Back To Search Results

Nonimmune Hydrops Fetalis

Editor: Heba Mahdy Updated: 8/11/2024 11:34:48 AM

Introduction

Hydrops fetalis is characterized by abnormal interstitial fluid accumulation in fetal body compartments, such as the peritoneal cavity, pleura, and pericardium, or generalized skin edema. An alternative definition describes it as fluid accumulation in 2 fetal anatomical areas or as effusion in 1 site accompanied by anasarca.[1] Hydrops fetalis is typically classified into immune and nonimmune (NIHF) forms based on the underlying etiology. Immune hydrops fetalis, caused by red blood cell alloimmunization, has become rare due to the introduction of anti-D immune globulin prophylaxis.[2] In contrast, NIHF, which now accounts for 85% to 95% of hydrops cases, results from various conditions that disrupt fluid movement between vascular and interstitial compartments.[3][4]

Traditionally, according to the Society for Maternal-Fetal Medicine, hydrops fetalis is diagnosed during a prenatal ultrasound when 2 or more abnormal fluid collections are visualized, such as ascites, pericardial effusion, pleural effusion, or skin edema. However, some experts have adopted a revised definition, diagnosing hydrops fetalis with the presence of a single fetal fluid collection, such as increased nuchal translucency thickness (≥3.5 mm) or cystic hygroma.[5] With the widespread use of routine prenatal ultrasounds to assess fetal anatomy, hydrops fetalis is often identified early in pregnancy. Most NIHF cases detected early in pregnancy are secondary to genetic or developmental disorders, while those identified after 22 weeks are more commonly associated with structural anomalies (eg, cardiovascular, urological, or gastrointestinal), metabolic aberrations, or infectious conditions.[3] 

Although NIHF is easily identified, determining the underlying etiology is challenging; therefore, a thorough diagnostic evaluation is essential for tailoring management appropriately.[6] In fact, in 46% of cases, the etiology remains unknown.[7] Complications of NIHF can include fetal or neonatal death, preterm delivery, and maternal mirror syndrome.[5] The prognosis for patients with NIHF largely depends on the underlying cause.[8] Therefore, an in-depth understanding of the evaluation and management of NIHF is crucial for improving patient outcomes.

Etiology

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Etiology

Hydrops fetalis is associated with a broad spectrum of disorders, which are classified into 2 main categories—immune and NIHF.

Immune Hydrops Fetalis

Immune hydrops fetalis is primarily caused by red blood cell alloimmunization due to Rh or ABO incompatibility. In Rh incompatibility, the fetal blood carries paternal Rh-positive antigens, which are recognized as foreign by the immune system of an Rh-negative mother, leading to the production of maternal anti-D antibodies. In subsequent pregnancies with Rh-positive fetuses, these antibodies can be produced in larger quantities as the maternal immune system retains a memory of the antigen. A similar mechanism occurs in ABO incompatibility, where maternal antibodies target fetal red blood cells carrying A or B antigens not present in the maternal blood. This immune response can lead to severe fetal or neonatal complications, including anemia, jaundice, hydrops fetalis, or kernicterus. However, with the introduction of anti-D immune globulin, immune hydrops fetalis has become rare.[9][10] Please see StatPearls' companion resource, "Hemolytic Disease of the Fetus and Newborn," for more information.

Nonimmune Hydrops Fetalis

Currently, etiologies other than red blood cell alloimmunization account for approximately 85% to 95% of all cases of fetal hydrops.[3][4] The most common underlying causes of NIHF are cardiovascular, chromosomal, and hematologic disorders.[6] However, NIHF can be a clinical feature of a wide range of conditions that disrupt the fetal body's ability to regulate interstitial fluid. The below-mentioned etiologies are associated with NIHF.

Cardiac disorders: In approximately 20% of patients, an underlying cardiac condition is the cause of NIHF, typically due to a structural defect that leads to increased central venous pressure or diastolic ventricular dysfunction. Common conditions associated with this include paroxysmal supraventricular tachycardia, hypoplastic left heart syndrome, endocardial cushion defects, and congenital pulmonary airway malformation.[6] Please see StatPearls' companion resources, "Paroxysmal Supraventricular Tachycardia," "Hypoplastic Left Heart Syndrome," "Atrioventricular Canal Defects," and "Congenital Pulmonary Airway Malformation," for more information on these conditions.

Chromosomal anomalies: Genetic abnormalities are a common cause of NIHF. Although chromosomal disorders are often associated with cardiac or lymphatic defects, NIHF can also occur in syndromes without any associated structural abnormalities. Chromosomal anomalies frequently leading to NIHF include Turner, Down, and Edward syndromes, as well as other aneuploidies.[6] Please see StatPearls' companion resources, "Turner Syndrome," "Down Syndrome," and "Edward Syndrome," for more information.

Lymphatic abnormalities: Conditions that cause lymphatic dysfunction often present as NIHF, including congenital lymphatic dysplasia, lymphedema distichiasis syndrome, and Milroy disease.[5] Please see StatPearls' companion resource, "Lymphangiomas," for more information.

Infections: Infections such as parvovirus B19, cytomegalovirus, and syphilis in pregnant women are linked to anemia, anoxia, endothelial cell damage, and increased capillary permeability, all of which can lead to NIHF. Among these, parvovirus B19 is the most common infectious cause of NIHF.[6] Please see StatPearls' companion resources, "Parvoviruses," "Cytomegalovirus," and "Syphilis," for more information.

Metabolic diseases: Inborn metabolic disorders that lead to decreased red blood cell production, anemia, and reduced serum proteins, such as Niemann-Pick disease type C, Gaucher disease type 2, and β-glucuronidase enzyme deficiency, are associated with NIHF.[5][6]

Fetal tumors: Fetal tumors such as sacrococcygeal teratoma, hepatic tumors, and neuroblastomas can cause NIHF due to increased cardiac demand or occupied space.[4] Please see StatPearls' companion resources, "Myelomeningocele," "Congenital Hemangioma," and "Neuroblastoma," for more information.

Renal and gastrointestinal conditions: Renal and gastrointestinal pathologies, such as congenital nephrotic syndrome, prune belly syndrome, volvulus, diaphragmatic hernia, and meconium peritonitis, can lead to decreased plasma oncotic pressure and are associated with NIHF.[11] Please see StatPearls' companion resources, "Congenital Nephrotic Syndrome," "Prune Belly Syndrome," "Volvulus," and "Diaphragmatic Hernia," for more information.

Hematologic causes: Conditions such as congenital dyserythropoietic anemia, Fanconi anemia, α-thalassemia, hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and leukemias can lead to NIHF due to high cardiac output or fetal anemia.[6][5] Please see StatPearls' companion resources, "Glucose-6-Phosphate Dehydrogenase Deficiency," "Hereditary Spherocytosis," "Fanconi Anemia," "Alpha Thalassemia," "Pyruvate Kinase Deficiency," for more information.[6]

Twin-twin transfusion syndrome: NIHF is often observed in monochorionic multiple gestations complicated by twin-twin transfusion syndrome, primarily due to high cardiac output failure in the affected fetuses.[12][6] Please see StatPearls' companion resource, "Twin-Twin Transfusion Syndrome," for more information.

Epidemiology

NIHF prevalence ranges from approximately 1 per 1700 to 3000 pregnancies overall; however, the incidence in live-born infants is about 1 in 4000 due to the high fetal mortality rate associated with some underlying etiologies and pregnancy terminations.[11] The widespread use of anti-D immunoglobulin, available since 1968, has markedly reduced the prevalence of RhD alloimmunization and associated immune fetal hydrops. Consequently, NIHF now accounts for nearly 90% of hydrops fetalis cases.[13]

Pathophysiology

Hydrops fetalis can occur in conditions that either increase fluid transudation from the vascular compartment or delay lymphatic return to circulation. These mechanisms include:

  • Increased capillary hydrostatic pressure
  • Reduced plasma oncotic pressure
  • Obstructed lymphatic flow
  • Damaged peripheral capillaries [11]

The exact pathophysiology of NIHF is not fully understood and largely depends on the specific fetal effects of the underlying etiology. For instance, decreased ventricular filling during diastole is a common mechanism in tachyarrhythmias, while increased central venous pressure, resulting from elevated right heart pressure, is typically observed in cardiac tumors and subendocardial fibroelastosis. Obstructed lymphatic drainage in the thoracic and abdominal cavities can occur due to masses such as cystic hygroma, as well as increased capillary permeability and decreased osmotic pressure associated with congenital infections and nephrosis. Consequently, management should primarily focus on addressing and reversing the underlying diseases.[14][6]

Hypoxia is another consequence of NIHF, leading to increased catecholamines and reduced hepatic and renal blood flow due to the redistribution of blood to the brain, heart, adrenals, and ductus venosus. This results in the activation of the renin-angiotensin system, increased antidiuretic hormone levels, and decreased albumin. These mechanisms elevate central venous pressure and impair lymphatic return to systemic circulation, exacerbating intravascular volume loss and resulting in severe and progressive edema in the fetus.[15]

History and Physical

Maternal Clinical Features

NIHF is primarily diagnosed through fetal clinical features observed on ultrasound imaging. Maternal presentation is often asymptomatic; however, in cases of polyhydramnios or mirror syndrome, clinical findings may include uterine enlargement, headache, visual disturbances, shortness of breath, and oliguria.[6]

Neonatal Clinical Features

Neonates with NIHF present with clinical findings similar to those observed on fetal ultrasound. However, intrauterine fetal demise and neonatal death are common. Surviving neonates may exhibit ascites, pleural effusion, and general edema.[16] Clinical features can vary based on the underlying etiology and may include cyanosis due to cardiac disease, hypotonia from congenital myopathy or hypothyroidism, hepatomegaly, cardiomyopathy, facial dysmorphism indicative of a metabolic storage disease, and dermatitis associated with TORCH infections (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex).[17][18][19][20][21] Please see StatPearls' companion resource, "TORCH Complex," for more information.

Evaluation

Fetal Ultrasound Findings

The primary clinical criteria for diagnosing NIHF involve detecting 2 or more abnormal fetal fluid collections on fetal ultrasound. Common findings include pleural effusion, ascites, pericardial effusion, and generalized skin edema (eg, skin thickness >5 mm).[11] Additional features associated with NIHF may include:

  • Placentomegaly
  • Polyhydramnios (Please see StatPearls' companion resource, "Polyhydramnios," for more information.)
  • Hepatosplenomegaly
  • Pneumothorax
  • Cystic hygroma (Please see StatPearls' companion resource, "Cystic Hygroma," for more information.)
  • Chylothorax [44][45]

Polyhydramnios and placentomegaly, typically defined as placental thickness of 4 cm or more in the second trimester or 6 cm or more in the third trimester, are not part of the core ultrasound criteria for NIHF but are frequently observed.[22] These findings can occur alone or alongside other NIHF features. As many imaging characteristics of NIHF overlap with those of other conditions, it is crucial to consider differential diagnoses.[16][23] Furthermore, NIHF features may lead to secondary complications. For example, significant ascites can compress the bowel and lead to pulmonary hypoplasia.[24] Pleural effusion may be unilateral or bilateral, potentially leading to respiratory distress, lung hypoplasia, and associated respiratory or circulatory complications that can affect prognosis. Additionally, placentomegaly and polyhydramnios have been linked to an increased risk of preterm delivery in some studies.[25]

Additional Diagnostic Studies 

As NIHF is a symptom of various underlying conditions affecting the fetal body's fluid management, determining the etiology through diagnostic studies is essential. The underlying cause directly impacts symptom development and prognosis. When NIHF is identified incidentally on prenatal ultrasound, additional structural abnormalities should be investigated using ultrasound imaging and fetal echocardiogram, as these may indicate the underlying etiology, such as a fetal cardiac abnormality.[6] Fetal heart rate monitoring, umbilical artery pulsatility index, end-diastolic flow, and middle cerebral artery (MCA) Doppler assessment are also valuable for detecting underlying causes. An MCA Doppler peak systolic velocity greater than 1.5 is considered diagnostic of fetal anemia.[26]

Red blood cell alloimmunization should be ruled out initially by confirming the maternal blood type and Rh antigen status and performing an antibody screen, typically included in routine prenatal laboratory studies. Additional laboratory tests may be required to further investigate the etiology of NIHF, including a maternal complete blood count, Kleihauer-Betke stain, thyroid hormone levels, and tests for parvovirus B19 and TORCH titers.[22][6] Genetic etiologies should be considered if RBC alloimmunization is excluded and no structural cause is identified. This involves offering fetal karyotyping, fluorescence in situ hybridization studies, exome sequencing, and chromosomal microarray analysis, typically via amniocentesis or fetal blood sampling procedures.[5][22]

Treatment / Management

The primary management approach for NIHF is tailored according to the underlying etiology and the gestational age at which hydrops manifest. Careful evaluation and monitoring, along with effective resuscitation techniques, are crucial for improving the survival rates of affected neonates. For pregnancies with a lethal etiology, options include pregnancy termination or supportive care.[6][22](A1)

For underlying NIHF pathologies that are treatable, therapeutic strategies aim to address the specific etiology and may include:

  • Intrauterine transfusions for fetal anemia.
  • Antiarrhythmic agents for fetal cardiac arrhythmias.
  • Drain or shunt placement for pleural effusion or chylothorax.
  • Corticosteroids for congenital pulmonary airway malformations.
  • Fetal therapy with sympathomimetics for atrioventricular block with ventricular rates less than 55 bpm.
  • Laser coagulation of placental vessel anastomoses in twin-twin transfusion syndrome.[6][22]
  • (A1)

Clinicians must also consider antenatal and intrapartum management of the pregnancy, including fetal monitoring for signs of deterioration with antenatal testing, determining delivery indications and mode, ensuring availability of an appropriate facility for delivery and neonatal resuscitation, and consulting specialists (such as neonatal cardiologists and cardiovascular surgeons).[11][6][22] Delivery considerations are influenced by several clinical factors. Generally, delivery is often reasonable for pregnancies with NIHF at 34 weeks or more gestational period, depending on the underlying etiology. In cases with NIHF and stable maternal-fetal conditions, delivery by 37 to 38 weeks may be considered if indications for earlier delivery or clinical worsening do not exist.[6](A1)

Postnatal management of NIHF involves several critical steps, including initial resuscitation to stabilize the neonate and identifying and treating the underlying cause. Most infants with hydrops fetalis require endotracheal intubation due to respiratory depression. Procedures such as thoracentesis, paracentesis, and occasionally cardiocentesis may be necessary to manage pleural effusion, ascites, and pericardial effusion. A blood transfusion may be required in cases of severe anemia.[6][22] Despite aggressive treatment, survival rates can be as low as 10%, with survivors at risk for neurodevelopmental and cognitive deficits. The recurrence rate is notably high in mothers whose infants have chromosomal abnormalities or Rh incompatibility. Therefore, autopsies, including histopathologic evaluation, placental examination, and molecular and genetic studies, may be performed to determine the cause of NIHF.[27](A1)

Differential Diagnosis

Any potential etiology of NIHF should be considered in the differential diagnoses, as mentioned below. (Please refer to "Nonimmune Hydrops Fetalis" in the Etiology section for more information.)

  • Neonatal hemochromatosis
  • Congestive cardiac failure
  • Twin-twin transfusion syndrome
  • Hepatitis B
  • Hypercalcemia
  • Hypernatremia
  • Hypothrombinemia
  • Maternal diabetes
  • Fetal abdominal cysts
  • Obstructed bowel
  • Obstructed urinary system [28]

Prognosis

The prognosis of hydrops fetalis primarily depends on the underlying cause, gestational age at diagnosis, timing of delivery, extent of fetal edema, and intrauterine interventions.[29] Neonates with thoracic causes and bronchopulmonary malformations generally have a better prognosis, whereas those with chromosomal abnormalities, structural defects, or genetic metabolic disorders often face a poorer prognosis.[30]

Long-term survival in hydrops fetalis largely depends on the underlying disease, the effectiveness of fetal therapies to address hydrops, and the gestational age at delivery rather than the specific anatomical manifestations of hydrops. The cardiovascular profile score can be a useful prognostic indicator for fetuses with NIHF, particularly those with high cardiothoracic ratios. Patients with NIHF who receive fetal interventions for their underlying condition often experience improved survival, particularly when hydrops can be resolved without preterm delivery. Although specific physiological parameters, such as MCA peak systolic velocity, do not predict survival, the cardiovascular profile score is valuable for predicting outcomes, especially in cases with a high cardiothoracic ratio. Additionally, the observation that various disease processes and cardiac abnormalities can lead to the common finding of fluid in 2 compartments suggests an underlying fetal distress mechanism that remains to be fully understood.[4]

Complications

The complications associated with hydrops fetalis include:

  • Spontaneous miscarriage
  • Intrauterine fetal demise
  • Preterm delivery
  • Perinatal deaths
  • Early neonatal deaths

Infants who survive hydrops fetalis may experience complications such as appendiceal rupture, cystic hygroma, intestinal obstruction, and severe neurodevelopmental delay. The most serious maternal complication is mirror syndrome, where the mother exhibits symptoms similar to those of her hydropic fetus. Clinical features of mirror syndrome often overlap with preeclampsia and may include pulmonary edema, peripheral edema, headache, visual disturbances, oliguria, elevated uric acid and liver function tests, low platelet count, and anemia.[31][32]

Deterrence and Patient Education

Patient counseling on NIHF, including its prognosis and management strategies, is essential. For pregnancies with a lethal etiology, options such as pregnancy termination or supportive care should be discussed.[6][22] Furthermore, patients should be informed about antenatal and intrapartum management, including fetal monitoring, delivery indications, delivery mode, delivery and neonatal resuscitation facility requirements, and the need for specialist consultation to facilitate shared decision-making.[11][6][22]

Clinicians should ensure patients are informed about potential postpartum procedures, such as endotracheal intubation, thoracentesis, paracentesis, and blood transfusion, which may be necessary. Additionally, patients should be made aware of the possible outcomes for the neonate if survival occurs, including potential neurodevelopmental and cognitive defects. Counseling should also address the risk of NIHF recurrence, particularly in autosomal recessive disorders.[6][22] 

Enhancing Healthcare Team Outcomes

Close collaboration among healthcare providers such as obstetricians, maternal-fetal medicine specialists, radiologists, neonatologists, nurses, and pharmacists, as well as social workers, is crucial in managing NIHF. The interprofessional healthcare team focuses on the well-being of both the mother and fetus, ensuring early detection of fetal hydrops symptoms through careful evaluation and monitoring. Pharmacists contribute by managing medications and educating patients, while nurses provide essential support and education to the woman and her family. They also facilitate follow-up care and timely reporting of changes. Social workers offer emotional and financial support and collaborate with the family on genetic consultations and future pregnancy planning. This coordinated approach enhances clinical outcomes and supports the emotional well-being of pregnant women and their families.

References


[1]

Kontomanolis EN, Fasoulakis Z. Hydrops Fetalis and THE Parvovirus B-19. Current pediatric reviews. 2018:14(4):239-252. doi: 10.2174/1573396314666180820154340. Epub     [PubMed PMID: 30124157]


[2]

. Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstetrics and gynecology. 2017 Aug:130(2):e57-e70. doi: 10.1097/AOG.0000000000002232. Epub     [PubMed PMID: 28742673]


[3]

Kosinski P, Krajewski P, Wielgos M, Jezela-Stanek A. Nonimmune Hydrops Fetalis-Prenatal Diagnosis, Genetic Investigation, Outcomes and Literature Review. Journal of clinical medicine. 2020 Jun 8:9(6):. doi: 10.3390/jcm9061789. Epub 2020 Jun 8     [PubMed PMID: 32521801]


[4]

Derderian SC, Jeanty C, Fleck SR, Cheng LS, Peyvandi S, Moon-Grady AJ, Farrell J, Hirose S, Gonzalez J, Keller RL, MacKenzie TC. The many faces of hydrops. Journal of pediatric surgery. 2015 Jan:50(1):50-4; discussion 54. doi: 10.1016/j.jpedsurg.2014.10.027. Epub 2014 Oct 29     [PubMed PMID: 25598092]

Level 2 (mid-level) evidence

[5]

Sparks TN, Lianoglou BR, Adami RR, Pluym ID, Holliman K, Duffy J, Downum SL, Patel S, Faubel A, Boe NM, Field NT, Murphy A, Laurent LC, Jolley J, Uy C, Slavotinek AM, Devine P, Hodoglugil U, Van Ziffle J, Sanders SJ, MacKenzie TC, Norton ME, University of California Fetal–Maternal Consortium, University of California, San Francisco Center for Maternal–Fetal Precision Medicine. Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis. The New England journal of medicine. 2020 Oct 29:383(18):1746-1756. doi: 10.1056/NEJMoa2023643. Epub 2020 Oct 7     [PubMed PMID: 33027564]


[6]

Society for Maternal-Fetal Medicine (SMFM), Norton ME, Chauhan SP, Dashe JS. Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. American journal of obstetrics and gynecology. 2015 Feb:212(2):127-39. doi: 10.1016/j.ajog.2014.12.018. Epub 2014 Dec 31     [PubMed PMID: 25557883]

Level 1 (high-level) evidence

[7]

Sparks TN, Thao K, Lianoglou BR, Boe NM, Bruce KG, Datkhaeva I, Field NT, Fratto VM, Jolley J, Laurent LC, Mardy AH, Murphy AM, Ngan E, Rangwala N, Rottkamp CAM, Wilson L, Wu E, Uy CC, Valdez Lopez P, Norton ME, University of California Fetal–Maternal Consortium (UCfC). Nonimmune hydrops fetalis: identifying the underlying genetic etiology. Genetics in medicine : official journal of the American College of Medical Genetics. 2019 Jun:21(6):1339-1344. doi: 10.1038/s41436-018-0352-6. Epub 2018 Nov 9     [PubMed PMID: 30410095]


[8]

Quinn AM, Valcarcel BN, Makhamreh MM, Al-Kouatly HB, Berger SI. A systematic review of monogenic etiologies of nonimmune hydrops fetalis. Genetics in medicine : official journal of the American College of Medical Genetics. 2021 Jan:23(1):3-12. doi: 10.1038/s41436-020-00967-0. Epub 2020 Oct 21     [PubMed PMID: 33082562]

Level 1 (high-level) evidence

[9]

Kemper AR, Newman TB, Slaughter JL, Maisels MJ, Watchko JF, Downs SM, Grout RW, Bundy DG, Stark AR, Bogen DL, Holmes AV, Feldman-Winter LB, Bhutani VK, Brown SR, Maradiaga Panayotti GM, Okechukwu K, Rappo PD, Russell TL. Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics. 2022 Sep 1:150(3):. pii: e2022058859. doi: 10.1542/peds.2022-058859. Epub     [PubMed PMID: 35927462]

Level 1 (high-level) evidence

[10]

de Winter DP, Kaminski A, Tjoa ML, Oepkes D. Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape. BMC pregnancy and childbirth. 2023 Jan 7:23(1):12. doi: 10.1186/s12884-022-05329-z. Epub 2023 Jan 7     [PubMed PMID: 36611144]

Level 1 (high-level) evidence

[11]

Swearingen C, Colvin ZA, Leuthner SR. Nonimmune Hydrops Fetalis. Clinics in perinatology. 2020 Mar:47(1):105-121. doi: 10.1016/j.clp.2019.10.001. Epub 2019 Oct 7     [PubMed PMID: 32000919]


[12]

Randenberg AL. Nonimmune hydrops fetalis part I: etiology and pathophysiology. Neonatal network : NN. 2010 Sep-Oct:29(5):281-95     [PubMed PMID: 20829175]


[13]

Steurer MA, Peyvandi S, Baer RJ, MacKenzie T, Li BC, Norton ME, Jelliffe-Pawlowski LL, Moon-Grady AJ. Epidemiology of Live Born Infants with Nonimmune Hydrops Fetalis-Insights from a Population-Based Dataset. The Journal of pediatrics. 2017 Aug:187():182-188.e3. doi: 10.1016/j.jpeds.2017.04.025. Epub 2017 May 19     [PubMed PMID: 28533037]


[14]

Apkon M. Pathophysiology of hydrops fetalis. Seminars in perinatology. 1995 Dec:19(6):437-46     [PubMed PMID: 8822328]


[15]

Faye-Petersen OM, Heller DS. Pathology of the stillborn infant for the general pathologist: part 2. Advances in anatomic pathology. 2015 Mar:22(2):71-93. doi: 10.1097/PAP.0000000000000060. Epub     [PubMed PMID: 25664943]


[16]

Huang YY, Chang YJ, Chen LJ, Lee CH, Chen HN, Chen JY, Chen M, Hsiao CC. Survival of Hydrops Fetalis with and without Fetal Intervention. Children (Basel, Switzerland). 2022 Apr 8:9(4):. doi: 10.3390/children9040530. Epub 2022 Apr 8     [PubMed PMID: 35455574]


[17]

Knilans TK. Cardiac abnormalities associated with hydrops fetalis. Seminars in perinatology. 1995 Dec:19(6):483-92     [PubMed PMID: 8822332]


[18]

Afifi AM, Bhatia AR, Eyal F. Hydrops fetalis associated with congenital myotonic dystrophy. American journal of obstetrics and gynecology. 1992 Mar:166(3):929-30     [PubMed PMID: 1550167]

Level 3 (low-level) evidence

[19]

Narchi H. Congenital hypothyroidism and nonimmune hydrops fetalis: associated? Pediatrics. 1999 Dec:104(6):1416-7     [PubMed PMID: 10610498]

Level 3 (low-level) evidence

[20]

Sun A. Lysosomal storage disease overview. Annals of translational medicine. 2018 Dec:6(24):476. doi: 10.21037/atm.2018.11.39. Epub     [PubMed PMID: 30740407]

Level 3 (low-level) evidence

[21]

Leung KKY, Hon KL, Yeung A, Leung AKC, Man E. Congenital infections in Hong Kong: an overview of TORCH. Hong Kong medical journal = Xianggang yi xue za zhi. 2020 Apr:26(2):127-138. doi: 10.12809/hkmj198287. Epub 2020 Apr 2     [PubMed PMID: 32245914]

Level 3 (low-level) evidence

[22]

Mardy AH, Chetty SP, Norton ME, Sparks TN. A system-based approach to the genetic etiologies of non-immune hydrops fetalis. Prenatal diagnosis. 2019 Aug:39(9):732-750. doi: 10.1002/pd.5479. Epub 2019 Jun 26     [PubMed PMID: 31087399]


[23]

Jensen KK, Oh KY, Patel N, Narasimhan ER, Ku AS, Sohaey R. Fetal Hepatomegaly: Causes and Associations. Radiographics : a review publication of the Radiological Society of North America, Inc. 2020 Mar-Apr:40(2):589-604. doi: 10.1148/rg.2020190114. Epub     [PubMed PMID: 32125959]


[24]

Jha P, Feldstein VA, Revzin MV, Katz DS, Moshiri M. Role of Imaging in Obstetric Interventions: Criteria, Considerations, and Complications. Radiographics : a review publication of the Radiological Society of North America, Inc. 2021 Jul-Aug:41(4):1243-1264. doi: 10.1148/rg.2021200163. Epub 2021 Jun 11     [PubMed PMID: 34115536]


[25]

Berger VK, Sparks TN, Jelin AC, Derderian C, Jeanty C, Gosnell K, Mackenzie T, Gonzalez JM. Non-Immune Hydrops Fetalis: Do Placentomegaly and Polyhydramnios Matter? Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2018 May:37(5):1185-1191. doi: 10.1002/jum.14462. Epub 2017 Oct 27     [PubMed PMID: 29076544]


[26]

Expert Panel on Women’s Imaging:, Glanc P, Nyberg DA, Khati NJ, Deshmukh SP, Dudiak KM, Henrichsen TL, Poder L, Shipp TD, Simpson L, Weber TM, Zelop CM. ACR Appropriateness Criteria(®) Multiple Gestations. Journal of the American College of Radiology : JACR. 2017 Nov:14(11S):S476-S489. doi: 10.1016/j.jacr.2017.08.051. Epub     [PubMed PMID: 29101986]


[27]

Rodríguez MM, Chaves F, Romaguera RL, Ferrer PL, de la Guardia C, Bruce JH. Value of autopsy in nonimmune hydrops fetalis: series of 51 stillborn fetuses. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2002 Jul-Aug:5(4):365-74     [PubMed PMID: 12016530]


[28]

Machin GA. Differential diagnosis of hydrops fetalis. American journal of medical genetics. 1981:9(4):341-50     [PubMed PMID: 6794370]


[29]

An X, Wang J, Zhuang X, Dai J, Lu C, Li X, Yan Y. Clinical Features of Neonates with Hydrops Fetalis. American journal of perinatology. 2015 Nov:32(13):1231-9. doi: 10.1055/s-0035-1552934. Epub 2015 Jun 12     [PubMed PMID: 26070120]


[30]

Nassr AA, Ness A, Hosseinzadeh P, Salmanian B, Espinoza J, Berger V, Werner E, Erfani H, Welty S, Bateni ZH, Shamshirsaz AA, Popek E, Ruano R, Davis AS, Lee TC, Keswani S, Cass DL, Olutoye OO, Belfort MA, Shamshirsaz AA. Outcome and Treatment of Antenatally Diagnosed Nonimmune Hydrops Fetalis. Fetal diagnosis and therapy. 2018:43(2):123-128. doi: 10.1159/000475990. Epub 2017 Jun 24     [PubMed PMID: 28647738]


[31]

Lebel RR, Avery JM, Broome PJ, Gregg AR, Alan C, Mostafa M. Fetal peritonitis due to appendiceal rupture: a rare complication of hydrops. Fetal and pediatric pathology. 2008:27(3):121-5. doi: 10.1080/15513810802077495. Epub     [PubMed PMID: 18633765]

Level 3 (low-level) evidence

[32]

Meng D, Li Q, Hu X, Wang L, Tan S, Su J, Zhang Y, Sun W, Chen B, He S, Lin F, Xie B, Chen S, Agrawal PB, Luo S, Fu C. Etiology and Outcome of non-immune Hydrops Fetalis in Southern China: report of 1004 cases. Scientific reports. 2019 Jul 24:9(1):10726. doi: 10.1038/s41598-019-47050-6. Epub 2019 Jul 24     [PubMed PMID: 31341179]

Level 3 (low-level) evidence