eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Hydrops Fetalis: Treatment & Medication

Author: Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP, Clinical Assistant Professor of Pediatrics, Vanderbilt University Medical Center
Contributor Information and Disclosures

Updated: Aug 20, 2008

Treatment

Medical Care

The diagnosis and management of hydrops fetalis continue to be challenges for perinatologists and neonatologists. Mortality rates are high, and treatment options are limited.The single most important factor to ensure proper treatment of the fetus with hydrops is a precise and detailed diagnosis. Until the underlying pathophysiology is clearly understood and the extent of the abnormalities leading the development of hydrops is completely defined, any attempt at treatment is futile and potentially harmful.

  • Once the underlying problems are completely understood, address the question of whether the abnormalities present are compatible with life, whether fetal survival would be at the cost of an unacceptably poor quality of life, and what the consequences may be for future generations. Currently, parental involvement and guidance are fundamental requirements and require full knowledge by the parents of all possible potential consequences.
  • If the decision is made to continue the pregnancy, the next steps are to decide whether to intervene with invasive fetal treatment and to determine at what point preterm delivery represents less risk for the fetus than continued gestation. Because major uncertainties about these questions are inevitable, regardless of the underlying cause, full parental involvement is essential.
  • Decisions about fetal treatment are often uncertain because the necessary evidence for a diagnosis is not available. Although many anecdotal approaches are found in the literature, no properly designed clinical trials are available for the clinician concerned with evidence-based management.
    • Many treatment schemes are recognized; however, all are based on the biases and experiences of the individual authors. In such circumstances, treatment decisions are difficult, particularly for the prudent clinician who requires evidence to balance risks against benefits of a specific treatment.
    • To further complicate the issue, spontaneous remission of the hydropic process has been reported in hundreds of cases. Underlying causes in these cases include cardiac arrhythmias, twin-to-twin transfusion syndrome, pulmonary sequestration, cystic adenomatoid malformation of the lung, lysosomal storage diseases, cystic hygroma with or without Noonan syndrome, both parvovirus and CMV infections, placental chorangioma, and idiopathic ascites or pleural effusions. Clinicians and parents must completely understand that decisions at this point basically are uncertain and arbitrary.
  • Unproven high-risk treatments are easier to accept when they consist of procedures targeted to correct the underlying pathophysiology leading to fetal hydrops. Thus, the most widely accepted management schemes include fetal transfusion to correct anemia (regardless of cause), drug treatments for cardiac arrhythmias, correction or reduction of space-occupying lesions that impede cardiac venous or lymphatic return, and procedures designed to stop fetal loss of blood, regardless of cause.
  • Treatment reported for fetal arrhythmias has included doing nothing, administering drugs, and immediate delivery.
    • If fetal maturity permits, the most simple and direct approach is obviously delivery of the affected fetus and direct neonatal treatment of the arrhythmia.
    • When fetal immaturity prevents this approach, use of drugs has generally been accepted as appropriate. However, whether this is justified is not supported by any evidence from controlled clinical trials, and the frequency with which spontaneous cessation of the arrhythmia and remission of the hydrops has been reported should promote more skepticism and caution about fetal drug treatment than generally has been standard.
    • Drugs have been administered to the mother (oral, intramuscular, intravenous), to the fetus (intraperitoneal, intramuscular, intravenous via cordocentesis), and to both, attempting to correct fetal arrhythmias.
    • Even fetal pacing has been reported. As perhaps expected, the failures are infrequently reported while the successes serve as topics for case or case-series reports (ie, reporting bias). Such treatment is not without risk, partly consequent to the drugs used and not uncommonly related to the mode of administration.
    • Drugs used have included digitalis, furosemide, flecainide, verapamil, amiodarone, propanolol, procainamide, quinidine, adenosine, sotalol, terbutaline, corticosteroids, and immunoglobulins; various combinations of these drugs have also been used. Although adenosine appears to be particularly effective with supraventricular arrhythmias, and corticosteroid therapy seems effective for complete fetal heart block associated with maternal collagen diseases, choice of drug remains empiric and arbitrary, until such time as definitive evidence from clinical trials becomes available.
    • The prudent clinician may choose the approach that offers the least risk to fetus and mother until more definitive data are available.
  • The success of intrauterine intraperitoneal fetal transfusion with packed RBCs in the treatment of the severely anemic fetus of the isoimmunized pregnancy has been a modern success story for perinatal medicine. Unfortunately, historic controls form the basis for this conclusion, and definitive evidence from randomized clinical trials will probably never be available.
    • The use of this procedure to correct fetal anemia from various other causes (eg, hemorrhage into a twin, from highly vascularized tumor masses, consequent to marrow aplasia with severe fetal infection, hemoglobinopathy) has been reported with many favorable outcomes. Again, whether this is real or a consequence of reporting bias is uncertain.
    • Nevertheless, fetal transfusion using the intraperitoneal route has apparently become accepted as the standard of care for the fetus with severe anemia.
  • However, more recently a more direct approach has been used with increasing frequency.
    • Reported routes of fetal administration of blood products have included percutaneous umbilical vein, intrahepatic umbilical vein, umbilical artery, and various combined approaches. Even intracardiac transfusions have been reported. Success has been claimed with fetal partial packed-cell exchange transfusion, maternal plasmapheresis, maternal promethazine or corticosteroid treatment, fetal intravenous Ig-G, fetal platelet transfusion, and fetal administration of human granulocyte-stimulating factor, again using various routes.
    • The use of more direct invasive methods may appear to increase fetal risk. This may not appear justified in view of the very low risks demonstrated to accompany the intraperitoneal route. The prudent clinician may be justified in taking a very cautious approach to these newer therapeutic techniques until such time as definitive evidence is available that the benefit-to-risk ratio of them is better.
  • Severe hemorrhage from friable, highly vascular tumor masses and acute, massive hemorrhage from one twin to another often result in quick fetal death. Although those who survive may appear to benefit from fetal transfusion, as described above, continued hemorrhage may make such efforts futile. Thus, a more aggressive approach in such conditions may be justified.
    • For example, surprising success has been reported with tumor debulking surgery for the fetus with sacrococcygeal tumor and with surgical removal of actively bleeding, highly vascularized fetal intraabdominal, thoracic, or placental masses.
    • Photocoagulation and radiofrequency thermal ablation techniques also demonstrate much promise in this regard. The information is preliminary; most of it comes from animal studies, and no extensive clinical trial experience in the human fetus is currently available. Nevertheless, life-threatening disease may justify life-threatening treatment in some cases, and use of such technology in situations of active fetal hemorrhage may hold considerable promise. Use of these techniques to correct massive arteriovenous shunting causing fetal hydrops also demonstrates real promise of effectiveness.
  • The twin-to-twin transfusion syndrome presents a somewhat more puzzling problem. The temptation to transfuse the anemic fetus is apparent in the literature; however, no evidence of overall benefit from this approach exists.
    • As noted earlier, if one twin has developed hydrops in this situation, the recipient twin develops hydrops, not the donor. Thus, volume reduction in the recipient or combined transfusion/reduction procedures to the twins appears to be more logical but has seldom been used as it does not correct the ongoing pathophysiology.
    • Feticide of the affected twin has often been reported; however, subsequent development of hydrops in the previously normal twin is surprisingly commonly reported. Thus, the management of the twin-to-twin transfusion syndrome is currently an unresolved problem. Examination of the cauterization of vessels in the placenta that appear to connect the circulation of the twins is ongoing.
  • Space-occupying masses, which impair venous or lymphatic return, are among the more important causes of fetal hydrops. Management varies depending on the type of lesion and from center to center. However, the fundamental basis for most treatments has been reduction or removal of the mass when immediate delivery is not practical.
    • Pleural effusions have been managed with single or serial fetal thoracenteses, pleurothoraco-amniotic shunts, and direct fetal surgical maneuvers to correct the underlying cause.
    • Pericardial effusions have been managed similarly with single or serial pericardiocenteses or continuous drainage maneuvers.
    • Ascites has also been treated with single or multiple taps, peritoneo-amniotic shunts, and intraperitoneal albumin. Successes and failures have been reported with all methods; no evidence suggests that one approach is any better than another because proper comparative trial data are not available.
    • Fetal surgery with definitive correction of the underlying anomaly has been reported with increasing frequency. Improved fetal survival with cystic adenomatoid malformation and with bronchopulmonary sequestration has been observed in several large series in which these direct corrective measures have been employed. Although this success has been measured against outcomes using historic controls, such measures make physiologic sense and, thus, demonstrate considerable promise.
  • Resuscitation and delivery room management of hydrops fetalis pose a unique set of problems for the neonatologist. The obstetrician must work collaboratively with the neonatologist as soon as hydrops is identified in the fetus.
    • Once hydrops has been diagnosed antenatally, make every effort to establish the cause; this is helpful in treating the infant at birth.
    • In addition to appropriate equipment and supplies, a skilled team of experienced health care professionals (neonatologists, nurses, respiratory therapists, radiograph technician, ultrasonography technician) should be present in the delivery room.
    • Perform or repeat antenatal ultrasonography examination to assess the presence and extent of pleural effusion, pericardial effusion, or ascites prior to delivery because the fluid may require aspiration in the delivery room to establish adequate ventilation and circulation.
    • Assessment of fetal hematocrit, pO2 and pH by percutaneous umbilical sampling, although risky, may be helpful in selected cases for early management.
    • After establishing the infant's airway and ventilation, place umbilical arterial and venous catheters to monitor arterial pressure, blood gases, and venous pressure.
    • Packed erythrocytes or whole blood crossmatched with the mother's blood should be available for partial exchange transfusion to correct severe anemia, even when due to nonimmune causes.
    • Anticipate and promptly correct metabolic derangements such as acidosis and hypoglycemia.
    • Surfactant deficiency and hypoplastic lungs may be associated with hydrops and are managed accordingly.
    • Drainage of the pleural cavity and abdominal cavities of pleural and acidic fluid may be necessary to adequately ventilate the infant.

Medication

The number of drugs that have been used for the correction of fetal arrhythmias reflects the amount of uncertainty about dosage, effectiveness, and hazards. Fetal pharmacokinetic studies are not available, and dosage schedules for these very immature infants are uncertain or derived from data on older and bigger infants and children. Thus, consider each case individually; be aware that therapeutic misadventures remain possible if not probable.

Cardiac glycosides

These are used for fetal cardiac failure. Positive inotropic agents (eg, digoxin) increase force of contraction of myocardium and are used to treat acute and chronic CHF. Digoxin may also be used for fetal supraventricular tachycardia (SVT) because it decreases AV conduction.


Digoxin (Lanoxin, Lanoxicaps)

Recommended dosages require considerable modification because of individual variations in sensitivity to drug in adults, children, and (probably) fetuses. Usually administered to mother; thus, adult dosages are used. Transplacental transfer is normally excellent; however, impaired fetal perfusion of placental circulation due to severe cardiac failure results in impaired drug pickup; thus, fetal drug levels may be much lower than maternal concentrations.

Adult

400-750 mcg PO initial loading dose; 100-375 mcg PO 6-8 h after initial dose; repeat in 6-8 h
400-600 mcg IV initial loading dose; 100-300 mcg in 6-8 h; repeat in 6-8 h

Pediatric

Preterm infants 29 weeks' gestation or less: 5-10 mcg/kg IV initial loading dose, followed by 2-5 mcg/kg in 6-8 h; repeat 2-5 mcg/kg in 6-8 h
Extrapolation of this data to preterm fetus has been made, with direct IM or IV administration
Much higher doses have been used; in 1 report, 88 mcg/kg/dose IM repeated in 12-24 h was used successfully
Pharmacokinetic data to support this extrapolation are not available

Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, PO amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, and verapamil
Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, PO colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid; uncertain in preterm fetus

Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; carotid sinus syndrome; uncertain in preterm fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use is supported by very little evidence

Loop diuretics

These are used to treat fetal edema. They promote excretion of water and electrolytes by kidneys and are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites.


Furosemide (Lasix)

Diuretic, in conjunction with digoxin, that has been used in management of fetal hydrops. Both transplacental (maternal administration) and direct fetal routes have been used. No satisfactory pharmacokinetic data are available to support these recommendations.

Adult

20-80 mg PO initial dose; if no diuresis, may be repeated in 6-8 h with 40-120 mg dose

Pediatric

2 mg/kg PO initial dose; if no diuresis, 3-4 mg/kg may be repeated in 6-8 h

Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently; uncertain in premature fetus

Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion; uncertain in premature fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Usual electrolyte monitoring is not available

Antiarrhythmic agents

These agents alter electrophysiologic mechanisms responsible for arrhythmia and are used to treat fetal arrhythmia.


Quinidine (Cardioquin, Quinalan, Quinidex, Quinora)

Scant data to support use in fetus.

Adult

324-648 mg PO of gluconate (202-403 mg of base quinidine) q8h for 3-4 doses

Pediatric

Fetal or preterm: Not established

Phenytoin, rifampin, and phenobarbital may decrease concentrations; toxicity increased when taken with ritonavir, sparfloxacin, beta-blockers, amiodarone, verapamil, cimetidine, alkalinizing agents, or nondepolarizing and depolarizing muscle relaxants; may enhance effect of anticoagulants; uncertain in premature fetus

Documented hypersensitivity; complete AV block or intraventricular conduction defects, presently taking ritonavir or sparfloxacin; uncertain in premature fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use limited by scant data


Verapamil (Calan, Calan SR, Covera-HS, Verelan)

Anecdotal use.

Adult

240-320 mg/d PO divided tid

Pediatric

Fetal or preterm: Not established
<2 years: Not recommended (see precautions)

May increase carbamazepine, digoxin, and cyclosporine levels; coadministration with amiodarone can cause bradycardia and decrease in cardiac output; when administered concurrently with beta-blockers may increase cardiac depression; cimetidine may increase levels; may increase theophylline levels; uncertain in the premature fetus

Documented hypersensitivity; severe CHF; sick sinus syndrome or second-degree or third-degree AV block; hypotension (<90 mm Hg systolic); age <2 y or weight <15 kg; uncertain in premature fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Limited data to support use in fetus; IV use in neonates and young infants may cause apnea bradycardia, hypotension, cardiac arrest, and potential death


Amiodarone (Cordarone)

Limited use in fetus.

Adult

Loading: 800-1600 mg PO qd

Pediatric

Fetal or preterm: Not established

Increases effects and blood levels of theophylline, quinidine, procainamide, phenytoin, methotrexate, flecainide, digoxin, cyclosporine, beta-blockers, and anticoagulants; ritonavir increases toxicity; cardiotoxicity of amiodarone is increased by ritonavir, sparfloxacin, and disopyramide; coadministration with calcium channel blockers may cause additive effect and decrease myocardial contractility further; cimetidine may increase amiodarone levels; uncertain in premature fetus

Documented hypersensitivity; complete AV block; intraventricular conduction defects; patients taking ritonavir or sparfloxacin; uncertain in premature fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Limited information about usefulness and risks


Adenosine (Adenocard)

Recent use has been promising; however, most information is in form of case reports.

Adult

6 mg IV over 1-2 s; may be repeated in 1-2 min, with dosage increase not to exceed 12 mg if arrhythmia does not resolve
For rapid IV use only

Pediatric

50 mcg/kg IV over 1-2 s; has been repeated at 1- to 2-min intervals with 100 mcg/kg dosage; not to exceed total dose of 12 mg
In one report, single dose of as much as 150 mcg/kg was administered successfully through umbilical venous route
For rapid IV use only

Documented hypersensitivity; second-degree or third-degree AV block or sick sinus syndrome (except in patients with functioning artificial pacemaker); atrial flutter; atrial fibrillation; ventricular tachycardia; uncertain in premature fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Limited data to support use; use in fetus requires direct administration by cordocentesis


Procainamide (Procanbid, Pronestyl)

Use in children well established; however, little data available on use in preterm neonate or fetus.

Adult

250-500 mg PO q3-6h
1000 mg IM loading dose followed by 250 mg q3h
100-200 mg IV repeated in 5 min prn, not to exceed 1000 mg, maintain with 1-6 mg/min by continuous infusion

Pediatric

20-30 mg/kg/d IM divided q4-6h, not to exceed 4 g/d
3-6 mg/kg IV over 5 min, maintained with 20-30 mcg/kg/min by continuous infusion
Preterm and fetus: 1.5-2 mg/kg IV over 20-30 min has been used

Can expect increased levels of procainamide metabolite NAPA in patients taking cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim, and quinidine; may increase effects of skeletal muscle relaxants, quinidine, lidocaine, and neuromuscular blockers; ofloxacin inhibits tubular secretion of procainamide and may increase bioavailability; when taken concurrently with sparfloxacin, may increase risk of cardiotoxicity; uncertain in premature fetus

Patients diagnosed with complete, second-degree, or third-degree heart block, if pacemaker is not in place; torsade de pointes; documented hypersensitivity; SLE; uncertain in premature fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Limited data available concerning use in very preterm neonates and fetuses


Sotalol (Betapace)

Recent use in fetal arrhythmias has been promising; however, data are scarce, and definitive pharmacokinetic studies have not been performed.

Adult

80-160 mg PO q12h

Pediatric

Fetal or preterm: Not established

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effect; cardiotoxicity may increase when administered concurrently with calcium channel blockers, quinidine, and flecainide; toxicity increases when coadministered with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, phenothiazines, and catecholamine-depleting agents

Documented hypersensitivity; sinus bradycardia, second-degree and third-degree AV block

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Accumulation of drug with renal failure is worrisome, since renal perfusion is poor in hydropic fetus


Flecainide (Tambocor)

Limited data from infants suggest that half-life at birth may be prolonged. These data have not been extended backward to fetal life. Maternal (transplacental) use, in conjunction with digoxin, has been promising anecdotally.

Adult

50-100 mg PO q12h, may be increased prn, not to exceed 300-400 mg/d

Pediatric

Fetal or preterm: Not established

Amiodarone, cimetidine, and digoxin may increase plasma concentrations; beta-adrenergic blockers, verapamil, and disopyramide may have additive inotropic effects with coadministration; ritonavir may increase cardiotoxicity; uncertain in premature fetus

Documented hypersensitivity; third-degree AV block and myocardial depression; uncertain in premature fetus

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Lack of data still limits widespread use

More on Hydrops Fetalis

Overview: Hydrops Fetalis
Differential Diagnoses & Workup: Hydrops Fetalis
Treatment & Medication: Hydrops Fetalis
Follow-up: Hydrops Fetalis
Multimedia: Hydrops Fetalis
References
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References

  1. Pasman SA, Meerman RH, Vandenbussche FP, Oepkes D. Hypoalbuminemia: a cause of fetal hydrops?. Am J Obstet Gynecol. Apr 2006;194(4):972-5. [Medline].

  2. Blair DK, Vander Straten MC, Gest AL. Hydrops in fetal sheep from rapid induction of anemia. Pediatr Res. May 1994;35(5):560-4. [Medline].

  3. Shinbane JS, Wood MA, Jensen DN, et al. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J Am Coll Cardiol. Mar 15 1997;29(4):709-15. [Medline].

  4. Kitsirisakul B, Steger HF, Sanguansermsri T. Frequency of alpha-thalassemia-1 of the Southeast Asian-type among pregnant women in northern Thailand determined by PCR technique. Southeast Asian J Trop Med Public Health. Jun 1996;27(2):362-3. [Medline].

  5. Abrams ME, Meredith KS, Kinnard P, Clark RH. Hydrops fetalis: a retrospective review of cases reported to a large national database and identification of risk factors associated with death. Pediatrics. Jul 2007;120(1):84-9. [Medline].

  6. Bowman J, Harman C, Manning F, et al. Intravenous drug abuse causes Rh immunization. Vox Sang. 1991;61(2):96-8. [Medline].

  7. Nakayama R, Yamada D, Steinmiller V, Hsia E, Hale RW. Hydrops fetalis secondary to Bart hemoglobinopathy. Obstet Gynecol. Feb 1986;67(2):176-80. [Medline].

  8. Joshi DD, Nickerson HJ, McManus MJ. Hydrops fetalis caused by homozygous alpha-thalassemia and Rh antigen alloimmunization: report of a survivor and literature review. Clin Med Res. Nov 2004;2(4):228-32. [Medline].

  9. Essary LR, Vnencak-Jones CL, Manning SS, et al. Frequency of parvovirus B19 infection in nonimmune hydrops fetalis and utility of three diagnostic methods. Hum Pathol. Jul 1998;29(7):696-701. [Medline].

  10. Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Hum Pathol. Mar 1977;8(2):155-71. [Medline].

  11. Liley AW. Liquor amnii analysis in the management of the pregnancy complicated by Rhesus sensitization. Am J Obstet Gynecol. 1961;82(6):1359-1370.

  12. Adzick NS, Harrison MR, Crombleholme TM, et al. Fetal lung lesions: management and outcome. Am J Obstet Gynecol. Oct 1998;179(4):884-9. [Medline].

  13. Anand A, Gray ES, Brown T, et al. Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med. Jan 22 1987;316(4):183-6. [Medline].

  14. Andres RL, Brace RA. The development of hydrops fetalis in the ovine fetus after lymphatic ligation or lymphatic excision. Am J Obstet Gynecol. May 1990;162(5):1331-4. [Medline].

  15. Aubard Y, Derouineau I, Aubard V, et al. Primary fetal hydrothorax: A literature review and proposed antenatal clinical strategy. Fetal Diagn Ther. Nov-Dec 1998;13(6):325-33. [Medline].

  16. Azancot-Benisty A, Areias JC, Oberhansli I, et al. European Study on Maternal and Fetal Management of Fetal Supraventricular Tachyarrhythmia: Proposed Protocol for an International Project. J Matern Fetal Investig. Jun 1998;8(2):92-7. [Medline].

  17. Bajoria R, Sullivan M, Fisk NM. Endothelin concentrations in monochorionic twins with severe twin-twin transfusion syndrome. Hum Reprod. Jun 1999;14(6):1614-8. [Medline]. [Full Text].

  18. Barron SD, Pass RF. Infectious causes of hydrops fetalis. Semin Perinatol. Dec 1995;19(6):493-501. [Medline].

  19. Bejar R, Vigliocco G, Gramajo H, et al. Antenatal origin of neurologic damage in newborn infants. II. Multiple gestations. Am J Obstet Gynecol. May 1990;162(5):1230-6. [Medline].

  20. Blickstein I. The twin-twin transfusion syndrome. Obstet Gynecol. Oct 1990;76(4):714-22. [Medline].

  21. Bond SJ, Harrison MR, Schmidt KG, et al. Death due to high-output cardiac failure in fetal sacrococcygeal teratoma. J Pediatr Surg. Dec 1990;25(12):1287-91. [Medline].

  22. Brace RA. Effects of outflow pressure on fetal lymph flow. Am J Obstet Gynecol. Feb 1989;160(2):494-7. [Medline].

  23. Brans YW, Milstead RR, Bailey PE, Cassady G. Blood-volume estimates in Coombs-test-positive infants. N Engl J Med. Jun 27 1974;290(26):1450-2. [Medline].

  24. 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. Dec 1990;163(6 Pt 1):1785-7. [Medline].

  25. Cowan RH, Waldo AL, Harris HB, et al. Neonatal paroxysmal supraventricular tachycardia with hydrops. Pediatrics. Mar 1975;55(3):428-30. [Medline].

  26. Daniel SJ, Cassady G. Non-immunologic hydrops fetalis associated with a large hemangioendothelioma. Pediatrics. Nov 1968;42(5):828-33. [Medline].

  27. De Groot CJ, Oepkes D, Egberts J, Kanhai HH. Evidence of endothelium involvement in the pathophysiology of hydrops fetalis?. Early Hum Dev. Mar 2000;57(3):205-9. [Medline].

  28. Dieck D, Schild RL, Hansmann M, Eis-Hubinger AM. Prenatal diagnosis of congenital parvovirus B19 infection: value of serological and PCR techniques in maternal and fetal serum. Prenat Diagn. Dec 1999;19(12):1119-23. [Medline].

  29. Driscoll SG. Hydrops fetalis. N Engl J Med. Dec 22 1966;275(25):1432-4. [Medline].

  30. Dumez Y, Mandelbrot L, Radunovic N, et al. Prenatal management of congenital cystic adenomatoid malformation of the lung. J Pediatr Surg. Jan 1993;28(1):36-41. [Medline].

  31. Faber JJ, Anderson DF. Angiotensin mediated interaction of fetal kidney and placenta in the control of fetal arterial pressure and its role in hydrops fetalis. Placenta. May 1997;18(4):313-26. [Medline].

  32. Gembruch U, Knopfle G, Chatterjee M, et al. First-trimester diagnosis of fetal congenital heart disease by transvaginal two-dimensional and Doppler echocardiography. Obstet Gynecol. Mar 1990;75(3 Pt 2):496-8. [Medline].

  33. Gest AL, Bair DK, Vander Straten MC. The effect of outflow pressure upon thoracic duct lymph flow rate in fetal sheep. Pediatr Res. Nov 1992;32(5):585-8. [Medline].

  34. Gest AL, Hansen TN, Moise AA, Hartley CJ. Atrial tachycardia causes hydrops in fetal lambs. Am J Physiol. Apr 1990;258(4 Pt 2):H1159-63. [Medline].

  35. Gest AL, Martin CG, Moise AA, Hansen TN. Reversal of venous blood flow with atrial tachycardia and hydrops in fetal sheep. Pediatr Res. Sep 1990;28(3):223-6. [Medline].

  36. Giacoia GP. Severe fetomaternal hemorrhage: a review. Obstet Gynecol Surv. Jun 1997;52(6):372-80. [Medline].

  37. Gudmundsson S, Huhta JC, Wood DC, et al. Venous Doppler ultrasonography in the fetus with nonimmune hydrops. Am J Obstet Gynecol. Jan 1991;164(1 Pt 1):33-7. [Medline].

  38. Haak MC, Oosterhof H, Mouw RJ. Pathophysiology and treatment of fetal anemia due to placental chorioangioma. Ultrasound Obstet Gynecol. Jul 1999;14(1):68-70. [Medline].

  39. Hagay Z, Reece A, Roberts A, Hobbins JC. Isolated fetal pleural effusion: a prenatal management dilemma. Obstet Gynecol. Jan 1993;81(1):147-52. [Medline].

  40. Haverkamp F, Noeker M, Gerresheim G, Fahnenstich H. Good prognosis for psychomotor development in survivors with nonimmune hydrops fetalis. Br J Obstet Gynaecol. Feb 2000;107(2):282-4. [Medline].

  41. Hirata GI, Masaki DI, O'Toole M, Medearis AL, Platt LD. Color flow mapping and Doppler velocimetry in the diagnosis and management of a placental chorioangioma associated with nonimmune fetal hydrops. Obstet Gynecol. May 1993;81(5 ( Pt 2)):850-2. [Medline].

  42. Khouzami AN, Kickler TS, Callan NA, et al. Devastating sequelae of alloimmune thrombocytopenia: an entity that deserves more attention. J Matern Fetal Med. May-Jun 1996;5(3):137-41. [Medline].

  43. Kirshon B, Moise KJ Jr, Mari G, et al. In utero resolution of hydrops fetalis following the death of one twin in twin-twin transfusion. Am J Perinatol. Apr 1990;7(2):107-9. [Medline].

  44. Knilans TK. Cardiac abnormalities associated with hydrops fetalis. Semin Perinatol. Dec 1995;19(6):483-92. [Medline].

  45. Mahone PR, Sherer DM, Abramowicz JS, Woods JR Jr. Twin-twin transfusion syndrome: rapid development of severe hydrops of the donor following selective feticide of the hydropic recipient. Am J Obstet Gynecol. Jul 1993;169(1):166-8. [Medline].

  46. Miller E, Fairley CK, Cohen BJ, Seng C. Immediate and long term outcome of human parvovirus B19 infection in pregnancy. Br J Obstet Gynaecol. Feb 1998;105(2):174-8. [Medline].

  47. Moise AA, Gest AL, Weickmann PH, McMicken HW. Reduction in plasma protein does not affect body water content in fetal sheep. Pediatr Res. Jun 1991;29(6):623-6. [Medline].

  48. Moise KJ Jr, Carpenter RJ Jr, Hesketh DE. Do abnormal Starling forces cause fetal hydrops in red blood cell alloimmunization?. Am J Obstet Gynecol. Oct 1992;167(4 Pt 1):907-12. [Medline].

  49. Moya FR, Grannum PA, Riddick L, et al. Atrial natriuretic factor in hydrops fetalis caused by Rh isoimmunisation. Arch Dis Child. Jul 1990;65(7 Spec No):683-6. [Medline].

  50. Moya FR, Grannum PA, Widness JA, et al. Erythropoietin in human fetuses with immune hemolytic anemia and hydrops fetalis. Obstet Gynecol. Sep 1993;82(3):353-8. [Medline].

  51. Muller-Hansen I, Hackeloer BJ, Kattner E. [Pre- and postnatal diagnosis and treatment of hydrops fetalis--an interdisciplinary problem]. Z Geburtshilfe Neonatol. Jan-Feb 1998;202(1):2-9. [Medline].

  52. Murphy JJ, Blair GK, Fraser GC. Coagulopathy associated with large sacrococcygeal teratomas. J Pediatr Surg. Oct 1992;27(10):1308-10. [Medline].

  53. Nimrod C, Davies D, Harder J. Ultrasound evaluation of tachycardia-induced hydrops in the fetal lamb. Am J Obstet Gynecol. Sep 1987;157(3):655-9. [Medline].

  54. Nimrod C, Keane P, Harder J, et al. Atrial natriuretic peptide production in association with nonimmune fetal hydrops. Am J Obstet Gynecol. Sep 1988;159(3):625-8. [Medline].

  55. O-Prasertsawat P, Suthutvoravut S, Chaturachinda K. Hydrops fetalis due to Bart hemoglobinopathy at Ramathibodi Hospital (1978-1987): a 10-year review. J Med Assoc Thai. Feb 1990;73 Suppl 1:65-8. [Medline].

  56. Owen J, Colvin EV, Davis RO. Fetal death after successful conversion of fetal supraventricular tachycardia with digoxin and verapamil. Am J Obstet Gynecol. May 1988;158(5):1169-70. [Medline].

  57. Paladini D, Chita SK, Allan LD. Prenatal measurement of cardiothoracic ratio in evaluation of heart disease. Arch Dis Child. Jan 1990;65(1 Spec No):20-3. [Medline].

  58. Phibbs RH, Johnson P, Tooley WH. Cardiorespiratory status of erythroblastotic newborn infants. II. Blood volume, hematocrit, and serum albumin concentration in relation to hydrops fetalis. Pediatrics. Jan 1974;53(1):13-23. [Medline].

  59. Potter EL. Universal edema of the fetus unassociated with erythroblastosis. Am J Obstet Gynecol. 1943;46:130-134.

  60. Revillon Y, Jan D, Plattner V, et al. Congenital cystic adenomatoid malformation of the lung: prenatal management and prognosis. J Pediatr Surg. Aug 1993;28(8):1009-11. [Medline].

  61. Rice HE, Estes JM, Hedrick MH, et al. Congenital cystic adenomatoid malformation: a sheep model of fetal hydrops. J Pediatr Surg. May 1994;29(5):692-6. [Medline].

  62. Rodis JF, Borgida AF, Wilson M, et al. Management of parvovirus infection in pregnancy and outcomes of hydrops: a survey of members of the Society of Perinatal Obstetricians. Am J Obstet Gynecol. Oct 1998;179(4):985-8. [Medline].

  63. Ross BA. Congenital complete atrioventricular block. Pediatr Clin North Am. Feb 1990;37(1):69-78. [Medline].

  64. Saleeb S, Copel J, Friedman D, Buyon JP. Comparison of treatment with fluorinated glucocorticoids to the natural history of autoantibody-associated congenital heart block: retrospective review of the research registry for neonatal lupus. Arthritis Rheum. Nov 1999;42(11):2335-45. [Medline].

  65. Sharma RS, Yu V, Walters WA. Haemoglobin Bart's hydrops fetalis syndrome in an infant of Greek origin and prenatal diagnosis of alpha-thalassaemia. Med J Aust. Oct 20 1979;2(8):404, 433-4. [Medline].

  66. Shimokawa H, Sumioki H, Miyamoto S, et al. Is human atrial natriuretic peptide in fetal blood useful as a parameter to detect the decompensated state of the fetal heart?. J Perinat Med. 1988;16(5-6):485-6. [Medline].

  67. Shiraishi S, Kinukawa N, Nakano H, Sueishi K. Immunohistochemical distribution of vascular endothelial growth factor in the human placenta associated with hydrops fetalis. Pediatr Pathol Lab Med. Jan-Feb 1997;17(1):65-81. [Medline].

  68. Silberbach M, Anderson DF, Reller MD. Effect of atrial natriuretic peptide on vascular permeation in the ovine fetus. Pediatr Res. May 1994;35(5):555-9. [Medline].

  69. Silberbach M, Woods LL, Hohimer AR, et al. Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: effects of a non-peptide antagonist for atrial natriuretic peptide receptor. Pediatr Res. Nov 1995;38(5):722-8. [Medline].

  70. Silverman NH, Schmidt KG. Ventricular volume overload in the human fetus: observations from fetal echocardiography. J Am Soc Echocardiogr. Jan-Feb 1990;3(1):20-9. [Medline].

  71. Simpson JM, Sharland GK. Fetal tachycardias: management and outcome of 127 consecutive cases. Heart. Jun 1998;79(6):576-81. [Medline]. [Full Text].

  72. Strasburger JF, Huhta JC, Carpenter RJ Jr, et al. Doppler echocardiography in the diagnosis and management of persistent fetal arrhythmias. J Am Coll Cardiol. Jun 1986;7(6):1386-91. [Medline].

  73. Sun CC, Panny S, Combs J, Gutberlett R. Hydrops fetalis associated with Gaucher disease. Pathol Res Pract. Sep 1984;179(1):101-4. [Medline].

  74. Tannirandorn Y, Fisk NM, Shah V, et al. Plasma renin activity in fetal disease. J Perinat Med. 1990;18(3):229-31. [Medline].

  75. Thorpe-Beeston JG, Nicolaides KH. Cystic adenomatoid malformation of the lung: prenatal diagnosis and outcome. Prenat Diagn. Aug 1994;14(8):677-88. [Medline].

  76. Tongsong T, Wanapirak C, Piyamongkol W, Sudasana J. Prenatal sonographic features of sacrococcygeal teratoma. Int J Gynaecol Obstet. Nov 1999;67(2):95-101. [Medline].

  77. Ulm B, Svolba G, Ulm MR, et al. Male fetuses are particularly affected by maternal alloimmunization to D antigen. Transfusion. Feb 1999;39(2):169-73. [Medline].

  78. van der Straten MC, Gest AL. Hemolytic anemia without an increased central venous pressure does not cause hydrops in fetal sheep (Abstract). Clin Res. 1993;41:771A.

  79. van Engelen AD, Weijtens O, Brenner JI, et al. Management outcome and follow-up of fetal tachycardia. J Am Coll Cardiol. Nov 1 1994;24(5):1371-5. [Medline].

  80. Venkat-Raman N, Sebire NJ, Murphy KW. Recurrent fetal hydrops due to mucopolysaccharidoses type VII. Fetal Diagn Ther. 2006;21(3):250-4. [Medline].

  81. Ville Y, Proudler A, Kuhn P, Nicolaides KH. Aldosterone concentration in normal, growth-retarded, anemic, and hydropic fetuses. Obstet Gynecol. Oct 1994;84(4):511-4. [Medline].

  82. Watson J, Campbell S. Antenatal evaluation and management in nonimmune hydrops fetalis. Obstet Gynecol. Apr 1986;67(4):589-93. [Medline].

  83. Weiner CP, Pelzer GD, Heilskov J, et al. The effect of intravascular transfusion on umbilical venous pressure in anemic fetuses with and without hydrops. Am J Obstet Gynecol. Dec 1989;161(6 Pt 1):1498-501. [Medline].

  84. Weiner CP, Robillard JE. Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease. Am J Obstet Gynecol. Dec 1988;159(6):1353-60. [Medline].

  85. Whitecar PW, Moise KJ Jr. Sonographic methods to detect fetal anemia in red blood cell alloimmunization. Obstet Gynecol Surv. Apr 2000;55(4):240-50. [Medline].

  86. Wolf RB, Moore TR. Amniotic fluid and nonimmune hydrops fetalis. In: Fanaroff and Martin's Neonatal-Perinatal Medicine. 8th ed. 2006:409-28.

  87. Yaegashi N, Niinuma T, Chisaka H, et al. The incidence of, and factors leading to, parvovirus B19-related hydrops fetalis following maternal infection; report of 10 cases and meta-analysis. J Infect. Jul 1998;37(1):28-35. [Medline].

  88. Yamada A, Kasugai M, Ohno Y, et al. Antenatal diagnosis of twin-twin transfusion syndrome by Doppler ultrasound. Obstet Gynecol. Dec 1991;78(6):1058-61. [Medline].

  89. Yamada H, Kato EH, Furuta I, et al. Hematopoietic cytokine levels and in vitro colony formation assay in fetal anemia. Semin Thromb Hemost. 1998;24(5):485-90. [Medline].

  90. Zankl A, Osterheld MC, Vial Y, Beurret N, et al. Right-sided diaphragmatic eventration: a rare cause of non-immune hydrops fetalis. Neonatology. 2007;92(1):14-8. [Medline].

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Further Reading

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Keywords

hydrops foetalis, hydrops, fetal hydrops, universal edema of the newborn, nonimmune hydrops, fetal edema, fetal subcutaneous tissue edema, placental edema, hydramnios, maternal-fetal blood group incompatibilities, maternal isoimmunization to fetal blood group antigens, isoimmune hemolytic disease, immune hydrops, homozygous alpha-thalassemia, Bart hydrops, congenital malformations, premature delivery, fetal fluid accumulations, fetal thoracentesis

fetal paracentesis, fetal surgical procedures, maternal ABO-factor isoimmunization, Rh D hemolytic disease, drug use, collagen disease, thyroid disease, diabetes, organ transplant, blunt abdominal trauma, coagulopathy, use of teratogenic drugs, sexually transmitted diseases, hemoglobinopathy, viral illness, fetomaternal transfusion, herpetic lesions, chancre, hemolytic disease of newborn, erythroblastosis, glucose phosphate isomerase deficiency, pyruvate kinase deficiency, G-6-PD deficiency, congenitaldyserythropoietic anemia, Diamond-Blackfan syndrome, lethal hereditary spherocytosis, spectrin synthesis defects, congenital erythropoietic porphyria

Günther disease, leukemia with Down syndrome, leukemia with Noonan syndrome, Bart hemoglobinopathy, Parvovirus B19, B19V, intracranial hemorrhage, intraventricular hemorrhage, hepatic laceration, placental subchorial hemorrhage, sacrococcygeal teratoma, fetomaternal hemorrhage, twin-to-twin transfusion, isoimmune fetal thrombocytopenia, fetal anemia, fetal aplastic anemia, malformation syndromes, fetal hemorrhage, placental choriocarcinoma, placental chorangioma, partial placental abruption

reduced fetal body movements, sinusoidal fetal heart rate patterns, fetal acardia, fetus papyraceous, stuck twin, vanishing twin, velamentous cord insertion, atrial natriuretic factor, fetal meconium peritonitis, lysosomal storage disorders, cystic hygroma, cystic adenomatoid malformation of the lung, fibroelastosis, prenatal closure of foramen ovale, prenatal closure of ductus arteriosus, idiopathic arterial calcification, AV block, atrial flutter, tachyarrhythmia, congenital heart block, maternal collagen disease, congenital syphilis, lethal multiple pterygium syndromes, fetal coagulopathy, bronchopulmonary sequestration, tension hydrothorax

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Contributor Information and Disclosures

Author

Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP, Clinical Assistant Professor of Pediatrics, Vanderbilt University Medical Center
Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

David N Sheftel, MD, Director, Division of Neonatology, Clinical Associate Professor, Department of Pediatrics, Lutheran General Children's Hospital of Park Ridge, Chicago Medical School
David N Sheftel, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Arun K Pramanik, MD, MBBS, Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center
Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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