Nonimmune Hydrops Fetalis
Jan 2009 – by R. Tamura, MD
Hydrops fetalis is defined as the presence of excessive fluid in two or more fetal compartments and includes: skin edema, pleural effusion, pericardial effusion, ascites and polyhydramnios. Fetal hydrops can be immune or nonimmune. Since the management of Rh disease with the use of Rho (D) immune globulin and appropriate screening has decreased the incidence of immune fetal hydops, 90% of fetal hydrops is nonimmune and encompasses all cases that are not due to red cell alloimmunization by Rh(D), Kell or other red cell antigens.
The pathogenesis of nonimmune fetal hydrops (NHF) depends on the underlying cause or disease process but is generally due to one or more of the following: perturbations in colloid osmotic pressure due to liver disease, increased capillary permeability secondary to heart failure (low as well as high output), obstruction of venous return to the heart, obstruction of lymphatic drainage of the thoracic or abdominal cavities, volume overload resulting in myocardial compromise, direct myocardial injury and possibly hypoalbuminemia.
NHF clinically presents as uterine size greater than dates due to polyhydramnios, decrease in fetal movement, fetal compromise detected on fetal testing and by prenatal ultrasound findings. Prenatal diagnosis of NFH is made when increased amounts of fluid are seen in at least two fetal compartments as outlined above. An early sign of NFH is ascites which surrounds the intraabominal organs and outlines the liver and intestines and must be deferentiated from pseudoascites. Pleural effusions may be seen in the thoracic cavity, may compress the lungs and if longstanding may cause pulmonary hypoplasia. Magnetic resonance imaging (MRI) may be useful in predicting lung volume and may assist in the determination of fetal compromise due to pulmonary hypoplasia. Pericardial effusions may be difficult to quantitate as physiologic pericardial fluid is present in most fetuses. As a general rule, pericardial fluid should be more than 3 to 4 mm and even fluid collections of up to 7 mm may be clinically insignificant. Skin edema is usually a late sign of NHF and subcutaneous or scalp edema of greater than 5 mm is pathologic. Subcutaneous fat and hair on the scalp may at times be mistaken for excessive skin edema. Polyhydramnios is defined as an amniotic fluid index of greater than 24 cm or vertical pocket of amniotic fluid of greater than 8 cm (useful when assessing fluid volume in multiple gestations or in fetuses with anomalies where pockets of free fluid are difficult to discern). Polyhydramnios is present in the majority of cases of NHF and is usually the first indication for ultrasound evaluation of the fetus. Finally, the placenta may be abnormal in appearance (intervillous edema) and in thickness (greater than 6 cm, for example in certain infections and thin or compressed with polyhydramnios).
The etiologies of NHF are myriad and while in 50% to 85% of cases can be determined antenatally, about 10% are idiopathic. Some of the common types of disease states associated with NHF:
1. Chromosome disorders: aneuploidy is found in about 10% of cases (Turner syndrome, Trisomies 21, 18, and 12 and triploidy. The prognosis is poor and NHF is thought to result from fluid accumulation due to cystic hygromas, obstruction or abnormalities in the lymphatic system and/or cardiac defects. Management depends on the specific chromosomal aneuploidy, associated fetal defects and maternal condition.
2. Metabolic storage diseases: a large group of autosomal recessive disorders that may present in the fetus with the resultant hydrops due to the accumulation of abnormal amounts of metabolites in the liver and in other abdominal viscera that cause congestion. No therapy is available at present but diagnosis is important since the recurrence risk may be as high as 25%.
3. Cardiovascular anomalies: accounts for 40% of NHF cases and are due to structural defects, arrhythmias and vascular abnormalities. Common intracardiac structural defects include atrioventricular septal defects, hypoplastic left heart, isolated ventricular and atrial septal defects. Amniocentesis/chorionic villous sampling and genetic counseling should be offered to the patient since the risk of aneuploidies and recurrence in future pregnancies is increased. Tachy- and bradyarrhythmias may result in NHF due to high (caused by excessive venous congestion)or low (caused by low cardiac output)cardiac failure. Tachyarrhythmias are treated by administration of heart rate controlling drugs to the mother or directly to the fetus. When Graves disease is the cause for the tachyarrythmia, propylthiouracil or methimazole can be given to the mother. Brachyarrhythmias are usually the result of structural cardiac defects that involve the conduction system of the heart such as the AV nodal region or maternal autoimmune disorders wherein maternal IgG antibodies transverse the placenta and damage the conduction system. Vascular abnormalities include chorioangiomas of the placenta, fetal tumors such as saccrococcygeal teratomas or neuroblastomas, hemangiomas, umbilical cord aneurysms and obstruction of the vena cava, portal vein, or femoral vessels. NHF is the result of arteriovenous shunts that cause high output failure.
4. Thoracic abnormalities: these lesions such as congenital adenomatoid malformations of the lung, cause NHF by increasing intrathoracic pressure and obstructing venous return to the heart which results in peripheral venous congestion. Lymphatic system obstruction may also occur leading to lymphedema. Pertubations in fluid exchange may result in polyhydramnios. Pleural effusions are associated with a worse prognosis when present earlier in gestation due to the greater likelihood of pulmonary hypoplasia. Pleuroamniotic shunt placement in fetuses with large pleural effusions may improve survival.
5. Anemia (e.g. alpha thalassemia): accounts for as much as 25% of NHF and is the result hemorrhage, hemolysis, defective red cell production or abnormal hemoglobin production. The pathogenesis involves high output cardiac failure. Hydrops may resolve in some cases when the anemia is corrected and therapy can be offered in the form of intrauterine transfusions when it persists.
6. Infectious disease: Is the cause of NHF in up to 8% of cases with infectious agents such as TORCH organisms and parvovirus B19, syphyllis, varicella, adenovirus and coxsackie virus. Although the mechanism for NHF is not clearly understood with all infections, with Parvovirus B 19, the viral destruction of red blood cells, hepatocytes and myocardial cells causes a transient aplastic crisis, hepatitis and myocarditis which result in decrease colloid osmatic pressure, probable hypoalbuminemia, and myocardial compromise. Sonographic signs of infection include: calcification in the brain, liver and pericardium; microcephaly, cerebral ventriculomegaly; hepatospenomegaly; and growth restriction.
7. Gastrointestinal malformations: gastrointestinal tract anomalies such as midgut volvulus result in ascites, edema and polyhydramnios.
8. Multiple gestations: monchorionic twin gestations are at risk for twin-to-twin transfusion syndrome that may result in NHF.
9. Other: skeletal and neuromuscular anomalies such as chondrodysplasia and arthrogryposis and syndromes such as Noonan, multiple pterygia, Neu-Laxova, Pena-Shokier and congenital nephrosis may be associated or present as NHF. Of note congenital nephrosis may be characterized with elevated maternal serum alphafetoprotein levels.
Evaluation for hydrops includes: detailed patient history regarding ethnicity, genetic abnormalities, metabolic diseases, recent exposure to infections; detailed ultrasound examination for structural defects; Doppler assessment for middle cerebral artery peak systolic velocity for detection of anemia. Laboratory tests include: complete blood count with RBC indices, blood type and screen, serologies for IgG for viruses, Kleihauer-Betke acid elution stain for fetomaternal hemorrhage, fetal karyotye determination and amniotic fluid assessment as indicated and umbilical blood sampling as indicated.
The management of NHF is dependent on the etiology and hydropic fetuses have a high mortality depending on gestational age at onset, presence of pleural effusions and polyhydramnios. Specific management options may include pregnancy termination, therapeutic interventions when appropriate and supportive care as needed. Antenatal surveillance includes nonstress testing, biophysical profile, and Doppler studies as needed. Delivery should occur at a tertiary center with antenatal and intrapartum coordination by obstetric, neonatal and pediatric subspecialty personnel.
Specific points to consider:
- Hydops fetalis is defined as fluid in at least two body compartments and specific findings are: skin/scalp edema, pleural effusion, pericardial effusion, ascites and polyhydramnios.
- Etiologies for NHF are heterogeneous and detailed above.
- Genetic evaluation and fetal karyotype are useful.
- Ascites is generally an early sign and skin/scalp edema a late sign of NHF.
- Multiple pathogeneses may explain NHF with a single etiology for example Parvoviris B 19.
- Management and therapy are determined by the etiology.
- Careful maternal surveillance is recommended due to increased risk for pre-eclampsia, mirror syndrome, labor dystocia and postpartum hemorrhage.
- Antenatal monitoring and coordination of care between obstetric, neonatal and pediatric specialist is recommended.
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- Callen, PW. (Ed) Ultrasonography in Obstetrics and Gynecology 4th Edition Saunders, Philadelphia 2000. Pages 489-516.
- Lockwood, JL and Julien, S. Nonimmune hydrops fetalis. UpToDate. Pages 1 -16.