Targeted first-trimester prenatal diagnosis before fetal reduction in triplet gestations and subsequent outcome.

OBJECTIVE: To assess the feasibility of targeted first-trimester ultrasound evaluation in triplet gestations and to report the outcome in reduced and expectantly managed triplets. METHODS: This was a retrospective analysis of 127 triplets at 11-14 weeks with targeted ultrasound examination including nuchal translucency (NT) screening. RESULTS: One or more abnormal findings were observed in 33 of 381 fetuses (8.7%), including increased NT (n = 18), malformations (n = 4), aneuploidy (n = 3), relative intrauterine growth restriction (n = 2) or spontaneous demise (n = 13). Of 63 patients (49%) who chose reduction, selective termination due to abnormal findings was performed in 13 fetuses. The rates of complete abortion <24 weeks were 9.8% and 3.2% for those with expectant management and fetal reduction, respectively. Expectantly managed triplets delivered significantly earlier (31.1 +/- 3.8 vs. 35.6 +/- 3.3 weeks) (P < 0.01) with a lower mean birth weight (1483 +/- 552 g vs. 2305 +/- 557 g) (P < 0.01) and a lower number of liveborn fetuses (85.6% vs. 97.4%) (P < 0.01) than those reduced. CONCLUSION: Targeted first-trimester ultrasound is feasible and reliable in triplet gestations and should be an integral part of the counseling process. It results in more accurate selection for those who consider fetal reduction. Our data further support fetal reduction as a valuable strategy to improve perinatal outcome in triplet pregnancies.

Familial ovarian dysgerminomas (Swyer syndrome) in females associated with 46 XY-karyotype.

An asymptomatic woman (age 38 years) with a family history of ovarian malignancies was referred for presymptomatic genetic testing of mutations in the BRCA genes. A familial Swyer syndrome with the occurrence of dysgerminomas is the most likely diagnosis. However, in our case, all known causes of this heterogeneous disorder have been excluded pointing to the existence of another yet unknown genetic locus. The family history revealed three affected paternal aunts. Two of them developed ovarian malignancies at 13 and 15 years of age, and died at ages 19 and 20. The third aunt, 82 years old, was affected by this disease at the age of 35. She underwent hormonal treatment for 3 years starting at the age of 15 because of primary amenorrhea. Under this treatment she developed nearly complete secondary sexual characteristics. Karyotype analysis revealed a normal male karyotype (46 XY, QFQ). Pelvic ultrasound showed an uterus of normal size, incompatible with an androgen resistance syndrome or a defect in testosterone biosynthesis. We excluded a mutation in the sex-determining region on chromosome Y (SRY) by direct sequencing of the SRY gene. An involvement of the subtelomeric region of chromosome 9p (9p 24.3) recently reported to be involved in XY-sex reversal phenotypes was excluded by molecular testing for loss of heterozygosity as well as fluorescence in situ hybridization studies. Analyses of the DAX1 gene in the dosage sensitive sex reversal locus on chromosome Xp21 by Southern blot analysis showed no duplications.

[Significance of prenatal diagnosis of lip-jaw-palatal clefts]. / Bedeutung der pränatalen Diagnostik von LKG-Spalten.

UNLABELLED: AIMS AND PATIENTS: Visualization of sonographic anatomy of the fetal face has acquired special importance, as conspicuous features in the phenotype facilitate the diagnosis of syndrome-like or chromosomally induced clinical conditions. Between 1990 and 1999, an orofacial cleft was diagnosed sonographically in 70 fetuses at the Clinic for Prenatal Diagnosis and Therapy of Bonn University Hospital. The aim of the study was to investigate whether the type of cleft correlates with the prevalence of associated anomalies or with karyotyping after amniocentesis. The types of associated anomalies and the neonatal outcome of these 70 fetuses were also reexamined. RESULTS: We found a clearly positive correlation with the type of cleft, both for the associated anomalies and for the karyotype. The size of the cleft was much smaller with normal karyotypes than in the case of fetuses with trisomy 18. The trisomy 13 fetuses displayed the most pronounced clefts. None of the fetuses with an isolated lip cleft had an associated anomaly; all were born alive and could be treated surgically. In contrast, all the fetuses with a median cleft had severe associated anomalies that were incompatible with life. Associated anomalies occur more frequently with bilateral cleft lip and palate than with unilateral clefts. The fetuses with a unilateral cleft had a higher survival rate than those with a bilateral cleft. The most common associated anomaly in cleft fetuses is located in the region of the central nervous system. DISCUSSION: Early sonographic information on cleft formation in combination with the karyotype can give rise to differentiated obstetric measures up to the point of termination of pregnancy in the event of an infaust prognosis.

Fetal cleft lip and palate: sonographic diagnosis, chromosomal abnormalities, associated anomalies and postnatal outcome in 70 fetuses.

OBJECTIVE: The aim of this study was to determine the relationship between facial clefts, associated malformations and chromosomal abnormalities. STUDY DESIGN: Sonograms of 70 fetuses with cleft lip with or without cleft palate were prospectively and retrospectively evaluated in our tertiary referral center for the nature of the cleft lip or palate and for the nature of the associated anomalies. Additionally, karyotyping was performed in 63 of the 70 patients (90%). RESULTS: The frequency of additional anomalies and the mortality rate in this selected population varied with the type of cleft. None of the fetuses presenting an isolated cleft lip had additional anomalies and all survived. All fetuses presenting a median facial cleft had concurrent anomalies (particularly of the central nervous system (90%)) and a fatal outcome. Associated defects were more frequent in fetuses with bilateral clefts (72%) than in those with unilateral clefts (48%). Fetuses with a unilateral cleft lip with or without cleft palate had a better survival rate (52%) than those with a bilateral cleft lip with or without cleft palate (35%). The frequency and type of chromosomal abnormalities varied with the type of cleft. The highest rate of chromosomal abnormalities was found in fetuses with median clefts (82%). CONCLUSIONS: Although no conclusions regarding the prevalence of chromosomal or other anomalies in patients with a cleft lip with or without cleft palate in the general population could be drawn, the study revealed a strong relationship between the type of facial cleft, associated malformations, chromosomal abnormalities and fetal outcome.

Diagnosis of a fetal mesoblastic nephroma by 3D-ultrasound.

We report a case of a fetal renal tumor detected prenatally on 3D-ultrasound. As the lesion was well encapsulated the initial sonographic diagnosis was that of a nephroblastoma. Volume calculation by the 3D technique gave a reliable estimation of the tumor size. Contrary to all published case reports concerning antenatally diagnosed mesoblastic nephromas, there was no polyhydramnios. Elective delivery was performed by Cesarean section at 38+ weeks gestation. The neonate underwent left nephrectomy on the second day of life. The subsequent course was uneventful without recurrence of the tumor.

Prenatal diagnosis of abnormalities of the fetal venous system.

OBJECTIVE: To present our experience in the prenatal diagnosis of anomalies of fetal veins using high-resolution color Doppler ultrasound. DESIGN: An observational study of 16 fetuses with abnormalities of the umbilical, portal, hepatic and caval venous system being diagnosed at the Division of Prenatal Diagnosis and Therapy (Bonn, Germany) over the past 5 years. The abnormality of the venous system, the underlying embryologic disorder and the outcome of the pregnancy are presented and compared with the literature. RESULTS: In group A, eight fetuses had an abnormal course of the umbilical vein with a patent (n = 3) or absent (n = 5) ductus venosus. No portal veins and absent or abnormal hepatic veins were visualized by color Doppler sonography. Six fetuses (75%) did not have an associated malformation and have survived. Two pregnancies with fetal hydrops due to a small heart and to Turner's syndrome were terminated or ended in fetal demise. In group B, seven of eight fetuses with an abnormal caval system had a situs ambiguus or an atrial isomerism. A cardiac defect was detected in six cases (86%). These six pregnancies ended in four terminations of pregnancy and two infant deaths due to the severity of the congenital cardiac defect. One child with a normal heart and a child with an isolated abnormal course of the lower inferior vena cava are developing well. CONCLUSIONS: In a targeted fetal scan the course of the umbilical vein, ductus venosus, the portal and hepatic veins and inferior vena cava should be carefully examined using color Doppler. Any suspicious finding should be followed by a detailed assessment of the specificity of this abnormality taking into consideration the embryologic development of the fetal venous system together with the associated malformations.

Agenesis of the ductus venosus and its correlation to hydrops fetalis.

Absence of the ductus venosus is a rare vascular anomaly. We report a late onset of a hydrops fetalis seen in a fetus at 34 completed weeks of gestation. A persistence of the cranial parts of the left and right umbilical veins and of the paired cranial vitelline veins with an absent ductus venosus led to a bilateral hydrothorax, ascites and skin-edema. Postnatally the hydrops resolved within 7 days most probably due to the change from the fetal to the adult circulation. The abnormal venous system was confirmed by angiography. Agenesis of the ductus venosus can manifest in two different morphologic patterns: The umbilical vein drains exclusively into the left branch of the intrahepatic portal vein or the umbilical vein drains into the inferior vena cava or directly into the right atrium by-passing the liver completely. In both patterns, the preferential direction of the flow towards the foramen ovale is not present. While the first pattern leads to hyperperfusion of the liver parenchyma, the latter would result in reduced perfusion and oxygenation. Our findings suggest that agenesis of ductus venosus might induce hydrops fetalis. We conclude, that in every case of hydrops fetalis the venous system should be evaluated by ultrasonography prenatally and/or immediately postnatally.

[Maternal and fetal digoxin level in fetofetal transfusion syndrome (FFTS)]. / Maternale und fetale Digoxinspiegel bei fetofetalem Transfusionssyndrom (FFTS).

BACKGROUND: Even though invasive intrauterine techniques for the treatment of TTTS such as punction of amniotic fluid and laser coagulation of placental vascular anastomoses are established methods in specialized centers, invasive methods are not always sufficiently successful. In conservative treatment of TTTS oral or intravenous maternal digoxin therapy in order to improve fetal cardiac insufficiency in combination with or after failure of invasive techniques is an useful method. PATIENTS AND METHODS: We investigated 12 TTTS pregnancies and 4 singleton pregnancies, which had been treated by maternal digoxin treatment for TTTS or arrhythmias, respectively. At birth, which was performed by means of caesarian section, venous cord blood samples of the newborns and venous maternal blood samples were collected, centrifugated and stored at minus 20 degrees C. Digoxin determinations were performed by radioimmunoassay. RESULTS: Fetal digoxin levels varied between 0.38 and 1.73 ng/ml, maternal levels ranged from 0.97 to 3.23 ng/ml. The fetomaternal digoxin gradient reached a mean of 0.56 (range 0.35 to 1.09). Donator and acceptor gradients were comparable and increased with birth weight or gestational week, respectively. CONCLUSIONS: In cases of pregnancies with TTTS a relatively high maternal digoxin level is necessary, especially during early gestational weeks, in order to reach therapeutical levels in the fetal circulation. Too low dosages might be responsible for unfavourable results in digoxin treatment of TTTS. Whether the maturation of placental villi during gestation could be the reason for increasing digoxin gradients requires further investigations.

Perinatal management of fetal hemolytic disease due to Rh incompatibility combined with fetal alloimmune thrombocytopenia due to HPA-5b incompatibility.

We report out experience in the perinatal management of a complex case of fetal hemolytic disease primarily due to Rhesus incompatibility combined with fetal alloimmune thrombocytopenia. The lowest fetal hemoglobin and platelet levels were 2.6 g/dl and 13,000/microliter, respectively. Intrauterine treatment consisted of six transfusions of packed red cells into the umbilical vein and one transfusion of platelets. The neonate required four transfusions of packed red cells to correct her hyporegenerative erythropoiesis. Postnatal management also included one platelet transfusion, intravenous immunoglobulins and erythropoietin. Although some degree of fetal thrombocytopenia may invariably be found in fetal red cell incompatibility, other rare causes need to be excluded.

Intrauterine management of fetal parvovirus B19 infection.

OBJECTIVES: The aim of our study was to determine the outcome of pregnancies after intrauterine management of fetal parvovirus B19 infection. DESIGN: Retrospective study. SUBJECTS: A total of 37 cases of maternofetal parvovirus B19 infection, 35 of which were associated with hydrops fetalis, were referred to our tertiary level center between 1989 and 1996. With regard to fetal hydrops, no apparent cause other than parvovirus B19 infection was found in any patient. METHODS: In all patients, cordocentesis was performed to assess the degree of fetal anemia. When anemia was present, cordocentesis was followed by intrauterine transfusion with packed red cells into the umbilical vein. Further management depended on the degree of fetal anemia and gestational age and included follow-up fetal blood sampling/transfusion as well as ultrasound examinations as deemed appropriate. RESULTS: Packed red cell transfusion was performed in 30 patients with significant fetal anemia (Z-score 1.6-7.8 below the mean for gestational age). The fetal hemoglobin values ranged from 2.1 to 9.6 g/dl. Serum levels of platelets in the transfusion group were 9-228 x 10(9)/l with Z-scores in the range of < 1 to 3.8 below the mean. During treatment and follow-up, there were five intrauterine deaths (13.5%), one neonatal death (2.7%) and 31 live births (83.8%). CONCLUSIONS: Fetal parvovirus infection can lead to marked anemia and hydrops formation. Cordocentesis allows precise assessment of fetal anemia which can then be corrected by intravenous transfusion. Under this regimen, the outcome proved favorable in the majority of fetuses, even those that were severely anemic.

Endoscopic laser surgery versus serial amniocenteses in the treatment of severe twin-twin transfusion syndrome.

OBJECTIVE: Severe twin-twin transfusion can be treated by either serial amniocenteses with removal of large volumes of amniotic fluid or by endoscopic laser coagulation of the communicating vessels. We investigated the benefit of laser surgery in comparison to serial amniocenteses in terms of pregnancy outcome. STUDY DESIGN: The data used in this comparative study were collected from 116 patients with severe twin-twin transfusion syndrome between 17 and 25 weeks' gestation. The patients were grouped according to the treatment center. The first group comprised 73 patients (median gestational age 20.7 weeks) treated in Hamburg by fetoscopic laser coagulation of the vascular placental anastomoses between January 1995 and May 1997. The second group comprised 43 patients (median gestational age 20.4 weeks), fulfilling identical diagnostic criteria and treated in Bonn by serial amniocenteses between 1992 and 1996. RESULTS: The overall fetal survival rate was not significantly different (61%, 89/146, vs 51%, 44/86; P =.239). There was a significantly higher proportion of pregnancies with >/=1 survivor in the laser-treated group (79%, 58/73, vs 60%, 26/43; P =.033). The number of cases with spontaneous intrauterine fetal death of both fetuses was significantly lower in the laser-treated group (3%, 2/73, vs 19%, 8/43; P =.003). The incidence of abnormal ultrasonographic findings in the brain was significantly lower among surviving neonates after laser surgery than after amniocenteses (6%, 5/89, vs 18%, 8/44; P =. 03). For pregnancies with >/=1 live-born baby, a significantly longer interval between first intervention and delivery (median 90 vs 72 days, P =.022) leading to a significantly higher gestational age at delivery (median 33.7 vs 30.7 weeks, P =.018) was observed for the laser-treated group. The birth weights of the donor fetuses were significantly higher in the laser-treated group (median 1750 vs 1145 g, P =.034), and a trend toward higher birth weight was also found for recipient fetuses (median 2000 vs 1560 g, P =.076). CONCLUSIONS: These findings indicate that endoscopic laser coagulation of placental vascular anastomoses offers a more effective alternative to serial amniocenteses as a treatment of severe second-trimester twin-twin transfusion syndrome.

Perinatal hypophosphatasia: diagnosis and detection of heterozygote carriers within the family.

We report on two families in which one or two children had a severe disorder of skeletal development detected by prenatal ultrasonography. The children died postnatally and showed typical radiological and biochemical findings of perinatal hypophosphatasia. Biochemical analysis revealed a low activity of alkaline phosphatase (AP) and a high value of pyridoxal-5-phosphate (PLP), one of its natural substrates. The screening for mutations of the tissue nonspecific alkaline phosphatase (TNSALP) gene showed homozygosity for a point mutation (G 317 --> D) in the two affected children of the first family. The affected child of the second family was homozygous for a nonsense mutation (R 411 --> X). Family screening revealed that the determination of AP and PLP is helpful for detection of heterozygotes. However, heterozygote children had values of AP in the lower normal range during phases of rapid growth. The determination of PLP proved to be more sensitive in these cases. It should be kept in mind that during the last trimester of gestation there is an increase in maternal AP activity and a normalization of PLP due to placental AP, which is not affected. Therefore, in the course of a prenatal diagnosis in an index case, paternal blood should be analyzed in parallel. For detailed genetic counseling and early prenatal diagnosis in following pregnancies, the possibility of mutation analysis should be used.

Triplet pregnancy with acardius acranius after preimplantation diagnosis.

OBJECTIVE: To report the first case of fetal malformation after preimplantation diagnosis for Duchenne muscular dystrophy (DMD). DESIGN: Case report. SETTING: Perinatal center in a university hospital. PATIENT(S): A conductor for DMD in her third pregnancy. INTERVENTION(S): Preimplantation diagnosis was performed in an outside hospital. In our center, a dichorionic triplet pregnancy with acardius acranius was diagnosed. The anastomosis between the "pump"-twin and the fetus with acardius was embolized with histoacryl to prevent worsening cardiac insufficiency of the "pump"-twin. MAIN OUTCOME MEASURE(S): Pregnancy outcome. RESULT(S): The anastomosis between the "pump"-twin and the fetus with acardius was occluded successfully. Premature preterm rupture of membranes led to rapid labor and delivery at 24 + 5 weeks' gestation. The smaller girl died of severe hyaline membrane disease, whereas the other infant had no major clinical problems and has developed well. CONCLUSION(S): There might be an association between embryo biopsy and fetal malformations. The setting up of a birth register after embryo biopsy is strongly recommended.

Fetal parvovirus B19 infection and meconium peritonitis.

A 33-year-old primigravida at 26 weeks gestation presented with fetal hydrops and fetal anemia following prior parvovirus B19 infection. The fetus required two intrauterine transfusions of packed red cells. At 35 weeks gestation, a cesarean section was performed for obstetric reasons. As a consequence of a prenatal bowel perforation, the neonate developed meconium peritonitis, for which she needed laparotomy. This case demonstrates that there may be an association between intrauterine parvovirus infection and meconium peritonitis, the latter possibly caused by vascular injury in fetal life.

[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.

[Ileus in late pregnancy--sequela of follicle puncture within the scope of in vitro fertilization?]. / Ileus in der Spätschwangerschaft--Folge der Follikelpunktion im Rahmen der In-vitro-Fertilisation?

Complications in connection with the puncture in in-vitro fertilisation (IVF) occur normally relatively soon after the operation. This is a report on a patient in her 28th week of gestation, operated on by laparotomy for ileus. Retrospectively this acute event must be seen as a very rare late complication connected with the puncture. It must be stressed that patients should be informed about this eventually.