Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (702 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Abnormal accumulation of serous fluid in two or more fetal compartments, such as SKIN; pleura; pericardium; placenta; peritoneum; amniotic fluid. General fetal edema may be of non-immunologic origin, or of immunologic origin as in the case of erythroblastosis fetalis.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Fetal Hydrops; Hydrops, Fetal; Edema, Fetal; Fetal Edema; Immune Hydrops Fetalis; Hydrops Fetalis, Immune; Hydrops Fetalis, Non-Immune; Non-Immune Hydrops Fetalis.
Where it fits in the MeSH classification
- Broader topics
- Erythroblastosis, Fetal; alpha-Thalassemia; Edema
Related concepts
- Pleura
- Pericardium
- Placenta
- Peritoneum
- Amniotic Fluid
- Edema
- Erythroblastosis Fetalis
Research landscape
PubMed indexes 2,728 records tagged with the MeSH heading “Hydrops Fetalis” (counts retrieved 2026-10-29). 445 of them (16.3%) were published from 2020 onward, and the busiest period so far is through 1999 with 903 records.
Reviews account for 381 records (14.0%) and meta-analyses for 11. Randomized controlled trials number 1 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 903 |
| 2000-2009 | 686 |
| 2010-2019 | 694 |
| 2020 onward | 445 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 381 | 14.0% |
| Meta-analyses | 11 | 0.4% |
| Randomized controlled trials | 1 | 0.0% |
Method: PubMed query "Hydrops Fetalis"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia | 2015 | Research article Design not recorded in structured metadata | 271 | cc by PMID 26387913 · DOI · PMC4578306 |
| Dietary fatty acids fine-tune Piezo1 mechanical response | 2019 | Research article Design not recorded in structured metadata | 239 | cc by PMID 30867417 · DOI · PMC6416271 |
| EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis | 2016 | Research article Design not recorded in structured metadata | 86 | cc by PMID 27400125 · DOI · PMC4966301 |
| Diagnosis and management of mirror syndrome: a case series with emphasis on the potential role of the sFLT-1/PlGF ratio in clinical practice | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 41815925 · DOI · PMC12975112 |
Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Piezo1 ion channels are mediators of mechanotransduction in several cell types including the vascular endothelium, renal tubular cells and erythrocytes.
- Closing excerpt
- Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphoedema.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (131 words)
Piezo1 ion channels are mediators of mechanotransduction in several cell types including the vascular endothelium, renal tubular cells and erythrocytes. Gain-of-function mutations in PIEZO1 cause an autosomal dominant haemolytic anaemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of PIEZO1 loss of function in humans has not previously been documented. Here we discover a novel role of this channel in the lymphatic system. Through whole-exome sequencing, we identify biallelic mutations in PIEZO1 (a splicing variant leading to early truncation and a non-synonymous missense variant) in a pair of siblings affected with persistent lymphoedema caused by congenital lymphatic dysplasia. Analysis of patients' erythrocytes as well as studies in a heterologous system reveal greatly attenuated PIEZO1 function in affected alleles. Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphoedema.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 26387913 · DOI · PMC4578306
Dietary fatty acids fine-tune Piezo1 mechanical response [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals.
- Closing excerpt
- Beyond Piezo1, our findings demonstrate that cell-intrinsic lipid profile and changes in the fatty acid metabolism can dictate the cell's response to mechanical cues.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. The Piezo1 channel mediates mechanoelectrical transduction and regulates crucial physiological processes, including vascular architecture and remodeling, cell migration, and erythrocyte volume. The identity of the membrane components that modulate Piezo1 function remain largely unknown. Using lipid profiling analyses, we here identify dietary fatty acids that tune Piezo1 mechanical response. We find that margaric acid, a saturated fatty acid present in dairy products and fish, inhibits Piezo1 activation and polyunsaturated fatty acids (PUFAs), present in fish oils, modulate channel inactivation. Force measurements reveal that margaric acid increases membrane bending stiffness, whereas PUFAs decrease it. We use fatty acid supplementation to abrogate the phenotype of gain-of-function Piezo1 mutations causing human dehydrated hereditary stomatocytosis. Beyond Piezo1, our findings demonstrate that cell-intrinsic lipid profile and changes in the fatty acid metabolism can dictate the cell's response to mechanical cues.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30867417 · DOI · PMC6416271
EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue.
- Closing excerpt
- Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (182 words)
Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are nonimmune conditions that present with generalized edema of the fetus, and approximately 15% of these nonimmune cases result from a lymphatic abnormality. Here, we have identified an autosomal dominant, inherited form of lymphatic-related (nonimmune) hydrops fetalis (LRHF). Independent exome sequencing projects on 2 families with a history of in utero and neonatal deaths associated with nonimmune hydrops fetalis uncovered 2 heterozygous missense variants in the gene encoding Eph receptor B4 (EPHB4). Biochemical analysis determined that the mutant EPHB4 proteins are devoid of tyrosine kinase activity, indicating that loss of EPHB4 signaling contributes to LRHF pathogenesis. Further, inactivation of Ephb4 in lymphatic endothelial cells of developing mouse embryos led to defective lymphovenous valve formation and consequent subcutaneous edema. Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 27400125 · DOI · PMC4966301
Diagnosis and management of mirror syndrome: a case series with emphasis on the potential role of the sFLT-1/PlGF ratio in clinical practice [4]
Abstract reading summary — source excerpts
- Opening excerpt
- ObjectiveTo characterize the maternal clinical, ultrasound, and laboratory parameters, maternal and perinatal outcomes of mirror syndrome, and to discuss the role of sFlt-1/PlGF biomarkers in diagnosis and management.
- Closing excerpt
- The sFlt-1/PlGF ratio may assist in differentiating mirror syndrome from preeclampsia and in identifying women at risk for adverse outcomes.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (240 words)
ObjectiveTo characterize the maternal clinical, ultrasound, and laboratory parameters, maternal and perinatal outcomes of mirror syndrome, and to discuss the role of sFlt-1/PlGF biomarkers in diagnosis and management.MethodsWe conducted a case series including all cases of mirror syndrome diagnosed at a tertiary reference center in Brazil. Clinical, laboratory, ultrasound, and biomarker data were collected, along with maternal and perinatal outcomes.ResultsNine cases of mirror syndrome were identified, with a mean gestational age at diagnosis of 27+6 weeks. The most frequent maternal findings were lower limb edema (n=7), hypertension (n=8), and proteinuria (n=8). Ultrasound demonstrated fetal hydrops (n=7), polyhydramnios (n=6), and placentomegaly (n=7). Laboratory abnormalities included abnormal proteinuria/creatinuria ratio in 5/8 women tested, elevated 24-hour proteinuria in all 5, anemia in 7, thrombocytopenia in 3, and elevated creatinine in 1. The sFlt-1/PlGF ratio was measured in 5 women; 4 had abnormal results, with 3 above 85, all of whom developed maternal complications or fetal death. Resolution occurred after a mean of 3.4±3.6 days, due to fetal death (n=3), delivery (n=5), or fetal surgery (n=1). In one monochorionic twin pregnancy complicated by twin-anemia-polycythemia sequence, biomarker normalization after intrauterine death of the hydropic twin allowed safe prolongation of the pregnancy and term delivery of the co-twin.ConclusionMirror syndrome should be suspected in pregnancies presenting with preeclampsia-like features in the setting of fetal hydrops or polyhydramnios. The sFlt-1/PlGF ratio may assist in differentiating mirror syndrome from preeclampsia and in identifying women at risk for adverse outcomes.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41815925 · DOI · PMC12975112
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis [5]
- Research article Hydrops fetalis caused by alpha-thalassemia: an emerging health care problem [6]
- Research article Hydrops revisited: literature review of 1,414 cases published in the 1980s [7]
- Research article Mirror syndrome: a systematic review of fetal associated conditions, maternal presentation and perinatal outcome [8]
- Research article Transient leukaemia--a benign form of leukaemia in newborn infants with trisomy 21 [9]
- Research article Etiology of nonimmune hydrops fetalis: a systematic review [10]
References
- Lukacs V, Mathur J, Mao R, Bayrak-Toydemir P, Procter M, Cahalan SM, et al.. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. . 2015. PMID 26387913 · DOI · PMC4578306
- Romero LO, Massey AE, Mata-Daboin AD, Sierra-Valdez FJ, Chauhan SC, Cordero-Morales JF, et al.. Dietary fatty acids fine-tune Piezo1 mechanical response. . 2019. PMID 30867417 · DOI · PMC6416271
- Martin-Almedina S, Martinez-Corral I, Holdhus R, Vicente A, Fotiou E, Lin S, et al.. EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis. . 2016. PMID 27400125 · DOI · PMC4966301
- Behenck GS, Curtois F, El Beitune P, Jimenez MF, Vettorazzi J, da Silva MB, et al.. Diagnosis and management of mirror syndrome: a case series with emphasis on the potential role of the sFLT-1/PlGF ratio in clinical practice. . 2026. PMID 41815925 · DOI · PMC12975112
- Society for Maternal-Fetal Medicine (SMFM), Norton ME, Chauhan SP, Dashe JS. Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet Gynecol. 2015. PMID 25557883 · DOI
- Chui DH, Waye JS. Hydrops fetalis caused by alpha-thalassemia: an emerging health care problem. Blood. 1998. PMID 9516118 · DOI
- Machin GA. Hydrops revisited: literature review of 1,414 cases published in the 1980s. Am J Med Genet. 1989. PMID 2688420 · DOI
- Braun T, Brauer M, Fuchs I, Czernik C, Dudenhausen JW, Henrich W, et al.. Mirror syndrome: a systematic review of fetal associated conditions, maternal presentation and perinatal outcome. Fetal Diagn Ther. 2010. PMID 20357423 · DOI
- Zipursky A. Transient leukaemia--a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol. 2003. PMID 12648061 · DOI
- Bellini C, Hennekam RC, Fulcheri E, Rutigliani M, Morcaldi G, Boccardo F, et al.. Etiology of nonimmune hydrops fetalis: a systematic review. Am J Med Genet A. 2009. PMID 19334091 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.