Nonimmune hydrops fetalis
- Charles J Lockwood, MD, MHCM
Charles J Lockwood, MD, MHCM
- Section Editor — Obstetrics
- Senior Vice President, USF Health
- Dean, Morsani College of Medicine
- Professor, Obstetrics and Gynecology
- University of South Florida
- Svena Julien, MD
Svena Julien, MD
- Assistant Professor of Gynecology and Obstetrics
- Division of Maternal-Fetal Medicine
- Johns Hopkins University
- Section Editors
- Louise Wilkins-Haug, MD, PhD
Louise Wilkins-Haug, MD, PhD
- Section Editor — Prenatal Diagnosis and Genetics
- Professor of Obstetrics, Gynecology, and Reproductive Biology
- Harvard Medical School
- Deborah Levine, MD
Deborah Levine, MD
- Section Editor — Imaging
- Professor of Radiology
- Director of Ob/Gyn Ultrasound
- Department of Radiology
- Beth Israel Deaconess Medical Center
- Joseph A Garcia-Prats, MD
Joseph A Garcia-Prats, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
Hydrops fetalis refers to abnormal fluid collections in fetal soft tissues and serous cavities. Nonimmune hydrops fetalis (NIHF) comprises the subgroup of cases not caused by red cell alloimmunization (eg, Rh(D), Kell).
The prevalence of NIHF ranges from 1/1500 to 1/3800 births [1-5]. Wide variations in reported prevalence are due to differences in definitions, populations, thoroughness of evaluation, and whether late pregnancy terminations were included.
The widespread use of Rh(D) immune globulin has dramatically decreased the prevalence of Rh(D) alloimmunization and associated hydrops. As a result, NIHF now accounts for almost 90 percent of hydrops cases .
The pathogenesis of NIHF is incompletely understood. Fluid homeostasis within the vascular and interstitial compartments is controlled by both hydrostatic and osmotic pressures as demonstrated by the Starling equation. Cellular mechanisms also regulate fluid movement and contribute to the Starling forces. Dysregulation of the net fluid movement between the vascular and interstitial spaces leading to NIHF can be caused by fetal disorders with one or more of the following features :
●Obstructed lymphatic drainage in the thoracic and abdominal cavities
- Sohan K, Carroll SG, De La Fuente S, et al. Analysis of outcome in hydrops fetalis in relation to gestational age at diagnosis, cause and treatment. Acta Obstet Gynecol Scand 2001; 80:726.
- Carlson DE, Platt LD, Medearis AL, Horenstein J. Prognostic indicators of the resolution of nonimmune hydrops fetalis and survival of the fetus. Am J Obstet Gynecol 1990; 163:1785.
- Castillo RA, Devoe LD, Hadi HA, et al. Nonimmune hydrops fetalis: clinical experience and factors related to a poor outcome. Am J Obstet Gynecol 1986; 155:812.
- Callen P. Ultrasonography in Obstetrics and Gynecology, 4th ed, WB Saunders, Philadelphia 2000.
- Anandakumar C, Biswas A, Wong YC, et al. Management of non-immune hydrops: 8 years' experience. Ultrasound Obstet Gynecol 1996; 8:196.
- Bellini C, Hennekam RC. Non-immune hydrops fetalis: a short review of etiology and pathophysiology. Am J Med Genet A 2012; 158A:597.
- Jones DC. Nonimmune fetal hydrops: diagnosis and obstetrical management. Semin Perinatol 1995; 19:447.
- Dizon-Townson DS, Dildy GA, Clark SL. A prospective evaluation of fetal pericardial fluid in 506 second-trimester low-risk pregnancies. Obstet Gynecol 1997; 90:958.
- Di Salvo DN, Brown DL, Doubilet PM, et al. Clinical significance of isolated fetal pericardial effusion. J Ultrasound Med 1994; 13:291.
- Romero R, Pilu G, Jeanty P, et al. Prenatal Diagnosis of Congenital Anomalies, Appleton and Lange, Norwalk, CT 1988.
- Arcasoy MO, Gallagher PG. Hematologic disorders and nonimmune hydrops fetalis. Semin Perinatol 1995; 19:502.
- Chitkara U, Wilkins I, Lynch L, et al. The role of sonography in assessing severity of fetal anemia in Rh- and Kell-isoimmunized pregnancies. Obstet Gynecol 1988; 71:393.
- Redman CW, Sargent IL. Placental debris, oxidative stress and pre-eclampsia. Placenta 2000; 21:597.
- Stepan H, Faber R. Elevated sFlt1 level and preeclampsia with parvovirus-induced hydrops. N Engl J Med 2006; 354:1857.
- Nakamura K, Itoh H, Sagawa N, et al. A case of peripartum cardiomyopathy with a transient increase of plasma interleukin-6 concentration occurred following mirror syndrome. J Perinat Med 2002; 30:426.
- Vidaeff AC, Pschirrer ER, Mastrobattista JM, et al. Mirror syndrome. A case report. J Reprod Med 2002; 47:770.
- van Selm M, Kanhai HH, Gravenhorst JB. Maternal hydrops syndrome: a review. Obstet Gynecol Surv 1991; 46:785.
- Braun T, Brauer M, Fuchs I, et al. Mirror syndrome: a systematic review of fetal associated conditions, maternal presentation and perinatal outcome. Fetal Diagn Ther 2010; 27:191.
- Heyborne KD, Chism DM. Reversal of Ballantyne syndrome by selective second-trimester fetal termination. A case report. J Reprod Med 2000; 45:360.
- Pirhonen JP, Hartgill TW. Spontaneous reversal of mirror syndrome in a twin pregnancy after a single fetal death. Eur J Obstet Gynecol Reprod Biol 2004; 116:106.
- Livingston JC, Malik KM, Crombleholme TM, et al. Mirror syndrome: a novel approach to therapy with fetal peritoneal-amniotic shunt. Obstet Gynecol 2007; 110:540.
- Okby R, Mazor M, Erez O, et al. Reversal of mirror syndrome after selective feticide of a hydropic fetus in a dichorionic diamniotic twin pregnancy. J Ultrasound Med 2015; 34:351.
- Mascaretti RS, Falcão MC, Silva AM, et al. Characterization of newborns with nonimmune hydrops fetalis admitted to a neonatal intensive care unit. Rev Hosp Clin Fac Med Sao Paulo 2003; 58:125.
- Bellini C, Hennekam RC, Fulcheri E, et al. Etiology of nonimmune hydrops fetalis: a systematic review. Am J Med Genet A 2009; 149A:844.
- 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; 212:127.
- Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000; 342:9.
- Borna S, Mirzaie F, Hanthoush-Zadeh S, et al. Middle cerebral artery peak systolic velocity and ductus venosus velocity in the investigation of nonimmune hydrops. J Clin Ultrasound 2009; 37:385.
- Ismail KM, Martin WL, Ghosh S, et al. Etiology and outcome of hydrops fetalis. J Matern Fetal Med 2001; 10:175.
- Graves GR, Baskett TF. Nonimmune hydrops fetalis: antenatal diagnosis and management. Am J Obstet Gynecol 1984; 148:563.
- Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012; 367:2175.
- Shaffer LG, Rosenfeld JA, Dabell MP, et al. Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound. Prenat Diagn 2012; 32:986.
- McCoy MC, Katz VL, Gould N, Kuller JA. Non-immune hydrops after 20 weeks' gestation: review of 10 years' experience with suggestions for management. Obstet Gynecol 1995; 85:578.
- Verma J, Thomas DC, Sharma S, et al. Inherited metabolic disorders: prenatal diagnosis of lysosomal storage disorders. Prenat Diagn 2015; 35:1137.
- Molyneux AJ, Blair E, Coleman N, Daish P. Mucopolysaccharidosis type VII associated with hydrops fetalis: histopathological and ultrastructural features with genetic implications. J Clin Pathol 1997; 50:252.
- Burin MG, Scholz AP, Gus R, et al. Investigation of lysosomal storage diseases in nonimmune hydrops fetalis. Prenat Diagn 2004; 24:653.
- Dreux S, Salomon LJ, Rosenblatt J, et al. Biochemical analysis of ascites fluid as an aid to etiological diagnosis: a series of 100 cases of nonimmune fetal ascites. Prenat Diagn 2015; 35:214.
- Kessel I, Makhoul IR, Sujov P. Congenital hypothyroidism and nonimmune hydrops fetalis: associated? Pediatrics 1999; 103:E9.
- Lallemand AV, Doco-Fenzy M, Gaillard DA. Investigation of nonimmune hydrops fetalis: multidisciplinary studies are necessary for diagnosis--review of 94 cases. Pediatr Dev Pathol 1999; 2:432.
- Forouzan I. Hydrops fetalis: recent advances. Obstet Gynecol Surv 1997; 52:130.
- Yinon Y, Chitayat D, Blaser S, et al. Fetal cardiac tumors: a single-center experience of 40 cases. Prenat Diagn 2010; 30:941.
- Rychik J, Khalek N, Gaynor JW, et al. Fetal intrapericardial teratoma: natural history and management including successful in utero surgery. Am J Obstet Gynecol 2016; 215:780.e1.
- Crawford DC, Chita SK, Allan LD. Prenatal detection of congenital heart disease: factors affecting obstetric management and survival. Am J Obstet Gynecol 1988; 159:352.
- Hess DB, Hess LW. Fetal Echocardiography, Appleton and Lange, Stamford, CT 1999.
- Copel JA, Friedman AH, Kleinman CS. Management of fetal cardiac arrhythmias. Obstet Gynecol Clin North Am 1997; 24:201.
- Machin GA. Hydrops revisited: literature review of 1,414 cases published in the 1980s. Am J Med Genet 1989; 34:366.
- Malin GL, Kilby MD, Velangi M. Transient abnormal myelopoiesis associated with Down syndrome presenting as severe hydrops fetalis: a case report. Fetal Diagn Ther 2010; 27:171.
- Xu J, Raff TC, Muallem NS, Neubert AG. Hydrops fetalis secondary to parvovirus B19 infections. J Am Board Fam Pract 2003; 16:63.
- Barron SD, Pass RF. Infectious causes of hydrops fetalis. Semin Perinatol 1995; 19:493.
- von Kaisenberg CS, Jonat W. Fetal parvovirus B19 infection. Ultrasound Obstet Gynecol 2001; 18:280.
- Yinon Y, Grisaru-Granovsky S, Chaddha V, et al. Perinatal outcome following fetal chest shunt insertion for pleural effusion. Ultrasound Obstet Gynecol 2010; 36:58.
- Wada S, Jwa SC, Yumoto Y, et al. The prognostic factors and outcomes of primary fetal hydrothorax with the effects of fetal intervention. Prenat Diagn 2017; 37:184.
- Rustico MA, Lanna M, Coviello D, et al. Fetal pleural effusion. Prenat Diagn 2007; 27:793.
- Bieber FR, Petres RE, Bieber JM, Nance WE. Prenatal detection of a familial nuchal bleb simulating encephalocele. Birth Defects Orig Artic Ser 1979; 15:51.
- Thornton CM, Stewart F. Elejalde syndrome: a case report. Am J Med Genet 1997; 69:406.
- Grethel EJ, Hornberger LK, Farmer DL. Prenatal and postnatal management of a patient with pentalogy of Cantrell and left ventricular aneurysm. A case report and literature review. Fetal Diagn Ther 2007; 22:269.
- Büchner M, Dostert S, Falkert A, et al. Perinatal diagnosis of a lymphedema-distichiasis syndrome (LD). Prenat Diagn 2007; 27:1069.
- Stevenson DA, Pysher TJ, Ward RM, Carey JC. Familial congenital non-immune hydrops, chylothorax, and pulmonary lymphangiectasia. Am J Med Genet A 2006; 140:368.
- Wieacker P, Muschke P, Pollak KH, Müller R. Autosomal recessive non-immune hydrops fetalis caused by systemic lymphangiectasia. Am J Med Genet A 2005; 132A:318.
- Deurloo KL, Devlieger R, Lopriore E, et al. Isolated fetal hydrothorax with hydrops: a systematic review of prenatal treatment options. Prenat Diagn 2007; 27:893.
- Picone O, Benachi A, Mandelbrot L, et al. Thoracoamniotic shunting for fetal pleural effusions with hydrops. Am J Obstet Gynecol 2004; 191:2047.
- Pellegrinelli JM, Kohler A, Kohler M, et al. Prenatal management and thoracoamniotic shunting in primary fetal pleural effusions: a single centre experience. Prenat Diagn 2012; 32:467.
- Aubard Y, Derouineau I, Aubard V, et al. Primary fetal hydrothorax: A literature review and proposed antenatal clinical strategy. Fetal Diagn Ther 1998; 13:325.
- Yang YS, Ma GC, Shih JC, et al. Experimental treatment of bilateral fetal chylothorax using in-utero pleurodesis. Ultrasound Obstet Gynecol 2012; 39:56.
- Sepulveda W, Wong AE, Herrera L, et al. Endoscopic laser coagulation of feeding vessels in large placental chorioangiomas: report of three cases and review of invasive treatment options. Prenat Diagn 2009; 29:201.
- Gimovsky AC, Luzi P, Berghella V. Lysosomal storage disease as an etiology of nonimmune hydrops. Am J Obstet Gynecol 2015; 212:281.
- Wraith JE. Lysosomal disorders. Semin Neonatol 2002; 7:75.
- Gort L, Granell MR, Fernández G, et al. Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops fetalis. Prenat Diagn 2012; 32:1139.
- Heinonen S, Ryynänen M, Kirkinen P. Etiology and outcome of second trimester non-immunologic fetal hydrops. Acta Obstet Gynecol Scand 2000; 79:15.
- Wy CA, Sajous CH, Loberiza F, Weiss MG. Outcome of infants with a diagnosis of hydrops fetalis in the 1990s. Am J Perinatol 1999; 16:561.
- Santo S, Mansour S, Thilaganathan B, et al. Prenatal diagnosis of non-immune hydrops fetalis: what do we tell the parents? Prenat Diagn 2011; 31:186.
- Iskaros J, Jauniaux E, Rodeck C. Outcome of nonimmune hydrops fetalis diagnosed during the first half of pregnancy. Obstet Gynecol 1997; 90:321.
- Tulzer G, Gudmundsson S, Wood DC, et al. Doppler in non-immune hydrops fetalis. Ultrasound Obstet Gynecol 1994; 4:279.
- Huang HR, Tsay PK, Chiang MC, et al. Prognostic factors and clinical features in liveborn neonates with hydrops fetalis. Am J Perinatol 2007; 24:33.
- Moldenhauer JS. Ex Utero Intrapartum Therapy. Semin Pediatr Surg 2013; 22:44.
- Stoffan AP, Wilson JM, Jennings RW, et al. Does the ex utero intrapartum treatment to extracorporeal membrane oxygenation procedure change outcomes for high-risk patients with congenital diaphragmatic hernia? J Pediatr Surg 2012; 47:1053.
- Désilets V, Audibert F, Society of Obstetrician and Gynaecologists of Canada. Investigation and management of non-immune fetal hydrops. J Obstet Gynaecol Can 2013; 35:923.
- Schwartz SM, Viseskul C, Laxova R, et al. Idiopathic hydrops fetalis report of 4 patients including 2 affected sibs. Am J Med Genet 1981; 8:59.
- Cumming DC. Recurrent nonimmune hydrops fetalis. Obstet Gynecol 1979; 54:124.
- Etches PC, Lemons JA. Nonimmune hydrops fetalis: report of 22 cases including three siblings. Pediatrics 1979; 64:326.
- CLINICAL MANIFESTATIONS
- Fetal findings
- Maternal findings
- - Mirror syndrome
- Course of pregnancy
- POSTDIAGNOSTIC EVALUATION
- General approach
- DISORDERS ASSOCIATED WITH HYDROPS AND ANTEPARTUM MANAGEMENT
- Cardiovascular abnormalities
- - Structural
- - Arrhythmias
- Thoracic and lymphatic abnormalities
- Twin gestation
- Genitourinary malformations
- Gastrointestinal malformations
- Placental and umbilical cord lesions
- Fetal tumors
- Inborn errors of metabolism
- Skeletal dysplasias
- PREGNANCY AND DELIVERY MANAGEMENT
- STILLBORNS AND NEONATES
- RECURRENCE RISK
- SUMMARY AND RECOMMENDATIONS