In utero, signs of hydrops fetalis include larger than normal uterine size for dates and decreased fetal movement. Although many times there are no signs or symptoms and a fetus is discovered to have hydrops fetalis during a routine ultrasound exam.

Maternal conditions such as pre-eclampsia, preterm labor, birth trauma, retained placenta and post-partum hemorrhage have been associated with an increased incidence of hydrops fetalis [7].

• Splenomegaly

  […] persistence of Langhans layer Still born or macerated baby Sonography to detect scalp, skin edema Failure of heart (High output cardiac failure) Effusion and echogenic bowel on USG Tissue anoxaemia Anemia, Acidosis Liver damage due to anoxia Icterus Splenomegaly [medicowesome.com]

  Compound heterozygosity for α(0)-thalassemia (α(0)-thal) and Hb CS (- -(SEA)/α(CS)α) results in Hb H/Hb CS disease, which is generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. [ncbi.nlm.nih.gov]

  The baby had generalized edema and hepato-splenomegaly of 3 and 4 cm under costal margins, respectively. [nature.com]

• Pallor

  […] in neonates, resulting in a 'puffy', plethoric or hydropic appearance that may be due to various etiologies Clinical Ascites, edema, ↓ protein or chronic intrauterine anemia, hepatosplenomegaly, cardiomegaly, extramedullary hematopoiesis, jaundice, pallor [medical-dictionary.thefreedictionary.com]

  Mild forms may cause: Liver swelling Change in skin color (pallor) More severe forms may cause: Breathing problems Bruising or purplish bruise-like spots on the skin Heart failure Severe anemia Severe jaundice Total body swelling An ultrasound done during [nlm.nih.gov]

  Mild forms may cause: Liver swelling Change in skin color (pallor) More severe forms may cause: Breathing problems Bruising or purplish bruise-like spots on the skin Heart failure Severe anemia Severe jaundice Total body swelling Exams and Tests An ultrasound [ufhealth.org]

• Pathologist

  Author Affiliations *Pathologist, Boston Hospital for Women (Lying-in Division); assistant clinical professor, Department of Pathology, Harvard Medical School. [nejm.org]

  Knisely AS: The pathologist and the hydropic placenta, fetus, or infant. Semin Perinatol 19:525–531, 1995. CrossRef PubMed Google Scholar 22. [link.springer.com]

  […] before visiting doctor every thing was perfect.My husband and I were very joyful,but after 3d ultrasound all our sweet dreams were died,I also was going to die.doctor told us the pregnancy had to be finished.After c-section we delivered the fetus to pathologist [healthypages.com]

• Multiple Congenital Anomalies

  Autoimmune Lymphoproliferative Syndrome Type IV, Schimmelpenning– Feuerstein-Mims Syndrome, Noonan Syndrome AD 100 15 of 15 PIEZO1 Dehydrated Hereditary Stomatocytosis, Hereditary Lymphedema AD,AR 99.98 107 of 107 PIGA Multiple Congenital Anomalies- [igenomix.es]

• Pleural Effusion

  effusion - guidance (IPG190) Source: National Institute for Health and Care Excellence - NICE - 27 September 2006 Evidence-based recommendations on insertion of pleuro–amniotic shunt for treating fetal pleural effusion during pregnancy Read Summary - [evidence.nhs.uk]

  Pleural effusions – In the chest, pleural effusions may be seen outlining the lungs, just inside the chest wall. [symptoma.com]

  The aim of this study was to clarify the prognostic factors of HF with pleural effusion. [ncbi.nlm.nih.gov]

• Diarrhea

  Some patients have a rash, diarrhea and vomiting. In between attacks the patient are asymptomatic. Genetics HIDS is caused by a mutation in the MVK-gene. This leads to a deficiency of the enzyme mevalonate kinase. It is a recessive disorder. [jessazh.be]

  In addition to chills and fever, patients may have abdominal pain, vomiting or diarrhea, headache, and arthralgias. [merckmanuals.com]

  […] degrees C Lymphadenopathy (90%) at the neck at fever episodes Abdominal pain as by Acute abdomen Splenomegaly (large spleen at 50%) Polyartralgi (joint pain) (80%) during fever episodes Eczema: macular with transition to papules, urticaria, EN or petechia Diarrhea [bindevevssykdommer.no]

  Clinical description The disease usually begins in the first year of life and consists of recurrent attacks of fever along with abdominal pain, vomiting and diarrhea. [orpha.net]

• Abdominal Distension

  On admission to the nursery he was pale, jaundiced, and oedematous, with abdominal distension and hepatosplenomegaly. His birthweight was 2032 g. Initial investigations again showed features of haemolytic anaemia (table 1). [fn.bmj.com]

  Note edema of face and abdominal distension (A). The thoracic cavity is filled by the pericardial sac distended by effusion and cardiomegaly; there is massive hepatomegaly (B). Pictures courtesy of Prof H.A. Heggtveit. [bloodjournal.org]

• Hepatomegaly

  Author information 1 Department of Pathology, Chulalongkorn University, Bangkok, Thailand. [email protected] Abstract Massive hepatomegaly is a common finding in hydrops fetalis (HF) arising from hemoglobinopathies. [ncbi.nlm.nih.gov]

  Langhans layer Still born or macerated baby Sonography to detect scalp, skin edema Failure of heart (High output cardiac failure) Effusion and echogenic bowel on USG Tissue anoxaemia Anemia, Acidosis Liver damage due to anoxia Icterus Splenomegaly and hepatomegaly [medicowesome.com]

  Both hepatomegaly and jaundice are typically transient but may take weeks to months to resolve. [frontiersin.org]

  […] of fluid +/- edema involving at least two fetal components, which may manifest as: fetal pleural effusion fetal pericardial effusion fetal ascites generalized body edema: fetal anasarca/nuchal edema/cystic hygroma placental enlargement polyhydramnios hepatomegaly [radiopaedia.org]

• Heart Disease

  Previous studies have found an association of heterozygous missense alterations in GATA5 with a broad variety of heart diseases; however, the clinical relevance of the identified susceptibility variants has remained unclear. [ncbi.nlm.nih.gov]

  Chapter 58 Hydrops Fetalis First published: 20 February 2018 Summary Fetal echocardiography has progressed to be able to diagnose many forms of congenital heart disease and to assess the prognosis of cardiac lesions based on their anatomy and presentation [onlinelibrary.wiley.com]

  See Hemolytic disease of the newborn. [medical-dictionary.thefreedictionary.com]

• Fetal Disorder

  Numerous disorders including fetal disorders, maternal diseases (e.g., severe maternal anemia, diabetes and maternal indomethacin use) and placental/cord abnormalities have been associated with NIHF. [jpnim.com]

• Skin Edema

  Skin edema – The presence of skin edema is a late sign of fetal hydrops. Pathologic skin edema appears as subcutaneous tissue thickness on the chest or scalp greater than 5mm. [symptoma.com]

  Severe cases frequently had skin edema and high rate of asphyxia at birth and difficult resuscitation. Timely intrauterine interventions were helpful for successful resuscitation. [ncbi.nlm.nih.gov]

  Rh antibody on serology Oedema Polyhydramnios Placental tissue is hyperplastic Swelling of villi with undue persistence of Langhans layer Still born or macerated baby Sonography to detect scalp, skin edema Failure of heart (High output cardiac failure [medicowesome.com]

  These include ascites, pleural effusions, pericardial effusion, and generalized skin edema (defined as skin thickness >5 mm). [emedicine.medscape.com]

• Skin Rash

  Hyper IgD Syndrome (HIDS) presents with longer episodes of flare-ups than CAPS, and a different rash. Once the attack is over, patients are free of symptoms, but it may take awhile for the joint pain and skin rash to fully disappear. [autoinflammatory.org]

  Signs include cervical lymphadenopathy, splenomegaly, arthritis, skin lesions (maculopapular rash, petechiae, or purpura), and orogenital aphthous ulcers Prof Ariyanto Harsono MD PhD SpA(K) 8 9.  Cutaneous signs of HIDS o Skin rash affects up to 80% [slideshare.net]

  It is considered an auto-inflammatory disease, with recurrent episodic or chronic unexplained inflammation, characterized by periodic episodes of fever, and other symptoms such as joint pain, swollen lymph nodes, skin rash, headaches, and abdominal pain [rarediseases.info.nih.gov]

Prenatal diagnosis is established by ultrasound examination. The following conditions, which are indicative of hydrops fetalis, may be seen on ultrasound:

• Ascites – Fluid in the intra-abdominal organs (liver, bladder). 
• Pleural effusions – In the chest, pleural effusions may be seen outlining the lungs, just inside the chest wall. Long standing effusions developing prior to 20 weeks of gestation may hamper the grown and development of the lung tissue, which can lead to pulmonary hypoplasia. 
• Pericardial effusion – Pericardial effusions can be measured using M-mode ultrasonography. 
• Skin edema – The presence of skin edema is a late sign of fetal hydrops. Pathologic skin edema appears as subcutaneous tissue thickness on the chest or scalp greater than 5mm. 
• Polyhydraminos – Polyhydraminos is defined as amniotic fluid index greater than 24 cm or a maximum vertical pocket greater than 8 cm. It is present in 40% to 75% of pregnancies complicated by hydrops fetalis [8]. 
• Placentomegaly – The placenta may be larger than normal due to intravillous edema. A placental thickness of greater than 5 cm is considered abnormal and should be further evaluated [9] [10].

• Human Parvovirus B19

  Unitermos: Parvovírus humano B19, Diagnóstico pré-natal, Hidropsia fetal, Ultra-som Introduction Human parvovirus B19 (HPV B19) is a small, nonenveloped desoxyribonucleic acid (DNA) virus that exclusively infects humans (4). [scielo.br]

  Discussion Parvovirus B19 Parvovirus B19 is a small, single-stranded, nonenveloped DNA virus of the Parvoviridae family. It is the only strain known to be pathogenic in humans. [jabfm.org]

  Identification of human parvovirus B19 infection in idiopathic nonimmune hydrops fetalis. Am J Obstet Gynecol 1996;174:37-42. Xu J, Raff TC, Muallem NS, Neubert AG. Hydrops fetalis secondary to parvovirus B19 infections. [iame.com]

  Human parvovirus B19 is a single-stranded DNA virus that usually infects rapidly dividing cell lines, such as erythroid progenitor cells. [emedicine.com]

• Pleural Effusion

  effusion - guidance (IPG190) Source: National Institute for Health and Care Excellence - NICE - 27 September 2006 Evidence-based recommendations on insertion of pleuro–amniotic shunt for treating fetal pleural effusion during pregnancy Read Summary - [evidence.nhs.uk]

  Pleural effusions – In the chest, pleural effusions may be seen outlining the lungs, just inside the chest wall. [symptoma.com]

  The aim of this study was to clarify the prognostic factors of HF with pleural effusion. [ncbi.nlm.nih.gov]

• Leukocytosis

  Abstract Transient myeloproliferative disorder is a self limiting disorder characterized by leukocytosis with the presence of megakaryoblasts in the peripheral blood and bone marrow, anemia, thrombocytopenia, and organomegaly. [ncbi.nlm.nih.gov]

  What is the underlying diagnosis for this infant’s chylothoraces, hypoproteinaemia, and leukocytosis? 1. Immune hydrops 2. Trisomy syndrome 3. Congenital infection 4. Congenital lymphoma 5. Inborn error of protein metabolism Figure 1. [hkmj.org]

  Nonspecific abnormalities include leukocytosis and elevated acute-phase reactants during fever; elevated urinary mevalonic acid during attacks helps confirm the diagnosis. Gene testing is available but is negative in 25% of patients. [merckmanuals.com]

  Lowering reaction (SR), CRP, leukocytosis, ferritin These are classification criteria used in research and not necessarily to make the diagnosis in clinical practice. [bindevevssykdommer.no]

Management consists of a search of the etiology of hydrops since treatment of the underlying condition may allow treatment and prevent recurrence with future pregnancies.

Evaluation consists of:

• Obtaining a patient and family history to evaluate for heritable disorders associated with hydrops such as thalassemia, metabolic disorders and genetic syndrome; inquiry about recent exposure to infectious agents – parvovirus B 19 is the most common etiology of hydrops, accounting for almost 15% of cases. 
• An ultrasound exam to look for major fetal structural abnormalities should be performed. 
• Laboratory tests can also be performed on the mother: complete blood count, serology to evaluate for viral infections such as CMV, parvovirus, toxoplasmosis. 
• Laboratory tests can be performed on the fetus: fetal karyotype and genetic microarray molecular testing can be done using amniocenteses or fetal blood sampling. 

Treatment depends on the etiology and symptoms at birth. For example, oxygen or mechanical breathing support may be provided at birth to a fetus with difficult breathing, removal of excessive fluid from the pleural space and abdomen may be performed at the time of birth, medications may be administered to help the fetus’s kidneys remove the excess fluid.

Hydrops is a poor prognostic indicator for perinatal survival. Prognosis depends upon the etiology, the gestational age at onset and whether pleural effusions are present. In general, the earlier hydrops occurs, the worse the prognosis. Maternal-fetal medicine specialists and neonatologist should be involved in the management of any pregnancy with a diagnosis of hydrops fetalis.

Careful surveillance of maternal status is key because of increased risk of preeclampsia, dystocia during labor and postpartum hemorrhage. Delivery should be performed at a medical center with a neonatal intensive care unit.

The etiology remains unclear. Some of the known causes of hydrops fetalis include:

• Hematologic problems such as fetal hemorrhage
• Disorders of red blood cell production
• Genetic hemolytic disorders
• Congenital infections such as syphilis, cytomegalovirus (CMV), parvovirus
• Genetic abnormalities or syndromes
• Tumors such as diaphragmatic hernia, sacrococcygeal teratomas, polycystic kidneys
• Cardiovascular abnormalities attributed to structural problems of the heart, arrhythmias, vessel abnormalities

The incidence of non-immune hydrops fetalis ranges from 1/1500 to 1/3800 births [1] [2] [3] [4]. Non-immune hydrops fetalis is associated with an overall perinatal mortality rate of 50 to 98%.

In the fetus, cellular mechanisms including the presence of membrane proteins such as aquaporin and the extracellular glycocalyx within the membrane serve to regulate fluid movement. A dysregulation of these mechanisms and/or proteins results in abnormal fluid movement causing hydrops fetalis.

The abnormal fluid movement can be a result of: obstructed lymph drainage in the thoracic and abdominal cavities, increased capillary permeability resulting in infection, increased venous pressure due to heart failure or obstructed venous blood return to the heart, reduction in osmotic pressure resulting in liver disease, nephropathy or non-immune mediated anemia, and/or abnormal levels of aldosterone and atrial natriuretic factor [5] [6].

There is no guideline for the prevention of hydrops fetalis.

Hydrops fetalis refers to the abnormal accumulation of fluid collections in at least two compartments, in the fetus: ascites (abdominal cavity), pleural effusion (lining of lungs), pericardial effusion (around the heart), skin edema (anasarca), polyhydraminos (excess amniotic fluid).

There are two types of hydrops fetalis: immune and non-immune. Immune hydrops (erythroblastosis fetalis) occurs when the maternal immune system attacks the fetal blood cells. Immune hydrops fetalis is no longer present in many developed countries due to the use of RhoGAM iummoglobulin (Ig) prophylaxis given in at-risk mothers.

Non-immune hydrops fetalis results when a disease or other complication interferes with the fetus’s ability to regulate fluid. 

Hydrops fetalis occurs when large amounts of fluid builds up in a baby’s tissues, while it is inside the mother. The fluid results in swelling and other problems in the fetus. There are two kinds of hydrops fetalis: immune and non-immune. Immune hydrops fetalis occurs when cells in the mother’s immune system attacks the baby’s cells. This type of hydrops fetalis is no longer common in developed countries due to the invention of Rhogam. Non-immune hydrops fetalis occurs for unknown reasons, possibly due to an infection or other fetal abnormality.

What are the symptoms?

Often times, there are no symptoms and a fetus is discovered to have hydrops fetalis when a routine ultrasound is performed. Other times, the mother starts to experience problems during her pregnancy such as preeclampsia. Hydrops fetalis may be diagnosed after the birth of the baby, if the baby has difficulty breathing or other problems at the time of birth.

How is it diagnosed?

Diagnosis can be made during pregnancy or after the baby is born through: ultrasound, fetal blood sampling or amniocentesis.

What is the treatment?

Hydrops fetalis can be life-threatening. The treatment depends on the cause of the fluid build-up. For example, oxygen or mechanical breathing support may be provided at birth to a fetus with difficult breathing, removal of excessive fluid from the pleural space and abdomen may be performed at the time of birth, medications may be administered to help the fetus’s kidneys remove the excess fluid.

Maternal-fetal medicine specialists and neonatologist should be involved in the management of any pregnancy with a diagnosis of hydrops fetalis. Delivery should be performed at a medical center with a neonatal intensive care unit.

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2. Carlson DE, Platt LD, Medearis AL, Horenstein J. Prognostic indicators of the resolution of nonimmune hydrops fetalis and survival of the fetus. Am J Obstet Gynecol. 1990;163(6 Pt 1):1785.
3. Castillo RA, Devoe LD, Hadi HA, Martin S, Geist D. Nonimmune hydrops fetalis: clinical experience and factors related to a poor outcome. Am J Obstet Gynecol. 1986;155(4):812.
4. Callen, P. Ultrasonography in Obstetrics and Gynecology, 4th ed, WB Saunders, Philadelphia 2000.
5. Ville Y, Proudler A, Abbas A, Nicolaides K. Atrial natriuretic factor concentration in normal, growth-retarded, anemic, and hydropic fetuses. Am J Obstet Gynecol. 1994;171(3):777.
6. Ville Y, Proudler A, Kuhn P, Nicolaides KH. Aldosterone concentration in normal, growth-retarded, anemic, and hydropic fetuses. Obstet Gynecol. 1994;84(4):511.
7. Stepan H, Faber R. Elevated sFlt1 level and preeclampsia with parvovirus-induced hydrops. N Engl J Med. 2006;354(17):1857.
8. Romero, R, Pilu G, Jeanty P, Ghidini A, Hobbins J. Prenatal Diagnosis of Congenital Anomalies. Appleton and Lange, Norwalk, CT 1988.
9. Arcasoy MO, Gallagher PG. Hematologic disorders and nonimmune hydrops fetalis. Semin Perinatol. 1995;19(6):502.
10. Chitkara U, Wilkins I, Lynch L, Mehalek K, Berkowitz RL. The role of sonography in assessing severity of fetal anemia in Rh- and Kell-isoimmunized pregnancies. Obstet Gynecol. 1988;71(3 Pt 1):393.