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Medical Issues in Pregnancy
Of the over 70 million women of reproductive age in the United States, women are increasingly entering pregnancy at a later age. The mean age was 27.1 years in 2020, up from 23 years in 1994. Pregnancy, which has always served as a stress test for a woman’s health, is now becoming even more of a challenge as women, especially non-White women ( E-Fig. 221-1 ), experience it with more underlying comorbid medical conditions that can be exacerbated during pregnancy or at the time of labor and delivery. , The most common complication is bleeding, which accounts for about 75% of cases of severe maternal morbidity in the United States. However, other conditions that are significantly associated with severe maternal morbidity and mortality ( E-Fig. 221-2 ) include hypertension, diabetes, peripartum cardiomyopathy, thromboembolic disease, sepsis (most commonly from pyelonephritis), suicide, acute fatty liver of pregnancy, and thyroid storm.
Maternal mortality rates (per 100,000 live births) by race/ethnicity in the United States, 2018-2020.
Adapted from the Hoyert DL. Maternal mortality rates in the United States, 2020. NCHS Health E-Stats. 2022. https://www.cdc.gov/nchs/data/hestat/maternal-mortality/2020/E-stat-Maternal-Mortality-Rates-2022.pdf . Accessed March 13, 2022.
Causes of pregnancy-related death in the United States, 2014-2017. (Adapted from the Centers for Disease Control and Prevention Pregnancy Mortality Surveillance System. https://www.cdc.gov/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm . Accessed November 18, 2021.)
General Principles
Because of physiologic changes in pregnancy, maternal drug concentrations (and thus embryo-fetal exposure) are altered from the nonpregnant state. Physiologic changes include alterations in circulating binding proteins, volume of distribution, cardiac output, gastrointestinal transit and absorption, hepatic metabolism, and renal clearance ( Fig. 221-1 and Table 221-1 ). Despite these differences, it is not appropriate to withhold an indicated, or necessary, intervention, simply because of pregnancy or lactation. Comprehensive counseling, including the obstetrician as well as medical surgical experts, and shared-decision making are key to understanding not only the theoretical risks but also the benefits, indications, and alternatives.
TABLE 221-1
NORMAL PHYSIOLOGIC CHANGES IN PREGNANCY
From Rosene-Montella K. Common medical problems in pregnancy. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 26th ed. Philadelphia: Elsevier Saunders; 2020.
| CARDIAC |
| Cardiac output increased 40% Blood volume increased 30-50% Heart rate increased 10-20 beats/min Blood pressure decreased 10-15 mm Hg ECG changes related to widened thorax, dextrorotation of heart, elevation of diaphragm |
| PULMONARY |
| Upper airway hyperemia and glandular hyperactivity leading to increased edema and friability Nasal congestion, gestational rhinitis, snoring Difficult airway management and failed intubation Minute ventilation increased (owing to an increase in tidal volume, not respiratory rate, which remains unchanged), which leads to relative respiratory alkalosis (pH 7.4-7.45) Pa o 2 100-105 mm Hg Pa co 2 28-32 mm Hg |
| RENAL |
| Increased GFR to 150-180 mL/min/1.73 m 2 Serum creatinine concentration <0.8 mg/dL Increased renal excretion of bicarbonate, limiting buffering capacity in patients who become acidotic Decreased oncotic pressure |
| ALTERED PHARMACOKINETICS |
| Increased renal and hepatic clearance of drugs Altered absorption Altered protein binding Increased volume of distribution |
ECG = electrocardiogram; GFR = glomerular filtration rate.
These physiologic changes generally progress throughout gestation.
Women who enter pregnancy with medical conditions have an increased risk of complications, including preterm birth, preeclampsia, fetal growth restriction, stillbirth, and maternal morbidities. As a general rule, if the medical condition is optimized prior to conception ( Table 221-2 ), the risk of complications to the mother and the fetus is decreased. Many medical conditions affect fetal development, so enhancing access to care before conception or after delivery for intervening births must be a priority and become a central focus of health policy and advocacy. For example, hyperglycemia in the first trimester in diabetic women is associated with diabetic embryopathy, manifested by anencephaly, microcephaly, congenital heart disease, renal anomalies, and caudal regression ( Fig. 221-2 ). Because organogenesis occurs within the first 8 weeks of gestation, glycemic control ( Chapter 210 ) should be optimized prior to conception, aiming for a hemoglobin A 1C level less than 6.0. Optimal control of other conditions, such as systemic lupus erythematosus ( Chapter 245 ), can improve the outcome of pregnancy if conception occurs while the disease is in remission.
TABLE 221-2
PRECONCEPTION INTERVENTIONS FOR PATIENTS WITH MEDICAL ILLNESSES
From Rosene-Montella K, Keely EJ, Lee RV, Barbour LA, eds. Medical Care of the Pregnant Patient . 2nd ed. Philadelphia: ACP Press/American College of Physicians; 2008.
| TYPE 1 AND TYPE 2 DIABETES MELLITUS |
| Discuss importance of hemoglobin A 1c before conception Evaluate for microvascular complications Obtain remission proliferative retinopathy Discuss contraindication of ACE inhibitor in pregnancy Discontinue thiazolidinediones and statins Consider change to insulin therapy for type 2 diabetic patients on oral agents unless using metformin for ovulation induction in PCOS Discuss probable need to reduce insulin dose in first trimester |
| THYROID DISEASE |
| Screen for hypothyroidism in women at risk Normalize TSH and free T 4 before pregnancy Counsel women taking levothyroxine on need to increase dose soon after conception Diagnose cause of hyperthyroidism and consider ablative therapy for women with Graves disease requiring high doses of PTU |
| CHRONIC HYPERTENSION/RENAL DISEASE |
| Rule out secondary causes of hypertension if appropriate Evaluate extent of end-organ disease Quantify GFR and proteinuria Discuss drugs of choice for hypertension and replace ACE inhibitor Discuss risk for superimposed preeclampsia and use of low-dose aspirin for women at significant risk for preeclampsia |
| THROMBOEMBOLIC DISEASE |
| Consider evaluation for congenital or acquired thrombophilias in women with previous VTE, previous poor obstetric outcome, or family history Discuss risks of warfarin in pregnancy, need to discontinue warfarin by 4 to 6 weeks’ gestation, and conversion to unfractionated or low-molecular-weight heparin Discuss options to combined oral contraceptives |
| EPILEPSY |
| Determine whether patient is a candidate for withdrawal of antiepileptic drugs Consider monotherapy with most effective agent at lowest dose possible Prescribe folate at 1 to 4 mg/day Discuss possible ineffectiveness of low-dose contraceptives with phenobarbital, phenytoin, and carbamazepine Consider discontinuing valproate |
| CARDIAC DISEASE |
| Obtain baseline echocardiography if congenital disease, stenotic lesion, or pulmonary hypertension suspected Evaluate for coronary artery disease in women with multiple risk factors |
| ASTHMA |
| Verify patient’s asthma action plan and peak flowmeter use Discuss relative safety of all asthma medications except leukotriene modifiers |
| SYSTEMIC LUPUS ERYTHEMATOSUS AND AUTOIMMUNE DISEASE |
| Evaluate for renal and cardiopulmonary disease and antiphospholipid, anti-Ro, anti-La antibodies Avoid pregnancy if disease is active Discuss relative safety of most immunosuppressants |
ACE = angiotensin-converting enzyme; GFR = glomerular filtration rate; PCOS = polycystic ovary syndrome; PTU = propylthiouracil; T 4 = thyroxine; TSH = thyroid-stimulating hormone; VTE = venous thromboembolism.
Medications
For most medical conditions, treatment of women who wish to become pregnant or are pregnant does not differ from routine care, except for the avoidance of drugs that are known to be unsafe for the fetus or situations in which drugs of proven safety are substituted for drugs of unknown safety. The care of all women of childbearing age should avoid medications known to be associated with abnormal fetal development ( Table 221-3 ) unless adequate contraceptive methods ( Chapter 220 ) are ensured.
TABLE 221-3
MEDICATIONS TO AVOID IN WOMEN OF CHILDBEARING AGE CONSIDERING PREGNANCY
| Angiotensin-converting enzyme inhibitors Angiotensin-receptor blocking agents Cyclophosphamide Danazol Doxycycline Efavirenz Endothelin-receptor antagonists—bosentan, ambrisentan, macitentan Leflunomide Methotrexate |
Mycophenolate mofetil Phenytoin Radioiodine Retinoids—isotretinoin, acitretin, bexarotene Ribavirin Tamoxifen Trastuzumab Valproic acid Warfarin (except during the second and third trimesters in patients who have mechanical heart valves) |
Radiation Exposure
Radiographs can cause an electrochemical reaction that damages tissue ( Chapter 18 ), thereby resulting in pregnancy loss, fetal growth restriction, congenital malformations, microcephaly, or intellectual disability. Importantly, the impact of radiation on the fetus depends on gestational age. Below a threshold dose (0.05 Gy or 5 rad), radiation poses no risk, and the threshold for gross malformations is about 0.2 Gy (20 rads). Imaging should not be withheld if it is needed for diagnosis, but expert consultation should be obtained, and patients must be counseled regarding risks and benefits. Guidelines no longer require verification of pregnancy status for radiographs that do not directly expose the pelvis ( Table 221-4 ).
TABLE 221-4
IMAGING TECHNIQUES AND PREGNANCY VERIFICATION
Adapted from American College of Radiology. ACR–SPR practice parameter for imaging pregnant or potentially pregnant adolescents and women with ionizing radiation. https://www.acr.org/-/media/ACR/Files/Practice-Parameters/Pregnant-Pts.pdf . Accessed November 18, 2021.
| PREGNANCY VERIFICATION NOT REQUIRED | PREGNANCY VERIFICATION REQUIRED |
|---|---|
| Chest radiography | Interventional fluoroscopic procedures of the abdomen or pelvis |
| Extremity radiography | Diagnostic angiography of the abdomen or pelvis |
| Head/Neck diagnostic examination | Hysterosalpingography |
| Mammography | Standard-dose CT protocols of the abdomen or pelvis |
| CT imaging outside of abdomen or pelvis (except hip) | Diagnostic nuclear Medicine PET/CT |
CT = computed tomography; PET = positron emission tomography.
Laboratory Test Results
The physiologic changes in pregnancy alter the normal range of many laboratory values (see Appendix ). For example, the increase in plasma volume relative to red blood cell volume results in a physiologic anemia and dilutional decreases in blood levels of albumin, creatinine, and platelets. By comparison, white blood cell levels, particularly neutrophils, and cholesterol, and fibrinogen levels increase across gestation ( Table 221-5 ).
TABLE 221-5
SELECTED LABORATORY VALUES IN PREGNANCY ACCORDING TO TRIMESTER COMPARED WITH NONPREGNANT INDIVIDUALS
Adapted from Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol . 2009;114:1326-1331.
| 1st TRIMESTER | 2nd TRIMESTER | 3rd TRIMESTER | NONPREGNANT | |
|---|---|---|---|---|
| Hematocrit (%) | 31.0-41.0 | 30.0-39.0 | 28.0-40.0 | 35.4-44.4 |
| Platelets (×10 9 /L) | 174-391 | 155-409 | 146-429 | 165-415 |
| Albumin (g/dL) | 3.1-5.1 | 2.6-4.5 | 2.3-4.2 | 4.1-5.3 |
| Fibrinogen (mg/dL) | 244-510 | 291-538 | 373-619 | 233-496 |
| Alkaline Phosphatase (U/L) | 17-88 | 25-126 | 38-229 | 33-96 |
| Cholesterol (mg/dL) | 141-210 | 176-299 | 219-349 | <200 |
| Creatinine (mg/dL) | 0.4-0.7 | 0.4-0.8 | 0.4-0.9 | 0.5-0.9 |
Cardiopulmonary Resuscitation
When clinically indicated, cardiopulmonary resuscitation (CPR; Chapter 50 ) in a pregnant woman is essential for both maternal and fetal health. Because cardiac arrest is often accompanied by obstetric emergencies, such as amniotic fluid embolism ( Chapter 68 ), understanding the impact of pregnancy on effective resuscitation is critical to optimize outcome. The pregnant woman is at higher risk of hypoxemia, and the gravid uterus causes aortocaval compression when supine. In addition, the gravid uterus elevates the diaphragm, thereby decreasing functional residual capacity by 10 to 25%. Standard high-quality CPR—meaning unchanged hand location, compression depth, and rate—should be initiated immediately along with continuous manual left uterine displacement ( E-Fig. 221-3 ) if the uterus is palpated at or above the umbilicus. Manual left uterine displacement allows for optimal chest compressions while relieving aortocaval compression. If resuscitative efforts are not successful, a perimortem cesarean delivery should begin within 4 minutes so as to minimize fetal neurologic damage and improve maternal resuscitative efforts. The delivery should be performed at the site of maternal resuscitation, with ongoing resuscitative efforts, rather than transporting the mother to a separate delivery setting.
Medical Disorders of Pregnancy
Hypertensive Disorders of Pregnancy
The hypertensive disorders of pregnancy can be divided into four distinct types: (1) chronic hypertension, (2) preeclampsia and eclampsia, (3) gestational hypertension, and (4) preeclampsia superimposed on chronic hypertension.
Chronic Preexisting Hypertension
Definition
Chronic hypertension in pregnancy is hypertension that was present before pregnancy, is diagnosed before 20 weeks of gestation, or is diagnosed during pregnancy and does not resolve postpartum. The threshold for defining chronic hypertension in pregnancy is evolving, but recent data suggest 140/90 mm Hg rather than the prior definition of a systolic blood pressure up to 160 mm Hg or a diastolic blood pressure up to 100 mm Hg.
Epidemiology
Chronic hypertension is present in 0.9 to 1.5% of pregnant women when using current definition of 140/90 mm Hg in pregnancy and may result in significant maternal, fetal, and neonatal morbidity and mortality, especially in the context of superimposed preeclampsia. Indeed, superimposed preeclampsia develops in as many as 20 to 50% of pregnant women who have chronic hypertension requiring therapy or systolic blood pressure above 140 mm Hg. The rate of maternal chronic hypertension is increasing, and the largest increase is among non-Hispanic Black women.
Pathobiology
Chronic hypertension results in pathologic injury to multiple organ systems ( Chapter 64 ), and adverse outcomes of pregnancy are directly related to the severity, duration, and existing end-organ effects of hypertension before pregnancy and whether superimposed preeclampsia develops. Chronic hypertension, which is a potential precipitant of cardiomyopathy and cerebrovascular events, is associated with a five-fold risk for maternal death, and hypertension is responsible for 6.6% of current pregnancy-related deaths (see Fig. 221-2 ). Both systolic and diastolic blood pressures normally decline gradually during the first half of pregnancy, so it can be difficult to assess the burden of hypertension in women who enter prenatal care at later gestational ages.
Clinical Manifestations and Diagnosis
Assessment for possible end-organ effects of underlying chronic hypertension during pregnancy should include measurement of baseline levels of serum creatinine and electrolytes, measurement of urine protein : creatinine ratio, and a 24-hour quantification of proteinuria. Approximately 11% of women with chronic hypertension have proteinuria (>300 mg/day) at baseline. These baseline assessments are useful for comparison if superimposed preeclampsia may later be suspected.
An echocardiogram should assess for left ventricular hypertrophy, which may be present in about 25% of pregnant women who receive antepartum treatment for chronic hypertension and which portends a significantly greater risk for subsequent or superimposed preeclampsia. The diagnosis of superimposed preeclampsia can be challenging and is typically based on the development of significantly worsening hypertension or of new-onset features, such as headache or vision disturbances with scotomata.
Treatment
Treatment of chronic hypertension ( Chapter 64 ) may differ somewhat during antepartum care, at delivery, and postpartum. In all these settings, immediate antihypertensive therapy is mandatory for women with hypertension at or above 160/110 mm Hg. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are contraindicated during pregnancy due to their potential teratogenic risks (see Table 221-3 ), so they should not be used in women of childbearing age ( Chapter 220 ). In general, β-blockers, calcium channel blockers, and methyldopa (see Tables 64-7 and 64-9 ) are routinely used during the antepartum period given their safety profiles during pregnancy.
To optimize perinatal outcomes, the goal blood pressure for pregnant women whose chronic hypertension is treated with antihypertensive medications is a blood pressure of 140/90 mm Hg. Control to a target diastolic blood pressure below 85 mm Hg is no better in terms of fetal outcomes and is only marginally better for reducing the frequency of progression to severe hypertension. Fetal growth may be compromised if blood pressure is treated more aggressively.
Stage-based protocols using checklists, referred to as “safety bundles,” have recently been developed through both national and state-based programs for standardization of response. Acute intrapartum antihypertensive therapy emphasizes timely treatment ( Table 221-6 ). Superimposed preeclampsia also requires magnesium sulfate prophylaxis (either a 4- or 6-g intravenous loading dose, followed by continuous infusion of 2 g per hour) and prompt delivery. After delivery, persistent postpartum hypertension is typically managed with β-blockers and calcium channel blockers (see Table 64-7 ), as used during the antepartum period, for safe lactation and future childbearing considerations. After discharge, twice-daily self-measurement of blood pressure with physician-guided titration of medication can improve blood pressure control.
TABLE 221-6
URGENT MANAGEMENT OF SEVERE HYPERTENSION (≥160/110 mm Hg) IN PREGNANCY AND THE IMMEDIATE POSTPARTUM PERIOD
| DRUG | DOSE |
|---|---|
| ORAL | |
| Nifedipine IR | 10-20 mg initially and 20 min later, followed by 10-20 mg q 2-6h to a maximum of 180 mg |
| INTRAVENOUS | |
| Labetalol (preferred) | 10-20 mg then 1-2 mg/min (or 20-80 mg q 10-30 min) to a maximum of 300 mg |
| or | |
| Hydralazine | 5 mg initially then 0.5-10 mg/hr (or 5-10 mg q 20-40 min) to a maximum of 20 mg |
Prevention
In women with well-controlled blood pressure, perinatal outcomes are similar to outcomes in women without chronic hypertension, so a goal for prevention is to control blood pressure before conception. Screening for hypertension should be conducted throughout pregnancy. , Since women who have chronic hypertension are at increased risk for developing preeclampsia, they should begin taking daily low-dose aspirin (81 mg) between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continue until delivery. Initiating treatment after 28 weeks of gestation is unlikely to be beneficial. Aspirin should not be used in women who have risk factors for gastrointestinal hemorrhage (e.g., bleeding disorders or peptic ulcer).
Prognosis
In patients with chronic hypertension, preeclampsia tends to have an earlier onset and to be more severe, so the prognosis for the woman and her fetus is worse than in either condition alone.
Hypertensive Disorders Unique to Pregnancy
The threshold for gestational hypertension and preeclampsia is new-onset blood pressure at or above 140/90 mm Hg. Gestational hypertension is the diagnosis in the absence of proteinuria, whereas preeclampsia is associated with new-onset proteinuria during pregnancy and affects virtually every organ system.
New-onset is arbitrarily defined as at 20 weeks’ gestation or later, and proteinuria serves as an objective measure of the endothelial damage caused by preeclampsia. Preeclampsia is further sub-divided into: early-onset (<34 weeks) and late-onset (≥34 weeks). , Eclampsia is defined by new-onset tonic-clonic, focal, or multifocal seizures in the absence of other causative conditions such as epilepsy ( Chapter 372 ), cerebral arterial ischemia and infarction ( Chapter 58 ), intracranial hemorrhage ( Chapter 377 ), or drug use ( Chapter 365 ).
Epidemiology
The most common hypertensive disorder of pregnancy is gestational hypertension, which occurs in 6 to 17% of nulliparous patients and 2 to 4% of parous patients. Preeclampsia is identified in 5 to 8% of all pregnancies, with higher risks in women who are young and nulliparous and in older women who have comorbid conditions such as chronic hypertension. A prior history of preeclampsia raises risks by about eight-fold. Non-Hispanic Black women, obese patients, and women with a family history are also higher risk. The incidence of eclampsia in high-resource settings is now 1 in 2000 to 3000 deliveries.
Pathobiology
The mechanisms by which pregnancy provokes hypertension remain unsolved but likely involve genetic, immunologic, and angiogenic responses to hormonal changes and increased blood volume. The first stage, which involves faulty endovascular trophoblastic remodeling, results in a second stage of endothelial dysfunction with overproduction of anti-angiogenic factors—soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng)—that enter the maternal circulation. The phenotypic expression of the preeclampsia syndrome represents a spectrum of disease, with end-organ consequences. Hemoconcentration is a hallmark. Cardiac function becomes compromised owing to an increased afterload, and aggressive fluid support may result in pulmonary edema.
Clinical Manifestations and Diagnosis
The diagnostic clinical manifestations of the preeclampsia syndrome ( Table 221-7 ) are a blood pressure of 140/90 mm Hg or greater accompanied by proteinuria (≥300 mg/24 hours or a urine protein/creatinine ratio of ≥0.3). Following the initial documentation of proteinuria and the establishment of the diagnosis of preeclampsia, additional quantifications of proteinuria are no longer necessary. The neurologic symptoms represent posterior reversible encephalopathy syndrome.
TABLE 221-7
CRITERIA FOR PREECLAMPSIA WITH SEVERE FEATURES
Data from American College of Obstetricians and Gynecologists. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol . 2020;135:e237-e260.
| FEATURES |
| SBP ≥160 mm Hg or DBP ≥110 mm Hg on two occasions 4 hours apart (unless antihypertensive therapy initiated) |
| Thrombocytopenia (<100,000/μL) |
| Elevated liver function tests (>2 times normal) |
| Severe persistent right upper quadrant pain |
| Epigastric pain unresponsive to medications |
| Renal insufficiency (creatinine >1.1 mg/dL or double baseline) |
| Pulmonary edema |
| New-onset headache |
| Visual disturbances |
DBP = diastolic blood pressure; SBP = systolic blood pressure.
Eclampsia, which is often preceded by neurologic complaints, such as new-onset headache or vision disturbances, should be considered in any pregnant or immediately postpartum patient who presents with convulsions at or near term. The diagnosis depends on the exclusion of other causes of seizures. In most cases, the convulsions are followed by a post-ictal state with an elevated respiratory rate in response to hypercarbia, transient hypoxia, and lactic acidemia. If intracranial bleeding is a concern, immediate brain imaging with CT scanning is indicated. In many cases, eclampsia can be corroborated when an MRI demonstrates signs of reversible encephalopathy, classically in the occipital and parietal cortical regions.
Treatment
The medical treatment of gestational hypertension is similar to the management of chronic hypertension. Treatment of preeclampsia aims to prevent eclampsia by using magnesium sulfate (either a 4- or 6-g intravenous load, followed by 2-g per hour infusion) to prevent seizures, immediately treating severe hypertension (160/110 mm Hg or greater; see Table 221-4 ), and effecting prompt delivery of the fetus. In the absence of contraindications, (e.g., myasthenia gravis; Chapter 390 ), a patient with convulsions late in pregnancy or early in the postpartum period should empirically be given magnesium sulfate to prevent recurrent seizures even while evaluation is underway. If seizures persist despite ongoing magnesium sulfate prophylaxis, an additional 2-g loading dose should be considered, and agents that significantly depress respiratory function should be avoided. Magnesium sulfate is cleared by the kidney, so women with compromised renal function merit close observation for toxicity, which is manifested by diminished reflexes and respiratory depression. Treatment with calcium gluconate (1 g intravenously over 2 to 5 minutes) and discontinuation of the magnesium sulfate reverses respiratory depression.
Delivery is the only cure for preeclampsia-eclampsia. However, emergent cesarean delivery is not recommended for an eclamptic event in the absence of clinical evidence for placental abruption. Fetal compromise often resolves with maternal supportive care in the minutes following the seizure.
Women should be evaluated for possible fluid overload and pulmonary edema because the majority of women with preeclampsia develop pulmonary edema after birth. Volume expansion with agents, such as albumin, may aggravate pulmonary function, and their use is not routinely recommended. Careful fluid management, diuretics (e.g., furosemide 20 mg intravenously), for pulmonary edema afterload reduction with acute intrapartum antihypertensive agents (e.g., labetalol 10 to 20 mg intravenously, hydralazine 5 to 10 mg intravenously, or immediate-release nifedipine 10 mg orally), airway management, and respiratory support are key.
Preeclampsia and eclampsia also can present during the 6 weeks postpartum. Early diagnosis is critical, and management is the same (e.g., seizure prophylaxis and antihypertensive therapy) as when they present prior to delivery.
Peripartum Cardiomyopathy
Definition
Peripartum cardiomyopathy is defined by left ventricular dysfunction and the development of cardiac failure without another known cause in the final month of pregnancy or up to 5 months postpartum ( Chapter 47 ). It is one of the reasons why cardiovascular-related conditions are now responsible for more than 33% of pregnancy-related deaths in the United States (see E-Fig. 221-2 ).
Epidemiology
The worldwide incidence of peripartum cardiomyopathy is approximately 1 per 1000 pregnancies but varies by geographic area and ethnicity. In Africa, for example, peripartum cardiomyopathy develops in as many as 1 per 100 pregnancies. In the United States, non-Hispanic Black women have a 5- to 15-fold increased risk compared with other ethnic groups. The overall incidence of peripartum cardiomyopathy in the United States has increased from 1 in 4350 births in the early 1990s to 1 in 2230 births, perhaps in part owing to heightened awareness and improved access to echocardiography, but also likely owing to the obesity epidemic, increasing maternal age, fertility-assisted treatments, and multifetal pregnancies.
Pathobiology
Physiologic cardiovascular adaptations to pregnancy include increased blood volume, stroke volume, heart rate, and cardiac output. The current theory is that peripartum cardiomyopathy affects genetically susceptible women who have one of several gene mutations, including TTNC1 , TTN , and STAT3 . In these susceptible patients, the pregnant state results in substantial secretion of prolactin by the maternal pituitary and high levels of antiangiogenic molecules by the placenta. The 16-kDa prolactin fragment (vasoinhibin) causes myocardial damage, which is compounded by secretion of high levels of the vascular endothelial growth factor inhibitory molecules, such as soluble fms-like tyrosine kinase (sFlt-1).
Clinical Manifestations and Diagnosis
Patients with peripartum cardiomyopathy typically present with symptoms of heart failure ( Chapter 45 ) in late pregnancy or within 5 months postpartum. An echocardiogram ( Chapter 43 ) should be obtained to exclude valvular heart disease ( Chapter 60 ), pericardial disease ( Chapter 62 ), or segmental wall motion abnormalities that might suggest ischemic heart disease or a coronary artery dissection ( Chapter 58 ). Peripartum cardiomyopathy is ultimately a diagnosis of exclusion after careful assessment of cardiac function by physical examination, laboratory testing, and echocardiography ( Fig. 221-3 ). Transthoracic echocardiography is considered diagnostic when it demonstrates diffuse systolic dysfunction with a left ventricular ejection fraction less than 45%, motion-mode fractional shortening less than 30%, or a left ventricular end-diastolic dimension greater than 2.7 cm/m 2 in the absence of other causes of heart failure, such as hypertensive cardiomyopathy, superimposed preeclampsia, sepsis, or the use of tocolytic β-mimetics agents (e.g., terbutaline).
Treatment
The diagnosis of peripartum cardiomyopathy is most frequently made postpartum. For women who are diagnosed before delivery, however, prompt delivery is typically recommended after maternal stabilization. Diuretics, fluid restriction, supplemental oxygen, and management with antihypertensive therapy are the mainstays of immediate care consistent with standard heart failure management ( Chapter 46 and 47 ). Calcium channel and β-blocking agents (see Table 221-4 ) are commonly used for acute blood pressure control before delivery. After delivery, treatment emphasizes ACE inhibitors and angiotensin-receptor blocking agents to decrease afterload ( Chapter 46 ). To inhibit prolactin, women should not breast-feed. Bromocriptine (1.25 mg to 2.5 mg once daily) may be added if traditional measures are not successful, but use is controversial. Because of the increased risk of thromboembolism, prophylactic anticoagulation with low-molecular-weight heparin (see Table 70-3 ) is typically instituted. For severe, unremitting heart failure, ventricular-assist devices and extracorporeal membrane oxygenation have been used. Reliable contraception is critical to allow for potential recovery and assessment before future pregnancy is attempted.
Prevention
No specific strategies prevent peripartum cardiomyopathy, but control of blood pressure and underlying cardiovascular disease should be optimized before pregnancy. Vigilance may allow for earlier diagnosis of women who have symptoms of heart failure near term and after delivery, thereby allowing earlier treatment before severe clinical deterioration.
Prognosis
Serial echocardiography is recommended to evaluate left ventricular function at 1- to 3-month intervals, and the long-term trajectory of cardiac function is typically clear by 6 months postpartum. In the United States, approximately two-thirds of patients recover ventricular function, but about one-third have a left ventricular ejection fraction persistently below 45%. The risk of recurrence among women who recover left ventricular function during or after subsequent pregnancy is approximately 20%. Women who do not recover should avoid future pregnancies.
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