Medical Care
The diagnosis and management of hydrops fetalis continue to be challenges for perinatologists and neonatologists. Mortality is 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.
If prenatally diagnosed, the mother should be referred to a high-risk center for further management and multidisciplinary counseling due to the high risk of fetal demise. [48] Close coordination between obstetric and neonatal specialists is essential. [36] Prenatal steroids should be administered if preterm delivery is anticipated.
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 pregnancies. Currently, parental involvement and guidance are fundamental requirements and require the full parental knowledge of all the 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.
Fetal intervention
Possible fetal interventions include fetal transfusion for profound fetal anemia, maternal antiarrhythmic medications (eg, digoxin) for fetal arrhythmia, and in-utero surgery (eg, fetal thoracocentesis/paracentesis, surgical resection).
Decisions about fetal treatment are often uncertain and difficult, because the necessary evidence for a diagnosis as well as for balancing the risks against the benefits of a specific treatment 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. Likewise, many treatment schemes are recognized, but all are based on the biases and experiences of the individual authors.
To further complicate the issue, spontaneous remission of the hydropic process has been reported in hundreds of cases. The 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, parvovirus and cytomegalovirus (CMV) infections, placental chorangioma, and idiopathic ascites or pleural effusions. Clinicians and parents must completely understand that decisions at this are essentially 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.
Fetal arrhythmias
Treatment options reported for fetal arrhythmias have included doing nothing, administering drugs, and immediate delivery. If fetal maturity permits, the most simple and direct approach is 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 strategy 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 [PO], intramuscular [IM], intravenous [IV]), to the fetus (intraperitoneal [IP], IM, IV via cordocentesis), and to both, in an attempt to correct the fetal arrhythmias. Even fetal pacing has been reported. As perhaps expected, treatment failures are infrequently reported whereas 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.
The agents used have included digitalis, furosemide, flecainide, verapamil, amiodarone, propranolol, procainamide, quinidine, adenosine, sotalol, terbutaline, corticosteroids, and immunoglobulins; various combinations of these drugs have also been administered. 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, the 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 the fetus and the mother until more definitive data are available.
Fetal anemia
Intrauterine IP fetal transfusion
The success of intrauterine IP fetal transfusion with packed red blood cells (PRBCs) in the treatment of the severely anemic fetus of an 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 intrauterine IP fetal transfusion 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 IP route has apparently become accepted as the standard of care for the fetus with severe anemia.
Intravascular (umbilical vein [UV]) transfusion
A more direct approach has been used with increasing frequency: Intravascular (UV) transfusion of packed RBCs is the treatment of choice for fetal anemia, replacing IP transfusion. Hydrops or fetal anemia (hematocrit [Hct] level <30%) is an indication for UV transfusion in infants with pulmonary immaturity.
Intravascular fetal transfusion is facilitated by maternal and fetal sedation with diazepam and by fetal paralysis with pancuronium. Packed RBCs are given by slow-push infusion after cross-matching with the mother's serum. The cells should be obtained from a CMV-negative donor and irradiated to kill the lymphocytes to avoid graft-versus-host disease. Transfusions should achieve a posttransfusion Hct level of 45%–55% and can be repeated every 3-5 weeks.
Indications for delivery include pulmonary maturity, fetal distress, complications of percutaneous umbilical blood sampling, or 35-37 weeks' gestation.
The survival rate for intrauterine transfusions is 89%; the complication rate is 3%. Complications include rupture of the membranes and preterm delivery, infection, fetal distress requiring emergency cesarean delivery, and perinatal death.
Routes of fetal administration of blood products
Reported routes of fetal administration of blood products have included percutaneous UV, intrahepatic UV, 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 IV immunoglobulin (Ig) G, fetal platelet transfusion, and fetal administration of human granulocyte-colony stimulating factor (G-CSF), again using various routes.
The use of more direct invasive methods may seem to increase fetal risk. This may not appear justified in view of the very low risks demonstrated to accompany the IP route. Prudent clinicians may be justified in taking a very cautious approach to these relatively newer therapeutic techniques until such time as definitive evidence is available that the benefit-to-risk ratio of them has improved.
Fetal hemorrhage
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 a 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 their potential effectiveness.
Twin-to-twin transfusion syndrome
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 also surprisingly commonly reported. Thus, the management of the twin-to-twin transfusion syndrome remains 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
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 and pericardial effusions and ascites
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, peritoneoamniotic shunts, and IP albumin. Successes and failures have been reported with all these methods; there is no evidence to suggest that one approach is any better than another, because proper comparative trial data are not available.
Underlying fetal anomalies
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 case 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.
Perinatal management
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. Note the following:
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Once hydrops has been diagnosed antenatally, make every effort to establish the cause; this is helpful in treating the infant at birth. Perform or repeat antenatal ultrasonographic 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.
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Assessment of fetal hematocrit, partial pressure of oxygen (pO2), and pH by percutaneous umbilical sampling, although risky, may be helpful in selected cases for early management.
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In addition to appropriate equipment and supplies, a skilled team of experienced healthcare professionals (neonatologists, nurses, respiratory therapists, radiograph technician, ultrasonography technician) should be present in the delivery room.
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Inform the blood bank or have type O-negative blood available in the delivery room for immediate transfusion through umbilical catheters. If the fetus is severly anemic, PRBC transfusion can be life saving and may improve the resuscitation outcomes. If blood transfusion is required in the delivey room, before the blood is tranfused, obtain blood samples for a complete blood cell (CBC) count, newborn diagnostic screening, and other laboratory tests.
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After establishing the infant's airway and ventilation, place umbilical arterial and venous catheters to monitor arterial pressure, blood gases, and venous pressure.
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PRBCs or whole cross-matched blood should be available for transfusion or partial exchange transfusion to correct severe anemia in the neonatal intensive care unit (NICU).
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Anticipate and promptly correct metabolic derangements such as acidosis and hypoglycemia.
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Surfactant deficiency and hypoplastic lungs may be associated with hydrops and are managed accordingly.
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Drainage of the pleural and abdominal cavities of pleural and ascitic fluid, respectively, may be necessary to adequately ventilate the infant.
Consultations
Fetal hydrops should be considered a medical emergency that requires urgent referral to a maternal-fetal medicine specialist, allowing for detailed and comprehensive ultrasonographic examination and early identification of any treatable causes. Referral to a geneticist is also essential to plan for additional investigations.
Autopsy should be strongly recommended in all cases of nonimmune fetal hydrops . Fetal blood, tissue, DNA, and amniotic fluid should be collected for storage. The preservation of a potentially dividing fetal cell line (amniocytes, skin biopsy) is indicated for future biochemical or molecular genetic testing. Placental examination (microscopy, histopathology) focusing on tumors, fetal anemia, infection, and metabolic disorder is indicated. [39, 49]
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Chest radiograph revealing the presence of pleural effusion, severe edema, and bilateral chest tubes.
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Chest and abdomen radiograph revealing the presence of severe edema and ascites.
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Chest and abdomen radiograph revealing the presence of severe edema, pleural effusion, and bilateral chest tubes. An umbilical artery catheter, umbilical vein catheter, and endotracheal tube are in place.
