Hydrops fetalis (HF) indicates excessive fluid accumulation within the fetal extravascular compartments and body cavities. HF is not a diagnosis in itself but a symptom, and the end-stage of a wide variety of disorders. In the era before routine immunization of Rhesus (Rh) negative mothers, most cases of hydrops were due to erythroblastosis from Rh alloimmunization, but nowadays, nonimmune hydrops fetalis (NIHF) is more frequent, representing 76-87% of all described HF cases. We performed a systematic review of the pertinent literature based on the QUality Of Reporting Of Meta-analyses (QUOROM) recommendations, using a QUOROM flowchart and QUOROM checklist. At initial screening 33,345 articles were retrieved. The various inclusion and exclusion criteria aimed at obtaining data that were as unbiased yet as complete as possible decreased the numbers dramatically, and eventually a total of 225 relevant NIHF articles were identified, describing 6,361 individuals. We established 14 different diagnostic categories and provide the pathophysiologic background of each, if known. All 6,361 patients were subclassified into one of the following diagnostic categories: Cardiovascular (21.7%), hematologic (10.4%), chromosomal (13.4%), syndromic (4.4%), lymphatic dysplasia (5.7%), inborn errors of metabolism (1.1%), infections (6.7%), thoracic (6.0%), urinary tract malformations (2.3%), extra thoracic tumors (0.7%), TTTF-placental (5.6%), gastrointestinal (0.5%), miscellaneous (3.7%), and idiopathic (17.8%).

Hydrops fetalis is an excessive fluid accumulation within the fetal extra vascular compartments and body cavities. Non-immune hydrops fetalis (NIHF), due to causes other than Rh alloimmunization, is the cause in >85% of all affected individuals. Herein we present an update of our earlier systematic literature review [Bellini et al., 2009] using all publications between 2007 and 2013. We excluded most of the initial 31,783 papers by using strict selection criteria, thus resulting in 24 relevant NIHF publications describing 1,338 individuals with NIHF. We subdivided the affected individuals into 14 classification groups based on the cause of NIHF (percentage of the total group): Cardiovascular (20.1%), Hematologic (9.3%), Chromosomal (9.0%), Syndromic (5.5%), Lymphatic Dysplasia (15.0%), Inborn Errors of Metabolism (1.3%), Infections (7.0%), Thoracic (2.3%), Urinary Tract Malformations (0.9%), Extra Thoracic Tumors (0.7%), TTTF-Placental (4.1%), Gastrointestinal (1.3%), Miscellaneous (3.6%), Idiopathic (19.8%). We discuss the results of the review. There may be some shifts in the percentages of etiological categories as compared to the previous review, but the small numbers within each category make drawing firm conclusions hazardous. We highlight the need for multi-center series of NIHF cases collected and classified using the same schemes in diagnostic work-ups to allow for comparisons of larger numbers of cases.

Microsurgical LVA have a place in the treatment of peripheral lymphedema, and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment.

Hydrops fetalis is an excessive accumulation of fetal fluid. Hydrops is traditionally classified into either immune or non-immune hydrops (NIHF), but in practice, nowadays in the Western world >90% of hydrops is of non-immune origin. The basis of the disorder is an imbalance in the regulation of fetal fluid movement between the vascular and interstitial space. We previously suggested a diagnostic flow-chart for NIHF. In this short review we describe the main mechanisms leading to NIHF.

The Hennekam syndrome is an infrequently reported heritable entity characterized by lymphedema, lymphangiectasia, and developmental delay. Here we add an additional 8 patients, and compare their findings to the 16 cases from the literature. The lymphedema is usually congenital, can be markedly asymmetrical, and, often, gradually progressive. Complications such as erysipelas are common. The lymphangiectasias are present in the intestines, but have also been found in the pleura, pericardium, thyroid gland, and kidney. Several patients have demonstrated congenital cardiac and blood vessel anomalies, pointing to a disturbance of angiogenesis in at least some of the patients. Facial features are variable, and are chiefly characterized, in a typical patient, by a flat face, flat and broad nasal bridge, and hypertelorism. Facial features are thought to mirror the extent of intrauterine facial lymphedema, or may be caused by lymphatic obstruction that affects the early migration of neural crest tissue. Other anomalies have included glaucoma, dental anomalies, hearing loss, and renal anomalies. The psychomotor development varies widely, even within a single family, from almost normal development to severe mental retardation. Convulsions are common. The existence of 10 familial cases, equal sex ratio, increased parental consanguinity rate (4/20 families), and absence of vertical transmission are consistent with an autosomal recessive pattern of inheritance. It seems likely that most (but not all) manifestations of the entity can be explained as sequences of impaired prenatal and postnatal lymphatic flow, suggesting that the causative gene(s) should have a major function in lymphangiogenesis.