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Etiology of nonimmune hydrops fetalis: A systematic review

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%). © 2009 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics Wiley
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