VII. Management of pregestational diabetes A. General
1. In diabetes and pregnancy, fetal glucose levels are similar to maternal glucose levels. Consequently, if maternal glucose control is poor, the fetus will also have hyperglycemia.
2. Fetal hyperglycemia has been associated with increased incidence of congenital malformations, fetal cardiac septal hypertrophy, spontaneous abortion, unexplained fetal death, and preterm birth.
3. Potential maternal sequelae of PDM include those experienced by anyone with poorly controlled PDM (i.e., infection, hypertension, coronary heart disease, retinopathy, nephropathy, neuropathy, ketoacidosis), as well as those effects specific to pregnancy (preeclampsia and polyhydramnios).
B. Symptoms of PDM include diaphoresis, tremors, blurred or double vision, weakness, hunger, confusion, paresthesias of lips and tongue, anxiety,
palpitations, nausea, headache, and stupor. All of these symptoms may herald a hypoglycemic event. Patients and family members should be instructed in the treatment of hypoglycemia (i.e., consumption of milk, crackers, bread), including the administration of glucagon.
C. Preconceptual and pregnancy workup
1. The patient should have a preconceptual history and physical examination, an ophthalmologic examination, and measurement of an ECG.
Echocardiography and a cardiologic consultation should also be obtained if there is presence of, or concern for, cardiac disease.
2. The patient should be advised to maintain tight glucose level control.
3. Measurement of HbA1C may be helpful in evaluating glucose control and assessing risk of fetal malformations. HbA1C levels of 10% or higher are associated with significant risk of fetal malformations. If the HbA1C level is within the normal range, risk appears to be similar to that of nondiabetic women.
4. A 24-hour urine measurement of creatinine clearance and protein excretion should also be performed for evaluation of kidney function.
5. The patient should be started on folate 400 µg/day for spina bifida prophylaxis.
6. The patient should be encouraged to maintain an appropriate activity level or exercise program.
D. The recommended diet for the pregnant woman consists of 1800–2400 kilocalories made up of 15–20% protein, 50–60% carbohydrates, and up to 20% fat.
1. The patient should be encouraged to maintain tight glucose control.
2. A nutritional consultation should also be provided as part of preconceptual and pregnancy counseling.
3. If obesity is present, a weight loss program may be considered before conception.
E. Medical treatment
1. In patients with type 1 DM, insulin requirements are usually increased 50–100% in pregnancy, whereas in patients with type 2 DM, insulin needs usually more than double.
2. The American Diabetic Association recommends the use of human insulin for pregnant women with DM and for women with DM considering pregnancy.
a. Patients taking oral hypoglycemic agents or a regimen of 70/30 mixed (NPH/regular) insulin are switched to human NPH and regular insulin.
b. Oral hypoglycemic medications are not currently used. However, there is some investigational evidence that the newer hypoglycemic agents will be useful in managing diabetes in pregnancy in the near future.
3. Insulin requirements increase throughout gestation, from approximately 0.7 U/kg (body weight)/day during weeks 6–18, to 0.8 U/kg/day during weeks 18–26, to 0.9 U/kg/day during weeks 26–36, and to 1.0 U/kg/day during weeks 36–40.
4. The goals for glucose control for the preconceptual and pregnant patient are the following levels:
Fasting: 60–90 mg/dL
5. Patients with PDM are usually continued on their normal prepregnancy insulin regimen while initial assessment of diabetic control and paneling (recording of blood glucose levels) are performed. Goal glucose values should be discussed with the patient and adjustments in the insulin dosing made
accordingly.
6. If patients are compliant and are still unable to control glycemia, then a long-acting insulin (i.e., ultralente) may be used before breakfast and dinner, together with a short-acting insulin (regular or humalog) before each meal.
7. If intermittent insulin dosing does not result in good glucose control, then use of an insulin pump providing continuous subcutaneous infusion may be necessary.
a. Dosing with the insulin pump must be managed carefully, as the risk of severe hypoglycemia in pregnancy is increased and this, coupled with continuous infusion, may worsen the situation.
b. Although hyperglycemia can have deleterious effects on the patient and fetus, hypoglycemia, if severe, can cause seizures and even death. Thus, patients in whom an insulin pump is to be used must be carefully selected to avoid serious maternal and fetal sequelae.
8. Hospitalization is usually necessary during pregnancy when there is severe hypoglycemia, severe hyperglycemia, a concurrent infection, or obstetric indications.
F. Fetal monitoring and pregestational diabetes
1. During the first trimester, minimal fetal monitoring is required (i.e., assessment for heart tones by Doppler ultrasonography at each visit during the latter portion of the first trimester).
2. During the second trimester, measurement of maternal serum alpha-fetoprotein levels, along with levels of unconjugated estriol and human chorionic gonadotropin, represents the triple screen, which is typically performed at 16–18 weeks' gestation.
a. Ultrasonography (usually at 18–20 weeks) helps to date the pregnancy and evaluate the fetus for genetic abnormalities and other congenital anomalies that may be present.
b. Fetal cardiac anomalies are the most common congenital anomalies with PDM, and so a fetal echocardiogram is recommended at 19–22 weeks' gestation.
3. In the third trimester, the fetus should be monitored as follows.
a. Regular fetal surveillance should be initiated for all pregnancies in insulin-requiring diabetic women.
b. Fetal surveillance should be performed frequently in the presence of maternal vascular disease, hypertension, ketoacidosis, pyelonephritis, preeclampsia, and poor patient compliance.
c. In well-controlled DM without associated complications of hypertension and vascular disease, minimal ongoing evaluation of the fetus may be required.
d. In poorly controlled or complicated DM, the incidence of fetal compromise and death is much higher, and therefore frequent fetal evaluation is required.
e. Repeat obstetrical ultrasonographic examinations for fetal growth may be considered at 28–30 weeks and then at 36–38 weeks.
f. If the patient has evidence of microvascular disease, monthly ultrasonographic examinations starting at 24–26 weeks may be necessary to closely follow fetal growth to assess for intrauterine growth restriction (IUGR).
4. Tests commonly used for fetal assessment are the nonstress test, biophysical profile, and contraction stress test.
5. Timing of fetal testing varies.
a. In a situation in which the patient has extensive complications of DM (i.e., coronary artery disease, nephropathy), fetal assessment may begin at 28 weeks' gestation.
b. For those women with good glucose control and minimal to no complications, regular fetal evaluation may begin at 32–34 weeks.
c. Typically, fetal surveillance such as the nonstress test begins around 32 weeks and occurs twice weekly until delivery.
6. Another method of fetal evaluation is Doppler umbilical artery velocimetry.
a. In pregnant women at risk for vascular disease, Doppler ultrasonographic studies of the umbilical artery can help in assessing fetal outcome.
b. Umbilical artery waveforms obtained via Doppler ultrasonography should show a progressive decline in the systolic/diastolic (S/D) ratio from early pregnancy until term.
c. At 30 weeks, the S/D ratio for the umbilical artery should be below 3.0.
d. The uterine artery S/D ratio should peak around 14–20 weeks and then remain below 2.6 to 26 weeks' gestation.
e. An elevated umbilical S/D ratio is associated with fetal growth restriction and preeclampsia. With increased resistance of the placenta, the systolic pressure of the umbilical artery increases, which causes an elevated ratio.
G. Preterm labor and pregestational diabetes
1. When the patient with DM develops preterm labor, the choice of tocolytics is limited.
2. Sympathomimetics (i.e., terbutaline sulfate, ritodrine hydrochloride) should be avoided because they are known to exacerbate hyperglycemia and may result in ketoacidosis.
3. Indomethacin may be used as long as maternal renal disease or poorly controlled hypertension is absent. Indomethacin should not be given after 32 weeks' gestation.
4. Magnesium sulfate is the tocolytic agent of choice in the presence of preterm labor.
5. Corticosteroids should be given if there is risk of preterm delivery. Caution should be used, however, because of their hyperglycemic effects.
H. Labor, delivery, and diabetes
1. The timing of delivery in an insulin-requiring diabetic patient is important.
2. Factors to be considered in choosing the delivery date are maternal glycemic control, presence or absence of maternal complications, estimated fetal weight, fetal well-being (as indicated by antenatal testing), and amniotic fluid volume.
3. In many patients with well-controlled DM, labor may be induced at 39–40 weeks.
4. Amniocentesis is recommended before elective delivery for patients without accurate gestational dating or for gestations of less than 39 weeks.
5. An elevated lecithin/sphingomyelin (L/S) ratio (ratio at lung maturity is 2.0 or higher) is associated with a low incidence of RDS, even if phosphatidylglycerol (PG) is absent.
6. L/S values are affected by blood and meconium. If these are present in amniotic fluid, L/S would not be a good indicator of fetal lung maturity, in contrast to PG level.
7. PG level is useful if blood, meconium, or other contaminants are present in the amniotic fluid.
8. Amniocentesis may need to be repeated until fetal lung maturity is achieved.
9. If antenatal testing gives nonreassuring results, the decision to deliver the fetus requires determination of the risks to the fetus of remaining in utero compared to the risks of delivery of a premature infant.
10. It is essential that the patient be euglycemic during the intrapartum period (glucose level of 100 mg/dL or less).
a. Maternal hyperglycemia results in fetal hyperglycemia, which then causes fetal hyperinsulinemia. The neonate is then at increased risk of severe hypoglycemia as it loses the maternal infusion of glucose from the umbilical cord and the hyperinsulinemia persists, which can cause seizures and death.
b. During labor and delivery, continuous intravenous (IV) infusion of insulin and dextrose is the optimal means of glycemic control.
c. With elective induction of labor, the patient should receive her normal insulin dose the previous evening. On the morning of her induction, the patient's normal insulin dose should be withheld.
d. Depending on the glucose level on admission, the patient should be started on IV fluids and should be managed as follows:
1. Normal saline should be continued until the patient reaches active labor, or when glucose levels fall below 70 mg/dL.
2. During active labor or when glucose level is less than 70 mg/dL, IV administration of 5% dextrose (with lactated Ringer's or normal saline) should be started. The infusion fluid is adjusted based on blood glucose levels (Table 13-5).
TABLE 13-5. LOW-DOSE CONTINUOUS INSULIN INFUSION FOR LABOR AND DELIVERY
e. Short-acting insulin boluses may be added to bring glucose levels to the target range of 80–100 mg/dL.
f. Blood glucose values should be checked every 1–2 hours and the insulin and fluids adjusted accordingly.
g. In type 1 DM, exogenous insulin is essential for tissue use of glucose; a low-dose insulin drip should be maintained and hypoglycemia managed with glucose infusion.
11. Determination of the route of delivery in an elective procedure remains controversial.
a. If fetal macrosomia is suspected, a trial of labor could ensue.
b. If the estimated fetal weight exceeds 4000 g, the risk of shoulder dystocia and traumatic birth injuries increases.
c. With a suspected birth weight of 4500 g or greater, a cesarean section is indicated.
12. Management of elective cesarean section
a. The patient should withhold her morning insulin dose.
b. Glucose levels should be monitored frequently during and immediately after surgery.
c. After delivery, glucose levels should be checked every 4–6 hours, while administering 5% dextrose with lactated Ringer's or normal saline (at approximately 125 mL/hour).
d. The requirement of tight glucose control during labor and delivery is relaxed.
e. During the initial postpartum period, short-acting insulin is used only when glucose levels are higher than 150 mg/dL.
f. Once the patient is taking a full diabetic diet, insulin can be started at one-third to one-half the antepartum dosage or a dosage comparable to her pregestational dosage.
VIII. Diabetes-associated maternal complications
A. Diabetic ketoacidosis (DKA) is a metabolic emergency that can be life threatening to both mother and fetus. In pregnant patients, DKA can occur at lower blood glucose levels (i.e., less than 200 mg/dL) and more rapidly than in nonpregnant diabetic patients. Although maternal death is rare with proper
treatment, fetal mortality as high as 50% after a single episode of DKA has been reported. Medical illness, usually in the form of infection, is responsible for 50% of cases of DKA; an additional 20% results from neglect of dietary or insulin therapy, or both. In 30% of cases, no precipitating cause is identified.
Antenatal administration of steroids to promote fetal lung maturity can precipitate or exacerbate DKA in pregnant diabetic women.
1. DKA results from either a relative or an absolute deficiency of insulin and an excess of anti-insulin hormones.
a. The resulting hyperglycemia and glucosuria lead to an osmotic diuresis, which results in the loss of urinary potassium and sodium, as well as fluid loss.
b. Insulin deficiency increases lipolysis and therefore hepatic oxidation of fatty acids, which leads to the formation of ketones and the development of metabolic acidosis.
2. Diagnosis
a. Signs and symptoms include abdominal pain, nausea and vomiting, polydipsia, polyuria, hypotension, rapid and deep respirations, and impaired mental status, which can vary from mild drowsiness to profound lethargy.
b. The diagnosis is made by documenting hyperglycemia, acidosis, ketonemia, and ketonuria.
c. Ketoacidosis usually is defined as a plasma glucose level of more than 300 mg/dL (although effects have appeared at lower levels during pregnancy), plasma bicarbonate level of less than 15 mEq/L, and arterial pH of less than 7.3.
3. Management
a. Initial treatment consists of vigorous IV hydration. One liter of normal saline should be administered in the first hour, followed by 250 mL/hour thereafter. Three to 5 L may be required in the first 24 hours.
b. Initial insulin therapy consists of administration of regular insulin at 0.1 U/kg IV push, then an IV infusion of 5–10 U/hour. If glucose levels do not decrease by 25% in the first 2 hours of treatment, the amount of insulin infused should be doubled. Five percent dextrose in water should be started when glucose levels reach 250 mg/dL. The insulin infusion rate should be decreased to 1–2 U/hour when the serum glucose level is found to be below 150 mg/dL. IV insulin and glucose administration should be continued until urine ketones are cleared.
c. Potassium replacement (20–40 mEq/L) should be started with the initial insulin therapy unless potassium levels are above 5.5 mEq/L, or if urine output is inadequate.
d. Sodium bicarbonate may be added for patients with an arterial pH lower than 7.10.
e. Levels of plasma glucose, electrolytes, and arterial blood gases need to be monitored approximately every 4 hours.
f. When the patient is able to tolerate oral food, her usual insulin regimen may be restarted.
B. Hypoglycemia. The strict glycemic control that is recommended during pregnancies complicated by diabetes places patients at increased risk for
hypoglycemic episodes. The presence of hyperemesis in early pregnancy also predisposes these patients to severe hypoglycemia. Up to 45% of pregnant patients with type 1 DM experience episodes of hypoglycemia serious enough to require emergency room care or hospitalization. Severe hypoglycemia may have a teratogenic effect in early gestation. The potential adverse effects on the developing fetus are not yet fully understood.
1. Symptoms include nausea, headache, diaphoresis, tremors, blurred or double vision, weakness, hunger, confusion, paresthesias, and stupor.
2. When evaluating blood glucose levels, one must keep in mind that other factors may be involved in altering blood glucose values.
a. The Somogyi phenomenon is a rebound hyperglycemia after an episode of hypoglycemia and is secondary to a counterregulatory hormone release.
It manifests as widely varied blood glucose levels over a short period of time (i.e., 2:00–6:00 am), with or without symptoms. Treatment of this phenomenon involves decreasing insulin for the critical time period (i.e., 2:00–6:00 am). If the Somogyi phenomenon is taking place, hypoglycemia resolves and glucose levels stabilize.
b. The dawn phenomenon is an early morning increase in plasma glucose, possibly as a response to growth hormone. The patient is treated by increasing her insulin dose at bedtime to maintain euglycemia.
c. Differentiating between these two phenomena requires checking the blood glucose level around 3:00 am. If the patient is hypoglycemic, the Somogyi phenomenon may be in effect, and she should consider decreasing her insulin dose at bedtime. If she is euglycemic, she is appropriately treated; if
she is hyperglycemic, she may have the dawn phenomenon and needs to increase her bedtime dose of insulin.
3. Diagnosis. The diagnosis is made if the patient is symptomatic or has a blood glucose level lower than 60 mg/dL, or both.
4. Treatment. If the patient is experiencing mild symptoms and is otherwise alert and oriented, oral complex carbohydrates should be given (i.e., milk, bread, crackers). If the patient is compromised or severely symptomatic and at risk of aspiration, an ampule of dextrose 10% should be given by IV push immediately, and IV fluids (5% dextrose with Ringer's solution or normal saline) should be started.
C. Retinopathy. Proliferative retinopathy is the most common manifestation of vascular disease in diabetics and is one of the principal causes of blindness in adults in the United States. Diabetic retinopathy is believed to be a direct consequence of hyperglycemia, and it is related to the duration of the disease process. The prevalence of any form of retinopathy has been found to be approximately 2% within 2 years of onset of type 1 DM and 98% among patients who have had diabetes (types 1 and 2) for at least 15 years. Retinopathy is classified as either background simple retinopathy or proliferative diabetic retinopathy. Progression to proliferative disease during pregnancy rarely occurs in patients who have either no retinal disease or only background changes.
If proliferative retinopathy is present, however, it may worsen in pregnancy and lead to blindness if untreated. If benign retinopathy is diagnosed early in gestation, ophthalmologic follow-up should be performed in each trimester. The presence of proliferative changes calls for more frequent examinations, or therapy, or both. Photocoagulation for diabetic retinopathy is accomplished safely during pregnancy.
D. Nephropathy is a progressive disease characterized by increased glomerular permeability to protein, glomerular scarring, and, eventually, renal failure.
Diabetic nephropathy develops slowly, appearing an average of 17 years after the onset of DM, and has an estimated prevalence among diabetic pregnant women of 6%. Diabetic nephropathy is of particular concern in the pregnant patient because of its association with chronic hypertension, preeclampsia, fetal growth retardation, nonreassuring fetal heart tones, preterm delivery, and perinatal death (fetal and neonatal).
1. The diagnosis is made in the presence of persistent proteinuria of more than 3 g/day, serum creatinine level higher than 1.5 mg/dL, hematocrit less than 25%, and hypertension with mean arterial pressure higher than 107 mm Hg. Creatinine clearance level is an important prognostic indicator because a clearance of less than 50 mL/minute has been associated with a high incidence of severe preeclampsia and fetal loss.
2. Patients with diabetic nephropathy require intensive maternal and fetal surveillance throughout gestation. With intensive management, a fetal survival rate of over 90% has been reported.
E. Atherosclerosis is present in many diabetic patients.
1. A complete history and physical examination should be performed to elicit any evidence of ischemic heart disease, heart failure, peripheral vascular disease, or cerebral ischemia.
2. Evaluation of a pregnant patient with DM should always include an ECG. A maternal echocardiogram and cardiologic consultation should be obtained if clinically indicated.
3. Maternal mortality is increased among diabetic patients with ischemic heart disease. Therefore, preconceptual counseling is essential. If conception occurs, termination of the pregnancy may be considered to preserve the health of the patient.
F. Spontaneous abortion
1. Miscarriage among patients with PDM has been reported to range between 6% and 29% and is associated with poor glucose control during the periconceptual period.
2. No increase in incidence of abortion is found in diabetic women with good periconceptual glucose control.
G. Polyhydramnios is a common complication during diabetic pregnancies, with a reported incidence of 3–32%. The incidence of polyhydramnios in diabetic patients is 30 times that in nondiabetic controls. Even though polyhydramnios can be associated with abnormalities of the fetal CNS and GI system, no cause
G. Polyhydramnios is a common complication during diabetic pregnancies, with a reported incidence of 3–32%. The incidence of polyhydramnios in diabetic patients is 30 times that in nondiabetic controls. Even though polyhydramnios can be associated with abnormalities of the fetal CNS and GI system, no cause