UNASSIGNED: Noninvasive prenatal testing (NIPT) is the most common method for prenatal aneuploidy screening. Low fetal fraction (LFF) is the primary reason for NIPT failure. Consequently, factors associated with LFF should be elucidated for optimal clinical implementation of NIPT.
UNASSIGNED: In this study, NIPT data from January 2019 to December 2022 from the laboratory records and obstetrical and neonatal data from the electronic medical records were collected and analyzed. Subjects with FF >3.50% were assigned to the control group, subjects with FF <3.50% once were assigned to the LFF group, and subjects with FF <3.50% twice were assigned to the repetitive low fetal fraction (RLFF) group. Factors, including body mass index (BMI), gestational age, maternal age, twin pregnancy, and in vitro fertilization (IVF) known to be associated with LFF were assessed by Kruskal-Wallis H test and logistic regression. Clinical data on first trimester pregnancy-associated plasma protein-A (PAPP-A), beta-human chorionic gonadotropin (β-hCG), gestational age at delivery, birth weight at delivery, and maternal diseases were obtained from the hospital\'s prenatal and neonatal screening systems (twin pregnancy was not included in the data on gestational age at delivery and the control group did not include data on maternal diseases.), and were analyzed using Kruskal-Wallis H test and Chi-square test.
UNASSIGNED: Among the total of 63,883 subjects, 63,605 subjects were assigned to the control group, 197 subjects were assigned to the LFF group, and 81 subjects were assigned to the RLFF group. The median of BMI in the three groups was 22.43 kg/m2 (control), 25.71 kg/m2 (LFF), and 24.54 kg/m2 (RLFF). The median gestational age in the three groups was 130 days (control), 126 days (LFF), and 122/133 days (RLFF). The median maternal age in the three groups was 29 (control), 29 (LFF), and 33-years-old (RLFF). The proportion of twin pregnancies in the three groups was 3.3% (control), 10.7% (LFF), and 11.7% (RLFF). The proportion of IVF in the three groups was 4.7% (control), 11.7% (LFF), and 21.3% (RLFF). The factors significantly associated with LFF included BMI [2.18, (1.94, 2.45), p < 0.0001], gestational age [0.76, (0.67, 0.87), p < 0.0001], twin pregnancy [1.62, (1.02, 2.52), p = 0.0353], and IVF [2.68, (1.82, 3.86), p < 0.0001]. The factors associated with RLFF included maternal age [1.54, (1.17, 2.05), p = 0.0023] and IVF [2.55, (1.19, 5.54), p = 0.016]. Multiples of the median (MOM) value of β-hCG and pregnant persons\' gestational age at delivery were significantly decreased in the LFF and RLFF groups compared to the control group.
UNASSIGNED: According to our findings based on the OR value, factors associated strongly with LFF include a high BMI and the use of IVF. Factors associated less strongly with LFF include early gestational age and twin pregnancy, while advanced maternal age and IVF were independent risk factors for a second LFF result.
Body mass index, gestational age, maternal age, twin pregnancy, and in vitro fertilization are associated with fetal fraction. We added the repetitive low fetal fraction population and used a large normal population as a control to identify the main factors associated with low fetal fraction.

OBJECTIVE: This study aimed to investigate the effects of low-dose radiation on the abdominal aorta of mice and vascular endothelial cells.
METHODS: Wild-type and tumor-bearing mice were exposed to 15 sessions of low-dose irradiation, resulting in cumulative radiation doses of 187.5, 375, and 750 mGy. The effect on the cardiovascular system was assessed. Immunohistochemistry analyzed protein expressions of PAPP-A, CD62, P65, and COX-2 in the abdominal aorta. Microarray technology, Gene Ontology analysis, and pathway enrichment analysis evaluated gene expression changes in endothelial cells exposed to 375 mGy X-ray. Cell viability was assessed using the Cell Counting Kit 8 assay. Immunofluorescence staining measured γ-H2AX levels, and real-time polymerase chain reaction quantified mRNA levels of interleukin-6 (IL-6), ICAM-1, and Cx43.
RESULTS: Hematoxylin and eosin staining revealed thickening of the inner membranes and irregular arrangement of smooth muscle cells in the media membrane at 375 and 750 mGy. Inflammation was observed in the inner membranes at 750 mGy, with a clear inflammatory response in the hearts of tumor-bearing mice. Immunohistochemistry indicated increased levels of PAPP-A, P65, and COX-2 post-irradiation. Microarray analysis showed 425 up-regulated and 235 down-regulated genes, associated with processes like endothelial cell-cell adhesion, IL-6, and NF-κB signaling. Cell Counting Kit 8 assay results indicated inhibited viability at 750 mGy in EA.hy926 cells. Immunofluorescence staining demonstrated a dose-dependent increase in γ-H2AX foci. Reverse transcription quantitative PCR results showed increased expression of IL6, ICAM-1, and Cx43 in EA.hy926 cells post 750 mGy X-ray exposure.
CONCLUSIONS: Repeated low-dose ionizing radiation exposures triggered the development of pro-atherosclerotic phenotypes in mice and damage to vascular endothelial cells.

BACKGROUND: Changes in circulating pregnancy-associated plasma protein A (PAPP-A) have been observed in women with a placenta accreta spectrum (PAS). However, no consensus has been reached according to the previous studies. Our study investigated the relationship between circulating PAPP-A and PAS risk through a systematic review and meta-analysis.
METHODS: Studies comparing the circulating level of PAPP-A between pregnant women with and without PAS were obtained by searching the Medline, Cochrane Library, Embase, CNKI, and Wanfang databases from the inception of the databases until February 12, 2023. Heterogeneity was considered in the pooling of results via a random-effects model.
RESULTS: Eight observational studies were obtained for the meta-analysis, which included 243 pregnant women with PAS and 1599 pregnant women without PAS. For all these women, the first-trimester circulating level of PAPP-A was measured by immunoassay and reported as multiples of the median (MoM) values. The pooled results showed that compared to those who did not develop PAS, women with PAS had significantly higher first-trimester serum level PAPP-A (mean difference: 0.43 MoM, 95% confidence interval [CI]: 0.30 to 0.56, P < .001; I2 = 32%). Furthermore, a high first-trimester serum PAPP-A level was related to a high PAS risk (odds ratio: 2.89, 95% CI: 2.13 to 3.92, P < .001; I2 = 0%). Sensitivity analysis which excluded one study at a time, also obtained similar results (p all < 0.05).
CONCLUSIONS: Pregnant women with a high serum PAPP-A level in the first trimester may be at an increased risk for PAS.

BACKGROUND: Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21.
METHODS: This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care.
RESULTS: When cut-off values of free beta subunit of human chorionic gonadotropin (free β-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively.
CONCLUSIONS: The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.

UNASSIGNED: To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers.
UNASSIGNED: This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free β-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11-13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24-28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test.
UNASSIGNED: GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53-0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68-0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P<0.001).
UNASSIGNED: A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.

This study was aimed to investigate the role of interleukin-1β (IL-1β) in cigarette smoke extract (CSE)-induced apoptosis in vascular smooth muscle cells and the underlying mechanism in a rat derived cell line.
Rat thoracic aortic smooth muscle cells (A7r5) were divided into six groups including control, CSE (model), CSE+ overexpression empty vector (OvExp-EV), CSE+IL-1β knockdown (KD), and CSE+ IL-1β knockdown empty vector (KD-EV). The mRNA expression levels of IL-1β and pregnancy-associated plasma protein A (PAPP-A) were detected by quantitative polymerase chain reaction (qPCR). The apoptosis of A7r5 cells was detected by flow cytometry. The expression levels of inflammatory mediators (TNFα, IL-6 and IL-8) and apoptotic proteins (Bax and Bcl-2) were determined by western blot.
CSE induced significant apoptosis in vascular smooth muscle cells (P < 0.01) and elevated the mRNA levels of IL-1β and PAPP-A (P < 0.01). CSE administration increased protein expression of Bax, TNF-α, IL-6, and IL-8, with significantly reduced Bcl-2 expression (P < 0.01). IL-1β knockdown significantly decreased cell apoptosis via regulating the expression of these proteins (P < 0.05 or P < 0.01).
IL-1β is involved in CSE-induced PAPP-A expression and apoptosis in vascular smooth muscle cells, which might be considered as a target for preventing of cardiovascular diseases caused by cigarette smoking.

The aim of this study was to investigate the correlation and predictive value of serum miR-146b-5p expression during the first trimester of pregnancy with pre-eclampsia (PE). In total, 32 normal pregnant women (the control group) and 58 subjects with PE were randomly selected from eligible case data. The serum levels of miR-146b-5p, pregnancy associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) were then detected. Next, we established predictive models of single or multiple markers for PE. The levels of miR-146b-5p in the mild pre-eclampsia (mPE) and severe pre-eclampsia (sPE) groups were higher than the control group and there were significant differences between the three groups (F = 3.424, P = 0.037). The statistical results of the model before and after 200 times 10-fold cross-validation were as follows: miR-146b-5p (AUC = 0.723 vs AUC = 0.710); miR-146b-5p + BMI + MAP + free β-hCG MoM + PAPP-A MoM (AUC = 0.929 vs AUC = 0.851). We found that expression levels of miR-146b-5p in the first trimester were significantly higher in the serum of pregnant women with PE than in the normal pregnancy group. A prediction model in combination with miR-146b-5p and other markers improved the early predictive value for PE.IMPACT STATEMENTWhat is already known on this subject? Pre-eclampsia is a complex systemic disease with hypertension as the main clinical manifestation and causes extensive damage to the body. Some existing maternal biochemical markers have limited value in predicting PE, and new biomarkers with high sensitivity and specificity are urgently needed in clinical practice. There are a variety of abnormal expression miRNAs in PE, however, the relationship between miR-146b-5p and PE has yet to be fully elucidated.What do the results of this study add? We first found that expression levels of serum miR-146b-5p in the first trimester were significantly higher in PE than in a normal pregnancy group. A prediction model a combination of miR-146b-5p and other maternal characteristics and biochemical markers can improve the early predictive value for PE.What are the implications of these findings for clinical practice and/or further research? PE progresses rapidly and has become a severe target organ complication when discovered. Therefore, the early prediction of a high risk of PE, along with early intervention and prevention measures, are of great significance. Compared to maternal biochemical markers, combination of miR-146b-5p and maternal characteristics and biochemical markers can improve the early predictive value for PE.

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a de novo deletion of 4q34.1→qter associated with low pregnancy associated plasma protein-A (PAPP-A) and low placental growth factor (PlGF) in the first-trimester maternal serum screening, congenital heart defect (CHD) on fetal ultrasound and a false negative non-invasive prenatal testing (NIPT) result.
METHODS: A 40-year-old, primigravid woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). First-trimester maternal serum screening at 12 weeks of gestation revealed low PAPP-A [0.349 multiples of the median (MoM)] and low PlGF (0.299 MoM) and showed a risk for fetal trisomy 21 and trisomy 13. However, NIPT detected no genomic imbalance and a normal result. Nevertheless, level II ultrasound revealed ventricular septal defect, single umbilical artery and a small brain midline cyst. Amniocentesis revealed a karyotype of 46,XX,del(4)(q34.1) and a 17.8-Mb deletion of 4q34.1q.35.2 on array comparative genomic hybridization (aCGH) analysis. The parental karyotypes were normal. The pregnancy was terminated at 23 weeks of gestation, and a malformed fetus was delivered with craniofacial dysmorphism. Postnatal cytogenetic analysis of the placenta confirmed the prenatal diagnosis. There was a 17.8-Mb deletion of 4q34.1q.35.2 encompassing the genes of HAND2, SORBS2 and DUX4. Polymorphic DNA marker analysis on the parental bloods and cord blood showed a paternal origin of the deletion.
CONCLUSIONS: An abnormal first-trimester maternal serum screening result along with abnormal fetal ultrasound should alert the possibility of fetal aneuploidy, and amniocentesis is indicated even in the presence of a normal NIPT result.

UNASSIGNED: Down syndrome (DS), also known as trisomy 21 syndrome, is a common and most harmful congenital chromosomal genetic disease. This study is aimed at exploring the effect of B-ultrasound NT scan in early pregnancy combined with serum screening in early and middle pregnancy for Down syndrome.
UNASSIGNED: A total of 168 pregnant women who were diagnosed and treated in the obstetric clinic of our hospital from January 2019 to December 2021 were selected as the research objects. B-ultrasound NT scanning and serum detection in the early and middle trimester of pregnancy were performed, respectively. The accuracy of single detection and combined detection was analyzed and compared with the results of amniotic fluid cell chromosome examination as the gold standard.
UNASSIGNED: There were 4 cases of DS and 165 cases of non-DS. The serum PAPP-A, AFP, and UE levels in DS group were lower than those in non-DS group. β-HCG level and NT value were higher than those in non-DS group (all p < 0.05). Among 168 pregnant women, 5 cases were diagnosed as abnormal by ultrasonography, and 1 case was diagnosed as normal. By serological test, 20 cases with high risk of DS were diagnosed in 4 cases, and 148 cases with low risk of DS were diagnosed in 2 cases. Among 168 cases examined by serology combined with ultrasound, 10 cases with high risk of DS were found, and 4 cases were diagnosed; 158 cases had low risk of DS, and 0 cases were diagnosed. The negative predictive value, specificity, and coincidence rate of DS screening by the three methods were higher, and the positive predictive value and coincidence rate of combined screening were the highest (p < 0.05). The screening risk of Down syndrome was correlated with pregnancy outcome. The abnormal pregnancy rate in high-risk group was significantly higher than that in low-risk group, and the difference was statistically significant (p < 0.05). ROC curve showed that the sensitivity, specificity, and AUC of the combined detection were greater than those of serology and NT.
UNASSIGNED: The application of B-ultrasound NT scan in early pregnancy combined with early and mid-term serum comprehensive screening in the screening of Down\'s infants is helpful to improve the diagnostic coincidence rate and reduce the occurrence of misdiagnosis.

Congenital heart disease (CHD) is well established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive prenatal diagnosis of fetal CHD. This study used data-independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9%, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD. Congenital heart disease (CHD) is well-established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive prenatal diagnosis of fetal CHD. We used data independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9 %, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD.