort studies have found an association between adverse fetal outcomes and maternal hyperglycemia (3; 4; 5).

Rationale
  • Euglycemia during pregnancy reduces fetal cardiac and neurologic anomalies and fetal macrosomia.

Obtain specialty consultation for help in managing complications of diabetes in pregnant women or before conception. 
  • Obtain consultation with a:

    • Nephrologist if proteinuria is detected in a pregnant patient

    • Ophthalmologist for management of diabetic retinopathy

    • Cardiologist in pregnant patients with coronary artery disease

    • Neurologist in women with neuropathy or autonomic dysfunction

Evidence
  • In a prospective study to determine the effects of pregnancy on diabetic retinopathy, pregnancy was associated with progression after adjustment for glycosylated hemoglobin measurements (P<0.005; adjusted OR, 2.3) (27).

  • In a study of 31 continuous diabetic pregnancies, 71% developed nephrotic range proteinuria. In all of these patients, proteinuria reverted to previous levels after delivery (26).

  • In a case study of 311 diabetic pregnant women with proteinuria, 31% to 58% developed preeclampsia. The increased risk persisted after controlling for parity, chronic hypertension, retinopathy and glycemic control (30).

  • A 50-year series of diabetic patients showed increased maternal mortality in those women with ischemic heart disease (28).

  • In one series of diabetic patients being evaluated for renal transplantation, the authors found virtually no significant coronary disease by angiography if the patient was younger than 45 years, the diabetes duration was <25 years, and there were no ST-T wave changes on ECG (34).

Rationale
  • Conditions such as retinopathy and neuropathy may progress during pregnancy.

  • Diabetic women with coronary artery disease have increased mortality rates during pregnancy.

  • Neuropathy, particularly autonomic neuropathy, may complicate the management of diabetes in pregnancy and thus should be identified and treated before the onset of pregnancy.

Hospitalize pregnant women with elevated glucose levels and poor outpatient control. 
  • Consider hospitalizing pregnant patients when:

    • Fasting whole-blood glucose levels consistently exceed 70 to 100 mg/dL

    • 2-hour postprandial levels exceed 140 mg/dL

Evidence
  • In a systematic review of cohort studies, major fetal malformations were associated with elevated glycohemoglobin levels in early pregnancy on a dose-response curve. The total proportion of infants with malformation from the pooled data were 2.2% in mothers with moderately elevated glycohemoglobin levels, 8.6% in mothers with high glycohemoglobin levels, and 26.6% in mothers with the highest glycohemoglobin levels. Pre-conception care of diabetic women with efforts to control glucose have shown a decrease in major congenital anomalies (2.5% of women with pre-conception care compared with 7.8% of women with no pre-conception care [pooled data]) (25).

  • In a systematic review, 17% to 29% of infants born to women with untreated gestational diabetes weighed >4000 g at birth compared with 10% of infants born to women in the general population (35).

  • In a Cochrane review meta-analysis of three small randomized, controlled trials on different intensities of glycemic control in pregnant women with pre-gestational diabetes, fasting blood glucose under 115-120 mg/dL was associated with improved fetal and maternal outcomes, with evidence of harm (increased preeclampsia, caesareans, and birth weights greater than 90th percentile) for ‘loose’ control (fasting blood glucose above 120 mg/dL) (36).

  • A meta-analysis of 13 randomized, controlled trials of different intensities of specific treatments for diabetes in pregnancy showed a significant reduction of shoulder dystocia in women with more intensive treatment (OR, 0.31 [CI, 0.14 to 0.70]). In women specifically treated for gestational diabetes, shoulder dystocia was significantly less common in the treatment group (OR, 0.40 [CI, 0.21 to 0.75]), and large-for-gestational-age infants were significantly less likely in treated women (OR, 0.48 [CI, 0.38 to 0.62]) (37).

Rationale
  • There is an association between elevated maternal glucose or elevated glyco-hemoglobin levels during embryogenesis and high rates of pregnancy loss and major congenital malformations.

  • Organogenesis of the fetus may take place before pregnancy is diagnosed.

  • High glucose levels in late pregnancy increase the risk of fetal macrosomia.

Hospitalize pregnant women with evidence of ketoacidosis. 
  • Immediately hospitalize pregnant women with evidence of ketoacidosis.

  • Search for secondary causes of ketoacidosis, including infection.

Evidence
  • Consensus.

Rationale
  • Ketoacidosis is a dangerous medical condition commonly associated with type 1 diabetes, and it may occur with increased frequency during pregnancy.

Comments
  • Treatment for ketoacidosis does not change during diabetic pregnancy.

Stress the importance of diet and exercise in pregnant diabetic patients to control glucose levels. 
  • Consider recommending to pregnant diabetic patients:

    • A calorie restriction of 30% to 33% in pregnant women with diabetes and a BMI >30

    • Limiting carbohydrate intake to 35% to 40% of calories

    • A program of moderate exercise

Evidence
  • A guideline from the Endocrine Society on diabetes and pregnancy recommended medical nutrition therapy for all pregnant women with diabetes (either gestational diabetes or preconception diabetes), and that patients follow Institute of Medicine guidelines for weight gain during pregnancy. In addition, the guideline recommended that pregnant women with diabetes limit carbohydrates to 35% to 45% of total calories, divided among three meals and two to four snacks (13).

  • A small randomized, controlled trial of obese women with gestational diabetes showed a reduction in 24-hour mean glucose levels from 121 mg/dL to 97.3 mg/dL in women assigned to a diet of 1200 calories per day compared with women on 2400 calories per day; however, maternal ketonuria of unknown clinical significance was also seen (38; 39).

  • In a controlled trial, calorie restriction of 33% and 50% in obese women with gestational diabetes decreased maternal glucose levels by 10% to 20% and reduced triglyceride levels when compared with insulin therapy (40).

  • In a 12-week controlled trial of obese pregnant women, half of whom had previous gestational diabetes, all of the women had higher triglycerides while on a 55% carbohydrate diet than while on a 40% carbohydrate diet and comparable weight loss (41).

  • A small randomized, controlled trial showed increased cardiac fitness in women with gestational diabetes who exercised 30 minutes 3 to 4 days per week and achieved 70% of estimated maximal heart rate. No complications were seen (42).

  • A small randomized, controlled trial showed reduced glucose levels in women with gestational diabetes who performed upper-extremity aerobic exercise (43).

  • A small randomized study showed a decreased need for insulin in overweight women with gestational diabetes assigned to resistance exercise (44).

Rationale
  • Calorie restriction may reduce hyperglycemia in obese diabetic pregnant patients.

  • Carbohydrate restriction may decrease maternal glucose levels and improve maternal and fetal outcomes in diabetic pregnancies.

  • Moderate exercise may reduce glucose levels in diabetic pregnancies.

  • Maternal hyperglycemia is associated with fetal malformations and macrosomia.

Comments
  • Little data exist concerning women with pre-gestational diabetes and diet or exercise. Consensus in patients with diabetes mellitus stresses the importance of diet and exercise for weight and glycemic control.

Use metformin, glyburide, or insulin in patients with gestational diabetes or pregnant women with pre-gestational diabetes to achieve optimal glycemic control, with the goal of fasting glucose levels of ≤95 mg/dL and 2-hour postprandial glucose levels of ≤140 mg/dL.  
  • Target a goal fasting blood glucose level ≤95 mg/dL and a 2-hour postprandial glucose level ≤140 mg/dL.

  • In women diagnosed with gestational diabetes:

    • Begin diet therapy immediately and instruct patients to check fingerstick glucose levels frequently.

    • After 1 week, if glucose levels are not meeting goals, add either insulin (if fasting glucose >110 mg/dL), glyburide, or metformin.

  • In women treated with insulin, adjust dosing frequently to achieve target glucose levels.

  • See table Drug Treatment for Diabetes in Pregnancy.

Evidence
  • A guideline from the Endocrine Society on diabetes and pregnancy recommended glycemic targets for pregnant women with diabetes, including a fasting blood glucose level ≤95 mg/dL (<90 mg/dL if possible without side effects), a 1-hour postprandial glucose level ≤140 mg/dL, a 2-hour postprandial glucose level ≤120 mg/dL, and an HbA1c <7% (or even <6.5% if possible without side effects). The guideline recommended that women with gestational diabetes be treated with dietary therapy, but that those who do not achieve glycemic control after 1 week be treated with glyburide. The guideline recommended insulin for women with higher blood glucose levels and metformin only for women who cannot (or choose not to) take glyburide or insulin (13)

  • The 2014 Standards of Medical Care in Diabetes from the American Diabetes Association recommended that pregnant women with diabetes achieve an HbA1c <7% (1).

  • A 2005 guideline from the American College of Obstetricians and Gynecologists recommended checking hemoglobin A1c each trimester in pregnancy, with a goal of 6% or less (29).

  • A 2013 systematic review for the U. S. Preventive Services Task Force of the benefits and harms of treatments for gestational diabetes included five randomized trials and six cohort studies comparing various treatments to no treatment. There was moderate quality evidence that treated patients had less preeclampsia and that their babies had less shoulder dystocia and macrosomia compared to untreated patients. Treated patients had more physician visits. There was no apparent difference in rates of cesarean delivery of induction of labor (45).

  • A 2010 meta-analysis of six trials comparing either metformin or glyburide to insulin therapy found no difference between oral agents and insulin in either glycemic control or pregnancy outcomes (14).

  • A 2007 meta-analysis of the association between congenital abnormalities and pre-pregnancy glycemic control included seven cohort studies. For each 1-SD unit increase in glycated hemoglobin, the associated risk of a congenital malformation increased by an OR of 1.2 (CI, 1.1 to 1.4) (46).

  • A 2010 systematic review and cost-effectiveness evaluation of continuous subcutaneous insulin infusion (i.e., insulin pump) found no evidence that continuous subcutaneous insulin infusion is superior to analogue-based multiple daily injections in pregnancy (16).

  • In an open-label, randomized clinical trial of metformin versus insulin, no difference in fetal macrosomia or other fetal morbidity was observed, but there was a trend toward more cesarean sections in women treated with metformin (47).

  • A 1998 narrative review noted that the risks of major congenital malformations and fetal macrosomia were inversely related to glycemic control (48).

Rationale
  • There is an association between elevated maternal glucose or glycohemoglobin levels and high rates of pregnancy loss, major congenital malformations, and fetal macrosomia.

  • Reducing glycosylated hemoglobin levels may decrease complications.

Comments
  • Postprandial blood glucose levels are likely a better predictor of pregnancy outcome than preprandial measures of glycemic control (49).

Switch all women with pre-gestational diabetes to glyburide, metformin, or insulin before conception. 
  • Stop oral diabetic medication other than glyburide or metformin 3 months before conception.

  • Switch women with poor glycemic control to insulin in order to rapidly control glucose levels.

  • See table Drug Treatment for Diabetes in Pregnancy.

Evidence
  • A guideline from the Endocrine Society on diabetes and pregnancy recommended that pregnant women with diabetes who do not meet glycemic targets with diet alone be treated with either glyburide or insulin (if fasting blood glucose >110 mg/dL), reserving metformin as a second-line agent (13).

  • A meta-analysis of six trials comparing either metformin or glyburide to insulin therapy found no difference between oral agents and insulin in either glycemic control or pregnancy outcomes (14).

  • A 2007 meta-analysis of the association between congenital abnormalities and pre-pregnancy glycemic control included seven cohort studies. For each 1-SD unit increase in glycated hemoglobin, the associated risk of a congenital malformation increased by an OR of 1.2 (CI, 1.1 to 1.4) (46).

  • In an open-label, randomized clinical trial of metformin versus insulin, no difference in fetal macrosomia or other fetal morbidity was observed, but there was a trend toward more cesarean sections in women treated with metformin (47).

Rationale
  • Oral hypoglycemics do not allow for subtle and immediate adjustments in maternal glucose levels.

Stop ACE inhibitor therapy and review the patient's other medications before conception. 
  • Do the following before conception:

    • Stop all ACE inhibitors and angiotensin-receptor blockers

    • Treat hypertension with other agents, most commonly nifedipine or methyldopa

    • Stop cholesterol-lowering drugs

    • Stop aspirin therapy

    • Review other medications and stop potential teratogens

    • Avoid use of antioxidants for prevention of preeclampsia

  • See table Drugs to Avoid in Pregnancy.

  • See module Hypertension in Pregnancy.

Evidence
  • The 2014 Standards of Medical Care in Diabetes from the American Diabetes Association recommended stopping potentially toxic medications such as ACE inhibitors, angiotensin-receptor blockers, statins, and some oral medication for diabetes. The guideline recommended that pregnant women with diabetes achieve an HbA1c <7% (1).

  • A 2013 guideline from the Endocrine Society on diabetes and pregnancy recommended that women with diabetes taking an ACE inhibitor or angiotensin-receptor blocker stop those medications before conception if possible (13).

  • A 2010 NICE guideline on the management of hypertensive disorders in pregnancy recommended antihypertensive medication for patients with gestational hypertension and BP ≥150/100 mm Hg. The guideline recommended oral labetolol as the first-line agent with a goal systolic blood pressure of <150 mm Hg and diastolic blood pressure of 80 to 100 mm Hg.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended antihypertensive medication for patients with chronic hypertension and systolic BP ≥160/100 mm Hg or diastolic BP ≥105 mm Hg, with a goal systolic blood pressure of 120 to 160 mm Hg and diastolic blood pressure of 80 to 105 mm Hg. The guideline recommended labetolol, nifedipine, and methyldopa as first-line agents.

  • A 2012 systematic review of pregnancy outcomes after exposure to ACE inhibitors and angiotensin-receptor blockers included 72 studies. Overall, 48% of newborns exposed to ACE inhibitors and 87% exposed to angiotensin-receptor blockers had complications (P<0.0001), including death, respiratory distress syndrome, renal failure, limb defects, cerebral complications, oligohydramnios, and intrauterine growth retardation (17).

  • In a surveillance study of lovastatin exposures during pregnancy, the overall rate of normal outcomes was 85%, and the following rates of occurrence were found: congenital anomalies, 4%; spontaneous abortions, 8%; and fetal deaths or stillbirths, 1% (18).

  • In one case-controlled study, 3 of 14 newborns exposed to aspirin within 1 week of delivery had minor hemorrhaging compared with 1 of 17 controls (19). In two retrospective studies, mothers of 1291 malformed infants were found to have consumed aspirin during pregnancy more frequently than mothers of normal infants (20; 21).

  • In a randomized, controlled trial of 762 women with type 1 diabetes mellitus randomly allocated to 1000 mg vitamin C and 400 IU vitamin E (alpha-tocopherol) or placebo, rates of preeclampsia did not differ between vitamin (15%, n=57) and placebo (19%, n=70) groups (RR, 0.81 [CI, 0.59 to 1.12]). No adverse maternal or neonatal outcomes were reported (50).

Rationale
  • ACE inhibitors and angiotensin-receptor blockers have been associated with fetal malformations.

  • No adverse maternal effects are likely to occur with a 9-month hiatus from cholesterol-lowering agents, and because HMG-CoA reductase inhibitors have been implicated as possible teratogens, the risks of their use outweigh the benefits to the mother.

  • Daily aspirin therapy may lead to maternal and newborn hemorrhage, increased perinatal mortality, intrauterine growth retardation, and teratogenic effects.

Comments
  • Many diabetic women are on a variety of medications; therefore, pre-conception planning should include a review of all drugs and their potential for teratogenesis.

Recommend smoking cessation in all women with diabetic pregnancies. 
  • Stress the importance of smoking cessation at each visit in diabetic women who are pregnant or planning pregnancies.

  • See module Smoking Cessation.

Evidence
  • The 2014 Standards of Medical Care in Diabetes from the American Diabetes Association recommended advising all patients with diabetes not to smoke (1).

  • Epidemiologic evidence suggests that smoking and type 2 diabetes synergistically increase risk of macrovascular disease (51; 52).

Rationale
  • Cigarette smoking increases the risk of diabetic complications and may result in intrauterine growth retardation.

Comments
  • These data are derived from studies of nonpregnant patients.

Continue foot care in women with pre-gestational diabetes. 
  • Stress the importance of continuing daily foot inspection, proper foot coverings, and toenail care in women with pre-gestational diabetes.

Evidence
  • A randomized, controlled trial has shown that patient education and increased surveillance results in decreased serious foot lesions (53).

  • Cohort data suggest a similar relationship between surveillance, education, and a lower risk of foot lesions (54).

  • A 2004 American Diabetes Association guideline discussed preventive foot care in patients with diabetes (55).

Rationale
  • Foot care may reduce the complications of diabetic foot ulcers in patients with diabetes.

Comments
  • These data are derived from studies of non-pregnant patients.

Instruct all diabetic women of childbearing potential on the need for pre-conception planning. 
  • Ensure effective birth control at all times unless the patient is trying to conceive and is in good diabetic control.

  • Counsel women with type 1 or type 2 diabetes on the risks of fetal malformation associated with unplanned pregnancies and poor metabolic control.

  • Plan the pregnancies of diabetic women to achieve fasting whole-blood glucose levels of 70 to 100 mg/dL and 2-hour postprandial levels of <140 mg/dL at least 8 to 12 weeks before conception.

  • Arrange for a certified diabetic educator instruction on diabetes self-management.

Evidence
  • In a meta-analysis of 14 cohort studies, the pooled rates of major and minor fetal anomalies were lower in diabetic women who had received pre-conception care (2.1%) compared with those who had not (6.5%; RR, 0.36 [CI, 0.22 to 0.59]) (2).

  • Population-based cohort studies have found an association between adverse fetal outcomes and maternal hyperglycemia (3; 4; 5).

Rationale
  • There is an association between elevated maternal glucose or glycohemoglobin levels during embryogenesis and high rates of pregnancy loss and major congenital malformations.

Comments
  • Pre-conception counseling should include advice on folic acid intake, vaccinations for rubella and varicella, weight control, and a review of current diseases and medications in addition to an assessment of diabetes management.

Stress the importance of diet and exercise to control glucose levels in pregnant diabetic patients. 
  • Provide nutritional counseling consistent with the American Diabetes Association recommendations.

  • Consider recommending to pregnant diabetic patients:

    • A 30% to 33% calorie restriction in pregnant women with diabetes and a BMI >30

    • Limiting carbohydrate intake to 35% to 40% of calories

    • A program of moderate exercise

Evidence
  • A small randomized, controlled trial of obese women with gestational diabetes showed a reduction in 24-hour mean glucose levels from 121 mg/dL to 97.3 mg/dL in women assigned to a diet of 1200 calories per day as compared with women on 2400 calories per day; however, maternal ketonuria of unknown clinical significance was also seen (38; 39).

  • In a controlled trial, calorie restriction of 33% and 50% in obese women with gestational diabetes decreased maternal glucose levels by 10% to 20% and reduced triglyceride levels when compared with insulin therapy (40).

  • In a 12-week controlled trial of obese pregnant women, half of whom had previous gestational diabetes, all of the women had higher triglycerides while on a 55% carbohydrate diet than while on a 40% carbohydrate diet and comparable weight loss (41).

  • A small randomized, controlled trial demonstrated increased cardiac fitness in women with gestational diabetes who exercised 30 minutes, 3 to 4 days per week, and achieved 70% of estimated maximal heart rate. No complications were seen (42).

  • A small randomized, controlled trial showed reduced glucose levels in women with gestational diabetes who performed upper-extremity aerobic exercise (43).

  • Two small randomized studies have shown a decreased need for insulin in overweight women with gestational diabetes assigned to resistance exercise (44; 56).

  • Two cohort studies have prospectively examined the role of exposure to diabetes in utero on childhood growth, later obesity, and risk for type 2 diabetes in the offspring: the Pima Indian Study (57) and the Diabetes in Pregnancy Study at Northwestern University in Chicago (58).

  • The excess growth experienced by offspring of diabetic mothers is not due to genetic factors alone but is also the direct consequence of exposure to maternal altered intrauterine environment as shown in a study of 58 siblings (59). In another study of 150 HNF-1-α gene mutation carriers in utero, maternal diabetes resulted in diagnoses of diabetes in the carriers at a younger age (60).

  • In utero exposure to diabetes confers risks for the development of cardiovascular disease later in life that are independent of adiposity and may be in addition to genetic predisposition to diabetes as shown in a study comparing 61 children born to diabetic mothers as compared with 57 control children of nondiabetic mothers (61), and in a study of 42 Pima Indian children born to diabetic mothers in whom most had higher levels of hemoglobin A1c and systolic blood pressure and lower levels of high-density lipoprotein independent of age, gender, or percent body fat (62).

Rationale
  • Calorie restriction may reduce hyperglycemia in obese diabetic pregnant patients.

  • Carbohydrate restriction may decrease maternal glucose levels and improve maternal and fetal outcomes in diabetic pregnant patients.

  • Moderate exercise may reduce glucose levels in diabetic pregnant patients.

  • Maternal hyperglycemia is associated with fetal malformations and macrosomia.

Comments
  • Little data exist concerning women with pre-gestational diabetes and diet or exercise. Consensus opinion on patients with diabetes mellitus stresses the importance of diet and exercise for weight and glycemic control.

Continue preventive foot care in women with pre-gestational diabetes. 
  • Stress the importance of continuing daily foot inspection, proper foot coverings, and toenail care in women with pre-gestational diabetes.

Evidence
  • There is consensus opinion in the American Diabetes Association guidelines on preventive foot care (55).

Rationale
  • Foot care may reduce the complications of diabetic foot ulcer in patients with diabetes.

Recommend smoking cessation in all women with diabetic pregnancies. 
  • Urge smoking cessation at each visit in diabetic women who are pregnant or planning pregnancy.

  • See module Smoking Cessation.

Evidence
Rationale
  • Cigarette smoking increases the risk of diabetic complications and may result in intrauterine growth retardation.

Teach patients and family members to recognize hypoglycemia and to treat it appropriately. 
  • Teach patients and family members to recognize the signs and symptoms of hypoglycemia and about its treatment.

Evidence
  • Consensus.

Rationale
  • Intensive diabetic control during pregnancy and the pre-conception period increases the risk of maternal hypoglycemia.

Counsel patients on the need for an ophthalmology exam before conception or in early pregnancy.  
  • Obtain a dilated retinal exam before pregnancy.

Evidence
  • In a prospective study to determine the effects of pregnancy on diabetic retinopathy, pregnancy was associated with progression after adjustment for glycosylated hemoglobin measurements (P<0.005; adjusted OR, 2.3) (27).

Rationale
  • Retinopathy may worsen during pregnancy.

Review blood glucose logs at every visit and adjust insulin accordingly. 
  • Encourage pregnant diabetic women to check glucose levels fasting and 2 hours after every meal, and to record the levels with time of day, food intake, activity, and insulin doses given.

  • Adjust insulin to achieve fasting whole blood glucose levels of 70 to 100 mg/dL and 2-hour postprandial levels of <140 mg/dL.

  • Inform women about the signs and symptoms of hypoglycemia and develop an action plan to treat it acutely.

  • Monitor hemoglobin A1c levels every 2 to 3 months and aim for normal levels.

  • Continue frequent, daily blood glucose testing after delivery.

Evidence
  • Population-based cohort studies have found an association between adverse fetal outcomes and maternal hyperglycemia (3; 4; 5).

  • Case series have reported decreased insulin requirement after delivery in women with pre-gestational diabetes (63).

Rationale
  • Hyperglycemia during pregnancy is associated with fetal malformations and fetal macrosomia.

  • Hypoglycemia is a frequent complication of tight glucose control.

  • In the postpartum period, altered schedules, lactation, and changing physiology may change a woman's insulin requirements.

Review diabetes drugs after delivery and make changes as necessary. 
  • Adjust insulin in patients with type 1 pre-gestational diabetes postdelivery according to multiple, daily blood glucose testing to maintain hemoglobin A1c at <7%.

  • Stop insulin in women with gestational diabetes after delivery and monitor glucose levels.

  • Consider the reinstitution of oral diabetes medication in women with type 2 pre-gestational diabetes postdelivery.

Evidence
  • Case series have reported decreased insulin requirement after delivery in women with pre-gestational diabetes (63).

  • There is limited evidence available outlining the risks and benefits to the breast-feeding infant when the mother is taking oral hypoglycemic agents (64).

Rationale
  • In the postpartum period, altered schedules, lactation, and changing physiology may change a woman's insulin requirements.

  • Gestational diabetes is generally a transient state, and insulin resistance decreases immediately postpartum.

  • Women on oral agents before pregnancy can usually restart them after delivery.

Comments
  • The effect of oral diabetes drugs on breast-feeding infants is largely unknown. The issue should be addressed in conjunction with the infant's primary care provider.

  • The term ‘gestational diabetes' covers a wide array of physiologic syndromes, including types 1 and 2 diabetes first detected during pregnancy and pregnancy-related insulin resistance. Therefore, postpartum diabetes care should be individualized.

Screen women with pre-gestational diabetes for the development or worsening of diabetic complications during pregnancy. 
  • Refer patients with pre-gestational diabetes for a dilated retinal exam early in pregnancy and postpartum.

  • Measure blood pressure and screen for proteinuria at each prenatal and postpartum visit.

  • Ask about symptoms of neuropathy at each prenatal and postpartum visit.

  • Screen women with type 1 diabetes for thyroid disease postpartum.

Evidence
  • In a prospective study to determine the effects of pregnancy on diabetic retinopathy, pregnancy was associated with progression after adjustment for glycosylated hemoglobin measurements (P<0.005; adjusted OR, 2.3) (27).

  • In a study of 31 continuous diabetic pregnancies of women with pre-gestational diabetes, 71% developed nephrotic range proteinuria. In all of these patients, proteinuria reverted to previous levels after delivery (26).

  • In a case study of 311 diabetic pregnant women with proteinuria, 31% to 58% developed preeclampsia. The increased risk persisted after controlling for parity, chronic hypertension, retinopathy, and glycemic control (30).

  • In a small, prospective study of women with type 1 diabetes, the incidence of postpartum thyroid disease was 25%, which is three times higher than a similar nondiabetic population (65).

Rationale
  • Retinopathy and severe nephropathy may worsen during pregnancy.

  • Hypertensive disorders frequently complicate diabetic pregnancies.

  • Patients with neuropathy need increased counseling on the importance of foot care.

  • There is a 5% to 10% coincidence of hyperthyroidism or hypothyroidism and type 1 diabetes.

Plan future pregnancies postpartum. 
  • Recommend birth control immediately postpartum.

  • Stress the importance of pre-conception counseling.

Evidence
  • In a meta-analysis of 14 cohort studies, the pooled rates of major and minor fetal anomalies were lower in diabetic women who had received pre-conception care (2.1%) compared with those who had not (6.5%; RR, 0.36 [CI, 0.22 to 0.59]) (2).

Rationale
  • Pregnancies in women with diabetes have more favorable outcomes if they are planned.

After delivery, classify patients found to be diabetic during pregnancy and arrange for long-term follow-up. 
  • Continue home glucose monitoring in women found to be diabetic during pregnancy at least 6 weeks postpartum to determine if they have underlying type 1 or 2 diabetes or if their hyperglycemia resolves.

  • Counsel patients with transient gestational diabetes on the long-term need for diabetes screening.

  • Recommend nutrition and exercise consistent with American Diabetes Association guidelines to patients with transient hyperglycemia of pregnancy after delivery.

  • Encourage breast feeding.

Evidence
  • In a systematic review of the literature, the cumulative incidence of diabetes ranged from 2.6% to >70% in studies that examined women 6 weeks postpartum to 28 years postpartum (66).

  • Professional consensus exists within the American College of Obstetricians and Gynecologists that discharge planning should include a 75-gram oral glucose tolerance test at 6 weeks postpartum with cutoffs of 100 mg/dL fasting for impaired fasting glucose, 140 mg/dL for impaired glucose tolerance, and 126 mg/dL fasting and 200 mg/dL for overt diabetes (67).

  • The American Academy of Pediatrics recommends that all infants be exclusively breast-fed for the first 6 months of life, and breast-feeding should continue, complemented by solids, until at least 1 year of age and beyond for as long as mutually desired by mother and child; review maternal medications and their compatibility with breast-feeding (68).

Rationale
  • Women may be diagnosed with diabetes during pregnancy, which may be a self-limited condition or may indicate chronic diabetes mellitus.

  • A history of gestational diabetes increases the likelihood of developing type 2 diabetes mellitus.

Table Grahic Jump Location
 Laboratory and Other Studies for Diabetes in Pregnancy

Swipe to view table

TestSensitivity (%)Specificity (%)Notes
Fasting plasma glucose95.4% for fasting plasma glucose ≥79 mg/dl100% for fasting plasma glucose ≥92 mg/dl69
Serum glucoseLevels should be checked with the first antepartum labs in women at high risk or in a patient with symptoms of hyperglycemia.
Patients with pre-gestational diabetes ideally should be doing frequent fingerstick glucose levels before and during pregnancy
Hemoglobin A1c in pre-gestational diabetic pregnanciesIdeally <1% above normal before conception for pre-gestational diabetic pregnancies.
24-hour urinary excretion of total protein in pre-gestational diabetic pregnanciesPatients with protein excretion of >190 mg per 24 hours are at risk for hypertensive disorders during pregnancy.
Serum TSH in pregnancies of type 1 diabeticsAn increased prevalence of subclinical hypothyroidism has been reported in pregnant diabetic patients (32) and may be associated with poor pregnancy outcomes (70).
Glucose tolerance testing71-8378-87Generally recommended to diagnose gestational diabetes, though guidelines remain inconsistent.
See table Glucose Thresholds for Diagnosis of Gestational Diabetes Mellitus
ECG before conceptionA 50-year series of diabetic patients showed increased maternal mortality in those women with ischemic heart disease in the perinatal period (28)

ECG = electrocardiogram; TSH = thyroid-stimulating hormone.

Table Grahic Jump Location
 Drug Treatment for Diabetes in Pregnancy

Swipe to view table

Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
blackboxiconMetformin (Glucophage)Regular-release: 500 mg qd, up to 2000 mg total daily dose, dosed bid-tidGI side effects, diarrheablackboxicon Rare lactic acidosis. Avoid with: CKD (SCr >1.4 in women or >1.5 in men), HF, hepatic disease
Glyburide (Diabeta)1.25-20 mg total daily dose, dosed qd or bid. Start at 2.5 mg qdHypoglycemia, weight gainAvoid if CrCl<50. Caution with hepatic disease
Insulin/Insulin analogsSC injection. Individualize dosingHypoglycemia, hypokalemia, weight gainCaution in CKD or hepatic diseaseTarget fasting glucose of 70-100 mg/dL and 2-hour postprandial level of <140 mg/dL

blackboxicon = black box warning; bid = twice daily; CKD = chronic kidney disease; CNS = central nervous system; CrCl = creatinine clearance; GI = gastrointestinal; IM = intramuscular; IV = intravenous; PO = oral; q12hr = every 12 hours; qd = once daily; qid = four times daily; SC = subcutaneous; SCr = serum creatinine; tid = three times daily

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

Table Grahic Jump Location
 Glucose Thresholds for Diagnosis of Gestational Diabetes Mellitus

Swipe to view table

Time75 Gram Oral Glucose Load1100 Gram Oral Glucose Load2
Plasma Concentration (mg/dl)Plasma Concentration (µmol/L)Plasma Concentration (mg/dl)Plasma Concentration (µmol/L)
Fasting925.1955.3
1 hour18010.018010.0
2 hour1538.51558.6
3 hourNANA1407.8

1Only one venous plasma concentration must be met for a positive diagnosis.

2Two or more of the venous plasma concentrations must be met or exceeded for a positive diagnosis.

The test should be done in the morning after an overnight fast of between 8 and 14 hours after at least 3 days of unrestricted diet (>150 g carbohydrate per day) and unlimited physical activity. If the fasting state represents a barrier to appropriate screening, a 50-gram oral glucose tolerance test with a blood glucose level of 140 mg/dL at 1 hour as a cutoff may still be alternately used as a screening test, if a fasting confirmatory test can be performed later (67).

Table Grahic Jump Location
 Drugs to Avoid in Pregnancy

Swipe to view table

AgentMechanism of ActionDosageBenefitsSide EffectsNotes
ACE inhibitorBlocks the conversion of angiotensin I to angiotensin IIVariable
5-40 mg/d
Do not use in pregnancyFetal teratogenScreen for ACE inhibitor use in pregestational diabetic patients and stop before conception
Angiotensin-receptor blockerBlocks angiotensin II receptor sitesVariable
25-100 mg/d
Do not use in pregnancyFetal teratogenScreen for angiotensin-receptor blocker use in pregestational diabetic patients and stop before conception
AspirinCyclo-oxygenase inhibitor81-325 mg/dDo not use in pregnancyMaternal and newborn hemorrhage, increased perinatal mortality, intrauterine growth retardation, and teratogenic effectsIn one case-controlled study, 3 of 14 newborns exposed to aspirin within 1 week of delivery had minor hemorrhaging compared with 1 of 17 controls (19).
In two retrospective studies, mothers of 1291 malformed infants were found to have consumed aspirin during pregnancy more frequently than mothers of normal infants (20; 21)
HMG-CoA reductase inhibitorsDecreases synthesis of cholesterol in the liverVariableDo not use in pregnancyPossible teratogenIn a surveillance study of lovastatin exposures during pregnancy, normal outcomes were 85%, congenital anomalies 4.0%, spontaneous abortions 8.0%, and fetal deaths/stillbirths 1.0% (18)

ACE = angiotensin-converting enzyme; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A.

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ACEangiotensin-converting enzyme
BMIbody mass index
CIconfidence interval
ECGelectrocardiogram
HMG-CoA3-hydroxy-3-methylglutaryl coenzyme A
HNFhepatocyte nuclear factor
ORodds ratio
RRrisk ratio
SDstandard deviation
TSHthyroid-stimulating hormone

Guidelines

Diabetes and pregnancy: an endocrine society clinical practice guideline.

Hypertension in Pregnancy

Hypertension in Pregnancy

Screening for Gestational Diabetes Mellitus

Executive summary: standards of medical care in diabetes--2014.

Screening for gestational diabetes mellitus: a systematic review for the U.S. Preventive Services Task Force

Management of diabetes from preconception to the postnatal period: summary of NICE guidance

Managing preexisting diabetes for pregnancy: summary of evidence and consensus recommendations for care

Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications

Gestational diabetes mellitus

Screening and diagnosis of gestational diabetes mellitus (committee opinion)

Systematic Reviews

Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review.

Intensive Insulin Therapy in Hospitalized Patients: A Systematic Review

Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis.

Induction of labour for suspected fetal macrosomia (Cochrane Review)

Treatments for gestational diabetes (Cochrane Review)

Elective delivery in diabetic pregnant women (Cochrane Review)

Dietary advice in pregnancy for preventing gestational diabetes mellitus (Cochrane Review)

Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis

Preconception care: a systematic review

DOI: 10.7326/d942
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
Disclosures:
Elisha L. Brownfield, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Justin B. Moore, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations.
Deborah Korenstein, MD, FACP, Editor in Chief, ACP Smart Medicine, has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. Richard B. Lynn, MD, FACP, Editor, ACP Smart Medicine, has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.
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