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.

Maternal and fetal tuberous sclerosis complicating pregnancy: a case report and overview of the literature.

Tuberous sclerosis complex (TSC) is an autosomal-dominant phakomatosis that can result in cardiac and central nervous system lesions and may adversely impact fetal and maternal health. We report a case of a 19-year-old primagravida with TSC whose pregnancy was complicated by preeclampsia, preterm labor, and fetal demise. The fetus, also affected with TSC, was diagnosed with a cardiac rhabdomyoma on ultrasound at 24 gestational weeks and intracranial tubers on fetal magnetic resonance imaging at 26 gestational weeks. Hydrops fetalis developed in the 30th gestational week. Fetal demise occurred during induction of labor. A systematic review of the medical literature was conducted. Our objective was to quantify maternal and fetal morbidity and mortality associated with TSC. We identified 36 additional cases of fetal TSC with cardiac rhabdomyoma diagnosed prenatally. Including our case, we also identified 23 pregnancies (17 mothers) complicated by maternal TSC. Rates of complications are calculated. We conclude that pregnancies complicated by maternal or fetal TSC deserve careful vigilance. Although benign histologically, cardiac rhabdomyomas can result in fetal morbidity and mortality.

Maternal ABO-mismatched blood for intrauterine transfusion of severe hemolytic disease of the newborn due to anti-Rh17.

BACKGROUND: Clinically significant antibodies to high-incident antigens present a challenge in hemolytic disease of the newborn. Antigen-negative blood may be difficult to obtain for intrauterine transfusion (IUT). In these instances, maternal blood is de facto compatible regardless of an ABO mismatch. CASE REPORT: A group B/D-- woman with a history of hemolytic disease of the newborn due to anti-Rh17 (titer 256) presented to the obstetrical clinic at 12 weeks gestation for management of her third pregnancy. She consented to donate blood for possible IUT. STUDY DESIGN AND METHODS: Washed maternal packed cells were suspended in saline to 75 percent Hct and irradiated before transfusion. The fetus was transfused via the intrahepatic vein. RESULTS: Ultrasound examination at 19 weeks indicated a hydropic fetus. The fetal blood group was O Rh+, direct antiglobulin test 4+, and hemoglobin 22 g per L. A total of 368 mL of maternal blood was transfused during seven procedures. Labor was induced at 38 weeks, and a 2560-g male infant was delivered by Caesarian-section due to fetal distress. The infant grouped as B Rh+, direct antiglobulin test negative. No group O red blood cells were detected. The hemoglobin level was 143 g per L rising to 209 g per L at discharge 3 days later. The indirect bilirubin was 55 micromol/L and remained stable during the hospital stay. Phototherapy was discontinued after 1 day, and the infant was discharged without an exchange or top-up transfusion. CONCLUSIONS: Maternal ABO-mismatched blood is an alternate source for IUT in instances when antigen-compatible allogenic blood is unavailable.

Long term follow up of serostatus after maternofetal parvovirus B19 infection.

BACKGROUND: Maternofetal parvovirus B19 infection may result in fetal hydrops or abortion. Chronic infection has been associated with long term complications (polyarthritis, persistent aplastic anaemia, hepatitis). In pregnancy maternal immunosuppression caused by a TH2 dominant response to viral antigens has been observed. There is little information on long term reactivity to intrauterine infection. AIMS: To assess the serological status in children and their mothers after maternofetal parvovirus B19 infection and development of fetal hydrops. METHODS: A total of 18 children and their mothers, and 54 age matched control infants were studied. Main outcome measures were parvovirus B19 DNA, specific IgM and IgG against the virus proteins VP1/VP2, and NS-1 in venous blood. RESULTS: Parvovirus B19 DNA and antiparvovirus B19 (IgM) were undetectable in all sera. A significant larger proportion of maternal sera compared to study children's sera contained IgG against the non-structural protein NS-1. Mean levels of VP1/VP2 IgG antibodies were significantly lower in the children than in their mothers (48 (36) v 197 (95) IU/ml). There was no history of chronic arthritis in mothers and children. Five women had subsequent acute but transient arthritis postpartum, which was not correlated with antibodies against NS-1. CONCLUSIONS: Serological evidence of persistent infection after maternofetal parvovirus B19 disease could not be detected. Increased maternal prevalence of anti NS-1 (IgG) and increased levels of antiparvovirus B19 (IgG) may reflect prolonged viraemia compared to fetal disease.

A transgenic mouse model for non-immune hydrops fetalis induced by the NS1 gene of human parvovirus B19.

Human parvovirus B19 (B19) infection during pregnancy is associated with the adverse foetal outcome known as non-immune hydrops fetalis (NIHF). Although B19 is known to infect erythroid-lineage cells in vivo as well as in vitro, the mechanism leading to the occurrence of NIHF is not clear. To investigate the possible involvement of the B19 non-structural protein NS1 in NIHF, three independent lines of transgenic mice were generated that expressed NS1 under the control of the Cre-loxP system and the GATA1 promoter. Two of the three lines expressed NS1 in erythroid-lineage cells. Most of the transgenic mice died at the embryonic stage, some of which developed hydropic changes caused by severe anaemia at embryonic day 15.5 (E15.5). Histological examination of embryos at E15.5 showed significantly fewer erythropoietic islands in the liver parenchyma, whereas their hearts showed no abnormal signs, such as cardiomegaly and apoptotic cells. The NS1-transgenic mouse lines established here provide an animal model for human NIHF and suggest that NS1 plays a crucial role in the adverse outcome associated with intrauterine B19 infection in humans.

Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional Adrenomedullin gene.

Adrenomedullin, a recently identified potent vasodilator, is expressed widely and has been suggested to have functions ranging from reproduction to blood pressure regulation. To elucidate these functions and define more precisely sites of Adm expression, we replaced the coding region of the Adm gene in mice with a sequence encoding enhanced green fluorescent protein while leaving the Adm promoter intact. We find that Adm(-/-) embryos die at midgestation with extreme hydrops fetalis and cardiovascular abnormalities, including overdeveloped ventricular trabeculae and underdeveloped arterial walls. These data suggest that genetically determined absence of Adm may be one cause of nonimmune hydrops fetalis in humans.

Prenatal diagnosis of parvovirus B19-induced hydrops fetalis by chemiluminescence in situ hybridization.

Parvovirus B19 can be transmitted transplacentally from the infected mother to the fetus during pregnancy, and hydrops fetalis, abortion, or stillbirth can result. In our study we explored the use of chemiluminescence in situ hybridization to detect B19 DNA on cord blood cells, amniotic fluid cells, and pleuric fluid cells from several cases of hydrops fetalis. B19 DNA was detected by using digoxigenin-labeled probes immunoenzymatically visualized with the chemiluminescent adamantil-1,2-dioxetane phenyl phosphate substrate for alkaline phosphatase. The luminescent signal emitted from the hybridized probes was detected, analyzed, and measured with a high-performance, low-light-level imaging luminograph connected to an optical microscope and to a personal computer for the quantification and localization of the chemiluminescent emission inside individual cells.

[Fetal supraventricular tachycardia associated with anasarca: poor prognosis despite treatment. Apropos of two cases]. / Tachycardies supraventriculaires foetales avec anasarque: mauvais pronostic malgré le traitement. A propos de deux cas.

Two cases of foetal supraventricular tachycardia with hydrops with fatal outcomes illustrate the poor general prognosis of this condition. The absence of therapeutic consensus, of large series in the existing literature, does not prevent logical and reasonable management based on rhythmological, pharmacological and prognostic criteria. A combined approach associating antiarrhythmic therapy by the transplacental and intrafunicular approaches seems acceptable now that funicular puncture can be undertaken easily, and certain antiarrhythmic molecules suggest encouraging results. It is important to try to assess the haemodynamic tolerance by foetal Doppler echocardiography because the foetal prognosis depends on ischaemic cerebral lesions induced by anoxia, difficult to diagnose in utero: when observed, aggressive and occasionally dangerous therapies to foetus and mother may be justified in these extreme situations of foetoplacental hydrops.

Nonimmune hydrops fetalis due to congenital syphilis associated with negative intrapartum maternal serology screening.

We present an unusual case, in which a woman presenting with markedly decreased fetal movements at 29 weeks gestation following a recent increase in fundal height was noted sonographically to have fetal hydrops consisting of scalp edema, marked hepatomegaly, ascites, and polyhydramnios. No lethal structural congenital anomaly was noted. Admission laboratory examinations revealed a negative antibody screen and a negative RPR. Emergent cesarean section was performed due to prolonged fetal bradycardia during biophysical profile testing. The acidotic hydropic neonate weighing 1825 g was resuscitated yet succumbed at 3 hr of life following intravenous administration of antibiotics. Neonatal blood was RPR positive at 1:16. Postmortem pathology examination demonstrated severe multiorgan system failure secondary to overwhelming congenital syphilis. Extensive extramedullary hematopoiesis was noted and histopathology with Dieterle stains revealed numerous hepatic spirochetes. Postpartum reexamination of the maternal blood with serial dilutions revealed a positive RPR at 1:1024. This case emphasizes that initial negative screening for syphilis may be seen despite overwhelming infection, a condition that has been termed the "prozone effect."

Foetal anasarca in Awassi sheep.

Two anasarcous foetuses of Awassi sheep are described. The foetuses were removed from the dams by caesarean section because of dystocia due to failure of cervical dilation. Uterine incision was made in situ because uteri were so distended they could not be brought out from the site of incision. Large quantities of uterine fluids and abnormal thick placentas were found. One foetus weighed about 7 kg and the other 13 kg. The foetal heads were deformed: the upper jaw was prognathic and the left ear of the small foetus was cystic. Necropsy revealed subcutaneous musculature was soft and flabby and abdominal and thoracic cavities contained serosanguinous fluid. Histopathological examination revealed that only the larger foetus had focal aggregates of basophilic nucleated red blood cells and scattered megakaryocytes in the liver. We conclude that anasarca can occur in Awassi sheep, with and without associated extramedullary haematopoiesis.

[Modification of transplacental digoxin transfer in the isolated placental lobule]. / Einflussfaktoren des transplazentaren Digoxintransfers im isolierten Plazentalobulus.

Digoxin is widely used in the transplacental therapy of fetal tachyarrhythmia. Unfortunately, in cases with severe cardiac insufficiency and hydrops fetalis, transplacental passage of digoxin is often hampered and therapy therefore ineffective. The present study was designed to establish the isolated placental lobule to quantify transplacental digoxin passage under different experimental conditions. Ten human placentas were obtained immediately after delivery, and a lobule was dually perfused after cannulating a small artery and vein of the chorionic plate and piercing four catheters through the corresponding basal plate. Flow rates were 12 ml/min in the maternal circuit and 6 (I) respectively 3 ml/min (II) in the fetal circuit. The maternal circuit was spiked with digoxin to 6.18 +/- 0.40 ng/ml, and transplacental passage was calculated from repeated fetal and maternal perfusate samples (Fluorescence-Polarization-Immunoassay; TDx, Abbott Laboratories). Within three hours of recirculating perfusion with a fetal flow rate of 6 ml/min (I), digoxin concentrations in the maternal circuit (400 ml) declined to 3.56 +/- 0.09 ng/ml, whereas digoxin levels in the fetal compartment (200 ml) increased to 2.58 +/- 0.37 ng/ml. With a fetal perfusion rate of 3 ml/min (II), the efflux of digoxin out of the maternal circuit was lower (p < 0.05) and the influx in the total compartment was reduced (fetal digoxin concentrations reached only 26.9 +/- 10.6% vs. 39.1 +/- 5.5% of the initial maternal digoxin concentrations). These data suggest that severe fetal cardiac insufficiency with reduced placental perfusion may be in part responsible for the decrease of transplacental digoxin passage in fetuses with hydrops.

The sequential in utero death of heterokaryotic monozygotic twins. A case report and literature review.

A case of monozygotic twins in a 19-year-old primigravida is presented. Ultrasound examination at 15 weeks' gestation showed one twin to have a cystic hygroma and hydrops fetalis. The other twin appeared normal. The twins appeared to occupy the same amniotic cavity. Fluid was taken from the cystic hygroma under ultrasound guidance for karyotyping and this showed 45,XO chromosomes. Conservative management was adopted. Serial ultrasound examination showed deteriorating hydrops and at 26 weeks the first twin died. Intensive monitoring of the remaining twin was undertaken with weekly ultrasound, cardiotocography (CTG), and clotting screens. At 29 weeks' gestation the CTG and clotting were normal, but ultrasound revealed that multicystic encephalomalacia had developed in the second twin. A very thin dividing membrane was seen for the first time between the twins. The parents decided to terminate the pregnancy. Prior to an intracardiac potassium chloride injection, a fetal blood sample was taken which revealed 46,XX chromosomes and a normal clotting screen including natural anticoagulant levels. Labour was then induced. Delivery took place 5 h later and the woman made an uneventful recovery. The mechanism for genetic differences between monozygotic twins is discussed and the literature reviewed. A non-disjunction event around the time of splitting of the twins is proposed as the cause. The prognosis for the remaining twin is also discussed, as is the pathogenesis of the cerebral damage.

Comparison of pancuronium and vecuronium for fetal neuromuscular blockade during invasive procedures.

Neuromuscular blocking agents, used to arrest fetal motion for invasive intrauterine procedures, may cause temporary fetal heart rate changes. After 21 invasive procedures using either pancuronium bromide or vecuronium bromide, post-procedure fetal heart rate tracings were retrospectively compared. Pancuronium was associated with an increased fetal heart rate and decreased beat-to-beat variability for 2.5 hours after its use, whereas vecuronium caused no fetal heart rate changes. Vecuronium bromide offers advantages over pancuronium, because the decreased effect on the fetal heart allows better assessment of fetal well-being immediately following invasive intrauterine procedures.

Lethal alpha-thalassaemia created by gene targeting in mice and its genetic rescue.

Mutations at the alpha-globin locus are the most common class of mutations in humans, with deletion of all four adult alpha-globin genes resulting in the perinatal lethal condition haemoglobin Barts hydrops fetalis. Using gene targeting in mice, we have deleted a 16 kilobase region encompassing both adult alpha-globin genes. Animals homozygous for this deletion become hydropic and die late in gestation mimicking humans with hydrops fetalis. Introduction of a human alpha-globin transgene rescued these animals from perinatal death thus demonstrating the utility of this murine model in the development of cellular and gene based approaches for treating this human genetic disease.

Fetal urine production at different gestational ages: correlation to various compromised fetuses in utero.

To reveal which fetal life-threatening diseases significantly contribute to impairment of in-utero urine production and also to determine the gestational age at which time aberrant urine production becomes manifest, we observed 376 compromised fetuses (subject group) at 21-42 weeks' gestation using ultrasonography. A total of 358 uncomplicated fetuses, aged 21-40 weeks, were separately chosen as a control group. Statistical differences in the urine production rate between subject- and control-group fetuses were analysed using the Grubbs-Smirnoff test at corresponding gestational ages. Significant decreases were evident in: bilateral renal agenesis (100%) at 21-23 weeks; bilateral infantile polycystic kidney (100%) at 21-28 weeks; bilateral multicystic kidney disease (100%) at 21-31 weeks; donor fetuses with twin transfusion syndrome (TTS) (100%) at 21-28 weeks; post-term fetuses (100%) at 42 weeks; bilateral hydronephrosis (60%) at 21-38 weeks; non-immunologic hydrops fetalis (42%) at 21-35 weeks; intrauterine growth retardation (41%) at 29-40 weeks; and upper gastrointestinal tract obstruction (36%) at 30-38 weeks. Significant increases were noted in: recipient fetuses with TTS (100%) at 21-28 weeks, and unilateral hydronephrosis (36%) at 27-32 weeks. All indicate that urine production clearly delineates various fetal conditions in utero, in a closely disease-dependent relation to gestational age.

Congenital cystic adenomatoid malformation: a sheep model of fetal hydrops.

Congenital cystic adenomatoid malformation (CCAM) can be diagnosed in utero. Nonimmune hydrops associated with CCAM is a predictor of fetal demise. Fetuses with prenatally diagnosed large CCAM tumors and hydrops have undergone successful in utero resection. An animal model is needed to understand the pathophysiology of CCAM and hydrops. To create a model of CCAM and hydrops, the authors implanted an intrathoracic tissue expander in six fetal sheep at 120 days' gestation. The inflatable tissue expander was implanted in the right side of the chest, and arterial, venous, intrathoracic, and intraamniotic pressure catheters were placed. Each day, the expander was inflated with 25 to 50 mL of saline (maximum, 150 mL), ultrasound examination was performed, and all pressure measurements were taken. In all six fetuses, hydrops developed after expander inflation. Expander inflation correlated with an increase in central venous pressure (CVP) (4 +/- 2 mm Hg v 16 +/- 2 mm Hg [mean +/- SD]; P < .05). To simulate in utero CCAM resection, the expander was deflated in four hydropic sheep, resulting in return of the CVP to near baseline and resolution of hydrops. Silicone vascular casts of two postmortem sheep demonstrated lateral displacement and compression of the vena cavae by the expander. The authors successfully created a model of CCAM and hydrops by inflating an intrathoracic tissue expander in fetal sheep. Based on this model, hydrops associated with CCAM results from obstruction of cardiac venous return and central venous hypertension. This pathophysiology is reversed by expander deflation, which simulates in utero CCAM resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Disappearing fetal lung lesions.

Cystic adenomatoid malformations and sequestrations of the lung are uncommon but potentially devastating problems of the fetus and neonate. We have followed over 50 cases of fetal lung masses from the time of prenatal diagnosis. Serial prenatal ultrasonography demonstrated that 9 large pulmonary lesions dramatically decreased in size or disappeared completely. We conclude that the natural history of prenatally diagnosed fetal lung masses is highly variable. A huge mass associated with fetal hydrops has a dismal outcome. If hydrops is not present, then the initial impression concerning prognosis may not accurately predict outcome, because there may be marked improvement during fetal life.

Diagnosis and incidence of fetal parvovirus infection in an autopsy series: II. DNA amplification.

This study evaluates the practical utility of the polymerase chain reaction (PCR) as a diagnostic method for intrauterine fetal parvovirus infection in cases of hydrops fetalis. Paraffin-embedded, formalin-fixed fetal tissues from cases of hydrops fetalis were assessed for parvovirus B19 by histology and PCR in conjunction with 32P hybridization. Of 673 fetal and neonatal autopsies performed at Women and Infants' Hospital for the years 1985 through 1990, 32 cases were determined to have hydrops fetalis, of which five were positive for parvovirus infection by both histology and the PCR. PCR was not used in seven (22%) of the 32 hydrops cases because 1 microgram of DNA was not available for study. Histology was as sensitive as PCR in detecting parvovirus B19 in fetal autopsy tissues from cases of hydrops fetalis, and could be used reliably in each case to diagnose parvovirus infection. In our hands, histology is as sensitive as PCR and less labor-intensive. We would reserve PCR for cases without inclusions and with a strong suspicion of parvovirus infection, or for fluids in which histological analysis is not available.