From the Guidelines
Hydrops fetalis occurs due to an imbalance in fluid homeostasis, where the rate of fluid movement into the interstitial space exceeds the drainage capacity of the lymphatic system, leading to abnormal fluid accumulation in fetal tissues and body cavities. The primary mechanism involves several pathways, including increased hydrostatic pressure from heart failure, decreased plasma oncotic pressure from liver dysfunction or protein-losing conditions, lymphatic obstruction, or increased capillary permeability from inflammation 1. In non-immune hydrops, various conditions like cardiac abnormalities, chromosomal disorders, infections, or metabolic diseases disrupt the balance between hydrostatic and oncotic pressures, leading to pathological fluid accumulation. The etiologies of non-immune hydrops fetalis can be categorized into several causes, including:
- Cardiovascular: 17-35% of cases, resulting from increased central venous pressure 1
- Chromosomal: 7-16% of cases, resulting from cardiac anomalies, lymphatic dysplasia, and abnormal myelopoiesis 1
- Hematologic: 4-12% of cases, resulting from anemia, high output cardiac failure, and hypoxia 1
- Infectious: 5-7% of cases, resulting from anemia, anoxia, endothelial cell damage, and increased capillary permeability 1 The resulting edema manifests as skin edema, pleural effusions, pericardial effusions, ascites, and placental enlargement. Understanding these mechanisms is crucial for proper diagnosis and management of the underlying cause, which is essential for improving outcomes in affected fetuses. According to the Society for Maternal-Fetal Medicine (SMFM) clinical guideline #7, the underlying pathogenesis of non-immune hydrops fetalis is an imbalance in the regulation of fluid homeostasis 1.
From the Research
Pathophysiological Mechanisms of Hydrops Fetalis
The pathophysiological mechanisms behind hydrops fetalis involve an abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema 2. The edema occurs due to various factors, including:
- Lymphatic congestion attributable to an impairment of lymphatic flow and a delayed return of lymph to the vascular compartment 2
- Reduced adrenergic stimulation of the lymphatic system, which can result in a sluggish flow of lymph, engorgement of the lymphatic system, leakage of lymph into the pleura and interstitial spaces, and the production of chylothorax with non-immune hydrops fetalis (NIHF) 2
- Hemolytic disease of the fetus and newborn (HDFN), which can cause hydrops fetalis due to the destruction of red blood cells 3, 4
Causes of Edema in Hydrops Fetalis
The causes of edema in hydrops fetalis can be classified into immune and non-immune types. Non-immune hydrops fetalis (NIHF) is the most common type, and its causes remain undetermined in 15% of patients 2. Some possible causes of NIHF include:
- Congenital hypothyroidism, which can lead to reduced adrenergic stimulation of the lymphatic system and result in lymphatic congestion and edema 2
- Genetic disorders, which can be identified through genetic diagnostic tools such as next-generation sequencing panels or exome sequencing 5, 6
- Hemolytic disease of the fetus and newborn (HDFN), which can cause hydrops fetalis due to the destruction of red blood cells 3, 4