Fetal Karyotype Research Articles

Comparison of the ratio of second trimester fetal biometric measurements to fetal nasal bone length in fetuses with normal karyotype and trisomy 21.

In this study, we compared the ratio of second trimester fetal biometric measurements to nasal bone length (NBL) in fetuses with normal karyotype and trisomy 21 to determine their diagnostic prognostic value. The study included 148 pregnant women who obtained second-trimester ultrasonographic fetal anatomy and had amniocentesis (AS) for fetal karyotyping. The fetal karyotype results divided the groups into normal and trisomy 21 fetuses. Age, obstetric history, first and/or second trimester screening test risk ratios, fetal biometric measurements, and NBL mm, median (MoM) multiples, and percentile values were recorded and compared between groups. BPD/NBL ratios above 9.26 predict trisomy 21 in fetuses with 77.6% sensitivity and 86.1% specificity (p = 0.001). HC/NBL ratios above 34.50 predict trisomy 21 in fetuses with 77.8% sensitivity and 88.8% specificity (p = 0.001). FL/NBL ratios above 6.02 predict trisomy 21 in fetuses with 69.6% sensitivity and 72.2% specificity (p = 0.001). HL/NB ratios above 6.56 predict trisomy 21 in fetuses with 95.5% sensitivity and 47.2% specificity (p = 0.001). The NBL MoM value demonstrated a high diagnostic accuracy for normal-karyotype fetuses (p = 0.021). We found that BPD/NBL, HC/NBL, FL/NBL, and HL/NBL ratios differed between fetuses with a normal karyotype and those with trisomy 21, specifically the HC/NBL ratio, which predicted trisomy 21 with good diagnostic accuracy. In identifying normal-karyotype fetuses, the NBL MoM was highly accurate.

Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.

Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. Thirty studies were included (n=1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2=72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2=74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2=41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2=56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2=68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

#46 : Outcomes of Transfer Abnormally Chromosomal Embryos

Background and Aims: In some couples, there was no normal chromosomal embryos after preimplantation genetic testing (PGT) for aneuploidy (PGT-A), for structural chromosomal rearrangements (PGT-SR) or for monogenic (PGT-M). The couples decided to use the abnormal embryos for transfer after thorough genetic counselling. This study reports the outcomes of transfer abnormally chromosomal embryos. Method: This retrospective study was conducted from January 2020 to December 2022 at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. The abnormally chromosomal embryos that were considered for transfer included aneuploidy related to [Formula: see text]3 chromosomes (except trisomy 13, 18, 21 and monosomy X); or mosaicism has [Formula: see text]50% of aneuploidy after PGT-A, PGT-SR or PGT-M (except mosaic trisomy 13, 18, 21 and monosomy X). Results: 94 patients transferred 94 single abnormally chromosomal embryos. Out of 94 embryos, 62 were mosaic and 32 were aneuploid. Among the group of mosaic embryos, 25 (40.3%) had segmental, 32 (51.6%) had 1 or 2 chromosomal abnormalities and 5 (8.1%) had 3 or more. Among the group of aneuploid embryos, 4 (12.5%) had segmental, 13 (40.6%) had 1 chomosomal abnormalities, 5 (15.6%) had 2 chomosomal abnormalities and 10 (31.3%) complexes (both mosaic and aneuploid chromosome). Among 20 live births, 2 cases have normal fetal karyotype, and 11 cases have normal CNVs blood results. Conclusion: Mosaic embryos can be considered for transfer in cases having no normal embryos after PGT. More than 50% of babies born from chromosomally abnormal embryo transfer have normal chromosomal results.

Detection of Maternal Malignancy after Abnormal Noninvasive Prenatal Testing (NIPT)

Introduction: Noninvasive prenatal testing (NIPT) is routinely used to screen for fetal aneuploidies in chromosomes 13, 18 and 21. NIPT uses NGS based methods to detect fetal cfDNA in maternal circulation. In 2016, the American College of Obstetricians and Gynecologists recommended offering NIPT testing for all pregnant patients regardless of maternal age. Reports of maternal malignancy detected by NIPT have been increasing since its wide adoption into clinical practice, but subsequent management has not been standardized. We therefore report the outcomes of patients with abnormal NIPT evaluated and managed at a single institution. Methods: A case series ofpatients referred to Dana-Farber Cancer Institute between 2014 and 2022 for evaluation following an abnormal NIPT or for treatment of a cancer identified through NIPT. Results: Fourteen cases were included in this series. The median age at NIPT was 34 (range 29-42). Most patients (79%) had multiple chromosomal aneuploidy while 3 patients had ≤2 chromosomal abnormalities reported on their NIPT. Twelve patients (86%) underwent subsequent invasive prenatal testing: results were normal in all but one whose trisomy 12 finding led to early termination. Eleven patients (79%) underwent a whole-body MRI (WBMRI), 6 (55%) of which identified a suspicious finding that required biopsy. Of the 6 patients biopsied for a finding on WBMRI, 5 (83%) were found to have a malignancy. All patients who had a negative WBMRI did not have an identified malignancy. Of the total 14 cases, 10 (71%) underwent biopsies for abnormal findings and 8 (80%) of biopsies led to diagnosis of malignancy (or 57% of overall cohort). This was found to be Hodgkin lymphoma in 4 (29%), primary mediastinal large B cell lymphoma in 2 (14%) and triple negative breast cancer in 2 (14%) of the patients. Other causes of abnormal NIPT were uterine fibroids in 3 (21%), hepatic adenoma in 1 (7%), ovarian dermoid cyst in 1 (7%) and no abnormal findings in 1 (7%). Half of the patients received cancer treatment during pregnancy and the other half after pregnancy. Treatment included chemotherapy 6 (75%), chemotherapy/radiation 1 (12.5%) and surgery/chemotherapy 1 (12.5%). Post treatment, 6/8 (75%) patients achieved a complete metabolic response (CMR), one patient is still undergoing treatment and one patient (breast cancer) is deceased. Overall, there were 12 (86%) live births, one pregnancy termination and one patient with missing data. The median birthweight was 7.2 lbs (6.1-8.5 lbs). Two patients had NIPT with previous pregnancies. One patient had a normal NIPT and the other had an abnormal NIPT that was similar in two pregnancies, but she had a hepatic adenoma. Two patients with PMBCL had subsequent pregnancies and repeat NIPT after treatment were both normal . Conclusions: Specific abnormal NIPT results may be caused by maternal malignancy, especially where there is discordance with the fetal karyotype. A WBMRI without contrast is a safe and feasible initial approach for diagnosis and staging in these patients. Most tumors are lymphomas, for which treatment during and soon after pregnancy is possible with favorable maternal and fetal outcomes.

Genetic analysis of a fetus with mosaicism Y chromosome aberration

To carry out prenatal diagnosis for a fetus with mosaicism Yq deletion. A fetus with high risk of sex chromosomes indicated by non-invasive prenatal testing (NIPT) at Tianjin Medical University General Hospital in July 2021 was selected as the study subject. Prenatal diagnosis of the fetus was performed with combined G-banded chromosomal karyotyping, fluorescence in situ hybridization (FISH), copy number variation sequencing (CNV-seq), real-time fluorescence PCR (QF-PCR), and ultrasound examination. Analysis of the amniocytes at 23 gestational weeks had yielded a 45,X karyotype. However, FISH had shown signals of Y chromosome. Re-examination by cordocentesis had shown a mosaicism of 46,X,+mar[33]/45,X[17]. FISH showed that 69% of the cells had contained Y chromosome signals. The result of CNV-seq was seq[19]del(Y)(q11.1q12)(mos) chrY: g.13200001_ 28820000del (mosaicism rate = 64%), which suggested mosaicism for a Yq deletion, which encompassed the azoospermia factor (AZF) region. Deletion of the AZF region was verified by QF-PCR. The fetal karyotype was ultimately determined as mos46,X,del(Y)(q11.1)[33]/45,X[17]. Although ultrasound examination had shown no abnormality in the fetus, the couple had opted to terminate the pregnancy, and the induced fetus had a normal male appearance. The combined use of multiple techniques is beneficial for accurate and rapid prenatal diagnosis. For fetuses with mosaicism chromosomal abnormalities, it may be difficult to accurately predict the postnatal phenotype. It is therefore necessary to further explore their genotype-phenotype correlation in order to provide better guidance upon genetic counseling.

Gestational Trophoblastic Disease with Coexisting Progressing Pregnancy: Personalised Treatment Modalities.

Gestational trophoblastic disease (GTD) coexisting with a steadily progressing pregnancy is an extremely rare condition presented in the literature as a single case or case series of successful delivery. The purpose of this study was to describe five cases of GTD and present possible management strategies for such patients. Clinical data of five pregnancies with coexisting GTD were identified within the Almazov National Medical Research Centre from 2018 to 2021. Three cases of multiple pregnancies with complete hydatidiform moles and two cases of singleton pregnancies with intraplacental choriocarcinoma and invasive hydatidiform moles were identified. Three pregnancies were prolonged and ended with preterm deliveries. Malignant transformation of the GTD accounted for 60% of the cases. The condition of newborns was based on the level of prematurity and functional immaturity, and in all cases, it was aggravated by anemia. GTD coexisting with progressing pregnancy is threatened by the risks of preterm delivery, miscarriage, hemorrhage, and disease progression and requires monitoring in a multidisciplinary clinic experienced in the management of patients with malignant tumors during pregnancy. In cases of prolonged pregnancy against the background of GTD, we suggest the following monitoring during pregnancy: pelvic, abdominal ultrasound/MRI (without contrast), prenatal invasive fetal karyotype testing in cases of singleton pregnancy, lung X-ray/CT with uterine shielding, weekly assessment of β-hCG levels, and dynamic monitoring of the fetus. The following postnatal monitoring should be performed: morphological examination of the placenta, weekly assessment of β-hCG levels up to normalization, then monthly assessment up to six months, and control of β-hCG level of the newborn.

Outcome of partial agenesis of corpus callosum

The diagnosis of corpus callosum anomalies by prenatal ultrasound has improved over the last decade because of improved imaging techniques, scanning skills, and the routine implementation of transvaginal neurosonography. Our aim was to investigate all cases of incomplete agenesis of the corpus callosum and to report the sonographic characteristics, the associated anomalies, and the perinatal outcomes. We performed a retrospective analysis of cases from January 2007 to December 2017 with corpus callosum anomalies, either referred for a second opinion or derived from the prenatal ultrasound screening program in a single tertiary referral center. Cases with complete agenesis were excluded from the analysis. Standardized investigation included a detailed fetal ultrasound including neurosonogram, fetal karyotyping (standard karyotype or array comparative genomic hybridization) and fetal magnetic resonance imaging. The pregnancy outcome was collected, and pathologic investigation in case of termination of the pregnancy or fetal or neonatal loss was compared with the prenatal findings. The pregnancy and fetal or neonatal outcomes were reported. The neurologic assessment was conducted by a pediatric neurologist using the Bayley Scales of Infant Development-II and the standardized Child Development Inventory when the Bayley investigation was unavailable. Corpus callosum anomalies were diagnosed in 148 cases during the study period, 62 (41.9%) of which were excluded because of complete agenesis, and 86 fetuses had partial agenesis (58.1%). In 20 cases, partial agenesis (23.2%) was isolated, whereas 66 (76.7%) presented with different malformations among which 29 cases (43.9%) were only central nervous system lesions, 21 cases (31.8%) were non-central nervous system lesions, and 16 cases (24.3%) had a combination of central nervous system and non-central nervous system lesions. The mean gestational age at diagnosis for isolated and non-isolated cases was comparable (24.29 [standard deviation, 5.05] weeks and 24.71 [standard deviation, 5.35] weeks, respectively). Of the 86 pregnancies with partial agenesis, 46 patients opted for termination of the pregnancy. Neurologic follow-up data were available for 35 children. The overall neurologic outcome was normal in 21 of 35 children (60%); 3 of 35 (8.6%) showed mild impairment and 6 of 35 (17.1%) showed moderate impairment. The remaining 5 of 35 (14.3%) had severe impairment. The median duration of follow-up for the isolated form was 45.6 months (range, 36-52 months) and 73.3 months (range, 2-138 months) for the nonisolated form. Partial corpus callosum agenesis should be accurately investigated by neurosonography and fetal magnetic resonance imaging to describe its morphology and the associated anomalies. Genetic anomalies are frequently present in nonisolated cases. Efforts must be taken to improve ultrasound diagnosis of partial agenesis and to confirm its isolated nature to enhance parental counseling. Although 60% of children with prenatal diagnosis of isolated agenesis have a favorable prognosis later in life, they often have mild to severe disabilities including speech disorders at school age and behavior and motor deficit disorders that can emerge at a later age.

EP21.21: Diagnostic efficacy of chromosomal microarray versus conventional karyotype in fetuses with increased nuchal translucency

EP21.21: Diagnostic efficacy of chromosomal microarray versus conventional karyotype in fetuses with increased nuchal translucency

OP16.04: Diagnostic efficacy of conventional karyotype and chromosomal microarray in fetuses with normal and abnormal antenatal ultrasound

OP16.04: Diagnostic efficacy of conventional karyotype and chromosomal microarray in fetuses with normal and abnormal antenatal ultrasound

EP21.08: Diagnostic efficacy of conventional karyotype and chromosomal microarray in fetuses with markers and defects found on prenatal ultrasound

EP21.08: Diagnostic efficacy of conventional karyotype and chromosomal microarray in fetuses with markers and defects found on prenatal ultrasound

The effect of progesterone supplementation in women with threatened miscarriage on fetal fraction in non-invasive prenatal testing: A matched case-control study.

To evaluate the effect of progesterone use on fetal fraction (FF) in non-invasive prenatal testing (NIPT) due to the threat of first trimester miscarriage. This case control study included the pregnant who were referred to our clinic for non-invasive prenatal testing. The patients were categorized into three groups: Pregnant women with vaginal bleeding and using progesterone, pregnant women with vaginal bleeding and not using progesterone, and pregnant women without bleeding. The groups were formed by matching gestational week. Women with multiple pregnancy, BMI (body mass index) ≥25, abnormal fetal karyotype, and chronic disease were excluded from the study. Maternal characteristics, FF of the NIPT were recruited from the computer based medical records. A total of 10,275 NIPT tests were performed during the study period. 3% of the patients (n=308) were found at risk of miscarriage. 100 patients with a vaginal bleeding and 50 control patients were matched. The median value of the fetal fraction ratio was found to be 6.55 in pregnant women without vaginal bleeding, 7.05 in pregnant women who had vaginal bleeding and using progesterone, and 7.3 in pregnant women who had vaginal bleeding and did not use progesterone. Although the fetal fraction ratio was found to be higher in pregnant women with vaginal bleeding and lower in progesterone users, this situation could not reach the level of statistical significance (p=0.351). The fetal fraction rate in maternal blood is not affected in pregnant women who use progesterone due to vaginal bleeding in early gestational weeks.

Ultrasonographic characteristics, genetic features, and maternal and fetal outcomes in fetuses with omphalocele in China: a single tertiary center study

BackgroundPatients with omphalocele, a midline abdominal wall defect at the umbilical cord base, have a low survival rate. However, the long-term outcomes of fetuses with prenatally diagnosed omphalocele have scarcely been studied. Therefore, we investigated the ultrasonographic features, genetic characteristics, and maternal and fetal outcomes of fetuses with omphalocele and provided a reference for the perinatal management of such cases.MethodsA total of 120 pregnant females with fetal omphalocele were diagnosed using prenatal ultrasonography at the Fujian Provincial Maternity and Child Health Hospital from January 2015 to March 2022. Amniotic fluid or cord blood samples were drawn at different gestational weeks for routine karyotype analysis, chromosomal microarray analysis (CMA) detection, and whole exome sequencing (WES). The maternal and fetal outcomes were followed up.ResultsAmong the 120 fetuses, 27 were diagnosed with isolated omphalocele and 93 with nonisolated omphalocele using prenatal ultrasonography. Cardiac anomalies were the most observed cause in 17 fetuses. Routine karyotyping and CMA were performed on 35 patients, and chromosomal abnormalities were observed in five patients, trisomy 18 in three, trisomy 13 in one, and chromosome 8–11 translocation in one patient; all were non-isolated omphalocele cases. Six nonisolated cases had normal CMA results and conventional karyotype tests, and further WES examination revealed one pathogenic variant and two suspected pathogenic variants. Of the 120 fetuses, 112 were successfully followed up. Eighty of the 112 patients requested pregnancy termination. Seven of the cases died in utero. A 72% 1-year survival rate was observed from the successful 25 live births.ConclusionThe prognosis of fetuses with nonisolated omphalocele varies greatly, and individualized analysis should be performed to determine fetal retention carefully. Routine karyotyping with CMA testing should be provided for fetuses with omphalocele. WES is an option if karyotype and CMA tests are normal. If the fetal karyotype is normal and no associated abnormalities are observed, fetuses with omphalocele could have a high survival rate, and most will have a good prognosis.

Results of karyotype analysis and 22q11.2 (DiGeorge Syndrome critical region) deletion investigation in fetal cardiac system anomalies

The results of karyotype analysis and 22q11.2 ( DiGeorge Syndrome critical region) deletion investigation in fetal cardiac system anomalies 
 Objective: We aimed to determine the presence of accompanying chromosomal anomalies and 22q11.2 deletion in patients with cardiac system anomalies.
 Material and Methods: In our retrospective and cross-sectional study, 99 fetuses born with cardiac anomalies were evaluated in terms of chromosomal anomalies. 36 fetuses were evaluated for 22q11.2 deletion. Fetuses who were diagnosed with prenatal congenital heart defect and underwent invasive prenatal diagnostic tests for fetal karyotyping between 01.01.2010 and 30.06.2017 at a tertiary cancer center were included in the study.
 Results: Of 99 cases, 48 (48.4%) had only cardiac anomalies and 51 (51.5%) had non-cardiac anomalies. Chromosomal anomalies were found in 37 (37.4%) of the cases. Autosomal trisomy 18(43.2%) and autosomal trisomy 21(32.4%) were the most common chromosomal anomalies. The study results support the strong association of chromosomal changes and cardiac malformation, especially in septal defects, atrioventricular septal defects, and conotruncal malformations. Deletion was detected in one(2.8%) of 36 cases evaluated for 22q11.2 deletion. The fetus with this deletion had isolated tetralogy of fallot and had no extracardiac anomaly.
 Conclusion: In cases with cardiac anomalies, isolated or accompanied by extracardiac anomalies, investigations should be made in terms of underlying chromosomal diseases in the perinatal evaluation. In addition, the investigation of 22q11.2 deletion in fetuses with conotruncal cardiac anomalies should be included in prenatal genetic examination.
 Keywords: DiGeorge Syndrome, Fetal Anomalies, karyotype, trisomy, 22q11.2 Deletion Syndrome

Accidental discovery of copy number variation on chromosome 1 in a fetus with high risk of trisomy 13 suggested by NIPT

To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT). The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor. The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples. NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.

Mosaic variant of trisomy on chromosome 8 (Warkany syndrome): report on a rare clinical case in a newborn boy after IVF fertilization

Varkani syndrome or trisomy 8 mosaicism (T8M) - is a described chromosomal anomaly with a frequency of 1 : 25,000 to 1 : 50,000 births, which is more common in men than in women (5 : 1). In the Department of Pediatric Surgery at Almazov NMRC, a 28-year-old woman was admitted at 39 weeks' gestation with a aggravated somatic history. Pregnancy occurred with the support of auxiliary reproductive technologies: extorporepical fertilization due to the male factor, overpermation and asthenospermia caused by mumps transferred in childhood. Antenatally diagnosed: multiple congenital malformations of the fetus: agenesis of the corpus callosum, triventricularhydrocephalus, macrocephaly, bilateral ureterohydronephrosis; megacystis. The spouses were karyotyped, karyotypes 46, XX - normal female and 46, XY - normal male. According to the results of the karyogram, the fetal karyotype is 46, XY - normal male. From the first day of life, the child has clinical epileptic myolonic generalized attacks. According to the results of the study: Neurosonography confirmed the presence of a malformation of the brain. Echocardiography: Ventricular septal defect (VSD). Ultrasound of the abdominal organs revealed bilateral ureterohydronephrosis with expansion of the pelvicalyceal system and ureters. At the age of 28 days, due to the existing neurogenic disorder of the function of the bladder against the background of a fixed spinal cord in order to constant urine, vesicostomy is performed. Performed diagnostic laparoscopy: in the right iliac region spreads education with a diameter of 2 cm, which is a diverticular-cystic doubling of the ileum. A wedge-shaped resection of the base of the diverticulum was performed, the operation was completed by vesicostomy. Discharged home in a satisfactory condition at the age of 2 months. As a result of karyotyping of the newborn, the result mos47, XY, +8[7]/46, XY [9] was obtained - a mosaic variant of trisomy on chromosome 8. Mosaicism of trisomy 8 rare chromosomal anomaly. The clinical case described by us is characterized by a combination of severe congenital defects, which were not previously reported. This is the first time of the birth of a child with a trisomy of 8 chromosome after auxiliary reproductive technologies: extracurporeal fertilization.

Two cases of placental trisomy 21 mosaicism causing false-negative NIPT results

BackgroundNon-invasive prenatal testing (NIPT) using cell-free DNA has been widely used for prenatal screening to detect the common fetal aneuploidies (such as trisomy 21, 18, and 13). NIPT has been shown to be highly sensitive and specific in previous studies, but false positives (FPs) and false negatives (FNs) occur. Although the prevalence of FN NIPT results for Down syndrome is rare, the impact on families and society is significant.Case presentationThis article described two cases of foetuses that tested “negative” for trisomy 21 by NIPT technology using the semiconductor sequencing platform. However, the fetal karyotypes of amniotic fluid were 46,XY, + 21 der(21;21)(q10;q10) and 47,XY, + 21 karyotypes, respectively. Placental biopsies confirmed that, in the first case, the chromosome 21 placenta chimerism ratio ranged from 13 to 88% with the 46,XX, + 21,der(21;21)(q10;q10)[86]/46,XX[14] karyotype of placental chorionic cells (middle of fetal-side placental tissue). However, in the second case, of all the placental biopsies, percentage of total chimerism was less than 30%; and placental biopsies taken at the middle of maternal side and middle of fetal side, also had variable trisomy 2 mosaicism levels of 10% and 8%, respectively. Ultimately, the pregnancies were interrupted at 30 gestational age (GA) and 27GA, respectively.ConclusionsIn this study, we present two cases of FN NIPT results that might have been caused by biological mechanisms, as opposed to poor quality, technical errors, or negligence. Clinical geneticists and their patients must understand that NIPT is a screening procedure.

Prenatal Screening of Cytogenetic Anomalies -A Ten Year Retrospective Study on 1510 Cases

Introduction: Prenatal diagnostic is a diagnostic method which is used to prove the presence of chromosome changes, a large number of metabolic disorders and other morphological fetus abnormalities. Prenatal genetic testing mostly refers to the molecular genetic and cytogenetic methods used during pregnancy to diagnose genetic fetal conditions. Aim: To investigate the existence and incidence of cytogenetics abnormalities in fetuses. Material and Methods: The retrospective research is based on cytogenetic analysis of the 1510 amniotic fluid samples collected from pregnant women sent to the cytogenetic laboratory from January, 2012 to December, 2022. Results: The karyotype without visible structural and numerical changes was detected in 96.8% (1462/1510) cases. The fetal karyotype was abnormal in 3.2 % (48/1510) of the cases. Trisomy 21 was the most frequent chromosome aberration detected in 1.12% (17/1510) cases followed by pericentric inversion 9 (10/1510; 0.66%) and trisomy 18 (4/1510; 0.26%). Mosaics were detected in five cases (5/1510; 0.33%). Comparing the prevalence of chromosome abnormalities according to maternal age, we come to know the prevalence of chromosome aberrations in the group of females above age 35 (26/790; 17.2/1000) is higher than in the group of females under age 25 (7/95; 4.63/1000), but not significantly different (P= 0.09). Conclusion: Conventional cytogenetics maintains its role as a powerful diagnostic tool in detecting chromosomal changes during prenatal screening.

Amniotic Fluid Ischemia Modified Albumin as a Novel Prenatal Diagnostic Marker for Down Syndrome: A Prospective Case-Control Study

Aims: There is no study in the literature about ischemia-modified albumin (IMA) and hepatocyte growth factor (HGF) levels in amniotic fluid for Down syndrome cases. The aim of this study was to investigate the changes of IMA and HGF in Down syndrome cases at 16-20 weeks of gestation compared to normal fetuses. Methods: For this prospective case-control study, following reaching the number of 20 women (study group) who had the prenatal diagnosis of Down syndrome, maternal and gestational age-matched pregnant women with normal constitutional karyotype were selected for the control group (n = 74) from the stored amniotic fluid samples. Results: Mean women and gestational ages were comparable between the two groups. Amniotic fluid IMA (1.32 ± 0.13 vs. 1.11 ± 0.11 ABSU, respectively, p < 0.001) and HGF (2743.53 ± 1389.28 vs. 2160.12 ± 654.63 pg/mL, respectively, p = 0.008). Levels were significantly higher in pregnant women having Down syndrome fetuses compared with women having normal fetuses. The amniotic fluid IMA levels for the diagnosis of Down syndrome, and the sensitivity and specificity were calculated as 95.0% and 71.6% for the limit value 1.171 cm3, respectively. Conclusion: In cases with suspected Down syndrome, the diagnosis of Down Syndrome may be made in approximately 1 hour with high sensitivity and specificity by measuring the IMA level in the amniotic fluid sample taken for fetal karyotyping.

Amniotic fluid karyotype analysis and prenatal diagnosis strategy of 3117 pregnant women with amniocentesis indication.

Aim: To examine prenatal diagnosis strategies through fetal karyotype analysis for 3117 pregnant women with genetic amniocentesis indications. Materials & methods: According to the different indications for amniocentesis, the study was divided into 8 groups. The number of amniocentesis specimens, the number of abnormal karyotypes and the positive rate of each group were analyzed. Results: Compared with prenatal serum screening, noninvasive prenatal DNAtesting is more accurate and can effectively improve screening efficiency. Multiple prenatal diagnosis indicators (37.349%) were more likely to be detected than single prenatal diagnosis indicators (11.091%). Conclusion: None of the screening methods can completely replace amniocentesis, and for pregnant women with genetic indications for amniocentesis, amniocentesis is strongly recommended.

Prenatal Diagnosis of an Intrathoracic Left Kidney Associated with Congenital Diaphragmatic Hernia: Case Report and Systematic Review.

A congenital intrathoracic kidney (ITK) is a rare anomaly that is recognized to have four causes: renal ectopia with an intact diaphragm, diaphragmatic eventration, diaphragmatic hernia, and traumatic diaphragmatic rupture. We report a case of a prenatal-diagnosed ITK related to a congenital diaphragmatic hernia (CDH) and conducted a systematic review of all cases of the prenatal diagnosis of this association. A fetal ultrasound scan at 22 gestational weeks showed left CDH and ITK, hyperechoic left lung parenchyma, and mediastinal shift. The fetal echocardiography and karyotype were normal. Magnetic resonance imaging at 30 gestational weeks confirmed the ultrasound suspicion of left CDH in association with bowel and left kidney herniation. The fetal growth, amniotic fluid, and Doppler indices remained within the normal range over time. The woman delivered the newborn via an at-term spontaneous vaginal delivery. The newborn was stabilized and underwent non-urgent surgical correction; the postoperative course was uneventful. CDH is the rarest cause of ITK; we found only eleven cases describing this association. The mean gestational age at diagnosis was 29 ± 4 weeks and 4 days. There were seven cases of right and four cases of left CDH. There were associated anomalies in only three fetuses. All women delivered live babies, the herniated kidneys showed no functional damage after their surgical correction, and the prognosis was favorable after surgical repair. The prenatal diagnosis and counseling of this condition are important in planning adequate prenatal and postnatal management in order to improve neonatal outcomes.