Epidemiology

It occurs in between 1 in 600 and 1 in 4,000 pregnancies.^[1] This varies according to the population risk of the conditions listed under 'Aetiology', below. For example, in Thailand the expected frequency of hydrops, from homozygous alpha thalassaemia or Bart hydrops, is 1 in 500 to 1 in 1,500 pregnancies.^[2] In the Western world, more than 90% of cases are thought to be due to non-immune causes.^[3]

Aetiology^[1]

Haematological causes

Isoimmunisation (haemolytic disease of the newborn, erythroblastosis fetalis), antibodies to red cell antigens including Rh, ABO, Duffy and Kell. 

Other haemolytic disorders - eg, glucose-6-phosphatase dehydrogenase (G6PD) deficiency, glucose phosphate isomerase (GPI) deficiency, pyruvate kinase (PK) deficiency.

Disorders of red cell production - eg, congenital dyserythropoietic anaemia, Diamond-Blackfan syndrome, lethal hereditary spherocytosis, congenital erythropoietic porphyria (Günther's disease), alpha thalassemia (Bart's haemoglobinopathy).

Fetal haemorrhage - eg, intracranial or intraventricular, hepatic laceration or subcapsular, fetomaternal haemorrhage or twin-to-twin transfusion.

Cardiac causes

• Abnormalities of left ventricular outflow - eg, aortic valvular stenosis or atresia, coarctation of the aorta, truncus arteriosus, hypoplastic left heart, endocardial fibroelastosis.
• Abnormalities of right ventricular outflow - eg, pulmonary valvular atresia or insufficiency, Ebstein's anomaly, arteriovenous malformations, haemangiomas.
• No structural anomalies - eg, superior vena cava or Inferior vena cava occlusion, intrathoracic or abdominal masses, disorders of lymphatic drainage, arrhythmias; supraventricular tachycardia or congenital heart block (66-75% occur in pregnancies complicated by maternal collagen disease; prenatal closure of the foramen ovale or ductus arteriosus, myocarditis or idiopathic arterial calcification or hypercalcaemia).

Infective causes

• Parvovirus B19 (slapped cheek syndrome) - this is increasingly recognised as being important. Use of polymerase chain reaction diagnostic testing has demonstrated that perhaps 20% of hydrops fetalis is associated with this maternal/fetal infection.^[4]
• Cytomegalovirus (CMV).
• Syphilis.
• Herpes simplex virus.
• Toxoplasmosis.
• Hepatitis B.
• Adenovirus.
• Coxsackievirus type B.
• Listeria monocytogenes.
• Ureaplasma urealyticum.

Metabolic and other causes

• Inborn errors of metabolism - eg, glycogen-storage disease type IV; lysosomal storage diseases.
• Hypothyroidism and hyperthyroidism.
• Chromosomal syndromes - eg, trisomies 10,13,15,18 or trisomy 21 (Down's syndrome); Turner syndrome (45, X).
• Numerous other autosomal-recessive genetic disorders.

Tumours

Especially sacrococcygeal teratoma.

Management^[1]

This depends on an accurate diagnosis of the cause of the hydrops. Interventions are sometimes possible and helping the parents decide whether to continue the pregnancy or opt for a termination depends upon whether the abnormalities are compatible with the continued survival of the fetus and problems likely after birth.

• Parental involvement and guidance are fundamental requirements and require full knowledge by the parents of all possible potential consequences.
• If the decision is made to continue the pregnancy, the next step is to decide whether to intervene with invasive fetal treatment.
• Consideration should also be given to the point at which preterm delivery represents less risk for the fetus than continuing the pregnancy.
• Decisions about fetal treatment are inevitably uncertain, because a concrete evidence base is not available.
• Intrauterine intraperitoneal fetal transfusion with packed RBCs has been replaced by intravascular (umbilical vein) transfusion as the treatment of choice for fetal anaemia.
• Treatment for fetal arrhythmias has included doing nothing, administering drugs and immediate delivery if maturity permits. Fetal pacing has been reported.^[5] Various drugs have also been used. Adenosine is effective with supraventricular arrhythmias^[1] and maternal oral dexamethasone has been used in cases of hydrops-related fetal heart block.^[6] A combination of amiodarone and digoxin has been used for treatment of refractory atrial flutter.^[7]
• Surgery is occasionally used to correct malformations associated with hydrops - eg, cystic adenomatoid malformations and bronchial sequestration.

Prognosis

This depends on the underlying cause, although preterm birth at less than 34 weeks of gestation and a serum albumen concentration level of less than 2 g/dL are generally features of a poor prognosis.

Spontaneous remission has been reported in hundreds of cases. Underlying causes in these cases include cardiac arrhythmias, twin-to-twin transfusion syndrome, cystic hygroma with or without Noonan's syndrome,^[8] both parvovirus B19 and CMV infections and idiopathic ascites or pleural effusions.^[9]