bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental reaction and adaptability to the prenatal diagnosis of fetal defect or genetic disease leading to pregnancy interruption
Authors: Dallaire L. , Lortie G. , Des Rochers M. , Clermont R. , Vachon C.
Published: March 2007

The objective of the study was to evaluate the psychological reaction of two groups of parents to a pregnancy termination after they had undergone a prenatal diagnostic procedure. The analysis involved interviews with a study group of 76 patients who were at risk of giving birth to a child with a genetic disease or defect and a comparison group of 124 who had a pregnancy termination after a major anomaly had been detected by routine ultrasound and who were not at known risk for a genetic disease. Only patients in the study group had received counselling before the prenatal diagnosis and were aware that the fetus could be affected. The overall reaction of the comparison group was one of shock, denial of fetal abnormality, and guilt over ‘abandoning the fetus’. A feeling of guilt was expressed by patients in the comparison group (73 per cent versus 29 per cent) in the period immediately following the interruption. One‐third of patients in both groups felt obliged to undergo a therapeutic abortion. More patients in the study group than in the comparison group expressed the need to see a psychiatrist at the time of the study (19 per cent versus 7 per cent) and viewed future pregnancies as a replacement for the lost pregnancy (63 per cent versus 19 per cent). The recommendations of the study focus on information sessions to personnel, nursing support, analgesia during the expulsion period, an atmosphere of respect that should be present at the time that the fetus is viewed, the anticipation of mourning, and the long‐term follow‐up of the couple to ensure that counselling for future pregnancies and psychological support are provided when needed.
Prenatal diagnosis of familial ring 21 chromosome
Authors: Melnyk A. R. , Ahmed I. , Taylor J. C.
Published: March 2007

Ring chromosome 21 is a rare chromosome anomaly often associated with mental retardation and dysmorphic features. Less commonly, the ring chromosome can be familial and associated with a normal phenotype. Phenotypically normal female carriers, however, are at increased risk of having children with Down syndrome, mosaic monosomy 21, and variable duplication or deletion of chromosome 21. Because of the relative mitotic and meiotic instability of ring chromosomes, abnormal cytogenetic findings encountered during prenatal diagnosis may not reflect the true genetic status of the fetus. This is a report of a phenotypically normal female carrier of a familial ring 21 chromosome. Prenatal diagnosis on her twin pregnancy revealed a mosaic 46,XX,r(21)(p13;q22) (77 per cent)/45,XX, – 21 in one fetus and a normal male karyotype in the second. The pregnancy was carried to term. Both infants are completely normal, with a non‐mosaic ring 21 karyotype from the lymphocytes of one twin. The diagnostic uncertainty and problematic genetic counselling related to fetal cytogenetic abnormalities are the subjects of this report.
Blood transferrin receptor expression in chromosomally abnormal fetuses
Authors: Thilaganathan Baskaran , Meher‐Homji Nilaofer J. , Nicolaides Kypros H.
Published: March 2007

In a cross‐sectional study of 13 chromosomally abnormal fetuses, umbilical venous blood was obtained by cordocentesis at 17–32 weeks' gestation. Fetal blood transferrin receptor (CD71) expression (mean=79·8 per cent, range=60–98 per cent) and nucleated red cell count (mean=10·4 × 109 per 1, range=1·0–25·0 × 109 per 1) were significantly higher than the appropriate normal mean for gestation (z=3·92, P<0·0001 and z=3·69, P<0·001, respectively). These haematological changes in chromosomally abnormal fetuses would facilitate their prenatal diagnosis by analysis of fetal nucleated red blood cells isolated from the maternal circulation on the basis of CD71 expression.
46,XY,dup(10q) in direct CVS preparation and mosaic 48,XXXY,dup(10q) in CVS long‐term culture and fetal tissue
Authors: Sijmons R. H. , Sikkema‐Raddatz B. , Kloosterman M. D. , Briet J. W. , De Jong B. , Leschot N. J.
Published: March 2007

Chorionic villus sampling (CVS) was performed on a 40‐year‐old woman at 9 1/2 menstrual weeks because of advanced maternal age. The direct preparation showed 46,XY,dup(10)(q11.2q23.2). CVS long‐term culture and fetal tissue revealed a rare additional abnormality: 48,XXXY,dup(10)(q11.2q23.2). This abnormality represented the major cell line (>85 per cent in 691 cells) in an (XY)/XXY/XXXY/(XXXXY) mosaic (all cell lines presumably bearing the dup(10q); the presence of XY and XXXXY cell lines is uncertain). To our knowledge, this is the first report of trisomy 10q11‐q23 and of prenatally detected 48,XXXY in chorionic villi. The mosaic could have resulted from early post‐zygotic non‐disjunctions in a 46,XY,dup(10q) or 47,XXY,dup(10q) zygote. The results from DNA studies of four polymorphisms, mapped to Xp and Xq, support this theory. The literature on prenatally detected cases with sex chromosome tetrasomy and pentasomy and those with additional autosomal abnormalities is reviewed. The reported case underlines the problem of false‐negative findings when only direct CVS preparations are karyotyped.
Assessment and management of fetal agenesis of the corpus callosum
Authors: Gupta Janesh K. , Lilford Richard J.
Published: March 2007

Prenatal counselling for fetal agenesis of the corpus callosum is difficult as the prognosis until now has been so uncertain. We have reviewed the current world English literature to provide the best probabilistic information for prospective parents. In total, there are 70 cases where the diagnosis was made prenatally. The diagnosis of apparently isolated agenesis of the corpus callosum (in the absence of other sonographically detectable anomalies) appears to carry an excellent prognosis, with an 85 per cent chance of a normal developmental outcome and a 15 per cent risk of handicap. Fetal karyotyping is recommended as there is a 1 in 10 risk of aneuploidy. If other anomalies are detected prenatally, the outcome is very poor. Termination of pregnancy is advised in these circumstances.
Detection of fetomaternal haemorrhage associated with cordocentesis using serum α‐fetoprotein and the kleihauer technique
Authors: Van Selm Maria , Kanhai Humphrey H. H. , Van Loon Aren J.
Published: March 2007

Fetomaternal haemorrhage (FMH) was studied after 46 cordocenteses. α‐Fetoprotein (AFP) concentration and Kleihauer staining of maternal blood, taken both before and after the procedure, revealed increases in AFP values of more than 40 per cent in 30 per cent of the patients examined; fetal haemorrhage of more than 0.25 ml was detected in 46 per cent of the cases by the Kleihauer test. In the second trimester of pregnancy both techniques are comparable, while in the third trimester the Kleihauer technique appears to be more sensitive in detecting FMH after cordocentesis. An anterior position of the placenta is a risk factor for FMH.
Training obstetricians and midwives to present screening tests: Evaluation of two brief interventions
Authors: Smith D. K. , Shaw R. W. , Slack J. , Marteau T. M.
Published: March 2007

The objective of this study was to assess the effects of two brief training interventions to improve obstetricians' and midwives' explanations to patients of a routine prenatal screening test. Health professionals were randomly allocated to one of two intervention groups or a control group. Information‐giving about the test and communication skills were assessed at baseline, post‐training and 3‐month follow‐up from audiotaped consultations. Both intervention groups received a 1‐h training session involving small group discussions focused around a video. In addition, one group received individual feedback on their baseline and post‐training consultations. Twenty‐six midwives and nine obstetricians completed the study according to the protocol. Changes between baseline and post‐training, and between baseline and follow‐up, were computed. Information‐giving and communication skills improved significantly in subjects receiving training and feedback on their performance, with the greatest improvements occurring before feedback was given. Those receiving training without feedback significantly improved their communication skills and showed some improvement in information‐giving. These results show that modest improvements in communication can be made with relatively brief training. Greater and more sustained improvements may be found if all staff were trained, and trained on a regular basis.
Neutrophil and monocyte β2‐integrin expression in trisomic fetuses
Authors: Makrydimas G. , Thilaganathan B. , Plachouras N. , Nicolaides K. H.
Published: March 2007

Flow cytometry was used to measure neutrophil and monocyte β2‐integrin expression in fetuses with trisomy 18 (n=7) and trisomy 21 (n=7) at 20–25 weeks' gestation. The values were compared with those of 112 chromosomally normal fetuses. There were no significant differences in β2‐integrin expression between normal and aneuploid fetuses. These findings demonstrate that in trisomies 21 and 18, alteration in β2‐integrin expression is unlikely to contribute to the pathogenesis of immunological deficiencies that have been observed in these aneuploidies both prenatally and postnatally.
Lesch—Nyhan syndrome: Carrier and prenatal diagnosis
Authors: Alford R. L. , Redman J. B. , O'brien W. E. , Caskey C. T.
Published: March 2007

We report the results of carrier and prenatal diagnosis for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, Lesch—Nyhan syndrome, by carrier testing of 83 women and prenatal analysis of 26 pregnancies. Our diagnostic methodologies include mutation detection and linkage analysis for probands and their families and biochemical measurement of HPRT enzyme activity for at‐risk pregnancies. Identification of the mutation in the index case of each family permits precise carrier diagnosis using polymerase chain reaction (PCR) amplification of HPRT gene sequences and automated DNA sequencing. We demonstrate 100 per cent sensitivity for the detection of mutations in the HPRT gene of affected males and highly efficient carrier testing of at‐risk females. Two other molecular methods proven to have high utility include PCR‐based dosage analysis and linkage analysis by PCR amplification of a short tandem repeat (STR) in intron 3 of the HPRT gene. As a result, 45 at‐risk women, 56 per cent of those tested, were identified not to be carriers of their family's HPRT gene mutation. Seven of these women were the mothers of affected males and prenatal testing for future pregnancies was recommended because of the possibility of gonadal mosaicism. Thirty‐eight of these women were more distant relatives of affected males, thereby eliminating the need for future prenatal procedures. These studies illustrate the utility and precision of molecular methodologies for carrier and prenatal diagnosis of Lesch—Nyhan syndrome. These studies also illustrate that molecular diagnostic studies of affected males and carrier testing prior to pregnancy can clarify genetic risk predictions and eliminate unnecessary prenatal procedures.
Normal pregnancy after preimplantation DNA diagnosis of a dystrophin gene deletion
Authors: Liu Jiaen , Lissens Willy , Van Broeckhoven Christine , Löfgren Ann , Camus Michel , Liebaers Ingeborg , Van Steirteghem André
Published: March 2007

To perform preimplantation DNA diagnosis for Duchenne muscular dystrophy (DMD) in a female carrier of a dystrophin gene deletion of exons 3–18, we developed a polymerase chain reaction (PCR)‐based assay of exon 17 sequences. Exon 17 was efficiently amplified in all 50 single blastomeres of normal control embryos and in five blastomeres of one male embryo of the DMD carrier obtained after a first preimplantation diagnosis (PID) for gender determination. In ten blastomeres of another two male embryos of the DMD carrier, no PCR signals were observed, probably as a result of the deletion. After intracytoplasmic sperm injection, embryos were analysed for exon 17 and three of the four embryos showing normal PCR signals were replaced, resulting in a singleton pregnancy. Prenatal diagnosis showed a female karyotype and DNA analysis indicated that the fetus was not a DMD carrier.
Evaluation of maternal serum dimeric inhibin a as a first‐trimester marker of down's syndrome
Authors: Wallace E. M. , Grant V. E. , Swanston I. A. , Groome N. P.
Published: March 2007

While second‐trimester prenatal screening programmes for Down's syndrome have become established in prenatal care, it would be advantageous to be able to offer screening in earlier preganancy. To this end, we have evaluated a new potential maternal serum marker, dimeric inhibin A, as a possible first‐trimester marker. Dimeric inhibin A was measured in propsectively collected maternal serum from 23 cases of Down's syndrome and matched chromosomally normal controls, at 11–13 weeks' gestation. Levels of this protein were significantly elevated in the Down's pregnancies compared with the control pregnancies. The median multiple of the normal median (MOM) for the Down's samples was 2.46 (95 per cent confidence interval: 2.11–3.26, P<0.0001 vs. controls). These results suggest that dimeric inhibin A is a useful discriminator of Down's‐affected pregnancies from normal pregnancies in the first trimester and that sensitive screening in combination with maternal age and other possible markers may be practicable in the first trimester.
Sonographic depiction of fetal tooth germs
Authors: Ulm M. R. , Chalubinski K. , Ulm C. , Plöckinger B. , Deutinger J. , Bernaschek G.
Published: March 2007

Recently, sonography of the fetal face has gained increasing importance in prenatal diagnosis. It is not yet clear whether sonographic depiction of fetal tooth germs would have an influence on the prenatal diagnosis of ectodermal dysplasia syndromes. During routine malformation screening, horizontal sections of fetal jaws were visualized and examined for tooth germs in 124 pregnant women following sonographic ‘facing’. Histological jaw sections of fetuses that had died in utero at various gestational ages were produced in order to examine the degree of correspondence between the sonographic and histological findings. At least four tooth germs were found in the jaws of all fetuses between 19 and 34 gestational weeks (n=104). Although jaw visualization was possible between 14 and 18 gestational weeks (n=20), the exact number and location of the tooth germs could not be determined. Assessment of tooth germs may become increasingly important, as aplasia of the tooth germs is one of the principal signs of various hereditary ectodermal diseases.
Three‐dimensional ultrasound in prenatal diagnosis of skeletal dysplasia
Authors: Steiner Horst , Spitzer Dietmar , Weiss‐Wichert Peter H. , Graf Anton H. , Staudach Alf
Published: March 2007

A lethal form of bone dysplasia, platylospondylic lethal chondrodysplasia, was diagnosed prenatally using three‐dimensional ultrasound. The various types of three‐dimensional imaging mode provided diagnostic details not available by conventional two‐dimensional ultrasound. The diagnosis was made after referral in the 23rd week of gestation, allowing termination of pregnancy due to the poor prognosis. Prenatal sonograms were compared with postnatal radiographs.
Prenatal diagnosis of cleft lip at 11 menstrual weeks using embryoscopy in the Van der Woude syndrome
Authors: Dommergues M. , Lemerrer M. , Couly G. , Delezoide A. L. , Dumez Y.
Published: March 2007

On the basis of prenatal iden fication of a cleft lip by embryoscopy, a case of van der Woude syndrome was diagnosed at 11 menstrual weeks, allowing for early termination of pregnancy. The potential of embryoscopy to detect minor malformations in early pregancy is discussed from both the technical and the ethical point of view.
The fetal phenotype of partial 2q trisomy
Authors: Siffroi J. P. , Gomes D. Molina , Roume J.
Published: March 2007

A 22‐week‐old fetus with partial trisomy 2q (q24.1→qter) and 7q35 monosomy is described. To our knowledge, this represents the greatest unbalanced 2q chromosomal segment published in the literature. The clinical phenotype is in agreement with previous descriptions in children and allows us to propose a fetal phenotype for this chromosomal abnormality.
Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11.2–q13.3): Molecular genetics and clinical experience in 109 cases
Authors: Wirth B. , Rudnik‐Schöneborn S. , Hahnen E. , Röhrig D. , Zerres K.
Published: March 2007

Prenatal prediction in families at risk for autosomal recessive proximal spinal muscular atrophy (SMA) mainly of type I is often requested due to the high incidence and the fatal outcome of the disease. So far, only indirect genotype analysis can be performed in SMA families, since the gene has not yet been identified. We present our experience of 109 prenatal diagnoses obtained in 91 families by use of single‐ and multi‐locus polymorphic microsatellites of the region 5q11.2–q13.3. The marker combinations and specific features of the closest microsatellites are described in detail. From 137 requests for prenatal prediction of SMA between October 1991 and August 1994, 28 families were excluded, mostly because the clinical diagnosis was uncertain or doubtful. Others had to be classified as ‘SMA‐variants’ or showed autosomal dominant transmission of SMA. Of the 109 prenatal diagnoses performed, 29 fetuses were diagnosed to be at high risk (>99 per cent) of developing the disease, while in seven additional pregnancies no exact prediction could be made due to a recombination event in one parental haplotype. Altogether, recombinations between closely flanking markers were observed in 14 cases. In 35 cases, the parents decided to terminate the pregnancy. Of the remaining pregnancies, 32 could be followed beyond term. All infants were reported to develop normally without signs of SMA. Two children were born with transverse reduction defects of one hand, which was most likely related to early chorionic villus sampling at 9 and 10 weeks' gestation. No further abnormalities could be detected. The limits of indirect genotype analysis and the problems of diagnostic accuracy and heterogeneity of proximal SMA are discussed.
Attitudes to prenatal screening, diagnosis and research among pregnant women who accept or decline an alpha‐fetoprotein test
Authors: Jørgensen Finn Stener
Published: March 2007

The aim of the study was to describe the opinion of pregnant women who had accepted or declined an alpha‐fetoprotein (AFP) test, not only on AFP screening in general, but also on whether every pregnant woman should be offered amniocentesis (AC)/chorionic villus sampling (CVS) and an ultrasound scan for fetal malformations. An additional aim was to describe pregnant women's attitudes concerning continued research in the prenatal field. The study was performed as a questionnaire study in two regions over a 1‐year period from 1 October 1988 to 30 September 1989. Results are based on answers from 3331 women who had taken an AFP test and 336 women who had declined the offer of a test. A total of 79 per cent of the women thought that an AFP test, 70 per cent that an ultrasound scan for fetal malformations, and 26 per cent that AC or CVS should be offered to all pregnant women. Fifty‐nine per cent of the women were positive towards continued research in the prenatal field. Women who had had an AFP test were generally much more positive towards screening and research than women who had declined, who were generally against. Women who had left school without a high school degree were on average more positive towards the screening issues than women who had this degree. In conclusion, the results obtained in this study strongly suggest that women's attitudes are very dependent on how the prenatal screening programme is already organized in their local area.
The role of percutaneous umbilical blood sampling in the management of immune thrombocytopenic purpura
Authors: Garmel Sara H. , Craigo Sabrina D. , Morin Lucie M. , Crowley Jeanne M. , D'alton Mary E.
Published: March 2007

On consultation, percutaneous umbilical blood sampling (PUBS) was offered to women with immune thrombocytopenic purpura (ITP) to determine the mode and site of delivery prior to labour. Between January 1989 and December 1993, 41 pregnant women underwent PUBS. All women had a history of ITP, a platelet count less than 90 K, (+) antiplatelet antibody, and/or thrombocytopenia diagnosed early in pregnancy. PUBS was performed at term except in one patient with preterm labour, who underwent PUBS at 31 weeks' gestation. Patients with fetal platelet counts greater than 50 K returned to their referring physician for delivery. Records were complete in 39 pregnancies. Fetal blood was successfully obtained in 37 of 39 cases (95 per cent). Fetal platelet counts correlated with neonatal platelet counts in 36 of 37 cases (97 per cent). The interval between PUBS and delivery ranged from 0 to 31 days. Six of 37 fetuses (16 per cent) had significant fetal thrombocytopenia (<50 K). These six patients underwent Caesarean section. Vaginal delivery was recommended in all others. There were two procedure‐related complications. There were no cases of intraventricular haemorrhage in any of the neonates. In conclusion, there is a high incidence of fetal thrombocytopenia in women with ITP. PUBS reliably detects fetal thrombocytopenia and is therefore useful in the perinatal planning of the mode and site of delivery.
Ultrasound observation of amnion dysmorphism at 14.5–16 weeks
Authors: Zimmer Etan Z. , Bronshtein Moshe
Published: March 2007

The presence of chorio‐amniotic separation and amnion anomalies was recorded in 9500 patients referred for vaginal ultrasound examination at 14.5–16 weeks' gestation. In all patients with a change in the amnion, a search for fetal anomalies was performed and pregnancy outcome was checked. Amnion dysmorphism was observed in 30 cases. The main findings were a floating membrane which changed its configuration when the uterus was tilted and multiple intrauterine amniotic sheets. In no case was attachment of the fetus to the membranes noted. There was no fetal abnormality and pregnancy outcome was favourable in all patients. In conclusion, ultrasound visualization of amnion dysmorphism in early pregnancy is not associated with an adverse pregnancy outcome.
Thyroid antibodies are not a risk factor for pregnancies with down syndrome
Authors: Gustafsson Jan , Annerén Göran , Ericsson Ulla‐Britt , Svanberg Lars , Ivarsson Sten A.
Published: March 2007

The observation that thyroid disease is frequent in mothers of children with Down syndrome (DS) has suggested that maternal thyroid antibodies could be a factor predisposing to trisomy 21 in their offspring. In this study, the incidences of thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies were analysed with a sensitive solid‐phase immunosorbent radioassay in sera from 29 mothers giving birth to children with trisomy 21 and 87 control mothers. The serum samples were collected at delivery. There was no statistical difference regarding the proportion of thyroid antibodies (against Tg and/or TPO) in the two groups. Thyroid antibodies were detected in 6/29 (20.7 per cent) of the DS mothers and in 23/87 (26.4 per cent) of the control mothers. Among the women with thyroid antibodies, 4/6 (66.7 per cent) of the DS mothers and 12/23 (52 per cent) of the control mothers had antibodies against both Tg and TPO. There was no increase in the relative risk of having a child with DS if the titre of either Tg or TPO antibodies or both were positive, i.e. ≥ 1/5. The results indicate that the presence of thyroid antibodies in the serum of a pregnant woman has no prognostic value for the birth of an infant with DS.
New estimates of down syndrome risks at chorionic villus sampling, amniocentesis, and livebirth in women of advanced maternal age from a uniquely defined population
Authors: Halliday Jane L. , Watson Lyndsey F. , Lumley Judith , Danks David M. , Sheffield Leslie J.
Published: March 2007

Current measures of livebirth prevalence of Down syndrome are derived from data obtained up to 20 years ago, before the introduction of the prenatal diagnostic tests amniocentesis and chorionic villus sampling (CVS). For women aged 36–52 years, but who were not tested prenatally, we proposed to make a direct estimate of current livebirth prevalence of Down syndrome. We could also determine prevalence at the time of CVS and amniocentesis in women of the same age undergoing prenatal testing. Differences in these prevalences allow an estimation of the relative loss of Down syndrome during pregnancy. In Victoria, Australia, we identified 3041 women having CVS, 7504 having amniocentesis, and 13 139 having no test. Smoothed regression estimates of age‐specific livebirth prevalence were found to be higher than in the early studies. The estimate of spontaneous loss was 17 per cent between the time of CVS and amniocentesis, and 18 per cent after the time of amniocentesis. The latter figure is lower than previous estimates and may be explained by a greater likelihood of a Down syndrome fetus surviving to be liveborn, given the modern approach to early obstetric intervention. These current risk estimates of livebirth may be useful updates for genetic counselling, but perhaps more importantly, may be used as precise maternal age‐related risk figures, necessary in the design and implementation of prenatal screening programmes for Down syndrome.
Prenatal diagnosis in two cases of de novo complex balanced chromosomal rearrangements. Three‐year follow‐up in one case
Authors: Sikkema‐Raddatz B. , Sijmons R. H. , Tan‐Sindhunata M. B. , Van Der Veen A. Y. , Brunsting R. , De Vries B. , Beekhuis J. R. , Bekedam D. J. , Van Aken B. , De Jong B.
Published: March 2007

We report two cases of apparently balanced complex de novo chromosomal rearrangements (BCCR) detected prenatally at 17 weeks and 10 weeks of gestation, respectively. Chromosomes were studied using GTG‐banding and fluorescent in situ hybridization (FISH). In one case four chromosomes and in the other case three chromosomes were involved in the rearrangements. One of the pregnancies was terminated and no external or internal abnormalities were detected at autopsy. The other pregnancy continued to term. Level III ultrasound examination showed no abnormalities. The child is now 3 years old and has neither congenital anomalies nor evidence of delayed psychomotor development.
Prenatal exclusion of the hhh syndrome
Authors: Gray R. G. F. , Green A. , Hall S. , McKeown C.
Published: March 2007

Prenatal diagnosis of the hyperornithinaemia, hyperammonaemia, and homocitrullinuria syndrome is described by the analysis of ornithine incorporation in second‐trimester cultured amniotic fluid cells. An unaffected fetus was predicted and confirmed in the newborn child. This is the third reported prenatal diagnosis for this disorder and the second predicting an unaffected fetus.
Prenatal diagnosis of autosomal recessive osteopetrosis, infantile type, by X‐ray evaluation
Authors: Oǧur G. , Oǧur E. , Celasun B. , Basȩr Ï. , Ïmïrzalioǧlu N. , Öztürk T. , Alemdaroǧlu A.
Published: March 2007

Prenatal diagnosis for infantile osteopetrosis was attempted during the third pregnancy of a first‐cousin marriage whose family history revealed an affected previous child. At the 25th week of pregnancy, fetal X‐ray evaluation revealed marked sclerosis of osteopetrotic bone and metaphyseal splaying and clubbing of both femurs. The pregnancy was terminated and repeated X‐rays and histopathological examination of fetal bone (femur) confirmed the diagnosis.
Amniotic alpha‐fetoprotein in the prenatal diagnosis of congenital nephrotic syndrome of the finnish type
Authors: Morris Jonathan , Ellwood David , Kennedy Debra , Knight John
Published: March 2007

Congenital nephrosis of the Finnish type (CNF) is rare outside Finland, where the incidence may be as high as 1 in 2000 live births. Neonates with the disorder develop renal failure within the first months of life and without renal transplantation, the prognosis is extremely poor. This case report describes a woman's three pregnancies, two of which were affected with CNF.
Prenatal and presymptomatic diagnosis of the marfan syndrome using fluorescence pcr and an automated sequencer
Authors: Wang Mei , Mata John , Price Christopher E. , Iversen Patrick L. , Godfrey Maurice
Published: March 2007

The Marfan syndrome (MFS) is a heritable connective tissue disorder characterized by skeletal, ocular, and cardiovascular abnormalities. Defects in fibrillin, an elastin‐associated microfibrillar protein, are now known to cause MFS. Since the discovery of fibrillin as the gene responsible for MFS, requests for prenatal and presymptomatic diagnosis have become common‐place. Here we report the use of the polymerase chain reaction (PCR), using fluorescence labelled primers and an automated sequencer, to establish linkage data for “molecular diagnosis”. The mistaken clinical diagnosis of MFS based on the appearance of a common cardiovascular manifestation, mitral valve prolapse, and a positive family history is also discussed.
Normal fetal growth in women with antiphospholipid syndrome treated with high‐dose intravenous immunoglobulin (IVIG)
Authors: Valensise Herbert , Vaquero Elena , De Carolis Caterina , Stipa Elisa , Perricone Roberto , Arduini Domenico , Romanini Carlo
Published: March 2007

Antiphospholid antibodies are associated with fetal distress and fetal death. Although different therapeutic regimens have been used, the incidence of fetal growth retardation varies between 30 and 60 per cent of reported cases. We report the evolution of fetal growth in patients with antiphospholipid antibody syndrome treated with high‐dose intravenous immunoglobulins (IVIG). Fourteen patients with a history of recurrent spontaneous abortion and immunological diagnosis of antiphospholipid syndrome were followed longitudinally. Intravenous immunoglobulin at a dose of 0.5 g/kg body weight for two consecutive days was started from the fifth week of pregnancy and repeated every 4 weeks until the 33rd week of gestation. Fetal biometry was evaluated longitudinally from the appearance of the gestational sac at 4 weekly intervals. In the period between 26 and 34 weeks, the frequency of evaluation was increased to every 14 days. Data obtained were compared with a control group of 70 fetuses with uneventful pregnancies matched for gestational age. Neonatal weight is shown in relation to the centiles for the normal population. One patient out of 14 (7.1 per cent) developed gestational hypertension and abruptio placentae. No other pregnancy complications were seen. No proteinuria was found. The mean maternal age was 31.2±3.8 years. Median birth weight was 3433 g±287. The median centile of the birth weight was 65.3±18.6. Mean gestational age at delivery was 1.3 weeks. No fetal or neonatal growth retardation was seen. No significant differences were found in the biometrical parameters investigated in the various gestational ages vs. the control group (Student's t‐test not significant); a significant increase in head circumference (P< 0.001) and abdominal circumference (P< 0.05) was found at 36–37 weeks gestational age in the IVIG‐treated fetuses. The presence of antiphospholipid antibodies is considered detrimental for pregnancy outcome because of their negative effects on placental vascular perfusion and fetal transfer of metabolites. The use of IVIG seems to avoid or inhibit the reduced availability of nutrients for the fetal anabolic functions, as the expected reduction in fetal growth was not seen in our series.
Potter's syndrome in the second trimester—prenatal screening and pathological findings in 60 cases of oligohydramnios sequence
Authors: Scott R. J. , Goodburn S. F.
Published: March 2007

Fifty‐two second‐trimester and eight third‐trimester (>28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence (“Potter's syndrome”) were reviewed. Twenty‐eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a multiple malformation syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha‐fetoprotein (AFP) did not discriminate between cases with renal malformations and those without. Pulmonary hypoplasia was commoner in third‐trimester than in second‐trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second‐trimester cases, 50 per cent of cases had no malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post‐mortem examination is necessary to identify any underlying fetal cause.
Prenatal diagnosis of isovaleric acidaemia by enzyme and metabolite assay in the first and second trimesters
Authors: Kleijer W. J. , Van Der Kraan M. , Huijmans J. G. M. , Van Den Heuvel C. M. M. , Jakobs C.
Published: March 2007

Isovaleric acidaemia (IVA) is caused by a deficiency of isovaleryl CoA dehydrogenase. The diagnosis can be established biochemically by the demonstration of increased levels of isovalerylglycine (IVG) and 3‐hydroxyisovaleric acid in urine and by the deficiency of incorporation of radiolabel from [14C]isovaleric acid in macromolecules in cultured fibroblasts. This paper reports a consecutive series of 24 prenatal diagnoses in pregnancies at high risk, using both methods‐metabolite and indirect enzyme assay. Affected fetuses were diagnosed in four pregnancies: three in the second trimester and one recent case in the first trimester. The latter represents the first reported case of a first‐trimester diagnosis of IVA by direct analysis of chorionic villi. We also report the first demonstration of strongly accumulated IVG in the amniotic fluid in the 12th week of an affected pregnancy.
Social and geographical inequalities in prenatal care in Italy
Authors: Corchia Carlo , Mastroiacovo Pierpaolo , Lanni Roberta , Grimaldi Valentina , Scarano Gioacchino , Baronciani Dante
Published: March 2007

The purpose of this study was to find out possible differences in prenatal diagnosis (PD) by amniocentesis or chorionic villus sampling and ultrasound examination before 16 weeks' gestation (early ultrasound examination, EUE), according to area of residence and level of education of the mothers. Data come from a multicentre study in Italy involving 43 maternity hospitals (Mercurio project) and were collected through structured interviews a few days after delivery. Study subjects were 1541 mothers of single non‐malformed infants born between April 1992 and March 1994. Overall, the incidence of PD and EUE was 5.8 and 80 per cent, respectively. After adjustment for maternal age and other possible confounders, the odds ratios for PD were 2.19 (95 per cent confidence interval (CI)=1.26–3.81) when women residing in the northern regions were compared with those residing in the southern regions, and 2.06 (95 per cent CI=1.12–3.79) and 4.08 (95 per cent CI=1.97–8.42) when women with medium and high levels of education were compared with those with low level. For EUE, the odds ratios were 1.77 (95 per cent CI=1.32–2.36) and 2.88 (95 per cent CI=1.56–5.29) when comparing women with medium and high levels of education with those with low level. No relationship was found between area of residence and EUE. These geographical and social inequalities in prenatal care in Italy should be taken into account for the organization, delivery, and evaluation of pregnancy services in the coming years.
Chorionic villus sampling by biopsy forceps. Results of 1580 procedures from a single centre
Authors: Fortuny A. , Borrell A. , Soler A. , Casals E. , Costa D. , Carrio A. , Puerto B. , Seres A. , Cararach J. , Delgado R.
Published: March 2007

The results of a prospective series of 1580 chorionic villus sampling (CVS) procedures using biopsy forceps are presented. Most of the procedures (1442), including 11 sets of twins, were performed by the transcervical approach (TC‐CVS), using a curved‐shank thin forceps, and 138 by the transabdominal approach (TA‐CVS), using a trocar‐guided straight thin forceps. The mean gestational age for TC‐CVS was 10.9 weeks, and in 233 cases (16 per cent) the procedure was carried out between the 12th and 14th weeks. The mean gestational age for TA‐CVS was 16.7 weeks. The major indication for CVS was advanced maternal age (92.7 per cent in the TC and 91.8 per cent in the TA approach), and indications for abnormal ultrasound findings were more common in the TA approach (4.5 per cent) than in TC‐CVS (0.07 per cent). Although sampling was apparently accomplished in all the procedures, in 3.1 per cent of the TC‐CVS and 2.2 per cent of TA‐CVS procedures, the samples were less than 1 mg after dissection. A cytogenic report was obtained in 96.1 per cent of the TC‐CVS and 90.6 per cent of the TA‐CVS. Maternal serum alpha‐fetoprotein (MSAFP) was measured before and after TC‐CVS and the post‐CVS MSAFP was positively correlated with the sample weight. Second‐trimester amniocentesis following CVS was required in 5.2 per cent (TC‐CVS) and 6.5 per cent (TA‐CVS), due to the failure to obtain a cytogenetic report or diagnostic confirmation. The follow‐up to the 20th week was 100 per cent by ultrasound scan, and 88.6 per cent from the 21st week to 1 week after delivery. Fetal loss rates within 2 weeks of the procedure were 1.7 per cent (TC‐CVS) and 0.8 per cent (TA‐CVS) and total fetal loss accumulated to 1 week after delivery was 4.6 per cent (TC‐CVS) and 5.9 per cent (TA‐CVS). Factors found to increase significantly fetal loss in the TC‐CVS series were maternal age and the collection of very small samples, but not the number of forceps insertions.
Prenatal diagnosis of friedreich ataxia: Improved accuracy by using new genetic flanking markers
Authors: Monros E. , Smeyers P. , Ramos M. A. , Prieto F. , Palau F.
Published: March 2007

Friedreich ataxia is a neurodegerative disorder with autosomal recessive inheritance. Since the gene causing mutation has not yet been identified, prenatal, predictive, and carrier diagnoses are based on indirect haplotype analysis with closely linked markers. Until recently, only distal markers were available and their physical distance to the Friedreich ataxia (FRDA) gene remained elusive. The identification of close flanking markers that mark out the boundaries of the FRDA locus and reduce the critical genomic region which contains the gene allows for the first time misdiagnosis due to undetectable recombination to be avoided and diagnosis accuracy to be greatly improved. In this sense, we have verified a prenatal diagnosis in which the fetus was diagnosed as an unaffected carrier last year with a confidence of 95 per cent. By using the new flanking markers, the diagnosis improved and confidence reached almost 100 per cent.
Analysis of maternal serum alpha‐fetoprotein and free beta human chorionic gonadotrophin in the first trimester: Implications for down's syndrome screening
Authors: Berry Esther , Aitken David A. , Crossley Jennifer A. , Macri James N. , Michael Connor J.
Published: March 2007

The aim of this study was to determine the maternal population, pregnancy, serum alpha‐fetoprotein (AFP) and free β subunit of human chorionic gonadotrophin (FβhCG) parameters in a large series of women attending prenatal clinics before 15 weeks' gestation and to assess the practical problems of population screening for Down's syndrome in the first trimester using these markers. Serum samples were collected from 8600 women attending prenatal clinic booking visits. Maternal serum AFP and FβhCG medians were calculated for each day of gestation (49–104 days), using both dates and ultrasound estimates of gestation. The effects of maternal weight, twin pregnancies, and threatened abortion on AFP and FβhCG levels were analysed. The median age of the population was 27.1 years and the median weight 62.1 kg. Twenty‐six per cent of samples were collected before 70 days and 50 per cent before 78 days' gestation. Eighty‐nine per cent of all samples had gestational estimates by dates, 60 per cent by ultrasound and 52 per cent by both dates and ultrasound. The AFP median was 5 kU/1 at 49 days, 5.9 kU/1 at 70 days, and 17.9 kU/1 at 100 days. The peak median FβhCG level was 66.4 ng/ml at 64 days, falling to 20.6 ng/ml at 100 days' gestation. Both AFP and FβhCG levels showed log Gaussian distributions but the standard deviation for AFP was 20 per cent greater than that found in the second trimester. AFP and FβhCG levels showed an inverse relationship with maternal weight and were increased in twin pregnancies (1.68 and 1.97 multiples of the median, respectively). AFP and FβhCG can be readily measured in a large screening population in the first trimester. Down's syndrome screening protocols based on these markers could be refined by the use of gestations in individual days but AFP is likely to be a less effective marker and detection rates are likely to be lower than in the second trimester. To realize the potential of first‐trimester screening, more women should be encouraged to attend the prenatal clinic in early pregnancy and ultrasound dating should be carried out for all pregnancies at this stage.
Amniotic fluid analysis in a fetus with laryngeal atresia
Authors: Watson William J. , Munson David P.
Published: March 2007

Complete laryngeal atresia is a rare congenital malformation that is known to cause hypertrophy of the fetal lung in utero. A fetus with laryngeal atresia was found to have markedly immature amniotic fluid lung maturity studies at term. Inappropriately low amniotic fluid lung maturity studies may be an important clue to the diagnosis of this condition.
Demonstration of spontaneously dividing male fetal cells in maternal blood by negative magnetic cell sorting and fish
Authors: Zheng Yun‐Ling , Craigo Sabrina D. , Price Cathy M. , Bianchi Diana W.
Published: March 2007

We investigated a case of massive feto‐maternal bleeding by using negative magnetic cell sorting (MACS) and fluorescent in situ hybridization (FISH). A 37‐year‐old pregnant woman had an uncomplicated amniocentesis for advanced maternal age at 16 weeks' gestation. The fetal karyotype was 46, XY. At 19 weeks' gestation, she had a minor car accident and slight vaginal bleeding. A subsequent Kleihauer‐Betke test showed a 140 ml feto‐maternal haemorrhage. Serial sonographic examinations indicated a normal fetus and placenta. We performed FISH analysis on maternal peripheral blood at 25 weeks. Anti‐CD45 and MACS were used to deplete maternal leucocytes, enriching the proportion of fetal nucleated erythrocytes present. The isolated cells were analysed by using dual‐colour FISH with X and Y specific probes. Approximately 65 800 nucleated cells were obtained after MACS depletion. A total of 234 cells were analysed by FISH. The results revealed that 70 of the nucleated cells (30 per cent) were male with one X and one Y signal. Among these cells, six male metaphases were observed in spontaneously dividing cells.
Uniparental isodisomy for chromosome 16 in a growth‐retarded infant with congenital heart disease
Authors: Whiteford M. L. , Coutts J. , Al‐Roomi L. , Mather A. , Lowther G. , Cooke A. , Vaughan J. I. , Moore G. E. , Tolmie J. L.
Published: March 2007

We report a growth‐retarded infant with congenital heart disease and maternal isodisomy for chromosome 16. Non‐mosaic trisomy 16 was detected at mid‐trimester chorionic villus sampling, performed because biochemical screening indicated an increased Down's syndrome risk. Further karyotyping analysis of the placenta, after delivery, showed a 50 per cent mosaic trisomy 16. The infant had an atrioventricular (A‐V) canal defect, scoliosis, and several minor dysmorphic features. Although uniparental disomy for chromosome 16 has been reported previously, to our knowledge this is the first case of uniparental isodisomy for chromosome 16 which has been investigated with multiple DNA probes.
Prenatal diagnosis of GM2‐gangliosidosis B1 variant
Authors: Lemos M. , Pinto R. , Ribeiro G. , Ribeiro H. , Lopes L. , Miranda M. C. Sá
Published: March 2007

Prenatal diagnosis in a pregnancy at risk for a juvenile B1 variant of GM2‐gangliosidosis was carried out. The biochemical study of the cultured amniocytes and the affected fetal brain is reported. The results obtained show that the sulphated artificial substrate can be used in the diagnosis of B1 variant, but not the neutral one. The accumulation of GM2‐ganglioside in the fetal brain of the B1 juvenile form and an infantile form of GM2‐gangliosidosis (0 variant) was compared.
In utero diagnosis and treatment of fetal goitrous hypothyroidism, caused by maternal use of propylthiouracil
Authors: Van Loon Aren J. , Derksen Joke Th. M. , Bos Arie F. , Rouw Catrienus W.
Published: March 2007

A fetal goitre is a potentially dangerous phenomenon because of mechanical obstruction and possible fetal thyroid function disorders. In this report we describe a patient with Graves' disease diagnosed in early pregnancy and treated with propylthiouracil, which resulted in a large fetal goitre and fetal hypothyroidism. The diagnostic problems are discussed and we focus on the need for fetal thyroid hormone serum evaluation. The only reliable way to obtain information about the fetal thyroid status is percutaneous fetal umbilical cord blood sampling, since amniotic fluid levels do not properly represent the fetal thyroid function. Fetal hypothyroidism can thus be diagnosed in utero and treated with intra‐amniotic injections of thyroxine. The recommended dose and frequency of injections are only based on a few case reports and for that reason we performed a second fetal blood sampling 1 week later to evaluate our therapy. Weekly intra‐amniotic injections of 250 μg of thyroxine seem to be sufficient to reduce a fetal goitre and give a normal thyroid hormone level.
Maternal platelet size as a marker for fetal trisomies 18 and 13
Authors: Thilaganathan Baskaran , Meher‐Homji Nilaofer J. , Nicolaides Kypros H.
Published: March 2007

Maternal and fetal platelet size and glycoprotein expression were measured in 14 pregnancies complicated by fetal aneuploidy between 20 and 24 weeks' gestation. Flow cytometry was used to determine platelet size and surface glycoprotein Ib (GPIb) and GPIIIa expression both before and after stimulation with adenosine diphosphate (ADP). The data were compared with results obtained from 35 normal paired maternal and fetal controls. In fetuses affected with trisomies 18 and 13, but not trisomy 21, the maternal and fetal platelet sizes were significantly higher than those of the normal controls. Furthermore, the increase in fetal platelet size was significantly associated with the increase in maternal platelet size. Increase in maternal platelet size may be of potential value as a marker for fetal trisomies 18 and 13.