Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations.

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

Experience of copy number variation sequencing applied in spontaneous abortion.

PURPOSE: We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. METHODS: A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. RESULTS: Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30-34 years (P < 0.05). CONCLUSION: Chromosomal abnormalities are the most common cause of pregnancy loss, and maternal and gestational ages are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of the gestational age, modes of conception or previous abortion status.

Analysis of retest reliability for pregnant women undergoing cfDNA testing with a no-call result.

BACKGROUND: Determining the reasons for unreportable or no-call cell-free DNA (cfDNA) test results has been an ongoing issue, and a consensus on subsequent management is still lacking. This study aimed to explore potential factors related to no-call cfDNA test results and to discuss whether retest results are reliable. METHODS AND RESULTS: This was a retrospective study of women with singleton pregnancies undergoing cfDNA testing in 2021. Of the 9871 pregnant patients undergoing cfDNA testing, 111 had a no-call result, and their results were compared to those of 170 control patients. The no-call rate was 1.12% (111/9871), and the primary cause for no-call results was data fluctuation (88.29%, 98/111). Medical conditions were significantly more frequent in the no-call group than in the reportable results group (P < 0.001). After retesting, 107 (107/111, 96.40%) patients had a result, and the false-positive rate (FPR) of retesting was 10.09% (10.09%, 11/109). In addition, placental lesions were more frequent in the no-call group than in the reportable results group (P = 0.037), and 4 patients, all in the no-call group, experienced pregnancy loss. CONCLUSIONS: Pregnant women with medical conditions are more likely to have a no-call result. A retest is suggested for patients with a no-call result, but retests have a high FPR. In addition, pregnant women with a no-call result are at increased risk of adverse pregnancy outcomes. In conclusion, more attention should be given to pregnant women for whom a no-call cfDNA result is obtained.

Non-invasive prenatal testing for the diagnosis of congenital abnormalities: Insights from a large multicenter study in southern China.

Although non-invasive prenatal testing (NIPT) is widely used to detect fetal abnormalities, the results of NIPT vary by population, and data for the screening efficiency of NIPT positive predictive value (PPV) from different populations is limited. Herein, we retrospectively analyzed the NIPT results in a large multicenter study involving 52,855 pregnant women. Depending on gestational age, amniotic fluid or umbilical cord blood was extracted for karyotype and/or chromosome microarray analysis (CMA) in NIPT-positive patients, and the PPV and follow-up data were evaluated to determine its clinical value. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 chromosomal abnormalities, with a PPV of 45.1%. PPV for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosomal aneuploidies (SCAs), and copy number variations (CNVs) were 78.9, 35.3, 22.2, 36.9, and 32.9%, respectively. The PPVs for T21, T18, and T13 increased with age, whereas the PPVs for SCAs and CNVs had little correlation with age. The PPV was significantly higher in patients with advanced age and abnormal ultrasound. The NIPT results are affected by population characteristics. NIPT had a high PPV for T21 and a low PPV for T13 and T18, and screening for SCAs and CNVs showed clinical significance in southern China.

Using single nucleotide polymorphism array for prenatal diagnosis in a large multicenter study in Southern China.

Numerous studies have evaluated the use of single nucleotide polymorphism array (SNP-array) in prenatal diagnostics, but very few have evaluated its application under different risk conditions. Here, SNP-array was used for the retrospective analysis of 8386 pregnancies and the cases were categorized into seven groups. Pathogenic copy number variations (pCNVs) were found in 699 (8.3%, 699/8386) cases. Among the seven different risk factor groups, the non-invasive prenatal testing-positive group had the highest pCNVs rate (35.3%), followed by the abnormal ultrasound structure group (12.8%), and then the chromosomal abnormalities in the couples group (9.5%). Notably the adverse pregnancy history group presented with the lowest pCNVs rate (2.8%). Further evaluation of the 1495 cases with ultrasound abnormalities revealed that the highest pCNV rates were recorded in those cases with multiple system structure abnormalities (22.6%), followed by the groups with skeletal system (11.6%) and urinary system abnormalities (11.2%). A total of 3424 fetuses with ultrasonic soft markers were classified as having one, two, or three ultrasonic soft markers. The different pCNV rates in the three groups were statistically significant. There was little correlation between pCNVs and a previous history of adverse pregnancy outcomes, suggesting that genetic screening under these conditions should be evaluated on a case-by-case basis.

Genetic disorders and pregnancy outcomes of non-immune hydrops fetalis in a tertiary referral center.

OBJECTIVES: Non-immune hydrops fetalis (NIHF) is a non-specific symptom associated with a wide range of disorders. The prognosis of NIHF depends on the underlying etiology. In this study, we investigated the incidence of chromosomal abnormalities and Bart's hydrops fetalis in pregnancies associated with NIHF in South China. METHODS: We conducted a retrospective review of NIHF pregnancies referred to the Fujian Provincial Maternity and Children's Hospital between 2014 and 2018, excluding pregnancies with maternal alloimmunization. Routine karyotyping was performed on all 129 enrolled patients, and chromosomal microarray analysis was performed for 35 cases with a normal karyotype. In addition, α-thalassemia genotyping was performed to confirm the presence of Bart's hydrops fetalis. RESULTS: Chromosomal abnormalities were detected in 29.5% (38/129) of the cohort, including 37 cases with aneuploidy and one case with unbalanced structural rearrangement. Chromosomal microarray analysis performed on the 35 cases with a normal karyotype did not reveal any additional pathogenic variants. The proportions of chromosomal abnormalities declined with trimester progression, with frequencies of 65%, 30.1%, and 8.3% in the first, second, and third trimesters, respectively (p < 0.05). Bart's hydrops fetalis was detected in 34.9% (45/129) of the cohort. Among the 46 (35.6%) cases with unknown etiology, 23 cases had other ultrasonic abnormalities characterized by poor outcomes, whereas seven cases with multiple cavity effusions that resolved or remitted prior to birth showed normal development during the 3-4 years of follow-up. CONCLUSIONS: In South China, Bart's hydrops fetalis and chromosomal abnormalities are the most common genetic etiologies of NIHF. Generalized skin edema and accompanying ultrasonic abnormalities are predictive of adverse outcomes, highlighting the need for intensive monitoring and better pregnancy management of NIHF patients.

Fetal genetic findings by chromosomal microarray analysis and karyotyping for fetal growth restriction without structural malformations at a territory referral center: 10-year experience.

BACKGROUND: Prenatal invasive genetic testing is commonly recommended to pregnancies of early-onset FGR or FGR combined with a structural defect. Our study aimed to explore the genetic findings for FGR without structural malformations according to cytogenetic karyotyping and single nucleotide polymorphism array (SNP array) technology over a 10-year period. METHODS: A total of 488 pregnancies diagnosed with FGR without structural malformation were retrospectively reviewed. Cytogenetic karyotyping was performed on all the subjects, and SNP array was available from 272 of them. Based on the gestational age at onset, the cohort was classified into four groups: ≤ 24, 25-28, 29-32, and > 32 weeks of gestation. According to the ultrasound findings, they were grouped into isolated FGR, FGR with soft markers, and FGR with non-structural anomalies. In pregnancies of young maternal age, based on the results of maternal serum screening (MSS), they were categorized into high-risk and low-risk MSS groups. RESULTS: Nineteen (3.9%) cases of chromosomal abnormalities were detected by cytogenetic karyotyping, including 11 cases of numerical abnormalities, 5 cases of structural abnormalities, and 3 cases of mosaicism. Trisomy 21 was the most frequent abnormality. Abnormal karyotypes were more frequently observed in cases diagnosed at ≤ 24 weeks (7.2%) than those in any other group. Among pregnancies with normal karyotype, an incremental yield of 4.2% were revealed by SNP array technology regarding clinically relevant aberrations. The additional detection rates by SNP array in cases diagnosed at ≤ 24 weeks (6.5%), cases with soft markers (9.5%), and cases with high-risk MSS (12.0%) were higher than those in other groups within each classification. All the cases with abnormal karyotypes and 7 out of 11 pregnancies with clinically relevant anomalies revealed by SNP array alone resulted in pregnancy terminations. CONCLUSION: Chromosome abnormality is an important etiology for FGR with no associated structural malformations, and plays a crucial role in pregnancies decision-making. SNP array improves the detection of genetic anomalies especially in FGR diagnosed at ≤ 24 weeks, FGR combined with soft makers, and FGR combined with high-risk MSS.

Non-invasive prenatal testing for the diagnosis of congenital abnormalities: Insights from a large multicenter study in southern China

Although non-invasive prenatal testing (NIPT) is widely used to detect fetal abnormalities, the results of NIPT vary by population, and data for the screening efficiency of NIPT positive predictive value (PPV) from different populations is limited. Herein, we retrospectively analyzed the NIPT results in a large multicenter study involving 52,855 pregnant women. Depending on gestational age, amniotic fluid or umbilical cord blood was extracted for karyotype and/or chromosome microarray analysis (CMA) in NIPT-positive patients, and the PPV and follow-up data were evaluated to determine its clinical value. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 chromosomal abnormalities, with a PPV of 45.1%. PPV for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosomal aneuploidies (SCAs), and copy number variations (CNVs) were 78.9, 35.3, 22.2, 36.9, and 32.9%, respectively. The PPVs for T21, T18, and T13 increased with age, whereas the PPVs for SCAs and CNVs had little correlation with age. The PPV was significantly higher in patients with advanced age and abnormal ultrasound. The NIPT results are affected by population characteristics. NIPT had a high PPV for T21 and a low PPV for T13 and T18, and screening for SCAs and CNVs showed clinical significance in southern China.

APA scoring system: a novel predictive model based on risk factors of pregnancy loss for recurrent spontaneous abortion patients.

The aim of this study was to analyse the risk factors of pregnancy loss of patients with recurrent spontaneous abortion (RSA) and develop a scoring system to predict RSA. Clinical data of 242 cases, with RSA who were treated at Fujian Provincial Maternity and Children's Hospital, were selected. The factors of pregnancy loss for RSA patients were evaluated by univariate and multivariate analyses. There were 242 RSA patients, of whom 34 (14.0%) developed pregnancy loss. A multivariate analysis showed the following adverse risk factors for RSA: antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies. The pregnancy loss rates of antinuclear antibody spectrum group, protein S deficiency group and antiphospholipid antibodies group were 25.0%, 22.5% and 19.4%, respectively. Each of these factors contributed 1 point to the risk score. The pregnancy loss rates were 6.3%, 24.6%, 50% for the low-, intermediate- and high-risk categories, respectively (p < .001). The area under the receiver operating characteristic curve for the score of RSA was .733. Our findings suggest that this validated and simple scoring system could accurately predict the risk of pregnancy loss of RSA patients. The score might be helpful in the selection of risk-adapted interventions to decrease the incidence. Impact StatementWhat is already known on this subject? The live birth rate increases to 80%-90% after anticoagulant and/or immunosuppressive treatment in patients with RSA. However, there is still a high rate of re-abortion even after active treatment.What do the results of this study add? Antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies were independent risk factors for pregnancy loss. A novel predictive model based on these factors was then established and validated.What are the implications of these findings for clinical practice and/or further research? The newly developed score might be helpful in the selection of risk-adapted interventions to decrease the incidence. For patients in the intermediate-risk and high-risk groups, we should conduct more targeted studies and formulate corresponding therapies to improve the success rate of treatment.

Comprehensive Assessment of Fetal Bilateral Ventriculomegaly Based on Genetic Disorders, Cytomegalovirus Infection, Extra Prenatal Imaging and Pregnancy Outcomes in a Tertiary Referral Center.

OBJECTIVE: This retrospective study aimed to systematically evaluate the genetic disorders, cytomegalovirus (CMV) infection, extra ultrasound findings and outcomes of fetuses with bilateral ventriculomegaly (BVM). METHODS: Data from pregnancies with fetal BVM were obtained between 2014 and 2020. The cases were divided into groups of isolated bilateral ventriculomegaly (IBVM) and non-isolated bilateral ventriculomegaly (NIBVM) according to the presence of extra prenatal imaging. Subgroups of mild, moderate, and severe were determined according to lateral ventricle widths. The NIBVM group was further classified into pregnancies with soft markers, non-structural abnormalities, and structural abnormalities. RESULTS: A total of 353 pregnancies were enrolled, including 153 cases of IBVM and 200 cases of NIBVM. Conventional karyotyping was performed on 192 samples, and 15 cases of numerical abnormalities and 3 cases of unbalanced structural abnormalities were identified. Chromosomal microarray analysis (CMA) was concurrently performed on 108 of them and revealed additional 5 cases (4.7%) of copy number variants with clinical significance. CMV DNA testing was performed on 154 of the 192 cases that underwent invasive prenatal diagnosis, and a positive result was found in 2 (1.3%) cases. In the IBVM group, the percentage of favorable prognosis in the mild, moderate and severe pregnancies were 94.4%, 79.2%, and 4.8%, respectively, and the termination of pregnancy (TOP) rates were 4.6%, 20.8%, and 85.7%, respectively. In both the mild and moderate NIBVM, the TOP rates progressively increased and the favorable prognosis survival rates progressively decreased relative to the soft markers, non-structural abnormalities, and structural abnormalities, respectively. Approximately 94.1% of severe NIBVM ended in termination. CONCLUSION: Genetic disorders and fetal infection are important etiology of BVM. CMA is highly recommended for genetic disorders' evaluation. Pregnancies with severe BVM always ended in TOP, while in mild-to-moderate NIBVM, prenatal imaging by ultrasound and/or MRI plays important roles in the pregnancy outcomes.

Chinese mothers' intention to vaccinate daughters against human papillomavirus (HPV), and their vaccine preferences: a study in Fujian Province.

Little is known regarding Chinese mothers' intention to vaccinate their daughters against human papillomavirus (HPV) since the HPV vaccine was approved for use in China in 2016. The aim was to explore maternal HPV vaccination acceptance, preference for 2-, 4- or 9-valent HPV vaccine and acceptance of domestically manufactured HPV vaccines. Study participants were mothers of primary school children in Southeastern region of Fujian. An online cross-sectional survey was undertaken between June and August 2019. Among the total of 3,586 completed responses (response rate 28.5%), the intention to vaccinate daughter against HPV was high (83.3%). Higher maternal education and perceived benefit and barriers were associated with greater intention to vaccinate. Among mothers who did not intend to vaccinate their daughters, the three most common reasons were daughter being too young to receive HPV vaccination (40.6%), fear of side effects (31.9%) and vaccine price is too high (16.0%). The largest proportion (41.4%) preferred their daughter to be vaccinated with the 9-valent HPV vaccine (9vHPV). Greater preference for 9vHPVwas strongly associated with higher maternal education level and annual household income. The majority of mothers expressed a preference for imported HPV vaccine (56.3%). Our result indicates that lower intentions to vaccinate daughters against HPV among less educated and lower-income mothers may lead to significant social inequalities in HPV vaccine uptake in the country.

Peripheral Blood Inflammatory-Immune Cells as a Predictor of Infertility in Women with Polycystic Ovary Syndrome.

PURPOSE: This study aimed to investigate the inflammatory-immune cells in the peripheral blood of women with polycystic ovary syndrome (PCOS) and assessed the potential correlation between inflammatory-immune cells and infertility in PCOS women. MATERIALS AND METHODS: In this case-control study, the profiles of lymphocyte subsets were analyzed by flow cytometry. White blood cells (WBC), neutrophils (Neu), lymphocytes, Ferriman-Gallwey (F-G) score, testosterone, prolactin, follicle-stimulating hormone, luteinizing hormone, fasting blood glucose, and fasting plasma insulin were measured, together with body mass index. Association between inflammatory-immune cells and PCOS was evaluated. Moreover, inflammatory-immune cells of the PCOS women with infertility were evaluated, and the relative operating characteristic (ROC) curve and cutoff values were calculated. RESULTS: The number of WBC, Neu, and lymphocytes was higher in PCOS women than controls (P<0.05). The percentages of total T lymphocytes, CD4+T, and NK were significantly increased in the PCOS group (P<0.001). The CD4/CD8 ratio was obviously elevated for increasing CD4+T (P<0.05). Consequently, T%, CD4+T%, and NK% were found to be the independent risk factors of PCOS by ROC curve and multivariate logistic regression analysis. Furthermore, only NK% was significantly higher in PCOS women with infertility than those who had PCOS without infertility (P<0.001). To diagnose infertility in PCOS, the cutoff value of NK% was calculated as 16.43%. CONCLUSION: These findings suggest that the pathogenesis of PCOS is related to immune cells including T, CD4+T, and NK cells. NK cells are likely to be a potential predictive factor for PCOS women with infertility.

HPV vaccination intent and willingness to pay for 2-,4-, and 9-valent HPV vaccines: A study of adult women aged 27-45 years in China.

OBJECTIVE: This study aims to investigate acceptance and willingness to pay for HPV vaccination among adult women in China. METHODS: An online survey was sent to mothers aged 27-45 years of primary school pupils in the Fujian province, China. Participants completed questions about HPV related knowledge and health beliefs, intention to take the HPV vaccine and the willingness to pay for bivalent vaccine (2vHPV), quadrivalent vaccine (4vHPV), and 9-valent HPV vaccine (9vHPV). RESULTS: Of a total of 2339 complete responses, 58.3% reported intent to obtain HPV vaccine. Mothers who were younger in age, residing in urban, working in managerial or professional occupations, who knew someone with cervical cancer and who were able to make independent decisions about the HPV vaccine (vs. joint decision with spouse) were more likely to express intent to have HPV vaccination. Perceived barriers, cues to action and self-efficacy were three of the constructs in the health belief model that significantly influenced HPV vaccination intent. A higher proportion of participants expressed willingness to pay for 2vHPV (81.2%) and 4vHPV (75.9%), as compared to 9vHPV (67.7%). CONCLUSION: Adults women expressed moderate intention to receive the HPV vaccine. Intervention to address barriers to uptake of the HPV vaccine among adult women in China is warranted.

LZAP promotes the proliferation and invasiveness of cervical carcinoma cells by targeting AKT and EMT.

Objective: To explore the relationship and mechanism of LZAP in the occurrence and development of cervical cancer and to provide a new target and intervention method for the treatment of cervical cancer. Methods: Data mining and analysis of LZAP expression levels were performed using several online databases, including The Cancer Genome Atlas (TCGA). A cervical cancer cell line that stably overexpresses LZAP was established, and the effect of LZAP overexpression on cell proliferation, invasion, migration and tumor formation in vivo as well as its mechanism were explored. Results: Our study shows that the expression of LZAP is upregulated in cervical cancer. The overexpression of LZAP can significantly promote the proliferation, colony formation, and invasion and migration abilities of cervical cancer cells. The tumorigenesis test in nude mice showed that overexpression of LZAP could promote the tumorigenicity of cervical cancer cells in vivo. LZAP could also promote the phosphorylation of AKT at position 473 and the epithelial-mesenchymal transition (EMT). Conclusion: The expression of LAZP is increased in cervical cancer, which can enhance the invasion, metastasis, and EMT in cervical cancer cells by promoting AKT phosphorylation.

X-linked ichthyosis: Molecular findings in four pedigrees with inconspicuous clinical manifestations.

BACKGROUND: X-linked ichthyosis (XLI) is the second most common type of ichthyosis, which is characterized by wide and symmetric distribution of adherent, dry, and polygonal scales on the skin. Steroid sulfatase (STS) gene, which is located at chromosome Xp22.31, has been identified as the pathogenic gene of XLI. METHODS: In this study, chromosome karyotype analysis, bacterial artificial chromosomes-on-Beads™ (BoBs) assay, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP-array) were employed for the prenatal diagnoses in three pregnant women with high-risk serological screening results and a pregnant woman with mental retardation. RESULTS: STS deletion was identified at chromosome Xp22.31 in all four fetuses. Postnatal follow-up confirmed the diagnosis of ichthyosis in two male fetuses and revealed normal dermatological manifestations in other two female fetuses carrying ichthyosis. CONCLUSION: The results of the present study demonstrate that a combination of karyotypying, prenatal BoBs, FISH, and SNP-array may avoid the missed detection of common microdeletions and ensure the accuracy of the detection results, which provides a feasible tool for the reliable etiological diagnosis and better genetic counseling of XLI.