Amiodarone therapy for drug-refractory fetal tachycardia.

BACKGROUND: Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This study evaluates the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory fetal tachycardia with heart failure. METHODS AND RESULTS: Fetuses with incessant tachycardia and either hydrops fetalis (n=24) or ventricular dysfunction (n=2) for whom digoxin monotherapy and secondary antiarrhythmic agents (n=13) were not effective were treated transplacentally with a loading dose of oral amiodarone for 2 to 7 days, followed by daily maintenance therapy for <1 to 15 weeks. Digoxin therapy was continued throughout gestation. Newborns were studied by transesophageal pacing or ECG monitoring to determine the mechanism of tachycardia. Three fetuses were delivered urgently in tachycardia during amiodarone loading, and 3 required additional antiarrhythmic agents for sustained cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%) with reentrant supraventricular tachycardia, 2 of 2 with ventricular or junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone-related adverse effects were transient in 5 infants and 8 mothers. Mean gestational age at delivery was 37 weeks, with 100% survival. CONCLUSIONS: Orally administered amiodarone is safe and effective treatment for drug-refractory fetal tachycardia, specifically reentrant supraventricular tachycardia, junctional ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or ventricular dysfunction.

Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis.

BACKGROUND: Maternal anti-Ro and anti-La antibodies are associated with congenital heart block (CHB). Although endocardial fibroelastosis (EFE) has been described in isolated cases of autoantibody-mediated CHB, the natural history and pathogenesis of this disease are poorly understood. METHODS AND RESULTS: We retrospectively reviewed the clinical history, echocardiography, and pathology of fetuses and children with EFE associated with CHB born to mothers positive for anti-Ro or anti-La antibodies at 5 centers. Thirteen patients were identified, 6 with a prenatal and 7 with a postnatal diagnosis. Six mothers were positive for anti-Ro and anti-La antibodies, and 7 were positive for anti-Ro antibodies only. Only 1 mother had autoimmune disease. Severe ventricular dysfunction was seen in all fetal and postnatal cases. Four fetal and 3 postnatal cases had EFE at initial presentation. However, 2 fetal and 4 postnatal cases developed EFE 6 to 12 weeks and 7 months to 5 years from CHB diagnosis, respectively, even despite ventricular pacing in 6 postnatal cases. Eleven (85%) either died (n=9) or underwent cardiac transplantation (n=2) secondary to the EFE. Pathologic assessment of the explanted heart, available in 10 cases, revealed moderate to severe EFE in 7 and mild EFE in 3 cases, predominantly involving the left ventricle. Immunohistochemistry in 4 cases (including 3 fetuses) demonstrated deposition of IgG in 4 and IgM in 3 and T-cell infiltrates in 3 cases, suggesting an immune response by the affected fetus or child. CONCLUSIONS: EFE occurs in the presence of autoantibody-mediated CHB despite adequate ventricular pacing. Autoantibody-associated EFE has a very high mortality rate, whether developing in fetal or postnatal life.

Acute cardiovascular effects of fetal surgery in the human.

BACKGROUND: Prenatal surgery for congenital anomalies can prevent fetal demise or alter the course of organ development, resulting in a more favorable condition at birth. The indications for fetal surgery continue to expand, yet little is known about the acute sequelae of fetal surgery on the human cardiovascular system. METHODS AND RESULTS: Echocardiography was used to evaluate the heart before, during, and early after fetal surgery for congenital anomalies, including repair of myelomeningocele (MMC, n=51), resection of intrathoracic masses (ITM, n=15), tracheal occlusion for congenital diaphragmatic hernia (CDH, n=13), and resection of sacrococcygeal teratoma (SCT, n=4). Fetuses with MMC all had normal cardiovascular systems entering into fetal surgery, whereas those with ITM, CDH, and SCT all exhibited secondary cardiovascular sequelae of the anomaly present. At fetal surgery, heart rate increased acutely, and combined cardiac output diminished at the time of fetal incision for all groups including those with MMC, which suggests diminished stroke volume. Ventricular dysfunction and valvular dysfunction were identified in all groups, as was acute constriction of the ductus arteriosus. Fetuses with ITM and SCT had the most significant changes at surgery. CONCLUSIONS: Acute cardiovascular changes take place during fetal surgery that are likely a consequence of the physiology of the anomaly and the general effects of surgical stress, tocolytic agents, and anesthesia. Echocardiographic monitoring during fetal surgery is an important adjunct in the management of these patients.

Outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block. A single institution's experience of 30 years.

OBJECTIVES: We reviewed our institution's experience with isolated (congenital) third-degree atrioventricular block (CAVB) to identify pre- and post-natal predictors of mortality and the requirement for pacemakers in infancy and childhood. BACKGROUND: Because of the relative rarity of the disease, there is a paucity of data concerning the outcome of fetuses and children with isolated CAVB. METHODS: The medical records of all cases of CAVB encountered at our institution from January 1965 to December 1998 were analyzed. RESULTS: Of 102 cases identified, 29 were diagnosed in utero (F) at 26.1 +/- 5.6 weeks gestation, 33 as neonates (N; < or = 28 days), and 40 as children (C) at 5.7 +/- 4.8 years of age. Anti-Ro and/or anti-La were present in 95% of F and 90% of N, but only in 5% of C mothers tested (p < 0.0001). Patients with CAVB having F, N and C diagnosis had a mortality of 43%, 6% and 0%, respectively, in the first two decades of life. Increased mortality risk was associated with a fetal diagnosis of CAVB (13/15 deaths; p < 0.05), fetal hydrops (6/6 cases; p < 0.0001), endocardial fibroelastosis (5/5 cases; p < 0.0001) and delivery at < or = 32 weeks (4/6 cases; p < 0.05). Timing of pacemaker implantation differed significantly among F versus N (p < 0.05) and N versus C (p < 0.001) cases. At 20 years of age only 11% and 12% of CAVB patients with N and C diagnosis, respectively, were not paced. CONCLUSIONS: Pre-natal diagnosis of CAVB is associated with high fetal and neonatal mortality. Among survivors, whether the diagnosis is made before or after birth, most undergo pacemaker implantation by adulthood, with earlier intervention and a significantly greater need for reintervention among those diagnosed in utero.

Characteristics and outcomes of fetuses with pericardial effusions.

Little is known about the characteristics and outcomes of fetuses with pericardial effusions (PEs); therefore, this study sought to identify factors associated with fetal PEs and the natural histories and outcomes of fetuses with PEs. Large PEs are associated with a greater likelihood of structural heart disease, impaired cardiac function, and chromosomal abnormalities, and PEs with hydrops or extracardiac malformations are associated with death. Most fetal PEs resolve, and fetuses with isolated PEs have a very good prognosis.

Outcome of congenital cystic adenomatoid malformation of the lung after antenatal diagnosis.

OBJECTIVE: We evaluated the outcome of fetuses diagnosed with having congenital cystic adenomatoid malformation (CCAM) on ultrasonographic examination and managed conservatively. METHODS: A retrospective study of 19 cases of CCAM diagnosed antenatally in our hospital was conducted between 1990 and 2001. Complete clinical information was available for all patients, with a mean follow-up of 62 months. RESULTS: The median gestational age at which CCAM was diagnosed was 23 weeks and there were eight live births. With conservative postnatal management, seven neonates had no major complications and one developed bronchopneumonia. CONCLUSION: Taken together, the findings of the present study and a review of the literature strongly support the conservative management of selected neonates with CCAM.

Successful pregnancy in a Noonan syndrome patient after 3 unsuccessful pregnancies from severe fetal hydrops: a case report.

BACKGROUND: Noonan syndrome is a very rare disorder; its prevalence is 1/1,000-2,500 births. The special facial features, short stature, eventual cardiac anomalies and familiar history are the most important characteristics of the diagnosis. CASE: A Noonan syndrome patient delivered a healthy infant after a complicated delivery. The delivery followed 3 unsuccessful pregnancies. The previous pregnancies were terminated before the 24th gestational week because of general fetal hydrops as well as other malformations. CONCLUSION: In the prenatal care of a patient with Noonan syndrome the genetic and obstetric aspects are equally important. In establishing the diagnosis, ultrasonography is of utmost importance. As in our case, complications after cesarean section highlight the higher risk of delivery in women with Noonan syndrome.

[A neonatal case of anterior spinal artery syndrome presenting with bilateral arm paresis].

Anterior spinal artery syndrome is rare in children, especially in neonates. We present a girl with hydrops fetalis and hypothyroidism who developed flaccid paresis of both arms in the neonatal period (around day 25). MRI of the spine performed on day 52 revealed atrophic changes at C5-Th1 without Gd-DTPA-induced enhancement. Nerve conduction studies were also helpful in the diagnosis;in the upper limbs, motor potential was not elicited, while sensory nerve conduction velocity was normal. These clinical and laboratory findings suggested an atypical case of anterior spinal artery syndrome.

New manifestations of Neu-Laxova syndrome.

We report on a newborn boy with Neu-Laxova syndrome and spina bifida, bilateral cryptorchidism, and shallow orbital cavities. Association of these manifestations in Neu-Laxova syndrome is the first to be reported in the literature. This is the first report of Neu-Laxova syndrome from India.

Mucopolysaccharidosis type VII associated with hydrops fetalis: histopathological and ultrastructural features with genetic implications.

A case of mucopolysaccharidosis type VII (MPS VII, beta glucuronidase deficiency) causing fatal hydrops fetalis in the third trimester is presented. The diagnosis was suspected on histopathological examination by the presence of foam cells in many of the viscera and foamy change in the placental Hofbauer cells. Electron microscopy showed empty cytoplasmic inclusion bodies within macrophages and in the Hofbauer cells. Enzyme assay of cultured fibroblasts showed markedly deficient beta glucuronidase activity, thus confirming the diagnosis. A detailed and thorough histopathological examination of hydrops fetalis cases is important to detect subtle features of inherited metabolic disorders. Use of a structured necropsy protocol is recommended for cases of non-immune hydrops. Electron microscopy is a useful adjunct to light microscopy in cases where an inherited metabolic disorder is suspected. Precise necropsy diagnosis is important as there are implications for genetic counselling and possible prenatal diagnosis in subsequent pregnancies.

Endocardial fibroelastosis in infants with hydrops fetalis.

Endocardial fibroelastosis, defined as an endocardium in excess of 30 microns thick, was found in 10 out of 34 cases of hydrops fetalis in a review of 1589 perinatal necropsies carried out between 1976 and 1989. The infants comprised 16 cases of rhesus haemolytic disease, of whom three had endocardial fibroelastosis, and 18 cases of non-rhesus hydrops, of whom seven had endocardial fibroelastosis. Intrauterine congestive heart failure was thought to have been the probable cause of hydrops in eight of the 10 infants with endocardial fibroelastosis. None of an age matched control group without endocardial fibroelastosis had evidence of congestive cardiac failure. These observations support the hypothesis that endocardial fibroelastosis is an endocardial response to chronic prenatal myocardial stress.

Intrauterine intravascular transfusion for severe erythroblastosis fetalis: how much to transfuse?

Intrauterine intravascular transfusion is now believed to be a more precise method for treating fetal anemia in erythroblastosis fetalis than is intraperitoneal transfusion. Previously established guidelines for the volume of blood to be given in intraperitoneal transfusion at a specific gestational age are not applicable for intravascular transfusion. In 28 patients, intravascular transfusion was performed on 81 occasions between 19-34 weeks' gestation. The total number of transfusions ranged from one to six per patient. The aim at each procedure was to achieve a final hematocrit of 35-50%. Factors examined as likely to determine the volume of blood required included pre-transfusion hematocrit, post-minus pre-transfusion hematocrit (hematocrit increase), the hematocrit of the transfused blood, gestational age, estimated fetal weight, and interval from last transfusion. The factors found to be most predictive of total volume of blood required for transfusion were the hematocrit increase and either estimated fetal weight or gestational age.

Trisomy 21, fetal hydrops, and anemia: prenatal diagnosis of transient myeloproliferative disorder?

BACKGROUND: Aneuploidy is frequently cited as an etiology of hydrops fetalis. Traditionally, associated anomalies (specifically cardiovascular abnormalities) have been postulated as the causative factor. CASES: We report two cases of severe anemia associated with hydrops in fetuses that later proved to have Down syndrome. The hematocrit in both fetuses was markedly decreased. The white blood cell count was normal in one but greatly elevated in the other; the latter infant had thrombocytopenia. These findings are consistent with transient myeloproliferative disorder. CONCLUSIONS: Nonimmune fetal hydrops and trisomy 21 may be associated without cardiac or anatomical anomalies. Transient myeloproliferative disorder has been seen in neonates with trisomy 21 and may be a cause of hydrops in some aneuploid fetuses. Chromosomal analysis should not be excluded in the workup of nonimmune hydrops when anemia is found, and therapy may be withheld until karyotyping has been performed.

Transient hydrops fetalis associated with intrauterine cytomegalovirus infection: prenatal diagnosis.

BACKGROUND: Intrauterine cytomegalovirus infection is usually unrecognized during pregnancy. However, in some cases, ultrasound abnormalities can be observed in association with cytomegalovirus infection. CASE: The prenatal diagnosis of cytomegalovirus infection in a fetus with transient hydrops is reported. Fetal ascites was first recognized by routine ultrasound examination at 20 weeks' gestation. Hydrops fetalis was obvious at 23 weeks and completely resolved 1 week later. Cytomegalovirus was detected from amniotic fluid samples by centrifugal culture and direct immunofluorescent examination. The diagnosis of maternal primary infection could be established retrospectively by demonstrating immunoglobulin (Ig) G and IgM seroconversion on sequential sera. The pregnancy was electively terminated. Autopsy findings were consistent with fetal disseminated infection. CONCLUSION: Transient hydrops fetalis in association with intrauterine cytomegalovirus infection is infrequent. The resolution of hydrops fetalis could be explained by hepatic dysfunction of limited duration. Amniotic fluid culture is a reliable approach for diagnosing intrauterine cytomegalovirus infection, but does not predict the severity of the disease or the outcome of the pregnancy. The long-term clinical significance of intrauterine cytomegalovirus infection has to be established.

Nonimmune hydrops fetalis associated with genetic abnormalities.

The purpose of this review of the literature on nonimmune hydrops fetalis was to evaluate whether recent clinicopathologic studies have modified the relative incidence of the different associated conditions and the management of these pregnancies. We found 600 cases of nonimmune hydrops fetalis published since 1982. These cases were reviewed with particular attention to genetic causes and were compared with a literature review of 298 cases published before 1982. The mean gestational age at diagnosis varied from 24-29 weeks in the recent series, compared with 31-33 weeks in the earlier series. Genetically transmitted conditions accounted for more than 35% of the fetal and maternal disorders associated with nonimmune hydrops fetalis in the recent series, compared with 21% before 1982. The most frequently identified genetic abnormalities in our review were chromosomal disorders (15.7%), alpha-thalassemia (10.3%), skeletal dysplasia (4%), arthrogryposis multiplex syndromes (1.8%), multiple pterygium syndrome (1.5%), and lysosomal storage disorders (1.0%). These results confirm the need for systematic chromosome analysis in fetuses with nonimmune hydrops. From this review, we conclude that prenatal noninvasive and invasive techniques combined with detailed pathologic studies have improved the accuracy of diagnosis of the underlying causes of nonimmune hydrops fetalis and have influenced the management of these pregnancies.

Erythropoietin in human fetuses with immune hemolytic anemia and hydrops fetalis.

OBJECTIVE: To determine whether plasma erythropoietin is increased in fetuses with anemia due to Rh isoimmunization. METHODS: Hemoglobin and erythropoietin were measured in samples obtained by funipuncture from 15 fetuses with Rh isoimmunization (gestational age 26.2 +/- 5.0 weeks, mean +/- standard deviation) and from 13 control fetuses (23.1 +/- 6.7 weeks). Hemoglobin and erythropoietin also were determined in umbilical cord blood collected at birth from 20 term fetuses delivered by elective cesarean. RESULTS: Fetuses with Rh isoimmunization had lower hemoglobin and higher plasma erythropoietin measurements than mid-gestation controls (6.1 +/- 3.9 versus 10.7 +/- 1.5 g/dL and 105.5 +/- 168.1 versus 12.5 +/- 3.1 mU/mL, P < .05, respectively). Hemoglobin and plasma erythropoietin increased with gestational age in control fetuses. There was an inverse association between hemoglobin and plasma erythropoietin in control and Rh-isoimmunized fetuses (r = -0.56, P < .005). Using multiple linear regression, hemoglobin and gestational age were associated independently with plasma erythropoietin (overall F2,25 = 12.3, multiple r2 = 0.49, P < .001). Despite marked decreases in hemoglobin, fetuses below 24 weeks' gestation had minimal increases in plasma erythropoietin compared to fetuses above that gestational age. Mildly anemic Rh-isoimmunized fetuses (hemoglobin 11.6 +/- 2.0 g/dL) delivered vaginally had significantly higher erythropoietin levels in umbilical cord plasma than Rh-isoimmunized fetuses with comparable hemoglobin (10.9 +/- 3.5 g/dL) delivered by elective cesarean without labor (1246 +/- 856 versus 106 +/- 66 mU/mL, respectively, P < .05). CONCLUSION: Fetuses with anemia at mid to late gestation respond with increases in plasma erythropoietin, but these changes are substantially attenuated before 24 weeks' gestation.

Nonimmune hydrops fetalis, pulmonary sequestration, and favorable neonatal outcome.

BACKGROUND: The association of pulmonary sequestration and nonimmune fetal hydrops reportedly carries a very poor prognosis for survival. We describe three newborns with good outcomes despite the diagnosis of pulmonary sequestration; two cases were associated with hydrops fetalis and one with isolated fetal ascites. CASES: Two neonates with severe hydrops fetalis had pulmonary sequestration diagnosed postnatally. A third infant presented early in gestation with marked fetal ascites that regressed spontaneously before delivery; this infant also had pulmonary sequestration. Despite severe respiratory insufficiency requiring aggressive management, all three infants survived after surgical resection of the sequestered lung mass. CONCLUSION: These cases demonstrate the difficulties associated with antenatal counseling regarding long-term prognosis for infants with nonimmune hydrops and pulmonary sequestration. With optimal care in a tertiary perinatal center, a less pessimistic outlook than previously described in the literature may be appropriate.

Nuchal thickening or cystic hygromas in first- and early second-trimester fetuses: prognosis and outcome.

OBJECTIVE: To elucidate the relationship between nuchal abnormality, karyotype, and prognosis in fetuses with nuchal thickening or cystic hygroma observed between 10-15 weeks' gestation. METHODS: We reviewed all cases of fetal nuchal thickening (4 mm or greater) in 10-15-week fetuses over a 5-year period. Generalized hydrops and the presence of other anomalies were noted prospectively. We retrospectively measured the nuchal area and determined whether septations were present. Data consisted of karyotype, pathologic studies, and clinical follow-up of live-born infants. RESULTS: Of 100 consecutive fetuses, 29 were excluded because of pregnancy termination without karyotype or pathologic information. Of the remaining 71 fetuses, 63 had karyotyping. Abnormal karyotypes were found in 31 of 37 hydropic fetuses but in only 12 of 26 nonhydropic fetuses (P < .05). Fetuses with Turner syndrome had larger cystic hygromas than those with trisomy 18, trisomy 21, or normal karyotype (P < .05). There were ten normal live-born infants, none of whom was hydropic at the time of initial diagnosis and all of whom demonstrated spontaneous resolution of the nuchal thickening on subsequent sonograms. CONCLUSIONS: Fetuses with nuchal thickening or cystic hygromas demonstrated by ultrasound should have their karyotype determined. If the karyotype is normal and there are no hydrops or septations, the prognosis is good.

Spontaneous resolution of fetal cystic hygroma and hydrops in Turner syndrome.

On a routine ultrasound examination, a cystic hygroma and hydrops were noted at 21 weeks' gestation in a fetus with a 45,X karyotype. Serial studies demonstrated a marked reduction in the size of the cystic hygroma and complete resolution of ascites. At birth, the term infant had features characteristic of the Turner syndrome, including a webbed neck. A critical coarctation of the aorta required repair in the neonatal period. Our case provides glimpses of the intrauterine evolution of the Turner phenotype. We suggest that the possibility of survival when such lesions are detected prenatally may be greater than previously thought.

Outcome of isolated congenital complete heart block diagnosed in utero.

OBJECTIVE: To establish identifiable prenatal factors in fetal heart block which might predict death in utero, the need for intervention, or the probability of pacemaker requirement. SETTING: Tertiary referral unit for fetal echocardiography. SUBJECTS: 36 fetuses with congenital complete heart block and structurally normal hearts identified between 1980 and 1993. METHODS: Maternal anti-Ro antibody status was documented. Prenatal variables examined included absolute heart (ventricular) rate, change in rate, and development of hydrops fetalis. Postnatally, heart rate, need for pacing, and the indications for pacing were detailed. RESULTS: Of the total of 36 patients, there are 24 survivors; 11 are paced. Of those fetuses which died, two were electively aborted for severe hydrops, seven died in utero, two were immediate postnatal deaths, and one was an unrelated infant death. The trend was for the heart rate to decrease during fetal life and postnatally. Fetuses with deteriorating cardiac function did not always show the lowest heart rates. Bradycardia of less than 55 beats/min in early pregnancy or rapid decrease in heart rate prenatally were poor prognostic signs. Hydrops was also associated with bad outcome, 10 out of the 12 hydropic fetuses dying (83%). Of 10 fetuses presenting with a heart rate above 60/min, nine survived of whom three required pacing. Of seven presenting with heart rates of 50/min or less, only three survived and two of these required pacing. Of the two fetuses with negative maternal anti-Ro antibody status one died in utero and one required heart transplantation after pacemaker insertion. CONCLUSIONS: Isolated complete heart block identified in fetal life does not always have a good prognosis. An individual heart rate does not accurately predict the outcome in utero or the need for postnatal pacing. Regular, careful monitoring during pregnancy is required in order to optimise care and timing of any interventions.