Medical Disorders During Pregnancy-audio

Medical Disorders during Pregnancy
Each year, approximately 4 million births occur in the United States, and more than 130 million births occur worldwide. A significant proportion of these are complicated by medical disorders. In the past, many medical disorders were contraindications to pregnancy. Advances in obstetrics, neonatology, obstetric anesthesiology, and medicine have increased the expectation that pregnancy will result in a positive 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

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, 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 the lateral recumbent position may result in 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.

Preeclampsia

Approximately 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 pathophysiology of preeclampsia remains unknown, recent studies show excessive placental production of antagonists to both vascular epithelial growth factor (VEGF) (soluble fms-like tyrosine kinase 1 and sflt-1) and transforming growth factor β (TGF-β) (endoglin). These antagonists to VEGF and TGF-β disrupt endothelial and renal glomerular function resulting in edema, hypertension, and proteinuria. The renal histological feature of preeclampsia is glomerular endotheliosis. Glomerular endothelial cells are swollen 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, antiphospholipid antibody syndrome, and multiple gestation.

Severe preeclampsia is the presence of new-onset hypertension proteinuria accompanied by end organ damage. Features may include marked elevation blood pressure (>160/110 mmHg), severe proteinuria (>5 g/24 h), or evidence of central nervous system (CNS) dysfunction (headaches, blurred vision, seizures, coma), renal dysfunction (oliguria or creatinine > 1.5 mg/dL), pulmonary edema, hepatocellular injury (ALT > 2-fold the upper limits of normal), hematologic dysfunction (platelet count < 100,000/L or disseminated intravascular coagulation), or placental dysfunction (oligohydramnios or severe intrauterine growth restriction). 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.

Treatment: Preeclampsia

Preeclampsia resolves within a few weeks after delivery. For pregnant women with preeclampsia prior to 37 weeks gestation, delivery reduces the mothers morbidity but exposes the fetus to the risk of premature birth. The management of preeclampsia is challenging because it requires the clinician to balance the health of the mother and fetus simultaneously. In general, prior to term, women with mild preeclampsia may 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 but 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, but labetalol is associated with fewer episodes of maternal hypotension. Nifedipine is also commonly used in pregnancy. 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.

Magnesium sulfate is the treatment of choice for the prevention and treatment of eclamptic seizures. Large, randomized clinical trials have demonstrated the superiority of magnesium sulfate over phenytoin and diazepam, and the efficacy of magnesium sulfate in reducing the risk of seizure and, possibly, 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, once the decision to proceed with delivery is made, most patients carrying a diagnosis of preeclampsia should be treated with magnesium sulfate. Women who have had preeclampsia appear to be at increased risk of cardiovascular and renal disease later in life.

Regimens for the administration of magnesium sulfate for seizure prophylaxis in women in labor with preeclampsia

Intramuscular	Intravenous
10g ( 5g IM deep in each buttock)a	6-g bolus over 15 min
1-3 g/h by continuous infusion pump May be mixed in 100 mL crystalloid; if given by intravenous push, make up as 20% solution; push at maximum rate of 1 g/min 40-g MgSo4.7H20 in 1000 mL Ringers lactate; run at 25-75 mL(1-3 g/h)a
5g IM deep q4h, alternating sides	
aMade up as 50% solution
Chronic Essential Hypertension

Pregnancy 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). α-Methyldopa, labetalol, and nifedipine are the most commonly used medications for the treatment of chronic hypertension in pregnancy. α-Methyldopa is a relatively poor antihypertensive drug, but it has a long record of safe use in pregnancy. With the development of newer antihypertensives, also with long records of safe use in pregnancy, and with improved methods of fetal surveillance, we no longer recommend α-methyldopa as first-line therapy for the management of chronic hypertension. 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 Hypertension

This is the development of elevated blood pressure during pregnancy or in the first 24 h post-partum in the absence of preexisting chronic hypertension or proteinuria. Mild gestational hypertension that does not progress to preeclampsia has not been associated with adverse pregnancy outcome or adverse long-term prognosis.

Renal Disease

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 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 and medication changes can occur prior to pregnancy. In general, a prepregnancy serum creatinine level <133 μmolL (<1.5 mgdL) is associated with a favorable prognosis. When renal disease worsens during pregnancy, close collaboration between the internist and maternal-fetal medicine specialist essential so that decisions regarding delivery can be weighed in context of sequelae prematurity for neonate versus long-term mother respect to future function.

Cardiac Disease

Valvular Heart Disease

This most common cardiac problem complicating pregnancy.

Mitral Stenosis

This valvular likely cause death pregnancy. The pregnancy-induced increase blood volume, output, tachycardia transmitral pressure gradient pulmonary edema women mitral stenosis. Pregnancy long-standing stenosis may result hypertension. Sudden has been reported when hypovolemia occurs. Careful control heart rate, especially labor delivery, minimizes impact reduced ventricular filling times on function. Pregnant are at increased risk development atrial fibrillation other tachyarrhythmias. Medical management severe digoxin beta blockers recommended. Balloon valvulotomy carried out immediate postpartum period time particular concern secondary rapid volume shifts. monitoring fluid status should observed.

Mitral Regurgitation Aortic Stenosis

These generally well tolerated decrease systemic vascular resistance reduces failure these conditions. As rule, valve prolapse does not present problems pregnant patient, aortic stenosis, unless very severe, tolerated. In cases limitation activity or balloon valvuloplasty indicated.

Congenital Disease

The presence congenital lesion increases newborn. Prenatal screening fetus ultrasound Atrial septal defect usually pregnancy absence hypertension, provided womans prepregnancy favorable. Use air filters IV sets patients intracardiac shunts recommended.

Other Cardiac Disorders

Supraventricular complication Treatment same as nonpregnant fetal tolerance medications such adenosine calcium channel acceptable. necessary, pharmacologic electric cardioversion performed improve performance reduce symptoms. This by fetus.

Peripartum cardiomyopathy an uncommon disorder myocarditis, its etiology remains unknown. directed toward symptomatic relief improvement Many recover completely; others left progressive dilated cardiomyopathy. Recurrence subsequent reported, who do have normal baseline function after episode peripartum counseled avoid pregnancy.

Specific High-Risk Lesions

Marfan Syndrome

This autosomal dominant disease, high maternal morbidity. Approximately 15% Marfan syndrome develop major cardiovascular manifestation almost all surviving. An root diameter <40 mm considered outcome Prophylactic therapy advocated, although large-scale clinical trials performed. Ehlers-Danlos (EDS) premature labor, type EDS, there uterine rupture.

Pulmonary Hypertension

Maternal mortality setting hypertension high, primary contraindication Termination advisable circumstances preserve life mother. Eisenmenger syndrome, i.e., combination right-to-left shunting due abnormalities, occur frequently. Systemic hypotension loss, prolonged Valsalva maneuver, regional anesthesia; sudden dreaded complication. Management challenging, invasive hemodynamic recommended cases.

In vaginal less stressful hemodynamically than cesarean section, which reserved accepted obstetric indications.

Deep Venous Thrombosis Pulmonary Embolism

A hypercoagulable state characteristic deep venous thrombosis (DVT) occurs about 1 2000 pregnancies. procoagulants factors V VII, anticoagulant activity, including proteins C S. embolism one causes United States. women, DVT much more commonly leg right leg, compression iliac vein artery uterus. Activated protein caused factor Leiden mutation 25% carry allele. Additional genetic mutations include prothrombin G20210A (heterozygotes homozygotes) methylenetetrahydrofolate reductase C677T (homozygotes).

Treatment: Deep Thrombosis

Aggressive diagnosis suspected optimize fetus. general, diagnostic therapeutic modalities afforded patient utilized Anticoagulant low-molecular weight heparin (LMWH) unfractionated indicated DVT. LMWH epidural hematoma receiving anesthetic labor. Four weeks prior anticipated switched heparin. Warfarin contraindicated first trimester association chondrodysplasia punctata. second third trimesters, warfarin optic atrophy mental retardation. period, 7–10 days followed 3–6 months. breast-feeding women. For moderate DVT, mechanical prophylaxis warranted if they delivery.

Endocrine Disorders

Diabetes Mellitus

In fetoplacental unit induces metabolic changes, purpose shunt glucose amino acids while uses ketones triglycerides fuel her needs. These changes accompanied insulin resistance, part placental production steroids, growth hormone variant, lactogen. Although referred “accelerated starvation,” it better characterized ketosis.” overnight fast, plasma lower 0.8–1.1 mmol (15–20 state. use early fasting circulating concentrations range 2.2 (40 symptoms hypoglycemia. contrast concentration, hydroxybutyrate acetoacetate levels rise two four fast.

Treatment: Diabetes Mellitus Pregnancy

Pregnancy complicated diabetes mellitus higher perinatal morbidity rates. Preconception counseling treatment important diabetic contemplating malformations outcome. Folate supplementation incidence neural tube defects, greater frequency fetuses mothers. addition, optimizing key periods organogenesis anomalies sacral agenesis, caudal dysplasia, defect.

Once established, managed aggressively addition dietary this requires frequent often involves additional injections conversion pump. Fasting maintained <5.8 (<105 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 examination is important. Fetal macrosomia is associated with an increased risk of maternal and fetal birth trauma, including permanent newborn Erbs palsy. 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 avoid preterm delivery result in the best overall outcome for both mother and newborn. Preterm delivery is generally performed only for the usual obstetric indications (e.g., preeclampsia, fetal growth restriction, non-reassuring fetal testing) or for worsening maternal renal or active proliferative retinopathy.

Gestational Diabetes

Gestational diabetes occurs in approximately 4% of pregnancies. All 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 mgdL), the test is considered normal. Plasma glucose> 7.8 mmol/L (>140 mg/dL) warrants administration of a 100-g oral glucose challenge with plasma 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 sensitive criteria, using <7.5 mmol/L (<130 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. Adverse pregnancy outcomes for mother and fetus appear to increase with glucose as a continuous variable, making it challenging to define the optimal threshold for establishing the diagnosis of gestational diabetes.

Pregnant women with gestational diabetes are at increased risk of stillbirth, preeclampsia, and delivering infants who are large for their gestational age with resulting birth lacerations, shoulder dystocia, and birth trauma including brachial plexus injury. Their fetuses are at risk of hypoglycemia, hyperbilirubinemia, and polycythemia. Tight control of blood sugar during pregnancy and labor can reduce these risks.

Treatment: Gestational Diabetes

Treatment 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. Oral hypoglycemic agents such as glyburide and metformin have become more commonly utilized for managing gestational diabetes refractory to nutritional management. For women with gestational diabetes, within the 10 years after the index pregnancy there is a 40% risk of being diagnosed with diabetes. In women with a history of gestational diabetes, exercise, weight loss, and treatment with metformin reduce the risk of developing diabetes. All women with a history of gestational diabetes should be counseled about prevention strategies and evaluated regularly for diabetes.

Obesity

Pregnant women who are obese have an increased risk of stillbirth, congenital fetal malformations, gestational diabetes, preeclampsia, urinary tract infections, and post-date deliveries. Women contemplating pregnancy should attempt to achieve a healthy weight prior to conception. For morbidly obese women who have not been able to achieve weight loss with lifestyle changes, bariatric surgery may result in weight loss and improve pregnancy outcomes. Following bariatric surgery, women should delay conception for one year to avoid pregnancy during an interval of rapid metabolic changes.

Thyroid Disease

In pregnancy, the estrogen-induced increase in thyroxine-binding globulin increases 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.

Treatment: Hyperthyroidism in Pregnancy

Hyperthyroidism in pregnancy should be aggressively evaluated and treated. It is most commonly caused by Graves disease, but autonomously functioning nodules, gestational trophoblastic disease, thyroiditis, and hyperemesis gravidarum should also be considered. Methimazole crosses the placenta to a greater degree than propylthiouracil and has been associated with fetal aplasia cutis. However, propylthiouracil can be associated with liver failure. Some experts recommend propylthiouracil in the first trimester and methimazole thereafter. 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.

Testing for hypothyroidism using TSH measurements before or early in pregnancy may be warranted in symptomatic women and women with a personal or family history of thyroid disease. Using this case-finding approach, about 30% of pregnant women with mild hypothyroidism will remain undiagnosed, leading some to recommend universal screening. Children born to women with an elevated serum TSH (and a normal total thyroxine) during pregnancy have impaired performance on neuropsychologic tests. The goal of therapy for hypothyroidism is to maintain the serum TSH in the normal range, and thyroxine is the drug of choice. 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 measurements of TSH.

Hematologic Disorders

Pregnancy 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 , 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 , thrombotic thrombocytopenic purpura, and preeclampsia. Maternal thrombocytopenia may also be caused by disseminated intravascular coagulation (DIC), which is a consumptive coagulopathy characterized by thrombocytopenia, prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), elevated fibrin degradation products, and a low fibrinogen concentration. Several catastrophic obstetric events are associated with the development of DIC, including retention of a dead fetus, sepsis, abruptio placenta, and amniotic fluid embolism.

Neurologic Disorders

Headache appearing during pregnancy is usually due to migraine , 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) ; 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 . 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 Sydenhams chorea associated with rheumatic fever and streptococcal infection ; the chorea may recur with subsequent pregnancies. Patients with preexisting multiple sclerosis (MS) 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 , may manifest during pregnancy because of accelerated growth, possibly driven by hormonal factors.

Peripheral nerve disorders associated with pregnancy include Bells palsy (idiopathic facial paralysis), 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. Restless leg syndrome is the most common peripheral nerve and movement disorder in pregnancy. Disordered iron metabolism is the suspected etiology. Management is expectant in most cases.

Gastrointestinal and Liver Disease

Up to 90% of pregnant women experience nausea and vomiting during the first trimester of pregnancy. Hyperemesis gravidarum is a severe form that prevents adequate fluid and nutritional intake and may require hospitalization to prevent dehydration and malnutrition.

Crohns 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.

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. 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.

Infections

Bacterial Infections

Other than bacterial vaginosis, the most common bacterial infections during pregnancy involve the urinary tract . 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. Pregnant women who develop pyelonephritis need careful monitoring, including inpatient IV antibiotic administration due to the elevated risk of urosepsis and acute respiratory distress syndrome in pregnancy.

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, with a low risk of anaphylaxis, cefazolin is recommended. If the patient is at high risk of anaphylaxis, vancomycin is recommended. If the organism is known to be sensitive to clindamycin, this antibiotic may be used. 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. Postpartum endomyometritis is more common after cesarean delivery than vaginal delivery and develops in 5% of women after elective repeat cesarean section and in up to 25% after emergency cesarean section, following prolonged labor. Prophylactic antibiotics should be given to all patients undergoing cesarean section, and administration 30–60 minutes prior to skin incision may be preferable to administration at the time of umbilical cord clamping. As most cases of postpartum endomyometritis are polymicrobial, broad-spectrum antibiotic coverage with a penicillin, aminoglycoside, and metronidazole is recommended . 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.

Viral Infections

Cytomegalovirus Infection

Viral infection in pregnancy presents a significant challenge. The most common cause of congenital viral infection in the United States is cytomegalovirus (CMV). 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 difficult to predict which fetus will sustain a 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

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

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 four 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

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

The predominant cause of HIV infection in children is transmission of the virus from the mother to the newborn during the perinatal period. HIV 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. Advances in antiretroviral therapy now make it possible for many pregnant women to have no detectable viral load as they approach term. These women may elect to attempt a vaginal birth. To reduce the risk of mother-to-newborn transmission, women should be treated during the intrapartum interval with zidovudine and the newborn should also be treated after birth. Breast-feeding may also transmit HIV to the newborn and is therefore contraindicated in most developed countries for HIV-infected mothers.

Summary
Maternal death is defined as the death occurring during pregnancy or within 42 days of completion of the pregnancy from a cause related to or aggravated by the pregnancy, but not from accident or incidental causes. Maternal 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 13/100,000 live births in 2006. The most common causes of maternal death in the United States today are 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 patients reproductive plans as part of their overall health evaluation.

Global Considerations

The maternal mortality ratio in the United States is about 1 in 7500 live births. In some countries in Sub-Saharan Africa and Southeast Asia, the maternal mortality ratio is about 1 in 100 to 1 in 200 live births. The most common cause of maternal mortality in these countries is maternal hemorrhage. The high maternal death rate is due, in part, to inadequate resources, including lack of contraceptive and family-planning services, insufficient number of skilled birth attendants, limited availability of tocolytics, poor nutrition, and a high burden of infectious disease. The high rate of death from peripartum hemorrhage is due, in part, to inadequate access to anesthesia resources, blood-transfusion services, antibiotics, and skilled pelvic surgeons. Maternal death is a global public-health tragedy that could be improved with the application of modest resources.

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