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Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial evaluation

Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial evaluation
Literature review current through: Jan 2024.
This topic last updated: Mar 15, 2023.

INTRODUCTION — Pregnancy loss, also referred to as miscarriage or spontaneous abortion, is generally defined as a nonviable intrauterine pregnancy up to 20 weeks of gestation. Early pregnancy loss, which occurs in the first trimester (ie, up to 12+6 weeks gestation), is the most common type. Individuals experiencing pregnancy loss are evaluated for conditions that require emergency treatment and then counseled regarding the different management options, which include expectant, medication, and surgical management.

This topic will review the clinical presentation and initial evaluation of patients with pregnancy loss up to 20 weeks of gestation. Related content on risk factors and etiology, ultrasound diagnosis, treatment options, and management protocols is presented separately.

(See "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology".)

(See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

(See "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care".)

(See "Pregnancy loss (miscarriage): Description of management techniques".)

Content specific to individuals with recurrent pregnancy loss is discussed elsewhere.

(See "Recurrent pregnancy loss: Definition and etiology".)

(See "Recurrent pregnancy loss: Evaluation".)

(See "Recurrent pregnancy loss: Management".)

In this topic, we will use the term "patient" to describe genetic females. We recognize that not all people capable of pregnancy identify as female and we encourage the reader to consider the specific counseling needs of transmasculine and gender expansive individuals.

CLINICAL PRESENTATIONS

Uncomplicated bleeding and cramping — Uncomplicated bleeding and cramping, the most common symptoms of individuals with pregnancy loss, imply that the patient is hemodynamically stable, at low risk of becoming hemodynamically unstable based on the volume of bleeding, and without evidence of infection. Additional symptoms of uncomplicated pregnancy loss may also include a loss or reduction of pregnancy symptoms, such as decreased breast tenderness and/or nausea and vomiting. While bleeding in the first trimester of pregnancy is fairly common, not all individuals with first-trimester bleeding and/or cramping will experience pregnancy loss; other causes of these symptoms, such as ectopic pregnancy, should be excluded [1,2]. (See 'Differential diagnosis' below.)

Bleeding – Bleeding during pregnancy is common. The volume of vaginal bleeding with pregnancy loss varies considerably, particularly by gestational age, and patients often report passing clots or tissue. Generally, neither the volume of bleeding nor self-reported passage of tissue are sufficient to confirm pregnancy loss without further evaluation, which typically includes a pelvic ultrasound. (See 'Diagnosis' below.)

Incidence – In an observational study of 550 pregnant individuals, 117 (21 percent) experienced bleeding before 20 weeks gestation and 67 (12 percent of entire group) ended in loss [2]. Of the 117 individuals with bleeding, 59 (50 percent) experienced loss. Two additional losses occurred without bleeding. A different prospective study of over 400 pregnant people documented early pregnancy loss in 12 percent of those with first-trimester vaginal bleeding [3].

Timing of bleeding and pregnancy loss – A prospective study of 701 patients reported that isolated vaginal bleeding at six to eight weeks of gestation was associated with the greatest increased risk of pregnancy loss (risk difference 56 percent, 95% CI 38-75) [4]. However, as early pregnancy loss commonly occurs at six to eight weeks of gestation, bleeding is likely a symptom of loss and not the etiology.

Cramping and/or pain – The pain that occurs with pregnancy loss is often crampy in nature and can be mild to severe, especially during passage of gestational tissue. The pain can be constant or intermittent and is often associated with vaginal bleeding. Options for pain management for individuals experiencing pregnancy loss are discussed in expectant management. (See "Pregnancy loss (miscarriage): Description of management techniques", section on 'Expectant management'.)

As bleeding and cramping are also symptoms of other early pregnancy complications, including ectopic and molar pregnancy, pregnant individuals with vaginal bleeding or pelvic pain should be evaluated promptly. In these situations, ultrasound imaging is typically needed for a complete assessment, particularly in cases when the provider cannot confirm that pregnancy tissue has passed spontaneously (algorithm 1). (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation" and "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)

Complicated (hemorrhage and/or infection) — The most common complications associated with pregnancy loss are hemorrhage and infection, which can be severe, and at times require emergency intervention. Risk of both generally increases with increasing gestational age of loss beyond 13 weeks gestation.

Hemorrhage – While vaginal bleeding is common in patients with pregnancy loss, onset of severe hemorrhage can necessitate transfusion and surgical evacuation. Those with severe hemorrhage typically present with heavy vaginal bleeding combined with orthostatic vital signs, anemia, and/or tachycardia. The overall risk of severe hemorrhage that requires hospitalization is low at approximately 1 percent [5]. (See 'Hemorrhage' below.)

Infection – Signs and symptoms of infection include abdominal or pelvic pain, uterine tenderness, purulent discharge, and/or systemic signs of infection, such as fever, tachycardia, or hypotension. The incidence of intrauterine infection with pregnancy loss increases with increasing gestational age; it is approximately 15 percent in the first 12 weeks, then as much as 66 percent for losses between 12 and 24 weeks [6], particularly for those in whom there has been a long delay between symptom onset and diagnosis of pregnancy loss or between diagnosis of pregnancy loss and expulsion of the pregnancy [7]. Intrauterine infection can occur spontaneously or can follow medical or surgical interventions. Although infection may be asymptomatic and undiagnosed outside of study settings, patients diagnosed with clinically symptomatic infection are not candidates for expectant or medical management of pregnancy loss. Individuals with severe infection leading to hemodynamic instability have a septic abortion and require emergency evaluation and treatment. (See 'Septic abortion' below.)

Groups with increased risk – Individuals with poor access to health care or with delayed identification of pregnancy loss may be more likely to have spontaneous passage of gestational tissue (and resultant hemorrhage) or complications such as infection [8]. Individuals who may be less likely to expect or recognize their pregnancy early in gestation, such as adolescents, perimenopausal people, or those with irregular menses, might also be at higher risk of later presentation and/or complications.

Asymptomatic or incidental — Highly sensitive pregnancy tests and ultrasounds enable diagnosis of pregnancy loss before the onset of symptoms. (See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

Complete versus incomplete pregnancy loss — In addition to the presence or absence of symptoms, individuals with pregnancy loss can be further characterized by whether there is complete or incomplete emptying of the uterus. The presence of symptoms, as discussed above, and/or retained intrauterine tissue helps determine treatment options and helps guide patients in their decision-making.

Complete – This phrase is used to describe patients with an empty uterus after documentation of prior intrauterine pregnancy. This is important since an empty uterus can be seen by ultrasound in the setting of normal early pregnancy that is too early to visualize, miscarriage, or ectopic pregnancy. The phrase can be applied to those with an empty uterus following pregnancy loss or termination, regardless of how the loss or termination was managed.

Incomplete – This wording refers to tissue retained within the uterus (gestational sac or fetal or placental tissue). Incomplete pregnancy loss can occur after partial spontaneous passage of pregnancy tissue or following medical or surgical treatment. It is often symptomatic, but the absence of symptoms does not exclude the possibility of retained tissue.

DIAGNOSIS — Once an intrauterine pregnancy is identified on ultrasound, pregnancy loss is diagnosed if any subsequent ultrasound (performed routinely or for symptoms) shows no intrauterine pregnancy or loss of previously seen cardiac activity. Alternately, single-ultrasound criteria exist, and selection of criteria is tailored to the patient's preferences and clinical scenario. (See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

DIFFERENTIAL DIAGNOSIS — Most individuals with bleeding during pregnancy will not experience pregnancy loss [1,2]. Approach to the pregnant patient with bleeding is presented in detail in related content (algorithm 1).

(See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

(See "Ultrasonography of pregnancy of unknown location".)

PATIENT CATEGORIZATION BY CLINICAL PRESENTATION

Assess for alarm findings — Pregnant individuals of less than 20 weeks gestation who present with evidence of hemorrhage with hemodynamic instability and/or infection with evidence of sepsis syndromes require urgent, and often emergency, evaluation and treatment.

Clinically unstable patient – For those with life-threatening hemorrhage and/or infection who also have intrauterine products of conception, surgical evacuation of the pregnancy is indicated even if ultrasound criteria for pregnancy loss are not fully met, including the loss of fetal heart tones. Follow-up assessments of pregnancy viability should never delay appropriate care for a patient.

Clinically stable patient – For a clinically stable patient, providers should discuss the risks and benefits of delaying care to provide definitive diagnosis of pregnancy loss. For a highly desired pregnancy, patients often prefer to have a follow-up ultrasound, which may be warranted if they do not meet definitive criteria for pregnancy loss with one ultrasound. (See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

Hemorrhage — Urgent uterine aspiration is indicated for individuals with severe bleeding; emergency aspiration is warranted in the setting of unstable vital signs. Unstable vital signs may include orthostatic vital signs, hypotension, and/or tachycardia as well as laboratory evidence of anemia. Blood transfusion may be required.

(See "Pregnancy loss (miscarriage): Description of management techniques", section on 'Surgical management (uterine aspiration)'.)

(See "Overview of postpartum hemorrhage", section on 'Early recognition, assessment, and intervention'.)

In most cases, after the pregnancy is evacuated, the bleeding will rapidly resolve. In settings where outpatient or emergency department uterine aspiration is feasible, it is preferable to perform the procedure where it can be done most expeditiously. However, a clinically unstable patient (severe hypotension, for instance) may require stabilization and hospital transfer before or after a procedure can be performed. Ongoing bleeding after uterine aspiration is uncommon but, if it occurs, can be managed with uterotonics, similar to the management of bleeding after surgical pregnancy termination. (See "Pregnancy loss (miscarriage): Description of management techniques", section on 'Complications' and "First-trimester pregnancy termination: Uterine aspiration", section on 'Hemorrhage'.)

Septic abortion — Septic abortion refers to an infected uterus in the setting of pregnancy of less than 20 weeks gestation with clinical evidence of sepsis syndromes. Pregnancies ≥20 weeks gestation with intrauterine infection are typically referred to as having chorioamnionitis. Signs and symptoms include abdominal or pelvic pain, uterine tenderness, purulent vaginal discharge, and/or other systemic signs of infection (eg, fever, elevated white blood count). When not treated urgently, septic abortion progresses rapidly and can be lethal. Those who show signs of infection along with intrauterine products of conception (either from incomplete pregnancy loss or incomplete pregnancy termination) are not candidates for expectant or medication management. Patients with septic abortion typically require inpatient admission, rapid treatment with broad spectrum intravenous antibiotics, and immediate evacuation of the uterus (algorithm 2). Detailed discussions of septic abortion, including treatment, and sepsis syndromes are presented separately.

(See "Septic abortion: Clinical presentation and management".)

(See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis".)

(See "Evaluation and management of suspected sepsis and septic shock in adults".)

Evaluate clinically stable patients — Patients most commonly receive a diagnosis of pregnancy loss at the time of a routine ultrasound or an ultrasound performed for symptoms such as spotting or cramping. There is usually time to provide thorough counseling regarding the various management approaches, and the patient can consider the options and decide on their preferred management approach over the course of days or weeks.

For these patients, we take the following approach:

Confirm diagnosis and gestational age — In most cases, pregnancy loss is diagnosed with transvaginal ultrasound. The gestational age of the pregnancy as determined with ultrasound, not by last menstrual period dating, and influences the management options. Clinicians who receive referrals for pregnancy loss management should confirm that adequate diagnostic criteria have been met in stable patients. (See 'Diagnosis' above and "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

First trimester – First-trimester losses are those up to 12+6 weeks gestation.

Second trimester – Early second-trimester pregnancy loss is one that occurs after 13+0 and prior to 20+0 weeks of gestation [9]. Signs and symptoms of second-trimester pregnancy loss include bleeding, cramping/pain, or labor. Diagnosis of second-trimester pregnancy loss includes ultrasound documentation of intrauterine fetal death or spontaneous delivery.

Assess patient history — Clinically stable patients need complete medical evaluation with both individual and family histories to assess for medical comorbidities. Patients with conditions such as bleeding disorders, large uterine fibroids, or suspected molar pregnancy, or who are on an anticoagulation medication, may have a higher risk for bleeding and other complications with expectant, surgical, or medication management of pregnancy loss. Consultation with a clinician experienced with pregnancy loss management, when available, is advised for complex patients. Patient preferences, medical factors, and available resources will often make one treatment approach preferable.

As examples:

Favoring expectant management – Individuals who desire to avoid interventions, do not mind the unpredictable nature of pregnancy loss, and are able to receive follow-up care may prefer expectant management (ie, allowing the pregnancy tissue to pass on its own).

Favoring medication management – A patient with some uterine, cervical, or vaginal anomalies may have a pregnancy that is not easily reached with a uterine aspiration device, and thus, medication management may be the preferred option. This option may also be preferred by individuals who prefer to avoid uterine instrumentation but would also like a more predictable timeframe for pregnancy expulsion and miscarriage completion.

Favoring surgical management – A patient on therapeutic anticoagulation may have a higher bleeding risk with expectant or medication management, and in this case, surgical management may be preferable. Additionally, someone who prefers immediate and predictable completion of the pregnancy loss might choose surgical management.

Perform physical and laboratory examinations — Patients who present with confirmed or suspected pregnancy loss undergo speculum and bimanual evaluations in addition to general assessment. Handheld tone Doppler evaluation may be performed for pregnancies of 12 weeks gestation or greater. (See "The gynecologic history and pelvic examination", section on 'Components of the examination'.)

In clinical situations with access to ultrasound and laboratory services, transvaginal sonography and/or laboratory serum human chorionic gonadotropin (hCG) are the two key tests. Ultrasound is useful if available, as it has higher specificity and sensitivity than speculum or physical examination for a range of diagnoses associated with pregnancy problems.

Physical examination.

Speculum examination – Speculum examination is performed to assess for bleeding, including the source and quantity, and signs of infection (eg, frank pus from cervical os). Active pregnancy loss is suggested by bleeding coming from the cervix and an open cervical os. Traditionally, the findings of vaginal bleeding with an open cervix were diagnosed as an "inevitable abortion." However, this terminology is no longer preferred because, in practice, cervical dilation can be difficult to visually assess, and only 12 percent of patients with first-trimester bleeding experience pregnancy loss [2]. While some individuals with pregnancy loss have a visibly dilated cervix or pregnancy tissue present at the os, others (particularly those who are parous) have an external cervical os that appears dilated even with a normal pregnancy. Furthermore, a cervix that appears closed and has no active bleeding does not exclude pregnancy loss.

Bimanual examination – A bimanual examination can determine whether the external cervix is open and whether there is tissue within the cervical canal. Tenderness upon uterine palpation may indicate infection. Additionally, if ultrasound is not readily available, bimanual examination can estimate gestational age, which can then be compared with the patient's known gestational age to assess for discrepancy and possible pregnancy loss. However, uterine size may be difficult to assess in patients with obesity, uterine fibroids, or other uterine anomalies. Additionally, the patient's estimated gestational age may be incorrect. Thus, providers must be aware of the limitations of physical examination for diagnosing pregnancy loss.

Tone Doppler assessment – Absence of fetal heart tones on handheld Doppler in a pregnancy of 12 weeks or greater should prompt further evaluation for pregnancy loss, though it is not a criterion used for diagnosis. The ability to find heart tones varies by gestational age, patient habitus, uterus position, and fetal position.

Laboratory evaluation – Routine laboratory evaluation typically includes a blood type and antibody screen. The goal is to identify RhD-negative individuals who may benefit from anti-D immune globulin. Serum hCG is valuable in follow-up of patients with pregnancy of unknown location when used in conjunction with serial ultrasound imaging. Progesterone has limited utility in the diagnosis of pregnancy loss.

Blood type and RhD antigen screen – Tests for blood type and Rh status are performed to identify RhD-negative individuals who are at risk of developing Rh alloimmunization and in case blood type and antibody information is needed for transfusion.

-(See "Red blood cell antigens and antibodies", section on 'Rh blood group system'.)

-(See "RhD alloimmunization in pregnancy: Overview".)

-(See "RhD alloimmunization: Prevention in pregnant and postpartum patients".)

Serum hCG – There are no hCG levels or trends that are diagnostic for pregnancy loss, but relative changes can be helpful.

-Normal variations – Given the substantial variation in hCG levels at any gestational age, one hCG value is not sufficient for diagnosis of pregnancy loss, and a single hCG value <4000 milli-international units/mL should be interpreted with great caution. It is important to consider that the rate of hCG increase and trends may be unpredictable, particularly at low levels. Three serial hCGs are typically needed to establish a trend. In one section editor's experience, a dramatic drop in hCG >25 percent over 48 hours in the setting of uterine bleeding is highly suggestive of pregnancy loss and may be helpful if ultrasound is not readily available. (See "Human chorionic gonadotropin: Biochemistry and measurement in pregnancy and disease".)

In normal pregnancies, average hCG levels plateau at approximately 8 to 11 weeks and then decline [10]. In counseling patients about the probability of a viable pregnancy given a single hCG level and their ultrasound findings, we use data from an analysis of 651 pregnancies that concluded that discriminatory hCG levels at which structures would be predicted to be seen 99 percent of the time were 3510 milli-international units/mL for gestational sac, 17,716 milli-international units/mL for yolk sac, and 47,685 milli-international units/mL for embryonic pole [11].

-Pregnancy of unknown location – Serum hCG testing is commonly performed as part of the assessment for pregnancy of unknown location and is often helpful in excluding ectopic pregnancy. (See "Ultrasonography of pregnancy of unknown location" and "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)

Serum progesterone – Although low serum progesterone levels are associated with pregnancy loss, in clinical practice, this test is rarely used for diagnosis or management because of the high variability of progesterone levels in both normal and abnormal pregnancies [12]. In a study of 360 pregnant individuals with bleeding in early pregnancy at 6 to 10 weeks gestation, a cutoff of <35 nmol/L led to a positive predictive value for pregnancy loss of 68 percent and a negative predictive value of 91 percent [13]. Serum progesterone testing may be appropriate in some clinical settings, but the authors do not use this test for the diagnosis of pregnancy loss. (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Other testing'.)

Assess patient preferences and values — Some patients have a strong preference for one type of pregnancy loss management even before receiving detailed information about the risks and benefits of each option. Patients who have had a positive or negative experience with a previous pregnancy loss will often indicate a preference for management. This information is used to help tailor counseling about the different management options in a way that respects the individual's values. (See "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care", section on 'Use a patient-centered approach'.)

Discuss management options and treat — Clinically stable patients with pregnancy loss have the options of expectant, medication, and surgical management. Patient preferences and values are the main drivers of treatment selection.

(See "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care", section on 'Present treatment options'.)

(See "Pregnancy loss (miscarriage): Description of management techniques".)

Administer anti-D immune globulin in appropriate individuals — Use of anti-D immune globulin, and the timing, specific to individuals with pregnancy loss has not been established and is a point of active debate. A discussion of various guidelines and the authors' approaches are presented in related content. (See "Pregnancy loss (miscarriage): Description of management techniques", section on 'Prevention of alloimmunization'.)

Additional discussions of RhD alloimmunization are available:

(See "RhD alloimmunization in pregnancy: Overview".)

(See "RhD alloimmunization: Prevention in pregnant and postpartum patients".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pregnancy loss (spontaneous abortion)".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Pregnancy loss (The Basics)" and "Patient education: Bleeding in early pregnancy (The Basics)")

Beyond the Basics topics (see "Patient education: Pregnancy loss (Beyond the Basics)")

PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Pregnancy loss".)

SUMMARY AND RECOMMENDATIONS

Clinical presentation Bleeding and cramping are the most common presenting complaints of symptomatic individuals with pregnancy loss. However, most individuals with bleeding during pregnancy will not experience pregnancy loss. (See 'Clinical presentations' above.)

Uncomplicated pregnancy loss – Uncomplicated pregnancy loss implies that the patient is hemodynamically stable, at low risk of becoming hemodynamically unstable based on the volume of bleeding, and without evidence of infection. Pregnancy loss can also be an incidental finding on pelvic ultrasound. (See 'Uncomplicated bleeding and cramping' above.)

Complicated pregnancy loss – Individuals with complicated pregnancy loss typically present with hemorrhage and/or infection, which can be severe. Risk of both generally increases with increasing gestational age of loss beyond 13 weeks gestation. (See 'Complicated (hemorrhage and/or infection)' above.)

Asymptomatic loss – Highly sensitive beta human chorionic gonadotropin (hCG) tests and transvaginal ultrasounds enable diagnosis of pregnancy loss before the onset of symptoms. (See 'Asymptomatic or incidental' above.)

Complete versus incomplete – In addition to the presence or absence of symptoms, individuals with pregnancy loss can be further characterized by whether there is complete or incomplete emptying of the uterus. The presence of symptoms and/or retained intrauterine tissue helps determine treatment options and guide patients in their decision-making. (See 'Complete versus incomplete pregnancy loss' above.)

Diagnosis – Transvaginal ultrasound is generally performed in all pregnant individuals with signs or symptoms suggestive of pregnancy loss to confirm both an intrauterine gestation and evidence of viability. (See 'Diagnosis' above.)

Differential diagnosis – Most individuals with bleeding during pregnancy will not experience pregnancy loss. Approach to the pregnant patient with bleeding is presented in detail in related content (algorithm 1). (See 'Differential diagnosis' above and "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

Patient categorization by clinical presentation Patients with alarming findings, including severe hemorrhage and/or infection, receive emergency evaluation and treatment. The majority of patients are clinically stable, and there is usually time to provide thorough counseling regarding the various management approaches. (See 'Patient categorization by clinical presentation' above.)

Alarm findings – Pregnant individuals of less than 20 weeks gestation who present with evidence of severe hemorrhage with hemodynamic instability and/or infection with evidence of sepsis syndromes require urgent, and often emergency, evaluation and treatment. For those with life-threatening hemorrhage and/or infection, surgical evacuation of the pregnancy is indicated even if ultrasound criteria for pregnancy loss are not fully met, including the loss of fetal heart tones. Follow-up assessments of pregnancy viability should never delay appropriate care for an unstable patient. (See 'Assess for alarm findings' above.)

Clinically stable patients – Evaluation of clinically stable patients includes confirmation of pregnancy loss and approximate gestational age at the time of loss, physical examination, limited laboratory evaluation, and discussion of management options. There is usually time to provide thorough counseling regarding the various management approaches, and the patient can consider the options and decide over the course of days or weeks. (See 'Evaluate clinically stable patients' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Togas Tulandi, MD, MHCM, and Haya M Al-Fozan, MD, who contributed to an earlier version of this topic review.

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