INTRODUCTION — Although diseases of the pericardium may occur sporadically during pregnancy, there is no evidence that pregnancy increases the susceptibility to pericardial diseases [1]. The outcomes of pregnancies in women with pericardial disease are similar to those expected in the general population with pericardial disease. More difficult cases may require a multidisciplinary approach involving different subspecialties (eg, cardiology, internal medicine, maternal-fetal medicine, and neonatology).

Relatively few data are available to guide the management of pericardial disease during pregnancy. However, as with pregnancy in general, the major tenet of avoiding all medications and interventions that are not absolutely necessary should be followed.

This topic will discuss the clinical features, diagnosis, and management of pericardial effusion and acute (or recurrent) pericarditis during pregnancy. A broader discussion of pericardial disease in the general population is presented separately. (See "Acute pericarditis: Clinical presentation, diagnostic evaluation, and diagnosis" and "Acute pericarditis: Treatment and prognosis" and "Recurrent pericarditis" and "Diagnosis and treatment of pericardial effusion".)

FETAL PERICARDIAL FLUID — After 20 weeks of gestation, a small amount of pericardial fluid (<3 mm) can be detected in the normal fetus [1,2]. Larger fetal pericardial effusions should raise suspicion of disease conditions, such as nonimmune hydrops fetalis, fetal hemolytic disease due maternal antibodies to Rhesus or other red cell antigens, structural anomaly (eg, heart or diaphragm, teratoma), chromosomal abnormality, infection, or an immunopathy [3,4]. Because of the limited distensibility of the fetal pericardial sac, pathologic pericardial effusion may be the first sign of hydrops, detectable before the appearance of ascites, pleural effusion, and soft tissue edema. (See "Nonimmune hydrops fetalis", section on 'Fetal findings'.)

MATERNAL PERICARDIAL EFFUSION

Epidemiology and clinical features — Pericardial effusion has been reported in the first and second trimester in 15 to 20 percent of pregnancies and in approximately 40 percent of pregnant women during the third trimester [5]. In general, these effusions are asymptomatic, benign, transient, and resolve spontaneously without therapy. In the absence of signs or symptoms of acute pericarditis or cardiac tamponade, neither diagnostic testing (generally with echocardiography) nor specific treatment is required.

The following observations have been made regarding pericardial effusions in pregnancy:

●The effusion is usually small to moderate in size, with separation of the pericardial layers of less than 10 mm. When sampled, these effusions are usually found to be a transudate (hydropericardium) [5-8].

●Slightly elevated blood pressure and/or nonspecific ST-T changes have been reported in association with pericardial effusion [6,7].

●The clinical examination and electrocardiogram (ECG) are generally normal.

●The pericardial effusion is usually transient and disappears within two months following delivery [6].

●In the absence of signs or symptoms of acute pericarditis or cardiac tamponade, treatment is not required [5-8]. (See "Acute pericarditis: Treatment and prognosis" and "Cardiac tamponade".)

The signs and symptoms of cardiac tamponade may be masked during pregnancy due to the physiologic increase in circulating blood volume. This may lead to a larger pericardial effusion being present before signs or symptoms are detected.

Management and follow-up — For pregnant women who are identified as having a moderate or large pericardial effusion that is not felt to require immediate drainage, serial follow-up testing with echocardiography should be performed. Echocardiography examination should include Doppler recording of mitral inflow velocities and hepatic vein flow velocities as well as M-mode and 2D echocardiography to assess the hemodynamic impact of pericardial effusion. In general, if the patient remains asymptomatic and hemodynamically stable and the effusion is not increasing in size, we continue with serial echocardiograms every three months until the pericardial effusion is decreasing in size or resolved. For pregnant women with a small asymptomatic pericardial effusion, we repeat the echocardiogram only if clinically indicated by signs or symptoms suggestive of possible pericardial tamponade, as small pericardial effusions are usually benign and spontaneously resolve.

ACUTE PERICARDITIS

Epidemiology and etiology — There are no published data on the frequency of acute pericarditis in pregnancy. In particular there is nothing to suggest an incidence that is higher or lower than in the general population. (See "Acute pericarditis: Clinical presentation, diagnostic evaluation, and diagnosis", section on 'Epidemiology'.)

As in the general population, idiopathic acute pericarditis is the most frequent final diagnosis (table 1); the etiology is often presumed to be viral [9]. Infectious etiologies other than viral are less common than in the general population. Tuberculous pericarditis should be suspected especially in cases coming from endemic areas or in case of HIV infection [10,11]. (See "Etiology of pericardial disease".)

Clinical manifestations — Acute pericarditis can present in a variety of ways, depending on the underlying etiology. Patients with an infectious etiology may present with signs and symptoms of systemic infection such as fever and leukocytosis. Viral etiologies in particular may be preceded by "flu-like" respiratory or gastrointestinal symptoms. Patients with a known autoimmune disorder or malignancy may present with signs or symptoms specific to their underlying disorder. (See "Acute pericarditis: Clinical presentation, diagnostic evaluation, and diagnosis", section on 'Clinical features'.)

The major clinical manifestations of acute pericarditis include [12]:

●Chest pain – Typically sharp and pleuritic, improved by sitting up and leaning forward

●Pericardial friction rub – A superficial scratchy or squeaking sound best heard with the diaphragm of the stethoscope over the left sternal border

●Electrocardiogram (ECG) changes – New widespread ST elevation and/or PR depression

●Pericardial effusion

Diagnosis — The diagnosis of acute pericarditis is usually suspected based on a history of characteristic pleuritic chest pain, and is confirmed if a pericardial friction rub, typical ECG changes, or an effusion is present. Pericarditis should also be suspected in a patient with persistent fever and pericardial effusion or new unexplained cardiomegaly [10]. Additional testing, which typically includes blood work, chest radiography, electrocardiography, and echocardiography, can support the diagnosis but is frequently normal or unrevealing. The electrocardiogram is usually the first and one of the most helpful diagnostic tests in patients with chest pain and suspected acute pericarditis. Because ST segment elevations in a patient with chest pain may also be seen in patients with an acute coronary syndrome, careful evaluation of all ECG findings is critical. Echocardiography is often normal, but it is an essential part of the evaluation if there is evidence of an associated pericardial effusion and/or signs of cardiac tamponade. (See "Acute pericarditis: Clinical presentation, diagnostic evaluation, and diagnosis", section on 'Diagnosis'.)

The diagnosis of acute pericarditis in pregnancy is made using the same criteria (table 2) as in the general population [10,13]. Echocardiography is the imaging method of choice for diagnosis, evaluating the hemodynamic impact of pericardial fluid, absence of regional wall motion (when STEMI is considered), guidance for pericardiocentesis when needed, and follow-up [14]. Diagnostic x-rays of the chest, if indicated, produce almost no scatter to the fetus; any radiation received would not result in a measurably increased risk, especially if the maternal abdomen is shielded. Magnetic resonance imaging with gadolinium and nuclear isotope scans with gallium-67 are generally avoided unless necessary to significantly improve diagnostic performance and improve fetal or maternal outcome. (See "Diagnostic imaging in pregnant and nursing patients".)

Determination of risk and need for hospitalization — Many clinicians admit all new cases of acute pericarditis to the hospital, but this may not be necessary. A pregnant patient with uncomplicated acute pericarditis can undergo initial evaluation in a same-day hospital facility or clinic, although outpatient follow-up is required [15,16]. On the other hand, pregnant patients with high-risk features are at increased risk of short-term complications and have a higher likelihood of a specific disease, as is also the case in non-pregnant patients [15]. Hospital admission is indicated for high-risk patients in order to initiate appropriate therapy and a thorough etiologic evaluation.

Management — The management of pregnant women with acute pericarditis is similar to that in the general population (algorithm 1), with the notable exception that the impact of all medical therapies on the fetus must be considered. In addition to activity restriction, the therapy of acute pericarditis should be targeted as much as possible to the underlying etiology [17-21]. In patients with an identified cause other than viral infection, specific therapy appropriate to the underlying disorder is indicated. However, in developed countries, most cases of acute pericarditis in immunocompetent patients are idiopathic and considered to be most likely due to a viral infection. Because of the relatively benign course associated with the common causes of pericarditis (>80 percent of cases), it is at not necessary to search for the etiology in all patients. As such, most patients are treated for a presumptive viral cause with nonsteroidal anti-inflammatory drugs (NSAIDs). However, potential fetal problems with use of indomethacin and other COX inhibitors (eg, sulindac, nimesulide) are constriction of the ductus arteriosus and oligohydramnios. (See "Pericardial disease associated with malignancy" and "Tuberculous pericarditis" and "Purulent pericarditis".)

Most patients with acute pericarditis can be managed effectively with medical therapy alone. However, patients with a large pericardial effusion, a hemodynamically significant pericardial effusion, a suspicion of a bacterial or neoplastic etiology, or evidence of constrictive pericarditis should be evaluated for invasive therapies, such as pericardial drainage and/or pericardiotomy (pericardial window). (See "Acute pericarditis: Treatment and prognosis", section on 'Adjunctive therapies'.)

Activity restriction — Strenuous physical activity may trigger a recurrence of symptoms in patients with acute (or recurrent) pericarditis; therefore, such activity should be avoided at least until symptom resolution or preferably for two to three months following the cessation of symptoms. The approach to reintroduction of physical activities is discussed separately. (See "Acute pericarditis: Treatment and prognosis", section on 'Activity restriction'.)

Initial treatment — The general approach to the pharmacologic management of acute (or recurrent) pericarditis during pregnancy is similar to that for non-pregnant individuals (algorithm 1). Patients with a specific cause identified should have treatment tailored to that specific etiology, while patients with idiopathic pericarditis should receive anti-inflammatory therapy, with the exception that colchicine is not used in pregnant patients. (See 'Colchicine' below.)

●In patients with an identified cause other than viral or idiopathic disease, specific therapy appropriate to the underlying disorder is indicated.

●In acute viral or idiopathic pericarditis, the optimal approach to therapy varies before and after gestational week 20 due to the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on the ductus arteriosus in the second half of gestation.

•For pregnant women who are less than 20 weeks pregnant, we recommend NSAIDs, either aspirin (500 to 750 mg every eight hours) or ibuprofen (600 to 800 mg every eight hours).

•For pregnant women at gestational week 20 week or greater, NSAIDs are contraindicated and should not be started (or should be withdrawn if already in use). In this population, glucocorticoids are the preferred therapy as they have not been associated with birth defects after the first trimester, and neonatal adrenal suppression is rare. Dosing is similar to that recommended in recurrent pericarditis. Inducing maternal gestational diabetes is a potential concern. (See "Recurrent pericarditis", section on 'Glucocorticoids'.)

As is true for the use of all drugs during pregnancy, treatment of acute pericarditis must balance the benefits of therapy against the potential harm to the fetus. A list of common anti-inflammatory and immunosuppressive drugs used in the treatment of pericardial diseases is provided (table 3 and table 4).

One of the largest reports of pregnant women with pericarditis includes six cases (mean age 30 years, mean gestational age at delivery 38 weeks, and mean birth weight 2839 g), all with an idiopathic etiology [22]. Four women were treated with aspirin 800 mg three times daily with gradual tapering in three within 20 weeks of gestation. In one case, aspirin was continued until delivery. All women were treated with prednisone at a low to moderate dose (eg, 10 to 25 mg daily), in four cases during all the pregnancy and in two cases starting at the third trimester. Five pregnancies (83 percent) were uneventful; HELLP syndrome developed in the mother who was treated with aspirin until delivery. (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)

NSAID therapy — Nonsteroidal anti-inflammatory drugs (NSAIDs) are not teratogenic and can be safely used during the first and second trimester. After gestational week 20, all NSAIDs (except aspirin at less than 100 mg/day) can cause constriction of the ductus arteriosus and impair fetal renal function and the rates seem to increase dramatically after week 28. Thus aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), excluding COX-2 inhibitors, can be continued until the second trimester but should be withdrawn beginning at 20 weeks of gestation [13]. Because there are no data on selective COX-2 inhibitors, these medications should be avoided during pregnancy.

For pregnant women who are less than 20 weeks pregnant, we recommend NSAIDs rather than glucocorticoids as the initial treatment. The 2015 European Society of Cardiology (ESC) guidelines recommend high-dose aspirin (500 to 750 mg every eight hours) as the first choice of therapy, although other NSAIDs are allowed [13]. There is no evidence that ibuprofen is inferior to aspirin, and therefore it may also be used as first-line therapy. The initial administration of an NSAID should be at a full dose (ie, "attack dose") every six to eight hours to achieve better symptom control than with a lower dose (table 5). The attack dose is maintained empirically for one to two weeks or until complete symptom resolution. Tapering should be considered following the attack dose in an attempt to reduce the subsequent risk of recurrence. (See "Acute pericarditis: Treatment and prognosis", section on 'Nonsteroidal anti-inflammatory drugs'.)

Glucocorticoid therapy — As glucocorticoids are not teratogenic (although there may be a small increase in the risk of cleft palate when used in the first trimester), they are often used in the setting of pericarditis during pregnancy, especially if the woman is refractory to NSAIDs or is more than 20 weeks pregnant. In general, however, for women who are less than 20 weeks pregnant, aspirin or NSAIDs should be the initial treatment of choice [13]. (See "Acute pericarditis: Treatment and prognosis", section on 'Glucocorticoids'.)

Our approach to glucocorticoid dosing has been endorsed by the 2015 ESC guidelines (table 5) [13]. In our experience, rapid tapering of systemic glucocorticoids increases the risk of treatment failure and recurrence. Although high doses of glucocorticoids (eg, prednisone 1 mg/kg/day) have been recommended in the ESC guidelines, use of lower doses (eg, prednisone 0.25 to 0.50 mg/kg/day) may be equally efficacious. Generally, we do not start with total daily doses higher than 25 mg in pregnant women. These relatively lower doses may be useful in reducing the risk of steroid side effects, which have been reported in up to 25 percent of patients treated with high doses. (See "Major side effects of systemic glucocorticoids".)

We usually begin tapering glucocorticoids at two to four weeks, after resolution of symptoms and/or C-reactive protein normalization. Each decrement in prednisone dose should proceed only if the patient is asymptomatic, particularly for doses lower than 25 mg/day. A proposed tapering scheme follows:

●Daily dose 15 to 25 mg – Taper 2.5 mg/day every two to four weeks

●Daily dose <15 mg – Taper 1.25 to 2.5 mg/day every two to six weeks

Prednisone and prednisolone are metabolized by the placenta into inactive 11-keto forms, and only 10 percent of the active drugs may reach the fetus [23]. Prednisone and prednisolone appear to be safe if used at low to medium doses (eg, 10 to 25 mg daily) and are reasonable choices when glucocorticoids are required [22]. Rarely, maternal use of systemic glucocorticoids during first-trimester of pregnancy may lead to a small increase in orofacial clefts, from approximately 1:1000 births in the general population to a possible increase of three or four for every 1000 births [24]. A more extensive discussion of the risks of glucocorticoid therapy during pregnancy is presented separately. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Glucocorticoids'.)

Colchicine — The possible adverse effects of colchicine in pregnancy are not well studied. Potential teratogenicity cannot be absolutely excluded from animal data [25]. There is a general consensus that, unless there are compelling maternal indications, the drug is contraindicated during pregnancy and lactation [13]. It should be gradually stopped before conception.

Subsequent treatment of refractory symptoms — Immunosuppressive drugs beyond glucocorticoids are occasionally needed in recurrent cases [26,27]. Management of such cases requires adequate knowledge, experience, and co-management with other specialists. Among these drugs, azathioprine, intravenous immunoglobulins, and cyclosporine may rarely be used in selected cases during pregnancy, while methotrexate and cyclophosphamide are absolutely contraindicated and should be stopped prophylactically three months before a planned pregnancy.

Surgical therapy is rarely if ever indicated in pregnancy, but it has nevertheless been reported that pericardiectomy can be performed safely if absolutely necessary and does not impose a risk for subsequent pregnancies [28,29]. (See "Diagnosis and treatment of pericardial effusion", section on 'Pericardial fluid drainage'.)

Breast feeding — Following delivery, breastfeeding infants may be exposed to the medications if they are excreted into breast milk. Among the usual therapies prescribed for acute pericarditis in pregnancy, aspirin has the greatest potential for harm in infants due to the theoretical risk of Reye syndrome. (See "Acute toxic-metabolic encephalopathy in children", section on 'Reye syndrome'.)

Most NSAIDs are excreted into human breast milk, although generally in very small quantities. Several NSAIDs, including flufenamic acid, diclofenac, ibuprofen, indomethacin, mefenamic acid, naproxen, and piroxicam are considered consistent with breastfeeding by the American Academy of Pediatrics [30]. Aspirin (>100 mg/day) should be considered with caution (and preferably avoided) because of potential adverse effects for the infant [13,30]. A useful practice may be to postpone the NSAID dose until after breastfeeding in order to reduce the infant's exposure, although the 2015 ESC guidelines state that aspirin is "preferably avoided" during breastfeeding [13,31].

Breastfeeding is feasible during corticosteroid therapy, but should be postponed (four hours) with doses >40 mg/day [31].

PLANNING FOR PREGNANCY — In women with chronic recurrent pericarditis, pregnancy should be avoided during a period of disease activity. (See "Recurrent pericarditis".)

Women with recurrent pericarditis on therapy should be evaluated carefully prior to any planned pregnancy. In particular, colchicine is preferentially gradually stopped before conception and substituted with aspirin and/or low-dose prednisone [31]. General outcomes of pregnancy in patients with idiopathic recurrent pericarditis are good, especially when patients are carefully followed by multidisciplinary teams, according to standardized protocols [32].

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: Pericardial disease" and "Society guideline links: Management of cardiovascular diseases during pregnancy".)

SUMMARY AND RECOMMENDATIONS

●Pericardial effusion has been reported in the first and second trimester in 15 to 20 percent of pregnancies and in approximately 40 percent of pregnant women during the third trimester. In general, these effusions are asymptomatic, benign, transient, and resolve spontaneously without therapy. In the absence of signs or symptoms of acute pericarditis or cardiac tamponade, neither diagnostic testing (eg, follow-up echocardiography) nor specific treatment is required. (See 'Epidemiology and clinical features' above.)

●For pregnant women who are identified with a moderate or large pericardial effusion that is not felt to require immediate drainage, serial follow-up testing with echocardiography should be performed every three months until resolved. For pregnant women with a small asymptomatic pericardial effusion, we repeat the echocardiogram only if clinically indicated by signs or symptoms suggestive of possible pericardial tamponade. (See 'Management and follow-up' above.)

●The diagnosis of acute pericarditis is usually suspected based on a history of characteristic pleuritic chest pain and confirmed if a pericardial friction rub, characteristic electrocardiogram (ECG), or pericardial effusion is present. Pericarditis should also be suspected in a patient with persistent fever and pericardial effusion or new unexplained cardiomegaly. The diagnosis of acute pericarditis in pregnancy is made using the same criteria (table 2) as in the general population. (See 'Clinical manifestations' above and 'Diagnosis' above.)

●The management of pregnant women with acute pericarditis is similar to that in the general population (algorithm 1), with the notable exception that the impact of all medical therapies on the fetus must be considered. (See 'Management' above.)

•Strenuous physical activity may trigger recurrence of symptoms in patients with acute (or recurrent) pericarditis; therefore, such activity should be avoided until symptom resolution. (See "Acute pericarditis: Treatment and prognosis", section on 'Activity restriction'.)

•In patients with an identified cause other than viral or idiopathic disease, specific therapy appropriate to the underlying disorder is indicated.

•For pregnant women who are less than 20 weeks pregnant, we recommend NSAIDs rather than glucocorticoids (Grade 1B). We use aspirin (500 to 750 mg every eight hours) or ibuprofen (600 to 800 mg every eight hours). (See 'NSAID therapy' above.)

•For pregnant women at gestational week 20 week or greater, NSAIDs are contraindicated and should not be started (or should be withdrawn if already in use). In this population, glucocorticoids are the preferred therapy as they are safe in pregnancy. (See 'Glucocorticoid therapy' above.)

•Colchicine is not used in pregnant women with pericarditis due to unknown possible adverse effects and teratogenicity, although it is used for specific conditions (eg, familial Mediterranean fever) without reporting of significant side effects. (See 'Colchicine' above and "Management of familial Mediterranean fever", section on 'Pregnancy'.)