Neutrophil (granulocyte) transfusions in the new millennium

BACKGROUND: Ebstein anomaly is a rare tricuspid valve anomaly. Some fetuses with Ebstein's anomaly have concurrent severe cardiac function impairment, which results in hydrops fetalis. Most of these fetuses are inevitably terminally ill. No reports have demonstrated the potential prenatal therapy for fetuses under such conditions. CASE: Ebstein's anomaly and hydrops fetalis were detected at 28 weeks' gestation. Tricuspid regurgitation with congestive heart failure was observed. From 28 to 34 weeks' gestation, intrauterine therapy with digoxin, 0.75 mg/d, was administered. The fetal hydrops status improved gradually, while the tricuspid valve regurgitation persisted. At 36 weeks' gestation the fetus was delivered normally. During the neonatal phase, digoxin was continued and gradually tapered off. The tricuspid valve regurgitation and cardiomegaly gradually improved. CONCLUSION: The favorable outcome in this case supports the positive effect of prenatal digoxin therapy for Ebstein's anomaly with hydrops fetalis. In such conditions, upon the appearance of hydrops and congestive cardiac failure, immediate digoxin therapy may be useful. This successful trial encouraged us to manage such fetuses more aggressively.     

Incidence of normal hearing in acoustic neuroma]

In a 4 1/2 year period fetal, echocardiographic studies were performed on 1600 fetuses. In 55 with arrhythmia, 44 had supraventricular ectopic beats, resolved in all, and none had heart disease. Sustained arrhythmias occurred in 11 fetuses. Atrial flutter was present in 3 all with heart disease (Ebstein disease, right atrial tumour and WPW diagnosed after birth). Another 3 fetuses had supraventricular tachycardia (SVT), all with a normal heart. In the bradycardia group, 2 had complete heart block (CHB) associated with AVSD; 2 sinus bradycardia and one had non conducted atrial ectopic beats. Digoxin was the first choice drug for tachyarrhythmia therapy; association with Verapamil, Flecainide, Quinidine and Procainamide was used in 4 of the 6. One fetus with CHB received Orciprenaline with no results. Atrial flutter resolved or improved; in SVT 2 fetuses converted to sinus rhythm and one died in utero. All fetuses with CHB died in cardiac failure. Mortality was 27% (3 cases) in utero and global 36%. In our experience most fetal arrhythmias (90%) were transitory ectopic beats or non lasting bradycardia in normal heart and did not trigger other kinds of arrhythmias. In sustained arrhythmias, heart failure and heart disease had a negative effect on prognosis.     

Changes of venous blood flow velocity waveforms in fetuses with supraventricular tachycardia

Studies in the fetal lamb have shown that atrial pacing beyond a rate of 300-320 beats/min may be associated with dramatic changes of venous blood velocity waveforms, an increase of venous pressure by up to 75%, hydrops, polyhydramnios and placental edema. The aim of our study was to determine the 'critical' heart rate frequency in the human fetus. In 11 fetuses (five with and six without hydrops) with supraventricular tachycardia, pulsed wave Doppler analysis of flow velocity waveforms of the inferior vena cava, the ductus venosus and the left hepatic vein were performed before and after drug treatment. In ten cases cardioversion was achieved by in utero antiarrhythmic drug therapy; in one case treated with digoxin and flecainide the supraventricular tachycardia was decreased to 160-190 beats/min with disappearance of hydrops. Before intrauterine treatment of supraventricular tachycardia, pulsatile reversal of blood flow in the inferior vena cava, ductus venosus and left hepatic vein was visible, with monophasic forward flow during systole and reversed flow during diastole in ten of 11 fetuses. One fetus with supraventricular tachycardia of 195 beats/min showed a normal biphasic forward flow pattern. During drug-induced sinus rhythm, a normal biphasic forward venous blood flow pattern was shown in all ten cases. In five cases pulsatile reversal was demonstrated during a drug-induced reduction of the heart rate from 280 to 210 beats/min and a normal biphasic forward flow velocity waveform appeared during supraventricular tachycardia below 210 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatitis C in children after transfusion: assessment by look-back studies

A woman presented during two pregnancies (at 25 and 23 weeks' gestation, respectively) because the fetuses had rapid, irregular tachycardia and hydrops. After maternal drug treatment and achievement of slower fetal heart rates, the hydrops gradually resolved. Both babies were born full term with continuing atrial fibrillation. In the first, an ectopic atrial rhythm was temporarily achieved during high dose flecainide treatment but, in the younger sibling, all medications and repeated cardioversions failed even temporarily to convert the atrial fibrillation with an almost isoelectric baseline in ECG to sinus rhythm. Good rate control has been achieved with digoxin in both patients. No infective, immunological, or structural cause was found in either case, and thus an inherited aetiology is probable.     

In utero management of hydrops fetalis caused by critical aortic stenosis

Hydrops fetalis is rarely associated with congestive heart failure caused by obstructive left-sided heart lesions. There are rare cases of live born neonates with critical congenital valvar aortic stenosis and hydrops reported in the literature, all with fatal outcomes. This report describes, to the best of our knowledge, the first two newborns who were diagnosed prenatally to have hydrops fetalis caused by critical valvar aortic stenosis, who were treated prenatally with digoxin and who postnatally had successful percutaneous balloon aortic valvuloplasty. Both patients had not only left but right ventricular dysfunction. We speculate that right ventricular dysfunction was a contributing factor in the development of hydrops in these patients and in utero medical therapy with digoxin is associated with resolution of the hydrops before delivery.     

Accelerated radiotherapy regimen for malignant gliomas using stereotactic concomitant boosts for dose escalation

Parvovirus B19 (PV B19) infection was investigated in 29 pregnant women with fetal hydrops, after exclusion of feto-maternal incompatibility within red blood cell antigens, TORCH infections, feto-maternal hemorrhage and genetics reasons. The active viral infection was detected in 9 women (31%) by PCR amplification of DNA B19; in 2 of them IgM and IgG, in 1 IgM and in 4 IgG antibodies were also present. In 6 women (20%) IgG antibodies were only found, but not IgM and DNA B19, which confirmed infection in the past. In addition in 9 cases DNA B19 was evaluated in the fetal blood. The results in the mothers and their fetuses were concordant (4 positive, 5 negative). Our conclusion is that in nonimmune hydrops fetalis, PV B19 infection should be based on the viral DNA evaluation in the blood of mother (or fetus). IgM antibodies, in time of fetal disorders, might not be detected.     

Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease

OBJECTIVE: The aim of the study was to assess the developmental outcome of neonatal survivors of hemolytic disease of the neonate treated with modern intrauterine transfusion techniques. STUDY DESIGN: In this prospective, observational study, auditory evoked-response tests were performed in the nursery. Neurodevelopmental evaluation with the Gesell Developmental Schedules was performed between 9 and 18 months of corrected age to assess motor skills, language development, comprehension capacity, and social skills. The McCarthy Scales of Children's Abilities were administered between 36 and 62 months. RESULTS: Forty children who survived severe fetal hemolytic disease were followed up until 62 months old. Demographic data included gestational age at first intrauterine transfusion (26.4 +/- 3.7 weeks), median number of intrauterine transfusions (4, range 1-8), lowest fetal hematocrit (20.2% +/- 7.8%), peak fetal bilirubin (7.1 +/- 2.1 mg/dL), incidence of hydrops fetalis (45%), and mean gestational age at delivery (35.6 +/- 2.2 weeks). One case of severe bilateral deafness and 1 case of right spastic hemiplegia were diagnosed. The Gesell Developmental Schedules score was assessed between 9 and 18 months of corrected age in 22 infants. The global developmental quotient was 101.9 +/- 9.5 (mean for normal population is 100). Regression analysis revealed no correlation between the global developmental quotient and gestational age at the first intrauterine transfusion, gestational age at birth, or the severity of the fetal hemolytic disease (fetal hematocrit, fetal bilirubin, presence of hydrops fetalis, total number of intrauterine transfusions, duration of neonatal phototherapy, and number of neonatal exchange transfusions). Eleven of the 40 children were followed up until they were 62 months old, and the McCarthy Scales of Children's Abilities were administered. The mean cognitive index was 107.6 +/- 9.4 (90-109 is considered average). CONCLUSION: Despite severe fetal hemolytic disease, normal developmental outcome can be expected for children treated with intrauterine transfusions.     

Functional MR imaging of anomalies of the aorta

Non-immune hydrops fetalis caused by beta-glucuronidase deficiency (mucopolysaccharidosis VII). Study of a family with 3 affected siblings. We describe a family case of beta-glucuronidase deficiency with 3 consecutively affected siblings. The three fetuses showed hydrops at a very early stage. In the first and second pregnancy the hydrops was visible on ultrasound scan in the first trimester. In the second pregnancy this was highly suggestive for recurrence. The diagnosis of mucopolysaccharidosis type VII was suggested after pathologic examination of the first fetus and placenta, and confirmed by deficient beta-glucuronidase activity in cultured skin fibroblasts. In the second, as well as in the third pregnancy a prenatal biochemical diagnosis was possible on cultured chorionic villus cells. The third pregnancy was terminated before hydrops was visible on ultrasound scan. Pathologic findings in the 3 fetuses were similar. Vacuolated macrophages were found in all tissues, but were most prominent in placenta, liver, lymph nodes and bone marrow.     

Comparison of sotalol with digoxin-quinidine for conversion of acute atrial fibrillation to sinus rhythm (the Sotalol-Digoxin-Quinidine Trial)

We randomized 61 patients with paroxysmal atrial fibrillation (AF) ( < 48 hours from onset) to either sotalol or quinidine treatment. Conversion of rhythm was recorded by Holter monitoring. The starting 80 mg dose of sotalol was repeated at 2, 6, and 10 hours if AF persisted (heart rate > 80 beats/min), and if systolic blood was > or = 120 mm Hg. In the quinidine group, if heart rate > 100 beats/min, it was decreased with intravenous digoxin, whereafter 200 mg of oral quinidine sulfate was given maximally 3 times, each dose 2 hours apart. Conversion of AF to sinus rhythm occurred in 17 or 33 patients (52%) taking sotalol, and in 24 of 28 patients (86%) taking quinidine (p < 0.0001). Electric cardioversion was necessary in 39% of the former and in 14% of the latter group. The mean delay from first trial drug to sinus rhythm with the trial medication was 10.2 +/- 7.6 hours in the sotalol group and 4.0 +/- 2.9 hours in the quinidine group (p < 0.01). Treatment was discontinued in 16 patients taking sotalol (48%) because of asymptomatic bradycardia or hypotension, and in 20 taking quinidine (71%) because of rhythm conversion. Asymptomatic wide complex tachycardia (QRS > 0.12 second) was found in 13% and 27% of patients taking sotalol and quinidine, respectively. The longest RR intervals were 6.4 and 3.8 seconds in the sotalol and quinidine groups, respectively. Oral sotalol did not appear as effective as quinidine sulfate treatment in conversion of paroxysmal AF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombolytic therapy with tissue plasminogen activator for prevention of vasospasm in experimental subarachnoid hemorrhage: its efficacy and problems

Parvovirus B19 infection has been associated with fetal anaemia, hydrops, and in some cases demise. Most of the reported cases of fetal hydrops were detected in second-trimester fetuses. We report a series of three cases in which human parvovirus infection was associated with hydropic changes at an earlier gestational age. Spontaneous resolution of hydrops occurred in all fetuses. A greater understanding of the natural history of human parvovirus infection is needed prior to deciding on the mode of therapy (conservative management versus in utero fetal therapy).     

Obstetric outcome after RhD and Kell testing

The study was conducted to report on the use of molecular biology methods and pregnancy outcome in women sensitized to either Rhesus D (RhD) or Kell 1 (K1) antigens. Paternal RhD genotype was determined by DNA amplification of an RhD-specific sequence from single sperm cells. Paternal Kell phenotype was determined by serologic assays using peripheral blood samples, and the fetal RhD or Kell-type status were established by the polymerase chain reaction (PCR) with amniotic cells. Thirteen women (14 pregnancies, one with twins) sensitized to RhD and four sensitized to K1 antigens, comprised the study group. All had paternal heterozygosity to either D or K1 antigens. Nine fetuses were RhD positive and five were RhD negative. An additional woman underwent early spontaneous abortion. The nine RhD-positive fetuses underwent a total of 41 invasive procedures. One fetus with hydrops fetalis died in utero after intrauterine blood transfusion. All the remaining RhD-positive fetuses were delivered after 33 weeks gestation, and all those who were RhD negative were delivered at term. Four women were sensitized to the K1 antigen; in three, the fetus was found to be K1 negative, and in one, K1 positive, necessitating intrauterine blood transfusion. In all cases, the results of RhD or K1 genotype analyses from amniotic fluid were compatible with fetal/neonatal red blood cell RhD or Kell phenotypes. In conclusion, the use of molecular biology techniques represents a major advance in the clinical management of RhD and Kell alloimmunization.     

Association between hepatoblastoma and very low birth weight: a trend or a chance?

Nuchal vascular hamartoma was found in a newborn premature infant who presented with nonimmune hydrops fetalis, pulmonary hypoplasia due to bilateral pleural effusion and polyhydramnios in utero. The baby died 26 hours after birth despite maximal respiratory and circulatory support. Postmortem examination revealed a vascular hamartoma localized to the left posterolateral region of the neck. We suggest that nuchal vascular hamartoma may be associated with fetal hydrops, probably due to compromised lymph drainage.     

Psychotherapy and disclosure: recent court decisions

We report the prenatal diagnosis of a transient myeloproliferative disorder suggestive of leukaemia in a fetus with hepatosplenomegaly, hydrops and 47, XY, +21 karyotype. The initial fetal white blood cell count at 26 + 5 weeks' gestation was 190/nl with 70 per cent blast cells. Immunophenotyping of the large blasts revealed surface markers suggestive of an early stem cell differentiation arrest resulting in undifferentiated polyclonal myelopoiesis. The fetal heart tracing showed minimal beat-to-beat variability in the presence of high leukocyte counts. Serial fetal blood sampling showed decreasing blast cells in the peripheral blood and normalization of white blood cell counts. Although there was increasing hydrops, this period was marked by improvement of the fetal heart rate pattern. Finally the fetus developed pancytopenia with increasing hydrops, AV-valvular insufficiency and venous Doppler studies indicative of cardiac decompensation prior to intra-uterine death at 31 + 5 weeks' gestation. Post-mortem examination revealed marked liver and splenic necrosis without evidence of residual leukaemic infiltration in any organ. Fetal hydrops and hepatosplenomegaly may indicate an underlying haematopoietic disorder warranting further investigation. Furthermore, this case indicates that transient abnormal myelopoesis may result in a fulminant clinical picture much like true leukaemia. This may be due to increased vulnerability of the fetus or represent a disease mechanism unique to fetuses with chromosomal abnormalities.     

Antenatal diagnosis and surgical management of congenital cystic adenomatoid malformation of the lung

We experienced 12 cases of congenital cystic adenomatoid malformation of the lung (CCAM) including 6 cases diagnosed antenatally. They were classified into three groups according to the clinical manifestations. Group A was associated with hydrops fetalis (n = 3), group B presented with respiratory distress symptoms after birth (n = 6), and group C showed no respiratory symptoms (n = 3). All cases of group A were lost because of hydrops and respiratory failure due to pulmonary hypoplasia. Because a compression of the mass is thought to be a cause of hydrops, this group is considered to be a good indication for fetal treatment. All cases of group B showed progressive respiratory symptoms a few days after birth which were successfully treated surgically. In 2 of 3 cases of group C, the lesions decreased in size both antenatally and postnatally. We conclude that serial sonographic evaluations for fetal CCAM are important. If the fetus develops hydrops, fetal surgery is to be considered. If not, however, fetal surgery should not be done, because some lesions can shrink in size, or even disappear, while others can be treated successfully after birth by lobectomy or even segmentectomy.     

Nonimmune hydrops fetalis: fetal and neonatal outcome during 1983-1992

Prognostic factors for survival of 62 fetuses and neonates with nonimmune hydrops fetalis (NIHF) were studied retrospectively. Twenty-eight infants survived >/=28 days which is 45% for all fetuses and newborns diagnosed with NIHF and 61% for liveborns with unresolved NIHF. Univariate analysis identified that mortality was associated with the presence of >/=2 serous cavity effusions and a need for chest compressions at birth. Multivariate logistic regression analysis confirmed that the presence of >/=2 serous cavity effusions was significantly associated with mortality from NIHF <28 days after birth [OR = 48.2 (CI 3.6, 662.9) (p < 0.004)]. We conclude that, compared to published cases from the 1970s and early 1980s, survival of liveborns with NIHF seems improved. The decrease in stillbirths is more notable. The severity of hydrops at birth is the key determinant for survival.     

Monitoring cognitive disturbance in delirium with the ten-point clock test

Isolated bilateral pleural effusion with mediastinal compression leading to hydropic change of the fetus is unusual, and carries a high risk of perinatal death. This condition can be reversed in utero by performing ultrasound-guided shunting surgery. We describe a hydropic fetus at 30 weeks' gestation with rapid recurrence of pleural effusion after thoracentesis. The pleural effusion and hydrops resolved within 1 week after ultrasound-guided thoracoamniotic shunt and the fetal lungs were restored to their normal size. The fetus was born at 35 weeks' gestation and had an uneventful postnatal course. The technique of restoring cardiopulmonary function in utero through intrathoracic decompression offers a valuable alternative to repetitive prenatal thoracentesis or preterm delivery of fetuses with hydrops caused by bilateral pleural effusion.     

Knowledge of stroke in Hong Kong Chinese

Cervical ribs were observed in six hydropic fetuses with 45X karyotype. To test the usefulness of this observation in the macerated hydropic fetus where chromosome culture is problematic, a group of 36 hydropic fetuses was examined. Cases were chosen to include fetuses with several karyotypic and pathological abnormalities known to be associated with fetal hydrops. Whole-body anteroposterior radiographs were evaluated without knowledge of the fetal karyotype or pathological findings. Twenty-five fetuses had an abnormal karyotype, seven had a normal karyotype and in four culture failed. In the last group, the number of X, 21 and 18 chromosomes per nucleus was estimated using FISH. Radiographic analysis demonstrated that among the 16 fetuses with 45,X karyotype or a single copy of X and female phenotype, 12 had a pair of cervical ribs. Three other fetuses had a single cervical rib. Only one fetus had no cervical ribs. The last fetus had tubular hypoplasia of the aortic arch and persistent mesocolon. Twelve of the sixteen 45,X fetuses had tubular hypoplasia of the aortic arch. Seven had other cardiovascular anomalies, five had renal anomalies, and five had anomalies of intestinal rotation. Cervical rib appears to be more common than other frequently recorded associations of 45,X. It is a useful and easily demonstrated mark in the evaluation of the macerated hydropic fetus.     

The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA receptors in opiate withdrawal

The turnover rates of plasma lactate, normalized for O2 consumption rate, are higher in the fetus than in the adult. This occurs despite very low rates of fetal gluconeogenesis which preclude the recycling of lactate carbon into glucose. In an effort to establish the main routes of disposal of fetal plasma lactate, 12 midgestation ovine fetuses (age 74 +/- 1 days) were infused intravenously at constant rate with L-[U-14C]lactate for a 4-hour period. At the end of the infusion, the amounts of 14C retained by the fetus and by the placenta, and the distribution of the retained 14C in free and protein-bound amino acids and in lipids were measured. Of the total 14C infused, 17.0 +/- 1.4% was recovered in the placenta, 4.0 +/- 0.3% in the fetal liver, and 15.0 +/- 0.8% in the extrahepatic fetal tissues. Of the retained radioactive carbon, 45-57% was recovered in the free and protein-bound amino acid fractions and 11-17% in the lipid fractions. Approximately 90% of the 14C in the free amino acid fractions was present as glutamate/glutamine, serine, glycine, and alanine carbon. In conjunction with data on fetal CO2 production from lactate carbon, these results demonstrate that the main routes of fetal lactate disposal are oxidation and synthesis of nonessential amino acids and lipids.     

DNA synthesis is dissociated from the immediate-early gene response in the post-ischemic kidney

OBJECTIVE: Fetal growth and development are closely related to normal placental growth and function. We performed a study to determine the effect of a 10-day period of fetal hypoxemia induced by umbilical-placental hypoperfusion on tissue deoxyribonucleic acid synthesis rates in the 0.84 to 0.91 of gestation ovine fetus and placenta. STUDY DESIGN: Daily fetal placental embolization was performed in four chronically catheterized sheep fetuses until fetal arterial oxygen content decreased by approximately 30% compared with preembolization values. Five control fetuses received vehicle only. On experimental day 10, the deoxyribonucleic acid synthesis rate was determined by injecting tritiated thymidine (1 mCi/kg) intravenously approximately 8 hours before the end of the study. RESULTS: Fetal arterial oxygen decreased from 3.2 +/- 0.1 (SEM) mmol/L preembolization to 2.2 +/- 0.2 mmol/L on day 10 (p < 0.001) and remained unchanged in controls. On day 10 deoxyribonucleic acid synthesis rates were significantly reduced in embolized fetuses compared with controls, by 38% in cotyledons (83.0 +/- 15.1 vs 133.7 +/- 9.9 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05), 28% in the left ventricular wall (36.8 +/- 3.7 vs 51.0 +/- 4.7 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05), and 45% in the quadriceps muscle (15.4 +/- 4.0 vs 28.1 +/- 3.0 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05). Tritiated thymidine autoradiography demonstrated that cotyledonary deoxyribonucleic acid synthesis occurred exclusively in the fetal trophoblasts cells. CONCLUSION: We concluded that a reduction in cotyledonary, quadriceps muscle, and left ventricular myocardium deoxyribonucleic acid synthesis rates are the earliest adaptive mechanisms of fetal growth associated with development of umbilical-placental insufficiency. We speculate that alteration in the myocardial deoxyribonucleic acid synthesis rate could be a major contributing factor in the deterioration of fetal myocardial function associated with increased placental vascular resistance.     

Maximal lymph flow in the ovine fetus

OBJECTIVE: This study was designed to determine the maximal left thoracic duct lymph flow rate in late-gestation ovine fetuses. STUDY DESIGN: Chronically catheterized sheep fetuses (n = 8) with indwelling left thoracic lymph duct and vascular catheters were studied > or = 5 days after surgery at 136 +/- 1 (SE) days' gestation. To increase lymph flow rate, 4 L of warm lactated Ringer's solution were infused intravenously into the fetus over 4 hours, because this causes mild edema as determined ultrasonographically. RESULTS: During a 1-hour preinfusion period lymph flow rate was 0.53 +/- 0.06 ml/min. During the infusion increases occurred in fetal arterial (7.6 +/- 1.0 mm Hg) and venous (2.4 +/- 0.3 mm Hg) pressures (p < 0.001). Lymph flow rate increased and reached a plateau after 1 hour at 339% +/- 30% of preinfusion values (p < 0.001). When the infusion was terminated, fetal arterial and venous pressures rapidly returned to preinfusion levels. Lymph flow rate gradually decreased during the first 30 minutes and stabilized at 97% +/- 17% above control during the subsequent 30 minutes. Analysis of lymph flow rate as a function of outflow pressure revealed that the increases in flow occurred because of an upward shift in the plateau flow rate with no change in the stop-flow pressure. CONCLUSIONS: (1) Fetal left thoracic duct lymph flow rate can increase significantly above basal values and therefore is an important safety factor against fetal edema formation. (2) The maximal lymph flow rate appears to be 3.4 times normal when venous pressure is elevated and two times normal when venous pressure is normal.