After completing this article, readers should be able to: 1. Describe the common causes of nonimmune hydrops fetalis (NIHF). 2. Characterize the primary steps in antenatal investigation of NIHF. 3. Describe the clinical interventions required for in utero management of NIHF. 4. Delineate the procedures required for ongoing postnatal management of the neonate who has NIHF. 5. Describe the role of postmortem studies in NIHF. Hydrops fetalis has been a well-recognized fetal and neonatal condition throughout history. Until the latter half of the 20th century, it was believed to be due to Rhesus blood group isoimmunization of the fetus, although Potter described infants who had nonimmune causes of fetal hydrops. The advent of Rho (D) immune globulin resulted in a decline in the incidence of isoimmune fetal hydrops and increasing prominence of nonimmune causes of this severe and highly lethal fetal and neonatal condition. Nonimmune hydrops fetalis (NIHF) is as pathologic accumulation of fluid in the skin and one or more other body compartments of the fetus, including the pleural space, peritoneal cavity, pericardial sac, or placenta. Some authors define NIHF as edema of the skin plus fluid accumulation in two other compartments of the fetus, but the former definition is more common. NIHF is estimated to occur in 1 in 2,500 to 1 in 4,000 pregnancies, but the incidence varies with the ethnic population studied. For example, in Southeast Asia, NIHF is seen in 1 in 500 to 1 in 1,500 pregnancies. In this population, homozygous alpha thalassemia is common, accounting for 57% to 81% of cases of NIHF in some series, although a more recent study from Taiwan showed that homozygous alpha thalassemia accounted for only 31% of NIHF. Variations in the incidence of NIHF have been documented when an infectious epidemic occurs, such as with parvovirus B19 (erythema infectiosum). Fluid accumulates within …