Comparison of spontaneous fetal loss rates between women with singleton and twin pregnancies after mid-trimester amniocentesis - A historical cohort study.

OBJECTIVE: To assess and compare fetal loss rates before 28 weeks of singleton and twin pregnancies after mid-trimester amniocentesis. METHOD: This historic cohort study included 13 773 women with singletons and 426 women with twins undergoing mid-trimester amniocentesis from 1/2015 to 3/2017. Pregnancies resulting in termination or selective reduction before 28 weeks were excluded, as well as twin gestations undergoing single-puncture amniocentesis. Fetal loss rates were compared between singleton and twins taking into account maternal characteristics, amniocentesis procedure, and fetal chromosomal abnormalities. RESULTS: The rates of fetal chromosomal abnormalities were similar in singleton and twin gestations (1.13% vs 0.70%, P = .253). No difference was found in maternal or fetal characteristics, or amniocentesis procedure between the two groups. The fetal loss rate was significantly higher in twin compared with singleton pregnancies (1.91% vs 0.24%, P < .001, RR = 8.25 [95% CI: 4.51 to 15.09]). The fetal loss rate between monochorionic twins and dichorionic twins was similar (1.80% vs 1.78%, P = 1.000). CONCLUSIONS: Twin pregnancies have higher risk of fetal loss after mid-trimester amniocentesis, which cannot be explained by differences in rates of fetal chromosomal abnormalities, maternal characteristic, or amniocentesis technique.

Nonimmune hydrops fetalis: Genetic analysis and clinical outcome.

OBJECTIVE: To investigate the genetic causes and clinical outcomes of nonimmune hydrops fetalis (NIHF). METHODS: Cohort of cases of NIHF between July 2013 and December 2018. Initial genetic testing included quantitative fluorescence polymerase chain reaction for aneuploidies, karyotyping and chromosomal microarray analysis (CMA). In negative results, whole exome sequencing (WES) of the fetuses and parents was performed. Clinical post-natal follow-up assessments were conducted. RESULTS: One hundred and nine patients fulfilled the study inclusion criteria and were sequentially genetically assessed by karyotype, CMA and WES. Among them, 24.8% (27/109) had a clinically significant genetic abnormality: 21 (19%) had abnormal karyotypes; 3/72 had pathogenic/likely pathogenic copy number variants (additional yield = 4.2%); and 3 had single gene disorders. The pregnancy termination and live birth rates of the cases with positive genetic testing results were significantly different from those with negative results (92.6% vs 53.7% and 3.7% vs 31.7%, respectively, P < .05 for both). During clinical follow-up of the survivors, 3/23 (13.0%) children developed an additional phenotype. CONCLUSION: This study improves our understanding of the diagnostic yield of CMA and WES for NIHF. A genetic diagnosis of NIHF can help determine the fetal prognosis and recurrence risk and influence pregnancy decision-making.

Pregnancy outcome in foetuses with increased nuchal translucency - 10-years' experience in a prenatal medical practice.

This retrospective study describes pregnancy outcome for foetuses with increased nuchal translucency (NT) in relation to the degree of increase in a local specialised medical practice. Data from 7352 first trimester pregnancies examined by a single observer between 10/07 and 07/17 were screened. Three hundred and ninety-three foetuses (5.3%) that had an increased NT ≥ 95th percentile and available pregnancy outcome were identified. For this population, the frequencies of chromosomal abnormality, foetal malformation, intrauterine death (IUD) and termination of pregnancy (TOP) were determined in relation to the degree of NT thickness. Favourable pregnancy outcome decreased from 77.8% (lowest NT group, 95th percentile-3.5 mm) to 5% (highest NT ≥ 6.5 mm), whereas chromosomal abnormalities rose from 18.1% to 70%. An abnormal karyotype occurred in 39.2% of foetuses with increased NT. In euploid foetuses, cardiac defects were the most common structural abnormalities. The data largely matches with earlier studies conducted in large hospital-based settings. However, a rather high proportion of foetuses with abnormal karyotype was observed.IMPACT STATEMENTWhat is already known on this subject? Increased NT is associated with chromosomal abnormalities as well as an adverse perinatal outcome also in foetuses with a normal karyotype. The prevalence of an adverse outcome increases with NT thickness. These studies were conducted more than 10 years ago mainly in academic settings.What do the results of this study add? This study describes pregnancy outcome of a population of foetuses with increased NT that were examined in a medical practice by a single observer over a period of 10 years with state of the art ultrasound equipment. We observed a relatively large proportion of foetuses with abnormal karyotype. In euploid foetuses, increased NT was associated with a wide range of foetal malformations and genetic syndromes.What are the implications of these findings for clinical practice and/or further research? Even mildly increased NT thickness is associated with an adverse pregnancy outcome, underlining the importance of thorough ultrasound examinations. Specialised prenatal medical practices can provide state-of the art technology and provide improve parental counselling.

Genetic abnormalities seen on CVS in early pregnancy failure.

Objective: To determine the frequency and distribution of chromosome abnormalities in women with early pregnancy failure (EPF) detected by cytogenetic testing on chorionic villus sampling.Method: Retrospective observational cohort study of chromosomal analysis from transvaginal chorionic villus sampling (CVS) or reflex products of conception (POC) karyotype. CVS was offered as a training tool for Maternal Fetal Medicine fellows prior to manual vacuum aspiration for EPF 9-week gestation. POC were analyzed for cytogenetics if no results were obtained on CVS.Results: One hundred thirty samples were collected from December 2011 to April 2015. 33 (27.3%) cases had a normal karyotype and 88 (73.0%) cases had an abnormal karyotype. The most common group of abnormalities were trisomy, (n = 50, 41.3%), triploidy/tetraploidy, (n = 17, 14.0%), monosomy (n = 15, 12.4%), and structural rearrangements (n = 6, 5.0%). Nine (6.9%) samples were maternal decidua only. Abnormal karyotype in EPF was significantly increased in women by age group (p < .01) but not in women with a history of prior miscarriage (p = .5).Conclusion: Our cohort had a high detection rate of aneuploidy. The most common chromosomal abnormalities in EPF were: trisomy, followed by triploidy/tetraploidy, monosomy, and structural rearrangements. Maternal age had the strongest correlation with EPF associated with aneuploidy.

Chromosomal aberrations in women with primary and secondary amenorrhea: A cross-sectional study.

AIM: Among women of childbearing age, about 2-5% are affected by amenorrhea that is either primary or secondary. However, there are no data regarding the frequency and type of chromosomal abnormalities associated with amenorrhea in Saudi women. The present study aims to establish the frequency and pattern of chromosomal abnormalities in primary amenorrhea (PA) and secondary amenorrhea (SA) cases in a tertiary care center, Riyadh, Saudi Arabia. METHODS: This cross-sectional study was conducted between 2013 and 2016 on women referred to the Reproductive Endocrine and Infertility Medicine Department at a tertiary care center in Riyadh. Women were divided into two groups: PA and SA. After the initial diagnosis of amenorrhea based on medical history, physical examination, hormonal profile and ultrasonography, chromosome karyotype analysis was conducted on metaphase preparations following routine cytogenetics culture and harvest methods. RESULTS: Chromosomal tests were performed for 53 patients (42 with PA and 11 with SA) out of 79 referred patients with amenorrhea. About 19% of the 42 patients with PA and 1 patient (9.1%) diagnosed as SA showed an abnormal karyotype. The most common abnormal karyotypes observed were 46, XY and 45, X. CONCLUSION: The present study indicates that the chromosomal analysis after the exclusion of nongenetic causes should be essentially considered for the precise diagnosis and the development of more successful management for females with amenorrhea. This study also revealed that the prevalence of chromosomal abnormalities in women with PA and SA is similar to that reported in the literature.

Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study.

BACKGROUND: Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES). METHODS: In this prospective cohort study, two groups in Birmingham and London recruited patients from 34 fetal medicine units in England and Scotland. We used whole-exome sequencing (WES) to evaluate the presence of genetic variants in developmental disorder genes (diagnostic genetic variants) in a cohort of fetuses with structural anomalies and samples from their parents, after exclusion of aneuploidy and large CNVs. Women were eligible for inclusion if they were undergoing invasive testing for identified nuchal translucency or structural anomalies in their fetus, as detected by ultrasound after 11 weeks of gestation. The partners of these women also had to consent to participate. Sequencing results were interpreted with a targeted virtual gene panel for developmental disorders that comprised 1628 genes. Genetic results related to fetal structural anomaly phenotypes were then validated and reported postnatally. The primary endpoint, which was assessed in all fetuses, was the detection of diagnostic genetic variants considered to have caused the fetal developmental anomaly. FINDINGS: The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018. After exclusion of fetuses with aneuploidy and CNVs, 610 fetuses with structural anomalies and 1202 matched parental samples (analysed as 596 fetus-parental trios, including two sets of twins, and 14 fetus-parent dyads) were analysed by WES. After bioinformatic filtering and prioritisation according to allele frequency and effect on protein and inheritance pattern, 321 genetic variants (representing 255 potential diagnoses) were selected as potentially pathogenic genetic variants (diagnostic genetic variants), and these variants were reviewed by a multidisciplinary clinical review panel. A diagnostic genetic variant was identified in 52 (8·5%; 95% CI 6·4-11·0) of 610 fetuses assessed and an additional 24 (3·9%) fetuses had a variant of uncertain significance that had potential clinical usefulness. Detection of diagnostic genetic variants enabled us to distinguish between syndromic and non-syndromic fetal anomalies (eg, congenital heart disease only vs a syndrome with congenital heart disease and learning disability). Diagnostic genetic variants were present in 22 (15·4%) of 143 fetuses with multisystem anomalies (ie, more than one fetal structural anomaly), nine (11·1%) of 81 fetuses with cardiac anomalies, and ten (15·4%) of 65 fetuses with skeletal anomalies; these phenotypes were most commonly associated with diagnostic variants. However, diagnostic genetic variants were least common in fetuses with isolated increased nuchal translucency (≥4·0 mm) in the first trimester (in three [3·2%] of 93 fetuses). INTERPRETATION: WES facilitates genetic diagnosis of fetal structural anomalies, which enables more accurate predictions of fetal prognosis and risk of recurrence in future pregnancies. However, the overall detection of diagnostic genetic variants in a prospectively ascertained cohort with a broad range of fetal structural anomalies is lower than that suggested by previous smaller-scale studies of fewer phenotypes. WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness. FUNDING: UK Department of Health and Social Care and The Wellcome Trust.

First trimester cystic hygroma: does early detection matter?

OBJECTIVE: To describe the association of abnormal outcomes with fetal cystic hygroma detected when crown-rump length measures less than 45 mm, and to compare them to outcomes among fetuses with cystic hygroma detected when crown-rump length measures 45-84 mm. METHODS: We performed a retrospective cohort study of fetuses with first trimester nuchal cystic hygroma from 2005 to 2015. RESULTS: A total of 212 fetuses were included. Abnormal karyotype was found in 20 of 46 (43.4%) fetuses with cystic hygroma detected when crown-rump length measured below 45 mm, compared to 108 of 148 (73%) fetuses with cystic hygroma detected at crown-rump lengths of 45-84 mm (p = 0.001). There were no differences in rates of major structural anomaly (27% vs 36%; p = 0.53) or pregnancy loss (23% vs 7%; p = 0.22) among fetuses with normal karyotype. Those with cystic hygroma diagnosed at crown-rump lengths below 45 mm were more likely to have a normal neonatal outcome compared to cases diagnosed with crown-rump lengths of 45-84 mm (25% vs 11%; p = 0.02). CONCLUSION: Cystic hygroma detected when crown-rump length measures below 45 mm have lower rates of chromosomal abnormalities and a higher proportion of normal birth outcomes when compared to those detected later in the first trimester. © 2016 John Wiley & Sons, Ltd.

Karyotype analysis with amniotic fluid in 12365 pregnant women with indications for genetic amniocentesis and strategies of prenatal diagnosis.

We explored the strategies of prenatal diagnosis by foetal karyotype analysis in pregnant women with indications for genetic amniocentesis. Karyotype analysis of amniotic fluid was performed on 12365 pregnant women with indications for genetic amniocentesis. The detection rates and distributions of abnormal karyotypes were observed in a variety of indications for genetic amniocentesis. The detection rates of abnormal karyotype were 57.4% in either a mother or father with chromosomal abnormality, 8.5% in the pregnant women with pathological ultrasound finding (PUF), 2.79% in the pregnant women with advanced age (35 years and over) and 2.23% in the women with abnormal maternal serum screening (MSS) tests. Foetal abnormal karyotype was found in 86 pregnant women with PUF; of the 86 pregnant women, 42 had trisomy 13, 18 or 21. Of the 12365 pregnant women, foetal abnormal karyotype was found in 428 (3.46%); of the 428 foetuses, only 154 had trisomy 13, 18 or 21. In the pregnant women with abnormal MSS, 111 foetuses had abnormal karyotype, but only 36 foetuses had trisomy 13, 18 or 21. We conclude that (1) ultrasound is an important approach to prevent the birth of foetuses with chromosomal disease. (2) Non-invasive prenatal DNA detection cannot completely replace invasive prenatal diagnosis and MSS. (3) The strategies of prenatal diagnosis: Genetic amniocentesis is strongly recommended for the pregnant women with indications for genetic amniocentesis. For pregnant women who refuse invasive prenatal diagnosis, non-invasive prenatal DNA detection is first performed. If the results of non-invasive prenatal DNA detection are negative, the pregnant women are followed up by ultrasound; if the results of non-invasive prenatal DNA detection are positive, the pregnant women should undergo invasive prenatal diagnosis.

[PREIMPLANTATION DEVELOPMENT OF HUMAN EMBRYOS WITH NUMERICAL CHROMOSOME ABNORMALITIES IN VITRO].

The study was focused on morphokynetic characteristics of in vitro cultured human embryos that were considered to be aneuploid or euploid according to the preimplantation genetic screening results. Among all the embryos examined only 34.2% were chromosomally balanced, while others possessed isolated or combined chromosome abnormalities. Although morphological features of cleaving pathologic and euploid embryos did not differ significantly, on the fifth day of culture chromosomally balanced specimen formed "expanded" blastocyst twice as frequently as abnormal ones. Moreover, development of 38.4% of aneuploid embryos was compromised before the initiation of cavitation. Thus, prolonged embryo culture advances selection of samples with the highest implantation potential for the transfer on the basis of the morphokynetic characteristics and helps to avoid additional genetic testing.

The frequencies of the presence of embryonic pole and cardiac activity in early miscarriages with abnormal karyotypes.

AIMS: The objective of this study was to compare the frequencies of the presence of an embryonic pole and cardiac activity in miscarriages with normal and abnormal embryonic karyotypes. MATERIALS AND METHODS: From January 2008 to December 2012, 405 patients with early miscarriage were evaluated during pregnancy by regular ultrasound, and karyotyping was performed on chorionic villus tissue after curettage. The frequencies of the presence of an embryonic pole and cardiac activity were compared between patients with a normal embryonic karyotype and patients with an abnormal embryonic karyotype. RESULTS: Of the 405 samples, 224 cases (55.3%) had an abnormal karyotype, and 181 cases (44.7%) had a normal karyotype. The frequencies of the presence of an embryonic pole and cardiac activity in miscarriages with normal embryonic chromosomes (71.8% and 57.5%, respectively) were similar to those of miscarriages with abnormal embryonic chromosomes (74.1% and 62.1%, respectively). The frequencies of the presence of an embryonic pole and cardiac activity were higher in miscarriages with viable autosomal trisomies (trisomies 21, 13, and 18), monosomy X, and triploidy than in miscarriages with a normal karyotype or other abnormal karyotypes. CONCLUSIONS: The frequencies of the presence of an embryonic pole and cardiac activity are higher in miscarriages with viable autosomal trisomies, monosomy X, and triploidy than in miscarriages with a normal karyotype or other abnormal karyotypes.

Structural chromosomal abnormalities in couples with recurrent abortion in Egypt.

BACKGROUND/AIM: To evaluate the incidence of chromosomal abnormalities in couples who experience recurrent abortion and identify additional factors that may be predictive of abortion, such as parental age and unfavorable obstetric or abnormal semen analysis. MATERIALS AND METHODS: The present study examined 125 couples who had experienced recurrent abortion. All subjects provided a detailed personal medical history and ancestral history and underwent a physical examination. Women in the study group underwent biochemical testing and pelvic ultrasound examinations, and men underwent a semen analysis. RESULTS: Among the 125 couples tested, 8 c6uples (6.4%) displayed a balanced translocation, among which 7 (5.6%) showed a reciprocal translocation and 1 (0.8%) showed a Robertsonian translocation. All carriers of these translocations were aged <35 years. A significant proportion of carriers reported a poor obstetric history and a past fetal malformation. All male carriers had a normal semen analysis. CONCLUSION: Couples who experience ≥2 pregnancy losses of unknown origin should undergo a cytogenetic analysis, and findings showing a chromosomal abnormality in either parent must be followed by genetic counseling.

Prenatal examination and postmortem findings in fetuses with gastroschisis and omphalocele.

OBJECTIVE: This study compares prenatal ultrasound examination and autopsy findings in fetuses and infants with gastroschisis and omphalocele. METHOD: Criteria for inclusion in the study were an autopsy of fetuses/infants with gastroschisis or omphalocele performed between January 1985 and December 2009 and a prenatal ultrasound examination performed in a tertiary referral center. The results were organized into five categories depending on the degree of agreement. RESULTS: Of 11 cases with gastroschisis, only one was not detected at the prenatal ultrasound examination, and the rest had full agreement. Of 70 fetuses with omphalocele, two were not diagnosed at the prenatal ultrasound examination. Four (15%) had major autopsy findings not detected prenatally. The main diagnosis was correct in 64/70 (91%) and improved from 85% to 95% during this study period. The number of cases with major and minor autopsy findings not detected by ultrasound examination was reduced from 48% to 21%. Full agreement occurred in 46/70 (66%). CONCLUSION: This study shows that the correlation between prenatal ultrasound findings and postmortem examination is good and has improved over time. Comparing full agreement during the first 10 years with the last 15 years showed an improvement (p = 0.05) for fetuses with omphalocele.

[Cytogenetic profile in patients with primary myelodysplastic syndrome].

AIM: To analyze the prevalence of chromosome aberrations presented in the revised International Prognostic Scoring System (R-IPSS) in patients with de novo myelodysplastic syndrome (MDS). Subjects and methods. Chromosome aberrations were analyzed in 197 patients aged 14 to 86 years (median age 64 years) with de novo MDS. RESULTS: Karyotype abnormalities were revealed in 129 (65.5%) patients with de novo MDS. According to the IPSS criteria, the karyotypes found 52 (26.4%) patients were assigned to an intermediate prognostic group whereas in accordance with the R-IPSS guidelines, an intermediate karyotype group included chromosome abnormalities in 32 (16.2%) patients. Out of 5 R-IPSS prognostic types, the favorable karyotype group was the largest (48.2%). The very favorable and unfavorable karyotype groups comprised few patients with MDS: 3 and 3.6%, respectively. Despite the fact that it was not mentioned in the R-IPSS, a monosomal karyotype was verified in 24 (12.2%) patients There was a correlation of the (normal and complex) karyotype with bone marrow blast counts (r=0.469; p=0.000), but not with age. CONCLUSION: A variety of cytogenetic damages cannot identify the prognostic potential of all chromosome aberrations occurring in patients with MDS even if prognostic factors increased up to 5.

[Application and evaluation of invasive prenatal diagnostic techniques and analysis of chromosomal karyotype].

OBJECTIVE: To evaluate the safety, effectiveness and complications of serial invasive prenatal diagnostic techniques, and to investigate the prenatal diagnosis indication as well as to analyze the abnormal chromosomal karyotype. METHODS: We retrospectively studied all patients from March 2005 to May 2012 who received amniocentesis and cordocentesis in the prenatal diagnosis center of Second Xiangya Hospital. The indication of the procedure, successful rate and complications were evaluated, and 25 abnormal chromosome nuclear types were analyzed. RESULTS: A total of 669 patients received invasive prenatal diagnosis from March 2005 to May 2012 in Second Xiangya Hospital: 598 received amniocentesis and 71 cordocentesis carried out. Compared with the cordocentesis group, the amniocentesis group had higher achievement ratio (91.54% vs 100%, P<0.05), lower spontaneous abortion rate (1.41% vs 0.33%, P<0.05), fewer abnormal karyotypes (11.27% vs 2.84%, P<0.05) and lower expenditure (880 yuan vs 800 yuan, P<0.05). Positive screening, advanced maternal age, and ultrasonography abnormality were the top 3 indications of amniocentesis and cordocentesis. We found 25 abnormal karyotypes, including 6 cases of trisomy 21, 4 sex chromosomal abnormalities, 7 autosomal balanced translocations, 1 marker chromosome, and 7 mosaics. CONCLUSION: As a widely used invasive prenatal diagnosis, amniocentesis is safe and effective. The complications of cordocentesis are much higher than those of amniocentesis, which is not a proper routine procedure for prenatal diagnosis of abnormal karyotype. The analysis of karyotype not only can identify fetal chromosome abnormality, but also provide the scientific basis for pregnancy continuation, thus reducing the ratio of birth defect.

A retrospective analysis of amniocenteses performed for advanced maternal age and various other indications in Turkish women.

OBJECTIVE: Prenatal cytogenetic diagnostic methods for the diagnosis of fetal chromosomal anomalies have been used reliably over the last 40 years. Advanced maternal age has become a basic indication for amniocentesis. METHODS: We examined the results of the chromosome analyses of 3485 women that had amniocentesis for any reason during their antenatal care in our perinatology clinic in 2007-2009. Amniocentesis was performed for advanced maternal age in 1456 women (41.8%) and for other reasons in the remaining 2029 women (58.2%). Chromosomal anomalies were examined numerically and structurally. RESULTS: When the amniocentesis results of the patients were reviewed as numerically normal or abnormal; 40 (2.7%) of 1456 amniocentesis procedures performed for advanced maternal age, 5 (0.9%) of 531 procedures performed for an increased double-test risk and 14 (1.3%) of 1095 procedures performed for an increased triple test risk were found to have chromosomal aneuploidy. CONCLUSIONS: Maternal age is still the most prevalent indication for genetic amniocentesis other than positive prenatal screening tests. Among women with advanced maternal age, prenatal ultrasonography for soft markers of chromosomal aneuploidy accompanied with maternal serum biochemical screening tests should be evaluated during the decision making process of genetic amniocentesis.

Investigation of the frequencies of prenatally diagnosed fetal chromosomal abnormalities at a single institution.

The objective of this study was to investigate, retrospectively, the frequencies of fetal chromosomal abnormalities identified in 4176 prenatal cytogenetic examinations at the Xiamen Maternity and Child Health Care Hospital over the 5-year period from October 2005 to September 2010. The frequency of abnormal fetal karyotypes was 4.6%. Numerical chromosome abnormalities were identified in 150 cases. The frequency of trisomy 21 was by far the highest, followed by trisomy 18. Structural aberrations of chromosomes were identified in 43 cases, including 21 cases with balanced and 22 cases with unbalanced chromosomal aberrations. In addition, 16 cases of apparently de novo chromosomal aberrations and 27 cases of familial inheritances were observed. Increased awareness of the frequencies of fetal chromosome abnormalities is important for the improvement of prenatal care and providing the options of termination or continuation of the pregnancy. Data obtained in this study provide the basis of a database for genetic counseling.

Chorionic villus sampling for abnormal screening compared to historical indications: prevalence of abnormal karyotypes.

OBJECTIVE: To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). METHODS: Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. RESULTS: Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (χ(2) 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). CONCLUSIONS: Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk-based counseling and minimize morbidity.

Critical congenital heart disease--utility of routine screening for chromosomal and other extracardiac malformations.

Objective. Infants with critical congenital heart disease (CHD) can have genetic and other extracardiac malformations, which add to the short- and long-term risk of morbidity and perhaps mortality. We sought to examine our center's practice of screening for extracardiac anomalies and to determine the yield of these tests among specific cardiac diagnostic categories. Design. Retrospective review of infants admitted to the cardiac intensive care unit with a new diagnosis of CHD. Subjects were categorized into six groups: septal defects (SD), conotruncal defects (CTD), single-ventricle physiology (SV), left-sided obstructive lesions (LSO), right-sided obstructive lesions (RSO), and "other" (anomalous pulmonary venous return, Ebstein's anomaly). Screening modalities included genetic testing (karyotype and fluorescent in situ hybridization for 22q11.2 deletion), renal ultrasound (RUS), and head ultrasound (HUS). Results. One hundred forty-one patients were identified. The incidence of cardiac anomalies was: CTD (36%), SD (18%), SV (18%), LSO (14%), RSO (3%), and "other" (8%). Overall 14% had an abnormal karyotype, 5% had a deletion for 22q11.2, 28% had an abnormal RUS and 22% had abnormal HUS. Patients in SD and SV had the highest incidence of abnormal karyotype (36% and 17%); 22q11.2 deletion was present only in CTD and LSO groups (9% and 7%, respectively); abnormal RUS and HUS were seen relatively uniformly in all categories. Premature infants had significantly higher incidence of renal 43% vs. 24%, and intracranial abnormalities 46% vs. 16%. Conclusion. Infants with critical CHD and particularly premature infants have high incidence of genetic and other extracardiac anomalies. Universal screening for these abnormalities with ultrasonographic and genetic testing maybe warranted because early detection could impact short and long-term outcomes.

[Karyotype analysis of amniotic fluid cells and comparison of chromosomal abnormality rate during second trimester].

OBJECTIVE: To investigate the karyotypes of amniotic fluid cells and compare the incidence of chromosomal abnormality as well as to evaluate the clinical significance of abnormal karyotypes. METHODS: A total of 13 648 pregnant women came to Shanghai Jiai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University to do amniocentesis from September 1998 to November 2010, and 13 795 amniotic fluid specimens were successfully extracted and cultured, thus 13 795 fetuses received karyotype diagnosis. These fetuses were grouped according to different indications. If maternal age was ≥ 35, the fetuses were grouped into the advanced maternal age group (4065); and if maternal serum screening test revealed high-risk of trisomy 18 or trisomy 21, the fetuses were grouped into the high-risk serum screening group (6462); and those with abnormal signs of ultrasound screening were grouped into the abnormal ultrasound signs group (1539); and if either of the parents was with chromosome abnormalities, the fetus was grouped into the paternal/maternal abnormality group (108); whereas the remainder were grouped in other factors group (1621). The amniotic fluid cells were in-situ cultured on coverslips, harvested by conventional G-banded methods, and then analyzed by two doctors. In order to get rapid diagnosis, some pregnant women whose gestational age ≥ 26 weeks accepted fluorescense in situ hybridization (FISH). FISH was done on 78 uncultured amniotic fluid specimens using probes located at chromosome 13, 18, 21, X, Y. Some parents were required to analyze lymphocyte karyotype to help judging the origin of abnormal karyotype. RESULTS: (1) Classification and composition of abnormal karyotypes in each group: a total of 388 abnormal karyotypes were found among 13 795 fetuses, and the abnormal rate was 2.813% (388/13 795). Of the 388 fetuses, aneuploidy was the most common pattern which was up to 59.8% (232/388); autosomal structural abnormality rate was 24.7% (96/388); mosaicism was 12.4% (48/388). Other uncommon abnormal karyotypes included marker chromosome (5/388, 1.3%), sex chromosomal structural abnormality (4/388, 1.0%) and triploid (3/388, 0.8%). Aneuploidy was the most common in most groups except the paternal/maternal abnormality group. There were four cases of rare aneuploid in the advanced maternal age group, the high-risk serum screening group and the abnormal ultrasound signs group respectively. Every type of abnormality could be found in the abnormal ultrasound signs group, and autosomal structural abnormalities were concentrated in paternal/maternal abnormality group. Mosaicism mainly distributed in the high-risk serum screening group, accounting for 20.0% (29/145) of abnormalities in this group. (2) Abnormal types and the incidence: the most common type was trisomy 21 (138/388, 35.6%), followed by autosomal balanced structural rearrangements (80/388, 20.6%), mosaicism (48/388, 12.4%) and trisomy 18 (44/388, 11.3%). Others included non-balanced autosomal structural rearrangements (16/388, 4.1%), 45, X0 (16/388, 4.1%) and 47, XXY (15/388, 3.9%). (3) Lymphocyte karyotype analysis of the couples: parents of 153 fetuses were analyzed to determine the origin of abnormal karyotype. Fifty-eight familial and 95 de novo abnormalities were found. FISH results were the same with G-banding karyotype, and two of these were trisomy 21. CONCLUSIONS: Abnormal karyotype composition is different according to different maternal amniocentisis indications. There is a variety of abnormal karyotypes in the second trimester pregnancy, and the risk of fetal malformation is related with the kind of abnormal karyotype.