Common Medical and Surgical Conditions Complicating Pregnancy

Chapter 16 Common Medical and Surgical Conditions Complicating Pregnancy

The more common medical, infectious, and surgical disorders that may complicate pregnancy are covered in this chapter. The pharmacologic agents recommended for these disorders have been classified by the Food and Drug Administration (FDA) for fetal risk (see Box 7-1 on page 73). Up to date information on these drugs can be found at www.FDA.gov/ by selecting “Drugs” from the menu and searching for a specific agent.

Endocrine Disorders

Diabetes mellitus and thyroid disease are the two most common endocrine disorders complicating pregnancy.

DIABETES MELLITUS

Incidence and Classification

The prevalence of diabetes mellitus has greatly increased in the last 20 years. Reports show a rate of 3% to 8% of gestational diabetes mellitus (GDM). Pregestational diabetes is present in about 1% of pregnancies. Overall, 90% of diabetes in pregnant women is gestational and about 10% pregestational.

GDM is defined as glucose intolerance with onset or first recognition during pregnancy. Pregnancy is associated with progressive insulin resistance. Human placental lactogen, progesterone, prolactin, cortisol, and tumor necrosis factor are associated with increased insulin resistance during pregnancy. Studies suggest that women who develop GDM have chronic insulin resistance and that GDM is a “stress test” for the development of diabetes in later life. Most obstetricians use White’s classification of diabetes during pregnancy. This classification is helpful is assessing disease severity and the likelihood of complications (Table 16-1).

TABLE 16-1 WHITE’S CLASSIFICATION OF DIABETES IN PREGNANCY

Class	Description	Therapy
A₁	Gestational diabetes; glucose intolerance developing during pregnancy; fasting blood glucose and postprandial plasma glucose normal	Diet alone
A₂	Gestational diabetes with fasting plasma glucose >105 mg/dL; or 2-hr postprandial plasma glucose >120 mg/dL, or 1-hr postprandial plasma glucose >140 mg/dL	Diet and insulin
B	Overt diabetes developing after age 20 yr and duration < 10 yr	Diet and insulin
C	Overt diabetes developing between ages 10 and 19 yr or duration 10-19 yr	Diet and insulin
D	Overt diabetes developing before age 10 yr or duration 20 yr or more or background retinopathy	Diet and insulin
F	Overt diabetes at any age or duration with nephropathy	Diet and insulin
R	Overt diabetes at any age or duration with proliferative retinopathy	Diet and insulin
H	Overt diabetes at any age or duration with arteriosclerotic heart disease	Diet and insulin

Maternal and fetal complications of diabetes are listed in Table 16-2. Diabetes often coexists with the metabolic syndrome. Most fetal and neonatal effects are attributed to the consequences of maternal hyperglycemia, or, in the more advanced classes, to maternal vascular disease. Glucose crosses the placenta easily by facilitated diffusion, causing fetal hyperglycemia, which stimulates pancreatic β cells and results in fetal hyperinsulinism. Fetal hyperglycemia during the period of embryogenesis is teratogenic. There is a direct correlation between birth defects in diabetic pregnancies and increasing glycosylated hemoglobin levels (HbA_1C) in the first trimester. Fetal hyperglycemia and hyperinsulinemia cause fetal overgrowth and macrosomia, which predisposes to birth trauma, including shoulder dystocia and Erb’s’ palsy. Fetal demise is most likely due to acidosis, hypotension from osmotic dieresis, or hypoxia from increased metabolism coupled with inadequate placental oxygen transfer.

TABLE 16-2 MATERNAL AND FETAL COMPLICATIONS OF DIABETES MELLITUS

Entity	Monitoring
MATERNAL COMPLICATIONS
OBSTETRIC COMPLICATIONS
Polyhydramnios	Close prenatal surveillance; blood glucose monitoring, ultrasonography
Preeclampsia	Evaluation for signs and symptoms
Infections, e.g., urinary tract infection and candidiasis	Urine culture, wet mount, appropriate therapy
Cesarean delivery	Blood glucose monitoring, insulin and dietary adjustment to prevent fetal overgrowth
Genital trauma	Ultrasonography to detect macrosomia, cesarean delivery for macrosomia
DIABETIC EMERGENCIES
Hypoglycemia	Teach signs and symptoms; blood glucose monitoring; insulin and dietary adjustment; check for ketones, blood gases, and electrolytes if glucose > 300 mg/dL
Diabetic coma
Ketoacidosis
VASCULAR AND END-ORGAN INVOLVEMENT OR DETERIORATION (IN PATIENTS WITH PREGESTATIONAL DIABETES MELLITUS)
Cardiac	Electrocardiogram first visit and as needed
Renal	Renal function studies, first visit and as needed
Ophthalmic	Funduscopic evaluation, first visit and as needed
Peripheral vascular	Check for ulcers, foot sores; noninvasive Doppler studies as needed
NEUROLOGIC
Peripheral neuropathy	Neurologic and gastrointestinal consultations as needed
Gastrointestinal disturbance
Long-Term Outcome
Type 2 diabetes	Postpartum glucose testing, lifestyle changes (diet and exercise)
Metabolic syndrome	Lifestyle changes (diet and exercise)
Obesity	Lifestyle changes (diet and exercise)
Cardiovascular disease	Annual checkup by physician, lifestyle changes (diet and exercise)
Fetal and Neonatal Complications
Maintenance of maternal euglycemia will decrease most of these complications.
Macrosomia with traumatic delivery (shoulder dystocia, Erb’s palsy)	Ultrasonography for estimated fetal weight before delivery; consider cesarean delivery if estimated fetal weight > 4250-4500 g
DELAYED ORGAN MATURITY
Pulmonary, hepatic, neurologic, pituitary-thyroid axis; with respiratory distress syndrome, hypocalcemia	Avoid delivery before 39 weeks in the absence of maternal or fetal indications unless amniocentesis indicates lung maturity. Maintain euglycemia intrapartum.
CONGENITAL DEFECTS
Cardiovascular anomalies	Preconception counseling and glucose control, HbA_lc in the first trimester
Neural tube defects	Maternal serum alpha-fetoprotein screening; fetal ultrasonography and fetal echocardiogram; amniocentesis and genetic counseling
Caudal regression syndrome
Other defects, e.g., renal
FETAL COMPROMISE
Intrauterine growth restriction	Serial ultrasonography for fetal growth and estimated fetal weight, serial fetal surveillance with nonstress test, amniotic fluid index, and fetal Doppler. Avoid postdates pregnancy.
Intrauterine fetal death
Abnormal fetal heart rate patterns

In pregestational diabetes, maternal complications include worsening nephropathy and retinopathy, a greater incidence of preterm preeclampsia and a higher likelihood of diabetic ketoacidosis. Hypoglycemia is much more common because of the tighter control attempted during pregnancy. Fetal complications include an increased rate of abortions, anatomic birth defects, fetal growth restriction, and prematurity.

Diagnosis

Screening for gestational diabetes is generally performed between 24 and 28 weeks of gestation with a 50-g 1-hour oral glucose challenge test (GCT), given without regard to last oral intake. This timing will identify most gestational diabetic patients while providing several weeks of therapy to reduce potentially adverse consequences. Screening is advised at the first prenatal visit in pregnant women with risk factors such as maternal age greater than 25 years, previous macrosomic infant, previous unexplained fetal demise, previous pregnancy with GDM, family history of diabetes, history of polycystic ovarian disease, and obesity. If overt signs and symptoms of diabetes are present, a fetal scalp blood test should be undertaken first. If the first-trimester screen is negative, it should be repeated at 24 to 28 weeks. Glucose values above 130 to 140 mg/dL on a GCT are considered abnormal and have an 80% to 90% sensitivity in detecting GDM.

An abnormal screening GCT is followed with a diagnostic 3-hour 100-g oral glucose tolerance test. This involves checking the fasting blood glucose after an overnight fast, drinking a 100-g glucose drink, and checking glucose levels hourly for 3 hours. If there are two or more abnormal values on the 3-hour GTT, the patient is diagnosed with GDM (Table 16-3). If the 1-hour screening (50-g oral glucose) plasma glucose exceeds 200 mg/dL, a glucose tolerance test is not required and may dangerously elevate blood glucose values.

TABLE 16-3 THREE-HOUR ORAL GLUCOSE TOLERANCE TEST

Test	Maximal Normal Blood Glucose (mg/dL)
Fasting	95
1 hr	180
2 hr	155
3 hr	140

From Carpenter and Coustan.

Management

THYROID DISEASES

Normal Thyroid Physiology during Pregnancy

With the increase in glomerular filtration rate that occurs during pregnancy, the renal excretion of iodine increases, and plasma inorganic iodine levels are nearly halved. Goiters due to iodine deficiency are not likely if plasma inorganic iodine levels are greater than 0.08 μg/dL. Inorganic iodine supplementation up to a total of 250 μg/day is sufficient to prevent goiter formation during pregnancy.

THYROID FUNCTION TESTS.

The free thyroxine (free T₄) concentration is the only accurate method of estimating thyroid function that compensates for changes in thyroxine-binding globulin (TBG) capacity because serum levels of bound triiodothyronine (total T₃) and total T₄ are increased during pregnancy. Values of thyroid function tests during pregnancy are shown in Table 16-4.

TABLE 16-4 THYROID FUNCTION TESTS IN NONPREGNANT WOMEN AND IN MATERNAL AND CORD BLOOD AT TERM

FETAL THYROID FUNCTION

Before 10 weeks’ gestation, no organic iodine is present in the fetal thyroid. By 11 to 12 weeks, the fetal thyroid is able to produce iodothyronines and T₄, and by 12 to 14 weeks, it is able to concentrate iodine. Fetal thyroid-stimulating hormone (TSH), T₄, and free T₄ levels suggest that a mature, autonomous, thyroid-pituitary axis exists as early as 12 weeks’ gestation.

PLACENTAL TRANSFER OF THYROID HORMONE

Iodide freely crosses the placenta, but TSH does not. Limited transfer of T₄ occurs across the placenta and appears to be important for fetal neural development in the first trimester before fetal thyroid function begins. Thyroid hormone analogues such as propylthiouracil and methimazole, with smaller molecular weights, cross the placental barrier and could potentially cause fetal hypothyroidism.

Thyroid-releasing hormone (TRH) can cross the placental barrier, but there is no significant placental transfer because of circulating low levels. Thyroid-stimulating antibodies also cross the placenta and can potentially cause fetal thyroid dysfunction.

Maternal Hyperthyroidism

The incidence of maternal thyrotoxicosis is about 1 per 500 pregnancies. It is accompanied by an increased incidence of prematurity, intrauterine growth restriction (IUGR), superimposed preeclampsia, stillbirth, and neonatal morbidity and mortality. Graves’ disease is an autoimmune disorder caused by thyroid-stimulating antibodies and is the most common cause of hyperthyroidism. Other causes of hyperthyroidism in pregnancy include hydatidiform mole and toxic nodular goiter. Patients with Graves’ disease tend to have a remission during pregnancy and an exacerbation during the postpartum period. The increased immunologic tolerance during pregnancy may lead to a decrease in thyroid antibodies to account for the remission.

CLINICAL FEATURES

The clinical diagnosis of hyperthyroidism in pregnancy is difficult because many of the signs and symptoms of the hyperdynamic circulation associated with hyperthyroidism are present in a normal euthyroid pregnant individual. A resting pulse rate greater than 100 beats/minute that fails to slow with a Valsalva maneuver, eye changes, loss of weight, failure to gain weight despite normal or increased food intake, and heat intolerance are all helpful in making the clinical diagnosis.

INVESTIGATIONS

An elevated serum free T₄ level and a suppressed TSH level establish the diagnosis of hyperthyroidism. Infrequently, a free T₃ determination might be needed to diagnose T₃ thyrotoxicosis.

THERAPY

Because radioactive iodine treatment is contraindicated during pregnancy, medical treatment is generally employed. Thioamides are the mainstay of antithyroid therapy. They block the synthesis but not the release of thyroid hormone. Propylthiouracil (PTU) and methimazole (Tapazole) have been used interchangeably, although PTU has the added advantage of blocking conversion of T₄ to T₃, and methimazole may cause fetal gastrointestinal defects. Because these drugs readily cross the placenta, a concern during maternal treatment is the development of fetal goiter and hypothyroidism. Although there is no conclusive evidence that PTU treatment leads to cretinism or abnormalities in physical or intellectual development, up to 1% to 5% of children exposed in utero will develop a goiter. For this reason antithyroid drugs are reduced to the lowest dose that results in free T₄ levels within the upper range of normal. Levels should be checked every 2 to 4 weeks. Antithyroid therapy can often be discontinued after 30 weeks of gestation.

Propylthiouracil excretion in breast milk is minimal, and no changes occur in the thyroid function tests of breastfed neonates.

Surgical management of the hyperthyroid pregnant patient during the second trimester is recommended only if medical treatment fails.

Thyroid Storm

The major risk in a pregnant patient with thyrotoxicosis is the development of a thyroid storm. Precipitating factors include infection, labor, cesarean delivery, or noncompliance with medication. It is not uncommon to mistakenly attribute the signs and symptoms of severe hyperthyroidism to preeclampsia. In the former, significant proteinuria is usually absent. The maternal mortality of thyroid storm exceeds 25% despite good medical management. The signs and symptoms associated with a thyroid storm include hyperthermia, marked tachycardia, perspiration, and high output failure or severe dehydration.

Specific treatment is directed at (1) blocking β-adrenergic activity with propranolol, 20 to 80 mg every 6 hours; (2) blocking secretion of thyroid hormone with sodium iodide, 1 g intravenously; (3) blocking synthesis of thyroid hormone and conversion of T₄ to T₃ with 1200 to 1800 mg of PTU given in divided doses; (4) further blocking the deamination of T₄ to T₃ with 8 mg of dexamethasone per day; (5) replacing fluid losses; and (6) rapidly lowering the temperature with hypothermic techniques.

Neonatal Thyrotoxicosis

About 1% of pregnant women with a history of Graves’ disease give birth to children with thyrotoxicosis due to transplacental transfer of thyroid-stimulating antibodies. It is transient and lasts less than 2 to 3 months but is associated with a neonatal mortality rate of about 16%. Fetal thyrotoxicosis can be suspected if the baseline fetal heart rate consistently exceeds 160 beats/minute. A fetal goiter can often be identified by ultrasonography in such cases. This situation is associated with an increase in perinatal morbidity and mortality and should be treated prenatally and postnatally.

Hypothyroidism

Pregnant women on appropriate thyroid replacement therapy can expect a normal pregnancy outcome, but untreated maternal hypothyroidism has been associated with an increased risk for spontaneous abortion, preeclampsia, abruption, low-birth-weight or stillborn infants, and lower intelligence levels in the offspring.

The most important laboratory finding to confirm the diagnosis of hypothyroidism is an elevated TSH level. Other findings include low levels of serum free T₃ and free T₄. Once diagnosed, therapy such as levothyroxine should be started and serum TSH levels performed monthly with appropriate adjustments in levothyroxine dosage.

NEONATAL HYPOTHYROIDISM

Thyroid hormone deficiency during the fetal and early neonatal periods leads to generalized developmental retardation. The severity of symptoms depends on the time of onset and the severity of the deprivation.

The incidence of congenital hypothyroidism (cretinism) is about 1 in 4000 births. The etiologic factors include thyroid dysgenesis, inborn errors of thyroid function, and drug-induced endemic hypothyroidism. The most common cause of neonatal goiter is maternal ingestion of iodides present in cough syrup. The goiters associated with maternal iodine ingestion are large and obstructive, unlike those associated with maternal PTU treatment.

Heart Disease

The categories of heart disease in pregnancy include rheumatic and congenital cardiac disease as well as arrhythmias, cardiomyopathies and other forms of acquired heart disease. Better treatment of rheumatic fever and improvements in medical and surgical management of congenital heart disease has meant that in a modern tertiary referral center, about 80% of patients with cardiac disease in pregnancy now have congenital heart disease.

RHEUMATIC HEART DISEASE

The most common lesion associated with rheumatic heart disease is mitral stenosis. Regardless of the specific valvular lesion, patients are at higher risk for developing heart failure, subacute bacterial endocarditis, and thromboembolic disease. They also have a higher rate of fetal wastage.

Pure mitral stenosis is found in about 90% of patients with rheumatic heart disease. During pregnancy, the mechanical obstruction worsens as cardiac output increases. Asymptomatic patients may develop symptoms of cardiac decompensation or pulmonary edema as pregnancy progresses. Atrial fibrillation is more common in patients with severe mitral stenosis, and nearly all women who develop atrial fibrillation during pregnancy experience congestive heart failure. However, pulmonary congestion and heart failure develop in only half of women in whom atrial fibrillation predates pregnancy. Tachycardia can result in decompensation because cardiac output in patients with mitral stenosis depends on an adequate diastolic filling time.

CONGENITAL HEART DISEASE

Congenital heart disease includes atrial or ventricular septal defects, primary pulmonary hypertension (Eisenmenger’s syndrome), and cyanotic heart disease such as tetralogy of Fallot or transposition of the great arteries. If the anatomic defect has been corrected during childhood with no residual damage, the patient is expected go through pregnancy without complications. Patients with persistent atrial or ventricular septal defects and those with tetralogy of Fallot with complete surgical correction generally tolerate pregnancy well. However, patients with primary pulmonary hypertension or cyanotic heart disease with residual pulmonary hypertension are in danger of undergoing decompensation during pregnancy. Pulmonary hypertension from any cause is associated with an increased risk for maternal mortality during pregnancy or in the immediate postpartum period. In all these patients, care should be taken to avoid overloading the circulation and precipitating pulmonary congestion, heart failure, or hypotension with reversal of the left-right shunt, all of which may lead to hypoxia and sudden death. In general, significant pulmonary hypertension with Eisenmenger’s syndrome is a contraindication to pregnancy.

CARDIAC ARRHYTHMIAS

Supraventricular tachycardia is the most common cardiac arrhythmia. It is usually benign and occurs secondary to structural changes in the heart that have presumably been present since birth. Atrial fibrillation and atrial flutter are more serious and are usually associated with underlying cardiac disease.

PERIPARTUM CARDIOMYOPATHY

This entity is rare but occurs exclusively during pregnancy. Patients have no underlying cardiac disease, and symptoms of cardiac decompensation appear during the last weeks of pregnancy or within 6 months postpartum. Pregnant women particularly at risk for developing cardiomyopathy are those with a history of preeclampsia or hypertension and those who are poorly nourished. It appears to be a dilational cardiomyopathy with decreased ejection fraction. Hypertensive cardiomyopathy, ischemic heart disease, viral myocarditis, and valvular heart disease must be excluded in patients with cardiac dysfunction before the diagnosis can be made. The mortality rate is at least 20%. About 30% to 50% of patients have persistent cardiac dysfunction, and recurrence occurs in about 20% to 50% of patients in a subsequent pregnancy.

MANAGEMENT OF CARDIAC DISEASE DURING PREGNANCY

The New York Heart Association’s functional classification of heart disease is of value in assessing the risk for pregnancy in a patient with acquired cardiac disease and in determining the optimal management during pregnancy, labor, and delivery (Table 16-5). In general, the maternal and fetal risks for patients with class I and II disease are small, whereas risks are greatly increased with class III and IV disease or if there is cyanosis. However, the type of defect is important as well. Mitral stenosis and aortic stenosis carry a higher risk for decompensation than do regurgitant lesions. Other patients at high risk include those with significant pulmonary hypertension, a left ventricular ejection fraction less than 40%, Marfan syndrome, a mechanical valve, or a previous history of a cardiac event or arrhythmia.

TABLE 16-5 NEW YORK HEART ASSOCIATION’S FUNCTIONAL CLASSIFICATION OF HEART DISEASE

Class I	No signs or symptoms of cardiac decompensation
Class II	No symptoms at rest, but minor limitation of physical activity
Class III	No symptoms at rest, but marked limitation of physical activity
Class IV	Symptoms present at rest, discomfort increased with any kind of physical activity

Prenatal Management

As a general principle, all pregnant cardiac patients should be managed with the help of a cardiologist. A careful history and physical examination, along with an electrocardiogram and echocardiogram, should be performed. The patient should be counseled about risks associated with pregnancy and all options presented. Frequent prenatal visits are indicated, and frequent hospital admissions may be needed, especially for patients with class III and IV cardiac disease.

Avoidance of excessive weight gain and edema. Cardiac patients should be placed on a low-sodium diet (2 g/day) and encouraged to rest in the left lateral decubitus position for at least 1 hour every morning, afternoon, and evening to promote diuresis. Adequate sleep should be encouraged. If there is evidence of chronic left ventricular failure not adequately treated with sodium restriction, a loop diuretic and β blockers should be added. Aldosterone antagonists should be avoided because of their potential antiandrogen effects on the fetus.

AVOIDANCE OF STRENUOUS ACTIVITY

Individuals with significant heart disease are unable to increase their cardiac output to the same extent as healthy individuals to meet the increased metabolic demands associated with exercise.

AVOIDANCE OF ANEMIA

With anemia, the oxygen-carrying capacity of the blood decreases. Oxygen delivery to tissues is generally maintained by increased cardiac output. An increase in heart rate, especially with mitral stenosis, leads to a decrease in left ventricular filling time, resulting in pulmonary congestion and edema. Another factor that might lead to cardiac decompensation is the inability of the right ventricle to efficiently pump a percentage of the venous return.

ANTICOAGULATION

Women with mechanical valves require full anticoagulation with heparin in pregnancy. Warfarin may be restarted post partum.

Management of Delivery and the Immediate Postpartum Period

Cardiac patients should be delivered vaginally unless obstetric indications for cesarean are present. They should be allowed to labor in the lateral decubitus position with frequent assessment of vital signs, urine output, and pulse oximetry. Adequate pain relief is important. Pushing should be avoided during the second stage of labor because the associated increase in intraabdominal pressure increases venous return and cardiac output and can lead to cardiac decompensation. The second stage of labor can be assisted by performing an outlet forceps delivery or by the use of a vacuum extractor.

The immediate postpartum period presents special risks to the cardiac patient. After delivery of the placenta, the uterus contracts, and about 500 mL of blood is added to the effective blood volume. Cardiac output increases up to 80% above prelabor values in the first few hours after a vaginal delivery and up to 50% after cesarean delivery. To minimize the risk for overloading the circulation, careful attention is paid to fluid balance and prevention of uterine atony. Methergine should be avoided owing to its vasoconstrictor effects.

Of particular concern is the risk for endocarditis. The 2007 guidelines from the American Heart Association state that delivery does not increase the risk for infectious endocarditis. Antibiotic prophylaxis is only recommended for high-risk patients (e.g., prosthetic valves, unrepaired or incompletely repaired congenital heart disease, congenital heart disease repaired with prosthetic material, previous history of bacterial endocarditis and valvulopathy in heart transplants) if bacteremia is suspected (such as in the setting of chorioamnionitis).

Acute cardiac decompensation with congestive heart failure should be managed as a medical emergency. Medical management may include administration of morphine sulfate, supplemental oxygen, and an intravenous loop diuretic (e.g., furosemide) to reduce fluid retention and preload. β Blockers should not be used in the setting of acute heart failure. Vasodilators such as hydralazine, nitroglycerin, and rarely nitroprusside are used to improve cardiac output by decreasing afterload. Some patients may require inotropic support with dobutamine or dopamine. The use of digitalis is controversial. Angiotensin-converting enzyme inhibitors are contraindicated in pregnancy. Calcium channel blockers such as nifedipine may accelerate the progression of congestive heart failure and should be avoided. Continuous pulse oximetry can be very helpful in managing these patients. Monitoring with a pulmonary artery catheter can provide a good index of left ventricular function but is discouraged in those with pulmonary hypertension.

Autoimmune Disease in Pregnancy

An autoimmune disease is one in which antibodies are developed against the host’s own tissues. A summary of the interactions of primary immunologic disorders and pregnancy is shown in Table 16-6.

TABLE 16-6 AUTOIMMUNE DISEASE IN PREGNANCY

IMMUNE (IDIOPATHIC) THROMBOCYTOPENIA

In this condition thrombocytopenia occurs when peripheral platelet destruction exceeds bone marrow production. Idiopathic thrombocytopenia (ITP) is considered to be an autoantibody disorder in which immunoglobulins attach to maternal platelets leading to platelet sequestration in the reticuloendothelial system. ITP may be confused with gestational thrombocytopenia. The latter is unlikely to have a platelet count less than 70,000/μL, is not associated with bleeding complications, occurs late in pregnancy, and resolves after delivery.

Treatment

Therapy is usually not initiated unless platelet counts are less than 40,000/μL or petechial hemorrhages are present. Prednisone at a dose of 1 mg/kg per day is given initially, maintained for 2 to 3 weeks, then tapered slowly. Severe ITP can be treated with intravenous immunoglobulin (IVIG), or if the patient is Rh positive, anti-D antibody infusions, which can raise the platelet count within 12 to 48 hours. In patients with life-threatening hemorrhage, platelet transfusions, combined with high-dose steroids and IVIG, may be required. Splenectomy is a last resort for patients who fail to respond to medical therapy. Platelet transfusions are also indicated if the maternal platelet count is less than 20,000 before vaginal delivery, or less than 40,000 before cesarean delivery.

The neonate should be monitored for thrombocytopenia because placental transfer of maternal antiplatelet antibodies can occur. Rarely, neonatal intracranial hemorrhage occurs once the neonatal platelet count reaches its nadir after the first 2 to 3 days of life. There is no correlation between fetal platelet counts and neonatal outcome; thus, monitoring fetal platelet counts is not done in pregnancy. Vaginal delivery is generally carried out because there is no good evidence that the fetal outcome is improved by cesarean delivery, and surgery carries additional maternal risks.

SYSTEMIC LUPUS ERYTHEMATOSUS

Lupus occurs mainly in women. Associated antibodies include antinuclear, anti-RNP and anti-SM antibodies; anti-dsDNA is associated with nephritis and lupus activity; anti-Ro (SS-A) and anti-La (SS-B) are present in Sjögren’s syndrome and neonatal lupus with heart block; while antihistone antibody is common in drug-induced lupus. The diagnosis of systemic lupus is made if 4 or more of the 11 revised criteria of the American Rheumatism Association are present, serially or simultaneously (Table 16-7).

TABLE 16-7 AMERICAN RHEUMATISM ASSOCIATION 1997 REVISED CRITERIA FOR SYSTEMIC LUPUS ERYTHEMATOSUS

Criteria^∗	Comments
Malar rash	Malar erythema
Discoid rash	Erythematous patches, scaling, follicular plugging
Photosensitivity
Oral ulcers	Usually painless
Arthritis	Nonerosive involving two or more peripheral joints
Serositis	Pleuritis or pericarditis
Renal disorder	Proteinuria > 0.5 g/day or > 3+ dipstick, or cellular casts
Neurologic disorders	Seizures or psychosis without other cause
Hematologic disorders	Hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia
Immunologic disorders	Anti-dsDNA or anti-Sm antibodies, or false-positive VDRL, immunoglobulin M or G anticardiolipin antibodies, or lupus anticoagulant
Antinuclear antibodies	Abnormal titer of antinuclear antibodies

VDRL, Venereal Disease Research Laboratory.

∗ If four criteria are present at any time during course of disease, systemic lupus can be diagnosed with 98% specificity and 97% sensitivity.

From Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725, 1997. Copyright 1997 American College of Rheumatology. Reprinted with permission of John Wiley & Sons, Inc.

During pregnancy, lupus improves in one third of women, remains unchanged in one third, and worsens in the remaining third. A lupus flare can be life threatening, but it is difficult to differentiate a lupus flare from superimposed preeclampsia (and both may coexist). Often only a trial of therapy will distinguish between the two. Flares and active disease can generally be managed with steroids, such as prednisone, 1 mg/kg per day.

Fetal and neonatal complications include an increased rate of preterm delivery, fetal growth restriction, and stillbirth, especially when associated with antiphospholipid antibodies. These pregnancies require close monitoring, often with weekly maternal and fetal assessments once they reach the third trimester. There is about a 10% risk for neonatal lupus, which is characterized by skin lesions, hematologic manifestations such thrombocytopenia or hemolysis, systemic effects such as hepatic involvement, and occasionally congenital heart block.