What is hydrops fetalis?

Hydrops Fetalis

Hydrops fetalis is a serious fetal condition characterized by abnormal accumulation of fluid in at least two fetal compartments, including subcutaneous tissue, pleural cavity, pericardial cavity, or peritoneal cavity, with a poor prognosis and neonatal survival often less than 50% even in the absence of aneuploidy. 1

Definition and Classification

Hydrops fetalis is not a diagnosis itself but rather a symptom representing the end-stage of various disorders. It is typically classified into two categories:

1. Immune hydrops fetalis: Caused by red cell alloimmunization (accounts for 10-24% of cases)
2. Nonimmune hydrops fetalis (NIHF): Represents 76-87% of all hydrops cases and has multiple etiologies 1, 2

Pathophysiology

The common underlying pathophysiology across various etiologies is an imbalance in fluid regulation between vascular and extravascular compartments. This imbalance can result from:

• Increased central venous pressure
• Decreased plasma oncotic pressure
• Increased capillary permeability
• Obstruction of lymphatic flow

The specific mechanism depends on the underlying cause 1.

Etiology

The differential diagnosis of NIHF is extensive, with causes including:

1. Cardiovascular abnormalities (17-35%): Most common cause, including structural heart defects, arrhythmias, cardiomyopathies, and vascular abnormalities 1, 2

   • Right heart defects are most commonly associated with NIHF
   • Arrhythmias include tachyarrhythmias (supraventricular tachycardia, atrial flutter) and bradyarrhythmias (congenital heart block)

2. Chromosomal abnormalities (7-16%): Particularly Turner syndrome (45,X) and Down syndrome (trisomy 21) 1, 2

   • Turner syndrome is associated with 50-80% of cystic hygromas
   • Other aneuploidies include trisomies 13 and 18, and triploidy

3. Hematologic disorders (4-12%): Including hemoglobinopathies, hemolysis, fetomaternal hemorrhage, and congenital dyserythropoietic anemia 1, 3, 2

   • Alpha thalassemia is the most common hemoglobinopathy causing NIHF

4. Infectious causes (5-7%): Particularly parvovirus B19, cytomegalovirus, and toxoplasmosis 1, 2

5. Thoracic abnormalities (6%): Including congenital cystic adenomatoid malformation, pulmonary sequestration, and pleural effusions 1, 4, 2

6. Twin-twin transfusion syndrome (3-10%): Causing hypervolemia and increased central venous pressure 1, 2

7. Lymphatic dysplasia (5-6%): Leading to impaired venous return 1, 2

8. Urinary tract abnormalities (2-3%): Causing urinary ascites or nephrotic syndrome with hypoproteinemia 1, 2

9. Gastrointestinal disorders (0.5-4%): Leading to obstruction of venous return or protein loss 1, 2

10. Tumors (2-3%): Including sacrococcygeal teratomas and chorioangiomas 1, 4, 2

11. Inborn errors of metabolism (1-2%): Causing visceromegaly, decreased erythropoiesis, or hypoproteinemia 1, 2

12. Genetic syndromes: Including RASopathies such as Noonan syndrome and Noonan-like syndrome with loose anagen hair 5

13. Idiopathic (15-25%): Cases where no cause can be identified despite thorough evaluation 1, 6, 2

Diagnostic Approach

The diagnostic algorithm for hydrops fetalis includes:

1. Antibody screen (indirect Coombs test) to determine if immune or nonimmune 1

2. Detailed ultrasound examination including:

   • Assessment of all fetal compartments for fluid collections
   • Fetal echocardiography
   • Assessment for fetal arrhythmia
   • Middle cerebral artery Doppler evaluation for anemia (key decision point in the diagnostic algorithm) 1, 6

3. Genetic testing:

   • Karyotype and/or chromosomal microarray analysis regardless of whether structural anomalies are identified 1

4. Additional testing based on initial findings:

   • For suspected anemia: PCR for infections (parvovirus, CMV, toxoplasmosis)
   • For parents with MCV <80 fL: DNA testing for alpha-thalassemia
   • For specific anomalies: Targeted genetic testing 1

Management

Management depends on the underlying etiology and gestational age:

1. Etiology-specific treatment:

   • Fetal tachyarrhythmias: Maternal treatment with antiarrhythmic medications
   • Fetal anemia: Intrauterine transfusions
   • Treatable structural abnormalities: Consider fetal surgery in select cases 1, 4, 3

2. General management:

   • Corticosteroids and antepartum surveillance for:
     • Idiopathic cases
     • Etiologies amenable to prenatal or postnatal treatment
     • Cases where intervention is planned if fetal deterioration occurs
   • Delivery at a facility capable of stabilizing and treating critically ill newborns
   • Preterm delivery only for obstetric indications including development of mirror syndrome 1

Prognosis

The prognosis for hydrops fetalis is generally poor:

• Aneuploidy confers a particularly poor prognosis
• Even in the absence of aneuploidy, neonatal survival is often less than 50%
• Cardiovascular causes have reported mortality of up to 92%
• Prognosis depends on:
  • Underlying etiology
  • Response to therapy if treatable
  • Gestational age at detection and delivery 1, 4

Important Clinical Considerations

• Mirror syndrome is a form of severe preeclampsia that may develop in association with fetal hydrops and typically necessitates delivery 1
• Imaging pitfalls to avoid include mistaking abdominal wall muscles, physiologic pericardial fluid, or thick subcutaneous tissue as pathologic fluid accumulation 6
• Early diagnosis and prompt treatment of treatable causes are critical for improving outcomes 1, 6

Hydrops fetalis represents a serious condition with high mortality rates, requiring comprehensive evaluation to identify the underlying cause and guide appropriate management.