Showing papers on "Amniocentesis published in 2012"

Clinical Diagnosis by Whole-Genome Sequencing of a Prenatal Sample

Abstract: Conventional cytogenetic testing offers low-resolution detection of balanced karyotypic abnormalities but cannot provide the precise, gene-level knowledge required to predict outcomes The use of high-resolution whole-genome deep sequencing is currently impractical for the purpose of routine clinical care We show here that whole-genome “jumping libraries” can offer an immediately applicable, nucleotide-level complement to conventional genetic diagnostics within a time frame that allows for clinical action We performed large-insert sequencing of DNA extracted from amniotic-fluid cells with a balanced de novo translocation The amniotic-fluid sample was from a patient in the third trimester of pregnancy who underwent amniocentesis because of severe polyhydramnios after multiple fetal anomalies had been detected on ultrasonography Using a 13-day sequence and analysis pipeline, we discovered direct disruption of CHD7, a causal locus in the CHARGE syndrome (coloboma of the eye, heart anomaly, atresia of the

Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe

Abstract: The aim of this study is to quantify the prevalence and types of rare chromosome abnormalities (RCAs) in Europe for 2000–2006 inclusive, and to describe prenatal diagnosis rates and pregnancy outcome. Data held by the European Surveillance of Congenital Anomalies database were analysed on all the cases from 16 population-based registries in 11 European countries diagnosed prenatally or before 1 year of age, and delivered between 2000 and 2006. Cases were all unbalanced chromosome abnormalities and included live births, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. There were 10 323 cases with a chromosome abnormality, giving a total birth prevalence rate of 43.8/10 000 births. Of these, 7335 cases had trisomy 21,18 or 13, giving individual prevalence rates of 23.0, 5.9 and 2.3/10 000 births, respectively (53, 13 and 5% of all reported chromosome errors, respectively). In all, 473 cases (5%) had a sex chromosome trisomy, and 778 (8%) had 45,X, giving prevalence rates of 2.0 and 3.3/10 000 births, respectively. There were 1 737 RCA cases (17%), giving a prevalence of 7.4/10 000 births. These included triploidy, other trisomies, marker chromosomes, unbalanced translocations, deletions and duplications. There was a wide variation between the registers in both the overall prenatal diagnosis rate of RCA, an average of 65% (range 5–92%) and the prevalence of RCA (range 2.4–12.9/10 000 births). In all, 49% were liveborn. The data provide the prevalence of families currently requiring specialised genetic counselling services in the perinatal period for these conditions and, for some, long-term care.

Noninvasive prenatal diagnosis of common fetal chromosomal aneuploidies by maternal plasma DNA sequencing

Abstract: Objective: To develop a new bioinformatic method in the noninvasive prenatal identification of common fetal aneuploidies using massively parallel sequencing on maternal plasma. Methods: Massively parallel sequencing was performed on plasma DNA samples from 108 pregnant women (median gestation: 12+5 week) immediately before chorionic villus sampling (CVS) or amniocentesis. Data were analysed using a novel z-score method with internal reference chromosome. The diagnostic accuracies of the fetal karyotyping status were compared against two previously reported z-score methods – one without adjustment and the other with GC correction. Results: A total of 32 cases with fetal aneuploidy were confirmed by conventional karyotyping, including 11 cases of Trisomy 21, 10 cases of Trisomy 18, 2 cases of Trisomy 13, 8 cases of Turner syndrome (45, XO) and one case of Klinefelter syndrome (47, XXY). Using the z-score method without reference adjustment, the detection rate for Trisomy 21, Trisomy 18, Trisomy 13, Turner s...

Phthalates and Perfluorooctanesulfonic Acid in Human Amniotic Fluid: Temporal Trends and Timing of Amniocentesis in Pregnancy

Abstract: BACKGROUND: Measures of prenatal environmental exposures are important, and amniotic fluid levels may directly reflect fetal exposures during hypothesized windows of vulnerability. OBJECTIVES: We aimed to detect various phthalate metabolites and perfluorooctanesulfonic acid (PFOS) in human amniotic fluid, to study temporal exposure trends, and to estimate potential associations with gestational week of amniocentesis and maternal age and parity at amniocentesis. METHODS: We studied 300 randomly selected second-trimester amniotic fluid samples from a Danish pregnancy-screening biobank covering 1980 through 1996. We used only samples from male offspring pregnancies. We assayed the environmental pollutants by liquid chromatography/triple quadrupole mass spectrometry and analyzed data using generalized linear regression models. RESULTS: We detected the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) at a median concentration of 0.27 ng/mL [interquartile range (IQR): 0.20-0.37 ng/mL], the diisononyl phthalate (DiNP) metabolite mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP) at 0.07 ng/mL (IQR: 0.05-0.11 ng/mL), and PFOS at 1.1 ng/mL (IQR: 0.66-1.60 ng/mL). An increase of 1 calendar year was associated with 3.5% lower [95% confidence interval (CI): -4.8%, -2.1%] 5cx-MEPP levels and with 7.1% higher (95% CI: 5.3%, 9.0%) 7cx-MMeHP levels. For each later gestational week of amniocentesis, 5cx-MEPP was 9.9% higher (95% CI: 4.8%, 15.2%), 7cx-MMeHP was 8.6% higher (95: CI: 2.7%, 14.9%), and PFOS was 9.4% higher (95: CI: 3.3%, 15.9%). We observed no associations with maternal age or parity. CONCLUSIONS: Measured metabolite levels appeared to parallel decreasing DEHP exposure and increasing DiNP exposure during the study period. The environmental pollutant levels were positively associated with later gestational age at amniocentesis during pregnancy weeks 12-22. (Less)

Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature

Abstract: Objective To evaluate the results of prenatal chromosomal microarray analysis (CMA) on >1000 fetal samples referred for testing at our institution and to compare these data to published reports. Methods High resolution CMA was offered to women undergoing amniocentesis or chorionic villus sampling. Parental samples were obtained concurrently to exclude maternal cell contamination and assist interpretation of copy number variations. Results Clinically significant copy number variations were observed in 85/1115 cases (7.6%) overall, and in 45/1075 cases (4.2 %) if 40 abnormal cases with known chromosome abnormalities or familial genomic imbalances were excluded. Eighteen of the 1115 cases had variants of unclear clinical significance (1.6%). Indications yielding the most clinically significant findings were abnormal karyotype/fluorescence in situ hybridization (26/61, 42.6%), family history of chromosomal abnormality (13/137, 9.5%), abnormal ultrasound (38/410, 9.3%), abnormal serum screening (2/37, 5.4%) and advanced maternal age (5/394, 1.3%). Of 1075 cases having no previously known cytogenetic abnormality or family history, 18 (1.7%) had clinically significant genomic changes undetectable by conventional prenatal chromosome analysis. Conclusion Current experience confirms that the detection rate of CMA for prenatal chromosomal abnormalities surpasses that of conventional karyotype analysis and continues to improve with higher resolution arrays, while maintaining a low frequency of results of unclear clinical significance. © 2012 John Wiley & Sons, Ltd.

Pregnancy loss after chorionic villus sampling and genetic amniocentesis in twin pregnancies: a systematic review

Abstract: Objective To review the available evidence regarding pregnancy loss following first-trimester chorionic villus sampling (CVS) and mid-trimester genetic amniocentesis in twins. Methods We searched the MEDLINE database from January 1990 to May 2011 for randomized and cohort studies reporting on the risk of pregnancy loss after first-trimester CVS performed between 9 and 14 weeks and after genetic amniocentesis performed between 14 and 22 weeks. Where appropriate, we calculated pooled proportions and relative risks with 95% CI. Results No randomized studies were found. For CVS, nine studies fulfilled the inclusion criteria. The overall pregnancy-loss rate was 3.84% (95% CI, 2.48–5.47; n = 4). The rate of pregnancy loss before 20 weeks was 2.75% (95% CI, 1.28–4.75; n = 3) and before 28 weeks was 3.44% (95% CI, 1.67–5.81; n = 3). For amniocentesis, the overall pregnancy-loss rate was 3.07% (95% CI, 1.83–4.61; n = 4). The rate of pregnancy loss before 20 weeks was 2.25% (95% CI, 1.23–3.57; n = 2), before 24 weeks was 2.54% (95% CI, 1.43–3.96; n = 9) and before 28 weeks was 1.70% (95% CI, 0.37–3.97; n = 5). Pooled data from four case–control studies showed a higher risk (2.59% vs. 1.53%) of pregnancy loss before 24 weeks following amniocentesis (relative risk = 1.81; 95% CI, 1.02–3.19). There were no statistically significant differences in reported pregnancy loss between transabdominal and transcervical approaches, use of a single-needle system vs. a double-needle system and single uterine entry vs. double uterine entry in the CVS group. Similarly, in the amniocentesis group, there was no statistically significant difference in fetal loss between the single uterine entry vs. the double uterine entry. Conclusion In the absence of randomized studies, it is not possible to estimate accurately the excess risk following invasive procedures in twins. Currently available data show similar overall pregnancy-loss rates for both amniocentesis and CVS with the excess risk of around 1% above the background risk. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age

Abstract: Background: Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children. Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old. Finding: fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores. Conclusions: These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.

Genomic SNP array as a gold standard for prenatal diagnosis of foetal ultrasound abnormalities

Abstract: Background: We have investigated whether replacing conventional karyotyping by SNP array analysis in cases of foetal ultrasound abnormalities would increase the diagnostic yield and speed of prenatal diagnosis in clinical practice. Findings/results: From May 2009 till June 2011 we performed HumanCytoSNP-12 array (HCS) (http://www.Illumina. com) analysis in 207 cases of foetal structural abnormalities. HCS allows detecting unbalanced genomic abnormalities with a resolution of about 150/200 kb. All cases were selected by a clinical geneticist after excluding the most common aneuploidies by RAD (rapid aneuploidy detection). Pre-test genetic counselling was offered in all cases. In 24/207 (11,6%) foetuses a clinically relevant genetic abnormality was detected. Only 8/24 abnormalities would have been detected if only routine karyotyping was performed. Submicroscopic abnormalities were found in 16/ 207 (7,7%) cases. The array results were achieved within 1-2 weeks after amniocentesis. Conclusions: Prenatal SNP array testing is faster than karyotyping and allows detecting much smaller aberrations (~0.15 Mb) in addition to the microscopic unbalanced chromosome abnormalities detectable with karyotyping (~ > 5 Mb). Since karyotyping would have missed 66% (16/24) of genomic abnormalities in our cohort, we propose to perform genomic high resolution array testing assisted by pre-test counselling as a primary prenatal diagnostic test in cases of foetal ultrasound abnormalities.

Epidemiology and risk factors of amniotic band syndrome, or ADAM sequence.

Abstract: Amniotic band sequence (ABS) is the term applied to a wide range of congenital anomalies, most typically limb and digital amputations and constriction rings, that occur in association with fibrous bands (1). These alterations may be associated or not with cutaneous and visceral abnormalities.This work, which is a literature review, examines several studies that relate to cases of amniotic band syndrome (SBA). In particular, our attention was focused on the causes and pathogenesis of the SBA. These for the most part are still unknown, but from what we observe in different jobs, are due to a mechanism of vascular damage. Therefore in this paper we examine chemical risk factors, like smoking, drug use, maternal hyperglycemia, mechanical risk factors such as the puncture of the amniotic sac after amniocentesis. We also speak of the altitude as a risk factor related to blood pressure, of the increased incidence of disease in primigravid, in women with a low level of education, in which the pregnancy was not planned, and then we talk of a higher incidence in young fathers and of the role of familiarity.

Viral invasion of the amniotic cavity (VIAC) in the midtrimester of pregnancy.

Abstract: Introduction: The prevalence of viral infections in the amniotic fluid (AF) has not yet been ascertained The aim of this study was to determine the prevalence of specific viral nucleic acids in the AF and its relationship to pregnancy outcome Study design: From a cohort of 847 consecutive women undergoing midtrimester amniocentesis, 729 cases were included in this study after exclusion of documented fetal anomalies, chromosomal abnormalities, unavailability of AF specimens and clinical outcomes AF specimens were tested by quantitative real-time PCR for the presence of genome sequences of the following viruses: adenoviruses, herpes simplex virus (HSV), varicella zoster virus (VZV), human herpesvirus 6 (HHV6), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), parvovirus B19 and enteroviruses Viral nucleic acid testing was also performed in maternal blood and cord blood in the population of women in whom AF was positive for viruses and in a control group of 29 women with AF negative for viral nucle

An update on prenatal diagnosis and treatment of congenital adrenal hyperplasia.

Abstract: Congenital adrenal hyperplasia causes genital ambiguity in females affected with the severe form of the disease; yet the abnormality is preventable with prenatal dexamethasone treatment that must be given to the mother before the ninth week of gestation. In the period from 1978 to March 2011 we have made prenatal diagnosis in 719 pregnancies. Our results indicate that the average Prader score of those fetuses treated with dexamethasone was 1.7, which is much lower than the average Prader score of 3.73 in those not treated. While our data demonstrate no significant abnormalities in the long-range medical and cognitive outcomes in patients prenatally treated with dexamethasone, the current protocol involves invasive procedures such as chorionic villus sampling or amniocentesis, and all fetuses are treated unnecessarily for several weeks before the sex and the affection status of the fetus is known. We are collaborating with Dr. Dennis Lo in Hong Kong to develop a noninvasive protocol, whereby at the sixth to seventh week of gestation we can determine the sex and the affection status of the fetus by harvesting fetal DNA from the maternal plasma. The method will eliminate invasive procedures and unnecessary prenatal treatment and bring noninvasive prenatal diagnosis to underdeveloped areas where amniocentesis and chorionic villus sampling are not available.

Noninvasive prenatal genetic testing for fetal aneuploidy detects maternal trisomy X.

Abstract: Trisomy X is a sex chromosomal abnormality with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1000 female births. There is considerable variation in the phenotype, from asymptomatic and very mildly affected to significant physical and psychological features, leading only 10% of diagnosis ratio for those individuals with trisomy X. Current prenatal diagnosis of trisomy X relies on invasive prenatal tests such as karyotyping analysis. Although such tests allow accurate diagnosis, wide clinical use is limited by its complex operations and invasive nature with a 0.5% to 1% of procedure-related miscarriage. Recently, a newmethod based on massively parallel sequencing for cell-free DNA in maternal plasma was developed to detect fetal trisomy disorders. A rapid response statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis showed that the test currently available is only for fetal trisomy 21 and trisomy 18, which constitutes only about half of the fetal aneuploidy that would be identified through amniocentesis or CVS. Prior studies have shown that this massively parallel sequencing based noninvasive fetal trisomy test (the NIFTY test, which has no relationship with the ‘NIFTY’ trial on noninvasive prenatal diagnosis that was sponsored by the US National Institutes of Health) can not only detect trisomy 21 and trisomy 18, but also sex chromosomal aneuploidies. However, the effect of the maternal genetic background on the performance of the NIFTY test is not clear. Here we present a case in which maternal chromosome X materials affect the performance of the NIFTY. This case may provide a useful complement for the clinical application of the NIFTY test.

Invasive procedures for prenatal diagnosis: Any future left?

Abstract: Invasive diagnostic procedures (e.g chorionic villus sampling and amniocentesis) remain essential to the complete prenatal genetic diagnosis armamentarium. Both procedures are relatively safe in experienced hands, carrying procedure-related losses of about 1 in 400. Sensitivity of aneuploidy detection with either invasive test is near 100%, 10–15% higher than non-invasive protocols that use maternal serum analyte and fetal nuchal translucency screening. Application of cell-free fetal DNA for aneuploidy screening may or may not narrow this difference. Irrespective, invasive procedures are currently required for application of array comparative genome hybridisation.

Fetal varicella - diagnosis, management, and outcome.

Abstract: Fetal varicella syndrome (FVS) is due to transplacental infection by the Varicella zoster virus following maternal infection. The risks for the fetus and neonate depend on the timing. When varicella occurs around delivery, it often leads to disseminated neonatal varicella. When varicella occurs during pregnancy, transmission can occur, but is usually asymptomatic; some infants develop zoster postnatally and a few have FVS. Before 20 weeks' gestation, FVS can occur, with an incidence of about 1%. The lesions can affect the skin, limbs, central and autonomous nervous systems, eyes, cause calcifications, and growth retardation; mortality is high. Lesions typically follow one or several nerve territories, suggesting that damage results from in utero zoster following primary fetal infection. There has been little study of prenatal diagnosis of FVS. Serial ultrasound examination can detect various anomalies, magnetic resonance imaging can be of use to investigate for microphthamia and cerebral lesions, and amniocentesis can diagnose viral transmission. Prevention strategies include vaccination and post-exposure prophylaxis with immune globulin and/or antivirals. Perspectives for treating infected fetuses in utero require further research.

Fetal loss rate and associated risk factors after amniocentesis, chorionic villus sampling and fetal blood sampling.

Abstract: Purpose: To assess the total and procedure-related fetal loss rate and associated risk factors following amniocentesis (AC), chorionic villus sampling (CVS) and fetal blood sampling (FBS). Materials and Methods: We performed a retrospective analysis of patients with invasive diagnostics from 1993 to 2011 in two tertiary referral centers. We aimed to classify pregnancy loss after an invasive procedure and included the time after the invasive procedure and the result of targeted ultrasound/karyotype analysis in the analysis. Fetal losses occurring within two weeks after an invasive procedure were classified as procedure-related. Results: After excluding 1553 pregnancies with abnormal karyotype, fetal malformations and multiple insertions, 6256 cases were retrieved for final analysis. The total fetal loss rate was 1.5 %. The procedure-related fetal loss rate was 0.4 % for AC, 1.1 % for CVS and 0.4 % for FBS. Maternal vaginal bleeding in the first trimester was significantly associated with an increased procedure-related fetal loss rate (p= 0.008). The number of invasive procedures declined during the study period with increasing numbers of CVS in the first trimester. Conclusion: In our population the procedure-related fetal loss rate was 0.4 % after AC and 1.1 % and 0.4 % after CVS and FBS, respectively. Different gestational ages at the time of invasive procedures might account in part for those differences. Vaginal bleeding during the first trimester is associated with increased procedure-related fetal loss. Overall, declining numbers of invasive procedures are the result of changing attitudes toward invasive procedures and more sophisticated noninvasive prenatal screening programs over the last 20 years.

Noninvasive prediction of intra-amniotic infection and/or inflammation in preterm premature rupture of membranes.

Abstract: To develop a model based on noninvasive parameters to predict the probability of intra-amniotic infection and/or inflammation (IAI) in women with preterm premature rupture of membranes (PPROMs). Maternal blood was collected for determination of the C-reactive protein (CRP) level and white blood cell (WBC) count immediately after amniocentesis in 171 consecutive women with PPROMs. Intra-amniotic infection and/or inflammation was defined as a positive amniotic fluid (AF) culture and/or an elevated AF interleukin 6 level (≥2.6 ng/mL). A risk score based on a model including maternal blood CRP, WBC, parity, and gestational age was calculated for each patient. The model was shown to have an adequate goodness of fit (P = .516), and the area under the receiver–operating characteristic curve was 0.848, indicating very good discrimination. The noninvasive model based on maternal blood CRP, WBC, parity, and gestational age is highly predictive of IAI in women with PPROMs.

Antenatal Bartter Syndrome: A Review

Abstract: Antenatal Bartter syndrome (ABS) is a rare autosomal recessive renal tubular disorder. The defective chloride transport in the loop of Henle leads to fetal polyuria resulting in severe hydramnios and premature delivery. Early onset, unexplained maternal polyhydramnios often challenges the treating obstetrician. Increasing polyhydramnios without apparent fetal or placental abnormalities should lead to the suspicion of this entity. Biochemical analysis of amniotic fluid is suggested as elevated chloride level is usually diagnostic. Awareness, early recognition, maternal treatment with indomethacin, and amniocentesis allow the pregnancy to continue. Affected neonates are usually born premature, have postnatal polyuria, vomiting, failure to thrive, hypercalciuria, and subsequently nephrocalcinosis. Hypokalemia, metabolic alkalosis, secondary hyperaldosteronism and hyperreninaemia are other characteristic features. Volume depletion due to excessive salt and water loss on long term stimulates renin-angiotensin-aldosterone system resulting in juxtaglomerular hyperplasia. Clinical features and electrolyte abnormalities may also depend on the subtype of the syndrome. Prenatal diagnosis and timely indomethacin administration prevent electrolyte imbalance, restitute normal growth, and improve activity. In this paper, authors present classification, pathophysiology, clinical manifestations, laboratory findings, complications, and prognosis of ABS.

An overview of a 30-year experience with amniocentesis in a single tertiary medical center in Taiwan.

Abstract: Objective Amniocentesis is a popular and effective prenatal diagnostic tool for chromosomal disorders. It is well-established that the risk of chromosomal abnormalities increases with maternal age; however, other related indications are seldom reported. Herein, we report our 30-year experience with amniocentesis from a single medical center, focusing on the indications and rates of abnormality. Material and Methods A retrospective review of 16,749 pregnant women in the mid-trimester between January 1981 and December 2010 was conducted. The medical records were analyzed. Results The indications for amniocentesis were advanced maternal age (≥ 34 years old) ( n =10,970, 65.5%), increasing-risk maternal triple-marker Down's screening test (≥ 1/270) ( n =2090, 12.5%), history of abnormal offspring birth ( n =792, 4.7%), abnormal ultrasound findings ( n =484, 2.9%), parent with abnormal karyotype ( n =252, 1.5%), family history of chromosomal abnormality ( n =183, 1.1%), drug and radiation exposure ( n =165), abnormal chorionic villus sampling (CVS) results ( n =25), intrauterine fetal death ( n =50), and other non-specific causes ( n =1662, 9.9%). The rate of abnormality for each indication was 16% in the abnormal CVS group, 12% in the intrauterine fetal death group, 11.5% for parental chromosomal abnormality, 8.7% in the abnormal ultrasound finding group, 3.0% in the increasing-risk maternal triple-marker Down's screening test group, 2.5% in the advanced maternal age group, 1.5% for other non-specific causes, 1.4% for history of abnormal offspring birth, and 1.1% for family history of chromosomal abnormality. Conclusions Both parents with abnormal karyotype and abnormal ultrasound findings are indications for which consideration of further amniocentesis is highly recommended.

The promise of fetal cells in maternal blood

Abstract: Delaying childbirth increases the proportion of advanced maternal age pregnancies. This increases the number of pregnancies requiring invasive prenatal testing. Prenatal diagnosis of chromosomal aneuploidies and monogenic disorders requires fetal cells obtained through invasive procedures (i.e. chorionic villus sampling and amniocentesis). These procedures carry a risk of fetal loss, which causes anxiety to at-risk couples. Intact fetal cells entering maternal circulation have raised the possibility of non-invasive prenatal diagnosis. Rarity of fetal cells, however, has made it challenging. Fetal nucleated red blood cells are ideal candidate target cells because they have limited lifespan, contain true representation of fetal genotype, contain specific fetal cell identifiers (embryonic and fetal globins), and allow interrogation with chromosomal fluorescence in-situ hybridisation and possibly with array comparative genomic hybridisation. The utility of fetal nucleated red blood cells in non-invasive prenatal diagnosis has not reached clinical application because of the inconsistencies in enrichment strategies and rarity of cells.

The frequency and clinical significance of intra-amniotic inflammation in women with preterm uterine contractility but without cervical change: do the diagnostic criteria for preterm labor need to be changed?

Abstract: Objective: The objective of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm increased uterine contractility with intact membranes but without cervical change. Methods: Amniocentesis was performed in 132 patients with regular uterine contractions and intact membranes without cervical change. Amniotic fluid was cultured for bacteria and mycoplasmas and assayed for matrix metalloproteinase-8 (MMP-8). Intra-amniotic inflammation was defined as an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). Results: (1) Intra-amniotic inflammation was present in 12.1% (16/132); (2) Culture-proven intra-amniotic infection was diagnosed in 3% (4/132) of patients without demonstrable cervical change on admission or during the period of observation; and (3) Patients with intra-amniotic inflammation had significantly higher rates of preterm delivery and adverse outcomes, and shorter amniocentesis-to-delivery intervals than those without intra-a...

Association of pericentric inversion of chromosome 9 and infertility in romanian population.

Abstract: Background: One of the most common structural balanced chromosome rearrangements is pericentric inversion of chromosome 9; inv(9)(p11q12), which is consider to be the variant of normal karyotype and has been found in normal population. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility and recurrent abortions. The incidence is found to be about 1% - 3% in the general population. The aim of this study was to re-evaluate the clinical impact of inv(9)(p11q12)/(p11q13) in infertility. Materials and Methods: We investigated the karyotypes of 900 infertile couples (1800 individuals) admitted in our hospital for cytogenetic analysis. The control group consists of 1116 fetuses investigated by amniocentesis. This group was considered to be a sample of the fertile population, as the fetus being karyotyped is the result of a spontaneous pregnancy. Fetal karyotyping was made according to the standard indications for prenatal diagnosis (abnormal maternal serum screening results). Chromosomes from cultured peripheral blood lymphocytes and amniotic fluid were analyzed using Giemsa Trypsin-Giemsa (GTG) banding. The results of the two groups were compared. Results: 1800 infertile people were submitted for cytogenetic investigation. In the control group 97.73% had normal karyotype and 2.27% showed inversion of chromosome 9, while in the studied group 96.24% had normal karyotype and 3.76% showed inversion of chromosome 9. The incidence of inversion 9 in both male and female patients is not significantly higher comparing with normal population (p = 0.343, p< 0.05). Conclusions: Because a considerable proportion of patients with reproductive dysfunction had various cytogenetic abnormalities, the chromosomal analysis should be considered as a diagnostic tool in the evaluation of reproductive dysfunction (infertility in men due to spermatogenic disturbances and in recurrent spontaneous abortion in females).

Amniocentesis in twin pregnancies: a systematic review of the literature

Abstract: Objective Using published data, we sought to determine the amniocentesis-related loss rate in twin gestations.

Prenatal diagnosis for thalassaemia in Egypt: what changed parents' attitude?

Abstract: Objectives To present the current status of the prenatal diagnosis services and results from the largest thalassaemia center in Egypt treating 3000 patients. Traditionally, prenatal diagnosis has not been successful in reducing the births of affected children in Egypt, because the majority of women undergoing prenatal diagnosis continued to have affected pregnancies. Methods Seventy-one pregnant mothers at risk for β-thalassaemia underwent prenatal diagnosis by chorionic villus sampling (n = 57) or amniocentesis (n = 14) between 11 to 14 weeks of gestation. Molecular characterization of fetal DNA by reverse dot blot hybridization and polymerase chain reaction-amplification refractory mutation system techniques was conducted in all cases. Results Twenty-four women (33.8%) were found to have affected fetuses; 100% of these women opted to terminate the pregnancy. The change in attitude towards termination of pregnancy was related to in-depth counseling of the religious aspects towards prenatal diagnosis and termination of pregnancy. Forty-eight women (66.2%) with normal or carrier fetuses for β-thal requested human leukocyte antigen typing of the fetal material to determine if the fetus was a human leukocyte antigen match for their existing thalassaemic siblings. Conclusion This study demonstrates that prenatal diagnosis is feasible and acceptable in Egypt, a Muslim country, provided an in-depth discussion, which also addresses the religious considerations of prevention, is held with the couples. © 2012 John Wiley & Sons, Ltd.

Antepartum evaluation of the fetus and fetal well being.

Abstract: Despite widespread use of many methods of antenatal testing, limited evidence exists to demonstrate effectiveness at improving perinatal outcomes. An exception is the use of Doppler ultrasound in monitoring high-risk pregnancies thought to be at risk of placental insufficiency. Otherwise, obstetricians should proceed with caution and approach the initiation of a testing protocol by obtaining an informed consent. When confronted with an abnormal test, clinicians should evaluate with a second antenatal test and consider administering betamethasone, performing amniocentesis to assess lung maturity, and/or repeating testing to minimize the chance of iatrogenic prematurity in case of a healthy fetus.

Reproductive decisions after fetal genetic counselling

Abstract: A broad range of testing modalities for fetal genetic disease has been established. These include carrier screening for single-gene mutations, first-trimester and second-trimester screening for chromosome abnormalities and open neural-tube defects, prenatal diagnosis by means of chorionic villus sampling and amniocentesis, and preimplantation genetic diagnosis. Reproductive decisions before and after fetal genetic counselling represent the culmination of a dynamic interaction between prospective parents, obstetrician and genetic counsellor. The decision to undergo genetic testing before and after genetic counselling is influenced by a host of interrelated factors, including patient–partner and family relationships, patient–physician communication, societal mores, religious beliefs, and the media. Because of the complexity of personal and societal factors involved, it is not surprising that genetic counselling concerning reproductive decision-making must be individualised. A limited number of principles, guidelines and standards apply when counselling about testing for fetal genetic disease. These principles are that genetic counselling should be non-directive and unbiased and that parental decisions should be supported regardless of the reproductive choice. A critical responsibility of the obstetrician and genetic counsellor is to provide accurate and objective information about the implications, advantages, disadvantages and consequences of any genetic testing applied to prospective parents and their fetuses. These principles and responsibilities will be tested as newer technologies, such as array comparative genome hybridisation, non-invasive prenatal diagnosis and sequencing of the entire genome are introduced into the field of reproductive genetics and become routine practice.

Pregnancy outcome following mid-trimester amniocentesis

Abstract: To determine the institutional pregnancy complications rate associated with genetic amniocentesis and ascertain whether procedural variables or pre-existing factors may determine an increased risk of having a procedural-related fetal loss, we retrospectively evaluated all the consecutive amniocentesis, with known pregnancy outcome (n = 2990), performed between January 2001 and December 2009 by two very experienced clinicians. The patients who had counselling in the same period but declined to undergo amniocentesis represent the control group (n = 487). A total of 30 fetal losses occurred within 24 weeks' gestation (1%), while in the control group, we had four losses (0.8%). Procedural variables (transplacental sample, multiple needle insertions and gestational age) were not found to be predictive of increased fetal loss rate. Previous vaginal bleeding increased the risk of pregnancy loss after amniocentesis with an OR 4.1 (95% CI 2.0-8.7); on the contrary, a history of two or more miscarriages is not associated with a greater fetal loss rate, while the increased percentage (OR 3.4, 95% CI 1.2-9.0) in patients affected by uterine myoma appears connected, after the comparison with the control group, with the presence of fibroids rather than procedure.