Choice For Prenatal Diagnosis Research Articles

Clinical experience with multiplex ligation-dependent probe amplification for microdeletion syndromes in prenatal diagnosis: 7522 pregnant Korean women

BackgroundConventional cytogenetic analysis using G-band karyotyping has been the method of choice for prenatal diagnosis, accurately detecting chromosomal abnormalities larger than 5 Mb. However, the method is inefficient for detecting the submicroscopic deletions and duplications that are associated with malformations and mental retardation. This study evaluated the results of the multiplex ligation-dependent probe amplification (MLPA) P245 assay used for prenatal diagnosis in cases with unusual ultrasonographic findings or specifically where parents wanted to be tested. The objective was to compare the results from MLPA with those from conventional cytogenetic testing in order to determine their concordance and the additional diagnostic yield of MLPA over G-band karyotyping.ResultsOf the 7522 prenatal cases analyzed, 124 were found to have genomic imbalances (1.6%). Of those 124 cases, 41 had gene loss (33.6%), and 83 had gene gain (66.4%). Most of the cases with genomic imbalances (64.5%) showed no abnormal karyotype. In particular, all cases with a 4p16.3 deletion (Wolf-Hirschhorn syndrome) showed an abnormal karyotype, whereas all of those with a 22q11–13 deletion showed a normal karyotype. In most of the cases with pathogenic deletions, the indication for invasive prenatal testing was an increase in the nuchal translucency (NT) alone (51.2%). Other indications observed in the remaining cases were abnormal serum screening markers (14.6%), other ultrasonographic findings (9.8%), pregnancy through in vitro fertilization and fertility assistance (9.8%), and advanced maternal age(2.4%).ConclusionsThese results show that for fetuses with an enlarged NT or abnormal ultrasonographic findings and normal conventional karyotype, additional genetic investigation like molecular testing would be for identifying the microscopic genomic aberrations (microdeletions, microduplications) responsible for syndromic associations including structural anomalies and mental retardation.

MG-120 Chorionic villus sampling: 3 cases with discrepancies between ifish, array-cgh and karyotype

Background Chorionic villus sampling (CVS) is the method of choice for prenatal diagnosis (PND) in first-trimester pregnancies (10–13thweeks and 6 days), particularly for high risk of fetal abnormalities. This procedure allows earlier diagnosis in order to enable effective pregnancy management. Microarray analysis is now performed on CVS. Objectives/method We review 3 cases using fluorescence in situ hybridization on uncultivated nuclei (iFISH), CGH array results on DNA extraction from the entire villi and karyotype analyses on cultured CVS. Results Two cases showed normal iFISH profile for chromosomes 13, 18, 21, X and Y, while the CGH array revealed a weak mosaicism for monosomy X in one CVS case and for trisomy 18 in the other. Karyotypes showed 45, X and 47, XY, +18 in more than 95% of the cells. In the third case, the iFISH and the CGH array were normal, but the karyotype revealed a trisomy 9 in 76% of the cells. Conclusions CVS mosaicism and feto-placental discrepancies are rare phenomena occurring in ~1–2% of the PND. Cytogenetic analysis of CVS may give different results since CVS is from various placental cell lineages. Therefore, a cultured CVS (mesenchyme) analysis should be completed in order to reduce the incidence of false-positive or false-negative findings. In those cases, amniocentesis follow-up could be offered to complete the prenatal diagnosis.

Comparison of transcervical CVS versus transvaginal transmyometrial CVS for prenatal diagnosis: experience with 244 cases at an infertility center in Iran

Introduction Finding a more simple and low risk approach for chorion villus sampling (CVS) can improve our ability to develop this method and will increase the clinicians and patients utilization for prenatal diagnosis. Methods Women were continuously assigned transvaginal–transamyometrial (TVTM) chorionic villus sampling (CVS) and transcervical (TC) CVS in a quasi-experimental study. Results Data from 244 consecutive cases following prenatal diagnosis by transcervical (TC) CVS ( n=104) and transvaginal–transmyometrial (TVTM) CVS ( n=140) were evaluated. Fetal loss before 28 weeks of gestation took place in four cases (1.6%) of TC-CVS and in three cases (1.2%) of TVTM-CVS. Rate of spotting after CVS was 3.3% for TC and 2.5% for TVTM. Conclusions We believe that TVTM-CVS is a simple, safe and effective technique for prenatal diagnosis of genetic diseases. We recommend TVTM CVS procedure as the first choice for prenatal diagnosis.

Maternal serum screening for Down syndrome--opinions on acceptance from Swedish women.

Different screening procedures are becoming an important part of health care. Information about screening and its consequences can be difficult to both impart and understand. This study examined women's theoretical acceptance of a new screening procedure, before its introduction. A group of women (n = 823), who had made an informed choice about the form of foetal diagnosis they wished for, were also asked, in a questionnaire, about their opinion on the acceptability of serum screening for Down syndrome. The main purpose of the this was to ascertain their feelings when making a choice. Replies were received from 80.4%. The answers indicated that serum screening would be acceptable to 86% of the women who had chosen a second trimester ultrasound examination. Of the women who had chosen amniocentesis, 51% would consider the test acceptable as a first alternative. The ease with which the women were able to make their choice of prenatal diagnosis had bearing on their degree of acceptance of serum screening for Down syndrome.

Amniocentesis or chorionic villus sampling in multiple gestations? Experience with 500 cases

500 women with multiple pregnancies underwent amniocentesis or chorionic villus (CV) sampling at our department between January 1988 and July 1997. The aim of this retrospective study was to evaluate the laboratory aspects and the consequences of discordant results in these pregnancies in relation to the method of sampling. Uncertain results in one or both samples, requiring further investigation were more frequent in CV samples (eight times in 163 paired samples, 5 per cent) than in amniotic fluid (AF) samples (once in 298 paired samples, 0.3 per cent). Sampling one fetus twice (erroneous sampling) was seen only once among 163 pregnancies with two CV samples in our study. Cross contamination due to mixed sampling was discovered in two of seven pregnancies that underwent DNA diagnosis in CV and might be a rather regular occuring phenomenon. In none of the 500 pregnancies mixed sampling caused diagnostic dilemmas. A third sampling problem, maternal cell contamination caused a diagnostic problem once among the AF samples. Selective fetal reduction appeared safer after CV sampling than after amniocentesis. Subsequently, CV sampling instead of amniocentesis has become the method of choice for prenatal diagnosis in multiple pregnancies in our department.

Randomised comparison of amniocentesis and transabdominal and transcervical chorionic villus sampling

We have compared three methods of prenatal diagnosis in two large obstetric centres in Denmark. Women were randomly assigned transabdominal (TA) chorionic villus sampling (CVS), transcervical (TC) CVS, or second-trimester amniocentesis (AC); women at high genetic risk were randomised between the two CVS groups only. Analysis of 45 epidemiological variables showed the three procedure groups to be similar at enrolment. All women were followed up until completion of pregnancy. Among 3079 women at low genetic risk total fetal loss rates were 10·9% for TC CVS, 6·3% for TACVS, and 6·4% for AC (p<0·001). More women had bleeding after the procedure in the CVS groups (p<0·001), whereas more amniotic fluid leakage (p<0·001) was reported after AC. No uterine infections occurred in any group. No case of oromandibular-limb abnormality was seen in the CVS groups, but 1 child in the AC group had aplasia of the right hand. The two CVS approaches were compared among 2882 women at low and high genetic risk who were found to have cytogenetically normal fetuses. Rates of unintentional loss after the procedure were 7·7% for TC CVS and 3·7% for TA CVS (p<0·001; 95% Cl of difference 2·3-5·8%). At baseline ultrasound scanning after establishment of optimum sampling conditions, more TC than TA procedures (p<0·001) were judged not to be feasible. We found that TA CVS allows better access to the placental site than TC sampling, is an easier skill to acquire, and has the potential that more villi can be aspirated when needed. The risk of fetal loss is similar after TA CVS and AC. However, losses after AC are at a later stage and are therefore more distressing. TA procedures remain the first choice for prenatal diagnosis. Since, in our hands, TC sampling carries a greater risk to the fetus, we have abandoned TC CVS in our two study centres.