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This report describes a family in which eight individuals in three generations had mental retardation in association with a characteristic pattern of clinical problems and physical abnormalities including short stature, eczema, hernias, delayed puberty, dysmorphic facies and digital anomalies. The family history was consistent with a chromosomal rearrangement with transmission through balanced carriers. Routine ASG banding studies showed extra chromosomal material on a chromosome 16 but failed to demonstrate any differences between the affected individuals and the presumed carriers. However, subsequent studies utilizing trypsin banding and microspectrophotometry of individual chromosomes demonstrated that the affected individuals were partially trisomic for the distal band of the long arm of chromosome 5 and that 0.273 units of a chromosome 5 were translocated to chromosome 16. This definitive cytogenetic diagnosis permitted accurate prenatal diagnosis to be carried out on the fetus of a balanced carrier female. The application of these techniques to previously obscure familial dysmorphic syndromes is recommended.

DNA cytophotometry was used to resolve a cytogenetic ambiguity involving a possible deletion of part of the short arm of chromosome 18 in cells obtained by amniocentesis. Measurements of chromosomal DNA content were within normal limits. This is the first time that DNA cytophotometry has been used in cytogenetic diagnosis; it illustrates the potential of this new approach to cytogenetics.

To further characterize the clinical, radiographic and chondro-osseous morphologic changes in the Desbuquois syndrome, 7 patients from three sibships are described. They all had prenatal onset severe rhizomelic and mesomelic shortness with marked joint laxity and marked micrognathia. Radiographic changes were distinct, consisting of a supernumerary ossification center between the proximal phalanx of the index finger and the second metacarpal, and variable thumb changes. The femoral necks showed enlargement of the lesser trochanter with metaphyseal beaking, producing a characteristic “monkey wrench” (Swedish key) appearance. Growth plate cartilage showed dilated cisterns of rough endoplasmic reticulum in reserve zone chondrocytes. Three of the 7 cases were diagnosed prenatally by second trimester ultrasound and one case by fetoscopy. This syndrome exhibits significant phenotypic variability and must be differentiated from the Catel-Manzke syndrome which exhibits similar radiographic changes in the hands. © 1994 Wiley-Liss, Inc.

From 1978 to 1990, 263 fetuses with an elevated level of amniotic fluid alpha-fetoprotein (AF-AFP) (> 2.0 multiples of the median) were examined with targeted fetal sonography. All cases of AF-AFP elevation among 22,355 genetic amniocenteses were represented. Sonography correctly showed 32 open neural-tube defects, including 20 myelomeningoceles, and depicted 94% (63 of 67) of the anomalous fetuses. Two of five anomalous fetuses with normal sonograms, however, had extremely high AF-AFP levels leading to prospectively correct diagnoses of congenital nephrosis. Therefore, programmatically, 97% (65 of 67) of the anomalous fetuses were recognized. The three programmatic misdiagnoses were all detected in the neonatal period and surgically corrected; subsequent development was normal. The combination of an elevated AF-AFP level and a detailed sonogram allowed distinction between a normal and an anomalous fetus in 99% of cases. When elevated levels are noted, AF-AFP analysis followed by detailed sonography is hi...

Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS)

Currently, all methods of prenatal diagnosis require an invasive approach. The next step in the continuing challenge to make prenatal diagnosis more accessible is the development of a noninvasive test. The presence of fetal cells in the maternal circulation has been debated for several decades, but traditional attempts to identify the rare fetal cell within the pool of maternal cells have met with partial success at best. Today, with the aid of highly sensitive and specific techniques such as fluorescent activated cell sorting, polymerase chain reaction, and in-situ hybridization, the task of finding the "on-in-a-million" fetal cell is moving from the realm of the imagination into that of reality.

Four cases of multiple gestation with second trimester death of one fetus and subsequent damage to a survivor are reported. Monochorionic placentation was documented in three of the cases. Central nervous system lesions occurred in all cases, and bowel injury was noted in two of the damaged fetuses. Although rare maternal clotting problems have been reported in similar situations, none was noted in any of these four cases. Prior reports have indicated that losses in the first half of gestation were of no consequence to the surviving fetuses. These four cases contradict this suggestion, and indicate that close sonographic observation of the survivors is important in any multiple gestation where on fetus has died.

Sonograms of fetuses at risk for congenital lethal osteogenesis imperfecta (osteogenesis imperfecta type II) were retrospectively reviewed blindly and correlated with pregnancy outcomes. Six of eight cases of type II osteogenesis imperfecta were correctly diagnosed with use of the proposed criteria of multiple fractures, demineralization of the calvaria, and femoral length more than 3 standard deviations below the mean for gestational age. The two cases not diagnosed had sonographic abnormalities but did not meet all three criteria. Among 18 pregnancies genetically at risk for the disease but with normal outcomes, all sonograms were normal, meeting none of the proposed criteria. Among an additional 25 fetuses with osteochondrodysplasias, no case satisfied all three of the proposed diagnostic criteria. With use of strict standards for the diagnosis of type II osteogenesis imperfecta, this disease can be distinguished from other fetal skeletal abnormalities. In a pregnancy at risk for recurrence of osteogenesis imperfecta, a normal sonogram after 17 weeks excludes this lethal condition.

We have developed a two-colour immunocytochemical staining method for the detection of fetal and embryonic haemoglobin in erythroid cells. The method was applied to study these haemoglobin types in fetal red cells. Specimens from fetal blood (10 weeks), cord blood and fetal liver (14 weeks) as well as chorionic villus samples (10-13 weeks) were stained for gamma and epsilon chains using CY3 and FITC labelled antibodies. Morphometric analysis was applied to determine cell size. Samples from organs involved in early embryonic development contained relatively large erythroblasts expressing the epsilon globin chain (megaloblasts); later in gestation the gamma chain was co-expressed by the same cells which ultimately became smaller and contained HbF (alpha 2 gamma 2) only. This phenomenon was confirmed in CVS samples in which all cell types were abundantly present. Since fetal erythroblasts are considered candidate cells for non-invasive prenatal diagnosis using FISH, we studied the phenotype of erythroblasts circulating in the maternal blood. The majority of erythroblasts in maternal blood appeared to be of the relatively small gamma globin-containing cell type. However, careful screening of the same maternal blood samples also revealed erythroblasts expressing epsilon or epsilon and gamma globins simultaneously, although at low frequency. Control specimens from non-pregnant women did not show nucleated red cells expressing either of the haemoglobin types. These observations may contribute to the better recognition of fetal cells in the maternal blood for prenatal diagnosis.

Gastroschisis is a rare congenital anomaly characterized by the herniation of fetal intestines directly through an abdominal wall defect. It is associated infrequently with chromosomal or other nonbowel defects and can be treated surgically after delivery, with survival rates reported to be between 87 and 100%. We reviewed 21 cases of prenatally diagnosed gastroschisis to ascertain the effect of fetal growth retardation on perinatal outcome. Ten of the 21 fetuses (48%) were identified prenatally as growth retarded, although only seven of these ten truly had birth weights less than the 10th percentile. Three additional fetuses that had not been identified prenatally as growth retarded did, in fact, have birth weights less than the 10th percentile, for a total frequency of growth retardation at birth of 48% (10/21 fetuses). When compared to non-growth-retarded fetuses with gastroschisis, fetuses who were growth retarded, although more likely to have been delivered by emergency cesarean section, had shorter hospitalization times, were more likely to have undergone primary closure on the first day of life, and had fewer major complications. We conclude that growth retardation is common in fetuses with gastroschisis and the postnatal outcome in gastroschisis is not poorer for fetuses who are growth retarded.

Invasive prenatal testing has become an important way to evaluate fetuses at increased risk for hereditary disorders. In utero sampling of fetal skin, liver, and muscle may be required to diagnose before-birth disorders that cannot be diagnosed by analysis using chorionic villi or amniotic fluid. In the next few years, many of these conditions will be detected by DNA analysis, and the need for these procedures may decrease dramatically. First performed by fetoscopy, fetal tissue sampling is now most frequently done by inserting a biopsy needle under continuous ultrasonographic guidance. We describe the indications, techniques, complications, and experience with obtaining fetal skin, liver, and muscle biopsy specimens.

All current methods of fetal karyotyping are invasive and carry a definite, albeit small, procedure-related risk. Because of this and testing costs, only women older than 35 years who have a greater risk for fetal aneuploidy are currently offered prenatal testing. But this detects only 20% to 25% of fetuses with Down syndrome. It would be a tremendous advance to find a noninvasive technique for prenatal diagnosis that carries no procedure-related risk and could be offered to all pregnant women. We describe a possible technique for noninvasive prenatal diagnosis that aims to identify fetal cells in the peripheral maternal circulation and successfully garner them for prenatal testing. Early attempts at fetal karyotyping were hampered by inaccurate diagnostic methods and cumbersome cell-counting techniques. Today, improved capabilities of identifying and enriching for fetal cells, coupled with sensitive methods of analysis such as the polymerase chain reaction, bring renewed enthusiasm to this task. Many technical issues, as well as serious questions regarding the test's utility, still exist, however, and must be explored and answered before the capture of fetal cells in the maternal circulation translates into reality for noninvasive prenatal diagnosis.

One hundred and five patients who met the criterion of having an amniotic fluid pocket depth greater than 8.0 cm were categorized as polyhydramniotic. Of these cases, 82% were singleton pregnancies and 18% were twin pregnancies. The degree of polyhydramnios correlated directly with the probability that an anomaly would be detected. For the lowest rank group (pocket depth of 8 to 9.5 cm), 50% of fetuses manifested an anomaly, whereas the highest rank (16.0 cm or greater pocket depth) carried an 88% risk for an anomaly. Overall, 63% of pregnancies with polyhydramnios revealed anomalies. Sonography found all to be anomalous. There were three false diagnoses of potential anomalies. Monochorionic anomalies of twinning (twin transfusion syndrome and acardiac twin) and gastrointestinal anomalies among singletons were the most commonly seen abnormalities. However, a broad spectrum of anomalies was represented in the study group. Only five diabetic mothers were seen in our study cohort, and in each of them the pregnancy was further complicated by an associated fetal anomaly.

Carrier detection and prenatal diagnosis of Norrie disease (ND) were performed using the polymorphic L1.28, OTC, and 58-1 probes. L1.28 was polymorphic in 3 of the 5 ND families tested and informative in 2 families (40%). Probe 58-1 and OTC were informative in one of 3 families (33%) and in both of the 2 families (100%) tested, respectively. The major allele frequency was 73% in L1.28 (DXS7), 89% in 58-1 (DXS14), and 50% in OTC in our patient population. One of 5 families studies showed a recombination between probes (L1.28 and OTC) and the ND gene locus placing the ND locus proximal to L1.28 and OTC.

Chorionic-villus sampling is done in early pregnancy to obtain fetal cells for the prenatal diagnosis of genetic and chromosomal defects. Transcervical chorionic-villus sampling has been shown to be safe and effective in national trials. Recently, an alternative transabdominal technique has been suggested as potentially easier and safer.From April 1987 through September 1989, we prospectively compared transcervical and transabdominal chorionic-villus sampling in 3999 women with singleton pregnancies in whom the risk of a genetically abnormal fetus was increased. Women between 7 and 12 weeks of gestation underwent ultrasonographic evaluation of placental and uterine position. Those with active vaginal infections, active bleeding, or cervical polyps were excluded. If the obstetrician thought either sampling procedure was acceptable, the woman was asked to consent to random assignment to one of the two procedures. Both groups were followed to determine the outcome of pregnancy and the rate of spontaneous fetal loss after chorionic-villus sampling.Among the 3999 women who entered the study, sampling was attempted in 3873 (97 percent), 1944 of whom had been assigned to undergo transcervical sampling and 1929 to undergo transabdominal sampling. Of these 3873 women, sampling was eventually successful in 3863. Sampling was successful after a single insertion of the sampling instrument in 94 percent of the transabdominal procedures and 90 percent of the transcervical procedures. Among the women with cytogenetically normal pregnancies who had sampling because of maternal age, the rate of spontaneous fetal loss through 28 weeks of pregnancy was 2.5 percent in the transcervical-sampling group and 2.3 percent in the transabdominal-sampling group (difference, 0.26 percent; 95 percent confidence interval, -0.5 to 1.0 percent).Transabdominal and transcervical chorionic-villus sampling appear to be equally safe procedures for first-trimester diagnosis of fetal abnormalities.

In utero stem cell transplantation offers the potential for treating a number of genetic disorders. The combination of fetal immunotolerance and fetal marrow space makes the fetus an excellent transplant recipient. Experiments on the mouse, sheep and rhesus monkey have indicated that in utero transplantation is feasible. Human trials are currently beginning.

Cytogenetic data from the United States NICHD collaborative study of chorionic villus sampling (CVS) were used to evaluate the clinical significance of chorionic mosaicism. The 10,754 patients with normal cytogenetic results were compared with 108 patients (1.0 per cent) with placental mosaicism and 181 patients (1.6 per cent) with pseudo-mosaicism. Of the pregnancies intended to continue, the pregnancy loss rate was significantly greater in patients with placental mosaicism than in the cytogenetically normal cohort (8.6 vs. 3.4 per cent, p less than 0.05). However, there was no difference in the frequencies of abruptio placenta, preterm labour or delivery, small-for-gestational-age newborns, pregnancy-induced hypertension, or neonates with Apgar scores less than 7.

The accuracy of biochemical and molecular prenatal diagnoses using chorionic villi as the fetal source was assessed by seven centres participating in the NICHD collaborative study on the safety and accuracy of chorionic villus sampling (CVS) and amniocentesis. Of 601 pregnancies studied, biochemical methods were used to determine the diagnosis in 283 fetuses at risk for 35 different metabolic disorders. Fifteen different lysosomal storage diseases accounted for 81 per cent of the biochemical prenatal diagnoses performed, with 57 per cent of these pregnancies at risk for Tay-Sachs disease. No errors were made in the biochemical diagnoses that predicted affected or unaffected fetuses. However, the diagnoses of certain disorders (e.g., mucopolysacchariodosis type IH, metachromatic leukodystrophy, and Krabbe disease) occasionally required confirmatory studies in cultured amniocytes because the enzyme results were inconclusive in direct and/or cultured villi or due to the presence of a pseudodeficiency allele. Of these, only the diagnosis of a fetus at risk for Krabbe disease remained inconclusive after special studies to discriminate between mutant and pseudo-deficiency alleles. Recombinant DNA techniques were used to predict the diagnosis of 318 fetuses at risk for 16 different disorders in which the defective disease gene could be detected either directly or by linkage analysis to a nearby polymorphic marker. Of these, 32 per cent were for haemoglobinopathies, 25 per cent for cystic fibrosis, 24 per cent for Duchenne or Becker muscular dystrophy, and 7 per cent for haemophilias. Pregnancies at risk for known disorders with specific molecular lesions (e.g., sickle cell disease) were accurately diagnosed in direct and/or cultured villi. Diagnoses requiring analyses with closely linked polymorphic markers were occasionally uniformative or inconclusive. Maternal contamination was not reported in any biochemical or molecular-based diagnosis. These studies document the high accuracy and rapidity of both biochemical and mutation-specific prenatal diagnoses with direct and cultured chorionic villi.

The acardius syndrome is a rare complication of monozygotic twin pregnancies, occurring once in 35,000 births. The outcome is invariably fatal for the acardiac twin and for 50-75% of the normal twins. We present a surgical approach to the treatment of this problem involving hysterotomy and selective delivery of the acardiac twin, which we have used in five cases. In the first case, placental abruption shortly after the procedure led to fetal death. The next two cases resulted in cesarean delivery of the remaining healthy singleton at 35 weeks' gestation. The fourth and fifth cases were delivered at 27 and 28 weeks' gestation, respectively, the first because of preterm rupture of membranes 2 weeks after the procedure and the second because of partial placental abruption 8 weeks after surgery; both of these infants are now doing well. There were no residual maternal complications. We conclude that hysterotomy has direct applicability in the management of these high-risk pregnancies.

A few fetal diseases may benefit from surgical treatment before birth, but hysterotomy and subsequent delivery by cesarean section pose a risk to the otherwise unaffected mother. To assess maternal risk of mortality, morbidity, and reproductive potential after fetal surgery, we reviewed our experience with 17 highly selected women who underwent fetal surgery. Fifteen of these procedures were performed for one of two congenital anomalies: severe bilateral hydronephrosis and congenital diaphragmatic hernia. There were no deaths or serious maternal injuries. In the 14 women who continued pregnancy after hysterotomy, uterine irritability and preterm labor were frequent complications, requiring early confinement in most cases. There has been no detectable effect on future fertility, as indicated by eight subsequent normal pregnancies. We conclude that hysterotomy for fetal surgery can be accomplished without unduly endangering the mother's life or her future reproductive potential. However, morbidity related to premature labor remains a serious problem, and our ability to control uterine contractions after hysterotomy remains the limiting factor in human fetal surgery.The authors describe their experience with 17 highly selected women who underwent hysterotomy for fetal surgery for complex anomalies and then cesarean delivery through the Fetal Treatment Program at the University of California, San Francisco. Maternal risk of mortality, morbidity, and reproductive potential after fetal surgery were assessed. There were no deaths or serious maternal injuries, although the 14 women who continued their pregnancies experienced uterine irritability and preterm labor followed by premature delivery. Seven of the 17 women had eight subsequent normal pregnancies. The authors conclude from their experience that hysterotomy for fetal surgery can be performed without endangering a woman's life or her future fertility. Uterine irritability and premature labor remain serious problems. The authors believe that now is the time to rigorously examine the efficacy, safety, and cost-effectiveness of fetal therapies before they become accepted treatment.

Currently, all methods of prenatal diagnosis require an invasive approach. The next step in the continuing challenge to make prenatal diagnosis more accessible is the development of a noninvasive test. The presence of fetal cells in the maternal circulation has been debated for several decades, but traditional attempts to identify the rare fetal cell within the pool of maternal cells have met with partial success at best. Today, with the aid of highly sensitive and specific techniques such as fluorescent activated cell sorting, polymerase chain reaction, and in-situ hybridization, the task of finding the "on-in-a-million" fetal cell is moving from the realm of the imagination into that of reality.

In 2 fetuses with congenital cystic adenomatoid malformation (CCAM) with hydrops, in-utero resection of the enlarged pulmonary lobe reduced mediastinal shift and allowed expansion of normal lung tissue in both cases. In case 1, the 27-week-gestation fetus died from severe hydrops after premature delivery. In case 2, fetal CCAM resection was completed at 23 weeks' gestation. At 30 weeks a girl was delivered with no evidence of pulmonary hypoplasia. Fetal surgery can now be entertained for otherwise fatal space-occupying intrathoracic lesions.

MOST infants with congenital diaphragmatic hernia die because their lungs are inadequate to support extrauterine life. This remains true despite advances in postnatal care, including preoperative stabilization,1 , 2 pharmacologic treatment of persistent pulmonary hypertension of the newborn,3 , 4 and temporary support with extracorporeal membrane oxygenation.5 , 6 Recently, prenatal diagnosis has allowed us to define the natural history of fetal diaphragmatic hernia better: approximately 75 percent of fetuses with congenital diaphragmatic hernia detected before birth die despite optimal postnatal care.7 8 9 10 11 The neonatal outcome is related to the degree of pulmonary hypoplasia from in utero lung compression, which is determined by the timing and volume . . .

Ten fetuses with gastroschisis on whom a prenatal sonographic diagnosis and evaluation were available and who delivered at the University of California, San Francisco, were evaluated retrospectively. Six fetuses were delivered vaginally without mortality and minimal or absent morbidity. Four were delivered abdominally, 2 for unrelated obstetrical indications. A 3rd fetus had a suspected prenatal bowel perforation and was the sole mortality. Only 1 mother underwent primary cesarean section, specifically due to the fetal gastroschisis. Umbilical cord pH values were normal in those delivered vaginally. With careful ultrasound examination and immediate neonatal surgical capability in a level III perinatal center, vaginal delivery of fetuses with gastroschisis can be associated with excellent outcome. A multinational randomized study of the delivery mode of fetuses with gastroschisis is necessary and appropriate at this time.

A GENETIC deficiency of the plasma protease inhibitor α1-antitrypsin can lead to degenerative lung disease and fatal cirrhosis of the liver.1 , 2 The most common form of the deficiency, which occur...

Neural tube defects (NTDs) are among the most common congenital anomalies in the United States, with an estimated prevalence of 16 per 10,000 births. The measurement of amniotic fluid alpha-fetoprotein (AF-AFP) concentration has been used to detect NTDs since the early 1970s. When the AF-AFP concentration is elevated, ultrasonography is commonly used to confirm the presence of a NTD. In this study, patient charts, amniocentesis records, and ultrasound reports from a three-year period were reviewed. The 97 fetuses identified as being at high risk for NTDs were divided into four groups: those with high AF-AFP concentrations (Groups 1 and 2, with from 3 to 5 standard deviations (SD) above the mean and with more than 5 SD above the mean, respectively): those referred from other institutions because of suspicious sonographic results (Group 3); and those at risk because of a previous sibling with a NTD (Group 4). Ultrasonography was 100 per cent sensitive and 100 per cent specific in diagnosing NTDs. Thus, in pregnancies with an elevated AF-AFP concentration, ultrasonography can reliably identify normal fetuses as well as differentiate between those with NTDs and those with other congenital anomalies. Also, since AF-AFP concentrations decline after 20 weeks' gestation, ultrasonography may be a better test than a repeat amniocentesis in equivocal cases of AF-AFP elevation.

A congenitally malformed infant with a tetraploid chromosome complement who survived to 1 year of age is reported. The relationship of the polyploidy and the anomalies is discussed.

Seven cases of heterozygous achondroplasia were examined in utero. Although the head shape and growth were normal, the initially normal femur length showed a decrease in growth and fell below the lower 99 per cent confidence limit in all cases. The time of presentation of achondroplasia varied between 21 and 27 gestational weeks. This study suggests that the diagnosis of achondroplasia can be reasonably made when the femur is abnormally short. When the femoral length is appropriate prior to 30 weeks, more caution should be taken in interpretation. Because of the variability in presentation, the fetus could be normal or still could be affected.

The prenatal diagnosis of cystinosis is currently based on the increased amount of free-cystine present in amniotic fluid cells. Amniocyte cultures must be grown for at least 2 weeks to obtain sufficient cells for such measurements. Thus, the diagnosis cannot be made until close to 20 weeks gestational age by this method. We report a case in which chorionic villi were used for direct cystine measurement resulting in the in utero diagnosis of cystinosis at 9 weeks gestational age. The diagnosis was confirmed by the study of cultured chorionic villus cells, and of the 10-week abortus.

Seventeen cases of an aberrant sheet of tissue in the amniotic cavity are described to expand and clarify previous observations of this entity. The sheet of tissue demonstrates a thickened base and a free edge that undulates. The fetus moves freely about the sheet of tissue. There are no associated fetal deformities, and infants have no manifestations of the amniotic-band syndrome. Evidence suggests that these sheets may originate from "wrapping" of the amniochorionic membrane over a uterine synechia. These benign sheets of tissue should not be confused with the amniotic-band syndrome.

An association between short femur length (FL) relative to the biparietal diameter (BPD) measured in the second trimester and the Down syndrome recently has been reported by Benacerraf et al (1987). Fetuses meeting an easily calculated criterion were stated to have a high probability for trisomy 21. We compared the biometric data from a selected group of 229 normal second trimester fetuses with 30 fetuses of similar gestational age with karyotype-proven trisomy 21. We found a substantial difference in femur lengths of normal fetuses in our population compared to that reported by Benacerraf et al. The reason for the difference is unclear. Further, we were unable to demonstrate a statistically discernible deviation of measured versus predicted femur lengths in the Down syndrome cohort employing either the formula recommended by Benacerraf et al or a formula calculated from our normal cohort.

Selecting appropriate management for the fetus with bilateral congenital hydronephrosis depends on our ability to accurately assess the severity of existing renal damage and to predict the potential for recovery of renal and pulmonary function if the obstruction is relieved. We reviewed our experience with 20 fetuses with congenital bilateral hydronephrosis to determine the prognostic value of various criteria used to assess functional potential, including temporary catheter exteriorization to measure fetal urine output and composition. Based on autopsy, biopsy, or clinical outcome, ten fetuses were classified retrospectively as "poor function," and ten fetuses as "good function." The good function group could be distinguished from the poor function group by the following criteria: Amniotic fluid (AF) status at presentation (P less than .001), ultrasound appearance of the fetal kidneys (P less than .05), fetal urine sodium and chloride concentration and osmolarity (P less than .001), and hourly urine output (P less than .02), but not by fetal urine iothalamate excretion or potassium and creatinine concentrations (P greater than .05). Based on these results, we have identified prognostic criteria that accurately identify the fetus with "good function" from the fetus with "poor function." We also reviewed the clinical management of our last 12 unreported cases. Ten fetuses had undergone diagnostic catheter placement and in utero renal function testing. This led to placement of a therapeutic indwelling catheter-shunt in seven fetuses (three required multiple shunts) and a suprapubic vesicostomy in another. Catheter related complications, including three cases of chorioamnionitis, emphasize the need for better methods of in utero decompression in selected cases. Our ability to select appropriate management has improved markedly.

To evaluate the potential of in-utero transplantation of fetal haemopoietic stem cells (HSCs) for permanent engraftment as a treatment of congenital haemoglobinopathies, fetal rhesus monkeys were transplanted with HSCs derived from fetal livers. Five pregnant monkeys (60-62 days' gestation) were given an in-utero intraperitoneal injection of fetal liver cells (10(8)-10(9) cells/kg estimated fetal recipient body weight) derived from opposite sex donors at 59-68 days' gestation. Engraftment was confirmed by karyotype analysis of peripheral blood leucocytes and bone marrow; cells of donor sex were found among the recipient cells. Donor cell engraftment was apparent in four of five in-utero HSC transplant recipients at birth. Engraftment involved lymphoid (2.9-8.0% donor cells), erythroid (5.3-12.5%), and myeloid (8.5-15.4%) lineages and has persisted for up to 2 years without evidence of graft-versus-host disease.

Prenatal diagnosis of beta-thalassaemia and sickle-cell anaemia was attempted in 24 pregnancies. Adequate amounts of fetal blood (for studying globin-chain synthesis) were obtained in 22 cases. 4 cases of homozygous beta-thalassaemia and 2 of sickle-cell anaemia were diagnosed. The difference between the homozygous and non-homozygous states was well defined. Fetal bleeding from cord puncture and amnionitis resulted in the loss of three fetuses, and methods to avoid these complications are being devised. It is concluded that prenatal diagnosis of disorders of beta-globin synthesis is feasible.

Prenatal diagnosis of genetic defects was done using fetal blood sampling in 167 at-risk pregnancies, by fetal skin biopsy in 15 pregnancies, and by fetal liver biopsy in 8 pregnancies. Fetal blood sampling was done by fetoscopy through January 1985 and by sonographically directed percutaneous umbilical blood sampling since then. In our series, cytogenetics has become the major indication for fetal blood sampling, increasing from 6% of the cases with fetoscopy to 48% with umbilical blood sampling. Fetoscopy provided pure fetal blood in 61% of cases while umbilical blood sampling provided pure fetal blood 97% of the time. The corrected risk of fetal demise after percutaneous umbilical fetal blood sampling was 2% and after fetoscopy was 4%.

Wahrend der letzten 15 Jahre sind bemerkenswerte Fortschritte in der vorgeburtlichen Diagnostik erzielt worden. Das Endziel dieser Bemuhungen ist jedoch die Entwicklung von Therapiemoglichkeiten der diagnostizierten fetalen Storungen. Aufgrund der jungsten Entwicklungen auf dem Gebiet der aktiven fetalen Interventionen [5, 7, 14, 23] kann der Fetus immer mehr auch als Patient angesehen werden. Erste erfolgreiche Versuche wurden bereits unternommen, erfolgreiche Masnahmen zur Therapie des Fetus mit einem kongenitalen Defekt zu entwickeln [9, 15, 20]. Die Aufmerksamkeit der Offentlichkeit wurde zwar durch die ersten operativen Behandlungen anatomischer Fehlbildungen erregt, die ersten Versuche der pranatalen Therapie beschaftigten sich jedoch auch mit der medikamentosen Behandlung fetaler Storungen. Das erste und bekannteste Beispiel einer fetalen Therapie war allerdings die intrauterine Transfusion von roten Blutkorperchen bei Rhesusinkompatibilitat, die in einem anderen Kapitel dieses Buches dargestellt wird. In diesem Kapitel soll insbesondere auch auf die nichtoperativen Moglichkeiten einer pranatalen Therapie eingegangen werden.

A family has been identified in which an interstitial, apparently unbalanced deletion of the short arm of chromosome 5 could be traced through six individuals in 3 generations. Remarkably, all of the individuals with the deletion are completely asymptomatic and show no physical or mental abnormalities. The deletion was confirmed at the molecular level by identifying DNA probes that mapped within the deleted portion of chromosome 5. Through the use of somatic cell hybrids and quantitative Southern blots, we demonstrated that these individuals do indeed have an unbalanced deletion and are haploid for several million base pairs of DNA in 5p14 without showing any discernable phenotype.