Fetal Karyotype Research Articles

Prenatal diagnosis of cystic hygroma cases in a tertiary centre and retrospective analysis of pregnancy results

The aim of this study is to retrospectively examine invasive diagnostic methods, structural anomalies accompanying cystic hygroma, and pregnancy outcomes in cystic hygroma cases admitted to a tertiary centre. The population of the study consisted of 29 live foetuses with cystic hygroma in the foetal neck only in the first or second trimester. In the study, pregnant women who applied to our centre were included. Amniocentesis or chorionic villus sampling was performed for genetic analysis according to the weeks of the pregnant women who were diagnosed with cystic hygroma by ultrasound examination by two clinicians experienced in foetal anomaly. Of the pregnant women included in the study, 10 had normal karyotype, 12 had abnormal karyotype and 13 had structural abnormality. It is very important to provide genetic counselling to the families of foetuses with cystic hygroma with a multidisciplinary team approach consisting of neonatologists, paediatric surgeons and experienced sonographers. Implications for rehabilitation What is already known on this subject? Cystic hygroma, also known as cystic lymphangioma, is a congenital cystic malformation often seen in the first trimester, which occurs in the foetal neck due to the failure of the connections between the cervical lymphatic vessels and the jugular venous system to develop normally. Cystic hygroma may be isolated, but highly associated with foetal aneuploidy, hydrops fetalis, abnormal foetal nuchal translucency. What do the results of this study add? Invasive prenatal diagnostic tests (CVS or amniocentesis) should be performed in all patients with cystic hygroma, as cystic hygromas can be diagnosed by first trimester foetal genetic sonogram screening and are largely accompanied by chromosomal abnormalities. What are the implications of these findings for clinical practice and/or further research? In foetuses with cystic hygroma, foetal karyotyping, detailed sonography and their documentation, genetic counselling is important to families of cystic hygroma foetuses with a multidisciplinary team approach consisting of neonatologists, paediatric surgeons and maternal foetal medicine specialists, since there is a high risk for aneuploidy and foetal malformation.

Experience in the Application of Non-invasive Prenatal Screening for the Detection of Down Syndrome in Russia: A Retrospective Cohort Study

Objectives: Assessment the effectiveness of non-invasive prenatal screening (NIPS) for identifying pregnant women at high risk of giving birth to a child with Down syndrome. Materials and Methods: The retrospective cohort study included 25798 pregnant women who underwent NIPS in Russia from January 2013 to December 2018. 21042 and 4756 participants underwent tests from the Natera laboratory, USA (non-invasive prenatal test 1, NIPT-1) and the Genomed laboratory, Russia (non-invasive prenatal test 2, NIPT-2), respectively. Results: A high risk of trisomy 21 (T21) was detected in 544 cases (2.59%). The mean age in women at high risk of T21 was 37.3 years. According to the NIPT results, in patients who revealed a low risk of T21, the mean age was 33.8 years (P<0.001). In 535 cases, invasive prenatal diagnosis was performed. In 7 (1.3%) cases, the presence of T21 in the fetus was not confirmed. In 528 (97.3%) cases, T21 was confirmed by fetal karyotyping. Among women who revealed a low risk of T21 (N = 25086), in 4 cases (0.015%), fetal trisomy 21 was missed. Thus, the indicators of the effectiveness of NIPS in Russia in relation to T21 are as follows: sensitivity - 99.25%, specificity - 99.96%, PPV - 98.7%, NPV - 99.98%. In the first trimester, in the presence of fetal T21, the level of the fetal fraction of free-DNA is significantly lower. Conclusions: NIPS has good prospects for implementation in pregnancy management programs and increasing the effectiveness of prenatal detection of T21. The level of the fetal fraction is associated with the presence of fetal T21.

Invited Commentary: Role of the Radiologist in Pregnancy-associated Cancer.

Invited Commentary: Role of the Radiologist in Pregnancy-associated Cancer.

Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome

Initially provided as an alternative to evaluation of serum analytes and nuchal translucency for the assessment of pregnancies at high risk of trisomy 21, cell-free DNA screening for fetal aneuploidy, also referred to as noninvasive prenatal screening, can now also screen for fetal sex chromosome anomalies such as monosomy X as early as 9 to 10 weeks of gestation. Early identification of Turner syndrome, a sex chromosome anomaly resulting from the complete or partial absence of the second X chromosome, allows medical interventions such as optimizing obstetrical outcomes, hormone replacement therapy, fertility preservation and support, and improved neurocognitive outcomes. However, cell-free DNA screening for sex chromosome anomalies and monosomy X in particular is associated with high false-positive rates and low positive predictive value. A cell-free DNA result positive for monosomy X may represent fetal Turner syndrome, maternal Turner syndrome, or confined placental mosaicism. A positive screen for monosomy X with discordant results of diagnostic fetal karyotype presents unique interpretation and management challenges because of potential implications for previously unrecognized maternal Turner syndrome. The current international consensus clinical practice guidelines for the care of individuals with Turner syndrome throughout the lifespan do not specifically address management of individuals with a cell-free DNA screen positive for monosomy X. This study aimed to provide context and expert-driven recommendations for maternal and/or fetal evaluation and management when cell-free DNA screening is positive for monosomy X. We highlight unique challenges of cell-free DNA screening that is incidentally positive for monosomy X, present recommendations for determining if the result is a true-positive, and discuss when diagnosis of Turner syndrome is applicable to the fetus vs the mother. Whereas we defer the subsequent management of confirmed Turner syndrome to the clinical practice guidelines, we highlight unique considerations for individuals initially identified through cell-free DNA screening.

Prenatal screening and diagnosis for a fetus with mosaic sex chromosome abnormality

To carry out prenatal screening and diagnosis for a woman with advanced maternal age. Non-invasive prenatal testing (NIPT) was carried out to determine the risk of fetal chromosome aneuploidy. Aminiocentesis was proceeded for fetal chromosomal karyotyping and copy number variation sequencing (CNV-seq). The fetus was subjected to systematic ultrasound screening in the second trimester. NIPT has indicated there was a loss of fetal sex chromosome. Karotyping of the amniocyte showed a mosaic sex chromosome abnormality 45,X[53]/46,X,+mar[7]. The result of fetal DNA CNV-seq was seq[GRCh37]del(Yq11.1q12) chrY: g.13 104 553-28 819 361del, seq[GRCh37]del(Yp11.32p11.2) chrY: g.10 001-9 873 915del (mosaic ratio: 30%). Ultrasonography discovered that the fetus had renal dysplasia and male external genitalia. The karyotypes of the couple were both normal. Multiple genetic tests should be carried out for fetus with a high risk for chromosome aneuploidies signaled by NIPT. It is difficult to predict the post-natal phenotype for fetuses with mosaic sex chromosomal aneuploidies. The couple should be carefully counseled upon genetic counseling.

Case Report: Prenatal Whole-Exome Sequencing Identified a Novel Nonsense Mutation of the KCNH2 Gene in a Fetus With Familial 2q14.2 Duplication

Background: Pathogenic mutations in the KCNH2 gene were associated with long QT syndrome 2 (LQT2), which typically manifest in a prolonged QT interval and may lead to recurrent syncopes, seizure, or sudden death. Limited reports indicated that the KCNH2 mutations would result in LQT2 combined with tetralogy of fallot. Our goal was to present an additional case of LQT2 combined with the tetralogy of fallot in a fetus with a novel KCNH2 mutation. Case presentation: Enrolled in this study was a 23-year-old pregnant woman from Quanzhou Fujian province, China. In her pregnancy, fetal ultrasound anomalies were identified, including tetralogy of fallot, coronary sinus enlargement, and persistent left superior vena cava. No chromosomal abnormality was detected by fetal karyotype analysis. However, 238.1-kb duplication in the 2q14.2 region containing the GLI2 gene was observed in the fetus by chromosomal array analysis, which was inherited from the mother with normal clinical features and interpreted as a variant of uncertain significance (VOUS). Furthermore, whole-exome sequencing (WES) detection identified a novel nonsense c.1907C > G (p.S636*) mutation in the KCNH2 gene in the fetus, and it was classified as a likely pathogenic variant, according to the ACMG guidelines. Parental verification analysis indicated that c.1907C > G (p.S636*) mutation was inherited from the mother. Conclusion: In this study, we believe that 2q14.2 duplication may not be the reason for fetal heart defects; moreover, we described an additional case with KCNH2 gene mutation, which may lead to LQTS and be associated with congenital heart defects. In addition, our study further confirms the application value of the WES technology in prenatal genetic etiology diagnosis of fetuses with structural anomalies and unexplained structural variants.

The assessment of mesenchymal stem cells characteristics in cultured amniotic fluid cells

OBJECTİVES: To evaluate the morphological characteristics, immunophenotypic features, osteogenic, adipogenic, and chondrogenic differentiation capacities of in-vitro cultured amniotic cells during the culture process based on mesenchymal stem cell (MSC).
 MATERİAL/METHOD: This study used waste cells remaining after fetal karyotype determination with second-trimester amniotic cell culture. Cultured cells were morphologically evaluated daily. Selective subculture (SSC) was produced by the scraping method. Immunophenotypic features of primary and subculture amniotic cells were evaluated based on specific surface antigens. Specific growth mediums were used to assess their osteogenic, adipogenic, and chondrogenic differentiation abilities. Differentiation was confirmed using specific staining.
 RESULTS: Fifteen cases with 46,XY fetal cytogenetic analyses at 16+3-19+5 gestational weeks were included in the study. Amniotic fluid cells were evaluated morphologically in three classes as Amniotic fluid specific cell-type(AF), Fibroblastoid cell-type(FB1, FB2), and Epithelioid cell-type(E). The first cell adhesions occurred in the first 24-48 hours(36%) of cell culture, while the first colonies within three days(82%). SSC was produced in AF-SSC(n=4) and FB2-SSC(n=6) directions by mechanical scraping. Primary amniotic fluid cells and AF/FB-SSCs were positive for MSC immunophenotypic markers CD29,CD73,CD166,CD44,CD49e,CD90, while negative for CD34,CD45, and HLA-DR. Cells were shown to have osteogenic (Alizarin Red-S) and chondrogenic (Alcian Blue) differentiation potentials based on histochemical staining, while adipogenic (Oil Red-O) differentiation was not obtained.
 CONCLUSION: We believe that preliminary protocols and experiences to obtain MSCs from amniotic fluid-derived cells produced under routine prenatal diagnosis cell culture conditions can enable many promising pre-clinical/clinical studies and be the pioneer of "stem cell therapy applications" in many "incurable" diseases in the clinic.

Hysteroembryoscopy and hysteroscopic uterine evacuation of early pregnancy loss: A feasible procedure in selected cases.

Hysteroscopic uterine evacuation of early pregnancy loss using tissue removal devices seems to be a safe and feasible procedure in selected cases. The hysteroscopic approach allows the precise localisation of the gestational sac inside the uterine cavity. The endoscopic approach allows one to perform hysteroembryoscopy before uterine evacuation and this technique appears to be more accurate than dilatation & curettage for fetal chromosome karyotyping, with lower maternal cell contamination. This "under vision" procedure may reduce retained products of conception rates and risk of intrauterine adhesions formation.

P-398 HLA expression profile - the picture of successful pregnancy

Abstract Study question Which the difference of HLA profile expression among normal and abnormal karyotype? Summary answer In missed abortion groups, a significant decrease in HLA-G expression is observed in the chorionic villus structures in comparison with normal karyotype group. What is known already The study of pregnant alloimmunity confirms the relationship of recurrent miscarriage with the individual characteristics of the HLA I and II class system (Human leukocyte antigen), which can lead to impaired production of the mixed lymphocyte reaction blocking antibodies (MLR-Bf), anti-paternalcyto-toxicantibodies (APCA) and anti-idiotypic antibodies, Ab2, which are necessary for successful implantation and pregnancy development. For example, HLA-G is mainly restricted to the fetal–maternal interface on the extravillous cytotrophoblast, to placenta, amnion when HLA II class system mostly determinates in dNK, T-cells, macrophages. Study design, size, duration It was a prospective complex cohort study from 2016-2020 years with cytogenetics and pathomorphological investigations. The purpose of this study is to investigate HLA-DR expression in gravid endometrium, HLA-G and KIR2DL4 expression in chorionic villous among 3 groups (study included 115 cases of abortion material): group 1 – 36 cases after missed abortion with normal karyotype, group 2–35 cases after missed abortion with polyploidy and group 3–44 cases after induced abortion group (normal pregnancy). Participants/materials, setting, methods Criteria of inclusion: abortive material from 3 groups of women with missed or after induced abortion; 6-12 weeks, singleton pregnancy, cytogenetic of chorionic villous was obligatorily - normal fetal karyotype and polyploidy of fetus. In this work, we used: cytogenetic method and morphological study (histological-H&E stain, immunohistochemical, morphometric method). Immunohistochemical examination included quantitative and qualitative assessment of the expression of Anti-HLA-DR (mouse monoclonal), Anti-HLA-G (mouse monoclonal) and AntiKIR2DL1+KIR2DL3 + KIR2DL4 + KIR2DS4 (rabbit polyclonal). Main results and the role of chance By IHC the expression of HLA-G in extravillous trophoblast cells but the expression of HLA-DR and KIR2DL4 were detected in stroma, glands, the endometrial epithelium, both in groups.The HLA-G expression area in both groups with missed abortion didn’t differ statistically. But the expression of HLA-G in 3 group was strictly higher (in group 1 with a normal karyotype 37.7, in group 2-36.4, in the control group 67.09, p < 0.001). When divided into subgroups depending on the karyotype, the following data were obtained: in the group with a non-developing pregnancy with a normal karyotype of male fetuses, there is a tendency to lower expression of HLA-G molecules compared to female fetuses (32.96 (10.22) and 41 .45(9.36), respectively). Expression of the KIR2DL4 receptor was verified in chorionic villi (in the cytotrophoblast and syncytiotrophoblast), as well as in the structures of the endometrium, both in the glands, stroma, and in the surface epithelium, regardless of the karyotype. The expression area of the KIR2DL4 receptor did not differ statistically between the three groups (29.6, 33.1 and 27.55, p = 0.75). The expression area of the HLA-DR was detected in each group in gravid endometrium, but it hadn’t statistically differences (44.1, 38.2 and 42.5, p = 0.82). Limitations, reasons for caution No reasons for cautions Wider implications of the findings In missed abortion groups,a significant decrease in HLA-G expression is observed in the chorionic villus structures in comparison with the control group.The mechanism of abortion in groups with missed abortion with both normal karyotype and pathological karyotype of the fetus is identical.HLA-G molecule has a leading role in successful implantation. Trial registration number АААА-А20-120041390025-9

P-427 Pregnancy outcomes following recurrent first-trimester miscarriage: a retrospective cohort study

Abstract Study question What are the subsequent pregnancy outcomes (livebirths, miscarriages or other adverse pregnancy outcomes) in a cohort of women with recurrent miscarriage (RM)? Summary answer The overall live birth rate in women with RM was 62% (466/748), falling to 44% in women aged >40 and 54% in women with infertility. What is known already RM affects approximately 1% of women of reproductive age. RM is recognized as a prognostic indicator for subsequent pregnancies and adverse pregnancy outcomes including ante-partum hemorrhage, diabetes, preterm birth, small for gestational age and perinatal death. While RM has known associations with advanced maternal age, obesity, diabetes, thyroid dysfunction and endometriosis, approximately 50% of women/couples will be left without an explanation for their pregnancy loss, even after completing investigations. Study design, size, duration A retrospective cohort study was undertaken to identify subsequent pregnancy outcomes in women with RM, where RM referral criteria are 3 consecutive first-trimester miscarriages. Women attending the pregnancy loss clinic at a tertiary university hospital in the Republic of Ireland over a 12-year period (2008 - 2020) with a confirmed diagnosis of primary or secondary first-trimester RM were eligible for inclusion. In total, 923 charts were identified for review against the eligibility criteria. Participants/materials, setting, methods Women with non-consecutive first trimester miscarriages or ectopic pregnancy were excluded. Epidemiological and clinical information was gathered from paper and electronic medical records. Data were analysed descriptively using SPSS (Version 27). Main results and the role of chance Of 748 women identified, 332(44%) had primary RM, 416(56%) had secondary RM. The median age was 36(range 19-47) years with 12% aged under 29 and 64% of women aged ≥35. 142(19%) had a history of infertility with 43(5.7%) attending for ART. 12% of women had anti-nuclear antibodies(89/742), 8% had abnormal thyroid function tests(60/742), 4.7% were heterozygous carriers of the Factor V Leiden gene mutation(35/737), 1.5% had positive anti-cardiolipin antibodies(11/733), 2% were carriers of a Prothrombin gene mutation(7/343) and 1% had elevated HbA1c levels(7/742). Fetal karyotype was recorded in 141 pregnancies, with 111 abnormal results(78%;111/141). Trisomy(T) 16 was most common(17/111; 15%) followed by T21 and T22(n = 14; 13%). Parental karyotyping of 697 sets of parents identified 28 balanced translocations(4%; 28/697). Prescribed pharmacological treatments included high dose folic acid(75%; n = 548/728), aspirin(96%; 696/726), progesterone (52%; 389/728), tinzaparin(24%; 175/727), prednisolone(4%; 28/726), metformin(2%; 12/727) and hydroxychloroquine(1%; 7/727). 573 women had a subsequent pregnancy (76.6%); 359(62%; 359/573) had a live birth, 190 had a miscarriage(33%) and 18(3%) had an adverse pregnancy outcome such as ectopic pregnancy, stillbirth or second-trimester miscarriage. Including successive pregnancies over the study period, the overall live birth rate was 62%(466/748), falling to 44% in women aged >40 and 54% in women with infertility. Limitations, reasons for caution This work covers a 12-year period, and while the RM clinic staffing is largely unchanged, some changes in management of RM patients has occurred in this time, reflecting up-to-date evidence and greater public awareness. Furthermore, the adoption of an electronic health chart in 2017 may have affected data availability. Wider implications of the findings Our findings confirm RM occurs more frequently in women aged >35. Aneuploidy remains a leading cause of miscarriage. Age is a prognostic indicator for livebirth after RM. These findings will facilitate counselling in this cohort. The substantial rates of prescribed medications and infertility in women with RM merit further exploration. Trial registration number N/A

Fetal Aberrant Right Subclavian Artery: Associated Anomalies, Genetic Etiology, and Postnatal Outcomes in a Retrospective Cohort Study.

BackgroundAberrant right subclavian artery (ARSA) is becoming increasingly common in fetuses. However, there are relatively fewer studies regarding the genetic etiology of ARSA. We performed a genetic analysis of fetuses with ARSA and followed up on the pregnancy outcomes to evaluate the prognosis of the fetuses, providing information for prenatal and eugenic consultations.MethodsThis retrospective study included 112 pregnant females whose fetuses were diagnosed with ARSA from December 2016 to February 2021. Fetal karyotype analysis and single-nucleotide polymorphism (SNP) array were performed.ResultsThe 112 fetuses were divided into two groups: the isolated ARSA group (n = 48, 42.9%) and the non-isolated ARSA group (ARSA with other ultrasound abnormalities, n = 64, 57.1%). The total rate of pathogenic copy number variation (CNV) observed using karyotype analysis (3/8) and SNP array (5/8) was 7.1% (8/112). The rates of pathogenic CNV in the isolated and non-isolated ARSA groups were 4.2% (2/48) and 9.4% (6/64), respectively. No significant difference was observed between the two groups (P = 0.463). The results of genetic analysis influenced the parents’ decision to terminate the pregnancy. During the follow-up examination, fetuses with ARSA without pathogenic CNV were found to have normal growth and development after birth.ConclusionFetuses with isolated ARSA have a low probability of being diagnosed with pathogenic CNV. However, when ARSA is complicated with other ultrasound abnormalities, the risk of pathogenic CNV remarkably increases. Prenatal genetic counseling and SNP-array should be recommended for better assessment of fetal prognosis.

Diagnostic yield of exome sequencing in fetuses with multisystem malformations: systematic review and meta-analysis.

To determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with multisystem structural anomalies (at least two major anomalies in different anatomical systems). This was a systematic review conducted in accordance with PRISMA guidelines. Searching PubMed, Web of Knowledge and Cochrane database, we identified studies describing ES, whole-genome and/or next-generation sequencing in fetuses with multisystem malformations. Included were observational studies involving five or more eligible fetuses. A fetus was eligible for inclusion if it had at least two major anomalies of different anatomical systems and a negative CMA or karyotyping result. Only positive variants classified as likely pathogenic or pathogenic determined to be causative of the fetal phenotype were considered. A negative CMA or karyotype result was treated as the reference standard. The diagnostic yield of the primary outcome was calculated by single-proportion analysis using random-effects modeling. A subgroup analysis was performed to compare the diagnostic yield of the solo approach (fetus alone sequenced) with that of the trio approach (fetus and both parents sequenced). Seventeen articles with data on ES diagnostic yield, including 694 individuals with multisystem malformations, were identified. Overall, a pathogenic or likely pathogenic variant potentially causative of the fetal phenotype was found in 213 fetuses, giving a 33% (95% CI, 27-40%) incremental yield of ES. A stratified analysis showed similar diagnostic yields of ES using the solo approach (30%; 95% CI, 11-52%) and the trio approach (35%; 95% CI, 26-44%). ES applied in fetuses with multisystem structural anomalies was able to identify a potentially causative gene when CMA or karyotyping had failed to do so in an additional one-third of cases. No differences were observed between the solo and trio approaches for ES. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of pregnancies with first-trimester increased nuchal translucency and cystic hygroma in a tertiary maternity hospital in United Arab Emirates.

To study the outcome of pregnancies with first-trimester increased nuchal translucency and cystic hygromas. Retrospective study of 132 pregnancies with first-trimester increased nuchal translucency and cystic hygromas, between January 2015 to December 2018 at Corniche Hospital, Abu Dhabi, UAE. Fetal karyotyping, detailed ultrasound at 18-22 weeks and fetal echocardiography were offered to all women. Adverse outcomes included miscarriage, intrauterine fetal death, termination of pregnancy, neonatal death and structural abnormalities. Of the 132 pregnancies, 13 had NT > 95th percentile, 89 had NT ≥3 mm and 30 had cystic hygroma. Among 13 pregnancies with NT > 95th centile, 7.6% had abnormal karyotype. Among 89 pregnancies with NT ≥3 mm, 29.2% had abnormal karyotype, 13.4% miscarriage, 7.8% underwent TOP, 5.6% intrauterine fetal death, 1.1% neonatal death and 14.6% had structural abnormalities. Among 30 pregnancies with cystic hygroma, 40% had abnormal karyotype, 20% miscarriage, 13.3% TOP, 13.3% intrauterine fetal death, 6.6% had neonatal death and 20% had structural abnormalities. In our study, karyotype abnormalities increased with increasing nuchal translucency with highest risk in fetuses with cystic hygromas. Increased nuchal translucency was associated with adverse pregnancy outcome, which was higher in the group with NT≥6 mm and cystic hygromas.

Obstetrical and oncological outcomes of twin pregnancies with hydatidiform mole and coexisting fetus

ObjectiveTo evaluate the obstetrical and oncological progression of twin pregnancies with hydatidiform mole coexisting fetus (HMCF). Materials and methodsUsing a retrospective method based on patients from the Women's Hospital, Zhejiang University School of Medicine database between January 1990 and October 2020, 17 patients were histologically confirmed as having HMCF, and the patients' prenatal diagnosis, outcomes and development of gestational trophoblastic neoplasia (GTN) were reviewed. ResultsAmong these 17 cases, 11 (64.71%) cases were complete hydatidiform mole coexisting fetus (CHMCF), and 6 (35.29%) cases were partial hydatidiform mole coexisting fetus (PHMCF). The gestational age at diagnosis of CHMCF was significantly earlier than that of PHMCF [9 (8–24) vs. 18 (11–32) weeks, respectively, P < 0.05]. The live birth rate of PHMCF was slightly higher than that of CHMCF (33.33%; 18.18%), but this difference was not statistically significant. The overall rate of GTN incidence of HMCF was 47.06% (8/17), and the GTN rates of PHMCF and CHMCF were 33.33% (2/6) and 54.55% (6/11), respectively. There was no significant difference in the GTN rate between patients who chose to continue pregnancy and those who terminated pregnancy before 24 weeks of gestation. The GTN rate of patients with term delivery was not significantly higher than that of preterm delivery. ConclusionIn HMCF cases, the incidence rate of CHMCF was higher than that of PHMCF, and PHMCF is more difficult to diagnose in the early stage. Continuing pregnancy does not increase the risk of GTN compared to terminating pregnancy. In cases of HMCF, when the fetal karyotype is normal and maternal complications are controlled, it is safe to continue the pregnancy and extend it to term.

Factors associated with fetal karyotype in spontaneous abortion: a case-case study

BackgroundMost embryos that spontaneously abort during early pregnancy are found to have chromosomal abnormalities. The purpose of this study is to explore the factors involved in chromosome aberrations during embryogenesis.MethodsA case-case study was performed to compare the risk factors for spontaneous abortion with and without embryo chromosome aberration. A total of 160 cases of spontaneous abortion were enrolled from a tertiary general hospital in Kunming. KaryoLite BACs-on-Beads (KL-BoBs) and fluorescence in situ hybridization (FISH) were employed to determine chromosomal constitution of abortion chorion villus samples. Maternal serum levels of homocysteine (Hcy) were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Information about clinical background and environmental exposure was collected through a self-designed questionnaire. To identify the inherited chromosomal abnormalities, couples with chromosomal abnormalities in abortus were recalled for karyotyping.ResultsThe overall rate of chromosomal abnormalities was 62.5% (100/160, KL-BoBs combined with FISH) including 51.9% (83/160) aneuploidies, 6.3% (10/160) polyploidies, and 4.4% (7/160) structural abnormalities. Only one case of structural abnormality was found to be inherited from maternal balanced translocation. Compared to abortus with normal karyotype, abortus with abnormal karyotype showed a positive association with parental age and elevated maternal serum homocysteine (Hcy) level, but negative association with previous miscarriage and perceived noise.ConclusionsEmbryonic chromosomal aberrations accounted for the majority of spontaneous abortion cases. A combination of internal and external factors may induce spontaneous abortion through fetal chromosomal aberrations or other pathogenic mechanisms.

Human amniotic fluid as a source of stem cells.

Human amniotic fluid collected during amniocentesis contains a heterogeneous population of differentiated and undifferentiated cells. Properties and number of these cells vary depending on the gestational age and the presence of potential fetal pathologies. The aim of this study was to analyze the effects of maternal, fetal, and environmental factors on the success rates of amniotic fluid stem cell cultures, the number of human amniotic fluid stem cells (hAFSC), their growth rates in primary cultures, and the number of cell passages. The study included 355 patients qualified for genetic amniocentesis at the Prenatal Genetic Unit, Department of Obstetrics, Gynecology and Oncologic Gynecology, Nicolaus Copernicus University Medical College in Bydgoszcz in 2011–2017. The mean age of the study participants was 34 ± 6.2 years, and mean gravidity amounted to 2.48 ± 1.4. Amniotic fluid sample volume turned out to be a highly significant (p < 0.01) predictor of culture success, and the relationship was particularly evident in women older than 40 years. Another highly significant predictor of culture success was the presence of two cell populations in the sample (p < 0.01). The likelihood of culture success correlated significantly (p < 0.05) with the season of the year at the time of amniocentesis. The number of cell passages differed significantly depending on the maternal age (p < 0.01). The number of passages also showed a highly significant relationship with the season of the year the sample was obtained (p < 0.01). Younger maternal age was identified as a determinant of high passage number (≥3), and another highly significant determinant of high passage number was the presence of two cell populations in the amniotic fluid sample (p < 0.01). Percentage of successfully established hAFSC cultures and the number of passages depended on amniotic fluid volume, the presence of two cell populations within the sample, and the season of the year. Individual characteristics of the donors, such as age and gravidity, did not exert a significant effect on the number of isolated hAFSCs and the rate of their growth. Patients’ place of residence, fetal karyotype, transportation time, and purity of the samples did not affect the success rates for primary cultures and the number of passages.

Genome wide noninvasive prenatal testing detects microduplication of the distal end of chromosome 15 in a fetus: a case report

BackgroundNoninvasive prenatal testing (NIPT) is the most recent modality widely used in prenatal diagnostics. Commercially available NIPT has high sensitivity and specificity for the common fetal chromosomal aneuploidies. As future advancements in NIPT sequencing technology are becoming promising and more reliable, the ability to detect beyond aneuploidies and to expand detection of submicroscopic genomic alterations, as well as single-gene disorders might become possible.Case presentationHere we present a case of a 34-year-old pregnant woman, G2P1, who had NIPT screening which detected a terminal microduplication of 10.34 Mb on the long arm of chromosome 15 (15q26.1q26.3). Subsequent prenatal diagnostic testing including karyotype, microarray and fluorescence in situ hybridization (FISH) analyses were performed. Microarray testing confirmed and particularized a copy number gain of 10.66 Mb of the distal end of the long arm of chromosome 15. The G-banding cytogenetic studies yielded results consistent with unbalanced translocation between chromosome 15 and 18. To further characterize the abnormality involving the long arm of chromosome 18 and to map the genomic location of the duplicated 15q more precisely, FISH analysis using specific sub-telomeric probes was performed. FISH analysis confirmed that the extra duplicated segment of chromosome 15 is translocated onto the distal end of the long arm of chromosome 18 at band 18q23. Parental karyotype and FISH studies were performed to see if this unbalanced rearrangement was inherited from a healthy balanced translocation carrier versus being a de novo finding. Parental chromosomal analysis provided no evidence of a rearrangement between chromosome 15 and chromosome 18. The final fetal karyotype was reported as 46,XX,der(18)t(15;18)(q26.2;q23)dn.ConclusionsIn this case study, the microduplication of fetal chromosome 15q26.1q26.3 was accurately detected using NIPT. Our results suggest that further refinements in NIPT have the potential to evolve to a powerful and efficient screening method, which might be used to detect a broad range of chromosomal imbalances. Since microduplications and microdeletions are a potential reportable result with NIPT, this must be included in pre-test counseling. Prenatal diagnostic testing of such findings is strongly recommended.

A Nonimmune Hydrops Case.

A Nonimmune Hydrops Case.

Spectrum of Chromosomal Abnormalities Detected by Conventional Cytogenetic Analysis Following Invasive Prenatal Testing of Fetuses with Abnormal Ultrasound Scans.

The frequent association between malformations and chromosomal abnormalities is now well-established. This study looks at the incidence and type of chromosomal abnormalities detected by conventional cytogenetic analysis in women undergoing invasive tests following detection of fetal anomalies on antenatal scans as well as incidence of other genetic abnormalities detected by DNA analysis of fetuses with congenital anomalies that had a normal karyotype. A retrospective, observational study of pregnant women undergoing invasive testing following identification of fetal anomalies by ultrasonography was carried out in a tertiary care facility, Vellore, India, between 2011 and 2018. 169 women underwent an invasive diagnostic procedure following detection of fetal anomalies. The most common indication for doing fetal karyotype was the presence of major fetal structural anomalies (142/169, 84%) with over a third (48/142, 34%) having multisystem involvement. Fetal hydrops was the next most common indication, detected in 18/169 (10%) fetuses. Aneuploidy was seen 19 of 25 fetuses (76%) with an abnormal karyotype with autosomal aneuploidy accounting for 13 (68%) and sex chromosome aneuploidy for seven (37%) of the fetuses. One fetus had double aneuploidy. In fetuses with normal karyotype, no additional information was obtained from further genetic testing. The overall detection rate of chromosomal abnormalities in our study using conventional cytogenetic analysis was 14.8%, the majority (72%) being associated with structural malformations, 20% with non-immune hydrops and 4% with soft markers. Abnormal karyotypes were seen in 12.7% of fetuses with structural malformations.

Evaluation of prenatal central nervous system anomalies: obstetric management, fetal outcomes and chromosome abnormalities

ObjectiveTo study the outcomes of fetuses who were diagnosed with central nervous system (CNS) anomalies during prenatal period and to describe the obstetric management of those pregnancies.MethodsIn this retrospective study, fetuses who were detected to have central nervous system anomalies by prenatal ultrasound from January 2010 to December 2019 were recruited. Data regarding prenatal diagnosis and obstetric outcomes were retrieved from maternal and paediatric records. The prognosis of fetuses who were born alive was classified based on their neurodevelopmental outcome within two years of life.ResultsThere were a total of 365 fetuses with CNS anomalies within the 10-year study period, with a mean gestational age of 24.65±7.37 weeks at diagnosis. Ventriculomegaly (23.36%) was the commonest CNS anomalies seen. 198 (54.20%) of these fetuses had associated extra-CNS anomalies, with cardiovascular being the most common system involved. Fetal karyotyping was performed in 111 pregnancies, with chromosomal aberrations detected in 53 (49.07%) cases and culture failure in 3 cases. Majority of the chromosomal abnormalities were Edward syndrome (trisomy 18) and Patau syndrome (trisomy 13). Fetuses with congenital CNS anomalies and abnormal chromosomal karyotyping were more likely to be diagnosed earlier by prenatal ultrasound and tend to have poorer obstetric and neurocognitive prognosis. Prenatally, 86 (23.56%) of the cases were lost to follow up and likely to deliver elsewhere. Among the 279 cases whom their pregnancy outcomes were available, 139 (49.82%) pregnancies resulted in live births, 105 (37.63%) pregnancies were electively terminated, while the remaining 35 (12.54%) pregnancies ended in spontaneous loss. The decision of termination of pregnancy largely depends on mean diagnostic gestational age, presence of chromosomal aberrations and abnormal amniotic fluid volume in those fetuses. Two years after delivery, only 75 (53.96%) children out of 139 live births were still alive, 43 (30.93%) died and 21 (15.11%) cases were lost to follow-up. 32 (23.02%) children with prenatally diagnosed CNS anomalies had normal neurodevelopmental outcome. The presence of multiple CNS anomalies and involvement of extra-CNS anomalies indicated a poorer neurodevelopmental prognosis.ConclusionLess than 50% of fetuses with prenatally diagnosed CNS anomalies resulted in live births. Even if they survive till delivery, 36.45% of them passed away within 2 years and 62.79% of children who survived till 2 years old had neurodevelopmental disability.