What causes pericardial effusion in an unborn fetus?

Causes of Pericardial Effusion in an Unborn Fetus

Fetal pericardial effusion is most commonly caused by heart failure, followed by chromosomal abnormalities (particularly Turner syndrome and trisomy 21), cardiac arrhythmias, infections, and hydrops fetalis—with normal fetal pericardial fluid measuring ≤2 mm in depth after 20 weeks' gestation. 1

Normal vs. Pathological Fetal Pericardial Fluid

• Normal fetal pericardial fluid can be detected by echocardiography after 20 weeks' gestation and measures 2 mm or less in depth. 1
• Any pericardial fluid depth exceeding 2 mm should raise concern for underlying pathology and warrants comprehensive investigation. 1

Primary Causes of Fetal Pericardial Effusion

Cardiovascular Causes (Most Common)

• Heart failure is the single most common cause of fetal pericardial effusion, accounting for 13 of 44 cases (30%) in one series and representing 17-35% of nonimmune hydrops fetalis cases. 2, 1
• Cardiac structural defects causing in utero congestive heart failure lead to increased central venous pressure and subsequent pericardial fluid accumulation. 1
• Fetal tachyarrhythmias (supraventricular tachycardia and atrial flutter) can cause pericardial effusion through hemodynamic compromise. 1
• Fetal bradyarrhythmias, particularly congenital heart block from maternal anti-Ro/SSA and anti-La/SSB antibodies, can result in pericardial effusion with poor prognosis when hydrops develops. 1

Chromosomal Abnormalities

• Turner syndrome (45,X) and Down syndrome (trisomy 21) account for 7-16% of nonimmune hydrops fetalis cases and are particularly common when identified early in gestation. 1
• Turner syndrome is associated with 50-80% of cystic hygromas, which result from lymphatic dysplasia and lack of communication between the lymphatic system and venous drainage. 1
• Other aneuploidies including trisomies 13,18, and triploidy can present with pericardial effusion, often due to associated cardiovascular malformations. 1

Infectious Causes

• Maternally transmitted infections including mycoplasmal infections, cytomegalovirus, parvovirus B19, and other viral pathogens can cause fetal pericardial effusion. 1
• Infectious causes account for 5-7% of nonimmune hydrops fetalis cases through mechanisms of anemia, anoxia, endothelial cell damage, and increased capillary permeability. 1
• Fetal renal cystic dysplasia with oligohydramnios was associated with pericardial effusion in 6 of 44 cases, with 4 showing microscopic evidence of pericarditis on postmortem examination. 2

Hematologic Causes

• Fetal anemia from hemoglobinopathies (particularly alpha thalassemia), hemolysis, fetomaternal hemorrhage, or red cell aplasia accounts for 4-12% of nonimmune hydrops fetalis. 1
• Alpha thalassemia is the most common hemoglobinopathy causing nonimmune hydrops, accounting for 28-55% of cases in Southeast Asian populations and about 10% in other series. 1

Immune-Mediated Causes

• Rh disease and other blood group alloimmunization can cause fetal pericardial effusion through hemolysis and high-output cardiac failure. 1
• Maternal autoimmune antibodies (anti-Ro/SSA, anti-La/SSB) associated with Sjögren syndrome or lupus can cause congenital heart block and subsequent pericardial effusion. 1

Metabolic and Protein Disorders

• Hypoalbuminemia from various causes leads to decreased colloid osmotic pressure and pericardial fluid accumulation. 1
• Inborn errors of metabolism account for 1-2% of nonimmune hydrops fetalis through mechanisms of visceromegaly, decreased erythropoiesis, and hypoproteinemia. 1

Other Structural Causes

• Thoracic abnormalities (6% of cases) cause vena caval obstruction or increased intrathoracic pressure with impaired venous return. 1
• Twin-twin transfusion syndrome (3-10% of cases) causes hypervolemia and increased central venous pressure in the recipient twin. 1
• Urinary tract abnormalities (2-3% of cases) can cause urinary ascites or nephrotic syndrome with hypoproteinemia. 1
• Lymphatic dysplasia (5-6% of cases) causes impaired venous return and fluid accumulation. 1
• Tumors including chorioangiomas (2-3% of cases) cause anemia, high-output cardiac failure, or hypoproteinemia. 1

Clinical Significance and Prognosis

• Isolated fetal pericardial effusion (IFPE) resolves spontaneously in approximately 86.8% of cases, but carries an overall morbidity rate of 34.2% and mortality rate of 15.7%. 3
• More than one-third of fetuses with isolated pericardial effusion develop pathological conditions including metabolic disease, chromosomopathies, cardiomyopathy, or neurodevelopmental disorders. 3
• The presence of other ultrasound alterations and abnormal first-trimester screening are significantly associated with pathology in fetuses with pericardial effusion. 3
• Fetal pericardial effusions are always a manifestation of another disease process, often presenting as fetal hydrops, and the etiologic origin differs from that in children or adults. 2

Diagnostic Approach

• Comprehensive fetal echocardiography should be performed to assess cardiac structure, function, and rhythm when pericardial effusion >2 mm is detected. 1
• Maternal serologic testing for anti-Ro/SSA and anti-La/SSB antibodies should be obtained when fetal bradycardia or heart block is present. 1
• Karyotype analysis or chromosomal microarray should be offered given the 7-16% incidence of chromosomal abnormalities. 1
• Maternal screening for infections (TORCH panel, parvovirus B19) and assessment for alloimmunization should be performed. 1
• Parental mean cell volume screening can identify alpha thalassemia carriers (MCV <80 fL). 1
• Exhaustive prenatal and postnatal follow-up is recommended to enable early intervention for associated pathologies. 3

Critical Pitfalls to Avoid

• Do not assume isolated fetal pericardial effusion is benign—comprehensive evaluation is mandatory given the 34.2% morbidity rate despite frequent spontaneous resolution. 3
• Do not delay evaluation for cardiac arrhythmias, as transplacental antiarrhythmic therapy can successfully treat fetal tachyarrhythmias causing hydrops. 1
• Do not overlook maternal autoimmune screening in cases of fetal bradycardia, as congenital heart block from maternal antibodies carries poor prognosis once third-degree block develops. 1
• Recognize that 15-25% of nonimmune hydrops fetalis cases remain idiopathic despite comprehensive evaluation, but this should not preclude thorough investigation. 1