Harrison's Internal Medicine > Part 1. Introduction to Clinical Medicine > Chapter 7. Medical Disorders during PregnancyMedical Disorders during Pregnancy: IntroductionApproximately 4 million births occur in the United States each year. A significant proportion of these are complicated by one or more medical disorders. Three decades ago, many medical disorders were contraindications to pregnancy. Advances in obstetrics, neonatology, obstetric anesthesiology, and medicine have increased the expectation that pregnancy will result in an excellent outcome for both mother and fetus despite most of these conditions. Successful pregnancy requires important physiologic adaptations, such as a marked increase in cardiac output. Medical problems that interfere with the physiologic adaptations of pregnancy increase the risk for poor pregnancy outcome; conversely, in some instances pregnancy may adversely impact an underlying medical disorder.Hypertension(See also Chap. 241)In pregnancy, cardiac output increases by 40%, most of which is due to an increase in stroke volume. Heart rate increases by ~10 beats/min during the third trimester. In the second trimester of pregnancy, systemic vascular resistance decreases and this is associated with a fall in blood pressure. During pregnancy, a blood pressure of 140/90 mmHg is considered to be abnormally elevated and is associated with an increase in perinatal morbidity and mortality. In all pregnant women, the measurement of blood pressure should be performed in the sitting position, because for many the lateral recumbent position is associated with a blood pressure lower than that recorded in the sitting position. The diagnosis of hypertension requires the measurement of two elevated blood pressures, at least 6 h apart. Hypertension during pregnancy is usually caused by preeclampsia, chronic hypertension, gestational hypertension, or renal disease.PreeclampsiaApproximately 5–7% of all pregnant women develop preeclampsia , the new onset of hypertension (blood pressure >140/90 mmHg) and proteinuria (>300 mg/24 h) after 20 weeks of gestation. Although the precise placental factors that cause preeclampsia are unknown, the end result is vasospasm and endothelial injury in multiple organs. Excessive placental secretion of a soluble fms-like tyrosine kinase 1, a naturally occurring vascular endothelial growth factor antagonist, and decreased secretion of placental growth factor may contribute to the endothelial dysfunction, hypertension, and proteinuria observed in preeclampsia. Glomerular endothelial cells demonstrate swelling and encroach on the vascular lumen. Preeclampsia is associated with abnormalities of cerebral circulatory autoregulation, which increase the risk of stroke at near-normal blood pressures. Risk factors for the development of preeclampsia include nulliparity, diabetes mellitus, a history of renal disease or chronic hypertension, a prior history of preeclampsia, extremes of maternal age (>35 years or <15 years), obesity, factor V Leiden mutation, angiotensinogen gene T235, G20210A prothrombin gene mutation, antiphospholipid antibody syndrome, and multiple gestation.Severe preeclampsia is the presence of new-onset hypertension and proteinuria accompanied by central nervous system (CNS) dysfunction (headaches, blurred vision, seizures, coma), marked elevations of blood pressure (>160/110 mmHg), severe proteinuria (>5 g/24 h), oliguria or renal failure, pulmonary edema, hepatocellular injury (ALT > 2 x the upper limits of normal), thrombocytopenia (platelet count < 100,000/L), or disseminated intravascular coagulation. Women with mild preeclampsia are those with the diagnosis of new-onset hypertension, proteinuria, and edema without evidence of severe preeclampsia. The HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a special subgroup of severe preeclampsia and is a major cause of morbidity and mortality in this disease. The presence of platelet dysfunction and coagulation disorders further increases the risk of stroke.Preeclampsia: TreatmentPreeclampsia resolves within a few weeks after delivery. For pregnant women with preeclampsia prior to 37 weeks' gestation, delivery reduces the mother's morbidity but exposes the fetus to the risk of premature delivery. The management of preeclampsia is challenging because it requires the clinician to balance the health of both mother and fetus simultaneously and to make management decisions that afford both the best opportunities for infant survival. In general, prior to term, women with mild preeclampsia can be managed conservatively with bed rest, close monitoring of blood pressure and renal function, and careful fetal surveillance. For women with severe preeclampsia, delivery is recommended unless the patient is eligible for expectant management in a tertiary hospital setting. Expectant management of severe preeclampsia remote from term affords some benefits for the fetus with significant risks for the mother.The definitive treatment of preeclampsia is delivery of the fetus and placenta. For women with severe preeclampsia, aggressive management of blood pressures > 160/110 mmHg reduces the risk of cerebrovascular accidents. Intravenous labetalol or hydralazine are the drugs most commonly used to manage preeclampsia. Intravenous hydralazine may be associated with more episodes of maternal hypotension than labetalol. Alternative agents such as calcium channel blockers may be used. Elevated arterial pressure should be reduced slowly to avoid hypotension and a decrease in blood flow to the fetus. Angiotensin-converting enzyme (ACE) inhibitors as well as angiotensin-receptor blockers should be avoided in the second and third trimesters of pregnancy because of their adverse effects on fetal development. Pregnant women treated with ACE inhibitors often develop oligohydramnios, which may be caused by decreased fetal renal function.Magnesium sulfate is the treatment of choice for the prevention and treatment of eclamptic seizures. Two large randomized clinical trials have demonstrated the superiority of magnesium sulfate over phenytoin and diazepam, and a recent large randomized clinical trial has demonstrated the efficacy of magnesium sulfate in reducing the risk of seizure and possibly reducing the risk of maternal death. Magnesium may prevent seizures by interacting with N-methyl-D-aspartate (NMDA) receptors in the CNS. Given the difficulty of predicting eclamptic seizures on the basis of disease severity, it is recommended that once the decision to proceed with delivery is made, all patients carrying a diagnosis of preeclampsia be treated with magnesium sulfate (see Regimens, below).
Chronic Essential HypertensionPregnancy complicated by chronic essential hypertension is associated with intrauterine growth restriction and increased perinatal mortality. Pregnant women with chronic hypertension are at increased risk for superimposed preeclampsia and abruptio placenta. Women with chronic hypertension should have a thorough prepregnancy evaluation, both to identify remediable causes of hypertension and to ensure that the prescribed antihypertensive agents are not associated with an adverse outcome of pregnancy (e.g., ACE inhibitors, angiotensin-receptor blockers). -Methyldopa, labetalol, and nifedipine are the most commonly used medications for the treatment of chronic hypertension in pregnancy. Baseline evaluation of renal function is necessary to help differentiate the effects of chronic hypertension versus superimposed preeclampsia should the hypertension worsen during pregnancy. There are no convincing data that demonstrate that treatment of mild chronic hypertension improves perinatal outcome.Gestational HypertensionThis is the development of elevated blood pressure during pregnancy or in the first 24 h post partum in the absence of preexisting chronic hypertension and other signs of preeclampsia. Uncomplicated gestational hypertension that does not progress to preeclampsia has not been associated with adverse pregnancy outcome or adverse long-term prognosis.Renal Disease(See also Chaps. 272 and 280)Normal pregnancy is characterized by an increase in glomerular filtration rate and creatinine clearance. This occurs secondary to a rise in renal plasma flow and increased glomerular filtration pressures. Patients with underlying renal disease and hypertension may expect a worsening of hypertension during pregnancy. If superimposed preeclampsia develops, the additional endothelial injury results in a capillary leak syndrome that may make the management of these patients challenging. In general, patients with underlying renal disease and hypertension benefit from aggressive management of blood pressure. Preconception counseling is also essential for these patients so that accurate risk assessment can occur prior to the establishment of pregnancy and important medication changes and adjustments can be made. In general, a prepregnancy serum creatinine level <133 mol/L (<1.5 mg/dL) is associated with a favorable prognosis. When renal disease worsens during pregnancy, close collaboration between the nephrologist and the maternal-fetal medicine specialist is essential so that decisions regarding delivery can be weighed in the context of sequelae of prematurity for the neonate versus long-term sequelae for the mother with respect to future renal function.Cardiac DiseaseValvular Heart Disease(See also Chap. 230) This is the most common cardiac problem complicating pregnancy.Mitral StenosisThis is the valvular disease most likely to cause death during pregnancy. The pregnancy-induced increase in blood volume, cardiac output, and tachycardia can increase the transmitral pressure gradient and cause pulmonary edema in women with mitral stenosis. Pregnancy associated with long-standing mitral stenosis may result in pulmonary hypertension. Sudden death has been reported when hypovolemia has been allowed to occur in this condition. Careful control of heart rate, especially during labor and delivery, minimizes the impact of tachycardia and reduced ventricular filling times on cardiac function. Pregnant women with mitral stenosis are at increased risk for the development of atrial fibrillation and other tachyarrhythmias. Medical management of severe mitral stenosis and atrial fibrillation with digoxin and beta blockers is recommended. Balloon valvulotomy can be carried out during pregnancy.Mitral Regurgitation and Aortic Regurgitation and StenosisThese are generally well tolerated during pregnancy. The pregnancy-induced decrease in systemic vascular resistance reduces the risk of cardiac failure with these conditions. As a rule, mitral valve prolapse does not present problems for the pregnant patient, and aortic stenosis, unless very severe, is well tolerated. In the most severe cases of aortic stenosis, limitation of activity or balloon valvuloplasty may be indicated.Congenital Heart Disease(See also Chap. 229) The presence of a congenital cardiac lesion in the mother increases the risk of congenital cardiac disease in the newborn. Prenatal screening of the fetus for congenital cardiac disease with ultrasound is recommended. Atrial or ventricular septal defect is usually well tolerated during pregnancy in the absence of pulmonary hypertension, provided that the woman's prepregnancy cardiac status is favorable. Use of air filters on IV sets during labor and delivery in patients with intracardiac shunts is generally recommended.Other Cardiac DisordersSupraventricular tachycardia (Chap. 226) is a common cardiac complication of pregnancy. Treatment is the same as in the nonpregnant patient, and fetal tolerance of medications such as adenosine and calcium channel blockers is acceptable. When necessary, electrocardioversion may be performed and is generally well tolerated by mother and fetus.Peripartum cardiomyopathy (Chap. 231) is an uncommon disorder of pregnancy associated with myocarditis, and its etiology remains unknown. Treatment is directed toward symptomatic relief and improvement of cardiac function. Many patients recover completely; others are left with a progressive dilated cardiomyopathy. Recurrence in a subsequent pregnancy has been reported, and women should be counseled to avoid pregnancy after a diagnosis of peripartum cardiomyopathy.Specific High-Risk Cardiac LesionsMarfan Syndrome(See also Chap. 357) This is an autosomal dominant disease, associated with a high risk of maternal morbidity. Approximately 15% of pregnant women with Marfan syndrome develop a major cardiovascular manifestation during pregnancy, with almost all women surviving. An aortic root diameter <40 mm is considered to be associated with a favorable outcome of pregnancy. Prophylactic therapy with beta blockers has been advocated, although large-scale clinical trials in pregnancy have not been performed.Pulmonary Hypertension(See also Chap. 244) Maternal mortality in the setting of severe pulmonary hypertension is high, and primary pulmonary hypertension is a contraindication to pregnancy. Termination of pregnancy may be advisable in these circumstances to preserve the life of the mother. In the Eisenmenger syndrome, i.e., the combination of pulmonary hypertension with right-to-left shunting due to congenital abnormalities (Chap. 229), maternal and fetal death occur frequently. Systemic hypotension may occur after blood loss, prolonged Valsalva maneuver, or regional anesthesia; sudden death secondary to hypotension is a dreaded complication. Management of these patients is challenging, and invasive hemodynamic monitoring during labor and delivery is generally recommended.In patients with pulmonary hypertension, vaginal delivery is less stressful hemodynamically than cesarean section, which should be reserved for accepted obstetric indications.Deep Venous Thrombosis and Pulmonary Embolism(See also Chap. 256)A hypercoagulable state is characteristic of pregnancy, and deep venous thrombosis (DVT) occurs in about 1 in 2000 pregnancies. Pulmonary embolism is one of the most common causes of maternal death in the United States. In pregnant women, DVT occurs much more commonly in the left leg than in the right leg, due to the compression of the left iliac vein by the iliac artery and the uterus. Activated protein C resistance caused by the factor V Leiden mutation increases the risk for DVT and pulmonary embolism during pregnancy. Approximately 25% of women with DVT during pregnancy carry the factor V Leiden allele. The presence of the factor V Leiden mutation also increases the risk for severe preeclampsia. Additional genetic mutations associated with DVT during pregnancy include the prothrombin G20210A mutation (heterozygotes and homozygotes) and the methylenetetrahydrofolate reductase C677T mutation (homozygotes).Deep Venous Thrombosis: TreatmentAggressive diagnosis and management of DVT and suspected pulmonary embolism optimize the outcome for mother and fetus. In general, all diagnostic and therapeutic modalities afforded the nonpregnant patient should be utilized in pregnancy. Anticoagulant therapy with low-molecular-weight heparin (LMWH) or unfractionated heparin is indicated in pregnant women with DVT. LMWH may be associated with an increased risk of epidural hematoma in women receiving an epidural anesthetic in labor. One approach to this problem is to switch from LMWH to unfractionated heparin before the anticipated delivery date. Warfarin therapy is contraindicated in the first trimester due to its association with fetal chondrodysplasia punctata. In the second and third trimesters, warfarin may cause fetal optic atrophy and mental retardation. When DVT occurs in the postpartum period, LMWH therapy for 7–10 days may be followed by warfarin therapy for 3–6 months. Warfarin is not contraindicated in breast-feeding women.Endocrine DisordersDiabetes Mellitus(See also Chap. 338) In pregnancy, the fetoplacental unit induces major metabolic changes, the purpose of which is to shunt glucose and amino acids to the fetus while the mother uses ketones and triglycerides to fuel her metabolic needs. These metabolic changes are accompanied by maternal insulin resistance, caused in part by placental production of steroids, a growth hormone variant, and placental lactogen. Although pregnancy has been referred to as a state of "accelerated starvation," it is better characterized as "accelerated ketosis." In pregnancy, after an overnight fast, plasma glucose is lower by 0.8–1.1 mmol/L (15–20 mg/dL) than in the nonpregnant state. This is due to the use of glucose by the fetus. In early pregnancy, fasting may result in circulating glucose concentrations in the range of 2.2 mmol/L (40 mg/dL) and may be associated with symptoms of hypoglycemia. In contrast to the decrease in maternal glucose concentration, plasma hydroxybutyrate and acetoacetate levels rise to two to four times normal after a fast.Diabetes Mellitus in Pregnancy: TreatmentPregnancy complicated by diabetes mellitus is associated with higher maternal and perinatal morbidity and mortality rates. Preconception counseling and treatment are important for the diabetic patient contemplating pregnancy and can reduce the risk of congenital malformations and improve pregnancy outcome. Folate supplementation reduces the incidence of fetal neural tube defects, which occur with greater frequency in fetuses of diabetic mothers. In addition, optimizing glucose control during key periods of organogenesis reduces other congenital anomalies including sacral agenesis, caudal dysplasia, renal agenesis, and ventricular septal defect.Once pregnancy is established, glucose control should be managed more aggressively than in the nonpregnant state. In addition to dietary changes, this requires more frequent blood glucose monitoring and often involves additional injections of insulin or conversion to an insulin pump. Fasting blood glucose levels should be maintained at <5.8 mmol/L (<105 mg/dL) with no values >7.8 mmol/L (140 mg/dL). Commencing in the third trimester, regular surveillance of maternal glucose control as well as assessment of fetal growth (obstetric sonography) and fetoplacental oxygenation (fetal heart rate monitoring or biophysical profile) optimizes pregnancy outcome. Pregnant diabetic patients without vascular disease are at greater risk for delivering a macrosomic fetus, and attention to fetal growth via clinical and ultrasound examinations is important. Fetal macrosomia is associated with an increased risk of maternal and fetal birth trauma. Pregnant women with diabetes have an increased risk of developing preeclampsia, and those with vascular disease are at greater risk for developing intrauterine growth restriction, which is associated with an increased risk of fetal and neonatal death. Excellent pregnancy outcomes in patients with diabetic nephropathy and proliferative retinopathy have been reported with aggressive glucose control and intensive maternal and fetal surveillance.Glycemic control may become more difficult to achieve as pregnancy progresses due to an increase in insulin resistance. Because of delayed pulmonary maturation of the fetuses of diabetic mothers, early delivery should be avoided unless there is biochemical evidence of fetal lung maturity. In general, efforts to control glucose and maintain the pregnancy until the estimated date of delivery result in the best overall outcome for both mother and newborn.Gestational DiabetesAll pregnant women should be screened for gestational diabetes unless they are in a low-risk group. Women at low risk for gestational diabetes are those <25 years of age; those with a body mass index < 25 kg/m2, no maternal history of macrosomia or gestational diabetes, and no diabetes in a first-degree relative; and those not members of a high-risk ethnic group (African American, Hispanic, Native American). A typical two-step strategy for establishing the diagnosis of gestational diabetes involves administration of a 50-g oral glucose challenge with a single serum glucose measurement at 60 min. If the plasma glucose is <7.8 mmol/L (<140 mg/dL), the test is considered normal. Serum glucose > 7.8 mmol/L (>140 mg/dL) warrants administration of a 100-g oral glucose challenge with serum glucose measurements obtained in the fasting state, and at 1, 2, and 3 h. Normal values are plasma glucose concentrations <5.8 mmol/L (<105 mg/dL), 10.5 mmol/L (190 mg/dL), 9.1 mmol/L (165 mg/dL), and 8.0 mmol/L (145 mg/dL), respectively. Some centers have adopted more conservative criteria, using <7.5 mmol/L (<135 mg/dL) as the screening threshold, and values of <5.3 mmol/L (<95 mg/dL), <10 mmol/L (<180 mg/dL), <8.6 mmol/L (<155 mg/dL), and <7.8 mmol/L (<140 mg/dL) as the upper norms for a 3-h glucose tolerance test.Pregnant women with gestational diabetes are at increased risk of preeclampsia, delivering infants who are large for their gestational age, and birth lacerations. Their fetuses are at risk of hypoglycemia and birth trauma (brachial plexus) injury. Gestational Diabetes: TreatmentTreatment of gestational diabetes with a two-step strategy of dietary intervention followed by insulin injections if diet alone does not adequately control blood sugar [fasting glucose < 5.6 mmol/L (<100 mg/dL) and 2-h post-prandial <7.0 mmol/L (<126 mg/dL)] is associated with a decreased risk of birth trauma for the fetus. More recently the use of the oral hypoglycemic agent glyburide has become popular for managing gestational diabetes refractory to nutritional management. More data on the safety and efficacy of glyburide for the management of gestational diabetes are needed before it supplants insulin as the treatment agent of choice. For women with gestational diabetes, within the 10 years after the index pregnancy there is a 40% risk of being diagnosed with diabetes. All women with a history of gestational diabetes should be counseled about prevention strategies and evaluated regularly for diabetes. Thyroid Disease(See also Chap. 335) In pregnancy, the estrogen-induced increase in thyroxine-binding globulin causes an increase in circulating levels of total T3 and total T4. The normal range of circulating levels of free T4, free T3, and thyroid-stimulating hormone (TSH) remain unaltered by pregnancy.The thyroid gland normally enlarges during pregnancy. Maternal hyperthyroidism occurs at a rate of ~2 per 1000 pregnancies and is generally well tolerated by pregnant women. Clinical signs and symptoms should alert the physician to the occurrence of this disease. Many of the physiologic adaptations to pregnancy may mimic subtle signs of hyperthyroidism. Although pregnant women are able to tolerate mild hyperthyroidism without adverse sequelae, more severe hyperthyroidism can cause spontaneous abortion or premature labor, and thyroid storm is associated with a significant risk of maternal mortality.Hyperthyroidism in Pregnancy: TreatmentHyperthyroidism in pregnancy should be aggressively evaluated and treated. The treatment of choice is propylthiouracil. Because it crosses the placenta, the minimum effective dose should be used to maintain free T4 in the upper normal range. Methimazole crosses the placenta to a greater degree than propylthiouracil and has been associated with fetal aplasia cutis. Radioiodine should not be used during pregnancy, either for scanning or treatment, because of effects on the fetal thyroid. In emergent circumstances, additional treatment with beta blockers and a saturated solution of potassium iodide may be necessary. Hyperthyroidism is most difficult to control in the first trimester of pregnancy and easiest to control in the third trimester.The goal of therapy for hypothyroidism is to maintain the serum TSH in the normal range, and thyroxine is the drug of choice. Children born to women with an elevated serum TSH (and a normal total thyroxine) during pregnancy have impaired performance on neuropsychologic tests. During pregnancy, the dose of thyroxine required to keep the TSH in the normal range rises. In one study, the mean replacement dose of thyroxine required to maintain the TSH in the normal range was 0.1 mg daily before pregnancy, and it increased to 0.15 mg daily during pregnancy. Since the increased thyroxine requirement occurs as early as the fifth week of pregnancy, one approach is to increase the thyroxine dose by 30% as soon as pregnancy is diagnosed and then adjust the dose by serial measurement of TSH.Hematologic DisordersPregnancy has been described as a state of physiologic anemia. Part of the reduction in hemoglobin concentration is dilutional, but iron and folate deficiencies are the major causes of correctable anemia during pregnancy.In populations at high risk for hemoglobinopathies (Chap. 99), hemoglobin electrophoresis should be performed as part of the prenatal screen. Hemoglobinopathies can be associated with increased maternal and fetal morbidity and mortality. Management is tailored to the specific hemoglobinopathy and is generally the same for both pregnant and nonpregnant women. Prenatal diagnosis of hemoglobinopathies in the fetus is readily available and should be discussed with prospective parents either prior to or early in pregnancy.Thrombocytopenia occurs commonly during pregnancy. The majority of cases are benign gestational thrombocytopenias, but the differential diagnosis should include immune thrombocytopenia (Chap. 109) and preeclampsia. Maternal thrombocytopenia may also be caused by catastrophic obstetric events such as retention of a dead fetus, sepsis, abruptio placenta, and amniotic fluid embolism.Neurologic DisordersHeadache appearing during pregnancy is usually due to migraine (Chap. 15), a condition that may worsen, improve, or be unaffected by pregnancy. A new or worsening headache, particularly if associated with visual blurring, may signal eclampsia (above) or pseudotumor cerebri (benign intracranial hypertension; Chap. 29); diplopia due to a sixth nerve palsy suggests pseudotumor cerebri. The risk of seizures in patients with epilepsy increases in the postpartum period but not consistently during pregnancy; management is discussed in Chap. 363. The risk of stroke is generally thought to increase during pregnancy because of a hypercoagulable state; however, studies suggest that the period of risk occurs primarily in the postpartum period and that both ischemic and hemorrhagic strokes may occur at this time. Guidelines for use of heparin therapy are summarized above (see "Deep Venous Thrombosis and Pulmonary Embolism"); warfarin is teratogenic and should be avoided.The onset of a new movement disorder during pregnancy suggests chorea gravidarum, a variant of Sydenham's chorea associated with rheumatic fever and streptococcal infection (Chap. 315); the chorea may recur with subsequent pregnancies. Patients with preexisting multiple sclerosis (Chap. 375) experience a gradual decrease in the risk of relapses as pregnancy progresses and, conversely, an increase in attack risk during the postpartum period. Beta interferons should not be administered to pregnant MS patients, but moderate or severe relapses can be safely treated with pulse glucocorticoid therapy. Finally, certain tumors, particularly pituitary adenoma and meningioma (Chap. 374), may manifest during pregnancy because of accelerated growth, possibly driven by hormonal factors.Peripheral nerve disorders associated with pregnancy include Bell's palsy (idiopathic facial paralysis, Chap. 379), which is approximately threefold more likely to occur during the third trimester and immediate postpartum period than in the general population. Therapy with glucocorticoids should follow the guidelines established for nonpregnant patients. Entrapment neuropathies are common in the later stages of pregnancy, presumably as a result of fluid retention. Carpal tunnel syndrome (median nerve) presents as pain and paresthesia in the hand, often worse at night, and later with weakness in the thenar muscles. Treatment is generally conservative; wrist splints may be helpful, and glucocorticoid injections or surgical section of the carpal tunnel can usually be postponed. Meralgia paresthetica (lateral femoral cutaneous nerve) consists of pain and numbness in the lateral aspect of the thigh without weakness. Patients are usually reassured to learn that these symptoms are benign and can be expected to remit spontaneously after the pregnancy has been completed.Judicious use of neuroimaging procedures is reasonable during pregnancy. Some centers require that formal consent be obtained from pregnant patients before MRI scans are administered. Experimental data indicate that high-field-strength MRI may be teratogenic to rodents; however, studies in pregnant MRI technicians have failed to show any risk to the fetus, even with chronic exposure. The paramagnetic MRI contrast agent gadolinium is usually not administered, particularly during the first trimester, because it crosses the blood-brain barrier. CT scanning of the brain is also considered safe, particularly as the procedure is fast, little radioactive scatter is produced, and pelvic contents are easily shielded; iodinated contrast media should be avoided whenever possible.Gastrointestinal and Liver DiseaseUp to 90% of pregnant women experience nausea and vomiting during the first trimester of pregnancy. Occasionally, hyperemesis gravidarum requires hospitalization to prevent dehydration, and sometimes parenteral nutrition is required.Crohn's disease may be associated with exacerbations in the second and third trimesters. Ulcerative colitis is associated with disease exacerbations in the first trimester and during the early postpartum period. Medical management of these diseases during pregnancy is identical to the management in the nonpregnant state (Chap. 289).Exacerbation of gall bladder disease is commonly observed during pregnancy. In part this may be due to pregnancy-induced alteration in the metabolism of bile and fatty acids. Intrahepatic cholestasis of pregnancy is generally a third-trimester event. Profound pruritus may accompany this condition, and it may be associated with increased fetal mortality. It has been suggested that placental bile salt deposition may contribute to progressive uteroplacental insufficiency. Therefore, regular fetal surveillance should be undertaken once the diagnosis of intrahepatic cholestasis is made. Favorable results with ursodiol have been reported.Acute fatty liver is a rare complication of pregnancy. Frequently confused with the HELLP syndrome (see "Preeclampsia," above) and severe preeclampsia, the diagnosis of acute fatty liver of pregnancy may be facilitated by imaging studies and laboratory evaluation. Acute fatty liver of pregnancy is generally characterized by markedly increased levels of bilirubin and ammonia and by hypoglycemia. Management of acute fatty liver of pregnancy is supportive; recurrence in subsequent pregnancies has been reported.All pregnant women should be screened for hepatitis B. This information is important for pediatricians after delivery of the infant. All infants receive hepatitis B vaccine. Infants born to mothers who are carriers of hepatitis B surface antigen should also receive hepatitis B immune globulin as soon after birth as possible and preferably within the first 72 h. Screening for hepatitis C is recommended for individuals at high risk for exposure.InfectionsBacterial InfectionsOther than bacterial vaginosis, the most common bacterial infections during pregnancy involve the urinary tract (Chap. 282). Many pregnant women have asymptomatic bacteriuria, most likely due to stasis caused by progestational effects on ureteral and bladder smooth muscle and later in pregnancy due to compression effects of the enlarging uterus. In itself, this condition is not associated with an adverse outcome of pregnancy. However, if asymptomatic bacteriuria is left untreated, symptomatic pyelonephritis may occur. Indeed, ~75% of cases of pregnancy-associated pyelonephritis are the result of untreated asymptomatic bacteriuria. All pregnant women should be screened with a urine culture for asymptomatic bacteriuria at the first prenatal visit. Subsequent screening with nitrite/leukocyte esterase strips is indicated for high-risk women, such as those with sickle cell trait or a history of urinary tract infections. All women with positive screens should be treated.Abdominal pain and fever during pregnancy create a clinical dilemma. The diagnosis of greatest concern is intrauterine amniotic infection. While amniotic infection most commonly follows rupture of the membranes, this is not always the case. In general, antibiotic therapy is not recommended as a temporizing measure in these circumstances. If intrauterine infection is suspected, induced delivery with concomitant antibiotic therapy is generally indicated. Intrauterine amniotic infection is most often caused by pathogens such as Escherichia coli and group B streptococcus. In high-risk patients at term or in preterm patients, routine intrapartum prophylaxis of group B streptococcal (GBS) disease is recommended. Penicillin G and ampicillin are the drugs of choice. In penicillin-allergic patients, clindamycin is recommended. For the reduction of neonatal morbidity due to GBS, universal screening of pregnant women for GBS between 35 and 37 weeks gestation with intrapartum antibiotic treatment of infected women is recommended.Postpartum infection is a significant cause of maternal morbidity and mortality. While rare after vaginal delivery, postpartum endomyometritis develops in 5% of patients having elective repeat cesarean section and in 25% of patients after emergency cesarean section following prolonged labor. Prophylactic antibiotics should be given to all patients undergoing cesarean section. As most cases of postpartum endomyometritis are polymicrobial, broad-spectrum antibiotic coverage with a penicillin, aminoglycoside, and metronidazole is recommended (Chap. 157). Most cases resolve within 72 h. Women who do not respond to antibiotic treatment for postpartum endomyometritis should be evaluated for septic pelvic thrombophlebitis. Imaging studies may be helpful in establishing the diagnosis, which is primarily a clinical diagnosis of exclusion. Patients with septic pelvic thrombophlebitis generally have tachycardia out of proportion to their fever and respond rapidly to intravenous administration of heparin.All patients are screened prenatally for gonorrhea and chlamydial infections, and the detection of either should result in prompt treatment. Ceftriaxone and azithromycin are the agents of choice (Chaps. 137 and 169).Viral InfectionsCytomegalovirus InfectionViral infection in pregnancy presents a significant challenge. The most common cause of congenital viral infection in the United States is cytomegalovirus (CMV) (Chap. 175). As many as 50–90% of women of childbearing age have antibodies to CMV, but only rarely does CMV reactivation result in neonatal infection. More commonly, primary CMV infection during pregnancy creates a risk of congenital CMV. No currently accepted treatment of CMV during pregnancy has been demonstrated to protect the fetus effectively. Moreover, it is impossible to predict which fetus will sustain life-threatening CMV infection. Severe CMV disease in the newborn is characterized most often by petechiae, hepatosplenomegaly, and jaundice. Chorioretinitis, microcephaly, intracranial calcifications, hepatitis, hemolytic anemia, and purpura may also develop. CNS involvement, resulting in the development of psychomotor, ocular, auditory, and dental abnormalities over time, has been described.Rubella(See also Chap. 186) Rubella virus is a known teratogen; first-trimester rubella carries a high risk of fetal anomalies, though the risk decreases significantly later in pregnancy. Congenital rubella may be diagnosed by percutaneous umbilical blood sampling with the detection of IgM antibodies in fetal blood. All pregnant women should be screened for their immune status to rubella. Indeed, all women of childbearing age, regardless of pregnancy status, should have their immune status for rubella verified and be immunized if necessary. The incidence of congenital rubella in the United States is extremely low.Herpesvirus(See also Chap. 172) The acquisition of genital herpes during pregnancy is associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. A recent cohort study of pregnant women without evidence of previous herpes infection demonstrated that ~2% of the women acquired a new herpes infection during the pregnancy. Approximately 60% of the newly infected women had no clinical symptoms. Infection occurred equally in all three trimesters. If herpes seroconversion occurred early in pregnancy, the risk of transmission to the newborn was very low. In women who acquired genital herpes shortly before delivery, the risk of transmission was high. The risk of active genital herpes lesions at term can be reduced by prescribing acyclovir for the last 4 weeks of pregnancy to women who have had their first episode of genital herpes during the pregnancy.Herpesvirus infection in the newborn can be devastating. Disseminated neonatal herpes carries with it high mortality and morbidity rates from CNS involvement. It is recommended that pregnant women with active genital herpes lesions at the time of presentation in labor be delivered by cesarean section.Parvovirus(See also Chap. 177) Parvovirus infection (human parvovirus B19) may occur during pregnancy. It rarely causes sequelae, but susceptible women infected during pregnancy may be at risk for fetal hydrops secondary to erythroid aplasia and profound anemia.HIV Infection(See also Chap. 182) The predominant cause of HIV infection in children is transmission of the virus from the mother to the newborn during the perinatal period. Exposures, which increase the risk of mother-to-child transmission, include vaginal delivery, preterm delivery, trauma to the fetal skin, and maternal bleeding. Additionally, recent infection with high maternal viral load, low maternal CD4+ T cell count, prolonged labor, prolonged length of membrane rupture, and the presence of other genital tract infections, such as syphilis or herpes, increase the risk of transmission. Breast-feeding may also transmit HIV to the newborn and is therefore contraindicated in most developed countries for HIV-infected mothers. There is no clear evidence to suggest that the course of HIV disease is altered by pregnancy. There is also no clear evidence to suggest that uncomplicated HIV disease adversely impacts pregnancy other than by its inherent infection risk.HIV Infection in Pregnancy: TreatmentThe majority of cases of mother-to-child (vertical) transmission of HIV-1 occur during the intrapartum period. Mechanisms of vertical transmission include infection after rupture of the membranes and direct contact of the fetus with infected secretions or blood from the maternal genital tract. Zidovudine (ZDV) administered during pregnancy and labor and to the newborn reduces the risk of vertical transmission by 70%. Cesarean section is associated with additional risk reduction compared to vaginal delivery, especially in women with a viral load >1000 copies/mL. Regardless of the mode of delivery, intrapartum ZDV should be provided.SummaryMaternal mortality has decreased steadily during the past 70 years. The maternal death rate has decreased from nearly 600/100,000 live births in 1935 to 8/100,00 live births in 2002. The most common causes of maternal death in the United States today are, in decreasing order of frequency, pulmonary embolism, obstetric hemorrhage, hypertension, sepsis, cardiovascular conditions including peripartum cardiomyopathy, and ectopic pregnancy. With improved diagnostic and therapeutic modalities as well as with advances in the treatment of infertility, more patients with medical complications will be seeking, and be in need of, complex obstetric care. Improving outcome of pregnancy in these women will be best obtained by assembling a team of internists, specialists in maternal-fetal medicine (high-risk obstetrics), and anesthesiologists to counsel these patients about the risks of pregnancy and to plan their treatment prior to conception. The importance of preconception counseling cannot be overstated. It is the responsibility of all physicians caring for women in the reproductive age group to assess their patient's reproductive plans as part of their overall health evaluation.Further Readings
| Alexander EK et al: Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med 351:292, 2005 |
| Bates SM et al: Use of antithrombotic agents during pregnancy: The Seventh ACCP Conference on antithrombotic and thrombolytic therapy. Chest 126:627S, 2004 |
| Buchanan TA, Xiang AH: Gestational diabetes mellitus. J Clin Invest 115:485, 2005 [PMID: 15765129] |
| Crowther CA et al: Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 352:2477, 2005 [PMID: 15951574] |
| Deneux-Tharaux C et al: Underreporting of pregnancy-related mortality in the United States and Europe. Obstet Gynecol 106:684, 2005 [PMID: 16199622] |
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