Endocrine disease during pregnancy is common and can either predate the pregnancy or be diagnosed during the pregnancy. It is important to understand the impact of the pregnancy on the individual endocrine disorder and the impact of the endocrine disorder on the pregnancy. In this chapter we review the pathophysiology, clinical presentation, and management during the puerperium of diabetes mellitus, thyroid disease, and pheochromocytoma.
KeywordsEndocrine disorder, Thyroid disease, Hyperthyroidism, Hypothyroidism, Diabetes mellitus, Pheochromocytoma
Diabetes Mellitus, 1056
Definition and Epidemiology, 1056
Clinical Presentation and Diagnosis, 1057
Interaction with Pregnancy, 1058
Obstetric Management, 1062
Anesthetic Management, 1063
Thyroid Disorders, 1065
Definition and Epidemiology, 1072
Clinical Presentation and Diagnosis, 1073
Interaction with Pregnancy, 1074
Medical and Surgical Management, 1074
Obstetric Management, 1076
Anesthetic Management, 1076
Definition and Epidemiology
Diabetes mellitus (DM) is a common metabolic disorder with a prevalence of approximately 8% in the general adult population worldwide. DM results from either an absolute deficiency in insulin secretion (type 1) or a combination of resistance to insulin in target tissues and inadequate insulin secretion (type 2). Although a combination of genetic and environmental factors contributes to both types, type 1 DM is primarily an autoimmune disorder. Type 2 DM occurs primarily in obese individuals and accounts for 90% to 95% of cases of DM in the United States. Gestational DM refers to DM or glucose intolerance that is first diagnosed during pregnancy and occurs in approximately 5% to 20% of pregnancies in the United States, depending on the screening test strategies implemented.
Insulin is a peptide hormone secreted by the beta cells of the islets of Langerhans in the pancreas that binds to specific cell-surface receptors in insulin-responsive target tissues (e.g., liver, skeletal muscle, fat). The intracellular effects of insulin are mediated by tyrosine kinase in the beta-subunit of the receptor through a cascade of distal protein kinase–mediated phosphorylations. Normal hepatic glucose metabolism represents a balance between the effects of insulin and several “counterregulatory” hormones (e.g., glucagon, cortisol, epinephrine [adrenaline], growth hormone). This control system for glucose homeostasis permits rapid adjustments in glucose metabolism in the fed and fasted states. Insulin is also an important anabolic regulator of lipid and amino acid metabolism ( Fig. 43.1 ). Insulin deficiency (absolute or relative) associated with DM results in abnormal metabolism of carbohydrates, lipids, and amino acids.
Acute and chronic complications occur in patients with DM ( Box 43.1 ). The three major acute complications are diabetic ketoacidosis (DKA), hyperglycemic nonketotic state, and hypoglycemia. DKA occurs predominantly in patients with type 1 DM. It may develop with a new source of insulin resistance (e.g., infection, trauma, stress) and/or as a result of failure to administer usual insulin doses. DKA results from decreased uptake of glucose by insulin-responsive tissues and greater use of free fatty acids as a hepatic energy source. The lack of insulin favors lipolysis, beta-oxidation of free fatty acids in the liver, and hepatic formation of acetoacetate and beta-hydroxybutyrate from the excess acetyl-coenzyme A generated by fatty acid oxidation. These biochemical events result in metabolic acidosis, hyperglycemia, and dehydration secondary to osmotic diuresis. Signs and symptoms of DKA include nausea, vomiting, weakness, tachypnea, hypotension, tachycardia, stupor, and acetone on the breath. The diagnosis of DKA depends on the laboratory findings of hyperglycemia, ketosis, and acidosis.
Hyperglycemic nonketotic state (HNS) occurs predominantly in patients with type 2 DM. Laboratory findings in HNS are hyperglycemia (blood glucose level often greater than 600 mg/dL [33.3 mmol/L]), hyperosmolality (greater than 320 mOsm/kg), and moderate azotemia (serum blood urea nitrogen [BUN] often greater than 60 mg/dL), without ketonemia or significant acidosis. The absence of significant ketosis in HNS may indicate an inhibition of lipolysis by hyperosmolality or low levels of insulin. DKA and HNS are probably related conditions; inadequate insulin therapy and infection are the most common precipitating events for both.
Hypoglycemia is a continuing health threat in diabetic patients, especially in patients receiving insulin therapy. Hypoglycemia results from an imbalance between insulin or oral hypoglycemic agents and available metabolic fuels. In hospitalized patients with DM, major risk factors for hypoglycemia include renal insufficiency and decreased caloric intake. Symptomatic awareness of hypoglycemia and counterregulatory responses may be inadequate in some diabetic patients with autonomic neuropathy. Problems with hypoglycemia awareness in patients receiving beta-adrenergic receptor antagonists can be minimized by using beta 1 -adrenergic receptor–selective antagonists. Factitious hypoglycemia results from a deliberate, inappropriate self-administration of insulin or an oral hypoglycemic agent.
In general, the rate of chronic complications increases with the duration of DM. The Diabetes Control and Complications Trial, a randomized multicenter study of patients with type 1 DM, demonstrated a positive relationship between tight glucose control and a lower incidence or rate of progression of retinopathy, nephropathy, and neuropathy. In a similar study of patients with type 2 DM—the UK Prospective Diabetes Study (UKPDS)—intensive glucose control lowered the incidence of microvascular complications but not of macrovascular complications or patient mortality. In contrast, antihypertensive therapy reduced the incidence of macrovascular complications and mortality in patients with both type 2 DM and chronic hypertension. DM may affect cardiovascular function as a result of coronary atherosclerosis, autonomic neuropathy, or development of a cardiomyopathy.
Clinical Presentation and Diagnosis
Box 43.2 lists the current diagnostic criteria for DM in nonpregnant patients.
Fasting plasma glucose ≥ 126 mg/dL (7 mmol/L). Fasting is defined as no caloric intake for at least 8 h. a
a In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.
Two-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test. The test should be performed as described by the World Health Organization, using an oral glucose load with the equivalent of 75 grams of anhydrous glucose dissolved in water. a
Hemoglobin A 1c ≥ 6.5%. a
A random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis.
Gestational DM is associated with (1) age greater than 35 years, (2) obesity, (3) family history of type 2 DM, (4) prior history of gestational DM, (5) history of polycystic ovarian syndrome, and (6) history of prior stillbirths or macrosomic babies. Several observational clinical studies, including the Hyperglycemia and Adverse Pregnancy Outcome study, have shown that adverse pregnancy outcomes are a continuous function of glucose intolerance in pregnancy. Box 43.3 lists the current recommendations of the American Diabetes Association (ADA) for screening and diagnosis of gestational DM, including one-step and two-step procedures. The choice between one-step and two-step screening strategies for gestational diabetes at 24 to 28 weeks’ gestation remains controversial. As diagnostic thresholds decrease for any disease process, the apparent prevalence in the population increases. The continuing debate over screening protocols for gestational DM centers on whether treatment of an expanded patient population is cost-effective and will improve outcomes.
Perform a 75-gram oral glucose tolerance test, with plasma glucose measurements when the patient is fasting and at 1 hour and 2 hours, at 24 to 28 weeks’ gestation in women not previously diagnosed with overt DM.
The oral glucose tolerance test should be performed in the morning after an overnight fast of at least 8 hours.
The diagnosis of gestational DM is made when any of the following plasma glucose values are met or exceeded:
Fasting: 92 mg/dL (5.1 mmol/L)
1 hour: 180 mg/dL (10 mmol/L)
2 hours: 153 mg/dL (8.5 mmol/L)
Perform a nonfasting 50-gram oral glucose load test, with a plasma glucose measurement at 1 hour, at 24 to 28 weeks’ gestation in women not previously diagnosed with overt DM.
If the plasma glucose level 1 hour after the glucose load is ≥ 130 mg/dL (7.2 mmol/L), then proceed to a 100-gram oral glucose tolerance test (Step 2).
The 100-gram oral glucose tolerance test should be performed when the patient is fasting.
Four blood samples are collected: fasting, 1 hour, 2 hours, and 3 hours.
The diagnosis of gestational DM is made if at least two of the four plasma glucose samples exceed the following criteria (either Carpenter-Coustan or National Diabetes Data Group).
|Sample||Carpenter-Coustan||Or||National Diabetes Data Group|
|Fasting||95 mg/dL (5.3 mmol/L)||105 mg/dL (5.8 mmol/L)|
|1 hour||180 mg/dL (10 mmol/L)||190 mg/dL (10.6 mmol/L)|
|2 hours||155 mg/dL (8.6 mmol/L)||165 mg/dL (9.2 mmol/L)|
|3 hours||140 mg/dL (7.8 mmol/L)||145 mg/dL (8.1 mmol/L)|
DM, Diabetes mellitus.
Glycosylated hemoglobin measurements are used as time-integrated estimates of glycemic control, although both analytical and physiologic factors may affect this relationship. The normal range for hemoglobin A 1c in nondiabetic pregnant women is 4.0% to 5.5%, compared with 4.8% to 6.5% in nondiabetic nonpregnant women.
Interaction with Pregnancy
How Does Pregnancy Affect Diabetes Mellitus?
Pregnancy is characterized by progressive peripheral resistance to insulin at the receptor and postreceptor levels in the second and third trimesters ( Fig. 43.2 ). The presumed mechanism involves an increase in counterregulatory hormones (e.g., placental lactogen, placental growth hormone, cortisol, progesterone) during pregnancy. The change in placental lactogen is a plausible mechanism, given that (1) a graph of serum lactogen level during pregnancy is similar in shape to that of insulin requirement in pregnant women with type 1 DM and (2) placental lactogen has growth hormone–like activity. Also, maternal adipokines probably are important factors in insulin resistance of pregnancy ; they facilitate the provision of maternal fuels for the fetus.
Gestational DM develops when a patient cannot mount a sufficient compensatory insulin response during pregnancy. In some patients, gestational DM can be viewed as a preclinical state of glucose intolerance that is not detectable before pregnancy. After delivery, most patients return to normal glucose tolerance but remain at increased risk for DM (predominantly type 2) in later life. The recurrence rate for gestational DM in a subsequent pregnancy is 35% to 70%.
In patients with pregestational DM, insulin requirement progressively increases during pregnancy because of peripheral insulin resistance. At term, the daily insulin requirement is approximately 1.0 insulin unit/kg, compared with 0.7 unit/kg before pregnancy. Insulin requirement may be higher in pregnancies with multiple gestation. During late pregnancy in normal healthy patients, basal and glucose-stimulated plasma insulin levels are twice the postpartum measurements. These changes reflect pregnancy-related increases in pancreatic islet cell mass and glucose sensitivity, probably secondary to the net effect of competing progesterone and lactogenic hormone stimuli in the endocrine pancreas. Near term, maternal overnight insulin requirements may decrease, presumably as a result of a “siphoning of maternal fuels” by the growing fetus during the overnight maternal fast.
Endogenous plasma insulin concentration during labor and delivery in nondiabetic parturients differs from exogenous insulin requirement in laboring diabetic women. In nondiabetic parturients, the plasma glucose concentration is only one of many factors that affect endogenous insulin secretion; glucose production and use are markedly higher during painful labor than postpartum. Plasma insulin concentration remains unchanged except for a brief increase during the third stage of labor and immediately postpartum. This finding suggests that glucose use during labor is largely independent of insulin. The pattern of plasma insulin concentrations is similar in nondiabetic patients with and without analgesia (e.g., nitrous oxide, meperidine [pethidine]).
In patients with type 1 DM, insulin requirement decreases with the onset of the first stage of labor. These patients may require no additional insulin during the first stage of labor, although insulin requirement is modified by (1) the level of metabolic control before labor, (2) the residual effect of prior doses of subcutaneous insulin, and (3) the glucose infusion rate. Insulin requirement increases during the second stage of labor via an unknown mechanism. The use of epidural analgesia or oxytocin does not affect exogenous insulin requirement during the first and second stages of labor. After delivery—either vaginal or cesarean—insulin requirement in women with type 1 DM decreases markedly for at least several days, although there is significant variability among individuals ( Fig. 43.3 ). Presumably, the decreased insulin requirement results from loss of counterregulatory hormones produced by the placenta. Pituitary growth hormone responsiveness to hypoglycemia is blunted in late pregnancy and may contribute to impaired counterregulatory responses during the postpartum period. Insulin requirement gradually returns to prepregnancy levels within several weeks of delivery in women with type 1 DM.
Before the discovery of insulin in 1921, pregnancies were rare in diabetic patients. Insulin therapy improved the rate of survival in women with severe DM, allowing these women to reach childbearing age and become pregnant. Maternal outcomes improved, but fetal and neonatal morbidity and mortality remained high.
In 1949, White proposed a classification system for DM during pregnancy based on 439 consecutive cases. Physicians caring for pregnant diabetic patients should be familiar with the White system, which has endured with some modifications ( Table 43.1 ). The system emphasizes the relationship among the duration of type 1 DM, vascular complications of type 1 DM, and poor fetal outcome. In the 1950s, fetal survival rates were as follows: class A, 100%; class B, 67%; class C, 48%; class D, 32%, and class F, 3%.
|Class||Age at Onset of Diabetes (Yr)||Duration of Diabetes (Yr)||Vascular Disease||Insulin Required|
|B||> 20||< 10||No||Yes|
|D a||< 10||or||> 20||Yes||Yes|
|R (proliferative retinopathy)||Any||Any||Yes||Yes|
|T (status post–renal transplantation)||Any||Any||Yes||Yes|
|H (ischemic heart disease)||Any||Any||Yes||Yes|
The incidence of DKA has decreased from 9% to between 0.5% and 3% of diabetic pregnancies, probably as a result of improvements in medical care and patient education. Similarly, the incidence of perinatal and maternal mortality from DKA during pregnancy has decreased in the past several decades. DKA during pregnancy occurs predominantly in patients with type 1 DM, but also in patients with type 2 DM or gestational DM. The higher risk for DKA during pregnancy reflects the metabolic adaptations of pregnancy, including peripheral insulin resistance.
During pregnancy, DKA occurs most commonly during the second and third trimesters. It is associated with (1) emesis, (2) infection, (3) poor compliance or noncompliance, (4) insulin pump failure, (5) use of beta-adrenergic receptor agonists, (6) use of corticosteroids, and (7) poor medical management. The infection rate in pregnant women with pregestational type 1 DM is 3.2 times higher than that in nondiabetic pregnant women. DKA may be the first clinical sign of type 1 DM during pregnancy. Beta-adrenergic receptor agonists, which are used to treat preterm labor, and corticosteroids, which are used to accelerate fetal lung maturity, both have counterregulatory pharmacologic effects that oppose insulin action. Beta-adrenergic receptor agonist tocolytic therapy, with or without concurrent corticosteroid therapy, and by any route of administration, can precipitate DKA during pregnancy. Beta-adrenergic receptor stimulation worsens glucose intolerance by stimulating glucagon secretion ; beta-adrenergic receptor agonists may be well tolerated in pregnant women with DM if higher insulin requirements are anticipated and doses are adjusted in response to frequent blood glucose determinations.
Nonreassuring fetal heart rate patterns during episodes of maternal DKA have been described. After appropriate medical management of maternal DKA, preterm uterine contractions stopped and fetal heart rate patterns normalized. The mechanism of fetal compromise during DKA is unclear, but it may be related to changes in uterine blood flow. Blechner et al. demonstrated that uterine artery blood flow is reduced by acute maternal metabolic acidosis. A single case report demonstrated reversible redistribution of fetal blood flow during an episode of maternal DKA on the basis of Doppler pulsatility indices of the umbilical and middle cerebral arteries.
There are three case reports of HNS during pregnancy. No conclusion can be drawn about HNS and pregnancy, except that HNS rarely occurs during pregnancy.
Hypoglycemia occurs in 33% to 71% of pregnant women with pregestational type 1 DM and is a significant health risk. This rate is 3 to 15 times higher than that in similar groups of nonpregnant patients with type 1 DM ; 80% to 84% of severe hypoglycemia episodes occur before 20 weeks’ gestation. The risk for hypoglycemia during pregnancy in patients with type 1 DM increases with tight glucose control. This pattern mirrors the clinical experience in nonpregnant women with type 1 DM, in which a threefold rise in the occurrence of severe hypoglycemia results from tight insulin control. In both pregnant and nonpregnant patients with type 1 DM, counterregulatory hormone response to hypoglycemia is impaired after intensive insulin therapy. Two small series suggest that acute mild to moderate maternal hypoglycemia is not associated with acute alterations in fetal well-being in pregnant women with type 1 DM.
The relationship between pregnancy and the development of macrovascular complications of DM is largely unknown. Patients with pregestational type 1 DM have higher systolic and diastolic blood pressure during pregnancy, and they are three times more likely than nondiabetic control subjects to have gestational hypertension. In women with pregestational type 1 DM, the risk for preeclampsia is increased with increased severity of diabetes (White classification), and proteinuria early in pregnancy is associated with an increased risk for adverse outcomes. Myocardial infarction is a rare complication. The effect of gestational hypertension on the progression of atherosclerotic disease in diabetic patients is unclear.
Pregnancy may accelerate the development of proliferative retinopathy, a microvascular complication of DM. Hyperglycemia and hypertension are also associated with the progression of retinopathy.
In contrast to diabetic retinopathy, pregnancy does not accelerate the progression of diabetic nephropathy, provided that antihypertensive therapy is effective. It is unclear whether pregnancy accelerates the progression of somatic or autonomic neuropathy in diabetic women.
How Does Diabetes Mellitus Affect the Mother and Fetus?
Both pregestational and gestational DM are associated with higher rates of gestational hypertension, polyhydramnios, and cesarean delivery. The incidence of cesarean delivery is higher in women with pregestational DM than in women with gestational DM. Trial of labor after cesarean delivery (TOLAC) in patients with gestational DM is associated with rates of operative vaginal delivery and repeat cesarean delivery that are higher than those found in nondiabetic controls. Pregestational DM—but not gestational DM—is associated with a twofold to threefold increase in the incidence of preterm labor and delivery.
Box 43.4 lists the fetal complications of maternal DM during pregnancy. Fetal macrosomia is a well-recognized complication of maternal DM. Most studies suggest that both pregestational DM and gestational DM result in an increased incidence of fetal macrosomia. Depending on the definition of macrosomia (4000 g versus 4500 g), pregestational DM results in fetal macrosomia in 9% to 25% of women—a fourfold to sixfold higher rate than in nondiabetic controls.
During Pregnancy and the Puerperium
Birth injury or trauma
Central nervous system: anencephaly, encephalocele, meningomyelocele, spina bifida, holoprosencephaly
Cardiac: transposition of great vessels, ventricular septal defect, situs inversus, single ventricle, hypoplastic left ventricle
Skeletal: caudal regression
Renal: agenesis, multicystic dysplasia
Gastrointestinal: anal or rectal atresia, small left colon
Intrauterine or neonatal death
Neonatal respiratory distress syndrome
Possible impairment of cognitive development
Macrosomia results in an increased risk for shoulder dystocia and birth trauma with vaginal delivery. Moreover, when comparisons are made within birth weight categories above 4000 g, pregnancies in diabetic women have a higher risk for shoulder dystocia than nondiabetic women. The use of intensive insulin therapy may reduce the risk for birth trauma in women with pregestational DM. Several mechanisms have been suggested for the development of fetal macrosomia in diabetic pregnancy. Maternal hyperglycemia can result in fetal hyperglycemia, with reactive fetal hyperinsulinemia and an anabolic response in the fetus. Shoulder dystocia may reflect the excessive growth of the fetal trunk (relative to the fetal head) in response to fetal hyperinsulinemia.
Women with pregestational DM are at increased risk for fetal anomalies (see Box 43.4 ). The incidence of major anomalies, estimated to be 6% to 10%, is five times higher than in nondiabetic controls. Overall, cardiovascular anomalies are most common, followed by anomalies of the central nervous system (CNS). Caudal regression syndrome is uncommon, but it is 200 times more likely in diabetic than in nondiabetic pregnancies. The incidence of major congenital anomalies in infants of women with gestational DM is 3% to 8%, which is lower than in infants of women with pregestational DM.
Mechanisms that may be involved in the development of fetal structural malformations in diabetic pregnancies include embryonic apoptosis and yolk sac vasculopathy. Most fetal structural malformations that occur during diabetic pregnancies are likely to have a multifactorial etiology. However, hyperglycemia during the period of critical organogenesis before the seventh week after conception is probably the single strongest etiologic factor in diabetic women and may be associated with embryonic oxidative stress.
Studies have suggested that patient education and strict glycemic control during the preconception period may reduce the rate of major congenital anomalies from 10% to 1% in patients with pregestational DM. The latter figure is similar to the baseline risk for major structural malformations in the general population. Strict glycemic control initiated during the preconception period also increases the incidence of maternal hypoglycemic episodes. These studies suggest that hypoglycemia is not a significant factor in the etiology of human malformations, because the rate of anomalies decreased 10-fold despite hypoglycemic episodes. Similarly, strict glycemic control before conception also has been associated with a threefold decrease in the incidence of spontaneous abortion in women with pregestational DM. Dicker et al. observed normal induced ovulation, in vitro fertilization, and early embryonic development in a small series of infertile patients with pregestational DM who attended a preconception diabetes clinic. However, only 36% of women with known pregestational DM receive appropriate medical care before conception.
During the 1950s to 1970s, the perinatal mortality rate in women with pregestational DM was 15% to 18%. Subsequent studies noted a decrease to 2%, a rate similar to that in nondiabetic controls. In contrast, one study noted a rate of 8%, three times greater than in nondiabetic controls. If the entire population is considered, the perinatal mortality rate likely remains higher in patients with pregestational DM than in nondiabetic controls. The rate in patients with gestational DM is intermediate between the rate in women with pregestational diabetes and the rate in nondiabetic controls.
Historically, intrauterine fetal death was responsible for approximately 40% of the perinatal deaths in women with DM; 68% of the stillbirths occurred between 36 and 40 weeks’ gestation. In contemporary reports, the ratio of intrauterine deaths to neonatal deaths in diabetic pregnancies has varied from 0 to 1.0. Fetal macrosomia is a risk factor for intrauterine fetal demise in both diabetic and nondiabetic pregnancies. Recurrent episodes of intrauterine hypoxia can occur in diabetic pregnancies that end in stillbirth; episodes of hypoxia may reflect reduced uteroplacental blood flow and changes in fetal carbohydrate metabolism. Congenital anomalies have now emerged as the leading cause of perinatal mortality in diabetic pregnancies. This change likely reflects better obstetric care during pregnancy, despite the lack of adequate glycemic control before conception.
Two series that involved women who delivered between 1950 and 1979 demonstrated an incidence of neonatal respiratory distress syndrome (RDS) in diabetic pregnancies that was 6 to 23 times that in nondiabetic controls. Respiratory distress is more common among newborns who are delivered preterm or who are surgically delivered without labor. Later studies of patients with both pregestational and gestational DM have not demonstrated a significant difference in the incidence of neonatal RDS between diabetic and nondiabetic pregnancies.
The level of glycemic control during pregnancy affects the amniotic fluid phospholipid profile. In pregnancies of patients with poorly controlled diabetes, there may be a higher incidence of immature amniotic fluid fetal lung profiles at 34 to 38 weeks’ gestation.
Neonatal hypoglycemia occurs in 5% to 12% of cases of pregestational and gestational DM. This represents a 6-fold to 16-fold higher risk for neonatal hypoglycemia than in nondiabetic controls. Neonatal hypoglycemia likely results from sustained fetal hyperinsulinemia in response to chronic intrauterine hyperglycemia. Clinical studies have demonstrated higher fetal insulin levels and exaggerated fetal insulin responses to acute maternal hyperglycemia in diabetic pregnancies. An acute increase in maternal glucose concentration, as might occur if a dextrose-containing solution is used for intravenous hydration during administration of neuraxial anesthesia, can lead to reactive neonatal hypoglycemia, even in nondiabetic women.
There is a twofold to fivefold higher incidence of neonatal hyperbilirubinemia in women with pregestational and gestational DM than in nondiabetic controls. Other associated factors include the severity of gestational DM and excess maternal weight gain during pregnancy. Both the etiology and the clinical significance of neonatal hyperbilirubinemia are unknown, although one study noted the absence of long-term morbidity.
Children of diabetic mothers are at increased risk for development of DM, likely from a combination of genetic and intrauterine environmental factors. Despite the well-known association of type 1 DM with human leukocyte antigen markers, studies of monozygotic human twins have suggested that genetic factors have a greater role in type 2 DM than in type 1 DM (100% versus 20% to 50% concordance, respectively). In addition, fathers with type 1 DM are five times more likely than mothers with the same disease to have a child with type 1 DM. The intrauterine environment also affects the development of glucose intolerance in offspring.
Some investigators have suggested that cognitive development may be impaired in the children of diabetic mothers, but this issue remains controversial.
Early, strict glycemic control is the best way to prevent fetal structural malformations in women with pregestational DM. Determination of hemoglobin A 1c concentrations may help the physician determine the adequacy of preconceptional glycemic control.
During pregnancy, the patient should frequently determine capillary blood glucose concentration using a reflectance meter. However, the ideal frequency of these measurements remains under investigation. Continuous glucose monitoring systems (e.g., transdermal, subcutaneous) have been used safely in pregnancy and enable remote monitoring. Glucose determinations guide adjustments in diet and insulin therapy. In general, insulin requirement increases progressively during the second and third trimesters. Both maternal and perinatal outcomes seem to improve when maternal glycemic control approaches that observed in normal pregnancies. Table 43.2 illustrates glycemic targets recommended by the American Diabetes Association for pregnant patients with either pregestational or gestational DM. Of course, strict glycemic control increases the risk for maternal hypoglycemia.
|Parameter||Pregestational DM a||Gestational DM a|
|Hemoglobin A 1c||6%–6.5%||6%–6.5%|
|Fasting plasma glucose||60–99 mg/dL (3.3–5.5 mmol/L)||≤ 95 mg/dL (5.3 mmol/L)|
|One-hour postprandial plasma glucose||100–129 mg/dL (5.6–7.2 mmol/L)||≤ 140 mg/dL (7.8 mmol/L)|