Guidelines Issued for Medical Care of Pregnant Women With Preexisting Diabetes

The American Diabetes Association (ADA) has issued consensus panel recommendations for the medical care of pregnant women with preexisting diabetes, including type 1 and type 2 diabetes. The new recommendations appear in the May issue of Diabetes Care. Subsequent guidelines will address obstetric and postpartum management.

“The intent is to help clinicians deal with the broad spectrum of problems that arise in management of diabetes before and during pregnancy, and to prepare diabetic women for treatment that may reduce complications in the years after pregnancy,” write Jennifer M. Block, BS, RN, CDE, from the Santa Clara Valley Medical Center, San Jose, California, and colleagues. “The recommendations are diagnostic and therapeutic actions that are known or believed to favorably affect maternal and perinatal outcomes in pregnancies complicated by diabetes.”

The evidence supporting these recommendations is reviewed in the book, Management of Preexisting Diabetes and Pregnancy, authored by the consensus panel and published in 2008 by the ADA. Because few randomized controlled trials (RCTs) have studied the management of diabetes and pregnancy, these recommendations are often based on RCTs in nonpregnant diabetic women or nondiabetic pregnant women as well as on peer-reviewed experience before and during pregnancy in women with preexisting diabetes.

The guidelines authors used the grading system adapted by the ADA to rate the underlying evidence, and they also reviewed and adapted existing diabetes and pregnancy guidelines and guidelines on diabetes complications and comorbidities.

Recommendations regarding management of preexisting diabetes for pregnancy address organization of preconception and pregnancy care, specifically initial evaluation and review of patient history and physical examination.

Other aspects of management of preexisting diabetes addressed in these guidelines include glycemic control in perinatal outcome and glycemic goals as well as evaluation of metabolic control, medical nutrition therapy, insulin therapy, use of oral antihyperglycemic agents for type 2 diabetes, physical activity and exercise, and behavioral therapy.

The second half of these guidelines focuses on managing complications of diabetes. Metabolic disturbances include diabetic ketoacidosis (DKA), maternal hypoglycemia, and thyroid disorders. Management of cardiovascular (CV) risk factors includes screening for cardiovascular disease (CVD), management of hypertension, and treatment of dyslipidemia.

Other complications of diabetes addressed in these guidelines include management of diabetic nephropathy, diabetic retinopathy, and diabetic neuropathies.

Highlights of some of the specific clinical recommendations include the following:

* Before pregnancy, women with diabetes and childbearing potential should be educated about the need for good glycemic control and should participate in effective family planning.
* Multidisciplinary, patient-centered team care, with regular follow-up visits, is helpful whenever feasible: before, during, and after pregnancy.
* Women with preexisting diabetes contemplating pregnancy should be evaluated and treated for diabetic nephropathy, neuropathy, retinopathy, CVD, hypertension, dyslipidemia, depression, and thyroid disease.
* Before conception, medication use should be evaluated because drugs often used to treat diabetes and its complications may be contraindicated or problematic in pregnancy. These include statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and most noninsulin therapies.
* As soon as possible before conception, or early in pregnancy, complete medical evaluation should detect diabetic, CV, thyroid, or obstetric complications; review history of eating patterns, physical activity or exercise, and psychosocial problems; counsel the patient on prognosis and set goals for patient participation; formulate a management plan with team care members; and plan for continuing care and laboratory testing.
* Effective contraception is recommended until stable, acceptable glycemia is achieved (E).
* To prevent excess spontaneous abortions and major congenital malformations, target hemoglobin A1c before pregnancy should be as close to normoglycemia as possible without significant hypoglycemia. The same goal is recommended throughout pregnancy to minimize maternal, fetal, and neonatal complications.
* Optimal glycemic goals throughout pregnancy are premeal, bedtime, and overnight blood glucose 60 to 99 mg/dL, peak postprandial blood glucose of 100 to 129 mg/dL, mean daily blood glucose level of less than 110 mg/dL, and hemoglobin A1clevels of less than 6.0%.
* Provision of basal and prandial insulin needs with intensified insulin regimens (multiple dose regimens of subcutaneous long-acting and short-acting insulins or continuous subcutaneous insulin infusion [CSII]) usually achieves the best results.
* Women taking the insulins detemir or glargine should be transitioned to NPH insulin 2 or 3 times daily, preferably before pregnancy.
* Because of the heightened risks for ketosis in pregnancy, patients using CSII should be well trained in detecting and treating unexplained hyperglycemia from insulin underdelivery resulting from pump or infusion site problems.
* Before conception, oral hypoglycemic agents should be stopped and insulin started and titrated to achieve acceptable glycemic control.
* Metformin, thiazolidinediones, meglitinide inhibitors, and incretin should be used during pregnancy only in the setting of approved clinical trials.
* Pregnant women with preexisting diabetes should be screened for depression, anxiety or stress, and disordered eating, and the team management plan should be adjusted as indicated.
* Protocols to manage DKA during pregnancy include correcting volume depletion, insulin infusion, monitoring and correcting electrolyte imbalances, detecting and treating precipitating factors, and continuous fetal monitoring. Initial DKA care should be provided in intensive or special care units with experience in high-risk pregnancy monitoring.

“Pregnancy profoundly affects the management of diabetes,” the guidelines authors conclude. “Clinicians can take advantage of the heightened motivation of pregnant diabetic women to teach behaviors and self-management skills that are expected to control CVD risk factors. For optimal long-term outcomes, we need to find ways to foster seamless continuation of intensified management in the years after pregnancy and in preparation for the next desired conception.”

Some of the guidelines authors have disclosed various financial relationships with Harvard, the National Institutes of Health, Abbott, Lilly, Lifescan, Medtronic, Pfizer, Novartis, NovoNordisk, Hemacue, Roche, sanofi-aventis, AstraZeneca, Takeda, and Bioniche Pharmaceuticals. The remaining study authors have disclosed no relevant financial relationships.

Diabetes Care. 2008;31:1060-1079.
Clinical Context

There is a paucity of RCTs of different aspects of management of diabetes and its complications during pregnancy. This review represents evidence based on women without diabetes, women before pregnancy, or peer-reviewed experience before and during pregnancy in women with diabetes. These 2008 ADA guidelines cover the management of preexisting diabetes and diabetic complications during pregnancy, and a consensus statement on obstetric and postpartum management follows.
Study Highlights

* Management of preexisting diabetes for pregnancy
o Multidisciplinary team care with discontinuation of drugs contraindicated during pregnancy is recommended before conception.
o Women should be educated on importance of long-term CV protection and glycemic control.
o Optimal glycemic control goals are premeal, bedtime, and overnight glucose levels of 60 to 99 mg/dL, peak postprandial glucose levels of 100 to 129 mg/dL, mean daily glucose levels less than 110 mg/dL, and hemoglobin A1c less than 6.0% to minimize maternal, fetal, and neonatal complications.
o Higher glucose targets may be used for women with hypoglycemia unawareness.
o Macrosomia occurs in up to two thirds of infants of mothers with diabetes, and midtrimester glucose level is the best predictor; too tight glucose control (< 80 – 90 mg/dL) is linked with fetal growth restriction. o Fetal hyperglycemia causes hypoxia and acidosis, which contributes to stillbirth. o Self-monitoring of glucose levels with fingerprick is optimal, with continuous monitoring a benefit in type 1 diabetes. o Urine ketone testing during illness or when glucose is above 300 mg/dL should be taught. o Target gestational weight gain should be lower than Institute of Medicine recommendations to prevent excess weight gain, and carbohydrate intake and timing of meals monitored. o Folate intake should be 600 µg daily. o Oral hypoglycemics should be stopped and insulin started and titrated. o Basal and prandial insulin needs should be supplemented with intensified insulin regimens, and detemir or glargine insulin should be substituted with NPH insulin 2 or 3 times daily. o Psychological management includes depression screening with appropriate treatment for major depressive disorder. * Management of diabetic complications o Clinicians should have a high index of suspicion for DKA in pregnant diabetic women with vomiting, nausea, and abdominal pain. o Women should be advised of the increased risk for severe hypoglycemia during early pregnancy and glucose targets raised for hypoglycemia unawareness. o Screening should be conducted for thyroid dysfunction with thyroid-stimulating hormone levels and thyroid peroxidase antibodies in all women with diabetes before or during early pregnancy, as autoimmune thyroid disease is common (35% – 40%). o Evaluation for CV risk is best performed before pregnancy, with screening for smoking, hypertension, dyslipidemia, albuminuria, and family history. o Blood pressure (BP) should be treated to less than 130 mm Hg systolic and less than 80 mm Hg diastolic in preconception period. o In addition to lifestyle changes, women with BP more than 140/90 mm Hg should be considered for pharmacotherapy-safe drugs during pregnancy: methyldopa, long-acting calcium channel blockers, and selected beta-adrenergic blockers. o ACE inhibitors and ARBs are contraindicated. o Low-density lipoprotein (LDL) cholesterol level should be less than 100 mg/dL in women without CVD and less than 70 mg/dL in women with CVD. o Cholesterol-lowering drugs except bile-acid–binding resins are unapproved for use in pregnancy. o Albuminuria and glomerular filtration rate should be assessed and dietary guidance to restrict protein intake provided by dieticians. o Dilated eye examination should be conducted in the first trimester. o Laser photocoagulation is indicated to prevent vision loss in those at high risk for proliferative retinopathy. o Women should be screened for symmetric distal polyneuropathy. Pearls for Practice * The ADA 2008 guidelines emphasize optimal glycemic control and screening for CVD and depression in the preconception and prenatal period. * Monitoring for diabetic complications during pregnancy should include screening for nephropathy, thyroid dysfunction, retinopathy, CVD, dyslipidemia, and hypertension.

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