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Pregestational (preexisting) diabetes mellitus: Obstetric issues and management

Pregestational (preexisting) diabetes mellitus: Obstetric issues and management
Literature review current through: Jan 2024.
This topic last updated: Sep 16, 2022.

INTRODUCTION — The maternal and fetal prognosis in pregnancies affected by pregestational (also called preexisting) diabetes has improved dramatically over the past century with the availability of insulin and the implementation of intensive glycemic control. The key elements in management of these pregnancies are:

Achieving and maintaining excellent glycemic control while avoiding hypoglycemia and diabetic ketoacidosis.

Screening, monitoring, and intervention for maternal medical complications and comorbidities (eg, retinopathy, nephropathy, hypertension, cardiovascular disease, thyroid disease), as well as obstetric complications (eg, nausea and vomiting of pregnancy, preeclampsia, preterm birth).

Screening and monitoring for fetal complications (eg, congenital anomalies, macrosomia, polyhydramnios, stillbirth) and anticipation of neonatal complications (eg, respiratory morbidity, birth trauma, neonatal hypoglycemia), with timely intervention to minimize adverse outcomes, when possible.

Most issues related to the obstetric management of pregnant patients with diabetes (type 1 or type 2) will be reviewed here. The obstetric management is largely based on clinical experience, data from observational studies, and expert opinion; there is limited evidence from randomized trials.

Four important additional issues are discussed in detail separately: preconception evaluation/counseling, antenatal glycemic management, intrapartum and postpartum glycemic management, and neonatal issues:

(See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

(See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control".)

(See "Pregestational (preexisting) and gestational diabetes: Intrapartum and postpartum glucose management".)

(See "Diabetic ketoacidosis in pregnancy".)

(See "Infants of mothers with diabetes (IMD)".)

Gestational diabetes is also discussed separately:

(See "Gestational diabetes mellitus: Screening, diagnosis, and prevention".)

(See "Gestational diabetes mellitus: Glucose management and maternal prognosis".)

(See "Gestational diabetes mellitus: Obstetric issues and management".)

CLASSIFICATION OF DIABETES IN PREGNANCY — The following classification system for diabetes in pregnancy is based on the mechanism of disease and correlates with pregnancy outcome [1]:

Type 1 diabetes (autoimmune beta cell destruction, usually leading to absolute insulin deficiency):

a. Without vascular complications

b. With vascular complications (eg, nephropathy, retinopathy, hypertension, atherosclerotic cardiovascular disease, etc)

Type 2 diabetes (progressive loss of insulin secretion, often in the setting of insulin resistance):

a. Without vascular complications

b. With vascular complications (eg, nephropathy, retinopathy, hypertension, atherosclerotic cardiovascular disease, etc)

Gestational diabetes (diabetes diagnosed during pregnancy and not clearly overt [eg, type 1 or type 2 diabetes])

Other diabetes (eg, genetic origin, drug- or chemical-induced)

This topic focuses on type 1 and type 2 diabetes; principles of management generally also apply to other forms of pregestational diabetes.

Traditionally, the severity of pregestational diabetes was categorized according to the White classification (table 1) [2], which attempts to provide a standardized definition for describing pregnant individuals with diabetes and has some correlation with pregnancy outcome [3,4]. Because the White classes are not mutually exclusive, the presence/absence of vascular complications, as described above, is a better predictor of adverse outcome than the specific White class [5,6].

FIRST TRIMESTER — Ideally, patients with pregestational diabetes have received preconception counseling to address maternal and fetal risks during pregnancy, worked with their providers to optimize glycemic control, and undergone preconception screening for common comorbidities (eg, retinopathy, nephropathy, neuropathy, hypertension, cardiovascular disease, thyroid dysfunction), with management of any issues that were identified. However, many pregnancies are unplanned and many patients do not receive preconception care; thus, a prenatal visit may be the clinician's first opportunity to assess the patient's baseline medical status and provide counseling.

Issues that should be covered in preconception and routine initial prenatal care counseling are discussed separately. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management" and "Prenatal care: Initial assessment".)

Maternal issues

Glycemic management — In the first trimester, the clinician should emphasize the importance of meticulous glucose self-monitoring and attention to glycemic control throughout pregnancy to reduce the risks of adverse pregnancy outcomes. Information on diet, insulin therapy, glucose monitoring, and glucose targets should be provided by clinicians with experience in management of diabetes during pregnancy. A team approach is often recommended to provide the necessary expertise. In addition to the obstetric providers, the team may include an endocrinologist, certified diabetes educator, nutritionist, and/or the patient's primary care provider.

Self-monitored glucose levels are obtained fasting and one or two hours after the first bite of each meal. In individuals taking insulin (which includes most patients with preexisting diabetes), glucose levels should also be obtained prior to administering insulin (eg, before meals, at bedtime). Target levels are:

Fasting, preprandial, and nocturnal glucose 70 to 95 mg/dL (3.9 to 5.3 mmol/L) and

One-hour postprandial glucose 110 to 140 mg/dL (6.1 to 7.8 mmol/L) or

Two-hour postprandial glucose 100 to 120 mg/dL (5.6 to 6.7 mmol/L)

For patients using continuous glucose monitoring, the target glucose range is 63 to 140 mg/dL (3.5 to 7.8 mmol/L), and the time in range goal is >70 percent.

Patients with pregestational diabetes often have extra prenatal visits to review self-monitored glucose values, but virtual methods of communication can also be used for frequent exchange of information about glucose values and adjustments in insulin therapy [7]. Glycemic management during pregnancy is discussed in detail separately. (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control".)

Insulin is the preferred therapy. Metformin is an option for some patients. There are limited data for other commonly used noninsulin agents such as GLP-1 agonists, SGLT-2 inhibitors, and DPP-4 inhibitors, which should be avoided. An increased frequency of congenital malformation or other harmful effects on the human fetus has not been observed, but animal studies have reported increased occurrence of fetal damage. For example, in animals, SGLT-2 inhibitors have caused renal toxicity at developmental periods equivalent to the second and third trimesters in humans and GLP-1 agonists have caused vascular (heart, blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities at maternal exposures below the maximum recommended human dose. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management", section on 'Patients on preconception noninsulin antihyperglycemic agents'.)

Hypoglycemia — The first trimester is a high-risk time for hypoglycemia [8], particularly for patients with type 1 diabetes. The contributing factors likely include increased efforts to obtain tight glycemic control, nausea and vomiting of pregnancy, and pregnancy-mediated increase in insulin sensitivity [9,10]. Patients experiencing significant hypoglycemia can benefit from loosened glycemic targets to restore hypoglycemia awareness and prevent serious hypoglycemia. Acute episodes of hypoglycemia are managed using standard approaches, with the exception that asymptomatic glucose levels in the upper 60s can be tolerated. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management", section on 'Management of hypoglycemia'.)

Nausea and vomiting — Nausea and vomiting, which is common and bothersome in early pregnancy, can make insulin management challenging. For example:

Vomiting and/or less food intake than anticipated can lead to hypoglycemia and fear of hypoglycemia. Recurrent hypoglycemia and fear of hypoglycemia make it difficult to administer the necessary doses of insulin to control postprandial hyperglycemia. Treatment of hypoglycemia can also cause rebound hyperglycemia.

Nausea and food aversions may lead to greater consumption of carbohydrates, which may lead to hyperglycemia.

For these reasons, we have a low threshold for initiating pharmacotherapy for nausea and vomiting in pregnant patients with diabetes. (See "Nausea and vomiting of pregnancy: Treatment and outcome".)

Clinicians should also consider whether the nausea and vomiting may be manifestations of gastroparesis; metoclopramide is often used to treat these cases. (See "Treatment of gastroparesis", section on 'Metoclopramide'.)

Routine laboratory tests and evaluation for comorbidities — As part of, or in addition to, the routine prenatal laboratory tests and evaluation obtained in the general obstetric population (see "Prenatal care: Initial assessment", section on 'Laboratory tests'), pregnant patients with diabetes should have the evaluations listed in the table (table 2) and described below.

Glycated hemoglobin — A glycated hemoglobin concentration (A1C) is obtained at the initial prenatal visit. In the absence of significant red blood cell abnormalities, A1C reflects the patient's average level of glycemic management over the prior few weeks to months and thus assists in counseling about the risks of early pregnancy loss, congenital malformations, preeclampsia, and other complications. However, a glycemia-independent decline of A1C typically occurs during pregnancy [11], so the reliability of the A1C level to reflect early-pregnancy glycemia may depend on the gestational age at measurement. (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control", section on 'Glycated hemoglobin (A1C)' and "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

Some clinicians, including the authors, recheck A1C throughout gestation as an additional marker of glycemic control (beyond the primary method of blood glucose self-monitoring or continuous glucose monitoring), as A1C is strongly correlated with the risk of adverse pregnancy outcomes [12,13]. Due to alterations in red blood cell production and turnover during pregnancy, an A1C can be obtained as frequently as monthly [14]; our practice is to obtain an A1C every 6 to 10 weeks.

Assessment of renal function and urine protein excretion — Nephropathy is a cardinal microvascular complication of diabetes; small amounts of proteinuria (microalbuminuria) indicate glomerular damage and precede the development of a decline in glomerular filtration rate. Many patients with preexisting diabetes may have unrecognized subclinical glomerular damage; thus, a serum creatinine along with quantification of urinary proteinuria should be obtained at the first prenatal visit.

The authors prefer to obtain a 24-hour collection to assess both urine protein and creatinine; this allows for direct comparison with collections that may be obtained later in pregnancy for preeclampsia evaluation. However, the quantification of urine protein can be performed on a random urine sample using the urinary protein-to-creatinine ratio, which is both reproducible and more convenient for the patient than a 24-hour collection. (See "Proteinuria in pregnancy: Diagnosis, differential diagnosis, and management of nephrotic syndrome".)

Chronic kidney disease increases the risk of adverse maternal and fetal outcomes (table 3) and the risk increases as the glomerular filtration rate declines. Evaluation and management of patients with nephropathy and outcomes of these pregnancies are discussed separately. (See "Pregnancy and contraception in patients with nondialysis chronic kidney disease".)

Dilated, comprehensive eye examination — This retinal examination should be performed by an ophthalmologist. Close follow-up is indicated during pregnancy, with the frequency determined by baseline findings. The American Diabetes Association (ADA) suggests eye examinations prepregnancy, in all three trimesters, and for one year postpartum, as indicated by degree of retinopathy and as recommended by the eye care provider [14]. (See "Diabetic retinopathy: Prevention and treatment", section on 'Pregnancy'.)

Clinical assessment for atherosclerotic vascular disease — Diabetes is associated with an increased risk of atherosclerotic vascular disease. An electrocardiogram (ECG) is indicated in individuals starting at age 35 years who have cardiac signs/symptoms or risk factors and, if abnormal, further evaluation should be performed [14]. Referral to a cardiologist is appropriate for patients with cardiac symptoms, regardless of the ECG result.

An ECG can be considered in asymptomatic patients, particularly if not previously performed, though its value in those under age 40 without symptoms or other cardiovascular risk factors has not been established. (See "Screening for coronary heart disease in patients with diabetes mellitus".)

Clinical assessment for neuropathy and gastroparesis — The main symptoms of diabetic polyneuropathy are numbness, tingling, pain, and weakness, starting distally in the toes and feet; the symptoms are usually worse at night. Cranial and peripheral mononeuropathies can also occur. Gastroparesis is an autonomic neuropathy and may be confused with nausea and vomiting of pregnancy. Evaluation and management of these comorbidities are discussed separately.

(See "Epidemiology and classification of diabetic neuropathy" and "Management of diabetic neuropathy".)

(See "Diabetic autonomic neuropathy of the gastrointestinal tract", section on 'Gastroparesis' and "Treatment of gastroparesis".)

Blood pressure measurement/management — Chronic hypertension is a common comorbid condition in individuals with diabetes. In the absence of prepregnancy recent normal blood pressure measurements, hypertension prior to 20 weeks of gestation suggests chronic hypertension rather than a hypertensive disorder of pregnancy (eg, preeclampsia, gestational hypertension).

We suggest an upper blood pressure limit of <140/90 mmHg for pregnant patients with diabetes, based on data from the 2022 Chronic Hypertension and Pregnancy (CHAP) trial [15] and in agreement with guidelines from the American College of Obstetricians and Gynecologists (ACOG) [16]. Data supporting the lower blood pressure limit to minimize the risk of placental underperfusion and, in turn, concern for impaired fetal growth are less clear. We believe it is reasonable to target the lower limit of blood pressure to ≥110/80 mmHg based on current ADA and ACOG guidelines and we would avoid blood pressures <90/60 mmHg. The ADA suggests a blood pressure target of 110 to 135/85 mmHg [14].

High-quality evidence supporting specific blood pressure targets in pregnant patients with chronic hypertension and diabetes is limited.

The CHAP trial evaluated treatment of mild chronic hypertension during pregnancy (defined by blood pressure ≥140/90 mmHg before 20 weeks of gestation or on antihypertensive therapy with a single medication) [15]. The 2408 participants included 380 with diabetes (16 percent). Participants were randomly assigned to a blood pressure goal of <140/90 mmHg (active treatment group) or to usual care (control group) where antihypertensive therapy was withheld or stopped at randomization unless severe hypertension developed (systolic pressure ≥160 mmHg or diastolic pressure ≥105 mmHg). Participants in the control group who went on to develop severe hypertension were begun on antihypertensive therapy and the goal blood pressure was also <140/90 mmHg.

Treatment to a goal <140/90 mmHg reduced the risk of the composite primary outcome (severe preeclampsia, preterm birth at <35 weeks of gestation, placental abruption, fetal or neonatal death) (30.2 versus 37.0 percent, adjusted risk ratio [aRR] 0.82, 95% CI 0.74-0.92) without significantly increasing the risk of small for gestational age birth weight (11.2 versus 10.4 percent, aRR 1.04, 95% CI 0.82-1.31). The composite risk reduction was similar for participants with versus without diabetes (RR 0.75 in those with diabetes); the risk of small for gestational age birth weight safety outcome was not reported separately for participants with diabetes.

Labetalol and extended-release nifedipine are antihypertensive drugs commonly used in pregnancy. Antihypertensive drug choice and dosing in pregnancy are reviewed in detail separately (see "Treatment of hypertension in pregnant and postpartum patients"). Use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) should be avoided in pregnancy because of adverse fetal/neonatal effects. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)

Body mass index (BMI) assessment — All pregnant patients should be counseled regarding the Institute of Medicine (IOM, now the National Academy of Medicine) weight gain recommendations, which are stratified and inversely related to preconception BMI.

Overweight BMI and obesity are common in patients with diabetes, particularly type 2 diabetes. Even in type 1 diabetes, insulin treatment itself can lead to weight gain. Clinicians caring for patients with both obesity and diabetes should be mindful of the potential morbidities of each condition, including adverse pregnancy outcome (eg, cesarean and preterm birth, fetal anomalies, large for gestational age [LGA] or macrosomic birth weight) and other health consequences [17-20]. Appropriate gestational weight gain is important for these individuals because gestational weight gain above IOM recommendations amplifies these risks and contributes to postpartum weight retention [21-25].

(See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control", section on 'Calorie requirements'.)

(See "Obesity in pregnancy: Complications and maternal management".)

(See "Gestational weight gain".)

(See "Overweight and obesity in adults: Health consequences".)

Thyroid-stimulating hormone in patients with type 1 diabetes — The prevalence of autoimmune thyroid dysfunction is increased in patients with type 1 diabetes. If thyroid-stimulating hormone (TSH) levels are elevated, thyroid peroxidase status is also checked. (See "Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus", section on 'Thyroid surveillance'.)

Urine culture — While assessment for and treatment of asymptomatic bacteriuria is part of routine prenatal care, it is particularly important in patients with diabetes because of a three- to fivefold greater propensity for asymptomatic bacteriuria in these patients. Treatment and follow-up of patients with asymptomatic bacteriuria are reviewed separately, and are the same in patients with versus without diabetes. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Asymptomatic bacteriuria'.)

Nonglycemic pharmacotherapy

Folic acid – Patients with diabetes should consume at least 400 mcg of folic acid daily to reduce the risk of neural tube defects (NTDs). Ideally, folic acid supplementation is begun prior to conception and continued throughout pregnancy. Higher doses of 1 to 5 mg daily, beginning before conception and continuing for the initial 12 weeks of gestation have sometimes been recommended. These data are reviewed separately. (See "Preconception and prenatal folic acid supplementation", section on 'Folic acid supplementation for preventing NTDs'.)

Low-dose aspirin – Pregestational diabetes is a risk factor for developing preeclampsia (pooled rate 11 percent, 95% CI 8.4-13.8 percent; pooled relative risk [RR] 3.7, 95% CI 3.1-4.3 [26]). The United States Preventive Services Task Force, ADA, and ACOG recommend that patients at high risk for preeclampsia, including all those with type 1 and type 2 diabetes, begin low-dose aspirin after 12 weeks of gestation [14,27,28].

Many providers, including the authors, prescribe 81 mg daily as is recommended by ACOG and the Society for Maternal-Fetal Medicine based on the results of a meta-analysis suggesting that lower doses are less effective [29], whereas the ADA recommends 100 to 150 mg daily [14]. Because a 100 or 150 mg dose is not available in the United States, the ADA states that a dose of 162 mg/day may be acceptable.

Data regarding efficacy and dosing of low-dose aspirin for prevention of preeclampsia are reviewed separately. Trials have included few patients with diabetes, so the effectiveness of this intervention is unclear in this population [30]. (See "Preeclampsia: Prevention", section on 'Low-dose aspirin'.)

Antihypertensive therapy – Ideally, patients receiving angiotensin-converting enzyme (ACE) inhibitors or receptor blockers for hypertension or nephropathy should have been taken off these medications prior to pregnancy because of their teratogenic potential. If not discontinued prior to pregnancy, they should be suspended during pregnancy. The risks of these drugs in pregnancy are reviewed in detail separately. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)

Appropriate drug choices and goal blood pressure are discussed above. (See 'Blood pressure measurement/management' above.)

Vaccination – Adults with diabetes are at increased risk from respiratory infection and should receive the pneumococcal vaccine as well as other standard vaccinations (eg, influenza vaccine, COVID-19).

More information on vaccination during pregnancy is available separately:

(See "Immunizations during pregnancy".)

(See "Pneumococcal vaccination in adults".)

(See "Seasonal influenza and pregnancy".)

(See "COVID-19: Overview of pregnancy issues", section on 'Vaccination in people planning pregnancy and pregnant or recently pregnant people'.)

Fetal issues

Congenital anomalies/early pregnancy loss — We inform patients with diabetes of the increased risk of congenital anomalies, including neural tube and cardiac anomalies [31], and provide more detailed discussion if A1C is markedly elevated. We explain that information about fetal development will be obtained from second-trimester fetal sonographic examination and, if performed, first-trimester ultrasound and maternal serum alpha-fetoprotein (MSAFP) results. (See 'Screening for neural tube defects' below and 'Screening for other congenital anomalies' below.)

Data from multiple studies have shown a higher risk of major congenital malformations and early pregnancy loss associated with increasing first-trimester A1C values (figure 1) [32-35]. Although A1C values from different laboratories may not have been comparable at the times these studies were conducted because of differences in methodology and a lack of standardization among laboratories, a value >1 percent above the upper limit of the normal range is associated with an increased risk of congenital anomalies.

Data on the relationship between A1C and congenital anomalies/early pregnancy loss are reviewed separately. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management" and "Measurements of chronic glycemia in diabetes mellitus".)

Ultrasound examination — First-trimester ultrasound has several benefits:

Documentation of fetal cardiac activity is reassuring as the rate of early pregnancy loss is higher in patients with diabetes, especially those with uncontrolled hyperglycemia.

Confirmation or readjustment of the estimated date of delivery is important because many of these pregnancies undergo scheduled delivery or have accelerated or, less commonly, restricted fetal growth in the late second or the third trimester. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)

Some major congenital abnormalities (eg, anencephaly) can be detected in the late first trimester by a detailed fetal anatomic survey using a transvaginal transducer. Sensitivity is lower earlier in gestation because of difficulty in visualizing small structures and because some abnormalities of organs, such as the gastrointestinal tract, brain, and kidney, can be visualized better in the more physiologically advanced fetus. In particular, the fetal heart, which is a common site of diabetic embryopathy, is optimally visualized in the second trimester at 18 to 22 weeks. (see "Overview of ultrasound examination in obstetrics and gynecology", section on 'Obstetric sonography')

Screening for aneuploidy

Maternal diabetes mellitus is not a risk factor for aneuploidy.

Patients with diabetes are offered prenatal screening and diagnosis for aneuploidy and other genetic conditions according to practices in use for the general obstetric population. First-trimester serum and ultrasound markers of aneuploidy are not affected by maternal diabetes, in contrast to the second-trimester quadruple test. Noninvasive screening using cell-free DNA is thought not to be affected by maternal diabetes, though low fetal fraction can be seen in patients with obesity. (See "Down syndrome: Overview of prenatal screening" and "Prenatal screening for common aneuploidies using cell-free DNA".)

SECOND TRIMESTER — Prenatal visits are scheduled every two to four weeks through the second trimester, but more frequently if complications arise or glycemic management is suboptimal. This schedule of visits should be individualized based upon the severity of the diabetes, the degree of glycemic control, and the presence of other pregnancy complications.

Maternal issues

Glycemic management — Glucose self-monitoring and targets are the same throughout pregnancy, though insulin requirements vary considerably. Close follow-up for glycemic control is especially important after 18 weeks of gestation, as insulin resistance resulting from placental hormones increases rapidly and, consequently, insulin requirements can rise quickly after this point [9]. Some programs review blood glucose values remotely via phone or electronic communication and will make needed insulin adjustments outside of in-person visits. (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control".)

Preeclampsia — Hypertensive disorders of pregnancy, including preeclampsia, are increased in patients with pregestational diabetes. The increased risk is likely related to both pregestational vascular disease (hypertension, nephropathy) and hyperglycemia itself [36].

The magnitude of risk is shown in the following studies:

In a study that documented A1C values before and during pregnancy, the risk of preeclampsia increased significantly with increasing A1C values above optimal levels [36]. Compared with A1C <6.1 percent at 26 weeks of gestation, the increased odds of preeclampsia with A1C 6.1 to 6.9 percent, 7.0 to 7.9 percent, and ≥8.0 percent were 2.1, 3.2, and 3.8, respectively. At 34 weeks of gestation, the increased odds of preeclampsia with A1C ≥7.0 and ≥8.0 percent were 3.3 and 8.0, respectively.

In a series of 462 patients with pregestational diabetes, the rate of preeclampsia in patients with White classification B, C, D, and F/R (table 1) was 11, 22, 21, and 36 percent, respectively [37]. The increased risk of preeclampsia with more long-standing disease is explained in part by the observation that impaired endothelium-dependent vasodilation appears to be related to the duration of diabetes [38].

Monitoring for preeclampsia is a routine component of prenatal care and preeclampsia prophylaxis with low-dose aspirin is indicated in patients at high risk, such as those with pregestational diabetes. Diagnosis and management of preeclampsia are similar to that in patients without diabetes, except among those who enter pregnancy with preexisting hypertension or proteinuria; in these patients, the diagnosis can be difficult and requires relying on other markers. (See "Preeclampsia: Clinical features and diagnosis" and "Preeclampsia: Antepartum management and timing of delivery" and "Hypertensive disorders in pregnancy: Approach to differential diagnosis".)

Fetal issues

Screening for aneuploidy — If screening/diagnosis was not performed in the first trimester, patients with diabetes are offered prenatal screening/diagnosis of aneuploidy and other genetic conditions according to practices in use for the general obstetric population. (See "Down syndrome: Overview of prenatal screening".)

Diabetes does not increase the risk of fetal aneuploidy. However, levels of maternal serum alpha-fetoprotein (MSAFP), unconjugated estriol (uE3), and inhibin A, which are components of some second-trimester Down syndrome screening tests, are significantly reduced in patients with diabetes, thereby mimicking the pattern suggestive of Down syndrome. Therefore, the laboratory requisition for biochemical marker screening should indicate that the patient has diabetes and the laboratory staff should adjust the multiples of the median (MoM) value accordingly. (See "Maternal serum marker screening for Down syndrome: Levels and laboratory issues", section on 'Diabetes mellitus'.)

Screening for neural tube defects — The prevalence of neural tube defects (NTDs) is higher in pregnancies complicated by pregestational diabetes mellitus. As an example, in a study from 1982 (before recommendations for folic acid supplementation and food fortification), NTDs occurred in 2 percent of pregnancies complicated by diabetes versus 0.1 to 0.2 percent of the general population [39]. In a study from 2004, NTDs occurred in 0.19 percent of pregnancies complicated by diabetes versus 0.07 percent of pregnancies without diabetes [40]. The lower prevalence in 2004 likely reflects trends in better periconceptional glucose control as well as increased periconceptional folic acid exposure.

We use ultrasound alone to screen for NTDs, but it may be used in combination with measurement of MSAFP. Since the median MSAFP level is 15 percent lower and the prevalence of NTDs is higher in pregnancies with diabetes than in those without diabetes, a lower threshold MSAFP value (eg, approximately 1.5 MoM) has typically been used in pregnancies with diabetes to obtain the same negative predictive value for NTDs as in those without diabetes. Laboratory requisitions for MSAFP typically ask providers to indicate if the patient has diabetes; however, the need for correction for diabetes independent of maternal weight has been challenged [41]. (See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management".)

Screening for other congenital anomalies — A detailed ultrasound examination of fetal anatomy is performed between 18 and 22 weeks of gestation; this is particularly important because of the increased prevalence of congenital anomalies in patients with diabetes. If the sonologist performing the ultrasound is aware of the diagnosis of diabetes, they can be particularly mindful of evaluating for anomalies common to such pregnancies (table 4). Early detection of congenital anomalies allows parents and clinicians to prepare for the birth of an infant who may require specialized care. Alternatively, some parents may choose pregnancy termination; such procedures are more easily and safely performed at earlier gestational ages.

Congenital heart disease – The heart is another focus of the fetal anatomy examination, which should include a four-chamber view and visualization of the outflow tracts. Detailed examination of the heart is important because congenital heart disease occurs more frequently in offspring of mothers with diabetes than in the general population and accounts for approximately one-half of diabetes-related major congenital anomalies [31,42]. As an example, in a series of 535 pregnant patients with preexisting diabetes, 30 (5.6 percent) gave birth to an infant with confirmed congenital heart disease; the rate was 8.3 percent in those with an A1C ≥8.5 percent versus 3.9 percent of those with an A1C below this level [43].

Some centers refer all patients with diabetes for fetal echocardiograms, while others restrict echocardiography to pregnancies at high risk, such as those with either abnormalities on imaging the four chambers and outflow tracts or elevated periconception/first-trimester A1C (eg, ≥8 percent in our practice). A selective approach is often acceptable because routine echocardiography detects few additional malformations in centers with high-volume, skilled, detailed obstetric ultrasound services [44,45]. (See "Congenital heart disease: Prenatal screening, diagnosis, and management".)

Conotruncal and ventricular septal defects are the most common cardiac anomalies in infants of mothers with diabetes. Significant augmentation of interventricular septal thickness may be noted in midtrimester fetuses of these pregnancies and often progresses during the course of pregnancy [46]. The hypertrophy primarily occurs in pregnancies with uncontrolled hyperglycemia. Although this condition is usually mild and asymptomatic in the neonate, congestive cardiomyopathy, which is a more diffuse process of hypertrophy and hyperplasia of the myocardial cells, can also occur. Both disorders are transient and managed with supportive care. (See "Infants of mothers with diabetes (IMD)", section on 'Ventricular hypertrophy'.)

Overall diagnostic performance – The performance of ultrasound for prenatal detection of congenital anomalies was illustrated in a retrospective study of pregnant patients with pregestational diabetes who received detailed sonography with fetal echocardiography at 18 to 22 weeks in one hospital system and subsequently gave birth to a liveborn or stillborn between 2011 and 2017 [47]:

Major anomalies were present in 7 percent of newborns

76 percent of the anomalies were detected prenatally

68 percent of the prenatally-detected anomalies were identified during the initial detailed fetal sonogram with echocardiography; another 8 percent were identified on follow-up sonography

Prenatal detection by organ system was over 85 percent for central nervous system, genitourinary, and musculoskeletal anomalies; 65 percent for cardiac anomalies; and 43 percent for craniofacial anomalies

THIRD TRIMESTER — In the third trimester, prenatal visits are as often as every one to two weeks until 36 weeks of gestation, and then weekly until birth. Depending on gestational age, fetal testing may occur more frequently.

Maternal issues

Glycemic management — Glucose self-monitoring and targets are the same throughout pregnancy. Continued control of blood glucose concentration during the third trimester is important to minimize the risk of fetal complications, such as accelerated growth, neonatal metabolic and physiologic disturbances, and stillbirth. Although accelerated growth and neonatal hypoglycemia remain common, third-trimester fetal demise is now rare in pregnancies complicated by diabetes, primarily because of better glycemic control. As in the late second trimester, frequent escalation of insulin doses is commonly required to maintain euglycemia, but insulin requirements generally plateau by 37 weeks of gestation and may decline slightly. A ≥15 percent decline in insulin requirements should prompt evaluation of fetal well-being. (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control", section on 'Insulin requirements in pregnancy' and "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control", section on 'Implications of falling insulin requirement'.)

Asymptomatic bacteriuria — Rescreening for asymptomatic bacteriuria with urine culture at the start of the third trimester is reasonable in patients who did not have bacteriuria on the initial test because they remain at high risk for developing bacteriuria.

Preeclampsia — Close monitoring for the development of hypertensive disorders of pregnancy (eg, preeclampsia, gestational hypertension, HELLP syndrome) is continued in the third trimester. (See 'Preeclampsia' above.)

Preterm birth — Compared with controls without diabetes or hypertension, patients with pregestational diabetes have higher rates of both indicated preterm birth (22 versus 3 percent, odds ratio [OR] 8.1, 95% CI 6.0-10.9) and spontaneous preterm birth (16 versus 11 percent, OR 1.6, 95% CI 1.2-2.2) [48]. Indicated preterm birth is primarily initiated because of preeclampsia [48,49], but both gestational and pregestational diabetes have been associated with indicated preterm birth independent of preeclampsia. The reasons for an increased risk of spontaneous preterm birth are not clear [50,51].

The indications for inhibition of preterm labor are similar to those in the general obstetric population. Our preferences for tocolytic therapy are nifedipine or indomethacin (for pregnancies less than 32 weeks of gestation). We avoid beta-adrenergic receptor agonists as they can cause severe hyperglycemia in patients with diabetes. (See "Inhibition of acute preterm labor".)

Antenatal glucocorticoids in patients at risk for preterm birth

Up to 33+6 weeks – If preterm birth of a potentially viable neonate ≤33+6 weeks of gestation is anticipated or planned, administration of betamethasone improves neonatal outcome, but close maternal glucose monitoring is essential. Transient hyperglycemia induced by glucocorticoids can be severe in patients with diabetes, even when glucose levels are closely monitored and treated [52,53]. The hyperglycemic effect begins approximately 12 hours after the first steroid dose and lasts for approximately five days [54,55]. In a series in which 16 patients with type 1 diabetes requiring insulin therapy were given betamethasone for fetal lung maturation, the insulin dose for the following five days increased by 6, 38, 36, 27, and 17 percent above baseline, respectively [54]. Our clinical experience has been that patients with insulin resistance or obesity may experience even greater increases in insulin requirement after steroid administration.

We preemptively increase subcutaneous insulin doses in patients receiving betamethasone, starting with the algorithm suggested by Mathiesen et al [54] and using additional correctional subcutaneous insulin along with rapid titration as needed. Capillary blood glucose concentrations are checked one to two hours before and after meals and at bedtime. Steroid administration, subsequent glucose monitoring, and management of glycemia is typically performed in hospitalized patients, but the process could be conducted in nonhospitalized patients who are able to closely monitor their glucose levels, promptly communicate with their providers, and adjust insulin doses accordingly.

In the Mathiesen et al algorithm for initial dosing, increments of insulin dose are related to the insulin dose at baseline (ie, on the day before the first betamethasone injection is administered):

Day 1 (first day of betamethasone) – Increase the bedtime insulin dose by 25 percent over the baseline dose

Day 2 and day 3 – Increase all insulin doses to 40 percent over the baseline dose

Day 4 – Decrease all insulin doses to 20 percent over the baseline dose

Day 5 – Decrease all insulin doses to 10 percent over the baseline dose.

Day 6 – Decrease insulin doses to the level before the betamethasone treatment

We initiate a continuous intravenous insulin infusion on the labor unit if values are persistently elevated despite escalation of the subcutaneous regimen or if initial values are above 180 mg/dL (10.0 mmol/L). (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '23+0 to 33+6 weeks'.)

34+0 and 36+6 weeks – Although administration of betamethasone also had potential benefits before preterm births between 34+0 and 36+6 weeks of gestation in a randomized trial (Antenatal Betamethasone for Women at Risk for Late Preterm Delivery [56]), patients with diabetes were specifically excluded from this trial, and, concordant with recommendations from specialty societies [57], we suggest not administering steroids to improve neonatal outcome in diabetic pregnancies at late preterm gestational ages. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '34+0 or more weeks'.)

Fetal issues

Risk of stillbirth — Patients with pregestational diabetes have a fivefold increased risk of stillbirth compared to those without diabetes [58]. The pathophysiology appears to be multifactorial, and may include congenital anomalies and fetal effects from maternal hyperglycemia and vascular disease (including preeclampsia):

Fetal hyperglycemia and hyperinsulinemia increase fetal oxygen consumption, which may induce fetal hypoxemia and acidosis if the oxygen needs of the fetus are not met [59-63].

Maternal vasculopathy and hyperglycemia can lead to reduced uteroplacental perfusion, which may be associated with reduced fetal growth [64].

Initiation and frequency of fetal surveillance — We begin twice-weekly antepartum surveillance (eg, nonstress test, biophysical profile) at 32 weeks of gestation to reduce the risk of stillbirth, in line with guidance from the American College of Obstetricians and Gynecologists (ACOG) [65]. In complicated pregnancies with fetal growth restriction, oligohydramnios, preeclampsia, or uncontrolled hyperglycemia, testing may start as early as 26 weeks of gestation. Any significant deterioration in maternal status or a ≥15 percent decline in insulin requirements necessitates reevaluation of the fetus. The frequency of fetal death (excluding fetuses with congenital malformations) with such protocols is approximately 3 per 1000 pregnancies in patients with type 1 diabetes [66].

Nonreassuring test results:

If nonreassuring fetal testing is related to a potentially reversible problem such as hyperglycemia or ketoacidosis, the fetus can often be resuscitated in utero by prompt correction of the mother's metabolic derangement. Pathologic fetal heart rate patterns will often revert to normal.

If nonreassuring fetal testing appears to be related to a nonreversible problem, the gestational age and the associated risk for sequelae of preterm birth strongly influence management. In preterm gestations, we try to delay delivery, at least long enough to treat the mother with betamethasone to accelerate fetal lung maturation (see 'Antenatal glucocorticoids in patients at risk for preterm birth' above). This can be done while monitoring the fetus more intensively or even continuously. The degree of compromise indicated by fetal surveillance helps to inform the relative risks and benefits of delaying delivery.

Although antepartum fetal testing is routinely performed in pregnancies complicated by pregestational diabetes [28], no data from large or randomized trials are available on which to base an evidence-based recommendation as to whether all or selected pregnancies complicated by diabetes should undergo fetal surveillance, when to start, what test to order, or how often to perform testing [67]. As a result, management is largely based on clinical experience and expert opinion and varies widely [68]. A National Institutes of Health workshop recognized the limitations of available data and concluded that, in managing pregnancies complicated by diabetes, it was "not clear which method [of antenatal testing], if any, is superior" [69].

Assessment of fetal growth — Pregnancies complicated by maternal diabetes without vascular disease are often associated with accelerated growth [70]. Maternal vascular disease (including preeclampsia) increases the risk of impaired fetal growth [4,71].

Initiation and frequency of growth measurements — We obtain an ultrasound examination at 28 to 32 weeks of gestation to assess fetal growth. In the absence of impaired fetal growth, the examination is repeated every four weeks to evaluate growth and, as term approaches, to assist with birth plans. (See 'Route' below.)

Accelerated fetal growth — The risk of fetal overgrowth is strongly related to the degree of glycemic control [72], but prepregnancy obesity and gestational weight gain likely play a role as well [73,74]. Fetal overgrowth impacts intrapartum and neonatal outcomes:

Maternal diabetes dramatically increases the risk of large for gestational age (LGA) birth weight, which increases the risk for a prolonged second stage of labor, shoulder dystocia, operative delivery, maternal and infant birth trauma, and perinatal death [75,76]. The risk of stillbirth is particularly high at ≥35 weeks [76]. Maternal diabetes also changes fetal anthropometric measurements compared with offspring of mothers without diabetes [77]; specifically, the chest-to-head and shoulder-to-head ratios are increased in neonates of people with diabetes requiring insulin [78]. These changes increase the likelihood of shoulder dystocia two- to sixfold compared with the population without diabetes [79] and increase the likelihood of dystocia-associated fetal morbidity, such as brachial plexus injury [80]. The correlation between shoulder dystocia and birth weight in patients with and without diabetes is shown in the table (table 5) [81]. (See "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies".)

Accelerated fetal growth is also associated with an increased risk of neonatal metabolic and physiologic disturbances. (See "Infants of mothers with diabetes (IMD)", section on 'Neonatal complications'.)

If present, accelerated fetal growth often becomes apparent at 26 to 28 weeks of gestation, which is the rationale for an early third-trimester ultrasound examination [42,82,83]. However, some fetuses do not exhibit accelerated fetal growth until the later in the third trimester, which is the rationale for ongoing monitoring [84].

The diagnosis of accelerated fetal growth is based on identification of an LGA fetus, ie, greater than the 90th percentile for fetuses of that gestational age (possibly including adjustments for fetal sex and ethnicity). At 40 weeks of gestation, the 90th percentile for birth weight in the United States is approximately 4060 grams [85].

The term "macrosomia" is a type of LGA that refers to a fetus that is greater than some defined weight regardless of gestational age or sex. Various authors and professional organizations have defined macrosomia as >4000, >4250, and >4500 grams. We use the ACOG threshold, which is >4500 grams because maternal and neonatal morbidity increases sharply above this level [86].

There is no highly reliable method for identifying LGA fetuses before birth, even though neonatal weight is an important predictor of neonatal morbidity and estimation of fetal weight at term is an important variable in birth planning [42,87,88] (see 'Route' below). In a review of studies of ultrasound for predicting estimated fetal weight (EFW) >4000 grams in patients with diabetes, sensitivity ranged from 33 to 83 percent and specificity ranged from 77 to 98 percent [42]. (See "Fetal macrosomia", section on 'Patients with diabetes'.)

Growth restriction — Growth restriction is most common in pregnancies with maternal vascular disease [4,71]. In one study including 53 patients with diabetic vascular disease, the frequencies of small and LGA newborns were 9 out of 53 and 4 out of 53, respectively [4]. The prenatal diagnosis, obstetric management, and outcome of fetal growth restriction are the same as in pregnancies without diabetes. (See "Infants with fetal (intrauterine) growth restriction" and "Fetal growth restriction: Pregnancy management and outcome", section on 'Prenatal care'.)

Polyhydramnios — Maternal diabetes is a common etiology of polyhydramnios. The mechanism for the increased amniotic fluid volume has not been clearly defined. Possibilities include fetal polyuria secondary to maternal and fetal hyperglycemia, decreased fetal swallowing, or an imbalance in water movement between the maternal and fetal compartments [89]. Polyhydramnios is frequently associated with accelerated fetal growth. (See "Physiology of amniotic fluid volume regulation".)

Diabetes-associated polyhydramnios is rarely severe, thus it rarely requires intervention for severe maternal symptoms. Fetal outcomes are more favorable than in pregnancies in which polyhydramnios is associated with serious fetal disorders such as neurologic disease, twin-to-twin transfusion, or other syndromes [90]. (See "Polyhydramnios: Etiology, diagnosis, and management in singleton gestations".)

DELIVERY

Timing — Timing is based on assessment of multiple factors, including gestational age, estimated fetal weight, and maternal glycemic control and comorbidities (eg, vascular disease or prior stillbirth).

For patients with well-controlled hyperglycemia and without macrosomia, we suggest delivery at 39+0 to 39+6 weeks of gestation. There is little maternal or newborn benefit and some potential harm in continuing pregnancy beyond 39 weeks. On the other hand, early-term (37+0 to 38+6 weeks) and late preterm (34+0 to 36+6 weeks) births are associated with increased newborn morbidity, even in patients without pregestational diabetes [91,92], and before 38.5 weeks of gestation, respiratory distress syndrome (RDS) is more likely to develop in infants of patients with diabetes than in those without diabetes because the endocrine changes associated with maternal diabetes delay fetal lung maturation [93,94]. Specifically, high fetal insulin levels enhance cellular hypertrophy and hyperplasia at the expense of cellular maturation, thus leading to macrosomia and immature lung function. In the era prior to the availability of fetal pulmonary maturity tests, RDS accounted for 52 percent of neonatal deaths among infants born to patients with pregestational diabetes [95].

For patients with impending macrosomia, we do not routinely induce patients before 39+0 weeks for this indication alone. Sonographic assessment of fetal weight is imprecise among fetuses >4000 grams and there is no high-quality evidence establishing a clear benefit of early induction in this setting in pregnancies complicated by pregestational diabetes. Macrosomia is a factor in choosing the route of delivery. (See 'Route' below.)

The largest randomized trial comparing the outcomes of induction versus expectant management of large for gestational age (LGA) fetuses specifically excluded patients with insulin-requiring diabetes. In this trial, 407 fetuses with estimated weight >95th percentile at 36 to 38 weeks (ie, 3500 grams at 36 weeks of gestation, 3700 grams at 37 weeks, 3900 grams at 38 weeks) were induced between 37+0 and 38+6 weeks and within three days, and 411 were managed expectantly [96]. The likelihood of vaginal birth was 14 percent higher with induction (95% CI 1 to 29 percent). Induction reduced the risk of significant shoulder dystocia by 68 percent (95% CI 12 to 85 percent), but without a statistical difference between groups in the number of fetuses with a fracture (two in the induction group versus eight in the expectant management group) and no brachial plexus injuries occurred in either group. The induction group had higher proportions of infants with a high bilirubin concentration and receiving phototherapy group, which are some of the morbidities expected with births <39+0 weeks of gestation.

For selected patients, we plan delivery before 39+0 weeks:

For patients with uncontrolled hyperglycemia, vascular disease, or prior stillbirth, we suggest delivery at 36+0 to 38+6 weeks because of the risk of stillbirth, consistent with guidance from the American College of Obstetricians and Gynecologists (ACOG) [97]. The timing of delivery within this range and the route depend on patient-specific factors and preferences, and may be evaluated within a framework of shared decision-making, balancing the risk of stillbirth from continued expectant management against the respiratory morbidity associated with late-preterm or early-term birth.

For patients with standard obstetric or medical indications for delivery (eg, preterm prelabor rupture of membranes, preeclampsia worsening maternal renal insufficiency or active proliferative retinopathy), delivery timing before 39+0 weeks and route are individualized, depending on the specific clinical scenario.

Recommendations of others – As reflected above, ACOG and the Society for Maternal-Fetal Medicine recommend [28,97,98]:

For patients with well-controlled glucose levels and no vascular disease: deliver at 39+0 to 39+6 weeks. Expectant management beyond 40+0 weeks is not recommended.

For patients with uncontrolled hyperglycemia or vascular disease: deliver at 36+0 to 38+6 weeks (or even earlier if severity of complications warrants earlier delivery).

Route

Patients without macrosomia – Maternal diabetes alone is not an indication for cesarean birth in the absence of the usual obstetric indications.

Patients with macrosomia – Macrosomia can be an indication for cesarean birth due to the risk of morbidity from shoulder dystocia [99-102]. It has been suggested that neonates with shoulder dystocia have greater shoulder and chest-to-head disproportion than macrosomic infants without this complication [78,103]. In particular, macrosomic infants of mothers with diabetes are more likely to exhibit this disproportion than infants of comparable weight of nondiabetic mothers [101].

We agree with the ACOG that prophylactic cesarean birth is reasonable to prevent brachial plexus injury when the EFW is greater than 4500 grams in a patients with diabetes (table 5), even though the diagnosis of macrosomia is imprecise [28,104]. If the patient has had a previous child with shoulder dystocia, then EFW, gestational age, and the severity of the prior neonatal injury, if any, should also be considered in making the decision about route of delivery [105]. (See "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies".)

Patients undergoing forceps- or vacuum-assisted vaginal birth – Since both diabetes and forceps- or vacuum-assisted vaginal birth are associated with an increased risk for shoulder dystocia, it is reasonable to perform a cesarean birth rather than an assisted vaginal birth in patients with diabetes, estimated fetal weight (EFW) >4000 grams, and a prolonged second stage [106]. This decision should be individualized, taking into account factors such as the past obstetric history, estimated fetal weight, fetal position, and station. (See "Assisted (operative) vaginal birth" and "Labor: Diagnosis and management of a prolonged second stage", section on 'Management'.)

Patients undergoing a trial of labor after a previous cesarean birth – Maternal diabetes is not a contraindication to a trial of labor after a previous cesarean birth (TOLAC); however, the success rate may be lower than in patients without diabetes (64 versus 74 percent in one study [107]). (See "Choosing the route of delivery after cesarean birth".)

Management — Specific issues for managing patients with pregestational diabetes on the labor unit include:

Scheduling – When an induction or cesarean birth is indicated, we schedule the procedure early in the morning, when possible, as this facilitates management of glucose and insulin in a fasting patient. (See "Pregestational (preexisting) and gestational diabetes: Intrapartum and postpartum glucose management".)

Glycemic management – Peripartum maintenance of maternal euglycemia is essential and generally requires hourly capillary glucose determinations, intravenous solutions containing dextrose, and intravenous or subcutaneous insulin if hyperglycemia is present. Management of glucose and insulin during labor, cervical ripening, induction, and cesarean birth is discussed separately. (See "Pregestational (preexisting) and gestational diabetes: Intrapartum and postpartum glucose management".)

Fetal monitoring – The fetal heart rate is continuously monitored on the labor and delivery unit, as these pregnancies are at increased risk for nonreassuring fetal heart rate patterns [108,109].

Analgesia and anesthesia – There are no contraindications to natural childbirth or neuraxial or general anesthesia. As in patients without diabetes, the choice of anesthetic technique should be based on patient and surgical factors, and intraoperative fluid boluses should consist of glucose-free solutions to prevent neonatal hypoglycemia. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)" and "Pharmacologic management of pain during labor and delivery".)

POSTPARTUM

Glycemic management — Insulin requirements drop sharply after delivery and are substantially lower than requirements prior to pregnancy [110]. Glucose monitoring and insulin dosing in the postpartum period are reviewed separately. (See "Pregestational (preexisting) and gestational diabetes: Intrapartum and postpartum glucose management", section on 'Type 1 diabetes'.)

Maternal issues

Breastfeeding – Breastfeeding should be encouraged and supported [28]. (See "Infant benefits of breastfeeding" and "Maternal and economic benefits of breastfeeding".)

Both insulin and metformin are compatible with breastfeeding. Patients with type 1 diabetes who breastfeed may have a basal insulin requirement that is approximately 15 percent lower than prior to pregnancy and this reduction can persist for at least six months after birth [111].

Patients with diabetes appear to have more problems with lactation and may benefit from consultation with a lactation specialist. (See "Common problems of breastfeeding and weaning".)

Postpartum depression – Postpartum depression appears to be more common among patients with diabetes (pregestational or gestational) than in patients without diabetes [112], so routine screening is especially important. The validated questionnaire most commonly used for screening pregnant and postpartum individuals is the Edinburgh Postnatal Depression Scale (figure 2A-B), but other validated tools can be used (table 6). (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis".)

Contraception

Patients without vascular disease – The United States Medical Eligibility Criteria for Contraceptive Use consider all hormonal methods acceptable for patients with diabetes and no vascular disease [113]; thus, selection should be based upon the same factors that apply to patients without diabetes (see "Contraception: Counseling and selection").

Although evidence from randomized trials is limited, both progestin-only methods and low-dose combined oral contraceptives appear to have only minor effects on glucose and fat metabolism [114]. However, depot medroxyprogesterone acetate (DMPA) may increase blood glucose levels; therefore, patients with diabetes and no vascular disease who elect to use DMPA should carefully monitor their blood glucose levels [115-117]. (See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits" and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

Patients with vascular disease – In patients with vascular disease, DMPA and combined estrogen-progestin contraceptives are generally avoided [113]. The progestin-releasing intrauterine device (IUD), copper IUD, and etonogestrel implant are highly effective contraceptive methods and have a lower risk of thromboembolic events than estrogen-progestin contraceptives [118].

Ophthalmologic follow-up – Ophthalmologic follow-up during the first year postpartum is advised since retinopathy can be aggravated during pregnancy or postpartum [14].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diabetes mellitus in pregnancy" and "Society guideline links: Shoulder dystocia and macrosomia".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Care during pregnancy for patients with type 1 or 2 diabetes (Beyond the Basics)" and "Patient education: Gestational diabetes (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Glycemic management – Meticulous attention to glycemic control throughout gestation is essential to minimize the risk of complications. Self-monitored glucose targets are (see 'Glycemic management' above):

Fasting, preprandial, and nocturnal glucose 70 to 95 mg/dL (3.9 to 5.3 mmol/L) and

-One-hour postprandial glucose 110 to 140 mg/dL (6.1 to 7.8 mmol/L) or

-Two-hour postprandial glucose 100 to 120 mg/dL (5.6 to 6.7 mmol/L)

For patients using continuous glucose monitoring, the target glucose range is 63 to 140 mg/dL (3.5 to 7.8 mmol/L), and the time in range goal is >70 percent

Insulin requirements across pregnancy – While glucose targets are the same throughout pregnancy, insulin requirements decrease in the first trimester so the risk for hypoglycemia increases. After 18 weeks of gestation, insulin requirements increase quickly until plateauing near 37 weeks of gestation. An unexpected ≥15 percent decline in insulin requirements should prompt an assessment of fetal well-being. (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control", section on 'Insulin requirements in pregnancy' and "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control", section on 'Implications of falling insulin requirement'.)

First trimester

Nausea and vomiting – We have a low threshold for treatment of nausea and vomiting of pregnancy as it facilitates insulin management and relieves maternal discomfort. Clinicians should also consider whether it may be a manifestation of gastroparesis. (See 'Nausea and vomiting' above.)

Maternal evaluation – In addition to routine prenatal assessments (see "Prenatal care: Initial assessment"), evaluations related to diabetes are listed in the table (table 2). (See 'Routine laboratory tests and evaluation for comorbidities' above.)

Noninsulin pharmacotherapy

-Folic acid (at least 400 mg orally daily) is begun prior to pregnancy or as soon as pregnancy is diagnosed for prevention of neural tube defects (NTDs). (See 'Nonglycemic pharmacotherapy' above.)

-Aspirin 81 to 162 mg is begun at 12 weeks of gestation for preeclampsia prophylaxis (patients with diabetes are at increased risk for preeclampsia). (See 'Nonglycemic pharmacotherapy' above and 'Preeclampsia' above.)

-In patients with hypertension, we recommend a goal blood pressure of less than 140/90 mmHg. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers should be avoided. (See 'Blood pressure measurement/management' above.)

Fetal evaluation – First-trimester obstetric ultrasound is useful to confirm cardiac activity and gestational age, and provide preliminary evaluation for major congenital malformations because pregestational diabetes is associated with increased risks for pregnancy loss, congenital anomalies, and preterm birth. (See 'Ultrasound examination' above.)

Second and third trimesters

Preeclampsia – Monitoring for preeclampsia is a routine component of prenatal care, but diagnosis may be more difficult in those with preexisting hypertension or proteinuria. (See "Hypertensive disorders in pregnancy: Approach to differential diagnosis".)

Fetal anatomic survey – Detailed ultrasound examination of fetal anatomy is performed between 18 and 22 weeks of gestation. Depending on local expertise, all patients with diabetes may be referred for fetal echocardiograms or echocardiography can be restricted to patients at high risk, such as those with abnormalities on imaging the four chambers and outflow tracts or elevated periconception A1C. (See 'Screening for other congenital anomalies' above.)

Antepartum fetal surveillance – Patients with pregestational diabetes are at increased risk of stillbirth. Twice-weekly antepartum fetal surveillance (nonstress test, biophysical profile) is begun at 32 weeks of gestation. (See 'Initiation and frequency of fetal surveillance' above.)

Assessment of fetal growth and amniotic fluid – We obtain an ultrasound examination at 28 to 32 weeks of gestation to assess for normal, accelerated, or restricted fetal growth, and repeat the examination every four weeks. Accelerated fetal growth and its complications (eg, shoulder dystocia) are common. Polyhydramnios, if present, is rarely severe. (See 'Assessment of fetal growth' above and 'Polyhydramnios' above.)

Antenatal corticosteroids – If a course of antenatal corticosteroids is administered to patients at high risk for preterm birth, blood glucose concentrations are checked frequently and hyperglycemia, which may become severe, is managed with increased insulin. (See 'Antenatal glucocorticoids in patients at risk for preterm birth' above.)

Tocolysis – Our preferences for tocolytic therapy are nifedipine or indomethacin (for pregnancies less than 32 weeks of gestation). We avoid beta-adrenergic receptor agonists as they can cause severe hyperglycemia in patients with diabetes. (See 'Preterm birth' above.)

Delivery (See 'Delivery' above.)

For patients with well-controlled hyperglycemia and without vascular complications or macrosomia, we suggest induction at 39+0 to 39+6 weeks of gestation (Grade 2C), in the absence of standard obstetric or medical indications for earlier intervention or cesarean birth.

For patients with uncontrolled hyperglycemia, vascular complications, or history of stillbirth and without macrosomia, we suggest induction at 36+0 to 38+6 weeks (Grade 2C), in the absence of standard obstetric or medical indications for earlier intervention or cesarean birth. The timing of birth within this range depends on patient-specific factors.

For patients with estimated fetal weight (EFW) >4500 grams, we suggest planned cesarean rather than vaginal birth (Grade 2B). The risk of shoulder dystocia is increased at birth weights >4000 grams and high at birth weights >4500 grams (table 5).

Since both diabetes and forceps- or vacuum-assisted vaginal birth are associated with an increased risk for shoulder dystocia, it is reasonable to perform a cesarean rather than an assisted vaginal birth in patients with diabetes and EFW >4000 grams.

Postpartum

Glycemic management – Insulin requirements drop sharply after delivery and are transiently lower than requirements prior to pregnancy. (See "Pregestational (preexisting) and gestational diabetes: Intrapartum and postpartum glucose management", section on 'Postpartum management'.)

Breastfeeding – Patients with diabetes are encouraged to breastfeed. Insulin and metformin are compatible with breastfeeding. (See 'Maternal issues' above.)

Postpartum depression – Clinicians should screen for postpartum depression, which appears to be more common in patients with diabetes. (See 'Maternal issues' above.)

Contraception – The United States Medical Eligibility Criteria for Contraceptive Use consider all hormonal methods acceptable for patients with diabetes and no vascular disease, but depot medroxyprogesterone may raise glucose levels so close self-monitoring is required.

In patients with vascular disease, combined hormonal contraceptives and depot medroxyprogesterone are avoided. (See 'Maternal issues' above.)

Surveillance for retinopathy – Eye examinations are continued for one year postpartum, as indicated by the degree of retinopathy. (See 'Dilated, comprehensive eye examination' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael F Greene, MD, who contributed to an earlier version of this topic review.

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Topic 4806 Version 80.0

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