bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for fetal Down syndrome with maternal serum hCG and oestriol: A prospective study
Authors: Herrou Michel , Leporrier Nathalie , Leymarie Pierre
Published: March 2007

We report the preliminary results of a prospective study aimed at evaluating the effectiveness of Down syndrome (DS) screening using second‐trimester measurement of maternal serum human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3) together with maternal age. Reference values for hCG, uE3, and the hCG/uE3 ratio in normal pregnancies were established from more than 3000 normal gestations and found to follow a log‐normal statistical distribution. Risk evaluation was made using reference values for affected pregnancies from retrospective studies. Screening of 10 000 women under 38 years resulted in 412 amniocenteses and the prenatal diagosis of six cases of DS, whereas four cases remained undetected until term. In a parallel study, diagnostic amniocentesis was performed in women over 38 years and in women with a previous affected child, and an evaluation of the risk of fetal DS based on serum hCG and uE3 levels was made in all cases. Fourteen cases of DS were detected. Median values for hCG and uE3 in the 24 affected pregnancies were close to the 90th and tenth centiles of the normal reference values, respectively, and thus are in good agreement with the values reported by others in retrospective studies.
Prenatal diagnosis of spina bifida aperta after first‐trimester valproate exposure
Authors: Omtzigt Juliette G. C. , Los Frans J. , Hagenaars Adriana M. , Stewart Patricia A. , Sachs Eva S. , Lindhout Dick
Published: March 2007

In the context of a prospective study on the adverse effects of anti‐epileptic drugs on fetal outcome, we evaluated our experience with prenatal diagnosis by ultrasonography and α‐ fetoprotein (AFP) determination in amniotic fluid. We compared these results with AFP values in maternal serum obtained prior to amniocentesis. From November 1985 to July 1990, amniocentesis at 16–18 weeks of gestation was performed in 267 pregnancies of 237 different women using anti‐epileptic drugs. Among 92 pregnancies with maternal valproic acid use, five (including one concordantly affected monozygotic twin‐pair) were terminated because of a spina bifida aperta, all prenatally diagnosed by AFP determination and acetylcholinesterase electrophoresis in amniotic fluid. The maternal serum AFP level was raised (⩾ 2.5 multiples of the median (MOM) for singleton pregnancies and ⩾ 4.5 MOM for twin pregnancies) in only two of these five affected pregnancies. We emphasize that maternal serum AFP levels may be unreliable for prenatal screening for fetal neural tube defects in women taking valproate and recommend that amniocentesis and fetal ultrasound examination should be offered directly.
Rare non‐mosaic trisomies in chorionic villus tissue not confirmed at amniocentesis
Authors: Dorfmann Andrew D. , Perszyk Jeane , Robinson Patricia , Black Susan H. , Schulman Joseph D.
Published: March 2007

This paper reports eight cases of non‐mosaic, rare, and typically lethal trisomies diagnosed in chorionic villi and not confirmed by amniocentesis. Four cases were 47,XX, + 16; two cases were 47,XX, +2; one was 47,XX, + 12; and one was 47,XY, +7. There have been no known complications in any of these gestations. These eight cases were found in a series of approximately 12 000 samples processed in our laboratory (0.07 per cent). We conclude that (1) rare non‐mosaic trisomy not reflecting the fetal condition is an occasional source of diagnostic ambiguity in chorionic villus sampling; and (2) when encountered, a follow‐up amniocentesis should be recommended to the patient to confirm or rule out the abnormality. We propose the term ‘confined placental abnormality’ to describe non‐mosaic trisomies and other related abnormalities found only in chorionic tissue.
Analysis of chromosome 21 copy number in uncultured amniocytes by fluorescence in situ hybridization using a cosmid contig
Authors: Zheng Y. L. , Ferguson‐Smith M. A. , Warner J. P. , Erguson‐Smith M. E. , Sargent C. A. , Carter N. P.
Published: March 2007

A comparison of the use of chromosome 21‐specific libraries, DOP‐PCR 21 paints, yeast artificial chromosome (YAC) clones, single cosmids, and a 21q cosmid contig as probes for the detection of the copy number of chromosome 21 in interphase cells by fluorescence in situ hybridization shows that the cosmid contig is a satisfactory probe for interphase analysis of chromosome 21. The contig cCMP21.a, which is 55 kb in length, is highly chromosome 21‐specific and produces intense, compact signals in a high proportion of interphase cells. A retrospective blind analysis of coded uncultured amniotic fluid samples correctly detected four trisomy 21 cases out of 49 samples.
Prenatal diagnosis of monosomy 18 and ring chromosome 18 mosaicism
Authors: Eiben B. , Unger M. , Stoltenberg G. , Rutt G. , Goebel R. , Meyer A. , Gamerdinger U. , Hammans W. , Hansen S. , Hauss H. , Vogel M. , Schwanitz G.
Published: March 2007

The case of monosomy 18/ring chromosome 18 mosaicism which was detected prenatally by amniocentesis is presented. The pregnancy was terminated in week 18. Autopsy showed complex malformation of the fetus consisting of cebocephaly, hypotelorism, microphthalmia, severe defects of brain development, and arrest of placental maturation.
Prenatal diagnosis of metabolic diseases on chorionic villi obtained before the ninth week of pregnancy
Authors: Minelli A. , Piantanida M. , Simoni G. , Rossella F. , Romitti L. , Brambati B. , Danesino C.
Published: March 2007

Nine pregnancies at risk for various metabolic disorders were monitored by prenatal diagnosis on chorionic villi obtained between the sixth and ninth weeks of pregnancy. A diagnosis of an affected fetus was made in five cases (Sandhoff, Tay—Sachs (2), Pompe's, GMI), while metachromatic leukodystrophy, GM1 (2), and Pompe's were excluded in four cases. It is concluded that chorionic villi are a reliable tissue for prenatal diagnosis of metabolic disorders also when obtained before the ninth week.
Chromosomal abnormalities associated with a single umbilical artery
Authors: Khong T. Y. , George K.
Published: March 2007

A single umbilical artery was seen in 10 out of 117 cytogenetically abnormal pregnancies. The abnormal karyotypes found to be associated with a single umbilical artery were trisomy 18 (n = 5), monosomy X (n = 2), triploidy (n = 1), sex chromosome (47,XYY; n = 1) and translocation (46t(X,5)(q13p15); n = 1). With the exception of the translocation case, all cases with a single umbilical artery had anatomical defects which were detectable ultrasonographically. This suggests that a single umbilical artery alone is not an indication for prenatal fetal karyotyping.
Prenatal diagnosis of Pallister–Killian syndrome: Resolution of cytogenetic ambiguity by use of fluorescent in situ hybridization
Authors: McLean S. , Stanley W. , Stern H. , Fonda‐Allen J. , Devine G. , Ellingham T. , Rosenbaum K.
Published: March 2007

We report a case of Pallister‐Killian syndrome initially diagnosed prenatally as tetrasomy 21. A 33‐year‐old primiparous woman was noted at 24 weeks' gestation to have moderate polyhydramnios. Ultrasonography showed diminished fetal stomach filling, hydronephrosis, and prominence of the cisterna magna. Cytogenetic analysis of cultured amniocytes was initially interpreted as mosaic tetrasomy 21: 46,XX/47,XX,+i(21q). The patient was then referred to our centre for genetic counselling. At 34 weeks' gestation, a dysmorphic infant was delivered and died within 30 min. Physical features were consistent with the Pallister‐Killian syndrome. Renal, gastrointestinal, and central nervous system anomalies were found at post‐mortem examination. Analysis of peripheral lymphocytes revealed 5 per cent of cells with a marker chromosome, while 92 per cent of cultured fibroblasts had this same marker. Fluorescent in situ hybridization (FISH) using an alpha‐satellite probe for chromosomes 13 and 21 failed to hybridize to the marker, while a chromosome 12 centromeric probe unequivocally identified it as an i(12p). Use of FISH can provide rapid, specific prenatal diagnosis of ambiguous marker chromosomes and improve prenatal counselling.
Fetal presentation of morquio disease type A
Authors: Beck Michael , Braun Susanne , Coerdt Wiltrud , Merz Eberhard , Young Elisabeth , Sewell Adrian C.
Published: March 2007

A fetus with mucopolysaccharidosis type IV A (Morquio type A) is described. The family had one affected child exhibiting symptoms of classical Morquio A disease, and late in the subsequent pregnancy prenatal diagnosis was requested. At 23 weeks' gestation, moderate ascites was detected by detailed ultrasound scan and keratan sulphate was found in the amniotic fluid. The pregnancy was terminated by prostaglandin induction and the diagnosis of mucopolysaccharidosis type IV A was confirmed by demonstration of a deficiency of N‐acetylgalactosamine‐6‐sulphate (GalNac‐6‐S) sulphatase in cultured amniotic cells and in post‐mortem fibroblast cultures. The activities of β‐galactosidase and arylsulphatase A were normal, ruling out Morquio disease type B and multiple sulphatase deficiency. These results indicate that mucopolysaccharidosis IV A (a disease that predominantly affects the skeletal system) may produce ascites in the fetus to such an extent that it can be detected by ultrasound.
Reproductive behaviour and prenatal diagnosis following genetic termination of pregnancy in women of advanced maternal age
Authors: Brandenburg H. , De Koning W. , Jahoda M. G. J. , Stijnen Th. , De Ridder M. A. J. , Sachs E. S. , Wladimiroff J. W.
Published: March 2007

One hundred and fifty‐one women of advanced maternal age who underwent genetic termination of pregnancy (TOP) were studied for their reproductive behaviour and the type of procedure for prenatal diagnosis in a subsequent pregnancy. A total of 59 women (39 per cent) had a further pregnancy. In all continuing pregnancies prenatal diagnosis was performed, of which 75 per cent consisted of chorionic villus sampling (CVS). Reproductive behaviour following a genetic termination was negatively correlated with maternal age and parity. Both reproductive behaviour and the choice to undergo a diagnostic procedure in the next pregnancy were independent of the type of diagnostic procedure in the previous affected pregnancy.
Prenatal detection of 45,X/46,XX/47,XXX mosaicism through amniocentesis: Mosaicism confirmed in cord blood, amnion, and chorion
Authors: Schwartz S. , Raffel L. J.
Published: March 2007

Sex chromosome mosaicism in amniotic fluid cells poses a serious dilemma in prenatal diagnosis. Chromosome analysis of 56 primary clones of amniocytes revealed three distinct cell lines. Nine cells (16.1 per cent) demonstrated a 45,X karyotype, 11 cells (19.6 per cent) a 47,XXX karyotype, and the remaining 36 cells (64.3 per cent) had a modal number of 46 chromosomes (46,XX). Cytogenetic evaluation of 100 cells from cord blood, amnion, and chorion following delivery confirmed this triple mosaicism. However, the distribution of the three karyotypes in the pre‐ and postnatal samples was not found in the same proportions. The cord blood had the most similar frequency to that of the amniotic fluid sample, while the chorion had a significantly increased frequency of 47,XXX cells (41 per cent) and a decreased frequency of 45,X cells (2 per cent). Physical examination of the infant at birth revealed no discernible phenotypic abnormalities. Parental karyotypes were normal. This case highlights the difficulty in determining whether a prenatally detected abnormality will be associated with postnatal phenotypic deviation.
Prenatal diagnosis of Huntington's disease (HD): Experiences with six cases and PCR
Authors: Thies Ulrike , Zühlke Christine , Bockel Barbara , Schröder Kirsten
Published: March 2007

In the course of a 2‐year predictive testing programme for Huntington's disease (HD), six couples from a total of 52 applicants requested prenatal testing. In each case, the pregnancy was in the first or second trimester when the couples were referred for DNA diagnosis. In five cases, exclusion testing was offered; in one case, a person at risk with an increased risk of being a gene carrier requested prenatal diagnosis. In all cases, informative markers for prenatal testing could be determined. Whenever possible, the newer technique of polymerase chain reaction (PCR) for D4S125 was applied to perform rapid prenatal diagnosis. Two couples withdrew before chorionic villus sampling was undertaken; prenatal diagnosis was completed in the remaining four cases. After exclusion testing, two pregnancies were determined to have an increased risk and two fetuses to have a low risk of being HD gene carriers.
Second‐trimester cancer antigen 125 and Down's syndrome
Authors: Van Blerk M. , Smitz J. , De Catte L. , Kumps C. , Van Der Elst J. , Van Steirteghem A. C.
Published: March 2007

This study explores if assay of cancer antigen 125 (CA 125) in maternal serum might aid the detection of Down's syndrome in the second trimester of pregnancy. CA 125 levels were determined retrospectively in stored maternal serum samples from ten Down's syndrome pregnancies and 78 controls matched for gestational and maternal age. In addition, second‐trimester amniotic fluid samples from nine Down's syndrome and 109 unaffected pregnancies were analysed for CA 125. Maternal serum CA 125 values for Down's syndrome pregnancies were lower, with the median being 0.72 multiples of the unaffected population median. The medians for affected and unaffected pregnancies did not differ significantly and there was a considerable overlap in the range of values of cases and controls. The distribution of amniotic fluid CA 125 levels for Down's syndrome pregnancies resembled that for controls. From our present results, we could not find an association between Down's syndrome and second‐trimester maternal serum or amniotic fluid CA 125 levels.
Prenatal detection of multiple copies of a familial supernumerary marker chromosome
Authors: Wolstenholme J. , Brummitt J. A. , English C. J. , Goodship J. A.
Published: March 2007

Direct preparations and long‐term cultures from a chorion villus biopsy, taken because of a known maternal additional marker chromosome, showed a 48,XX,+mar,+mar karyotype in all cells examined. The same karyotype was revealed in a subsequent amniotic fluid sample and in cord blood at delivery. Detailed examination of the child at delivery and at 1 year of age showed no evidence of phenotypic abnormality or developmental problems.
Fetal blood sampling and cytogenetic abnormalities
Authors: Liou Jui‐Der , Chen Chih‐Ping , Breg W. Roy , Hobbins John C. , Mahoney Maurice J. , Yang‐Feng Teresa L.
Published: March 2007

From September 1984 to April 1991, we performed cytogenetic analysis on fetal blood samples from 214 second‐and third‐trimester pregnancies. One hundred and thirty‐four cases were referred to consider the possibility of chromosomal mosaicism following amniocyte studies. The confirmation rate of mosaicism is at 0 per cent (0/9), 1·4 per cent (1/70), and 40 per cent (22/55) for cases of level I, level II, and level III mosaicism, respectively. Four out of 17 cases were positive for the diagnosis of fragile X syndrome. Of 63 cases with abnormal ultrasound findings, blood disorders, or other genetically related clinical conditions, 11 were found to have a chromosome abnormality. Fetal blood sampling is a valuable adjunct to other methods in the prenatal diagnosis of chromosomal mosaicism or pseudomosaicism. It is also useful when rapid cytogenetic diagnosis is desired because of malformations detected in pregnancies at a late gestational age.
An association between fetal abdominal wall defects and elevated levels of human chorionic gonadotropin in mid‐trimester
Authors: Schmidt D. , Rose E. , Greenberg F.
Published: March 2007

We analysed maternal serum human chorionic gonadotropin (hCG) in 16 pregnancies with fetal abdominal wall defects previously identified prenatally by elevated maternal serum alpha‐fetoprotein (AFP) or at birth. The AFP levels had a mean of 6·38 MOM (range 0·34–15·65), as expected with these defects. The hCG levels had a mean of 1·82 MOM (range 0·23–4·11). The hCG levels in five pregnancies (31·25 per cent) were above 2·30 MOM. Elevated levels of hCG may be associated with fetal abdominal wall defects.
Early genetic amniocentesis—4 years' experience
Authors: Kerber S. , Held K. R.
Published: March 2007

Four hundred and thirty early amniocenteses (EAC) from 10 to 14 weeks' gestation were compared with 300 routine amniocenteses (RAC) from 15 weeks' gestation (control A) and 733 routine amniocenteses from 16 to 18 weeks' gestation (control B) with regard to success rates, various growth parameters, and cytogenetic results. Using both in situ and trypsiniz‐ation techniques, the success rate was 99·8 per cent for EAC versus 100 per cent for RAC. The average turn‐around time for establishing a diagnosis was 8·4 days in EAC versus 8·3 days in 15 weeks' specimens (n.s.) and 7·7 days in 16 to 18 weeks' specimens (p ≦ 0·0001) for the last 200 samples. The banding quality of early specimens compared favourably with that of controls (both 500–550 bphs) and was much better than that in long‐term cultured chorionic villus sampling (CVS) (350–400 bphs). For level I and level II mosaicism, no statistically significant differences were noted between EAC and control group A. Comparing EAC with control group B, a significant increase in the number of numerical and structural single cell aberrations was observed (p ≦ 0·025 and p ≦ 0·001, respectively), whereas for multiple cell aberrations only the increase in numerical aberrations was statistically significant (p ≦ 0·001) (x2‐test). Clinical problems arising from the detection of mosaicism were solved in all cases by investigating parallel cultures. It is concluded that early amniocentesis is a reliable procedure which permits prenatal diagnosis of numerical and structural chromosome aberrations to a high standard.
Prospective maternal serum human chorionic gonadotropin screening for the risk of fetal chromosome anomalies and of subsequent fetal and neonatal deaths
Authors: Muller Françoise , Aegerter Philippe , Boue André
Published: March 2007

A prospective study of maternal serum human chorionic gonadotrophin (hCG) measurement for the selection of pregnancies with an increased risk of fetal trisomy 21 was undertaken in 24 000 pregnancies from 1 January 1989 to 31 December 1990. Maternal serum was sampled at 15‐18 weeks of gestation. hCG was measured in one laboratory, with one technique. This ‘hCG high level’ technique was developed for this screening. Amniocentesis was offered to each woman with a maternal serum hCG level above the cut‐off. The follow‐up of the pregnancies is known in 92 per cent of cases. The combination of hCG values and maternal age gave a detection efficiency of 63 per cent for trisomy 21 with rates of amniocentesis of 30 per cent for patients aged 37 years, 20 per cent for patients aged 35 or 36 years, and 5 per cent for patients under 35 years of age. Based on this prospective study, an individual risk was calculated combining the serum hCG value and maternal age. Seventy‐four per cent of trisomy 13, trisomy 18, triploidy, and 5p‐ deletion were detected either in the same selected group of women or in combination with ultrasonography performed when hCG values were very low. The follow‐up study showed that women who had high or low hCG values represented a group at high risk for fetal or perinatal death.
Detection of both the normal and mutant alleles in single cells of individuals heterozygous for the sickle cell mutation—prelude to preimplantation diagnosis
Authors: Monk Marilyn , Kenealy Mary‐Rose , Mohadjerani Soad
Published: March 2007

As a preliminary step to preimplantation diagnosis of sickle cell disease in unfertilized eggs or 8‐cell embryos of heterozygous parents, we established quality control for detection of the mutant and normal alleles of the beta‐haemoglobin gene using single buccal cells. Efficient polymerase chain reaction (PCR) amplification of a 680 base pair sequence of the beta‐globin gene spanning the site of the sickle cell mutation was obtained for 79 per cent of single heterozygous cells. In 71 per cent of cases, both alleles were detected. With this current efficiency, we predict that a clinical preimplantation diagnosis at the 8‐cell embryo stage could be carried out safely and reliably for a couple at risk of transmitting sickle cell disease to their children.
Umbilical cord haemangioma associated with an eruptive cutaneous haemangioma in a female infant
Authors: Weyerts Leah K. , Jones Marilyn C. , Grafe Marjorie , Scioscia Angela L.
Published: March 2007

We report a female infant noted prenatally to have an umbilical cord mass. At birth, a labial strawberry haemangioma was noted. She subsequently developed an abdominal mass which was discovered to be a proliferating haemangioma, continuous with both the labial and the umbilical stump lesions.
Prenatal diagnosis of Dandy‐Walker malformation in a family displaying X‐linked inheritance
Authors: Cowles T. , Furman P. , Wilkins I.
Published: March 2007

The diagnosis of Dandy‐Walker malformation was made on the ultrasonographic evaluation of a 33‐week male fetus. Pedigree analysis revealed a family history of isolated Dandy‐Walker malformation in three other males, suggesting an X‐linked recessive inheritance pattern.
Prenatal diagnosis of cytomegalovirus (CMV) infection: A preliminary report
Authors: Hogge W. Allen , Buffone Gregory J. , Hogge Joan S.
Published: March 2007

Eight patients were referred for prenatal diagnosis for suspected fetal cytomegalovirus infection (CMV): six for documented first‐trimester infection and two for abnormal ultrasound evaluation suggestive of fetal infection. Three methods of diagnosis were employed: (1) amniotic fluid viral cultures and CMV‐specific IgM in fetal serum; (2) amniotic fluid cultures and detection by polymerase chain reaction amplification of CMV‐specific DNA in chorionic villi; and (3) detection of CMV‐specific DNA in villus samples only. Amniotic fluid cultures detected all cases of infection, but CMV‐specific IgM was not a reliable indicator of infection in any case. DNA analysis correlated well with both culture results and clinical outcome.
Unusual segregation for 11q;22q parental translocation in a triplet pregnancy: Prenatal diagnosis in chorionic villi and amniotic fluid
Authors: Soler A. , Carrio A. , Perez‐Vidal M. T. , Borrell A. , Fortuny A.
Published: March 2007

The prenatal diagnosis of an 11q;22q translocation in a triplet pregnancy detected at the time of chorionic villus sampling (CVS) because of advanced maternal age is reported. Karyo‐types obtained from two apparently different CV samples showed the balanced form of translocation, while the one obtained from a third empty sac showed the unbalanced form: 46, XX, −22, + der(22)t(11;22). Second‐trimester amniocentesis confirmed the balanced translocation in one of the two viable fetuses and a normal karyotype in the other. The detected karyotypes derived from two different types of meiotic segregation, alternate and adjacent 1. To our knowledge, this is the first reported case of an unbalanced karyotype not due to a 3:1 meiotic segregation of this specific translocation.
Prenatal diagnosis of Hb H disease due to compound heterozygosity for South‐East Asian deletion and Hb constant spring by polymerase chain reaction
Authors: Ko Tsang‐Ming , Tseng Li‐Hui , Hsieh Fon‐Jou , Lee Tzu‐Yao
Published: March 2007

A pregnant woman has two children affected by moderately severe Hb H disease due to compound heterozygosity of South‐east Asian deletion and Constant Spring mutation. In her third pregnancy, transabdominal chorionic villus sampling was performed at the tenth gestational week to obtain fetal DNA. The polymerase chain reaction was used for detection of both the South‐east Asian deletion and the Constant Spring mutation. Hb H disease was diagnosed in the fetus. After genetic counselling, the couple elected to have the pregnancy terminated.
Prenatal detection of monosomy 21 mosaicism
Authors: Ghidini Alessandro , Fallet Shari , Robinowitz Jane , Lockwood Charles J. , Dische Renate , Willner Judith
Published: March 2007

We report a case of chromosomal mosaicism for monosomy 21 revealed in amniotic fluid cell culture. Ultrasound examination at 19 weeks' gestation showed in utero growth retardation and a complex cardiac malformation. A repeated amniocentesis confirmed the presence of monosomy 21 mosaicism. In view of the sonographically detected fetal abnormalities, termination of pregnancy was elected.
Heteroduplex formation: A potential source of genotyping error from PCR products
Authors: Hatcher Sandra L. S. , Lambert Que Trang , Teplitz Raymond L. , Carlson James R.
Published: March 2007

The formation of heteroduplexes from polymerase chain reaction (PCR) products has recently become a diagnostic tool that is routinely used for the prenatal detection of small deletions or insertions in a number of disease‐causing alleles. We present evidence illustrating that heterozygous PCR products can manifest ‘invisible’ heteroduplexes that can ultimately lead to genotyping errors. Justifications for these ‘invisible’ heteroduplexes and requisite parameters to optimize their detection are presented.
Mosaicism in chorionic villus sampling: An analysis of incidence and chromosomes involved in 2612 consecutive cases
Authors: Wang Boris B. T. , Rubin Cathi H. , Williams John
Published: March 2007

The incidence of chromosome mosaicism was analysed in 2612 consecutive chorionic villus sampling (CVS) cases. True mosaicism was found in five cases (0·19 per cent). Confined placental mosaicism (CPM) occurred in 51 cases (1·9 per cent). The chromosomes most frequently encountered in CPM were 2, 7, 8, and the sex chromosomes. Three types of CPM as proposed by Kalousek et al. (1992) were observed. Cases with CPM had a statistically significant association with spontaneous abortion (x2 = 3·92, p < 0·05). Based on the data analysed, we conclude that (1) CPM is as likely to occur in cultured chorionic villi as in the direct preparation; (2) as with amniocyte culture, chromosome 2 mosaicism occurs commonly in villus culture; (3) the incidence of false‐positive results can be greatly reduced and concern about maternal cell contamination can be alleviated by using both direct cyto‐trophoblast preparation and cultured chorionic stroma cells in all cases; and (4) follow‐up cytogenetic and obstetrical studies, such as ultrasound and fetal monitoring, should always be considered in cases where CPM is suspected.
Racial differences in maternal serum human chorionic gonadotropin and unconjugated oestriol levels
Authors: Kulch Peggy , Keener Sherry , Matsumoto Myles , Crandall Barbara F.
Published: March 2007

We assayed maternal serum samples from 134 black and 268 white women from 16 to 18 weeks of gestation for intact human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3). Serum from women with high ( ⩾ 2·5 MOMs) or low (risk for Down syndrome ⩾ 1/365) maternal serum alpha‐fetoprotein (MSAFP) levels were excluded. After correcting for maternal weight, we found that median hCG levels were 16 per cent higher in black women but uE3 levels were not significantly different. These results confirm three other studies for hCG and one study for uE3. Corrections are recommended for both maternal serum hCG and AFP before calculating the risk for Down syndrome in black women.
First‐trimester alpha‐fetoprotein screening for Down syndrome
Authors: Fuhrmann W. , Altland K. , Jovanovic V. , Holzgreve W. , Miny P. , Wenger D. , Rauskolb R.
Published: March 2007

Screening for Down syndrome and other chromosomal aneuploidies by biochemical parameters in maternal serum is well established for the second trimester. With screening as late as 16 weeks of gestation, the option of chorionic villus sampling (CVS) unfortunately is lost. In our study population, the maternal serum alpha‐fetoprotein (MSAFP) concentration was determined in 2471 women in the first trimester immediately prior to CVS. Although in this sample MSAFP tended to be lower in Down syndrome (DS) pregnancies than in pregnancies with a chromosomally normal fetus, at this early gestational age neither a fixed cut‐off level of 0·5 multiples of the normal median (MOM) nor one of 0·6 MOM was suitable for identifying pregnancies at higher risk for DS. This also applied to trisomy 18, although on average MSAFP in trisomy 18 pregnancies was lower than in normal and DS pregnancies.
Rapid detection of aneuploidy in uncultured chorionic villus cells using fluorescence in situ hybridization
Authors: Rao P. Nagesh , Hayworth Rosa , Cox Kelly , Grass Frank , Pettenati Mark J.
Published: March 2007

Rapid detection of aneuploidy using chromosome‐specific repetitive DNA probes and the potential diagnostic accuracy of fluorescence in situ hybridization (FISH) on interphase cells of chorionic villus samples (CVS) are presented. Analyses demonstrated the ability to correctly identify aneuploidy using FISH in uncultured CVS. Our preliminary investigation suggests that this technique offers a significant clinical potential to circumvent problems of culture, time, and cost in cytogenetic analysis.
‘Late’ chorionic villus sampling: Cytogenetic aspects
Authors: Dalprà L. , Nocera G. , Tibiletti M. G. , Martinoli E. , Oldrini A. , Agosti S. , Crosignani P. G.
Published: March 2007

Cytogenetic data about 145 chorionic villus samples obtained between the 13th and 35th week of gestation are reported. ‘Late’ chorionic villus sampling (CVS) was used to resolve different situations: failed amniotic fluid cell cultures (5 cases); confirmation of an abnormal karyo‐type, previously diagnosed as mosaic (14 cases); and ultrasound fetal malformation (23 cases). Most of the samples (103 cases) were analysed for the classical indications and in these cases, the principal aim was to obtain a rapid fetal karyotype. Excluding the cases used to check fetal karyotype, a chromosomal aberration was found in 11 out of 131 biopsies. In four cases of the group in which the fetal karyotype was checked (14 cases), the pathology observed at the first diagnosis was confirmed, while in the remaining ten cases the anomaly was not observed.
A prospective cytogenetic study of third‐trimester placentae in small‐for‐date but otherwise normal newborns
Authors: Kennerknecht Ingo , Krämer Sabine , Grab Dieter , Terinde Rainer , Vogel Walther
Published: March 2007

Data in the literature suggest that confined placental mosaicism might be associated with intrauterine growth retardation. However, this association may be coincidental and due to bias of ascertainment. We therefore started a prospective study based on the cytogenetic evaluation of placentae derived from growth‐retarded newborns. We further minimized possible bias by excluding those small‐for‐date infants displaying findings which already could explain intrauterine growth retardation (mothers who are smokers, multiple pregnancies, gestosis, dysmorphic infants). In a collection of 71 small‐for‐gestational age newborns, we did not see a single case of true confined placental mosaicism.
Economic assessment of maternal serum screening for Down's syndrome using human chorionic gonadotropin
Authors: Seror V. , Muller F. , Moatti J. P. , Le Gales C. , Boue A.
Published: March 2007

The effectiveness and costs of prenatal screening programmes for Down's syndrome using maternal serum markers will vary significantly depending on the biological cut‐off values chosen in order to select women, at each maternal age, who will be sent for amniocentesis. On the basis of the first French prospective study of human chorionic gonadotropin (hCG) measurement in maternal serum, this paper shows that the screening protocol currently used in France, where hCG cut‐off values are defined in order to offer amniocentesis to women of all ages with a 1 percent fetal risk of Down's syndrome, would detect 64·06 per cent of all cases of trisomy 21 at birth and would be highly profitable for the French social security system. On the basis of a representative sample of 100 000 pregnant women, the total costs of screening would reach $8 302 000 but would generate net potential savings of $32 186 000 in terms of life‐long costs of care for trisomic 21 children which would be ‘avoided’ by termination of pregnancy following a positive diagnosis of Down's syndrome. Economic assessment shows that cost‐benefit analysis would justify lower hCG cut‐off values and a higher detection rate of fetal Down's syndrome (74·45 per cent) than the current French protocol. This paper concludes that it is ethical and value‐laden issues, such as the consequences for women and couples of false positives and false negatives of screening, rather than economic and financial arguments that may set limits to the utilization of screening for Down's syndrome using maternal serum markers like hCG.
Erythroid‐specific antibodies enhance detection of fetal nucleated erythrocytes in maternal blood
Authors: Bianchi Diana W. , Zickwolf Gretchen K. , Yih Melissa C. , Flint Alan F. , Geifman Ossie H. , Erikson Marlena S. , Williams John M.
Published: March 2007

Fetal nucleated erythrocytes (NRBC) in maternal blood are a non‐invasive source of fetal DNA for prenatal genetic screening. We compared the effectiveness of three monoclonal antibodies for the separation of fetal cells from maternal blood by flow sorting. Mononuclear blood cells from 49 healthy pregnant women were incubated with antibody to CD 71, CD 36, and/or glycophorin A (GPA), employed singly or in combination with each other. These monoclonal antibodies recognize surface antigens on haematopoietic precursor cells. Successful isolation of fetal cells was defined as detection of Y chromosomal sequences in maternal blood from women carrying male fetuses, with absence of Y sequences when female fetuses were carried. Thus, gender prediction accuracy was used as a measure of fetal cell separation.

Using anti‐CD 71 to isolate fetal cells, gender prediction was 57 per cent correct; with anti‐CD 36, it was 88 per cent correct. Anti‐GPA, an erythrocyte‐specific antigen, used alone or in combination with anti‐CD 71 or 36, improved gender prediction to 100 per cent. We conclude that antibody to GPA improves the retrieval of fetal NRBC from maternal blood, permitting genetic analysis by the polymerase chain reaction.
Dystrophin gene analysis and prenatal diagnosis of Duchenne muscular dystrophy in Russia
Authors: Baranov V. S. , Gorbunova V. N. , Malysheva O. V. , Artemyeva O. V. , Kascheeva T. K. , Evgrafov O. V. , Polyakov A. V. , Lebedev V. M. , Kuznetzova T. V. , Shlykova S. N. , Mikhailov A. V. , Vakharlovsky V. G.
Published: March 2007

Of 126 families referred for counselling of Duchenne muscular dystrophy (DMD), DNA analysis has been suggested to 119 families with at least one affected child or with an affected close male relative of the woman at risk of being a DMD carrier. A large proportion (about 80 per cent) of the families were represented by sporadic cases (only one affected individual). By means of multiplex polymerase chain reactions with different sets of oligoprimers providing amplification of 10–11 different exons, altogether 49 dystrophin gene deletions were identified (41 per cent). Eighteen deletions clustered in the 5′ ‘hot spot’ region of DMD cDNA and 36 in the distal half of the central rod domain around exons 43–53. An unusually high frequency (18 per cent) of deletions involving exons 17–19 was discovered. Large deletions extending through both ‘hot spot’ regions and thus occupying over 30–40 exons were recorded in five cases (10 per cent). Seventy‐six of 94 families were found to be informative by RFLP analysis for intragenic or extragenetic DNA probes. Carrier status was ascertained in 20 and rejected in 32 female relatives in 40 DMD families. Eight DMD‐affected fetuses were diagnosed prenatally by direct deletion testing or by RFLP analysis. Feasible interpopulation variations in the dystrophin gene deletion pattern are discussed. The prospects for more effective prenatal diagnosis and carrier detection in high‐risk DMD families in Russia are briefly outlined.
Grief and mid‐trimester fetal loss
Authors: Seller Mary , Barnes Chris , Ross Sarah , Barby Teresa , Cowmeadow Pauline
Published: March 2007

Fetal loss through miscarriage or termination of pregnancy for genetic reasons often provokes the grief of bereavement. This is not fully understood, and the extent of the distress is often underestimated by professionals and family alike. We have examined elements of the normal bereavement process and have found that they may occur in specific and accentuated forms in mid‐trimester fetal loss. We discuss our findings in the light of the attachment theory—a psychodynamic model for understanding grief reactions.
Rapid karyotyping in ectopic pregnancies
Authors: Cohen Daniel , Bragos Irma , Berta Cesar , Fodor Mónica , Alonso Eduardo , Nasio César , Kreiman Liliana , Pineda Rafael
Published: March 2007

The aim of this study was to determine the feasibility of karyotyping ectopic Fallopian tube pregnancies utilizing dividing cytotrophoblast cells. Villi from 78 ectopic conceptuses were processed by the direct chromosome technique and cytogenetic diagnosis was successful in 60 cases (76‐9 per cent). The amount of villi obtained, as well as villus morphology, was correlated with cytogenetic success rate. Histological examination of the Fallopian tube was also carried out. A total of 47 cases were chromosomally abnormal (78‐3 per cent), which is the highest frequency of cytogenetic abnormalities reported to date.
Characterization of i(18p) in prenatal diagnosis by fluorescence in situ hybridization
Authors: Yu Loh‐Chung , Williams John , Wang Boris B. T. , Vooljs Marc , Weier Heinz‐Ulrich G. , Sakamoto Masaru , Ying Kuang‐Lin
Published: March 2007

A case is presented in which chorionic villus direct preparation and cultured chorionic villus cells revealed a 47,XX, + mar karyotype. The marker was a small metacentric chromosome and appeared to be i(18p)—isochromosome 18p. Follow‐up studies in both amniotic fluid and fetal fibroblasts confirmed the karyotype. In order to characterize the marker, a panel of biotinylated DNA probes was used, including a whole chromosome 18 probe, chromosome 18‐specific alpha satellite DNA, Yac clones, and a pan‐telomeric probe. These studies show that the marker is a monocentric i(18p) in which about 80 per cent of chromosome 18 alpha satellite DNA has been lost.
A large retinoblastoma detected in a fetus at 21 weeks of gestation
Authors: Maat‐Kievit J. A. , Oepkes D. , Hartwig N. G. , Vermeij‐Keers C. , Van Kamp I. L. , Van De Kamp J. J. P.
Published: March 2007

The facial tumour described here is the first reported case of a large retinoblastoma detected early in pregnancy and adds another item to the differential diagnosis of facial tumours visualized by prenatal ultrasound examination. Ultrasound examination of the fetal eyes can be offered in cases of retinoblastomas where prenatal DNA diagnosis is otherwise impossible.
Ultrasonographic features in a case of heterozygous achondroplasia at 25 weeks' gestation
Authors: Cordone Massimo , Lituania Mario , Bocchino Giancarlo , Passamonti Ubaldo , Tomà Paolo , Camera Gianni
Published: March 2007

Prenatal diagnosis of heterozygous achondroplasia at 25 weeks is described. First‐level fetal ultrasonography demonstrated short long bones of the lower limbs. Second‐level examination showed a large head; shortened femur, fibula, and tibia; a ‘trident’‐shaped hand; and an abnormal facial profile.
Prenatal diagnosis of exencephaly
Authors: Casellas M. , Ferrer M. , Rovira M. , Pla F. , Martinez M. A. , Cabero L.
Published: March 2007

This paper presents a sonographic diagnosis of exencephaly made during the last trimester of gestation. The sonogram showed the absence of bones in the cranial vault together with the presence of a disorganized cerebral mass, with loss of its normal anatomy. Post‐partum examination of the newborn confirmed the findings of the sonogram. We briefly review the characteristics of exencephaly, its aetiology, and its relationship to anencephaly.
Prenatal exclusion of X‐linked hydrocephalus‐stenosis of the aqueduct of sylvius sequence using closely linked DNA markers
Authors: Serville Françoise , Benit Paule , Saugier Pascale , Vibert Mireille , Royer Ghislaine , Pelet Anna , Chery Michèle , Munnich Arnold , Lyonnet Stanislas
Published: March 2007

X‐linked hydrocephalus‐stenosis of the aqueduct of Sylvius sequence (H‐SAS, MIM number 307 000) is a rare genetic disorder characterized by hydrocephalus, macrocephaly, adducted thumbs, spasticity, mental retardation, and cerebral malformations. This regularly lethal condition is usually diagnosed at birth or prenatally by ultrasound, but hydrocephalus may be moderate or even undetectable on fetal ultrasound examination. Moreover, since heterozygous women are asymptomatic, carrier detection is at present impossible before the birth of an affected son. Therefore, mapping the H‐SAS locus to distal Xq (Xq28) was of primary importance for genetic counselling and prenatal diagnosis. Here, we report prenatal exclusion of H‐SAS with a probability of 97.6 per cent in two male fetuses with a 50 per cent a priori risk of being affected using closely linked Xq28 DNA markers.
Prenatal diagnosis of ornithine transcarbamylase deficiency: Results in SPFASH mice
Authors: Monastiri K. , Rabier D. , Kamoun P.
Published: March 2007

Ornithine transcarbamylase (OTC) deficiency is a human X‐chromosome‐linked disease (McKusick 31125). The presence of OTC activity in the human placenta encouraged us to examine the possible diagnosis of the disease in an animal model (Spfash mice) by enzymatic assay on placental samples. A significant positive correlation (P< 0·02) was found between placental and hepatic activities; the pH dependence of OTC was similar in the placenta and liver when compared within normal or homozygous mutant mice. The apparent Km (ornithine) and Km (carbamoylphosphate) values of the enzyme did not show any significant differences when compared in both placentae and livers of normal fetuses. The use of OTC assay in the placenta for prenatal diagnosis of OTC deficiency in mouse fetuses obtained by the crossbreeding of Spfash/+ with +/Y has shown that our method has good diagnostic value. We made the diagnosis of OTC deficiency in male fetuses with a sensitivity and a specificity of 1·0. The + gene from the father in Spfash/ + animals is preferentially inactivated in extraembryonic tissues, explaining why very low placental OTC activity was observed in 12 of the 18 female fetuses studied. Because these 12 females have variable OTC activity in their livers, it is not possible to appreciate the true residual activity in their livers by measuring this activity in the placenta.
Short femur length associated with severe intrauterine growth retardation
Authors: Bromley Bryann , Brown Douglas L. , Benacerraf Beryl R.
Published: March 2007

Four fetuses with a femur measuring greater than two standard deviations below the mean compared with the biparietal diameter are presented. These four fetuses were subsequently determined to have severe intrauterine growth retardation and no evidence of skeletal dysplasias.
Evaluation of prenatal diagnosis of congenital heart disease
Authors: Stoll C. , Alembik Y. , Dott B. , Roth P. M. , De Geeter B.
Published: March 2007

Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of antenatal care in many countries. That an increasing number of fetal anomalies may be detected on prenatal ultrasound is beyond doubt. What is possible is not, however, always practical, especially when congenital heart diseases (CHDs) are concerned and when whole antenatal populations are screened rather than high‐risk groups. Thanks to our registry of congenital anomalies, a retrospective study was undertaken to evaluate the prenatal detection of CHDs by ultrasound scan in 131 760 consecutive pregnancies of known outcome from 1979 to 1988. Only 84 out of 912 malformed fetuses with CHDs without chromosomal anomalies were detected (9.2 per cent). The sensitivity of detection varied from around 38 per cent for malformations such as hypoplastic left heart and single ventricle to around 5 per cent for ventricular and atrial septal defects. The effectiveness of the detection of some forms of major congenital heart disease has increased dramatically since 1987 by including routine examination of the four‐chamber view and of the inflow and outflow tracts of the fetal heart. Our results stress the need to obtain a definite clear four‐chamber view, to perform scans at ⩾ 18 weeks of gestation, and to train sonographers in order to improve the prenatal detection of CHDs.
Antenatal thrombocytopenia in three patients with TAR (thrombocytopenia with absent radii) syndrome
Authors: Labrune Ph. , Pons J. C. , Khalil M. , Mirlesse V. , Imbert M. C. , Odièvre M. , Daffos F. , Tchernia G. , Frydman R.
Published: March 2007

Three fetuses with TAR (thrombocytopenia with absent radii) or TAR variant syndrome were found to be thrombocytopenic during the third trimester of the pregnancy. These findings indicate that fetal blood sampling, besides ultrasonography, skeletal radiographs, or even fetoscopy, may indeed contribute to the prenatal diagnosis of TAR syndrome, and thus may help in differentiating TAR syndrome from other syndromes with malformations of the upper limbs.
Maternal serum biochemical markers in pregnancies with fetal parvovirus B19 infection
Authors: Saller Devereux N. , Rogers Beverly Barton , Canick Jacob A.
Published: March 2007

Hydrops fetalis and fetal death caused by fetal parovirus B19 infection have been reported to be associated with elevated maternal serum alpha‐fetoprotein (AFP), based on a total of six cases. It has been suggested that the absence of AFP elevation may be reassuring. Maternal serum levels of the Down syndrome screening markers unconjugated oestriol and human chorionic gonadotropin in cases of fetal parvovirus infection have not been previously reported. We report four cases of hydrops fetalis and fetal death caused by fetal parvovirus infection, each with unremarkable second‐trimester levels of AFP, unconjugated oestriol, and human chorionic gonadotropin.
Follow‐up of pregnancies complicated by placental mosaicism diagnosed by chorionic villus sampling
Authors: Fryburg Julie S. , Dimaio Miriam S. , Yang‐Feng Teresa L. , Mahoney Maurice J.
Published: March 2007

Thirty‐nine (2.3 per cent) of 1724 chromosome studies from diagnostic chorionic villus samplings (CVS) done between 1983 and 1990 showed either level III (true) mosaicism (1.2 per cent) or level II (pseudo‐) mosaicism (1.1 per cent) for chromosomal aneuploidy. Follow‐up information on these 39 pregnancies was collected from questionnaires to families, paediatricians, and obstetricians. For all cases in which the pregnancy was continued and further testing was accomplished, the mosaicism was felt to be confined to the placenta. As compared with a control group of pregnancies evaluated by CVS with normal karyotypes, there was no increased incidence of pregnancy loss, congenital malformations, or developmental delay in the infants. Although intrauterine growth retardation occurred in several of the level III mosaic cases, adequate catch‐up growth has been demonstrated.