bluuebunny/crossref_metadata_2025 huggingface dataset:
Antenatal detection of neural tube defects: Comparison of biochemical and immunofluorescence methods
Authors: Bell J. E. , Barron L. , Raab G.
Published: March 2007

The aim of this study was to determine whether identification of glial cells in amniotic fluid samples could form a useful supplementary test in the antenatal diagnosis of neural tube defects (NTDs). In a 5‐year study, 1452 samples of middle trimester amniotic fluid were examined blind to the results of other antenatal diagnostic tests and to the outcome of pregnancy. Reasons for amniocentesis included raised serum alpha‐fetoprotein (329), previous NTD (73), and a family history of NTDs (71). Duplicate cytospin preparations were stained with Giemsa and an antibody to glial fibrillary acidic protein (GFAP), and on this basis a prediction of fetal NTD status was made which was not communicated to clinicians. Subsequent management of pregnancies was influenced only by the results of routine antenatal testing for NTDs. Twenty cases of NTDs occurred among the 1406 cases in which the outcome was subsequently known. Of these 20 cases, only five (four anencephalic, one spina bifida) were correctly predicted by immunofluorescent identification of GFAP‐positive cells in the amniotic fluid. The remaining 15 cases (two anencephalic, 13 spina bifida) were not so identified. In a further 18 cases, apparently GFAP‐positive cells were identified in the absence of NTDs. We conclude that GFAP immunofluorescence examination of routine amniocentesis samples of amniotic fluid is not a useful predictive test for NTDs.
Cardiac blood flow studies in fetuses with haemoglobin bart's disease
Authors: Ghosh A. , Tang M. , Leung M. P. , Fung L. M. , Ma H. K.
Published: March 2007

Blood flow across the atrioventricular valves and outflow tracts was measured in 55 normal fetuses and 32 fetuses with haemoglobin (Hb) Bart's disease between 18 and 26 weeks of gestation. The mean velocities remained unchanged in both normal and affected fetuses over the gestations studied. The volume flow across both atrioventricular valves and outflow tracts increased as the gestation advanced in both normal and affected fetuses, but was significantly higher in affected than in normal fetuses. The same magnitude of increased flow was found in both hydropic and non‐hydropic fetuses with Hb Bart's disease. These findings suggest that fetuses with severe and long‐standing anaemia have a remarkable cardiac compensatory mechanism for the maintenance of tissue oxygenation. In response to anaemia and circulatory loading, the cardiac chambers and outflow tracts enlarge proportionately up to twice the normal values. Because of this response and the operation of the Frank‐Starling mechanism, the heart is able to maintain a normal mean velocity of propulsion and the net output is increased to two to three times that in normal fetuses. Hydropic changes in these anaemic fetuses appear unrelated to cardiac failure as cardiac failure is not observed at the time that hydropic changes develop.
Prenatal sonographic detection of intra‐abdominal extralobar pulmonary sequestration: Report of three cases and literature review
Authors: White James , Chan Yuen‐Fu , Neuberger Sally , Wilson Toni
Published: March 2007

Three cases of intra‐abdominal extralobar pulmonary sequestration detected antenatally by ultrasound are reported. One case was associated with a large left diaphragmatic hernia. Sonographically, all the cases were found in the left supra‐renal region presenting as a well‐defined echogenic mass with cystic hypoechoic areas. The condition should be considered in the differential diagnosis of all antenatally detected upper abdominal echogenic masses, particularly when associated with a diaphragmatic hernia. Postnatal ultrasound‐guided fine needle aspiration biopsy in one case yielded respiratory type epithelium and this procedure could provide a reasonably confident diagnosis of the lesion.
Cystic Adenomatoid malformation of the lung: Prenatal diagnosis and outcome
Authors: Thorpe‐Beeston J. G. , Nicolaides K. H.
Published: March 2007

During an 8‐year period (1984–1992), we made the ultrasonographic diagnosis of cystic adenomatoid malformation (CAM) of the lung in 58 fetuses at 17–39 weeks' gestation. We reviewed the records of these fetuses and combined the data from 74 cases reported in the literature to determine the incidence of the different types of CAM, associated malformations, and outcome. The lesions were macrocystic in 78 (59 per cent) and microcystic in 54 (41 per cent) of the cases. CAM was left‐sided in 51 per cent, right‐sided in 35 per cent, and bilateral in 14 per cent of the fetuses. In 15 (11 per cent) of the fetuses there were additional malformations and 57 (43 per cent) were hydropic. The pregnancy was electively terminated in 44 (33 per cent) of the cases, including all those with bilateral CAM. There were six (5 per cent) intrauterine deaths, five in association with hydrops, and one with growth retardation and heart defect. Of the 82 (62 per cent) infants that were liveborn, 21 (26 per cent) died in the neonatal period, 15 before and six after surgery. Of the 61 survivors, 16 (26 per cent) did not require surgery. In the 88 cases where the pregnancy was not terminated, survival was better if the CAM was macrocystic (74 per cent versus 58 per cent for microcystic), if there was no hydrops (92 per cent versus 21 per cent for hydrops), and if the amniotic fluid volume was normal or decreased (82 per cent versus 53 per cent for polyhydramnios).
Four‐marker serum screening for Down's syndrome
Authors: Wald N. J. , Densem J. W. , Smith D. , Klee G. G.
Published: March 2007

The value of measuring the separate sub‐units of human chorionic gonadotrophin (free α‐hCG and free β‐hCG) instead of total hCG together with alpha‐fetoprotein (AFP) and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples relating to 75 singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the serum sample, supplemented by data from 970 white women with unaffected pregnancies. Using the four serum markers AFP, uE3, free β‐hCG, and free α‐hCG, in addition to maternal age, 65 per cent of Down's syndrome pregnancies were detected for a 5 per cent false‐positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, total hCG with maternal age). If gestation was based on an ultrasound scan examination, the detection rate was 72 per cent using the four serum markers compared with 67 per cent with the triple test. As an alternative illustration, if the detection rate was kept at 60 per cent and gestation was estimated by an ultrasound scan examination the four‐marker test reduced the false‐positive rate by one‐third from 3 per cent using the triple test to 2 per cent with the four‐marker test. Screening performance was hardly affected by adjusting marker levels for maternal weight. The four‐marker test is, both from a medical and from a financial perspective, the most effective method of prenatal screening for Down's syndrome suitable for routine use.
Maternal serum free α‐human chorionic gonadotrophin levels in twin pregnancies: Implications for screening for Down's syndrome
Authors: Wald N. J. , Densem J. W.
Published: March 2007

Maternal serum free α‐human chorionic gonadotrophin (free α‐hCG) levels were determined in twin and singleton pregnancies at 15–22 weeks of gestation using a set of stored serum samples relating to 200 twin pregnancies and 600 singleton control pregnancies matched for gestational age and duration of storage. Free α‐hCG values are, on average, 1·66 times greater in twin pregnancies than in singleton pregnancies (95 per cent confidence interval 1·56–1·76). If maternal serum free α‐hCG is used in screening for Down's syndrome, values in twin pregnancies can be adjusted using this result so that screening can be performed in twin pregnancies as well as in singleton pregnancies.
Late‐onset isolated cystic hygroma: The obstetrical significance, management, and outcome
Authors: Goldstein Israel , Jakobi Peter , Shoshany Gideon , Filmer Shlomo , Itskoviz Ioseph , Maor Bar
Published: March 2007

We add two cases of prenatally diagnosed late‐onset isolated cystic hygroma to the eight cases reported previously in the English literature. The obstetrical significance, management, and outcome of this entity are reviewed. A retrospective study of late‐onset isolated cystic hygromas delivered in one medical centre between 1978 and 1992 was made. The medical records of these newborns served as the basis of the present report. A Medline search of the English literature was carried out. Over a period of 15 years, we observed 11 cases of late‐onset congenital isolated cystic hygroma, two of whom had prenatal sonographic diagnosis. In one case, a Caesarean section was performed due to a huge lesion. All cases underwent surgical excision with a favourable outcome. Of the eight prenatally diagnosed cases reported previously, one died at birth due to inability to ventilate and two required a tracheostomy. Late‐onset isolated cystic hygroma should be differentiated from the early‐onset nuchal cystic hygroma. The differential diagnosis is important, as late‐onset isolated cystic hygroma does not require any prenatal intervention, but special awareness during labour and Caesarean section in extreme cases. Transport to a perinatal centre with expert neonatal, respiratory, and paediatric surgical care is recommended. The prognosis in general is favourable.
Prenatal sonographic appearance of foramina parietalia permagna
Authors: Salamanca Alberto , Gonzalez‐Gomez Francisco , Padilla Ma Carmen , Motos Miguel A. , Zorrilla Francisco , Sabatel Rosa Ma
Published: March 2007

Foramina parietalia permagna (FPP) is an extremely uncommon congenital defect, inherited as an autosomal dominant condition. Its characteristics are two symmetrical orifices in the parietal bones (not of fixed size) on both sides of the midline. This defect does not affect either the psychic or the physical development of the affected person. This paper describes the sonographic appearance of FPP in utero as an enlargement of the posterior fontanelle.
Prenatal ultrasound diagnosis of rhizomelic chondrodysplasia punctata in a primigravida
Authors: Sastrowijoto Suprapto H. , Vandenberghe Kamiel , Moerman Philippe , Lauweryns Joseph M. , Fryns Jean‐Pierre
Published: March 2007

Rhizomelic chondrodysplasia punctata (RCDP) is a sublethal autosomal recessive disorder characterized by skeletal dysplasia, microcephaly, mental retardation, congenital cataracts, joint contractures, skin changes, and failure to thrive. Prenatal ultrasound diagnosis has been reported during the second trimester of pregnancy. Prenatal diagnosis is also possible from the first trimester onwards by demonstration of peroxisomal dysfunction in cultured chorionic villous or amniotic fluid cells. In all cases reported hitherto, the prenatal diagnosis was established after the birth of a previous affected child. In contrast to these studies in pregnant multiparous women at risk for RCDP, we report on the first case of prenatal ultrasound diagnosis of RCDP at 19 weeks' gestation in a primigravida. In addition, a complex cardiac malformation associated with hypoplasia of the thymus (DiGeorge anomaly) is described.
Tetrasomy 12p (Pallister‐Killian syndrome): Ultrasound indicators and confirmation by interphase fish
Authors: Wilson R. D. , Harrison K. , Clarke L. A. , Yong S. L.
Published: March 2007

Tetrasomy 12p (Pallister‐Killian syndrome) is a mosaic aneuploidy syndrome in which the isochromosome is present in amniocytes with a much greater percentage than fetal lymphocytes. Two new cases identified by prenatal diagnosis are reported. Indications for prenatal diagnosis were advanced maternal age and fetal anomalies. The most consistent reported prenatal ultrasound findings for tetrasomy 12p include polyhydramnios with short femurs and a diaphragmatic hernia. Recognition of congenital malformation patterns prenatally may allow appropriate selection of tissue for chromosome analysis. Molecular cytogenetic analysis using fluorescence in situ hybridization was used retrospectively to confirm the presence of the isochromosome 12p in various formalin‐fixed fetal tissues. The levels of mosaicism detected in fetal and placental tissues were lower than those detected prenatally.
The association between alpha‐fetoprotein and βhcg levels prior to and following chorionic villus sampling in cases that spontaneously miscarried
Authors: Barkai G. , Reichman B. , Ries L. , Lusky A. , Lipitz S. , Goldman B.
Published: March 2007

Maternal serum alpha‐fetoprotein (AFP) and beta‐human chorionic gonadotropin (βhCG) measurements taken prior to chorionic villus sampling (CVS) in 21 patients who subsequently miscarried were compared with measurements in a control group of 113 patients with uneventful pregnancies. Patients with AFP levels of 10 iu/ml or more prior to the CVS had a 4·3 times greater risk of miscarriage (95 per cent confidence interval 1·3–13·6). AFP levels obtained 1 week after the CVS in the 13 patients with late miscarriages were higher than in the control group (P = 0·06). Patients miscarrying had a greater rise in AFP (P = 0·06) and a greater fall in βhCG levels (P = 0·04) following the CVS procedure, compared with the control subjects. Each 10‐unit change in the difference between AFP or βhCG levels prior to and 1 week following the CVS was associated with a significantly increased risk for late miscarriage. Elevated maternal serum AFP levels early in pregnancy and changes in AFP and βhCG levels following CVS may predict an increased risk for subsequent miscarriage.
Feto‐amniotic shunting—report of the experience of four european centres
Authors: Bernaschek Gerhard , Deutinger Josef , Hansmann Manfred , Bald Rainer , Holzgreve Wolfgang , Bollmann Rainer
Published: March 2007

Few reports concerning intrauterine shunting are available. We investigated the impact of this method. In order to evaluate intrauterine shunting and the complication rate for different indications, we sent a questionnaire to all German‐speaking level 3 centres. In four level 3 centres, 52 intrauterine catheters were inserted in 34 fetuses. The indications were uni‐ or bilateral hydrothorax in nine cases, cystic adenomatoid malformation of the lung in four cases, infravesical stenosis in 13 cases, and fetal ascites in eight cases. In three cases (6 per cent), difficulties occurred when the drain was inserted. In 15 cases (29 per cent), the function of the drain was reduced by dislocation or occlusion. The mortality rate caused by shunting was as high as eight per cent (four cases). The application of an intrauterine shunt currently represents a rarely performed ultrasound‐guided therapeutic intervention in the fetus. In all cases, the indication for shunting is to avoid compression of normal tissue by cystic structures. A high complication rate restricts the application of drainage to selected cases.
Fetal renal vein thrombosis, hydrops fetalis, and maternal lupus anticoagulant. A case report
Authors: Hage Marvin L. , Liu Rebecca , Marcheschi David G. , Bowie James D. , Allen Nancy B. , Macik B. Gail
Published: March 2007

Hydrops fetalis with fetal renal vein thrombosis in a mother with antiphospholipid antibody syndrome detected post‐partum suggests an underlying pathogenetic association that may provide new strategies for treatment of a lethal disorder.
Prenatal diagnosis of congenital gastric outlet obstruction
Authors: Weissman Ariel , Achiron Reuwen , Kuint Jacob , Lipitz Shlomo , Mashiach Shlomo , Avigad Itamar
Published: March 2007

A case of gastric outlet obstruction diagnosed prenatally at 22 weeks' gestation is described. The differential diagnosis and the clinical management of this rare condition are discussed, and an updated literature review is presented.
Prenatal diagnosis of congenital human cytomegalovirus infection
Authors: Nicolini Umberto , Kustermann Alessandra , Tassis Beatrice , Fogliani Roberto , Galimberti Andrea , Percivalle Elena , Revello Maria Grazia , Gerna Giuseppe
Published: March 2007

Fifteen fetuses at risk of congenital human cytomegalovirus (HCMV) infection underwent prenatal diagnosis at 16–30 weeks' gestation by a combination of amniocentesis and fetal blood sampling. HCMV was isolated from the amniotic fluid in six patients, but HCMV‐specific IgM was detected in only three of them. Two of the nine neonates, who were delivered following a negative prenatal diagnosis, had congenital HCMV infection diagnosed by virus isolation in the urine. The interval from infection to prenatal testing was 3 and 4 weeks in the two false‐negative cases and ⩾ 7 weeks in the true‐positive cases. Although timely testing for HCMV infection allows the option of termination of pregnancy, it may be flawed by false‐negative results.
Risk assessment of amniocentesis between 11 and 15 weeks: Comparison to later amniocentesis controls
Authors: Crandall Barbara F. , Kulch Peggy , Tabsh Khalil
Published: March 2007

We studied 693 consecutive early amniocenteses (prior to 15 weeks) and found a spontaneous abortion rate to 28 weeks' gestation of 1·5 per cent. A control group of women having standard amniocentesis (15–20 weeks) experienced a 0·6 per cent fetal loss in the same period. There were no other apparent differences between the two groups. Early amniocentesis results are generally available 4–6 weeks before standard amniocentesis and 1–3 weeks after chorionic villus sampling (CVS). Alpha‐fetoprotein (AFP) can be accurately assayed in 11‐ to 15‐week amniotic fluid samples but additional studies are necessary to determine the accuracy of neural tube defect (NTD) detection. Including the present study, over 5800 early amniocenteses have been reported and the results suggest that this is a relatively safe prenatal diagnostic test and an alternative to CVS and later amniocentesis.
Prenatal diagnosis of xeroderma pigmentosum and cockayne syndrome
Authors: Cleaver James E. , Volpe John P. G. , Charles Wayne C. , Thomas Gregory H.
Published: March 2007

In a study of fetal cells from a series of 12 pregnancies in ten families at risk for the ultraviolet light‐sensitive, DNA repair‐deficient diseases xeroderma pigmentosum (XP) and Cockayne syndrome (CS), we detected one XP and two CS homozygote fetuses. The diagnoses were confirmed by analysis of fetal skin fibroblasts or second amniotic samples after termination of the pregnancies. The measurement of ultraviolet light sensitivity and DNA repair depended on properties common to the seven excision repair‐deficient XP complementation groups (A‐G) and the two CS complementation groups (A, B). No XP variant families were included in the study, because the variant requires different testing techniques. Reliable and rapid diagnosis proved possible in all but one of the 12 pregnancies, supporting the use of these methods until the spectrum of mutations in the various XP and CS genes of the U. S. population is fully characterized and a DNA sequence‐based diagnostic procedure becomes available.
Postnatal confirmation of prenatally diagnosed trisomy 16 mosaicism in two phenotypically abnormal liveborns
Authors: Pletcher Beth A. , Sanz Maureen M. , Schlessel Jerrold S. , Kunaporn Suphat , McKenna Carrie , Bialer Martin G. , Alonso M. Lita , Zaslav Ann‐Leslie , Brown W. Ted , Ray James H.
Published: March 2007

Two phenotypically abnormal liveborns in whom trisomy 16 mosaicism was diagnosed prenatally by amniocentesis are described. Analysis of a percutaneous umbilical blood sample in one case revealed a normal chromosomal complement. Ultrasound examinations performed at the time of amniocentesis were normal. Serial sonography during the late second and third trimesters demonstrated progressive intrauterine growth retardation (IUGR) in both fetuses and a cardiac defect in one. At birth, both infants had dysmorphic features and multiple congenital anomalies. Trisomy 16 mosaicism was confirmed postnatally in both infants in skin fibroblasts; however, peripheral blood samples contained only chromosomally normal cells. The two mosaic trisomy 16 cases described in this report, together with the five confirmed cases reported previously, demonstrate the need for caution in the counselling of patients when trisomy 16 mosaicism is diagnosed prenatally in amniotic fluid samples. Such cases potentially can result in the birth of dysmorphic infants with significant birth defects, growth retardation, and possible developmental disabilities.
The causes and natural history of fetal ascites
Authors: Zelop Carolyn , Benacerraf Beryl R.
Published: March 2007

The purpose of this study was to examine the natural history and differential diagnosis of ultrasound‐detected, isolated fetal ascites. Retrospective review of our patient data base, from 1989 to 1993, revealed 18 patients with fetal ascites diagnosed sonographically. Fetuses presenting with generalized hydrops were excluded. One of the 18 fetuses with ascites had a chromosomal abnormality (trisomy 21), four fetuses had intrauterine infections, seven had gastrointestinal processes, two had genitourinary tract abnormalities, and four were labelled as ‘idiopathic’ (all four resulting in normal neonates). Seventeen of 18 fetuses survived; there was one fetal demise secondary to active syphilis. One fetus with parvovirus infection required intrauterine transfusion and did well. Two infants are developmentally retarded, including one with trisomy 21 and one with microcephaly secondary to cytomegalovirus infection. Fourteen of 18 fetuses had documented in‐utero resolution of the ascites. Eleven of the 18 were associated with polyhydramnios sometime during fetal life. None of the fetuses developed hydrops. In conclusion, fetal ascites can result from many different aetiologies, including gastrointestinal and genitourinary anomalies. Chromosomal abnormalities and viral aetiologies must also be considered. Fetuses who have isolated ascites can have a good outcome with resolution of the ascites antenatally.
Amniotic fluid digestive enzymes: Diagnostic value in fetal gastrointestinal obstructions
Authors: Muller Françoise , Dommergues Marc , Ville Yves , Lewin Fanny , Delvalez‐Morichon Nicole , Nihoul‐Fekete Claire , Bargy Fréderic , Dumez Yves , Boue André
Published: March 2007

The diagnostic value of amniotic fluid gamma‐glutamyl‐transpeptidase (GGTP) and intestinal alkaline phos‐phatase (iALP) was evaluated in 55 patients who underwent amniocentesis for karyotyping because fetal gastric or small bowel dilatation had been detected by ultrasound. Gastrointestinal malformation was confirmed in 46 cases and there was no gastrointestinal anomaly in nine cases. Prenatal ultrasound was suggestive of gastroduodenal dilatation in 34 cases (group I) and small bowel dilatation in 21 cases (group II). In group I, amniotic fluid GGTP above the 99th percentile was 71 per cent sensitive and 100 per cent specific for a true anatomical defect of the digestive tract (mainly duodenal atresia). In group II, high levels of GGTP and/or iALP were 69 per cent sensitive and 83 per cent specific for a fetal digestive tract anomaly. In other words, when digestive tract dilatations were diagnosed by prenatal sonography, abnormal amniotic fluid enzyme activities were strongly suggestive of such an anomaly, the possibility of which was not precluded by normal amniotic fluid iALP and GGTP activities. But amniotic fluid digestive enzyme activities do not help in defining the prognosis.
Prenatal diagnosis of the derivative chromosome 22 associated with cat eye syndrome by fluorescence in situ hybridization
Authors: Reeser Suzanne L. , Donnenfeld Alan E. , Miller Robert C. , Sellinger Beatrice S. , Emanuel Beverly S. , Driscoll Deborah A.
Published: March 2007

Cytogenetic studies of cultured amniocytes demonstrated a karyotype of 46, XX/47, XX,+mar. A bisatellited, dicentric, distamycin‐DAPI negative, NOR‐positive marker was present in 76 per cent of the metaphases examined. Similar markers have been associated with cat eye syndrome (CES). We report on the utilization of fluorescence in situ hybridization (FISH) with a 14/22 a‐satellite probe and a chromosome 22‐specific cosmid for locus D22S9 to determine the origin of the prenatally detected supernumerary marker chromosome. FISH studies demonstrated that the marker is a derivative of chromosome 22 and enabled us to provide the family with additional prognostic information.
Serum PAPP‐A and free β‐hCG are first‐trimester screening markers for down syndrome
Authors: Brambati B. , Tului L. , Bonacchi I. , Shrimanker K. , Suzuki Y. , Grudzinskas J. G.
Published: March 2007

Serum measurements of pregnancy‐associated plasma protein A (PAPP‐A) and the free β‐human chorionic gonadotrophin (hCG) subunit were made in 13 women with Down syndrome (DS) pregnancies and six other women with fetal aneuploidy ascertained at chorionic villus sampling (CVS), as well as 89 women with contemporaneous normal control pregnancies. Median serum PAPP‐A measurements (0·31 MOM, 95 per cent confidence interval (CI) 0·22–0·65 vs. normal 1·06, 95 per cent CI 0·89–1·20) were lower and free β‐hCG subunit measurements (1·13 MOM, 95 per cent CI 0·93–2·63 vs. normal 0·91, 95 per cent CI 0·79–1·03) were higher at statistically significant levels. Receiver operator characteristic (ROC) curves showed that the highest sensitivity for detection, 71·2 per cent (95 per cent CI 54·7–87·6 per cent), was for depressed PAPP‐A levels; the combination of low serum PAPP‐A levels, maternal age, and elevated free β‐hCG levels yielded a detection rate of 78·9 per cent (95 per cent CI 64·9–92·8 per cent) of the affected pregnancies at 8–12 weeks' gestation.
Prenatal detection of trisomy 21 in uncultured amniocytes by fluorescence in situ hybridization: A prospective study
Authors: Spathas D. H. , Divane A. , Maniatis G. M. , Ferguson‐Smith M. E. , Ferguson‐Smith M. A.
Published: March 2007

A prospective study was undertaken to evaluate the use of fluorescence in situ hybridization (FISH) for the detection of trisomy 21 in interphase nuclei of uncultured amniotic fluid cells. Five hundred cases were analysed in situ and classified as normal or abnormal; the results were subsequently checked against the cytogenetic findings. Four hundred and ninety‐three were correctly identified as normal with an 86·6 per cent average frequency of scored nuclei exhibiting two signals; six cases were correctly identified as trisomic for chromosome 21 with 81·7 per cent of scored nuclei exhibiting three signals; and one abnormal case involving an unbalanced chromosome 21·21 translocation was falsely scored as normal due to poor hybridization/detection efficiency. The method has been substantially improved and simplified so that it is suitable for the rapid detection of trisomy 21. As aneuploidy detection in interphase does not identify structural chromosome aberrations, it is not a substitute for fetal chromosome analysis.
Accuracy of amniotic fluid testing before 21 weeks' gestation in prenatal diagnosis of congenital cytomegalovirus infection
Authors: Donner Catherine , Liesnard Corinne , Brancart Françoise , Rodesch Frederic
Published: March 2007

Cytomegalovirus (CMV) is the most common cause of intrauterine infection. Recent publications show amniocentesis to have an 81–100 per cent sensitivity in antenatal diagnosis after 21 weeks' gestation. Testing before 21 weeks' gestation is less well documented. We performed 36 amniocenteses between 14 and 20 weeks' gestation. The sensitivity was 45 per cent and the specificity 100 per cent. Implications and possible causes of this low sensitivity are discussed.
Diagnosis of Bloom's syndrome by sister chromatid exchange evaluation in chorionic villus cultures
Authors: Howell R. T. , Davies Teresa
Published: March 2007

Cultures of a chorion biopsy taken from a pregnancy at risk of Bloom's syndrome revealed the high sister chromatid exchange frequency diagnostic of this rare disorder. To obtain the result, cultures were grown under standard conditions, with the addition of 10μM 5′;‐bromodeoxyuridine for the final 48 h of incubation. This result demonstrates the feasibility of early prenatal diagnosis of Bloom's syndrome.
The amplification refractory mutation system (ARMS): A rapid and direct prenatal diagnostic technique for β‐thalassaemia in Singapore
Authors: Tan J. A. M. A. , Tay J. S. H. , Lin L. I. , Kham S. K. Y. , Chia J. N. , Chin T. M. , Adb. Aziz Norkamar Bt. , Wong H. B.
Published: March 2007

β‐Thalassaemia major patients have chronic anaemia and since 3–4 per cent of Singaporeans carry the β‐gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of β‐major. Six mutations along the β‐gene were studied—41–42 (‐TCTT), IVSII #654 (C‐T), 17β (A‐T), – 28 TATA (A‐G), IVSI #5 (G‐C), and IVSI #1 (G‐T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54·6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele‐specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the β‐trait carrying the 41–42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the β‐trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at − 29 and an ATG‐AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG‐TAG) and codon 26 (GAG‐AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our β‐thalassaemia prenatal diagnosis programme in Singapore.
Measurement of fetal urine production in mild infantile polycystic kidney disease—A case report
Authors: Tsuda Hiroshi , Matsumoto Masahiko , Imanaka Motoharu , Ogita Sachio
Published: March 2007

It is generally recognized that the sonographic findings of infantile polycystic kidney disease (IPKD) are bilaterally enlarged kidneys, oligohydramnios, an absent fetal bladder, and the typical kidney texture. Since there is a broad spectrum of renal compromise with IPKD, in utero diagnosis is thought to be limited to the severe forms. This paper reports a mild case of IPKD, where the in utero diagnosis was established by measuring fetal urine production and amniotic fluid volume serially during pregnancy, and by ultrasonographic examination of fetal kidneys.
Intrauterine growth retardation and fetal transverse cerebellar diameter
Authors: Snijders Rosalinde J. M. , De Courcy‐Wheeler Richard H. B. , Nicolaides Kypros H.
Published: March 2007

In 103 small‐for‐gestational age (SGA) fetuses, the transverse cerebellar diameter (TCD), abdominal circumference (AC), head circumference (HC), and femur length (FL) were measured and their ratios calculated. In addition, umbilical venous blood samples were obtained by cordocentesis for measurements of fetal blood pH and erythroblast count. Compared with the AC, HC, and FL, the TCD was relatively mildly reduced. However, in the 28 fetuses with TCD >2 SDs (standard deviations) below the normal mean, the degrees of growth retardation, acidaemia, and erythroblastosis were more severe, and the incidence of perinatal death was higher than in the group with a normal sized TCD. Although in the group with TCD >2 SDs below the normal mean the TCD/AC ratio was increased, in the most severely growth‐retarded fetuses this ratio was usually within the normal range. Thus, in intrauterine growth retardation (IUGR), cerebellar size is reduced in proportion to the severity of the disease and therefore the TCD cannot be used to obtain reliable information on the gestational age of small fetuses and the TCD/AC ratio does not provide reliable information as to whether or not fetuses are growth‐retarded.
Enrichment of fetal cells from maternal blood by high gradient magnetic cell sorting (double MACS) for PCR‐based genetic analysis
Authors: Büsch J. , Huber P. , Pflüger E. , Miltenyi St. , Holtz J. , Radbruch A.
Published: March 2007

For simple and effective isolation of fetal cells from peripheral maternal blood, we combined depletion of maternal cells and enrichment of fetal cells by high‐gradient magnetic cell separation (MACS). First CD45+ and CD14+ cells were depleted from maternal peripheral blood mononuclear cells by MACS. From the depleted fraction, CD71+ erythroid cells were enriched up to 80 per cent by MACS. This ‘double‐MACS’ procedure yielded an average depletion rate of 780‐fold and an average enrichment rate of 500‐fold, with approximate recovery rates of 40–55 per cent. For paternity testing, cells from unseparated blood and the various fractions were analysed for polymorphism of the HLA‐DQ‐A1 locus and D1S80 locus by the polymerase chain reaction (PCR). In CD45−/CD71+ sorted cells from maternal blood, but not in unfractionated cells from maternal blood or CD45−/CD14− cells, paternal alleles could be detected. In the CD45−/CD71+ fraction, the relative frequency of paternal alleles compared with maternal alleles ranged from 1 in 20 to 1 in 200 (determined by titration and depending on the quality of separation and biological variation). In 7 out of 11 cases, between weeks 12 and 25 of gestation, we could identify paternal alleles by PCR, either HLA‐DQ‐A1 or D1S80. This double‐MACS procedure is simple, fast, efficient, and reliable for non‐invasive prenatal diagnosis.
Prenatal diagnosis of tuberous sclerosis. Use of magnetic resonance imaging and its implications for prognosis
Authors: Werner H. , Mirlesse V. , Jacquemard F. , Sonigo P. , Delezoide A. L. , Gonzales M. , Brunelle F. , Fermont L. , Daffos F.
Published: March 2007

Tuberous sclerosis (TS) is an autosomal dominant disorder with a high rate of de novo mutation. The real difficulty is to ascertain the diagnosis and to give the neurological prognosis in each case. Prenatal diagnosis of TS is generally based on ultrasonographic signs of multiple cardiac tumours, i.e. rhabdomyomas. Recent progress in magnetic resonance imaging (MRI) enables the diagnosis in a large proportion of cases based on typical brain lesions. It may have a role in the prenatal management of TS, although MRI images seem to underestimate the anatomical findings. Two cases in which TS was diagnosed prenatally are presented with reference to the value of MRI in the prenatal management and comparison with anatomical findings.
Early detection of abdominal pregnancy by maternal serum AFP+ screening
Authors: Bombard Allan T. , Nakagawa Sachiko , Runowicz Carolyn D. , Cohen Brian L. , Mikhail Magdy S. , Nitowsky Harold M.
Published: March 2007

We present two cases of abdominal pregnancy identified in our maternal serum screening programme—an additional, as yet unreported benefit of AFP+ (multiple analyte) maternal serum oncofetal antigen screening in pregnancy.
Gene therapy for cystic fibrosis: Will it affect the uptake of prenatal carrier screening?
Authors: Mennie M. E. , Compton M. E. , Liston W. A. , Brock D. J. H.
Published: March 2007

We report a study which examined whether the decision of 135 couples to accept prenatal cystic fibrosis (CF) carrier screening would be influenced by the advent of gene therapy. A majority (91 couples; 67 per cent) felt that gene therapy for CF would not influence their decision to be screened. Twenty‐two couples (16 per cent) stated that they would decline to be screened and an equal number felt ambivalent. Even if the life expectancy of a CF sufferer were increased by gene therapy to normal, 78 per cent of couples would still wish to avail themselves of prenatal carrier screening. A majority of women who decline screening do so because they are opposed to termination of pregnancy. The availability of gene therapy could increase the proportion of couples who accept screening.
Isolating fetal cells in maternal circulation for prenatal diagnosis
Authors: Simpson Joe Leigh , Elias Sherman
Published: March 2007

Fetal cells unequivocally exist in and can be isolated from maternal blood. Erythroblasts, trophoblasts, granulocytes and lymphocytes have all been isolated by various density gradient and flow sorting techniques. Chromosomal abnormalities detected on isolated fetal cells include trisomy 21, trisomy 18, Klinefelter syndrome (47,XXY) and 47,XYY. Polymerase chain reaction (PCR) technology has enabled the detection of fetal sex, Mendelian disorders (e.g. β‐globin mutations), HLA polymorphisms, and fetal Rhesus (D) blood type. The fetal cell type that has generated the most success is the nucleated erythrocyte; however, trophoblasts, lymphocytes and granulocytes are also considered to be present in maternal blood. Fetal cells circulate in maternal blood during the first and second trimesters, and their detection is probably not affected by Rh or ABO maternal‐fetal incompatibilities. Emphasis is now directed toward determining the most practical and efficacious manner for this technique to be applied to prenatal genetic diagnosis. Only upon completion of clinical evaluations could it be considered appropriate to offer this technology as an alternative to conventional invasive and non‐invasive methods of prenatal cytogenetic diagnosis.
Rapid prenatal diagnosis of 14 cases of triploidy using fish with multiple probes
Authors: Gersen Steven L. , Carelli Michael P. , Klinger Katherine W. , Ward Brian E.
Published: March 2007

Fluorescence in situ hybridization (FISH) of chromosome‐specific probes to interphase nuclei can rapidly identify aneuploidies in uncultured amniotic fluid cells. Using DNA probe sets specific for chromosomes 13, 18, 21, X, and Y, we have identified 14 fetuses where the hybridization pattern was consistent with a triploid chromosome constitution. In each case, the identification of fetal abnormalities by ultrasound examination initiated a request for rapid determination of ploidy status via prenatal FISH analysis of uncultured amniocytes. FISH produced a three‐signal pattern for the three autosomes in combination with signals indicating an XXX or XXY sex chromosome complement. This hybridization pattern was interpreted to be consistent with triploidy. Results were reported to the physician within 2 days of amniocentesis and subsequently confirmed by cytogenetics. These cases demonstrate the utility of FISH for rapid prenatal identification of triploidy, particularly when fetal abnormalities are seen with ultrasonographic examination.
Ultrasonographic scanning of placental thickness and the prenatal diagnosis of homozygous alpha‐thalassaemia 1 in the second trimester
Authors: Ko Tsang‐Ming , Tseng Li‐Hui , Hsu Pi‐Mei , Hwa Hsiao‐Lin , Lee Tzu‐Yao , Chuang Sou‐Ming
Published: March 2007

In order to evaluate the association between placental thickness (PT) and fetal homozygous alpha‐thalassaemia 1 before the appearance of classic ultrasound findings of haemoglobin (Hb) Bart's hydrops fetalis, a total of 473 pregnancies were collected. The control group included 422 normal pregnancies with a gestational age from 14 to 23 weeks and the study group included 51 affected fetuses in the same gestational period. Fetal biparietal diameter (BPD) and PT were measured by high‐resolution ultrasound. PT was evaluated against BPD. In the control group, the PT generally increased in parallel with the advancement of gestational age. All PT measurements in the study group were above the mean PT of their respective gestational week in the control group. Forty‐six (90 per cent) of the pregnancies in the study group had PT larger than the mean plus two standard deviations of the control group. This study suggests that ultrasound measurement of PT may be a useful aid in the prenatal diagnosis of Hb Bart's hydrops fetalis before its classic findings become apparent in the late second trimester or third trimester.
Molecular evidence of fetal‐derived chromosome 21 markers (STRs) in transcervical samples
Authors: Adinolfi Matteo , Sherlock Jon , Soothill Peter , Rodeck Charles
Published: March 2007

Transcervical cells (TCCs), collected by flushing or aspiration at 8–13 weeks of gestation, were analysed for the presence of fetal‐derived DNA sequences. DNA extracted from maternal peripheral blood, TCC samples, and placental tissue was amplified by the polymerase chain reaction (PCR) to detect small tandem repeat (STR) markers specific to chromosome 21. STR products of fetal origin could be clearly observed in four TCC samples. TCC samples collected by flushing or aspiration were also analysed by fluorescent in situ hybridization (FISH) using X and Y probes simultaneously: 46,XY cells could be detected in all TCC samples obtained from mothers with male fetuses.
Mosaicism of autosomes and sex chromosomes in morphologically normal, monospermic preimplantation human embryos
Authors: Harper Joyce C. , Coonen Edith , Handyside Alan H. , Winston Robert M. L. , Hopman Anton H. N. , Delhanty Joy D. A.
Published: March 2007

We have previously detected chromosome abnormalities in human embryos whilst identifying the sex for preimplantation diagnosis of X‐linked disease. In this study we assess the incidence of these abnormalities, both for sex chromosomes and autosomes 1 and 17, using dual fluorescent in situ hybridization (FISH). Sixty‐nine normally fertilized embryos of good morphology at the 6–10 cell stage (day 3 post‐insemination) were examined. The embryos were spread whole using HCl and Tween 20 to dissolve the cytoplasm. Thirty‐four embryos were analysed for the sex chromosomes and 35 for autosomes 1 and 17. All probes were directly labelled with fluorochromes allowing analysis in 2 h. Control lymphocytes demonstrated that the probes were of high specificity. For the sex chromosomes, five embryos were mosaic (15 per cent) with the remaining 29 being uniformly XX or XY. In no case was an XX nucleus found in an otherwise XY embryo, indicating that even though mosaicism for the sex chromosomes is present, such abnormalities would not lead to a misdiagnosis of sex. For the autosomes, 16 embryos were abnormal (46 per cent); one embryo was triploid, one was monosomic for chromosome 1, and ten others were diploid mosaics (three diploid/aneuploid, three diploid/polyploid, and four diploid/haploid). A further four embryos had variable chromosome numbers in the majority of nuclei which appeared to be the result of uncontrolled mitotic division. The presence of haploidy or double monosomy, which occurred in 15 per cent of nuclei, has important implications for the diagnosis of trisomies and dominant disorders.
Retrospective study of trisomy 18 in chorionic villi with fluorescent in situ hybridization on archival direct preparations
Authors: van Opstal Diane , van den Berg Cardi , Jahoda Milena G. J. , Brandenburg Helen , Los Frans J. , Veld Peter A. In'T
Published: March 2007

Trisomy 18 in direct chorionic villus preparations needs further investigation since the chromosome abnormality may be confined to the placenta and may not represent the actual fetal karyotype. We performed, retrospectively, fluorescent in situ hybridization (FISH) with the chromosome 18 centromere probe (L1.84) on interphase nuclei of destained slides of all cases of full trisomy 18 (n=22) and mosaic trisomy 18 (n=8) detected among 7600 first‐trimester chorionic villus samples during an 8‐year period (1985–1992). More nuclei displaying three signals were encountered in cases of full and mosaic trisomy 18 confirmed in fetal tissue than in non‐confirmed cases. FISH can be useful for the verification of trisomy 18 in direct chorionic villus preparations.
Prenatal diagnosis of 46, XX/47, XXY mosaicism: A case report
Authors: Cheng Wen‐Fang , Huang Su‐Cheng , Ko Tsang‐Ming
Published: March 2007

A case of 46,XX/47,XXY mosaicism was diagnosed at 22 gestational weeks by amniocentesis and fetal blood sampling. After genetic counselling, the couple elected to have the pregnancy terminated. Culture of the fetal skin and both gonads confirmed the prenatal diagnosis. In external appearance, the abortus had no remarkable findings except hypospadia. Histology of both gonads showed testicular tissue without evidence of ovarian components.
Prenatal diagnosis of medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood
Authors: Gregersen Niels , Winter Vibeke , Jensen Peter K. A. , Holmskov Anni , Kølvraa Steen , Andresen Brage S. , Christensen Ernst , Bross Peter , Lundemose Jytte B. , Gregersen Markil
Published: March 2007

Medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited disease with a carrier frequency of approximately 1:100 in most Caucasian populations. The disease is implicated in sudden unexpected death in childhood. A prevalent disease‐causing point mutation (A985G) in the MCAD gene has been characterized, thus rendering diagnosis easy in the majority of cases. Since the clinical spectrum of MCAD deficiency ranges from death in the first days of life to an asymptomatic life, there are probably other genetic factors—in addition to MCAD mutations—involved in the expression of the disease. Thus, families who have experienced the death of a child from MCAD deficiency might have an increased risk of a seriously affected subsequent child. In such a family we have therefore performed a prenatal diagnosis on a chorionic villus sample by a highly specific and sensitive polymerase chain reaction (PCR) assay for the G985 mutation. The analysis was positive and resulted in abortion. We verified the diagnosis by direct analysis on blood spots and other tissue material from the aborted fetus and from family members.
The influence of gravidity on Down's syndrome screening with free beta hCG
Authors: Spencer Kevin
Published: March 2007

Total human chorionic gonadotropin (hCG) levels have been shown in one previous small study to vary with gravidity. In order to establish if maternal serum free beta hCG was similarly affected, approximately 4500 pregnancies of varying gravidity were analysed. The results indicated that there was a 6 per cent higher median MOM in primigravid compared with multigravid women. The impact of such elevation in Down's syndrome screening programmes will be minimal.
An accessory marker derived from chromosome 20 and its co‐existence with a mosaic trisomy 20 cell line
Authors: Batista Denise A. S. , Escallon Cathleen , Blakemore Karin J. , Stetten Gail
Published: March 2007

We report a 16‐month‐old boy with delayed psychomotor development, dysmorphic features, and failure to thrive. He had a mosaic karyotype detected prenatally: mos 46,XY/47,XY,+r(20)/47,XY,+20. After birth, the abnormal cell lines were confirmed in a number of tissues. The small ring chromosome was identified using fluorescence in situ hybridization as derived from chromosome 20. We compared our patient with previously reported cases of mosaic trisomy 20 detected prenatally and associated with an abnormal phenotype. In an attempt to characterize an r(20) syndrome, we also compared our case with two similar reports in the literature.