Non-immune hydrops fetalis (ORPHA:363999)
Non-immune hydrops fetalis (NIHF), a form of HF, is a severe fetal condition defined as the excessive accumulation of fetal fluid within the fetal extravascular compartments and body cavities, and is the end-stage of a wide variety of disorders.
Epidemiology
The prevalence of NIHF is unknown as it is difficult to obtain when many cases are not diagnosed before intrauterine death or may spontaneously resolve antenatally. Currently, NIHF constitutes up to 90% of all HF cases.
Clinical description
NIHF presents during the gestational period and manifests as pleural and pericardial effusion, ascites and subcutaneous edema in the fetus. Decreased fetal movements may be noted prior to diagnosis. Often associated are polyhydramnios, fetal tachycardia, and antenatal hemorrhage. Mothers may develop massive anasarca, hypertension, and proteinuria (mirror syndrome). Death of fetus is usually due to heart failure and hypoxia. Surviving newborns may present with respiratory distress, pale skin, severe edema (mainly of abdomen) and enlarged liver and spleen. There is sometimes a risk of death of the mother.
Etiology
NIHF is the result of an increase in interstitial fluid production or, in turn, of an obstruction of lymphatic return. Causes can be: cardiovascular (21.7%; Ebstein malformation, tetralogy of Fallot), hematologic (10.4%; Hb Bart's HF), chromosomal (13.4%; Turner syndrome) and more rarely: infectious (TORCHES-CLAP (Toxoplasma gondii; Rubella virus; Cytomegalovirus; Herpes simplex virus; Enterovirus; Syphilis; Chickenpox virus; Lyme disease; Aids; Parvovirus B19)), syndromic (Costello syndrome, Meckel syndrome, thanatophoric dysplasia) or idiopathic. Other causes can include lymphatic dysplasia, inborn errors of metabolism (transaldolase deficiency, mucopolysaccharidosis, Niemann-Pick disease type C, GM1 gangliosidosis type 1), thoracic and urinary tract malformations, cardiac /extra thoracic tumors, and congenital diaphragmatic hernia.
Diagnostic methods
Decreased fetal movements, polyhydramnios, and maternal pre-eclampsia may lead one to suspect NIHF. Diagnosis is usually by ultrasound (showing fluid accumulations) during the 2nd to 3rd trimester of gestation. Having a placenta thickness of 5 mm or more, especially with a ''ground glass'' appearance on ultrasound may also be indicative of NIHF. Maternal laboratory tests such as blood typing, antibody screens for TORCHES-CLAP, hemoglobin electrophoresis, maternal anti-SSA/SSB antibodies as well as Kleihauer-Betke and alpha-fetoprotein tests, can also aid in the diagnosis of NIHF.
Differential diagnosis
The many disorders associated with HF are differential diagnoses such as neonatal hemochromatosis, twin-to-twin transfusion syndrome, congestive heart failure, hepatitis B, hypercalcemia, hypernatremia, hypothrombinemia, hypothyroidism and diabetes (in mother). Conditions that mimic full-blown HF include obstructed or mature bowel, fetal abdominal cysts and an obstructed urinary system.
Antenatal diagnosis
Prenatal diagnosis is by ultrasound.
Genetic counseling
If NIHF is due to a genetic disorder, counseling can be offered in regards to that disease.
Management and treatment
Treatment depends on the cause. Intrauterine treatment can involve thoraco-amniotic drainage, antiarrhythmic drugs (digoxin, sotalol, propranolol) and blood transfusion when anemia is present. In many cases, especially those caused by chromosomal abnormalities, the mother may choose to terminate the pregnancy. If the fetus comes to term it should be delivered at a tertiary care center where the neonate can receive intensive resuscitation procedures in the delivery room, intensive neonatal care, high frequency ventilation, parenteral nutrition, medications for the kidneys and removal of excessive fluid from around the lungs and abdomen as necessary.
Prognosis
In most cases, prognosis is poor with a perinatal mortality rate ranging from 55-98%, but it is dependent on etiology.

                            Last update: 
                            December 2013


                            - Expert reviewer(s): 
                            Dr Carlo BELLINI