Nonimmune Hydrops Fetalis

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Chapter 128 Nonimmune Hydrops Fetalis

128CHAPTER

Nonimmune Hydrops

Fetalis

Key Points

■ Nonimmune hydrops fetalis is a serious fetal

condition in which abnormal fluid accumulates in

at least two different fetal compartments, and in

which circulating antibodies against red-cell

antigens are absent in the mother.

■ Nonimmune hydrops fetalis is a heterogeneous

disorder, caused by a large number of underlying

pathologic processes. While the majority of cases

appear to be idiopathic, the most common

recognizable cause is cardiovascular pathology.

■ Following the sonographic detection of hydrops,

the most important step is to differentiate between

immune and nonimmune causes. Once immune

causes are excluded, a detailed anatomical survey

is needed to rule out congenital abnormalities,

which could be the cause of the hydrops.

■ Nonimmune hydrops can occur secondary to fetal

anatomical abnormalities (cardiac, thoracic,

gastrointestinal, neurologic, genitourinary,

vascular, or skeletal), placental/cord abnormalities,

fetal hematologic, neoplastic or metabolic

disorders, infection, fetal genetic anomalies, and

maternal abnormalities.

■ Maternal blood tests should include an indirect

Coombs antibody screen, maternal blood type,

Kleihauer–Betke stain, complete blood count with

differential and erythrocyte indices, hemoglobin

electrophoresis, and glucose-6-phosphate

dehydrogenase deficiency screen. Additional

maternal blood work should include TORCH titers,

syphilis screen, and parvovirus B19 IgG and IgM

titers.

■ Fetal echocardiography and invasive testing for

fetal karyotype should be offered.

■ While the optimal mode of delivery is uncertain,

cesarean section is advised for all potentially viable

fetuses due to the risk for soft-tissue dystocia.

■ Fetal therapy may be possible, including PUBS

with transfusion, maternal administration of

cardiac medications, and fetal shunt placement.

■ The long-term prognosis will depend on the

nature of the underlying abnormality.

■ The recurrence risk will depend on the underlying

etiology of the nonimmune hydrops.

CONDITION

Nonimmune hydrops fetalis (NIHF) is a serious fetal con-dition in which abnormal fluid accumulates in at least twodifferent fetal compartments, and in which circulating an-tibodies against red cell antigens are absent in the mother.Hydrops fetalis is associated with a pathologic increase in in-terstitial and total fetal body water, usually appearing in fetalsoft tissues and serous cavities. It may be either immunologicor nonimmunologic, depending on the presence or absenceof maternal antibodies against fetal red cell antigens. Whileit was previously thought that the majority of cases of hy-drops fetalis were secondary to maternal–fetal blood group

incompatibilities, it is now estimated that over 90% of casesare nonimmunologic (Santolaya et al., 1992).

NIHF is a heterogeneous disorder, caused by a largenumber of underlying pathologic processes. The majority ofcases appear to be idiopathic, although some investigatorshave stated that with thorough investigation an underlyingcause can be identified in as many as 84% of cases (Holzgreveet al., 1984; Norton, 1994; Wilkins, 1999). When prenatally di-agnosed cases of NIHF and cases of intrauterine fetal death areincluded, the success rate in discovering an underling causefor NIHF may be as low as 40% (Norton, 1994). The literatureon NIHF consists almost entirely of case reports or small caseseries, together with reviews of these case series. A review ofthese reports suggests that the most common recognizable

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Part II Management of Fetal Conditions Diagnosed by Sonography

cause of NIHF is cardiovascular pathology (accounting for17% to 35% of cases), followed by chromosomal abnormal-ities (accounting for 14% to 16% of cases), and hemato-logic disorders (accounting for 4% to 12% of cases) (Norton,1994). The remainder of causes of NIHF are rare conditions,many of which are difficult to diagnose prenatally. The rangeof possible underlying causes for NIHF is summarized inTable 128-1, listed in order of expected incidence.

Other than idiopathic cases, cardiac malformations ac-count for the majority of cases of NIHF (Knilans, 1995). Thereis no particular form of cardiac abnormality that always re-sults in hydrops, although the more severe the malformationthe greater the likelihood of hydrops developing. The com-mon mechanism of NIHF in cases of cardiac malformationor arrhythmia is the development of congestive heart failure,with increasing generalized fluid overload. The prognosis forfetuses with structural cardiac malformations and hydrops isextremely poor, with a mortality rate approaching 100% insome series (Crawford et al., 1988).

Chromosomal causes of NIHF are common; the mostfrequent is Turner syndrome, with its typical sonographicfinding of cystic hygroma. A wide range of other genetic syn-dromes is also associated with NIHF, such as arthrogrypo-sis, tuberous sclerosis, Pena–Shokeir syndrome, and Noonansyndrome (Jauniaux et al., 1990).

The underlying mechanism for the association of NIHFwith hematologic abnormalities is most likely severe fetalanemia leading to high-output cardiac failure (Arcasoy andGallagher, 1995). Fetal anemia can result from failure to man-ufacture normal hemoglobin (such as α-thalassemia), fetalhemorrhage (such as intracranial bleeding), hemolysis, (suchas glucose-6-phosphate dehydrogenase deficiency), or failureto form erythrocytes because of marrow destruction (such asparvovirus B19 infection).

Congenital cystic adenomatoid malformation (CCAM)is the most common thoracic lesion associated with hy-drops. Other thoracic causes of hydrops include bronchopul-monary sequestration, thoracic masses, and diaphragmatichernia. The underlying mechanism for the association ofhydrops with these thoracic conditions is most likely ob-struction to venous return because of increased intrathoracicpressure.

Congenital infection with a wide variety of organisms isa well-recognized cause of hydrops (Barron and Pass, 1995).Causative organisms include syphilis, cytomegalovirus, par-vovirus B19, toxoplasmosis, herpes simplex, rubella, andcoxsackievirus. Possible mechanisms for the association ofcongenital infection with hydrops include fetal anemia fromsuppression of erythrocyte production, fetal myocarditis, orfetal hepatitis. In some cases of congenital infection, such assyphilis, the presence of hydrops is associated with a very poorprognosis. In other cases, hydrops from congenital infectionmay be self-limited and may resolve spontaneously. Fetal par-vovirus B19 infection results in an aplastic crisis, which leadsto profound anemia, and hydrops, the outcome of which maybe either fetal death or spontaneous resolution without long-term morbidity (Morey et al., 1991; Levy et al., 1997).

A wide variety of structural fetal malformations hasbeen associated with the development of NIHF. These includeskeletal dysplasias, which may be associated with thoraciccompression, impairment of venous return, and subsequenthydrops. The association of other structural malformationswith NIHF, such as gastrointestinal, genitourinary, and neu-rologic abnormalities, may represent chance occurrences, asit is difficult to elucidate a plausible underlying mechanismfor hydrops in many cases.

Some fetal conditions, such as Finnish nephrosis andhepatic fibrosis, result in profound hypoproteinemia or cir-rhosis, which may subsequently lead to hydrops. The mech-anism for the association between metabolic disorders andNIHF is unclear, but may be related to soft-tissue swellingand obstruction of venous return to the heart. Certain non-cardiac fetal abnormalities may result in hydrops by causinghigh-output cardiac failure. Examples include sacrococcygealteratoma, neuroblastoma, placental chorioangioma, and um-bilical cord masses.

NIHF may very rarely occur in association with sig-nificant maternal medical illnesses, such as severe anemia,hypoproteinemia, or diabetes mellitus. The “mirror” syn-drome, also known as Ballantyne syndrome, is the combi-nation of fetal hydrops with generalized fluid overload and apreeclampsia-like state in the mother (Carbillon et al., 1997).In general, the maternal clinical features resolve only withdelivery of the fetus and placenta.

INCIDENCE

The precise incidence of NIHF is difficult to elucidate, as manycases are not detected prior to intrauterine fetal death, andsome cases may resolve spontaneously in utero. The generallyreported incidence of NIHF is 1 in 1500 to 1 in 4000 deliveries(Romero et al., 1988; Wilkins, 1999).

SONOGRAPHIC FINDINGS

The diagnosis of hydrops is made following the detectionof abnormal or increased fluid accumulation in at least twodistinct fetal body cavities. Examples include pericardial ef-fusion, pleural effusion, ascites, subcutaneous edema, cystichygroma, polyhydramnios, and placental thickening (Figures128-1 and 128-2). In general, skin thickness of at least 5 mmis required to diagnose subcutaneous edema, and a placentalthickness of at least 6 cm is required to diagnose placen-tomegaly (Romero et al., 1988). These features do not neces-sarily indicate hydrops; it should be noted that skin thicken-ing of at least 5 mm may be commonly seen in macrosomicfetuses. If abnormal fluid accumulation is confined to onlyone site, then the diagnosis of hydrops should not be used,and the case should be described simply in terms of the in-volved site, such as isolated ascites or isolated pleural effusion.

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Table 128-1

Conditions Associated with Nonimmune Hydrops Fetalis

Idiopathic hydrops Unknown cause

Cardiac malformation Hypoplastic left ventricle; Atrioventricular canal defect; Atrial septal defect; Ventricular septal defect; Tetralogy

of Fallot; Hypoplastic right ventricle; Ebstein’s anomaly; Truncus arteriosus; Transposition of great vessels;

Aortic stenosis or atresia; Pulmonary stenosis or atresia; Cardiomyopathy; Endocardial fibroelastosis;

Premature closure of ductus arteriosus; Premature closure of foramen ovale; Rhabdomyoma; Intrapericardial

teratoma

Cardiac arrhythmia Supraventricular tachycardia; Atrial flutter; Heart block; Bradyarrhythmias; Wolff–Parkinson–White syndrome

Chromosomal

abnormality

Trisomy 21; Trisomy 18; Trisomy 13; Turner syndrome; Triploidy; Tetraploidy; 18q+; 13q−; Others

Hematologic disorder Alpha-thalassemia; Parvovirus B19 infection; Fetomaternal transfusion; In utero hemorrhage;

Glucose-6-phosphate dehydrogenase deficiency; Fetal red cell enzyme deficiencies; Twin-to-twin transfusion

syndrome

Thoracic abnormality Congenital cystic adenomatoid malformation of lung; Bronchopulmonary sequestration; Diaphragmatic

hernia; Chylothorax; Pulmonary lymphangiectasia; Intrathoracic mass (teratoma, leiomyosarcoma);

Bronchogenic cyst

Genetic syndrome Arthrogryposis; Multiple pterygium syndrome; Noonan syndrome; Pena–Shokeir syndrome; Cornelia de Lange

syndrome; Tuberous sclerosis; Prune belly syndrome; Myotonic dystrophy; Neu–Laxova syndrome

Infectious disease Cytomegalovirus; Parvovirus B19; Toxoplasmosis; Syphilis; Herpes simplex; Rubella; Coxsackievirus; Varicella;

Respiratory syncytial virus

Skeletal dysplasia Achondroplasia; Achondrogenesis; Osteogenesis imperfecta; Hypophosphatasia; Short rib polydactyly;

Thanatophoric dwarfism; Asphyxiating thoracic dysplasia; Osteochondrodystrophy; Osteochondrodysplasia;

Chondrodystrophy; Chondrodysplasia

Gastrointestinal

disorder

Diaphragmatic hernia; Esophageal or intestinal atresia; Imperforate anus; Midgut volvulus; Meconium

peritonitis; Duodenal diverticulum; Intestinal duplication; Malrotation

Genitourinary disorder Congenital Finnish nephrosis; Hypoplastic kidney; Polycystic kidneys; Renal vein thrombosis; Bladder outlet

obstruction; Dysplastic kidneys

Hepatic disorder Hepatic fibrosis; Cholestasis; Polycystic liver disease; Biliary atresia; Hepatic calcification; Giant cell hepatitis;

Cirrhosis with portal hypertension; Hepatic necrosis

Neoplastic disorder Neuroblastoma; Teratoma; Congenital leukemia; Pulmonary leiomyosarcoma; Hemangioendothelioma of liver

Metabolic disorder Gaucher disease; GM1 gangliosidosis; Mucolipidoses; Mucopolysaccharidoses; Galactosialidosis; Carnitine

deficiency; Pyruvate kinase deficiency

Neurologic disorder Encephalocele; Fetal intracranial hemorrhage; Vein of Galen aneurysm; Porencephaly with absent corpus

callosum

Vascular disorder Arteriovenous malformation; Sacrococcygeal teratoma; Vena caval thrombosis; Hemangioendothelioma;

Arterial calcification; Cerebral angioma

Placenta/cord

abnormality

Chorioangioma; Chorionic vein thrombosis; Umbilical cord torsion; True knot of cord; Angiomyxoma of cord;

Placental hemorrhagic endovasculitis

Maternal abnormalities Mirror syndrome; Severe maternal anemia, diabetes mellitus or hypoproteinemia; Maternal indomethacin use

Adapted from:

Holzgreve W, Holzgreve B, Curry CJ: Nonimmune hydrops fetalis: diagnosis and management. Semin Perinatol 1985;9:52-57.

Romero R, Pilu G, Jeanty P, et al. Nonimmune hydrops fetalis. In Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins JC (eds): Prenatal Diagnosis of Congenital

Anomalies. Norwalk, Appleton And Lange, 1988;414-426.

Jones DC: Nonimmune fetal hydrops: diagnosis and obstetrical management. Semin Perinatol 1995;19:447-461.

Wilkins I: Nonimmune hydrops. In Creasy RK, Resnik R (eds): Maternal-Fetal Medicine (4th edition). Philadelphia, WB Saunders, 1999;769-782.

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Figure 128-1 Prenatal ultrasound image of fetus at 26 weekswith nonimmune hydrops. Sagittal view demonstrates extensiveascites and pleural effusions.

NIHF may initially present with an isolated fluid accumula-tion in one site, such as pleural effusion with congenital cysticadenomatoid malformation, but as intrathoracic pressure in-creases and venous return decreases, generalized hydrops maypresent.

Fetal ascites is diagnosed sonographically by the visu-alization of an echolucent rim encompassing the entire fetalabdomen in a transverse view (see Figure 128-1). Loops ofbowel and the outline of the fetal liver, spleen, bladder, anddiaphragm are generally more easily seen in the presence of

Figure 128-2 Prenatal ultrasound image of fetus at 30 weekswith nonimmune hydrops. Transverse view through fetal chestdemonstrates extensive pleural effusion with deviation of cardiacaxis to left.

ascites. Pericardial effusion is diagnosed by the appearance ofan echolucent rim of at least 1 to 3 mm thickness around bothcardiac ventricles. Pleural effusion, which may be unilateralor bilateral, also presents as an echolucent space outlining thediaphragm.

Other sonographic features of NIHF will depend onthe cause of the hydrops. A careful fetal anatomical survey,including fetal echocardiography, should be performed inall cases to detect any associated structural fetal malforma-tions. Measurement of the middle cerebral artery peak sys-tolic velocity using Doppler ultrasound can help identify casesof NIHF associated with fetal anemia (Hernandez-Andradeet al., 2004).

DIFFERENTIAL DIAGNOSIS

Following the sonographic diagnosis of hydrops the first stepis to differentiate between immune and nonimmune causes.This is easily accomplished by the performance of a maternalindirect Coombs test to screen for antibodies associated withblood group incompatibility.

Following the exclusion of immune causes of hydrops,each condition listed in Table 128-1 should be consideredwhen trying to determine the cause of NIHF. This is accom-plished by a review of maternal and paternal histories, de-tailed fetal sonographic survey, and the use of appropriatediagnostic laboratory studies.

ANTENATAL NATURAL HISTORY

The precise antenatal natural history of NIHF depends en-tirely on the underlying cause. The natural history of hydropsis poorly understood, so little information is available regard-ing prognostic factors to predict in utero progression. In gen-eral, NIHF is associated with a 75% to 90% fetal mortalityrate (Romero et al., 1988). The progression of fetal signs anddevelopment reflects the underlying cause. Cases of NIHF sec-ondary to fetal parvovirus B19 infection, for example, mayresult in intrauterine fetal death or may result in spontaneousresolution. By contrast, cases of NIHF associated with struc-tural cardiac malformation almost always result in intrauter-ine fetal death or early neonatal death. No series are availablefor review describing sufficient cases of NIHF caused by eachindividual underlying cause, to enable accurate prediction ofantenatal natural history.

MANAGEMENT OF PREGNANCY

Following the sonographic detection of hydrops, the preg-nant woman should be promptly referred to a tertiary carefacility, with availability of a multidisciplinary team con-sisting of perinatologists, neonatologists, clinical geneticists,

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and other pediatric subspecialists. Careful maternal and pa-ternal histories should be obtained, to evaluate for possiblehealth problems, family histories, or ethnic predisposition toany of the conditions listed in Table 128-1. Maternal bloodwork should include an indirect Coombs antibody screen,maternal blood type, Kleihauer–Betke stain, complete bloodcount with differential and erythrocyte indexes, hemoglobinelectrophoresis, and glucose-6-phosphate dehydrogenase de-ficiency screen. Additional maternal blood work should in-clude an evaluation for infectious diseases, including TORCH(toxoplasmosis, rubella, cytomegalovirus, and herpes sim-plex) titers, rapid plasma reagent test, and parvovirus B19IgG and IgM titers.

A detailed fetal sonographic anatomy survey should beperformed to evaluate for possible associated structural mal-formations. Because of the strong association between NIHFand cardiac malformations, fetal echocardiography shouldalso be performed, with particular attention paid to possiblefetal rhythm disturbances. Fetal heart rate monitoring for 12to 24 hours should be considered to rule out an underlyingfetal arrhythmia.

Invasive testing for fetal karyotype should also be of-fered. This can be performed by means of amniocentesis,with the use of fluorescence in situ hybridization or poly-merase chain reaction (PCR), to facilitate a rapid diagnosisof the common aneuploidies. While previously the preferredinvasive diagnostic procedure at late gestational age was a fe-tal percutaneous umbilical blood sample (PUBS), this is nowrarely necessary. The previously cited advantage of a PUBSwas that it allowed rapid determination of fetal karyotype,in addition to providing details of fetal hematocrit, plateletcount, liver-function tests, hemoglobin electrophoresis, andfetal IgM specific to the various infectious causes of NIHF. Inaddition, it also allowed the opportunity to transfuse the fetuswith packed red cells immediately if profound fetal anemia isdiagnosed. However, given the precision of middle cerebralartery Doppler evaluation in predicting the anemic fetus, andthe easy availability of either FISH or PCR for rapid chromo-some evaluation, the need for PUBS continues to decrease.Amniotic fluid (obtained either at the same time as a PUBSor by amniocentesis) may be sent for α-fetoprotein level (in-creased in Finnish nephrosis and sacrococcygeal teratoma),and polymerase chain reaction (PCR) testing for infectiousagents. Metabolic testing can also be performed on amnioticfluid when a specific disorder is suspected.

Following the laboratory and sonographic evaluation,a diagnosis of idiopathic NIHF, or NIHF secondary to a spe-cific condition, will be made. If a specific underlying causehas been discovered, patient counseling will be dictated by theparticular abnormality. In general, the presence of hydropstogether with a structural malformation, such as cardiac ab-normality, is associated with a very poor prognosis. Coun-seling should therefore also include the possibility of electivepregnancy termination, depending on the gestational age atpresentation. Patients should be counseled by a multidisci-plinary team that includes a perinatologist, neonatologist, ge-neticist, and appropriate additional pediatric subspecialists.

Options for fetal intervention to treat the underlying problemand hydrops are available and are discussed in the followingsection.

If expectant management of the fetus with NIHF is cho-sen, careful sonographic surveillance should be performed,including biophysical profiles on a frequent basis. The pre-cise timing of fetal surveillance testing is uncertain and de-pends on the gestational age at presentation. If the fetus isconsidered viable, it may be reasonable to admit the motherand perform daily fetal testing with nonstress tests or bio-physical profiles. If the hydrops appears to be resolving itwould be reasonable to decrease the frequency of testing,provided that fetal testing has been reassuring to date. Re-peat sonographic fetal anatomy surveys should be performedevery 2 weeks to confirm appropriate fetal growth and to im-prove the chances of detecting an underlying structural fetalmalformation.

Timing of delivery is also uncertain with NIHF. De-pending on the gestational age, premature delivery may beindicated if fetal testing becomes nonreassuring. Otherwise,the most common practice is to continue expectant manage-ment until 37 weeks of gestation, or until fetal lung matu-rity has been confirmed by amniocentesis. It is possible thatmature lecithin:sphingomyelin ratios may be less frequentlyobtained near term in the fetus with hydrops, as comparedwith nonhydropic fetuses (Romero et al., 1988). Expectantmanagement may also be complicated by preeclampsia in upto 50% of cases, and this may necessitate immediate pretermdelivery. In addition, NIHF is frequently associated with poly-hydramnios, which may precipitate preterm labor due to uter-ine overdistention. Periodic reduction amniocenteses may berequired to relieve maternal discomfort from severe polyhy-dramnios.

The optimal mode of delivery for the hydropic fetus isuncertain, as the overall prognosis is poor regardless of theform of delivery. Because of the risk of soft-tissue dystociaassociated with hydrops, it is generally advisable to deliver allpotentially viable fetuses with NIHF by cesarean. This shouldminimize the chances of maternal and fetal trauma. In casesin which the fetus is not expected to survive, the option oftherapeutic thoracentesis or paracentesis to optimize a vaginaldelivery is also reasonable. However, patients should be madeaware of the extremely small likelihood of neonatal survival.The optimal location of delivery should be a tertiary care cen-ter, with the immediate availability of skilled neonatologistsand other appropriate pediatric subspecialists.

FETAL INTERVENTION

The option of fetal therapy in select cases of NIHF is possible.The underlying pathology that is most amenable to prena-tal therapy is fetal anemia. When a diagnostic PUBS is un-dertaken for any fetus with NIHF, immediate transfusion ofpacked red cells, if profound fetal anemia is diagnosed, shouldbe performed. Arrangements prior to performance of a PUBS

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in such cases should include preparation of group O, irra-diated, packed red blood cells that are anticytomegalovirusnegative, Rho(D) negative, Kell negative, and cross-matchedcompatible with maternal serum. The unit of red cells shouldbe tightly packed with a hematocrit of at least 80%, and ablood transfusion setup should be primed as the diagnosticPUBS is performed. This will ensure that prompt intravascu-lar fetal transfusion can be performed as soon as significantfetal anemia is diagnosed, and prior to withdrawal of the nee-dle from the umbilical vein. Once a fetal hematocrit of lessthan 30% is detected, fetal intravascular transfusion shouldbegin. Fetal paralysis with pancuronium or vecuronium isgenerally not required in cases of hydrops, as fetal activity isoften minimal.

The volume of packed red cells to be transfused is de-rived using formulas that take into account the starting hema-tocrit, hematocrit of transfused blood, target hematocrit, anda correction factor for the volume of blood in the placentalcirculation. A commonly used formula for volume of bloodto be transfused is

VT = (desired final hematocrit − initial fetal hematocrit)

(donor blood hematocrit)

×(150) × (EFW)

where VT is volume of blood transfused, 150 is a placentalcorrection factor, and EFW is the estimated fetal weight inkilograms (Kaufman and Paidas, 1994). It is generally notadvisable to transfuse a hydropic fetus to a final hematocritthat is either greater than 25% or greater than four timesthe initial hematocrit (Radunovic et al., 1992). This has beenassociated with fluid overload and sudden intrauterine fetaldeath. In cases of NIHF secondary to fetal anemia, the goalof the first intrauterine transfusion should be a hematocritof 20% to 25%, and the transfusion should then be repeatedin 48 to 72 hours to bring the final hematocrit to a level of40% to 45%. For many fetuses with NIHF and anemia sec-ondary to parvovirus B19 infection, this transfusion may beall that is needed to maintain a normal fetal hematocrit, as theinitial insult to the fetal marrow is generally self-limiting. An-other therapeutic option for fetuses with NIHF and anemiais to perform a combined intravascular and intraperitonealtransfusion, with the intravascular aliquot of blood designedto provide an acute increase in fetal hematocrit and the in-traperitoneal aliquot designed to provide a slower sustainedincrease in hematocrit. To date there are no adequate seriescomparing these different approaches for the treatment ofNIHF secondary to fetal anemia.

Other forms of fetal intervention for NIHF includemedical therapy for the mother to correct fetal arrhythmias(see Chapters 42 and 54). Digoxin administration to preg-nant women has been successful in the treatment of fetal ar-rhythmias, with resolution of hydrops in some cases (Knilans,1995).

Surgical treatment for the fetus with NIHF is also possi-ble. Fetal thoracentesis may be performed under sonographicguidance with resolution of pleural effusions (Jones, 1995).

If repeat thoracenteses are needed, consideration should begiven to placement of a thoracoamniotic shunt. Such proce-dures are likely to be beneficial only for cases of NIHF in whichpleural effusions are secondary to intrinsic thoracic malfor-mations. Other surgical procedures that can be considered forfetuses with NIHF and underlying structural malformationsinclude open fetal surgical resection of thoracic masses orsacrococcygeal teratoma (Bullard and Harrison, 1995). How-ever, few data are available confirming whether such invasiveapproaches have a significant impact on fetal or neonatal out-come.

TREATMENT OF THE NEWBORN

Infants with hydrops should be delivered in a tertiary care cen-ter with immediate availability of a multidisciplinary neonatalresuscitation team. Immediate neonatal endotracheal intu-bation will almost certainly be needed, and such intubationscan be technically difficult (Carlton et al., 1989). A high-frequency ventilator and high airway-pressure settings maybe needed to achieve adequate gas exchange. Paracentesis andthoracentesis, with placement of bilateral chest tubes, mayalso be needed to allow adequate ventilation and effective gasexchange. Placement of umbilical artery and umbilical veinlines may be needed to aid in the resuscitation (McMahanand Donovan, 1995). Use of blood products, albumin, anddiuretics may be needed to effectively maintain adequateintravascular volume without significant fluid overload orsoft-tissue edema.

If the neonate can be stabilized in the delivery room,transport to a neonatal intensive care unit should be arrangedpromptly. This should be followed by a thorough physical ex-amination, with the aid of appropriate radiologic investiga-tions and echocardiography, to confirm absence of significantstructural malformation. If additional structural malforma-tions are detected, specific therapy should be tailored to theindividual abnormalities. Appropriate pediatric subspecialistconsultation, including a clinical geneticist, should also bearranged.

SURGICAL TREATMENT

Possible surgical treatments for fetal hydrops include fetalthoracoamniotic shunt placement for cases of NIHF asso-ciated with thoracic masses or persistent pleural effusions.Open fetal surgical resection of thoracic masses, such as con-genital cystic adenomatoid malformation (see Chapter 35)and bronchopulmonary sequestration (see Chapter 34), arealso possible (Bullard and Harrison, 1995). Open surgicalresection of fetal sacrococcygeal teratoma with associated hy-drops is also possible, although there are so few cases thatit is currently difficult to evaluate the role of such invasiveprocedures (see Chapter 115).

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LONG-TERM OUTCOME

The prognosis for infants with hydrops depends entirely onthe nature of any underlying abnormalities. The perinatalmortality rate ranges from 40% to 90%, depending on thecause, but may approach 100% in cases of NIHF associatedwith structural cardiac malformations (Romero et al., 1988;Wilkins, 1999; Jones, 1995). No long-term studies are avail-able for counseling parents on the likely survival or morbidityif a successful neonatal resuscitation is achieved.

GENETICS AND RECURRENCE RISK

A postmortem examination is indicated in all cases of NIHFthat result in fetal or neonatal death. This will maximize thenumber of cases in which a definite underlying cause is iden-tified and will facilitate appropriate genetic counseling andprediction of recurrence risk (Steiner, 1995). Recurrence ofidiopathic NIHF is rare, although case series of recurrenceshave been documented (Wilkins, 1999). In one case series,one mother had three consecutive pregnancies complicatedby recurrent idiopathic NIHF and another had two consec-utive pregnancies complicated by recurrent idiopathic NIHF(Onwude et al., 1992). Patients should therefore be madeaware that, while idiopathic NIHF is extremely rare, recur-rences can and do occur.

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Nonimmune Hydrops Fetalis

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Transcript of Nonimmune Hydrops Fetalis