eMedicine Specialties > Radiology > Obstetrics/Gynecology

Hydrops Fetalis

Author: Durre Sabih, MBBS, MSc, Visiting Faculty, Department of Nuclear Medicine, Pakistan Institute Applied Sciences and Nishtar Medical College; Director, Multan Institute of Nuclear Medicine and Radiotherapy
Coauthor(s): Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Zahida Sabih, MBBS, MSc,
Contributor Information and Disclosures

Updated: Jul 16, 2008

Introduction

Background

The hallmark of the disease is the abnormal accumulation of fluid in body cavities (pleural, pericardial, peritoneal) and soft tissues with a wall thickness of greater than 5 mm.^1,2,3,4,5 In addition, hydrops fetalis is associated with polyhydramnios and a thickened placenta (>6 cm) in as many as 30-75% of patients. Many affected fetuses also have hepatosplenomegaly.

Related eMedicine topics:

Thalassemia

Thalassemia, Alpha

Pathophysiology

The basic problem in hydrops fetalis is an imbalance in fluid homeostasis, with more fluid accumulating than can be resorbed. This imbalance can result from 2 broad categories of pathologies, namely, those of an immune origin and those of a nonimmune origin.

Immune-related hydrops fetalis (IHF) results from alloimmune hemolytic disease or Rh isoimmunization. The mother is sensitized and has antibodies against fetal blood cells, causing hemolysis in the fetus when circulated maternal antibodies (immunoglobulin G [IgG]) cross the placenta to reach fetal circulation. Most cases occur because of antibodies to D-positive Rh antigen, although some cases can occur because of antibodies to C-positive and E-positive Rh antigens. Rare blood group antibodies, such as the Kell (K) system and the Duffy (Fy) system, can also cause hydrops.

Nonimmune-related hydrops fetalis (NIHF) can result from primary myocardial failure, high-output cardiac failure, decreased colloid oncotic plasma pressure, increased capillary permeability, and obstruction of venous or lymphatic flow.6 Fetal cardiac anomalies are the most common cause of NIHF. Chromosomal anomalies are the second most common cause.^{1,2,3,4,5,7,8,9}

In addition to the causes of IHF, several conditions can cause NIHF. The most common cause of NIHF is a cardiovascular abnormality, followed by chromosomal abnormalities; however, the number of nonimmune-related causes that can and have resulted in hydrops fetalis is extensive and includes the following partial list:

• Fetal structural abnormalities
  • Cranial – Cerebral tumor, intracranial hemorrhage, and vein of Galen aneurysm
  • Cardiovascular – Arrhythmias (tachyarrhythmias, bradyarrhythmias), cardiac tumors (rhabdomyoma, hemangioma, hamartoma), cardiomyopathy, Ebstein anomaly, endocardial fibroelastosis, high-output failure (fetal angiomas, sacrococcygeal teratomas, vein of Galen aneurysm, twin-twin transfusion syndrome, twin-reversed arterial perfusion [TRAP] syndrome), myocardial infarction, myocarditis, premature closure of the foramen ovale, right or left heart hypoplasia,¹⁰ and single ventricle
  • Neck or thoracic masses – Congenital cystic adenomatoid malformation, cystic hygromas, diaphragmatic hernia, hydrothorax/chylothorax, mediastinal teratoma, pulmonary sequestration, and thoracic tumors
  • Gastrointestinal-tract abnormalities – Bowel atresias and volvulus, cirrhosis, hemochromatosis, hepatic tumors (hemangioendotheliomas), renal vein thrombosis, and urinary tract obstructions (lower or upper)
  • Chromosomal anomalies – Trisomy 21, trisomy 18, trisomy 13 triploidy, and XO syndrome (Turner syndrome)
• Anemias – α Thalassemia, congenital leukemia, fetomaternal hemorrhage, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, human parvovirus B19 (B19V) infection,¹¹ twin-twin transfusion syndrome (donor), and fetal closed-space hemorrhage
• Infection – Coxsackie virus, cytomegalovirus (CMV),¹² hepatitis A virus, leptospirosis, listerosis, B19V, rubella virus, syphilis, toxoplasmosis, and varicella virus
• Genetic disorders
  • Metabolic disorders – Gaucher disease,¹³ Hurler disease, hypothyroidism, hyperthyroidism, mucolipidosis, and mucopolysaccharidosis
  • Skeletal dysplasias – Achondrogenesis, achondroplasia, asphyxiating thoracic dystrophy, lethal osteoporosis, Noonan syndrome,¹⁴ short rib–polydactyly syndrome, and thanatophoric dysplasia
  • Fetal hypokinesis – Arthrogryposis, congenital myotonic dystrophy, Neu-Laxova syndrome, and Pena Shokeir syndrome
• Idiopathic disorders – Recurrent isolated hydrops
• Maternal disorders – Graves disease,¹⁵ severe anemia, severe diabetes mellitus, and severe hypoproteinemia
• Placental disorders – Chorioangioma, chorionic vein thrombosis, cord torsion (knot or tumor), umbilical artery aneurysm, and venous thrombosis

Thus, in summary, the conditions causing hydrops fetalis are diverse, but common mechanisms causing the fluid imbalance include cardiac failure resulting from myocardial disease, complex anatomic cardiac defects, or abnormal intracardiac or extracardiac shunts (high-output failure); abnormal blood composition with severe anemia or abnormal red cell physiology or counts; aberrations of lymphatic drainage; and masses in the abdomen or chest that hamper venous return.

Related eMedicine topics:

Hemolytic Disease of Newborn

Rh Incompatibility

Frequency

United States

Widely varying figures have been quoted, but 1 case per 600-4000 pregnancies is the estimated frequency.

International

Hydrops fetalis is more common in undeveloped countries than in industrialized countries. Figures from Thailand suggest an estimated incidence of 1 case per 500-1500 pregnancies because of an association with homozygous a thalassemia. The incidence of IHF has decreased with the development of better prophylaxis, and it is not considered a major problem in developed countries. However, in undeveloped countries, IHF still occurs in a small and declining number of cases.

Mortality/Morbidity

Mortality and mortality figures vary, but in general, the mortality rate is high.^{7,9,16,17,18,19,20}

• Treatment is reported to be successful in 10-40% of patients, depending on the cause of the disease and the sophistication of the available diagnostic and therapeutic options.
• Many cases of NIHF occur as a result of complex chromosomal or anatomic anomalies that worsen the prognosis.
• Other causes of poor prognosis include pulmonary hypoplasia caused by pleural and peritoneal fluid accumulation and an early onset of labor because of distention of the uterus caused by polyhydramnios and/or fetal body enlargement secondary to edema.

Race

Certain racial predilections exist for pathologic conditions that can lead to hydrops fetalis, such as the following:

• Predisposing factors include the severity of hemolysis in African populations and the variations in the a -chain structure in Asian and Mediterranean populations.
• In the Far East, a thalassemia is a major cause of NIHF. The condition is uniformly fatal and associated with a significant risk of maternal morbidity. The a thalassemia gene is found in 20-30% of the population in Southeast Asia.

Sex

X-linked chromosomal abnormalities are found in many fetuses with hydrops fetalis.

Age

Hydrops fetalis is exclusively a fetal condition. The earlier the diagnosis, the poorer the prognosis.

Anatomy

Hydrops fetalis is often diagnosed with routine sonograms in which the typical features are depicted. In other fetuses, a clinical suspicion of hydrops fetalis may exist because of a previous family history of a similarly affected baby or because ultrasonography is performed to evaluate polyhydramnios.²¹

Related Medscape topics:
Resource Center Neonatal Medicine
Specialty Site Radiology

Presentation

The conditions that cause hydrops fetalis are diverse; however, common mechanisms that cause the fluid imbalance can be identified. These causes include the following: (1) cardiac failure resulting from myocardial disease, arrhythmia, complex anatomic cardiac defects, or abnormal intracardiac or extracardiac shunts (high-output failure); (2) abnormal blood composition with severe anemia or abnormal red cell physiology or counts; (3) aberrations of lymphatic drainage; and (4) masses in the abdomen or chest that hamper venous return.

Sonograms depict anasarca (edema) and fluid collection in serous cavities, such as the pleural, pericardial, and peritoneal spaces. Polyhydramnios and an edematous thick placenta are often present.

Ascites may be small and may be just enough to form a film over the abdominal contents, or ascites may be extensive, with the contents of the abdomen, liver, and gut floating in the fluid (see Images 6-7 and 10). The ascites may extend into the scrotum to form a hydrocele.

Pleural effusions can be unilateral or bilateral (see Images below and Images 1-2 in Multimedia). Unilateral effusions indicate the presence of a process such as chylothorax. Large effusions can compress the mediastinal vessels, cause upper body edema, and interfere with esophageal functioning to cause secondary polyhydramnios.

Edema may be localized to one part of the body, or it may be generalized. Edema is seen most easily over the skull, over which a halo is formed (see Images 9 and 11). Edema may be seen in other parts of the body as well.

Placental thickening is a late occurrence, and when affected, the placenta is thicker than 4-5 cm over its entire extent.

The distribution and size of fluid accumulations may indicate the pathology. In IHF, ascites appears first, with edema and pleural collections appearing late.

The findings of specific organ pathology, for example, skeletal abnormalities or cardiac tumors, may indicate a specific cause in hydrops fetalis.

Preferred Examination

Immune-related hydrops fetalis

A history of a previously affected fetus in the family is of critical importance. Once IHF is suspected, maternal blood typing and antibody screening against Rh and a determination of minor blood types (eg, Kell, Duffy, MNSs) should be performed. In mothers in whom IgM is detected, no further workup is needed, but if IgG is detected, titers of Rh-positive antibodies in the maternal blood need to be determined. A titer that is greater than 1:16 is significant. If the titer results are significant, amniocentesis should be performed to assess the severity of fetal hemolysis and anemia.

Fetal anemia can be monitored either by direct sampling of the fetal blood by means of cordocentesis or by determining the delta optical density (OD) by using a wavelength of 450 μm in the amniotic fluid. This measurement gives an estimate of bilirubin levels during the third trimester. Delta OD results are plotted on the Liley 3-zone chart. The closer the results are to the third zone, the greater is the risk of IHF. A fetal hematocrit determination is the final test to be performed, and fetal transfusion should be considered in fetuses with a hematocrit level that is less than 40%.

Nonimmune-related hydrops fetalis

NIHF can result from a large number of causes, including chromosomal abnormalities, cardiac failure, tumors, and twin-twin transfusion syndrome. Extensive clinical workup is required to attempt to identify the specific etiology. In patients in whom NIHF is suspected, the search for a cause starts with a maternal evaluation. Initial clinical history taking should be directed toward the presence of hereditary or metabolic diseases, diabetes, infections, anemias, and the use of all medications.

Initial investigations include an indirect Coombs test to exclude immune causes, followed by the determination of routine blood counts and indices to exclude thalassemias; maternal blood chemistry testing for G-6-PD deficiency; Betke-Kleihauer testing for fetal-maternal transfusion; and screening for toxoplasmosis, other infections, rubella, CMV, and herpes simplex (TORCH) infection during intrauterine pregnancy.

Amniocentesis is needed to perform fetal karyotyping, amniotic fluid culturing, testing for CMV infections, assessment of α -fetoprotein (AFP) levels, testing for thalassemia, and determination of the lecithin-sphingomyelin (L/S) ratio. Karyotyping can also be performed with tissue obtained by chorionic villous sampling (CVS) or with fluid obtained from one of the fetal cavities. A chromosome count and karyotype can be obtained rapidly by using the fluorescent in situ hybridization (FISH) technique. The FISH technique can also help in the detection of specific deletions and chromosomal rearrangements, and the results are often available within 24-48 hours.

Fetal blood tests should include hemoglobin chain analysis for thalassemia and fetal serum albumin levels.

Initially, ultrasonographic findings suggest hydrops fetalis in most cases, and this modality can also be used for follow-up imaging to observe the progress of the condition if the pregnancy is continued.

Limitations of Techniques

Ultrasonographic findings are often reliably helpful in the diagnosis of the disease causing fetal hydrops, especially in fetuses in whom a chest mass or cardiac disease is present. However, in many fetuses, an exact etiology is not forthcoming after an ultrasonographic examination.

Blood tests performed in the mother can provide information regarding Rh and other immune causes of hydrops fetalis, as well as evidence of infection and metabolic diseases. However, invasive fetal testing must eventually be performed by means of amniocentesis or cordocentesis. Both methods pose a risk of fetal death.

Differential Diagnoses

Cystic Hygroma
Encephalocele
Polyhydramnios

Other Problems to Be Considered

Caput succedaneum
Crocodile skin
Fetal cystic hygromas
Isolated pericardial effusion
Isolated ascites
Idiopathic polyhydramnios
Macrosomia
Meconium ascites
Urinary ascites

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