Pulmonary embolism in pregnancy: Clinical presentation and diagnosis

INTRODUCTION — Pregnancy and the postpartum period are risk factors for lower extremity deep venous thrombosis (DVT) and pulmonary embolism (PE). The ideal approach to diagnosing PE in pregnancy requires a high index of clinical suspicion while avoiding overtesting. Such an approach ensures that few cases of PE are missed and minimizes the risk of radiation and contrast exposure.

The diagnosis of PE during pregnancy will be reviewed here. The epidemiology, pathogenesis, diagnosis, prevention, and treatment of DVT and PE during pregnancy are discussed separately.

●(See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis".)

●(See "Venous thromboembolism in pregnancy and postpartum: Treatment".)

●(See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

●(See "Venous thromboembolism in pregnancy: Prevention".)

We consider females who present with suspected PE during the postpartum period as nonpregnant adults and investigate accordingly. Our diagnostic approach in this population is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

CLINICAL PRESENTATION — The clinical manifestations of PE during pregnancy are nonspecific and are similar to nonpregnant individuals. However, suspecting PE is even more challenging during pregnancy due to the overlap with the symptoms of pregnancy itself. For example, dyspnea, one of the most common symptoms of PE, occurs in up to 70 percent of normal pregnancies, often stabilizing near term [1-4]. The clinical presentation of PE in nonpregnant patients and symptoms of pregnancy are discussed separately (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Clinical manifestations and diagnosis of early pregnancy", section on 'Clinical manifestations of early pregnancy' and "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes" and "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes".)

Signs and symptoms — PE has a wide variety of presenting features, ranging from asymptomatic to shock or sudden death. While pregnant patients were excluded from major trials that described the clinical presentation of PE, smaller trials suggest that pregnant patients have similar presenting features [5-7]. As examples:

●In a study of 38 pregnant individuals with confirmed PE, the four most common presenting features were dyspnea (62 percent), pleuritic chest pain (55 percent), cough (24 percent), and sweating (18 percent) [5].

●In an observational study that included 198 pregnant or postpartum patients with diagnosed PE, dyspnea at rest was reported in 54 percent, pleuritic chest pain in 52 percent, cough in 9 percent, and hemoptysis in 7 percent [8].

Chest radiograph — Despite poor diagnostic accuracy, we perform chest radiography in every pregnant patient in whom a PE is suspected. Our preference for chest radiography in this population is for the following reasons:

●The chest radiograph primarily evaluates alternative diagnoses (eg, pneumonia, pneumothorax, pulmonary edema, cardiomegaly). (See 'Differential diagnosis' below.)

●The chest radiograph helps decide what diagnostic test needs to be performed. Pregnant females are more likely to have a normal chest radiograph since they are typically younger and healthier than the general population of patients with a suspected PE. This improves the diagnostic accuracy of ventilation/perfusion (V/Q) scanning when compared with nonpregnant individuals [9] (see 'Ventilation/perfusion scan' below). In contrast, an abnormal chest radiograph decreases the diagnostic accuracy of V/Q scanning and should prompt the clinician to directly proceed to computed tomographic (CT) pulmonary angiography (CTPA).

The value of chest radiography for the interpretation of V/Q scans in nonpregnant patients is discussed separately [9]. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Chest radiograph'.)

Oxygenation measures — In pregnant patients suspected as having PE, we routinely perform peripheral oximetry. Importantly, normal oxygenation parameters do not confidently exclude the possibility of PE while abnormal oxygenation should raise the suspicion further for PE. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Laboratory tests' and "Measures of oxygenation and mechanisms of hypoxemia" and "Pulse oximetry".)

Arterial blood gas (ABG) analysis, while often performed, is neither sensitive nor specific diagnostically and is not always necessary. A respiratory alkalosis is a very common feature of both pregnancy and PE. As in the nonpregnant population, a normal arterial oxygen tension, arterial carbon dioxide tension, or alveolar-arterial difference is common with PE [10-12]. As an example, in one small retrospective study of ABGs in pregnant patients with documented PE, almost two-thirds had a normal alveolar-arterial difference [12].

Electrocardiography — Electrocardiographic findings are similar to those in the nonpregnant population. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Electrocardiography'.)

Differential diagnosis — In pregnant patients, the differential diagnosis of PE is similar to that in nonpregnant patients. The clinician should understand that PE can coexist with other conditions. Thus, the finding of an alternate diagnosis should lower the clinical suspicion for PE but does not always exclude PE or eliminate the need for diagnostic imaging. In most cases, chest radiography or CTPA will distinguish other serious etiologies from PE. Occasionally, echocardiography may be needed when peripartum cardiomyopathy needs to be excluded. The differential diagnosis of PE is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Differential diagnosis'.)

Specific to pregnancy is the following differential diagnosis:

●Pregnancy – Distinguishing pregnancy-related symptoms from PE is challenging. The acute development of symptoms (eg, dyspnea, chest pain) may favor a diagnosis of acute PE rather than pregnancy-related symptoms. However, subacute development of dyspnea may be seen as a consequence of pregnancy-related hormonal changes (ie, "dyspnea of pregnancy") but can also be due to chronic venous thromboembolism or acute embolism in a patient with pre-existing lung disease. (See "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes" and "Clinical manifestations and diagnosis of early pregnancy", section on 'Dyspnea' and "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)

●Peripartum cardiomyopathy – Dyspnea, tachycardia, and lower extremity swelling during pregnancy can be normal, due to PE, or related to heart failure. Heart failure is a clinically important diagnosis that needs to be distinguished from PE as it can also impact survival and warrants different therapy. Heart failure due to pre-existing (known or unknown) or newly developed peripartum cardiomyopathy is associated with more slowly progressive dyspnea and orthopnea. An echocardiogram should distinguish heart failure from PE. The signs and symptoms of peripartum cardiomyopathy are discussed separately. (See "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

●Subclinical underlying lung disease – Pregnancy may exacerbate underlying lung disease, of which the patient was unaware, such as lymphangioleiomyomatosis (LAM). LAM may be distinguished from PE on chest CT. (See "Sporadic lymphangioleiomyomatosis: Clinical presentation and diagnostic evaluation", section on 'Pulmonary'.)

DIAGNOSTIC APPROACH — Clinical practice guidelines for the evaluation of suspected PE in pregnancy have been issued by the American College of Obstetricians and Gynecologists [13,14], the American Thoracic Society and Society of Thoracic Radiology (2011) [15], the Society of Obstetricians and Gynaecologists of Canada (2014) [16], the Royal College of Obstetricians and Gynaecologists (2015) [17], the Society of Thrombosis and Hemostasis (Working Group in Women's Health) (2016) [18], the European Society of Cardiology and European Respiratory Society (2019) [19], and the American College of Radiologists [20].

Our approach to the diagnosis of PE deviates slightly from older guidelines as a result of the publication of newer algorithms in this population reporting the value of protocols that include D-dimer, CT pulmonary angiography (CTPA), and in some cases, compressive ultrasonography (CUS) of the lower extremities, which has led to a paradigm shift in practice (algorithm 1).

While waiting for diagnostic evaluation, we use the same approach to empiric anticoagulation as that described in the nonpregnant population. Further details are provided separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Empiric anticoagulation'.)

Determining pretest probability — A high index of clinical suspicion is critical to the successful diagnosis of suspected PE in pregnancy.

Clinical assessment — We use clinical assessment rather than pretest probability (PTP) scores to assess the likelihood of PE during pregnancy.

●We typically use gestalt suspicion to assess patients as having a low, intermediate, or high suspicion for PE based upon presenting features. Similar to nonpregnant patients, any one or combination of acute-onset dyspnea, pleuritic pain, hemoptysis, syncope, or hypoxemia, particularly in the setting of a normal chest radiograph, should raise the clinical suspicion for a PE during pregnancy. (See 'Clinical presentation' above.)

●Traditionally, clinical decision rules such as the Wells or revised Geneva scoring systems have had limited value during pregnancy [8]. This may be due to the high prevalence of baseline tachycardia and the low likelihood of certain risk factors that are typically listed on PTP scoring systems (eg, malignancy or recent surgery). However, successful use of the revised Geneva score (table 1) or YEARS criteria (clinical signs of deep venous thrombosis [DVT], hemoptysis, and PE as the most likely diagnosis) in conjunction with both D-dimer and targeted PE imaging has gained traction and may reduce the number of unnecessary scans performed for PE during pregnancy. These data are discussed separately. (See 'CT pulmonary angiography' below.)

To date, no studies have described a role for PE rule out criteria (PERC) in pregnant females. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'PERC rule'.)

The value of scoring systems in nonpregnant patients with suspected PE is described separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Determining the pretest probability of pulmonary embolism'.)

Low suspicion — For pregnant patients in whom the suspicion for PE is low, we typically measure the D-dimer level. This approach is supported by newer trials and several guideline groups [18,19,21-23]. (See 'CT pulmonary angiography' below.)

D-dimer — In pregnant patients with a low suspicion for PE, we use the D-dimer level to determine the need for further testing.

●For pregnant patients with a negative D-dimer (eg, <500 ng/mL) and low suspicion for PE, we do not typically proceed with further testing. Patients are observed clinically for the remaining duration of their pregnancy and postpartum period.

●For patients with a positive D-dimer (eg, ≥500 ng/mL) and low suspicion for PE, we proceed with further testing as outlined for patients with a moderate or high suspicion of PE (ie, CUS or pulmonary imaging). (See 'Selection of imaging modality' below.)

This approach is based upon the following data:

●Studies in pregnant females that use high-sensitivity D-dimer assays reported that a negative D-dimer in conjunction with a low suspicion is sufficient to exclude PE (ie, rate of venous thromboembolism in the subsequent three months is <1 percent) [21,22]. These studies are discussed below. (See 'CT pulmonary angiography' below.)

●In a systematic review of 45 studies that used a negative D-dimer in pregnant patients who had a low suspicion for PE, the three-month thromboembolic rate in those with a negative D-dimer was 0.32 percent, and the sensitivity and negative predictive value were 99.5 and 100 percent, respectively [23]. The "efficiency" of the D-dimer test (ie, the percentage of patients with a negative D-dimer) was 34 percent.

However, two caveats are the following:

●D-dimer becomes less useful with gestational age, such that fewer than 5 percent of pregnant patients with suspected PE in the third trimester have a negative D-dimer [21]. This is because D-dimer levels increase during the course of a normal pregnancy and slowly decline postpartum, rendering D-dimer less sensitive and specific than in nonpregnant patients, particularly when traditional cutoff values are used (eg, <500 ng/mL) [24-31].

●There is no agreed-upon pregnancy-adjusted reference ranges or single cutoff. Until robust data support an ideal cutoff value, we use the traditional cutoff value of 500 ng/mL.

The value of D-dimer in the nonpregnant population is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'D-dimer'.)

Intermediate or high suspicion — For pregnant patients with an intermediate or high suspicion for PE or patients with a positive D-dimer and low suspicion for PE, we proceed with further testing. While limited data suggest that D-dimer may also be useful in excluding PE in pregnant females with an intermediate suspicion for PE [21-23], we prefer not to use D-dimer until more robust data conclusively prove benefit in this subgroup. (See 'CT pulmonary angiography' below.)

Selection of imaging modality — Selecting the optimal imaging modality to evaluate for the presence of PE is controversial and practice varies widely. The risks and benefits of each modality need to be weighed separately in the context of patient preference, diagnostic accuracy, availability, comorbidities (eg, renal insufficiency or allergy to contrast) and amounts of radiation and contrast exposure. Occasionally, more than one test will be necessary to definitively diagnose PE. Our approach (algorithm 1), which is outlined in this section, uses clinical assessment for DVT and the chest radiograph findings to determine further testing. (See 'Manifestations of lower extremity venous thrombosis: compressive ultrasonography' below and 'Abnormal chest radiograph: CTPA' below and 'Normal chest radiograph: CTPA or V/Q' below.)

Manifestations of lower extremity venous thrombosis: compressive ultrasonography — For those in whom the clinical evaluation suggests coexistent lower extremity DVT (eg, leg pain, swelling, and/or erythema), we perform bilateral lower extremity proximal vein CUS. We do not support performing proximal CUS routinely or in the absence of symptoms. Signs and symptoms suggestive of a DVT are presented separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis".)

Based upon CUS findings, our approach is the following:

●If CUS is positive for DVT, no further diagnostic imaging is needed to justify treatment and we assume a diagnosis of PE in these circumstances. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)" and "Use of anticoagulants during pregnancy and postpartum".)

If there is concern for right ventricle (RV) strain, we perform echocardiography, although the value of this is prognostic rather than therapeutic, since thrombolysis is contraindicated during pregnancy unless needed as a life-saving measure. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically unstable patients'.)

●If CUS is negative but thrombus is suspected to be located in the calf or pelvic veins (or in the lung) or if CUS is not available, we perform pulmonary imaging (eg, CTPA or V/Q scan). (See 'Abnormal chest radiograph: CTPA' below and 'Normal chest radiograph: CTPA or V/Q' below.)

The rationale for this approach is based upon the high prevalence of DVT in patients with suspected PE who have symptoms suggestive of DVT and our preference to avoid radiation and contrast exposure, when feasible.

●We avoid routine CUS since the overall prevalence of DVT in pregnant patients suspected of having PE is estimated to be low [6] based upon limited data in pregnant patients and extrapolated data from nonpregnant individuals (in whom the prevalence of DVT is 9 to 12 percent) [32-35]. One study reported no cases of DVT in a subpopulation of 69 pregnant patients with suspected PE who routinely underwent evaluation for DVT by bilateral CUS or impedance plethysmography [6].

●However, performing CUS in patients symptomatic of DVT is based upon the greater likelihood of confirming DVT when symptoms are present. For example, the presence of two to three variables of the LEFt clinical prediction rule (left sided symptoms, edema, first trimester) was associated with DVT in 58 percent of pregnant patients [36]. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis".)

The diagnosis of DVT during pregnancy is discussed separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis".)

Abnormal chest radiograph: CTPA — When the chest radiograph is abnormal, we perform CTPA. CTPA is also the preferred modality when the diagnosis is in doubt by ventilation perfusion (V/Q) scan (eg, indeterminate/moderate probability V/Q scan), V/Q scanning is not available, and/or an alternate diagnosis is in question [15,37,38]. In contrast-allergic patients, we prefer to premedicate for the allergy and consider empiric anticoagulation while waiting for the CTPA rather than performing a V/Q scan where the risk of an indeterminate result is high and therefore, ultimately, not helpful. (See 'CT pulmonary angiography' below.)

Normal chest radiograph: CTPA or V/Q — When the chest radiograph is normal, V/Q scanning or CTPA are appropriate. In the past, V/Q scanning was the preferred test in pregnant patients with suspected PE who had a normal chest radiograph [2,6,7,15,39-46]. However, most clinicians, including us, now use CTPA as the primary modality for evaluating pregnant patients for PE. Our preference is based upon the practical rationale that CTPA is more readily available than V/Q scanning, may provide an alternate diagnosis in 12 to 13 percent of cases [43,44], is associated with lower doses of radiation than in the past, and has better interobserver agreement for radiologists than nuclear scans [43]. In support of this practice, one single-center retrospective study of 157 pregnant females reported that CTPA was used more commonly than V/Q scanning to diagnose PE in the first trimester (56 versus 21 percent), second trimester (58 versus 17 percent), and third trimester (70 versus 18 percent) [47]. In contrast-allergic patients, however, we perform V/Q scanning as a reasonable and equally diagnostic alternative to CTPA in the setting of a normal chest radiograph.

●If either V/Q scanning or CTPA excludes PE, no further testing is needed (ie, normal or very low probability V/Q or no filling defect on CTPA). (See 'Ventilation/perfusion scan' below and 'CT pulmonary angiography' below.)

●For those with a positive test, treatment is indicated (high probability V/Q or filling defect(s) on CTPA). (See 'Ventilation/perfusion scan' below and 'CT pulmonary angiography' below and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults".)

●For those with an indeterminate test result, we perform additional testing (eg, low or intermediate probability V/Q or ill-defined filing defect on CTPA). Although there is no clear guidance, options include lower extremity CUS, V/Q scan, or CTPA (either repeat testing or imaging that has not already been performed). Magnetic resonance or contrast-enhanced pulmonary angiography can be considered on a case-by-case basis but are rarely performed and poorly validated in pregnancy. (See 'Magnetic resonance pulmonary angiography' below and 'Contrast-enhanced pulmonary artery angiography' below.)

Limited data have compared CTPA with V/Q scanning in the pregnant population, and reports are conflicting [7,40,43,44]. A 2017 review of 11 retrospective studies reported a lower median sensitivity for CTPA than V/Q scanning (83 versus 100 percent) [48]. CTPA also had a slightly higher rate of inconclusive results (6 versus 4 percent). However, these studies were older, small, retrospective, and not performed using updated technology. Similar comparisons have not been performed between newer CT scanners and V/Q scanning.

DIAGNOSTIC IMAGING — In this section the diagnosis of PE and diagnostic accuracy of each test in the context of pregnancy are discussed. Our suggested approach to the evaluation of a pregnant patient suspected of having a PE is discussed above. (See 'Diagnostic approach' above.)

●V/Q scanning and CTPA – The two most common diagnostic imaging modalities are ventilation/perfusion (V/Q) scanning and CT pulmonary angiography (CTPA). Both can confidently exclude or confirm PE during pregnancy. (See 'Ventilation/perfusion scan' below and 'CT pulmonary angiography' below.)

●Magnetic resonance pulmonary angiography (MRPA) and contrast-enhanced pulmonary angiography – MRPA is not validated in pregnant females, and although contrast-enhanced pulmonary angiography had once been the gold standard for diagnosis of PE, neither test is commonly used in either pregnant or nonpregnant individuals. (See 'Magnetic resonance pulmonary angiography' below and 'Contrast-enhanced pulmonary artery angiography' below.)

●Echocardiography – Rarely, thrombus may be visualized in the right atrium, right ventricle (RV), or pulmonary artery to definitively diagnose PE. An enlarged RV may support a diagnosis of PE when PE is hemodynamically significant, but such a finding is not definitively diagnostic of PE itself. (See 'Echocardiography' below and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Echocardiography'.)

●Proximal CUS – Although a positive diagnosis of deep venous thrombosis (DVT) is made on proximal CUS and typically precludes the need for confirmatory imaging of the chest, it is not diagnostic of PE. (See 'Manifestations of lower extremity venous thrombosis: compressive ultrasonography' above.)

Diagnosis — A definitive diagnosis of PE is made by the demonstration of a high probability V/Q scan or visualization of a filling defect on contrast-enhanced pulmonary angiography, CTPA, or MRPA. Rarely, thrombus may be visualized on echocardiography or discovered pathologically in a resected pulmonary lobe or postmortem.

Occasionally, we make a clinically confident diagnosis of PE in patients with indeterminate imaging studies (eg, intermediate probability V/Q scan) in the context of high clinical suspicion. Indeterminate or nondiagnostic studies are reported when the V/Q scan is low or intermediate probability or when a filling defect is not clearly visualized on contrast studies (eg, embolus in a small peripheral pulmonary artery, poor contrast flow, image interference by motion or hardware artifact). In this situation, physician judgment and patient preference for anticoagulation should be strongly considered in the context of the maternal mortality of untreated PE and weighed against the risks of further testing and the risk of bleeding.

Ventilation/perfusion scan — V/Q scan reports in pregnancy are stratified into the same risk categories as nonpregnant patients:

●Normal/very low (also known as near normal) probability

●Low probability

●Intermediate probability

●High probability

In general, only normal/very low probability scans and high probability scans are considered diagnostic and confidently exclude or confirm PE, respectively [2]. In nonpregnant individuals, normal/very low probability scans are associated with a 0 to 6 percent chance of having a PE. In contrast, high probability scans are associated with a 56 to 96 percent chance of having a PE; all other scans (low and intermediate probability) are indeterminate and generally prompt further testing (table 2). Limited data support similar diagnostic utility in pregnant individuals:

●Studies in pregnant females suspected of having a PE report that V/Q scanning has a high diagnostic accuracy and negative predictive value when the chest radiograph is normal [6,7,15,43-46]. The vast majority of V/Q scans performed for suspected PE in pregnancy are normal/very low probability. Since the prevalence of a normal chest radiograph is high in pregnant patients, the likelihood of indeterminate (ie, nondiagnostic) V/Q scans is lower and of diagnostic V/Q scans is higher than in nonpregnant individuals. Supporting this hypothesis are retrospective studies in pregnant patients suspected of having a PE that confirm a rate of diagnostic V/Q scans (normal/very low or high probability) that ranges from 75 to 93 percent and of indeterminate scans (low probability/moderate probability) that ranges from 7 to 25 percent [6,7,43-46].

●Two studies describe perfusion (Q) scanning for the diagnosis of PE in pregnancy [44,46]. In these studies, Q scanning had a negative predictive value of 100 percent [46] and only 7 percent of scans were nondiagnostic [44]. Although V/Q scanning has not been directly compared with Q scanning, the advantage of Q scanning alone is that it decreases the radiation exposure to mother and fetus. Regardless, Q scanning is rarely, if ever, performed as a standalone test for PE.

The diagnostic accuracy of V/Q scanning in the nonpregnant population is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Ventilation perfusion scan'.)

CT pulmonary angiography — Older, small, retrospective studies reported that during pregnancy, CTPA had a high negative predictive value for excluding the diagnosis of PE [7,39,43,44] but may have a slightly higher rate of nondiagnostic studies (6 to 30 percent) than in the nonpregnant population [7]. However, newer studies using improved CT technology suggest that CTPA is diagnostically more useful during pregnancy than in the past, particularly when used in combination with protocols that incorporate clinical assessment and D-dimer levels to target imaging:

●In a multicenter prospective trial, 395 pregnant females with suspected PE underwent protocolized evaluation for PE using the revised Geneva score (calculator 1), high sensitivity D-dimer testing, and bilateral lower limb CUS [21]. PE was ruled out with a low or intermediate clinical pretest probability (PTP) based upon a low to intermediate Geneva score and a negative D-dimer. All patients with a high PTP or positive D-dimer underwent CUS; if CUS was negative, the patient underwent CTPA. V/Q scanning was performed if CTPA was inconclusive. Patients with a positive CUS, CTPA, or high probability V/Q scan were diagnosed with PE while PE was considered excluded in those with a negative workup. PE was diagnosed in 7.1 percent of patients. At three months, among those with a negative workup, no patient developed symptomatic venous thromboembolism.

Several limitations were associated with this study. The rate of protocol deviations was high (10 percent), indicating the difficulty of adhering to protocols like this during pregnancy. The proportion of patients with a negative D-dimer decreased with gestational age (25 percent during the first trimester, 11 percent during the second trimester, and 4 percent during the third trimester had a normal D-dimer), limiting the value of such a protocol as the pregnancy progresses. In addition, 6 percent of patients in whom PE was excluded received either prophylactic or therapeutic anticoagulation, which may have biased the results in favor of using this protocol.

●In another prospective study, 498 pregnant patients with suspected PE were evaluated using the three YEARS criteria (clinical signs of DVT, hemoptysis, and PE as the most likely diagnosis) and D-dimer levels [22]. PE was excluded in patients with zero YEARS items and a D-dimer level <1000 ng/mL and patients with ≥1 YEARS items and a D-dimer <500 ng/mL. Patients with clinical signs of DVT underwent CUS and were treated if CUS was positive but did not undergo CTPA. All other patients underwent CTPA; PE was diagnosed in those with a positive CTPA (4 percent). During the three month follow-up, DVT was diagnosed in one patient (0.21 percent) and no patient had a PE. Subgroup analysis determined that the efficiency was greatest during the first trimester when CTPA was avoided in 65 percent of patients compared with 32 percent in the third trimester.

Similar to the study above [21], there were several protocol violations (11 percent) and the value of the D-dimer and the protocol decreased with gestational age. In addition, the population studied only included those with a "clear" suspicion for PE rather than a mix of patients who truly have a low, intermediate, or high suspicion, which may have biased the results in favor of the algorithm.

In nonpregnant patients, the YEARS criteria have been shown to reduce the number of unnecessary CT scans performed during the evaluation of those with suspected PE, the details of which are discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'D-dimer'.)

Other imaging — MRPA and contrast-enhanced pulmonary angiography are rarely needed or performed and are poorly validated in pregnant patients. Echocardiography is not routinely performed and rarely reveals thrombus.

Magnetic resonance pulmonary angiography — The sensitivity and specificity of MRPA for the diagnosis of PE during pregnancy have not been evaluated. The diagnostic value of MRPA in the nonpregnant population is discussed in detail separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Magnetic resonance pulmonary angiography'.)

Contrast-enhanced pulmonary artery angiography — Contrast-enhanced pulmonary angiography (ie, digital subtraction angiography) was the historical gold standard for the diagnosis of PE. With the emergence of CTPA and high diagnostic accuracy of V/Q scanning in pregnant patients, it is rarely performed in this population.

Retrospective studies suggest that contrast-enhanced pulmonary angiography may not be as accurate as originally thought. In a post-hoc subpopulation analysis of 20 discordant cases derived from another study, contrast-enhanced pulmonary angiography was less sensitive than CTPA for the detection of emboli [49]. Compared with CTPA, contrast-enhanced pulmonary angiography had a higher number of false negative results (13 versus 2). Most of the thrombi missed on contrast-enhanced pulmonary angiography were subsegmental (eight cases).

The diagnostic value of contrast-enhanced pulmonary artery angiography in the nonpregnant population is discussed in detail separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Catheter-based pulmonary angiography'.)

Echocardiography — Echocardiography is not routinely performed in the diagnostic evaluation of pregnant patients suspected of having a PE. Occasionally, an echocardiogram can be performed to exclude pregnancy-related cardiomyopathy, to evaluate the size of the RV in a patient with confirmed PE, or in hemodynamically unstable patients, to potentially identify thrombus in the right atrium, RV, or pulmonary artery. However, none of these uses has been formally evaluated in pregnancy.

The role of echocardiography in the nonpregnant population is discussed in detail separately (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Echocardiography'.)

Radiation and contrast risk — The decision to select an imaging modality for the diagnosis of PE in pregnancy should be made in the context of radiation and contrast risk to both mother and fetus. In general, the risk of radiation (from V/Q scanning and CTPA) and iodinated contrast is considered low and must be weighed against the 20 to 30 percent risk of maternal mortality of untreated PE. Fetal exposure is clearly not a concern during the postpartum period.

Radiation — The International Commission of Radiologic Protection suggests that the radiation doses delivered in utero by imaging tests (such as those performed in the diagnosis of PE) present no measurable increased risk of fetal death or developmental abnormalities over the background incidence of these entities [50]. Such complications require doses above 50 milligray (mGy), which are much greater than those currently used in diagnostic imaging [51,52].

Similar to nonpregnant patients, low-level ionizing radiation assumes some cumulative risk for carcinogenesis, measured over a lifetime. It is likely that the mother assumes a greater carcinogenic risk (particularly, for breast cancer) than the fetus. The International Commission on Radiological Protection has estimated an increased risk of fatal childhood cancer to the age of 15 following in utero radiation exposure of 0.006 percent per mGy, which equates to a risk of 1 in 17,000 per mGy [50]. The estimated mean fetal radiation doses from CTPA are slightly lower than those from V/Q scan [52-55]. In a meta-analysis of 11 studies, the fetal radiation dose from CTPA ranged from 0.002 to 0.51 mGy and that of V/Q scintigraphy from 0.2 to 0.7 mGy [56]. The mean maternal dose ranged from 0.23 to 9.7 mGy with CTPA and 0.9 to 5.8 mGy with V/Q scan. The wide range of estimated exposures was due to the use of different types of equipment, technical protocols, and methodologies for calculating radiation dose. By comparison, the natural background radiation dose to the fetus during pregnancy is approximately 1 mGy and the estimated global average dose from background radiation that a mother receives is around 2.4 mGy/year [57-59].

Of concern is the theoretical increased risk of breast cancer due to the increased radiosensitivity of breast tissue in pregnant patients from glandular proliferation [60-62]. In a study of 991 patients, the mean radiation dose to the breast from CTPA ranged from 2 to 14 mGy [63]. In a retrospective cohort study of 473 pregnant and postpartum patients, the breast-absorbed dose for V/Q was 0.3 (±0.1) mGy and that of CTPA was 8 (±5.2) mGy [64]. A commonly quoted estimate of radiation-related breast cancer risk is that the delivery of 10 mGy of radiation to a pregnant patient's breast under 35 years of age increases the lifetime risk of developing breast cancer by 13.6 percent above the background risk [54,65]. It has been suggested, however, that this is an overestimate and that the lifetime risk of breast cancer for a 30-year-old patient exposed to 10 mGy of radiation is 1 in 5000, which equates to a lifetime increase in relative risk of 0.2 percent (assuming a 1 in 10 lifetime risk) [54,66,67]. However, limited data suggest no increased risk of breast cancer. In a retrospective population-based cohort study that included 5859 patients who had CTPA during pregnancy or ≤42 days postpartum and 1.3 million who did not, there was no evidence of an increased risk of maternal breast cancer over a median follow-up of 5.9 years starting from one year after the index delivery [68].

It is important to note that with current technology it is possible to obtain diagnostic quality CTPA images with considerably lower doses than those used in the above studies [53,60,69]. The radiation dose used should be 'as low as reasonably achievable' (ALARA principle).

Contrast — Iodinated and gadolinium contrast agents, when administered intravenously, cross the placenta to enter the amniotic fluid and the fetal circulation [70].

The major concern regarding the administration of iodinated contrast is the effect on neonatal thyroid function. Limited data suggest that the risk of neonatal hypothyroidism, due to fetal exposure to free iodine, is very low. A retrospective study of 344 pregnant patients who underwent CTPA for suspected PE found no abnormal levels of thyroxine in neonates at birth [71]. A subsequent study also reported that in 149 individuals who underwent CTPA for suspected PE, no newborns had thyroid dysfunction [72]. No animal studies have shown teratogenicity for iodinated contrast [73].

No fetal teratogenicity of gadolinium has been observed in human studies. However, teratogenicity for high doses or prolonged exposures to gadolinium has been observed in animals [73,74]. The risk of stillbirths and neonatal deaths with exposure to gadolinium during pregnancy is conflicting. One retrospective population-based study of first trimester exposure to gadolinium identified a slight increase in stillbirths and neonatal deaths [75] whereas another study demonstrated no increased risk [76]. (See 'Magnetic resonance pulmonary angiography' above.)

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: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)

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 5^th to 6^th 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 10^th to 12^th 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: Pulmonary embolism (blood clot in the lung) (The Basics)")

●Beyond the Basics topics (see "Patient education: Pulmonary embolism (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical manifestations – The manifestations of pulmonary embolism (PE) during pregnancy are similar to those in nonpregnant patients. However, the nonspecific presentation of PE poses extra challenges during pregnancy since symptoms of PE can overlap with the symptoms of pregnancy itself (eg, dyspnea). Many competing diagnoses can be excluded by chest radiography, but occasionally, echocardiography may be needed to exclude peripartum cardiomyopathy. (See 'Clinical presentation' above and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Clinical presentation'.)

●Diagnostic approach – We use clinical evaluation rather than scoring systems to assess the pretest probability of PE during pregnancy as low, intermediate, or high (algorithm 1). (See 'Determining pretest probability' above.)

•Low suspicion – For pregnant patients in whom the suspicion for PE is low, we typically measure the D-dimer level. This approach is based upon data which report that a negative D-dimer in conjunction with a low suspicion is sufficient to exclude PE (ie, rates of venous thromboembolism in the subsequent three months is <1 percent). However, no agreed-upon cutoff value exists and D-dimer becomes less useful with gestational age such that in the third trimester fewer than 5 percent of pregnant patients with suspected PE have a negative D-dimer. We use a cutoff of 500 ng/mL to distinguish a positive from a negative value. (See 'Low suspicion' above and 'D-dimer' above.)

-For pregnant patients with a negative D-dimer (eg, <500 ng/mL) and low suspicion for PE, we do not typically proceed with further testing and patients are observed clinically for the remaining duration of their pregnancy and puerperium.

-For patients with a positive D-dimer (eg, ≥500 ng/mL) and low suspicion for PE, we proceed with further testing as outlined for patients with a moderate or high suspicion of PE (ie, compressive ultrasonography [CUS] or pulmonary imaging).

•Intermediate or high suspicion – For pregnant patients with an intermediate or high suspicion of PE or patients with a positive D-dimer and low suspicion for PE, we proceed with further testing. The imaging modality of choice depends upon our clinical assessment for deep venous thrombosis (DVT) of the lower extremities and chest radiograph findings (see 'Intermediate or high suspicion' above and 'Selection of imaging modality' above):

-Evaluation for DVT – For those in whom the clinical evaluation suggests coexistent DVT, we perform bilateral proximal vein CUS. The rationale for this approach is based upon the high prevalence of DVT in patients with suspected PE who have symptoms suggestive of DVT and the preference to avoid radiation and contrast exposure. (See 'Manifestations of lower extremity venous thrombosis: compressive ultrasonography' above.)

If CUS is positive for DVT, no further diagnostic imaging is needed to proceed with treatment and a diagnosis of PE is usually assumed in these circumstances.

If CUS is negative (eg, thrombus is suspected to be located in the calf or pelvic veins or in the lung) or if CUS is not available, we perform pulmonary imaging.

-Chest radiograph findings – When the chest radiograph is abnormal, we perform CT pulmonary angiography (CTPA). This approach is based upon the increased risk of an intermediate probability result on ventilation perfusion (V/Q) scanning in this subgroup of pregnant patients, which commonly prompts additional imaging, usually CTPA. (See 'Abnormal chest radiograph: CTPA' above.)

When the chest radiograph is normal, either V/Q scanning or CTPA is appropriate. We often choose CTPA based upon the practical rationale that CTPA is more readily available than V/Q scanning, may provide an alternate diagnosis in 12 to 13 percent of cases, is associated with lower doses of radiation than in the past, and has better interobserver agreement for radiologists than nuclear scans. V/Q scanning is an alternative for those in whom CTPA is contraindicated. (See 'Normal chest radiograph: CTPA or V/Q' above.)

In general, the risk of radiation (from V/Q scanning and CTPA) and iodinated contrast is considered low. (See 'Radiation and contrast risk' above.)

●Diagnosis – A definitive diagnosis of PE is made by the demonstration of a high probability V/Q scan or visualization of a filling defect by contrast-enhanced imaging. Rarely, thrombus may be visualized on echocardiography, if performed. (See 'Diagnosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David R Schwartz, MD, who contributed to earlier versions of this topic review.