# Pregestational Diabetes in Pregnancy

## Overview and Classification

### Epidemiology

Pregestational diabetes -- either type 1 or type 2 -- complicates approximately 1 to 2% of pregnancies. Type 2 diabetes in pregnancy is becoming increasingly common due to rising obesity rates and younger age at diagnosis. Compared to gestational diabetes, pregestational diabetes carries substantially higher rates of adverse maternal and fetal outcomes.

### White Classification (Modified)

The White classification historically categorized diabetes in pregnancy by duration and the presence of end-organ complications. Class B refers to disease with onset at age 20 or older or duration less than 10 years. Class C indicates onset between ages 10 and 19 or duration of 10 to 19 years. Class D denotes onset before age 10, duration exceeding 20 years, or the presence of background retinopathy. Class F indicates diabetic nephropathy, Class R proliferative retinopathy, Class H ischemic heart disease, and Class T prior renal transplant. While less commonly used in routine clinical practice today, this classification still appears frequently on examinations.

| White Class | Criteria |
|---|---|
| B | Onset age ≥20 or duration <10 years |
| C | Onset age 10-19 or duration 10-19 years |
| D | Onset age <10, duration >20 years, or background retinopathy |
| F | Diabetic nephropathy |
| R | Proliferative retinopathy |
| H | Ischemic heart disease |
| T | Prior renal transplant |

## Preconception Counseling and Optimization

### Glycemic Targets Before Conception

Preconception glycemic optimization is the single most impactful intervention for reducing fetal risk. The A1C goal before conception is below 6.5%, ideally below 6.0%. Fasting glucose should be maintained between 70 and 95 mg/dL, and 1-hour postprandial glucose below 140 mg/dL. Every 1% reduction in A1C above 6.5% significantly reduces the risk of congenital malformations. When A1C exceeds 10%, the malformation rate climbs to 20 to 25%.

### Medication Review

Several medication changes must be made before or early in pregnancy. ACE inhibitors and ARBs are teratogenic and must be discontinued, with labetalol or nifedipine substituted for blood pressure control. Statins are traditionally avoided due to limited safety data. Oral hypoglycemic agents should generally be switched to insulin, which is the standard of care in pregestational diabetes per ACOG, although metformin may be continued in type 2 diabetes when patient preference and clinical context support its use. Folic acid supplementation should be increased to 4 mg daily (higher than the standard prenatal dose) because of the elevated risk of neural tube defects.

### Baseline Evaluation

A thorough baseline evaluation includes A1C, comprehensive metabolic panel (creatinine, electrolytes, liver function), urine albumin-to-creatinine ratio or 24-hour urine protein, thyroid function testing (TSH, especially important in type 1 diabetes due to the association with autoimmune thyroid disease), ophthalmologic examination with dilated fundoscopy, and an ECG if the patient has long-standing diabetes or cardiovascular risk factors.

<image>Infographic showing the preconception checklist for women with pregestational diabetes including A1C target, medication changes, folic acid supplementation, baseline labs, ophthalmologic exam, and renal assessment</image>

## Maternal Risks

### Obstetric Complications

Women with pregestational diabetes face elevated rates of several obstetric complications. Preeclampsia occurs in 15 to 20% of these pregnancies, with the risk increasing further in the setting of nephropathy or poor glycemic control. Cesarean delivery rates are higher due to macrosomia, labor dystocia, and fetal distress. Polyhydramnios develops from osmotic diuresis caused by fetal hyperglycemia. Preterm delivery may be either spontaneous or medically indicated. Shoulder dystocia risk is increased, and notably, this risk is elevated even at lower fetal weights compared to non-diabetic pregnancies. Diabetic ketoacidosis can occur at lower glucose levels in pregnancy than outside of pregnancy, a phenomenon called "euglycemic DKA."

### Diabetic Complications in Pregnancy

Preexisting diabetic complications may worsen during pregnancy. Retinopathy can progress, particularly with rapid glycemic correction, and screening should occur each trimester with referral for laser therapy if proliferative disease advances. Nephropathy may manifest as worsening proteinuria, and a baseline creatinine above 1.5 mg/dL is associated with poor outcomes. Nephropathy increases the risk of superimposed preeclampsia, preterm delivery, and intrauterine growth restriction. Neuropathy, particularly gastroparesis, may worsen nausea and vomiting and impair glycemic control. Cardiovascular disease, though rare in women of reproductive age, carries a high maternal mortality risk when present, particularly coronary artery disease.

## Fetal Risks

### Congenital Anomalies

The overall rate of congenital anomalies in pregnancies complicated by pregestational diabetes is 6 to 12%, representing a 2- to 4-fold increase over the background rate. The risk is directly related to first-trimester glycemic control as reflected by A1C. Cardiac anomalies are the most common, including ventricular septal defects, atrial septal defects, transposition of the great arteries, and coarctation of the aorta. Neural tube defects (anencephaly and spina bifida) occur at 4 to 10 times the background rate. Caudal regression syndrome, while rare, is the anomaly most specific to diabetic embryopathy. Other affected systems include the kidneys (renal agenesis), gastrointestinal tract (atresias), and skeleton.

### Growth Abnormalities

Macrosomia (estimated fetal weight above 4,000 g or the 90th percentile) occurs in 25 to 40% of pregnancies with pregestational diabetes. The growth pattern is characteristically asymmetric, with disproportionate increase in the abdominal circumference and subcutaneous fat due to fetal hyperinsulinism. Conversely, intrauterine growth restriction may occur in patients with vascular disease, nephropathy, or poor placental perfusion.

### Other Fetal/Neonatal Complications

Neonatal hypoglycemia results from persistent fetal hyperinsulinism after the maternal glucose supply is interrupted at delivery. Other neonatal complications include hyperbilirubinemia, polycythemia, respiratory distress syndrome (due to delayed surfactant production), and hypertrophic cardiomyopathy (which is reversible). The risk of stillbirth is 2 to 5 times higher than in non-diabetic pregnancies, with the highest risk occurring when glycemic control is poor.

<image>Illustration showing the pathophysiology of diabetic fetopathy, depicting maternal hyperglycemia crossing the placenta leading to fetal hyperglycemia, fetal pancreatic beta-cell hyperplasia, fetal hyperinsulinemia, and resulting macrosomia, organomegaly, and neonatal hypoglycemia</image>

## Antepartum Management

### Glycemic Monitoring and Targets

Self-monitoring of blood glucose should occur at minimum four times daily: fasting and 1 to 2 hours after each meal. The targets during pregnancy are fasting below 95 mg/dL, 1-hour postprandial below 140 mg/dL, and 2-hour postprandial below 120 mg/dL. Continuous glucose monitoring is increasingly used, and the CONCEPTT trial demonstrated improved neonatal outcomes with CGM in type 1 diabetes. A1C should be checked every 4 to 6 weeks, with a target below 6.0% if achievable without significant hypoglycemia.

### Insulin Management

Insulin requirements change substantially across the trimesters. In the first trimester, requirements may actually decrease due to nausea and increased insulin sensitivity, making this the period of highest hypoglycemia risk. In the second trimester, requirements increase as placental hormones (human placental lactogen, cortisol, and progesterone) create progressive insulin resistance. In the third trimester, this trend continues, and patients may require 2 to 3 times their pre-pregnancy insulin doses. A basal-bolus regimen is preferred, combining NPH or a long-acting analog with rapid-acting insulin at meals. Insulin analogs including lispro, aspart, detemir, and degludec are considered safe in pregnancy. Insulin pump therapy is effective for motivated patients and can reduce glycemic variability. Frequent dose adjustments based on glucose patterns are expected and necessary.

### Fetal Surveillance

Fetal surveillance in pregestational diabetes is intensive. A first-trimester dating ultrasound confirms viability and gestational age. Fetal echocardiography is performed at 18 to 22 weeks given the elevated risk of cardiac anomalies. A detailed anatomy survey is also completed at 18 to 22 weeks. Growth ultrasound begins at 28 to 32 weeks and is repeated every 4 weeks. Antenatal testing with nonstress testing or biophysical profile begins at 32 weeks and is performed twice weekly, with earlier initiation at 28 weeks if glycemic control is poor, vascular disease is present, or additional complications exist.

## Delivery Planning

### Timing

For well-controlled pregestational diabetes without complications, delivery is recommended at 39 weeks 0 days to 39 weeks 6 days. When glycemic control is suboptimal or complications such as vascular disease, nephropathy, or prior stillbirth are present, earlier delivery at 36 to 38 weeks may be indicated, with antenatal corticosteroids administered if delivery occurs before 37 weeks. Pregnancies should not routinely be allowed to continue beyond 39 to 40 weeks.

### Mode of Delivery

Vaginal delivery is preferred when there are no contraindications. Elective cesarean delivery should be offered when the estimated fetal weight is 4,500 g or greater (the ACOG threshold for diabetic patients). The risk of shoulder dystocia should be discussed with the patient.

### Intrapartum Glucose Management

During labor, the target glucose range is 70 to 110 mg/dL. Long-acting insulin is held or significantly reduced on the day of induction or delivery. An insulin drip with dextrose-containing IV fluids is used as needed, with glucose checked every 1 to 2 hours. If glucose exceeds 110 mg/dL, an insulin drip is initiated per protocol. If glucose falls below 70 mg/dL, a dextrose bolus is given and the drip is adjusted.

## Postpartum Management

Insulin requirements drop dramatically after delivery of the placenta, as the source of insulin-antagonizing placental hormones is removed. Women with type 1 diabetes should return to their pre-pregnancy insulin doses, with adjustments guided by ongoing glucose monitoring. Women with type 2 diabetes may resume pre-pregnancy oral agents if they are compatible with breastfeeding (metformin is safe during lactation). Glucose monitoring continues, and an A1C is checked at 6 to 12 weeks postpartum. Breastfeeding is strongly encouraged because it reduces insulin requirements in type 1 diabetes and provides metabolic benefits for both mother and infant. Effective contraception should be established before the next pregnancy to allow adequate time for glycemic optimization.

## Diabetic Ketoacidosis in Pregnancy

Diabetic ketoacidosis (DKA) in pregnancy is a medical emergency with a fetal mortality rate of 10 to 35%. It can develop at lower glucose levels than expected -- pregnant patients may present with glucose below 200 mg/dL, a phenomenon termed euglycemic DKA. Common triggers include missed insulin doses, infections, beta-mimetic tocolytics, corticosteroids, and severe emesis with dehydration. Management includes aggressive IV fluid resuscitation, continuous insulin infusion, meticulous electrolyte monitoring (particularly potassium), and continuous fetal monitoring. ICU admission is recommended. Maternal stabilization takes priority over fetal concerns, as treatment of the mother is the most effective way to improve fetal outcomes.

## Clinical Pearls

Pregestational diabetes carries significantly higher risks than gestational diabetes. Preconception optimization -- achieving an A1C below 6.5% before conception -- is the single most impactful intervention for reducing congenital anomalies.

Caudal regression syndrome is the congenital anomaly most specific to diabetic embryopathy, though cardiac anomalies (VSD, transposition, coarctation) are the most common overall.

Insulin requirements change dramatically across trimesters. Frequent dose adjustments are the norm, not the exception, and patients should be counseled to expect this.

DKA can present at relatively normal glucose levels in pregnancy ("euglycemic DKA"). A high index of suspicion should be maintained in any diabetic pregnant patient presenting with nausea, vomiting, and abdominal pain, even if glucose values appear reassuring.

Fetal echocardiography at 18 to 22 weeks is indicated for all pregnancies complicated by pregestational diabetes because of the substantially elevated risk of cardiac malformations.

CGM use in type 1 diabetic pregnancies improves neonatal outcomes, as demonstrated by the CONCEPTT trial, and should be offered when available.

Stillbirth risk is highest in the third trimester with poor glycemic control, which is the driving rationale behind the aggressive fetal surveillance protocols recommended in pregestational diabetes.

## References

- ACOG Practice Bulletin No. 201: Pregestational Diabetes Mellitus (2018, reaffirmed 2023)
- ADA Standards of Care in Diabetes -- 2024: Management of Diabetes in Pregnancy
- Feig DS et al. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT). Lancet. 2017;390:2347-2359
- Kitzmiller JL et al. Managing preexisting diabetes for pregnancy. Diabetes Care. 2008;31:1060-1079
- NICE Guideline NG3: Diabetes in Pregnancy (2020 update)
- Jensen DM et al. Peri-conceptional A1C and risk of serious adverse pregnancy outcome. Diabetes Care. 2009;32:1046-1048