Diabetes mellitus is the most common medical complication of pregnancy, affecting 2-3% of pregnancies. Ninety percent of cases represent gestational diabetes mellitus (GDM). GDM is carbohydrate intolerance with onset during the present pregnancy. Fifty percent of women who develop GDM will develop overt DM within 20 years. Women with overt DM who conceive have a 10-fold increase in the maternal mortality and a perinatal mortality rate of 4%. Most maternal deaths are caused by diabetic ketoacidosis (DKA), and most perinatal deaths are related to prematurity.
Classification of diabetes mellitus
The Priscilla White classification system is based on age at onset and duration of DM as well as vascular complications.
|Class A1||Diet-controlled GDM|
|Class A2||GDM complicated by insulin use, hypertension, polyhydramnios, macrosomia, or a prior stillbirth|
|Class B||Overt diabetes, with an onset after age 20 and a duration of less than 10 years|
|Class C||Overt DM, with an onset at 10 to 19 years of age or a duration of 10 to 19 years|
|Class D||Juvenile onset or a duration of 20 years or more|
|Class F||Diabetes associated with nephropathy|
|Class R||Diabetes associated with retinopathy|
|Class M||Diabetes associated with cardiomyopathy|
|Class T||Diabetes in renal transplant patients|
Diabetes and pregnancy
The incidence of major malformations is increased by fourfold in the offspring of women with overt diabetes. A major malformation may occur in 30%, and spontaneous abortions may occur in 35%. Common fetal malformations include central nervous system, cardiac, renal, and retinal anomalies. With excellent glycemic control before conception, rates of fetal malformation and spontaneous abortion are equal to those in the general population.
Maternal hyperglycemia causes fetal hyperglycemia and fetal hyperinsulinemia. The infant may develop macrosomia, birth trauma, intrauterine fetal death (IUFD), neonatal hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia, respiratory distress syndrome, and intrauterine growth restriction.
A normal periconceptional glycosylated hemoglobin (Hb A1c) level is associated with outcomes similar to those in women without DM. Measuring hemoglobin A1c is not useful once pregnancy is established.
Pregnancy has been associated with a twofold risk for the progression of maternal diabetic retinopathy. Proliferative retinopathy may lead to vision loss if untreated and thus it should be monitored and managed with photocoagulation. Renal function should be evaluated with a 24-hour urine collection for creatinine clearance and protein excretion.
Screening for DM is recommended for all women over 25 years of age at 24 to 28 weeks of gestation. Women with risk factors for DM are screened at the first visit; if that early initial screen is negative, it should be repeated at 24-28 weeks.
Risk factors for DM. Obese or overweight women, family history of diabetes, prior miscarriages or stillbirths without a specific reason, prior macrosomia of 9 lb or more, gestational diabetes in a previous pregnancy, hypertension and/or hyperlipidemia, prior baby with anomalies, 30 years old or more.
One hour after a 50-g oral glucose tolerance test, the level should be <140 mg/dL. If not, a 3-hour glucose tolerance test is necessary. A solution containing 100 g of glucose is used following 3 days of adequate carbohydrate intake. Two abnormal values are necessary diagnose of GDM.
|Time||Glucose level (mg/dL)|
Management of diabetes in pregnancy
For women of normal weight, the average caloric intake should range between 2200 and 2400 kcal, with protein accounting for 20-25% of a total energy intake and carbohydrate for 40-45%, resulting in a low-fat diet. Activity and diet should be consistent from day to day.
Euglycemia is essential during pregnancy. Reasonable goals include FBS of 60 to 80 mg/dL and 2-hour PP levels of 60 to 100 mg/dL. However, insulin is usually not started unless sustained levels of FBS $105 mg/dL and 2-hour PP $120 mg/dL are present. The insulin requirement is decreased in early pregnancy, and insulin requirement increases from 13 to 20 weeks to delivery.
Patients taking insulin should monitor their glucose levels daily. Patients on dietary management alone may have their fasting blood sugar (FBS) and 2-hour post-prandial (PP) levels checked in the clinic every 1 or 2 weeks.
|2 hours After meals||<120 mg/dL|
|From 2 AM to 6 AM:||60-90 mg/dL|
Initial insulin consists of a bedtime dose of intermediate-acting NPH insulin, 0.1 U/kg of actual body weight. Most patients require a combination of both intermediate-acting and short-acting (regular) human insulin in the morning and evening. Give 2/3 of total daily requirement in the AM; divide AM dose into 2/3 NPH and 1/3 regular. Give 1/3 of daily requirement in evening: 1/2 as NPH and 1/2 as regular insulin. Adjust doses by no more than 20% at a time. Evening dose may be to administered as separate injections of short-acting insulin at dinnertime and intermediate-acting insulin at bedtime to reduce the frequency of nocturnal hypoglycemia.
Glucose is monitored at home using 2-hour PP values, as these values give better measures of overall glycemic control than before-meal values.
Ultrasonography should be used to evaluate fetal growth, estimate weight, and detect hydramnios, neural tube defects, and anomalies. Because of an increase in anomalies in pregnancies complicated by overt (pre-gestational) diabetes, a fetal anatomic survey including echocardiography is recommended at 18 to 20 weeks.
The time of greatest fetal risk is in the third trimester. Fetal surveillance should closely monitor the status of the fetus because of the increased risk of IUFD. The usual interval between NSTs is 3 to 4 days.
In class A1, biophysical profile and amniocentesis are not necessary, and delivery by 40 weeks is recommended.
In classes A2, B, and C, twice-weekly nonstress tests (NSTs) are recommended from 34 weeks on. Delivery at 38 weeks can usually be accomplished if the amniocentesis reveals the presence of phosphatidyl glycerol (PG).
In classes D, F, or R, twice-weekly NSTs are recommended from 28 to 30 weeks on, with delivery at 36 weeks if PG is found. Diabetic pregnancies may proceed to term if glucose control has been satisfactory.
In women with well-controlled gestational diabetes, weekly biophysical fetal testing is initiated as early as 34 weeks gestation. More intensive biophysical fetal testing is recommended in patients who require insulin, with hypertension, or with a history of previous stillbirth.
Management of delivery
Effective glycemic control and antepartum fetal surveillance methods may obviate the need for elective preterm delivery to avoid IUFD.
The presence of PG at amniocentesis may be used as an indication for delivery. If PG is negative at amniocentesis, delivery may be postponed, and a repeat test should be planned. Increased fetal surveillance should be performed in the interim. In case of preterm labor, magnesium sulfate or a calcium channel blocker is preferred over $-sympathomimetics because of the tendency for hyperglycemia with the $-mimetics. Corticosteroids for fetal lung maturity should be administered with knowledge that hyperglycemia will result and additional insulin may be required.
Continuous infusion of insulin and glucose should be used to control maternal glucose levels during labor and delivery. In cases where insulin has been used during the pregnancy, capillary glucose levels should be evaluated at the bedside hourly to maintain plasma glucose at approximately 100 to 130 mg/dL.
Insulin therapy during labor
In patients with well-controlled diabetes who are scheduled for elective induction of labor, the usual dose of insulin is given at bedtime, and morning insulin is withheld. Once active labor begins, a constant infusion of 5% dextrose is given to supply caloric needs.
Short-acting insulin is infused if the patient becomes hyperglycemic.
|Blood Glucose (mg/100 mL)||Insulin Dosage (U/h)||Fluids (125 mL/h)|
|<100||0||5%dextrose/Lactated Ringer’s solution|
|100-140||1.0||Dextrose/Lactated Ringer’s solution|
|Dilution is 25 U of regular insulin in 250 mL of normal saline, with 25 mL flushed through line, administered intravenously.|
Cephalopelvic disproportion, shoulder dystocia and traumatic birth injuries are more likely with vaginal delivery of large infants of diabetic women. Performance of an ultrasound examination at term is usually not useful in these cases because of the large variation at extremes of weight between predicted and actual fetal weight.
Elective cesarean delivery
An estimated fetal weight of greater than 4500 g is an indication for cesarean delivery to avoid birth trauma.
Elective cesarean delivery is scheduled for early morning. The usual morning insulin dose is withheld, and glucose levels are monitored hourly. An insulin 5% dextrose is initiated and an insulin infusion is initiated. After delivery, intravenous dextrose is continued, and glucose levels are checked every 4-6 hours.
In the postpartum period, short-acting insulin is administered if the glucose level rises above 200 mg/dL.
For patients with pregestational diabetes, once the patient begins a regular diet, subcutaneous insulin can be reinstituted at dosages substantially lower than those given in the third trimester. It is helpful if the pregestational dose is known.