The main causes of nonimmune hydrops are enumerated below. However no definite cause of hydrops can be found in about 20% cases of nonimmune hydrops despite extensive investigations (so called idiopathic hydrops).

1. Hematologic disorders:
   • Homozygous α thalassemia
   • Hemolytic disorders (glucose-6-phosphatase deficiency)
   • Twin to twin tranfusion: chronic fetofetal transfusion of the twins
   • chronic fetomaternal hemorrhage/transfusion where the fetus may bleed into maternal circulation if the fetomaternal circulation becomes disrupted. This is sometimes caused by overt trauma but the exact cause cannot be identified in most cases. This condition can be proved by Kleihauer Betke test which detects fetal erythrocytes (containing the fetal variant of hemoglobin HbF) in maternal blood smear.
2. Cardiovascular:
   • Some congenital structural heart defects, for example hypoplastic left heart syndrome, Ebstein anomaly, premature closure of the foramen ovale
   • Vascular malformations with AV shunting in fetus or placenta (large chorangioma)
   • Nonstructural anomalies
   • Fetal supraventricular tachycardias  —  relatively common, the prognosis is excellent
   • Congenital AV block  —  this condition is found in pregnancies complicated by maternal systemic lupus erythematosus. The conduction system in the fetal heart is damaged by maternal antinuclear antibodies which cross the placental barrier.
   • Bradycardia associated with complex structural heart defects — asplenia/polysplenia syndromes, AV septal defect etc. The prognosis is very poor.
   • Acardius, see the chapter Acardius
   • Cardiac tumors (rhabdomyoma)
3. Intrauterine infections:
   • human parvovirus B19 may be the cause of as much as one third of all cases of hydrops fetalis. This highly contagious virus is the etiological agens of the fifth disease (erythema infectiosum) and severe aplastic anemia in patients with congenital hemolytic diseases. The virus directly attacks red cells precursors. The virus is transmitted tranplacentally and causes severe fetal anemia, hydrops or miscarriage. Itranuclear eosinophilic inclusions can be found in the nuclear red cells in fetal tissues. PCR is used to confirm the diagnosis. The virus is not teratogenic.
   • congenital syphilis
   • TORCH infections
4. Storage disorders: There is a wide range of rare metabolic conditions which have been described with fetal hydrops (Gaucher disease will be mentioned as the only example).
5. Chromosomal syndromes:
   • Turner syndrome, see the chapter Turner syndrome
   • Trisomies
6. Abdominal and thoracic tumors and masses:
   • congenital cystic adenomatoid malformation of lungs, see CCAM case study
   • tracheal/laryngeal atresia
   • diaphragmatic hernia
   • polycystic kidneys
   • fetal neoplasms (neuroblastoma)
7. Genetic syndromes:
   • chondrodysplasias
   • lethal multiple pterygium syndrome
   • tuberous sclerosis
8. Miscellaneous:
   • congenital nephrotic syndrome
   • GIT atresia and duplication
   • lower urinary tract obstruction