Refers to the abnormal accumulation of fluid in the skin, body cavities, umbilical cord, and placenta of an unborn baby. Hydrops fetalis (HF) can result from many different diseases and structural defects. HF is traditionally divided into two major categories: immune HF and nonimmune HF. Immune hydrops fetalis is caused by Rh incompatibility, and was the most common cause of HF until the advent of anti-Rh antibody treatment (RhoGAM®) during pregnancy. All other causes of HF are termed nonimmune HF. Nonimmune hydrops fetalis may be caused by chromosomal aberrations, other genetic disorders , infections, anemias, structural birth defects such as congenital heart disease, and many other conditions. Currently in the United States nonimmune HF consists of about 90% and immune HF consists of about 10% of cases.
HF occurs when a baby has a condition or birth defect that causes accumulation of excess fluid, known as edema, in the skin and other body cavities. Immune HF occurs when a mother's blood group is Rh negative (this means that she does not have the Rh protein on the surface of her blood cells) and her baby's blood group is Rh positive (the baby has the Rh protein on its blood cells). During the pregnancy a small amount of the baby's blood crosses into the mother's circulatory system. When this happens, the mother's immune system recognizes the Rh protein on the baby's blood cells as foreign and makes antibodies to the Rh protein. The antibodies can then cross back over to the baby and attack its blood cells, destroying them and causing anemia. The anemia causes heart failure, subsequent edema, and, ultimately, HF. The mother's immune response becomes greater with each subsequent pregnancy in which the baby has Rh-positive blood and thus the HF becomes worse. Administration of anti-Rh antibodies during all of an Rh-negative mother's pregnancies will prevent her from ever developing an immune response to Rh-positive blood and thus will prevent HF.
The most common causes of nonimmune HF include heart disease (congenital malformations and arrhythmia), chromosome aberrations (Turner syndrome and Down syndrome ), and anemia (alpha-thalassemia, fetomaternal transfusion, and twin-twin transfusion). Other causes include infections, metabolic disorders, and tumors. In all there are over 100 separate causes of nonimmune HF.
All disorders that cause HF do so by three common mechanisms that include heart failure, hypoproteinemia (low levels of protein in the blood stream), and vascular or lymphatic obstruction. Some disorders combine two or more of these mechanisms to cause HF. Most disorders cause some degree of heart failure. Anemia causes heart failure by increasing the work of the heart so much that it fails (this is termed high output heart failure). Isolated congenital heart disease or conditions that have congenital heart disease as a feature often will develop heart failure due to a poorly functioning heart (this is termed low output heart failure). Conditions that block the flow of blood or lymph can cause edema and HF. Examples include tumors and congenital malformations of the blood and lymphatic vessels. Conditions that lower that amount of protein in the blood can cause edema and HF by allowing fluid to easily leak out of the vessels and collect in the soft tissues and body cavities. Examples include metabolic conditions that damage the liver and prevent it from producing enough protein such as Gaucher disease and Sly disease.
Many causes of hydrops fetalis do not have a genetic etiology. Because the recurrence risk can range from 0–100% depending on the underlying cause, an accurate diagnosis is important. Infectious causes are not genetic and should not recur in subsequent pregnancies. Other causes of HF have a specific genetic profile. Immune causes are due to a difference in the antigens on the mother and baby's blood cells. This can recur in subsequent pregnancies if anti-Rh antibodies are not given to the mother. Recurrence can either be 50% or 100% depending on the father's Rh-antigen status.
If hydrops fetalis is caused by a chromosome aberration, the risk of recurrence is about 1%, as most of these conditions occur sporadically and are not inherited. Malformations causing HF, such as congenital heart disease, are most commonly inherited as multifactorial traits. This type of inheritance pattern is caused by multiple genes and environmental factors working in combination. The recurrence risk for a multifactorial trait is about 3–5% with each subsequent pregnancy.
Higher risk for recurrence occurs when a single gene condition is the cause of HF. Autosomal recessive conditions such as alpha-thalassemia, Gaucher disease, and Sly disease have a recurrence risk of 25% with each subsequent pregnancy. The X-linked recessive disorder G-6-P-deficiency has a recurrence risk of 50% with each additional male child and 0% for each additional female child.
Some dominant conditions can cause HF; these are often lethal and usually represent a new mutation in that child. In these cases the recurrence risk is about 1%. Other dominant conditions such as myotonic dystrophy and lymphedema distichiasis are variable and recurrence may be 50% with each child.
The incidence of HF in the United States is 1 in 3,000 pregnancies in all populations. In developing countries where Rh antibodies are not used, the rate can be much higher, due to a higher rate of immune HF cases. In Southeast Asia the most common cause is alpha-thalassemia. Alpha-thalassemia is so common in Southeast Asia that it remains as the most common cause of HF in the world today.
Signs and symptoms
All babies with HF have edema of the skin, soft tissues, and placenta. Often the body cavities will show fluid collections including the abdominal cavity (ascites), pleural cavity, and pericardial cavity. The back of the neck is particularly prone to fluid collections and can sometimes contain so much fluid that it appears as a large cystic mass called a cystic hygroma. Internal organs such as the liver, spleen, and heart can become enlarged with accumulated fluid. All of these signs may be seen in the newborn or before birth using ultrasonography.
Other signs of hydrops fetalis are variable and often depend on the underlying cause. Common to most causes of HF are decreased movements during the pregnancy, respiratory distress from poor lung development due to compression of the lungs by accumulated fluid, and heart failure.
HF is easily diagnosed at birth by the swollen appearance of an affected baby, but the diagnosis is often made during the pregnancy by ultrasonography. Determining the cause of the HF is more challenging, but necessary for possible treatment and recurrence risk assessment. Testing the mother for infections such as toxoplasmosis, rubella, cytomegalovirus (CMV), herpes, syphilis, and parvovirus B19 can rule out most infectious causes of HF. A high-resolution ultrasound will help determine if a baby has any major structural malformations or tumors that could cause HF. At the same time as the ultrasound a percutaneous umbilical artery blood sampling (PUBS) procedure can be done. This procedure consists of passing a needle through the mother's abdomen into the uterine cavity and then into the baby's umbilical cord to withdraw a small amount of blood. This blood is then used to test for Rh antibodies, anemia, chromosome aberrations, and other suspected conditions. These diagnostic steps will determine the cause for the HF in many cases, but sometimes the cause remains unknown.
Treatment and management
As discussed in the description section, immune HF is easily prevented by administration of anti-Rh antibodies to Rh negative pregnant women. Most nonimmune HF causes have no specific treatment other than early delivery and supportive care. HF caused by some types of anemia can be treated by a blood transfusion via a PUBS procedure. Fetal arrhythmia can often be treated by antiarrhythmia medications taken by the mother. Fetal operations are indicated for HF caused by sacrococcygeal teratomas (tumor seen in newborns) and some other structural malformations.
The prognosis is poor. A baby who is diagnosed by ultrasonography before birth has a less than 30% chance of survival. Babies who are born alive have a 50% chance of survival. The specific cause of HF influences the chances of survival with chromosome aberrations having a higher mortality rate and infectious etiologies having a lower mortality rate.
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Randall Stuart Colby, MD