Common Medical and Surgical Conditions Complicating Pregnancy

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

Complications

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

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

From Carpenter and Coustan.

Management

Antepartum Obstetric Management

Aside from achieving euglycemia, adequate surveillance should be maintained during pregnancy to detect and possibly mitigate maternal and fetal complications. In pregestational diabetic patients, or in those with GDMs diagnosed before 20 weeks, a first-trimester dating ultrasound followed by a detailed obstetric ultrasonic study, fetal echocardiogram, and maternal serum alpha-fetoprotein level should be obtained at 16 to 20 weeks to check for congenital malformations. Maternal renal, cardiac, and ophthalmic functions must be closely monitored. The HbA_1C should be obtained at the first prenatal visit, which is preferably scheduled early in the first trimester. Individuals with significantly elevated values (>8.5%) should be particularly targeted for careful ultrasonic assessment for congenital anomalies. Regular electronic, biochemical, and ultrasonographic fetal monitoring should be performed. For diabetic classes A, B, and C, fetal macrosomia is common and should be investigated, whereas for classes D, F and R, fetal growth restriction occurs more commonly.

Serial fetal testing should be performed in the third trimester. In patients with GDM on diet, fetal testing can be initiated at term; while in those on insulin, fetal testing should be initiated between 32 and 34 weeks of gestation or sooner if complications develop.

If the maternal state is stable, blood glucose is in the euglycemic range, and fetal studies indicate a healthy baby, spontaneous onset of labor at term may be awaited. Earlier intervention is indicated if these conditions are not met. For macrosomic babies, increased birth trauma to both mother and fetus should be kept in mind. Cesarean delivery may be elected for large fetuses (>4250 to 4500 g).

Intrapartum Management

Intrapartum management of a diabetic patient requires the establishment of maternal euglycemia during labor. This may be achieved by giving a continuous infusion of regular insulin. Plasma glucose levels are measured frequently, and insulin dosage is adjusted accordingly to maintain a plasma glucose level between 80 and 120 mg/dL. Not all insulin-dependent patients require exogenous insulin during labor. Continuous electronic fetal heart rate monitoring is recommended for all diabetic patients.

Postpartum Period

After delivery of the fetus and placenta, insulin requirements drop sharply because the placenta, which is the source of many insulin antagonists, has been removed. Many insulin-dependent diabetic patients may not require exogenous insulin for the first 48 to 72 hours after delivery. Plasma glucose levels should be monitored and lispro or regular insulin given when plasma glucose levels are elevated. Patients can be restarted on two thirds of the prepregnancy insulin dosage, with adjustments made as necessary. Gestational diabetic patients (with class A₁ and A₂ disease) frequently do not need insulin therapy postpartum. A fasting blood glucose or a 75-g oral glucose tolerance test should be performed at 6 to 12 weeks postpartum.

Patients should be counseled about changes in diet. The American Dietetic Association diet with the same distribution of carbohydrates, proteins, and fat should be maintained. If the mother is breastfeeding, 500 calories/day should be added to the prepregnant diet.

Sterilization should be discussed with patients who desire it and those with advanced vascular involvement.

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.

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.

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.

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.

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.

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.

Laboratory Studies

Laboratory tests are directed at assessing renal function, cardiovascular status, and the patency of the urologic tract.

Treatment

Treatment

Treatment is usually symptomatic. Patients are instructed to refrain from eating large and late meals, to avoid the recumbent position, especially after meals, and to use an extra pillow to elevate the head when sleeping. Antacids can be helpful and should be taken 1 to 3 hours after meals and at bedtime. A histamine-2 (H₂) blocker (cimetidine) or proton pump blocker (omeprazole) is indicated if there is no response to the above measures.

Treatment

Treatment of an acute exacerbation is the same for pregnant and nonpregnant patients, although some of the more experimental drugs should not be used during pregnancy. If diarrhea is the main complaint, dietary restriction of lactose, fruits, and vegetables is necessary. If a lactose-free diet is used, calcium supplementation is needed. Constipating agents, such as Pepto-Bismol and psyllium hydrophilic mucilloid (Metamucil), may be used daily and are quite effective. The use of diphenoxylate-atropine (Lomotil) or loperamide (Imodium) should be restricted to patients in whom conservative management fails. For those patients with mild to moderate symptoms, sulfasalazine may be beneficial. Recently, several antibiotic regimens have been used to treat Crohn disease.

Treatment

Local measures such as cold baths, bicarbonate washes, or phenol (0.5% to 1% in water-soluble creams) may be of some help. The best results have been obtained with ursodeoxycholic acid. It significantly ameliorates the pruritus and reduces serum levels of bile acids, aminotransferases, and bilirubin. Serial fetal surveillance is performed in the third trimester, with delivery at term if testing remains reassuring.

Investigations

Laboratory findings include an increase in prothrombin time (PT) and partial thromboplastin time (PTT), hyperbilirubinemia, hyperammonemia, hyperuricemia, and a moderate elevation of the transaminase levels. Hematemesis and spontaneous bleeding become manifest as disseminated intravascular coagulation (DIC) develops. Liver failure is indicated by elevated blood ammonia levels.

Treatment

Termination of pregnancy and intensive supportive care are indicated on diagnosis. Treatment is mainly directed at supportive measures, such as administration of intravenous fluids with 10% glucose to prevent dehydration and severe hypoglycemia. For the coagulopathy of hepatic failure, vitamin K supplementation is not effective, and fresh-frozen plasma or cryoprecipitate should be given.

With early recognition, immediate delivery, and advances in critical care management, maternal mortality is about 7% to 18%, and fetal mortality about 9% to 23%. In those who survive, recovery is complete, with no signs of chronic liver disease.

Treatment

When a clinical diagnosis of DVT is made, anticoagulant therapy should be started pending the results of a diagnostic workup. If the workup fails to identify any iliofemoral or calf thrombosis, therapy may be discontinued.

Treatment of proven DVT during pregnancy is initiated with either intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (enoxaparin sodium) to achieve full anticoagulation. The unfractionated heparin dose is adjusted to 1.5 to 2.5 times the control activated PTT (aPTT). Intravenous anticoagulation should be maintained for at least 5 to 7 days, after which treatment is converted to subcutaneous heparin, which must be continued for the duration of pregnancy and up to 6 weeks postpartum with weekly monitoring of the aPTT. Alternatively, enoxaparin can be administered at a dose of 1 mg/kg subcutaneously every 12 hours. Although anti–factor Xa levels can be used to monitor enoxaparin’s anticoagulant activity, they are not generally useful because of the long lag in receiving results. Both forms of heparin may be associated with thrombocytopenia and osteoporosis. Supplemental calcium and vitamin D are advised along with periodic platelet counts.

Warfarin is a vitamin K antagonist, which crosses the placenta, carries the risks for fetal hemorrhage and teratogenesis and, with few exceptions, should only be used in the postpartum period. The International Normalized Ratio (INR) is commonly used to measure the effects of warfarin, and the target INR is 2.5 (range, 2.0 to 3.0).

Obstetric Management

Pregnant asthmatic patients should be followed closely during pregnancy. The avoidance of dehydration, early and aggressive treatment of respiratory infections, and the avoidance of hyperventilation, excessive physical activity, and allergens are important. Serial measurements of peak expiratory flow rates can provide useful information on respiratory status. For those with mild intermittent asthma, a short-acting inhaled β₂ agonist can be used as needed. Patients with mild persistent asthma should be treated with a low-dose inhaled corticosteroid. The preferred treatment for moderate persistent asthma is a combination of a daily inhaled corticosteroid and a long-acting β₂ agonist. Those with severe persistent asthma may require the addition of a systemic corticosteroid. Alternative therapies include inhaled cromolyn sodium, leukotriene receptor antagonists, or sustained-release theophylline. Acute severe exacerbations must be treated aggressively with oxygen therapy, intravenous fluids, intravenous corticosteroids, and administration of β₂ agonists by nebulized aerosol and antibiotics if there is evidence of bacterial infection. A few patients may require endotracheal intubation and mechanical ventilation to maintain an adequate oxygen supply.

Serial fetal monitoring and ultrasonic assessment of fetal growth should be implemented. The timing of delivery is dependent on the status of both the mother and the fetus. If pregnancy is progressing well, there is no need for early intervention, and it is advisable to await the spontaneous onset of labor. Early delivery can be considered for fetal growth restriction or maternal deterioration.

Management of Labor and Delivery

Glucocorticoid therapy, including inhaled or high-potency topical use for more than 3 weeks, may suppress the hypothalamic-pituitary-adrenal axis. Delivery is probably associated with moderate surgical stress, and stress doses of steroids should be considered. A selective epidural block during labor reduces pain, anxiety, hyperventilation, and respiratory effort, all of which are known to aggravate the disease or precipitate an attack. Vaginal delivery should be anticipated. Cesarean delivery is performed only for obstetric reasons.

Treatment

If patients have no seizure activity for at least 2 years, antiepileptic drug (AED) therapy can be discontinued before conception. If patients are pregnant and their seizures are well controlled, no change in therapy should be attempted. The AED that is effective should be used. Monotherapy should be attempted using the lowest drug dose that will control the seizures. There is no ideal anticonvulsant in pregnancy, and all AEDs should be considered potential teratogens. Valproate should probably not be used because it is has been shown to be more teratogenic when compared with other AEDs.

Historically, the two most commonly used drugs for seizure treatment have been phenytoin (Dilantin) and phenobarbital. Phenobarbital at a dose of 100 to 250 mg/day may be given in divided doses. The serum levels are monitored, and the dose is increased gradually until a therapeutic level (10 to 40 μg/mL) is reached. Phenytoin may be given at 300 to 500 mg/day, in single or divided doses, to achieve serum levels of 10 to 20 μg/mL (1 to 2 μg/mL free level). Other first-generation AEDs include trimethadione, clonazepam (Klonopin), and carbamazepine (Tegretol). Second-generation AEDs include lamotrigine, topiramate, and gabapentin.

Women on AEDs should take 1 mg/day of folate supplementation. Those on carbamazepine or valproate should take 4 mg per day of folate supplementation. Oral vitamin K supplementation, 10 mg/day, should be considered in the last month of pregnancy for women taking enzyme-inducing AEDs (e.g., phenobarbital, carbamazepine, phenytoin, topiramate, oxcarbazepine). Phenytoin interferes with intestinal calcium absorption, leading to maternal and fetal hypocalcemia. In patients taking phenobarbital, primidone, or phenytoin, vitamin D supplements may be taken starting at about 34 weeks. Antacids and antihistamines should be avoided in patients receiving phenytoin because they lower plasma levels of phenytoin and may precipitate a seizure attack.

For the treatment of status epilepticus, immediate hospitalization is required. Management is similar to that in the nonpregnant adult. Patency of the airway and adequate oxygenation should be insured. After blood is drawn for plasma levels of anticonvulsants, intravenous diazepam (or lorazepam) should be given slowly, followed by a loading dose of phenytoin (at a rate no faster than 25 to 50 mg/minute with continuous cardiac monitoring). If seizure patterns continue, pentobarbital may be added, and the patient should be intubated and mechanically ventilated.

The management of labor and delivery follows obstetric indications. During labor and in the immediate postpartum period, anticonvulsant drugs must be continued. Postpartum, the dose of the anticonvulsant drug may be lowered, provided that a therapeutic level is maintained. Although anticonvulsants are excreted in breast milk in small amounts, breastfeeding is not contraindicated.

Complications

Pregnant patients with epilepsy have a twofold increase in such maternal complications as preeclampsia, abruption, hyperemesis, and premature labor. Fetal hypoxia is a potential consequence of maternal seizures, and there is a high incidence of intrauterine fetal demise. In the neonate, higher rates of coagulopathy, drug withdrawal symptoms, and neonatal morbidity and mortality are reported. Congenital anomalies are more common in neonates exposed to AEDs in utero compared with offspring of untreated women with epilepsy and women without epilepsy. The overall risk for major malformations is 4% to 6%. Small retrospective studies have raised the possibility of impaired cognitive and neurologic function in the offspring that may manifest later in life. The risk for a seizure disorder is greater among the children of mothers with epilepsy.

The Virus

HIV is an RNA retrovirus that replicates in certain cell types, in particular in helper T4 lymphocytes in the hematopoietic system and in cells of the central nervous system. As with all retroviruses, HIV contains a reverse transcriptase in its core. HIV has specific surface proteins gp120 and gp41 and core proteins p18 and p24. HIV infects a cell by making contact with the gp120 protein. It then enters the cell, releases its core RNA, makes a DNA copy of itself with its reverse transcriptase, and inserts this DNA into the host genome. This viral gene then either enters into a latent state or begins making viral RNA and proteins with production of an infectious virus.

Laboratory Diagnosis

Indirect serologic methods that detect HIV antibody include the enzyme-linked immunosorbent assay (ELISA), Western blot, and immunofluorescence assay (IFA) tests. The sensitivity of the ELISA is 93% to 99%, and the specificity is 99%. Although rare, false-positive ELISA results can occur, so a confirmatory test is always needed. The Western blot test, which identifies the presence of HIV core and envelope antigens, is 99% sensitive and 98.5% specific. False-positive Western blot results are extremely uncommon. Indirect serology with the capture ELISA technique can also identify HIV antigen (e.g., p24 antigen test). The virus can also be identified by direct tissue culture or by HIV DNA polymerase chain reaction.

Disease Course

Infection with HIV results in a chronic progressive disease. Seroconversion typically occurs 3 to 14 weeks after exposure but may take 6 months or more. In 90% of cases, seroconversion is associated with a mononucleosis-like syndrome or aseptic meningitis. Once the virus has been acquired, the patient enters an asymptomatic period, but lifetime infection should be assumed. Because HIV has a predilection for helper (T4) cells, a gradual destruction of the patient’s cell-mediated immunity occurs, rendering the host susceptible to opportunistic infections. Eventual reversal of the T4-to-T8 ratio to less than 1 is seen on laboratory analysis.

Typically, the patient develops asymptomatic lymphadenopathy, followed by the onset of constitutional symptoms (anorexia, fever, weight loss, diarrhea, nausea, and vomiting). Eventually, opportunistic infections, secondary cancers (Kaposi’s sarcoma, non-Hodgkin’s lymphoma), or neurologic diseases (dementia, neuropathy) develop. Opportunistic infections that may be seen include the following: Pneumocystis carinii pneumonia (PCP), tuberculosis, cryptococcal meningitis, cytomegalovirus (CMV) retinitis, atypical mycobacterial disease, cerebral toxoplasmosis, severe herpes, and cryptosporidiosis. The average interval from initial infection to the onset of AIDS in adults not receiving potent antiviral therapy is 10 years.

Pregnancy does not appear to accelerate the course of HIV infection. Pregnant women may be at increased risk for developing infectious complications during pregnancy. These infections include opportunistic infections, postpartum infections, antepartum urinary tract infections, and sexually transmitted diseases. No direct detrimental effects on perinatal outcome have been documented. Studies in the United States have not shown an increased risk for growth restriction, preterm labor, or premature rupture of the membranes. In children, the disease progresses more rapidly. Of infants infected with HIV, half develop AIDS in the first year of life, and 85% develop AIDS by age 3 years. Children have an extremely poor prognosis, the average survival time from diagnosis being 3 years.

Vertical Transmission

The risk for vertical transmission of HIV from an infected mother to her infant is between 20% and 30%. Such transmission accounts for 99% of cases of HIV infection in children. Vertical transmission may occur antepartum (transplacental), intrapartum, and postpartum. It is suspected that more than 50% of transmissions occur near the time of or during labor and delivery. Maternal-fetal transmission as a result of invasive procedures such as amniocentesis, chorionic villus sampling, umbilical blood sampling, or scalp electrode placement is theoretically possible, but the exact risk is unknown. Breastfeeding may increase the risk for transmission by 10% to 20%. There is no confirmed evidence that fetal HIV infection can result in structural anomalies. It appears that women with advanced disease, recent HIV infection, or preterm delivery have an increased risk for vertical transmission to their infants.

In 1994, Pediatric AIDs Clinical Trial 076 showed that the administration of the nucleoside reverse-transcriptase inhibitor zidovudine to the mother during pregnancy and labor and to the infant for 6 weeks postpartum reduced the maternal transmission to the newborn from 25.5% to 8.3%, with a 68% reduction in vertical transmission. More recently, potent antiretroviral therapy, which reduces the maternal plasma HIV RNA levels to less than 1000 copies per milliliter, has been shown to reduce the vertical transmission rate to only 1% to 2%.

The current management for pregnant women involves the use of multiple agents to minimize the development of drug resistance, and unless contraindicated, all drug regimens should include zidovudine. Antiretroviral drug classes currently used in pregnancy include nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs); non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors. A common regimen currently used is zidovudine plus lamivudine (Combivir) plus lopinavir and ritonavir (Kaletra). Pregnant women with HIV infection on nucleoside analogues should have liver enzymes and electrolytes monitored in the third trimester. Pregnant women on protease inhibitors should be screened for gestational diabetes at the initial visit in addition to the usual time at 24 to 28 weeks because these drugs can cause hyperglycemia. For women who are immunocompromised, with CD4 counts of 0.20 × 10⁹/L (200/μL) or below, prophylaxis against PCP, Mycobacterium avium complex infection, and others should be offered. Trimethoprim sulfamethoxazole is relatively safe for use in pregnancy and is the first choice for PCP prophylaxis.

Because the risk for vertical transmission increases with maternal plasma HIV RNA concentrations, the therapeutic goal is to keep the maternal viral load either undetectable or less than 1000 copies per milliliter. In general, pregnant women should be maintained on the same antiretroviral therapy they received in the nonpregnant state. Invasive fetal diagnostic procedures, such as amniocentesis and chorionic villus sampling, pose a theoretical risk for infecting the fetus and should probably be avoided.

Pregnant women should receive counseling on the risk for newborn infection and the delivery choices available. Women who have viral loads greater than 1000 should be offered a cesarean delivery, which may reduce vertical transmission under these conditions. Such cesarean deliveries should be scheduled at about 38 weeks of gestation to reduce the chance of labor or rupture of membranes. Women on antiretroviral therapy with viral loads less than 1000 HIV RNA copies per milliliter are at low risk (1% to 2%) of passing the virus on to the fetus or newborn. Vaginal delivery should be offered to such patients. All procedures should be avoided that may increase the risk for fetal HIV infection, including artificial rupture of membranes, invasive fetal heart rate monitoring, fetal blood sampling, assisted delivery (forceps or vacuum), or episiotomy. Once the membranes have ruptured, labor should be augmented with oxytocin to reduce the interval between membrane rupture and delivery.

Regardless of the mode of delivery, all women should continue to receive antiretroviral medications as prescribed. Zidovudine (2 mg/kg over 1 hour, followed by 1 mg/kg per hour) should be infused intravenously after the onset of labor or rupture of membranes until delivery or at least 3 hours before cesarean delivery.

In the United States, breastfeeding is not recommended and should be discouraged.

Screening for HIV Infection in Pregnancy

All pregnant women should be tested for HIV unless they refuse. When counseling an HIV-positive pregnant woman, it is necessary to discuss the risk for perinatal transmission. Counseling on disease prevention, including a discussion of safe sexual practices, information on zidovudine therapy, and avoidance of breastfeeding, is imperative. Reproductive options with respect to the present pregnancy and future family planning need to be addressed. Rapid HIV testing should be offered to pregnant women presenting intrapartum whose HIV status is unknown. If the rapid test is positive, zidovudine prophylaxis should be administered and confirmatory testing sent.

Diagnosis

The diagnosis of rubella is best made by serologic testing. The IgM response is a rapid one that begins at the onset of the rash and then declines and disappears by 4 to 8 weeks. IgG response also begins at the onset of the rash and remains elevated for life. The diagnosis can be made by the presence of a fourfold rise in the hemagglutination-inhibiting (HAI) antibody titer in paired sera obtained 2 weeks apart or by the presence of IgM. Rubella can also be diagnosed by culture and isolation of the virus during the acute phase of infection, although this technique is slow. The presence of IgM in cord blood or IgG in an infant after 6 months of age supports the diagnosis of perinatal rubella infection.

Impact on Pregnancy

Between 10% and 15% of adult women are susceptible to rubella. In a review of all cases of infants with congenital rubella syndrome (CRS) in the United States reported to the National Congenital Rubella Syndrome Registry from 1997 to 1999, 83% were born to Hispanic mothers and 91% were born to foreign-born mothers.

The disease course is unaltered by pregnancy, and the mother may or may not exhibit the full clinical disease. The severity of the mother’s illness does not have an impact on the risk for fetal infection. Rather, it is the trimester in which infection occurs that has the greatest impact on fetal risk. Infection in the first trimester carries up to 80% risk for development of CRS, whereas the risk for CRS drops to 30% to 50% later in pregnancy. CRS rarely occurs after 20 weeks of gestation. Components of CRS are outlined in Box 16-2.

Routine rubella susceptibility testing should be performed in all pregnant women with a single IgG level. Those who are nonimmune should be vaccinated in the immediate postpartum period. It is recommended that women not become pregnant for at least 3 months after vaccination. Nonetheless, there are no reports of CRS after rubella immunization, and inadvertent immunization of a pregnant woman is not considered an indication for therapeutic abortion. Follow-up antibody titers should be obtained because up to 20% fail to develop an antibody response. Women should be screened for rubella susceptibility at each pregnancy, because immunity can wane.

Rubella is not a contraindication to breastfeeding. There is no specific treatment for rubella, and routine prophylaxis with γ-globulin after exposure is not recommended because it has not been shown to change the risk for fetal involvement.

Diagnosis

The virus may be isolated on urine culture or by culture of other body secretions or tissues. Serologic testing is possible, with an elevation in IgM that peaks 3 to 6 months after infection and resolves by 1 to 2 years. IgG elevates rapidly and persists for life. Problems with serologic testing include (1) the prolonged elevation in levels of IgM, making delineation of timing of infection difficult, and (2) a 20% false-negative rate in IgM testing. In addition, the presence of IgG does not rule out the presence of persistent disease.

Impact on Pregnancy

CMV is the most common congenital viral infection in the United States, affecting 0.5% to 2.5% of all live-born infants per year, and it is postulated that each year about 40,000 infants are born with congenital CMV infection. Fetal infection can occur when the mother does not exhibit symptoms. There is a 40% to 50% maternal-infant transmission rate.

About 10% to 15% of infected infants are symptomatic at birth, exhibiting nonimmune hydrops, symmetrical IUGR, chorioretinitis, microcephaly, cerebral calcifications, hepatosplenomegaly, and hydrocephaly. About 80% to 90% are asymptomatic at birth but may later exhibit mental retardation, visual impairment, progressive hearing loss, and delayed psychomotor development (Box 16-3). Sensorineural hearing loss is the most frequent sequel of congenital CMV infection and is observed in 40% to 50% of symptomatic children. Recurrent CMV infection is associated with a much lower fetal risk, with a 0.15% to 1% maternal-fetal transmission rate. Few cases of severely affected infants have been reported.

Patients with a confirmed primary infection should have a detailed ultrasonic examination. Ultrasonic findings include fetal growth restriction, hydrocephaly, intracranial calcifications, microcephaly, echogenic bowel, hepatosplenomegaly, and nonimmune hydrops. If the ultrasound is normal, an amniocentesis should be performed to test for CMV by polymerase chain reaction (PCR). If the ultrasound shows signs of fetal anomalies, or the PCR test is positive, patients should be advised of options. Recently, hyperimmune anti-CMV globulin has been shown to be effective and can be offered. Ganciclovir has also been used in pregnancy with resolution of fetal CMV infection. The patient should also be advised of the option of termination.

Diagnosis

The diagnosis of chickenpox is usually determined by the patient’s clinical presentation, although the virus may be cultured from vesicles during the first 4 days of the rash. On serologic testing, varicella-zoster IgM will rise in 2 weeks on ELISA or complement fixation. Paired sera for IgG obtained 2 weeks apart may also detect infection.

Impact on Pregnancy

Between 5% and 10% of adult women are susceptible to the varicella virus. Acute varicella infection complicates 1 in 7500 pregnancies. Potential maternal complications include preterm labor, encephalitis, and varicella pneumonia. Maternal management should be symptomatic, but a chest x-ray should be considered to rule out pneumonia. Varicella pneumonia complicates 16% of cases and carries a mortality rate of up to 40%. If pneumonia is confirmed or suspected, the patient requires immediate hospital admission and institution of antiviral therapy because rapid respiratory decompensation is not uncommon.

A congenital varicella syndrome has been described. Diagnosis of the syndrome is based on IgM-positive cord blood and clinical findings in the newborn, which include limb hypoplasia, cutaneous scars, chorioretinitis, cataracts, cortical atrophy, microcephaly, and symmetrical IUGR. The risk for this fetal syndrome is 2% if maternal infection occurred between 13 and 20 weeks and 0.4% if maternal infection occurred before 13 weeks of gestation. Only rarely have cases been identified as a result of maternal infection past 20 weeks’ gestation. In the presence of fetal infection, ultrasound may reveal hydrops, organ calcifications, limb deformities, microcephaly, or growth restriction. However, no reliable methods of definitive prenatal diagnosis are available.

If maternal infection occurs 5 to 21 days before delivery and the infant develops infection, it is typically mild and self-limited. However, if maternal infection occurs between 5 days before delivery and 2 days after delivery, transplacental transfer of maternal protective antibodies to the fetus has not occurred, and the infant is at great risk for developing a fulminant infection with a 30% mortality rate. Varicella-zoster immune globulin (VZIG) should be given to these infants at birth, and they should be placed in contact isolation. The placenta and fetal membranes should be considered infectious.

For the exposed gravid woman who has no knowledge of a prior infection, a varicella IgG titer should be obtained immediately. If the patient proves to be nonimmune, VZIG should be administered within 6 days of exposure, although it is unclear whether this therapy modifies the disease course and risk to the fetus. Administration of VZIG is also recommended after exposure to zoster. Alternatively, VariZIG may be administered up to 96 hours after exposure. Varicella vaccine is composed of a live attenuated virus and, therefore, is contraindicated in pregnancy. Herpes zoster does not occur more frequently in pregnancy. If it does occur, it poses no risk to the fetus. If zoster develops close to delivery, varicella may be transmitted through contact with a lesion, so this should be avoided.

Impact on Pregnancy

The course of acute hepatitis is unaltered in pregnancy. Fetal infection may occur and is most likely if maternal infection occurs in the third trimester. Chronic active hepatitis is associated with an increased risk for prematurity, low birth weight, and neonatal death. Maternal prognosis is very poor if the disease is complicated by cirrhosis, varices, or liver failure.

The incidence of hepatitis B surface antigen (HBsAg) positivity (chronic carrier state) in pregnancy in the United States is 6 to 10 per 1000 pregnancies. Women who are asymptomatic HBsAg carriers are at no higher risk for antepartum complications than are the general population. However, newborns delivered to mothers positive for HBsAg have a 10% risk for developing acute infection at birth. This is in contrast to those delivered to mothers positive for both HBsAg and hepatitis Be antigen (HBeAg), in which the infant’s risk increases to 70% to 90%. Infection in the infant may be fulminant and lethal. If the infant survives, it has an 85% to 90% chance of becoming a chronic hepatitis carrier and a 25% chance of developing liver cirrhosis, hepatocellular carcinoma, or both. Therefore, it is recommended that all pregnant women be screened for HBsAg carriage during pregnancy. Women in high-risk groups (Box 16-4) should be rescreened in the third trimester if the initial screen is negative.

If a pregnant woman is found on screening to be HBsAg positive, liver function tests and a complete hepatitis panel should be performed. Household members and sexual contacts should be tested and offered vaccination if they are susceptible. Transmission to the infant is believed to occur by direct contact during delivery. Therefore, the newborn is given hepatitis immune globulin and hepatitis vaccine soon after delivery, which reduces the risk for infection to less than 10%. Pregnant women at high risk for becoming infected with hepatitis B who test negative for the HBsAg should be offered vaccination. Available vaccines are produced by recombinant DNA technology and are therefore safe for use in pregnancy. The Centers for Disease Control and Prevention (CDC) have recommended that all children receive vaccination against hepatitis B as well.

Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States. Vertical transmission in HCV RNA–negative pregnant women is about 1% to 3% vs. about 4% to 6% in HCV RNA–positive women. Coinfection with HIV has been shown to increase the risk for vertical transmission of HCV. In HIV-negative women, route of delivery does not influence vertical transmission. Amniocentesis is a potential risk for transmission. There is no clear evidence demonstrating an increased risk for HCV transmission in HIV-negative women who breastfeed.

There is currently no safe treatment for HCV infection during pregnancy. Given the lack of measures to prevent transmission and to treat the infection efficiently, universal screening in pregnancy is currently not recommended. Women with high risk factors (such as blood transfusion or organ donation before 1992, HIV or hepatitis B positive, intravenous drug use, high-risk sexual behavior) should be offered anti-HCV testing during pregnancy.

Impact on Pregnancy

Management in Pregnancy

Antenatal antiviral prophylaxis (valacyclovir and acyclovir) from 36 weeks until delivery is safe and has been shown to decrease asymptomatic viral shedding, decrease herpes outbreak at delivery, and reduce the need for cesarean delivery for genital herpes. Women with a prior history of herpes should be allowed to deliver vaginally if no genital lesions are present at the time of labor. Patients with active lesions, either recurrent or primary, at the time of labor should be delivered by cesarean birth. Those with active lesions at sites distant from the genital area may be delivered vaginally if the lesions are covered. Once delivered, isolation of the mother from her infant is not necessary as long as direct contact with lesions is avoided. Mothers may breastfeed so long as no lesions are present on the breasts.

Diagnosis

GBS grow readily on routine bacteriologic media and are easy to isolate from clinical specimens. A number of specific rapid assays for the detection of GBS have been developed, but none is sensitive enough for widespread use.

Impact on Pregnancy

GBS may be transferred from a colonized mother to her infant by vertical transmission at delivery. Transmission rates of 35% to 70% have been reported, with the highest transmission rates occurring in women with heavy vaginal colonization. Other risk factors for transmission are preterm labor or delivery, preterm rupture of membranes, low birth weight, prolonged rupture of membranes (>12 to 18 hours before delivery), intrapartum fever, and a history of previously delivering an infected infant.

GBS sepsis is the most common cause of neonatal sepsis in the United States, with 1 to 2 cases per 1000 live births per year reported. Neonatal infection with GBS is of two clinically distinct types: early-onset and late-onset disease. Late-onset GBS infection has been linked to a nosocomial source in the nursery, occurs after the first week of life (mean onset, 4 weeks), and usually is exhibited as meningitis (80%) or another type of focal infection. Early-onset GBS infection is characterized by its rapid onset and fulminant course, with presentation typically within the first 48 hours of life. Pathogenesis of this form of GBS sepsis is best explained by direct maternal-infant transmission at delivery. The infant presents with respiratory distress and pneumonia, and 30% of infants develop meningitis. Septicemia, shock, and death may result even when antibiotics are begun expediently. The overall infant mortality rate from early-onset disease is 50%. Preterm infants account for more than 90% of deaths. The risk for sepsis developing in a full-term infant with bacterial colonization is 1% to 2%, compared with 8% to 10% in the preterm infant.

GBS is the second most common cause of bacteriuria in pregnancy and is a major cause of puerperal infection. Infection with GBS accounts for 20% of cases of endomyometritis and is unique in its acute onset (within the first 48 hours postpartum) and typically fulminant course.

Treating carriers in labor will reduce the rate of transmission to the infant. Both the CDC and the Committee on Obstetric Practice of the American College of Obstetricians and Gynecologists support a screening program in which vaginal and rectal group B streptococci cultures are obtained at 35 to 37 weeks for all gravidas except those who have GBS bacteriuria during the current pregnancy or a previous infant with invasive GBS disease. Intrapartum antibiotic prophylaxis would be indicated for pregnant women with (1) a previous infant with invasive GBS disease, (2) GBS bacteruria during the current pregnancy, (3) positive GBS screening culture during the current pregnancy, or (4) unknown GBS status with one of the high-risk factors such as intrapartum fever (≥38°C), preterm delivery (<37 weeks of gestation), or prolonged membrane rupture (≥18 hours). Antibiotic prophylaxis is not indicated for those undergoing a scheduled cesarean delivery in the absence of labor or amniotic membrane rupture. Antibiotic prophylaxis is also not indicated for those who have risk factors but are GBS culture negative in the current pregnancy.

Impact on Pregnancy

Maternal infection can result in transplacental transmission to the fetus at any gestational age. Mothers with primary and secondary syphilis are more likely to transmit the infection, with more severe manifestations occurring in the fetus. Transmission rates for primary and secondary disease are between 50% and 80%. There is a wide range of fetal responses to infection.

Components of early congenital syphilitic infection include nonimmune hydrops, hepatosplenomegaly, profound anemia and thrombocytopenia, skin lesions, rash, osteitis and periostitis, pneumonia, and hepatitis. The perinatal mortality rate from congenital syphilis is roughly 50%.

Late congenital syphilis (diagnosed after 2 years of age) is a multisystem disease characterized by dental abnormalities (Hutchinson’s teeth, mulberry molars); saber shins; saddle nose deformity; interstitial keratitis; eighth nerve deafness; and failure to thrive.

Treatment

Treatment of the condition in pregnancy is the same as that in the nonpregnant state. Penicillin G is the therapy of choice. Patients with primary, secondary, or latent syphilis of less than 12 months’ duration are treated with a single dose of benzathine penicillin, 2.4 million U given intramuscularly. Those with syphilis of undetermined length or with latent infection for longer than 1 year receive this therapy weekly for 3 weeks. For patients with penicillin allergy, desensitization and use of penicillin is recommended. Patients with neurosyphilis require admission and prolonged intravenous penicillin therapy.

Women treated for syphilis during their pregnancy require careful follow-up with monthly VDRL or RPR titers to ensure that the treatment is successful. Patients with syphilis remain positive on FTA-ABS testing for the remainder of their lives. Sexual contacts should be referred for treatment and neonates evaluated and treated as indicated.

Impact on Pregnancy

The incidence of primary infection in pregnancy is 1 in 1000. In immunocompromised women such as those with AIDS, a reactivation of toxoplasmosis could occur that would potentially be associated with a risk for fetal infection. The risk for transmission to the fetus is 15% in the first trimester, 25% in the second trimester, and 65% in the third trimester. However, the severity of fetal infection is greatest with first-trimester infection, and congenital defects are rarely seen if the infection occurs after 20 weeks of gestation. About 15% of infants with congenital infection are symptomatic at birth. A classic triad of hydrocephalus, intracranial calcifications, and chorioretinitis is described. Of the asymptomatic infants, 25% and 50% exhibit later sequelae (Box 16-5).

Diagnosis

Maternal infection is usually suspected if toxoplasmosis IgM antibodies are detected on routine screening. Occasionally pregnant women may be tested because of mononucleosis-like symptoms. A reference laboratory is used to confirm primary toxoplasmosis infection. At about 18 to 20 weeks of gestation, amniocentesis for toxoplasmosis PCR should be offered to women with a confirmed diagnosis of primary toxoplasmosis to detect fetal infection.

Treatment

Toxoplasmosis is a self-limiting infection. Owing to the fetal risk, spiramycin is used for treatment of maternal primary infection, but it is obtainable in the United States only through special permission from the U.S. Food and Drug Administration. If fetal infection is identified, therapy with pyrimethamine and sulfadiazine plus folinic acid should be given and has been shown to reduce the severity of fetal damage. Most infected infants have no apparent physical abnormalities at birth, but without treatment, most of the infected infants develop morbidity related to chorioretinitis, hydrocephalus, or neurologic damage by the end of adolescence. Therefore treatment of infected infants in the first year of life is recommended. To prevent infection, pregnant women should be advised to avoid contact with cat litter or feces, to wear gloves while gardening, and to avoid ingestion of undercooked meat or unpasteurized goat’s milk and drink filtered water.

Appendicitis

Appendectomy for presumed acute appendicitis is the most common surgical emergency during pregnancy. The incidence of acute appendicitis in pregnancy is about 0.05% to 0.1%, and it is constant throughout the three trimesters. The usual symptoms of acute appendicitis, such as epigastric pain, nausea, vomiting, and lower abdominal pain, may be less apparent during pregnancy, although right lower quadrant pain is still the most common presentation. The differential diagnosis may be especially confusing (Box 16-6). The enlarging uterus displaces the appendix superiorly and laterally as pregnancy progresses (Figure 16-1). Tenderness and guarding are elicited more laterally than expected. The increased white blood cell count seen in normal pregnancy further confuses the issue. Surgery may be delayed, resulting in an increased rate of rupture, premature labor, infant morbidity, and, rarely, maternal death.

FIGURE 16-1 The changing position of the right colon and appendix as pregnancy progresses and the uterus enlarges.

Imaging studies can increase the accuracy of the diagnosis of appendicitis. The American College of Radiology recommends nonionizing radiation techniques such as ultrasonography and MRI for imaging in pregnant women. On ultrasound, the abnormal appendix can be visualized as a noncompressible tubular structure measuring 6 mm or greater in the region of the patient’s pain. Helical computed tomography has the disadvantage of radiation exposure, but appendicitis is suspected if right lower quadrant inflammation, an enlarged nonfilling tubular structure, or a fecalith is noted. The estimated fetal radiation exposure is about 250 mrad. Exposure to less than 5 rad (0.05 Gy) has not been associated with an increase in fetal anomalies or pregnancy loss. Table 16-8 shows the dose of ionizing radiation to the fetus from common diagnostic radiologic procedures.

TABLE 16-8 ESTIMATED FETAL EXPOSURE FROM SOME COMMON RADIOLOGIC PROCEDURES

∗ 1 rad = 0.01 gray (Gy).

† Exposure depends on the number of films.

Data from American College of Obstetricians and Gynecologists: Guidelines for diagnostic imaging during pregnancy. ACOG Committee Opinion No. 299. Obstet Gynecol 104:649, 2004.

If acute appendicitis is diagnosed, laparotomy with appendectomy should be carried out. A McBurney, transverse, or Rockey-Davis incision can be employed. Laparoscopic appendectomy may increase the risk for fetal loss. A potential concern is that carbon dioxide used for insufflation can be absorbed across the peritoneum into the maternal bloodstream and across the placenta, leading to fetal respiratory acidosis and hypercapnia. As gestation progresses, the likelihood increases that the pneumoperitoneum will decrease venous return, cardiac output, and uteroplacental blood flow. Laparoscopic appendectomy may be considered if specific recommendations are met (Table 16-9).

TABLE 16-9 SAGES GUIDELINES FOR LAPAROSCOPIC OPERATIONS DURING PREGNANCY AND PROPOSED GUIDELINES TO IMPROVE SAFETY OF THE PROCEDURE

SAGES, Society of American Gastrointestinal and Endoscopic Surgeons.

∗ Proposed guideline change.

† Proposed guideline.

From Moreno-Sanz CJ: Laparoscopic appendectomy during pregnancy: Between personal experiences and scientific evidence. Am Coll Surg 205:37-42, 2007.

Acute Cholecystitis and Cholelithiasis

An increase in serum cholesterol and lipid levels in pregnancy, along with biliary stasis, leads to a higher incidence of cholelithiasis, biliary obstruction, and cholecystitis. High levels of estrogens in pregnancy increase the saturation of cholesterol in the bile. Virtually all of the gallstones associated with pregnancy are composed of crystallized cholesterol. Ultrasonography has revealed a fairly high incidence of cholelithiasis in pregnancy (4%). The incidence of hospitalization for cholecystitis in pregnancy is 1% to 2%, but only 1 in 2000 pregnant women require cholecystectomy.

Nausea and vomiting, along with right upper quadrant tenderness and guarding, generally suggest biliary tract disease. An increasing white blood cell count with elevated alkaline phosphatase and bilirubin levels, jaundice in the presence of stones, or increased thickness of the gallbladder wall on ultrasonography serves to authenticate the diagnosis. Viral hepatitis must be considered in the differential diagnosis. Markedly elevated aspartate transaminase and alanine transaminase levels (>200 U/L), especially without leukocytosis, should suggest viral hepatitis.

Generally, cholecystitis can be managed medically in pregnancy. Parenteral fluids, gastric decompression, and dietary measures should be the primary approach. Endoscopic retrograde cholangiopancreatography (ERCP) can be safely performed in pregnancy with little ionizing radiation exposure to the fetus if the patient has cholangitis or pancreatitis due to a common bile duct stone. If symptoms and signs persist with progressive peritonitis despite medical management or ERCP, cholecystectomy is indicated. Laparoscopic cholecystectomy has been performed in pregnancy.

Acute Pancreatitis

Generally, pancreatitis is associated with cholecystitis, cholelithiasis, or alcoholism. It has also been associated with viral infections and drugs such as thiazide diuretics, furosemide, acetaminophen, clonidine, isoniazid, rifampin, tetracycline, propoxyphene, and steroids. It is less common in pregnancy, and the incidence in pregnancy varies from 1:1000 to 1:4000, increasing somewhat in the third trimester. However, the mortality rate associated with pancreatitis is significantly higher when it does occur in pregnancy.

The prime symptom of pancreatitis is severe, noncolicky epigastric pain radiating to the high back, which is relieved somewhat by leaning forward. Nausea and vomiting generally are present. Upper abdominal guarding may be difficult to assess in late pregnancy. Elevated serum amylase (>200 U/dL) and lipase levels generally confirm the diagnosis, although cholecystitis, peptic ulcer, diabetic ketoacidosis, and hyperemesis gravidarum may also be associated with elevations of serum amylase

Generally, the disease is self-limited and responds within 1 to 10 days to bed rest, parenteral fluids, pain relief, and nasogastric suction. Occasionally the disease becomes severe and protracted, with extensive pancreatic edema and autodigestion, massive ascites, hemoperitoneum, fever, and paralytic ileus. In such cases, maternal and fetal mortality is high, and peritoneal lavage, operative drainage, partial pancreatic resection, or some combination of these procedures may be required.

Bowel Obstruction

Bowel obstruction in pregnancy is usually associated with postoperative adhesions, although volvulus and intussusception are rare causes. It generally occurs in late pregnancy and is associated with traction on adhesions as the uterus enlarges. An upright x-ray of the abdomen showing characteristic dilated loops of bowel and air-fluid levels serves to confirm the obstruction.

Management does not differ from that in the nonpregnant patient. Nasogastric suction should be instituted and fluid and electrolyte balance carefully monitored. If the obstruction does not resolve after 48 to 96 hours, an exploratory laparotomy should be carried out through an appropriate vertical incision. If uterine contractions occur postoperatively, tocolytics may be employed.

Adnexal Torsion

Torsion of the uterine adnexa occurs somewhat more commonly in pregnancy, possibly because the supporting ligaments elongate as the gestation progresses. Ovarian tumors (e.g., cystic teratomas, corpus luteum cysts) may become ischemic if their vascular pedicles undergo torsion. Such ischemic events are usually heralded by the sudden onset of severe, intermittent abdominal pain, which may radiate to the flank and down the anterior thigh.

During the first and early second trimesters, a mass is usually felt on pelvic examination or is visualized by ultrasonography. Later in the pregnancy it may be impossible to palpate a mass clinically. Low-grade fever and leukocytosis may be present, and serum creatine phosphokinase levels may be elevated, depending on the extent of the infarction. In the first trimester, the differential diagnosis includes ectopic pregnancy and hemorrhagic corpus luteum; later in pregnancy, a degenerating myoma should be considered.

Although the pain may diminish somewhat after 24 hours, removal of the infarcted organ is indicated. If the excised ovary contains the corpus luteum, progesterone supplementation is generally necessary before 8 weeks’ gestation.

Abdominal Trauma

By far, the most common abdominal trauma in pregnancy occurs in automobile accidents. Abruptio placentae, uterine contusions, and fetal skull fractures may result. Abruptio placentae is treated expectantly unless fetal monitoring indicates fetal distress, in which case immediate abdominal delivery is in order if the fetus is at a gestational age that is considered “viable” (23 to 24 weeks or greater). Abdominal exploration may be necessary to stop bleeding and repair uterine lacerations. Lap-shoulder harness seat belts, rather than lap belts, are advisable for pregnant women after 12 weeks’ gestation.

Gunshot wounds of the abdomen are treated as in nonpregnant patients, with measures taken to stop bleeding and repair visceral or uterine injuries. So long as the pregnancy is intact, the uterus should not be disturbed. Careful monitoring of fetal well-being should be maintained before and after the operation.

Ovarian Tumors

Adnexal masses are not uncommon and are usually identified by pelvic examination or ultrasonography early in the pregnancy. Paraovarian cysts, corpus luteum cysts, and mature teratomas are the most common. About 50% to 70% are functional cysts (e.g., corpus luteum cysts) and spontaneously resolve as the gonadotropin levels fall during the second trimester. The risk for malignancy is about 3% to 7%, with germ cell and epithelial tumors both occurring. Abdominal and transvaginal ultrasonography should be used for initial diagnosis, and any complex mass that persists, or simple cyst that continues to enlarge, should be removed in the second trimester.