Application of Patient-Based Real-Time Quality Control Based on Artificial Intelligence Monitoring Platform in Continuously Quality Risk Monitoring of Down Syndrome Serum Screening.

BACKGROUND: Patient-based real-time quality control (PBRTQC) has gained attention because of its potential to continuously monitor the analytical quality in situations wherein internal quality control (IQC) is less effective. Therefore, we tried to investigate the application of PBRTQC method based on an artificial intelligence monitoring (AI-MA) platform in quality risk monitoring of Down syndrome (DS) serum screening. METHODS: The DS serum screening item determination data and relative IQC data from January 4 to September 7 in 2021 were collected. Then, PBRTQC exponentially weighted moving average (EWMA) and moving average (MA) procedures were built and optimized in the AI-MA platform. The efficiency of the EWMA and MA procedures with intelligent and traditional control rules were compared. Next, the optimal EWMA procedures that contributed to the quality assurance of serum screening were run and generated early warning cases were investigated. RESULTS: Optimal EWMA and MA procedures on the AI-MA platform were built. Comparison results showed the EWMA procedure with intelligent QC rules but not traditional quality rules contained the best efficiency. Based on the AI-MA platform, two early warning cases were generated by using the optimal EWMA procedure, which finally found were caused by instrument failure. Moreover, the EWMA procedure could truly reflect the detection accuracy and quality in situations wherein traditional IQC products were unstable or concentrations were inappropriate. CONCLUSIONS: The EWMA procedure built by the AI-MA platform could be a good complementary control tool for the DS serum screening by truly and timely reflecting the detection quality risks.

Prenatal aneuploidy screening in a low-risk Hispanic population: price elasticity and cost-effectiveness.

BACKGROUND: In October 2015, the Massachusetts Medicaid program temporarily stopped reimbursement for procedures in which the International Classification of Diseases, Tenth Edition, code for serum aneuploidy screening used by certain communities was stipulated. This change led to a substantial number of patients who went without aneuploidy screening for approximately 3 years. OBJECTIVE: This study aimed to determine the change in use and cost-effectiveness of prenatal aneuploidy serum screening in a low-risk Hispanic Medicaid population in Massachusetts. STUDY DESIGN: We conducted a retrospective chart review of Spanish-speaking pregnant patients younger than 35 years of age who underwent aneuploidy serum screening at a Massachusetts community health center. The study compared the aneuploidy serum screening rates for the periods before and after May 2016 when the Massachusetts Medicaid program, MassHealth, temporarily discontinued reimbursement for the screening. Based on these rates, we developed a Markov cohort simulation model to assess the economic value of reimbursed aneuploidy screening vs nonreimbursed or limited screening. Clinical outcomes included trisomy 21, live births, and therapeutic abortions for a trisomy 21 diagnosis. Economic outcomes included discounted quality-adjusted life years and lifetime medical costs, net health benefit, and incremental cost-effectiveness ratios. RESULTS: Before the MassHealth policy change, 69% (55/80) of pregnant individuals selected quad or sequential screens in comparison with only 9% (10/112) who selected screens after the policy change. Traditional aneuploidy serum screening in a low-risk (aged <35 years) Hispanic population was considered to be cost-saving (ie, led to lower incremental costs and higher incremental benefits when compared with nonreimbursed or limited screening). CONCLUSION: From a United States healthcare payer perspective, aneuploidy serum screening for Hispanic pregnant individuals under 35 years of age is economically advantageous when compared with limited screening.

The value of NIPT combined with serum cell-free DNA, estriol, AFP, and b-HCG levels in the recognition of trisomy 21 and 18 in the second trimester.

Background: This study aimed to evaluate the clinical application value of noninvasive prenatal testing from DNA (NIPT) and serum screening for screening in detecting fetal trisomy 21 and 18. Methods: As a retrospective analysis, we collected data from 1383 women (singleton pregnancy) who underwent serum screening and noninvasive prenatal testing from DNA (NIPT) in our department from May 2015 to September 2017 and calculated the diagnostic value of the two methods.

Developing and validating noninvasive prenatal testing for de novo autosomal dominant monogenic diseases in Vietnam.

Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.

Awareness About Folic Acid Supplementation in First-Trimester Pregnant Women of Rural Raipur District, Chhattisgarh, and Its Determinants: A Cross-Sectional Study.

BACKGROUND: Women are supplemented with folic acid (FA) during pregnancy as well as preconceptionally to prevent neural tube defects (NTDs) in newborns. To understand the importance of FA supplementation, women need to have awareness about the same, which in turn may be influenced by different factors. It is also known that both FA and vitamin B12 deficiency tend to cause NTDs in newborns and anemia. Very few studies have studied the relationship between hemoglobin, FA, and vitamin B12 levels. In this study, we aim to estimate the level of awareness of FA supplementation among pregnant women in the first trimester of pregnancy and the factors determining the presence of awareness regarding the same. Also, we aim to estimate any correlation between hemoglobin, FA, and vitamin B12 levels among a subset of pregnant women. METHODS: A cross-sectional study was conducted in the Abhanpur Block of Raipur district in Chhattisgarh among 399 pregnant women in their first trimester of pregnancy, in which their knowledge was assessed using a pretested semistructured questionnaire. Each participant's knowledge score regarding FA supplementation was calculated and scored based on six indicators and classified as low, intermediate, and high scores. Logistic regression was applied to find out any significant association between knowledge about FA supplementation with any other sociodemographic variables. Scatter plots were used to assess the correlation of FA with hemoglobin, vitamin B12, and knowledge scores among 104 participants. RESULTS: The majority (77.9%) of women had low knowledge scores with a mean score of 1.4 (0.15). It was found that only 45.6% of the participants knew the importance of FA supplementation, and the majority (23.1%) were informed by auxiliary nurse midwives (ANMs) followed by doctors. The majority (41.6%) of the study participants also did not know when to start FA, and only 1.3% knew that FA should be taken preconceptionally. On multivariable logistic regression, women who lived in joint families had significantly higher odds of having intermediate knowledge compared to those who lived in nuclear families. Although not statistically significant, there was a positive correlation between serum vitamin B12 and FA levels and also between hemoglobin and serum FA levels. However, a significant positive correlation was found between serum FA levels and the knowledge scores of the study participants. CONCLUSION: The majority of study participants had poor knowledge and awareness regarding FA supplementation. So, health education, as well as information, education, and communication (IEC) activities, is required to improve the knowledge about FA supplementation among women of reproductive age in the community. A better understanding of FA supplementation can lead to adherence to FA consumption and prevent NTDs among newborns.

Reconsidering the use of race adjustments in maternal serum screening.

The use of race in maternal serum screening is problematic because race is a social construct rather than a distinct biological classifier. Nevertheless, laboratories offering this testing are encouraged to use race-specific cutoff values for maternal serum screening biomarkers to determine the risk of fetal abnormalities. Large cohort studies examining racial differences in maternal serum screening biomarker concentrations have yielded conflicting results, which we postulate may be explained by genetic and socioeconomic differences between racial cohorts in different studies. We recommend that the use of race in maternal serum screening should be abandoned. Further research is needed to identify socioeconomic and environmental factors that contribute to differences in maternal serum screening biomarker concentrations observed between races. A better understanding of these factors may facilitate accurate race-agnostic risk estimates for aneuploidy and neural tube defects.

Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center.

OBJECTIVES: The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years. METHODS: We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded. RESULTS: Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012-2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017-2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis. CONCLUSIONS: Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes.

Women's Concerns and Experiences of Fetal Anomaly Screening Process: A Qualitative Study.

Background: Advanced technologies in antenatal screening provide complex and accurate information about the fetus that allows for early intervention, but it increases pregnant women's concerns about fetal health. This study aimed to investigate the concerns and experiences of Iranian pregnant women in the fetal anomaly screening process. Methods: This qualitative study was performed from September 2018 to June 2019 in Tehran, Iran. Twenty pregnant women who referred to prenatal care clinics, four specialists, and two midwives took part in this study. The sampling was done purposefully until data saturation. Qualitative interviews were analyzed using the content analysis approach and Graneheim and Lundman's method. The MAXQDA 10 was used for data management. Results: The pregnant women who participated in the study were 22-40 years old. The following 4 themes were obtained from the analysis: the challenge of deciding to perform the tests, bitter pregnancy experience, challenges of facing an abortion, and unmet needs of pregnant women by the health system. Conclusion: The findings indicate that pregnant women need real information and support. Designing and implementing interventions that reduce the psychological impact of performing fetal anomaly screening tests can highlight the potential benefits for pregnant women's health.

Molecular cytogenetic characterization of de novo concomitant distal 8p deletion of 8p23.3p23.1 and Xp and Xq deletion of Xp22.13q28 due to an unbalanced X;8 translocation detected by amniocentesis.

OBJECTIVE: We present molecular cytogenetic characterization of de novo concomitant distal 8p deletion of 8p23.3p23.1 and Xp and Xq deletion of Xp22.13q28 due to an unbalanced X;8 translocation detected by amniocentesis. CASE REPORT: A 33-year-old primigravid woman underwent amniocentesis at 18 weeks of gestation because of a Down syndrome risk of 1/52 at the first-trimester maternal serum screening calculated from 0.29 multiples of the median (MoM) of pregnancy associated plasma protein-A (PAPP-A), 1.14 MoM of free ß-hCG and 0.46 MoM of placental growth factor (PlGF). Amniocentesis revealed a karyotype of 45,X,add(8)(p23.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed a 137-Mb deletion of Xp22.13q28 and a 10.53-Mb deletion of 8p23.3p23.1. The karyotype thus was 45,X,der(8)t(X;8)(p22.13;p23.1). Prenatal ultrasound revealed pericardial effusion and skin edema. The pregnancy was subsequently terminated, and a 568-g malformed fetus was delivered with hypertelorism and low-set ears. The cord blood had a karyotype of 45,X,der(8)t(X;8)(p22.13;p23.1). aCGH analysis of the cord blood revealed the result of arr [GRCH37 (hg19)] 8p23.3p23.1 (191,530-10,724,642) × 1.0, arr Xp22.13q28 (18,194,098-155,232,907) × 1.0. CONCLUSION: aCGH analysis is useful elucidating the genetic nature of an aberrant chromosome with an additional maternal of unknown origin attached to a chromosome terminal region.

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.

Comparison of noninvasive prenatal screening with combined first-trimester screening as a frontline screening approach for common trisomies in a public hospital in Australia.

BACKGROUND: Combined first-trimester screening (cFTS) for fetal anomalies involves maternal serum screening for biochemical markers and measurement of the nuchal translucency (NT) by ultrasound. Noninvasive prenatal screening (NIPS) analyses cell-free DNA present in a maternal blood sample for presence of fetal chromosomal aneuploidies. AIMS: To compare NIPS with cFTS as frontline screening in a public hospital in Australia. MATERIALS AND METHODS: Women were offered NIPS in addition to the usual cFTS routinely offered to all women at a public hospital in NSW, Australia. The cFTS sample was collected at ten weeks' gestation and the NIPS sample at 12 weeks' gestation at the ultrasound appointment. RESULTS: In a low-risk population of 997 women, frontline NIPS had a screen-positive rate of 0.5% (5/997) vs 4.2% (42/997) with cFTS. cFTS correctly identified one trisomy 21 case and one trisomy 18 case; however, there were two trisomy 18 false negatives. Of five positive NIPS calls, four were correctly identified as trisomy 21 (one) and trisomy 18 (three); there were no NIPS false negatives. Overall, the false-positive rate with NIPS was 0.1% vs 4.0% by cFTS. CONCLUSIONS: The lower screen-positive rate with NIPS for common trisomies was a result of the significantly lower false-positive rate with NIPS. Consequently, NIPS as first-line screening, even if funded by the hospital, may provide cost savings. We believe NIPS should be used from ten weeks' gestation in conjunction with morphology ultrasound for routine first-trimester prenatal management.

A decade of non-invasive prenatal screening in Australia: National impact on prenatal screening and diagnostic testing.

Prenatal screening for aneuploidy has undergone immense changes over the past two decades. In 2013 cell-free DNA-based non-invasive prenatal testing (NIPT) became a new self-funded option primarily for Down syndrome screening, but also other aneuploidies and genetic conditions. The numbers of Medicare item claims for prenatal diagnostic procedures have halved since the introduction of NIPT, while billings for serum screening fell by 40% over the same period, on a background of steady births. Australia is now observing historically low rates of prenatal diagnostic testing. These data provide an informative snapshot of historic changes in prenatal screening and diagnosis, as our sector prepares for the impending impacts of other advances in genomics on maternity care. They also highlight the need to address equity and quality issues that arise when consumers must bear the full costs of improved genomic tests in the absence of Medicare funding.

Global Trends in Research on Cell-Free Nucleic Acids in Obstetrics and Gynecology during 2017-2021.

OBJECTIVES: The objectives of this study were to identify global trends in research on cell-free deoxyribonucleic acid (cfDNA) from a bibliometric perspective and provide researchers with new research hotspots. METHODS: In all, we extracted 5038 pieces of literature from PubMed and 527 articles from the Web of Science Core Collection (WoSCC) database related to cfDNA published from 1 January 2017 to 31 December 2021. For PubMed literature, we employed co-word, biclustering, and strategic diagram analysis to describe the trends in research on cfDNA in the said five years. Then, we used VOSviewer analysis for the WoSCC database to display the trends in research on cfDNA in obstetrics and gynecology during 2017-2021. RESULTS: Strategy diagram analysis of 95 major Medical Subject Headings terms extracted from 5038 pieces of literature indicated that cfDNA sequence analysis for non-invasive prenatal and genetic testing and its application in the fields of neoplasm genetics and diagnosis is a newly emerging immature theme of cfDNA. VOSviewer analysis of 527 articles showed the global trends in research on cfDNA in obstetrics and gynecology, for example, in terms of most influential authors, institutions, countries, journals, and five research hotspots: (1) cfDNA application in prenatal screening and prenatal diagnosis, (2) cfDNA application in assisted reproductive technology, (3) cfDNA application in pre-eclampsia, DNA methylation, etc., (4) cfDNA application in placental dysfunction and fetal growth restriction, and (5) cfDNA application in fetal chromosomal abnormalities (fetal aneuploidy). CONCLUSIONS: Comprehensive visual analysis provides information regarding authors, organizations, countries/regions, journals, research hotspots, and emerging topics in the field of cfDNA for obstetrics and gynecology research. This comprehensive study could make it easier to find a partner for project development and build a network of knowledge on this emerging topic.

Incidence of Down Syndrome by maternal age in Chinese population.

Objective: This study aims to estimate the maternal age-related risk of Down syndrome in an Asian population. Methods: We performed a retrospective data analysis including a total of 206,295 pregnant women who presented for second-trimester maternal serum screening for Down syndrome at Hubei Maternal and Child Health Hospital for the years 2008-2017. Cases were assigned to three groups: ≤26 years of age, 27-33 years of age, and ≥34 years of age. The incidence of Down Syndrome was calculated for each age group. The differences between groups were tested using the chi-square (χ2) test. Results: The incidence of Down syndrome in women ≤26 years of age, 27-33 years of age, and ≥34 years of age was 0.67‰, 0.29‰, and 2.07‰ respectively. Statistically significant difference was found between the three age groups (χ2 = 79.748, p < 0.05). Conclusion: Down syndrome rate was significantly higher in women ≥34 years of age. Younger women (≤26 years of age) had a significantly higher risk for Down's syndrome, compared to women aged 27-33.

A Cost-Effectiveness Analysis of Screening Strategies Involving Non-Invasive Prenatal Testing for Trisomy 21.

Introduction: In accordance with social development, the proportion of advanced maternal age (AMA) increased and the cost of non-invasive prenatal testing (NIPT) decreased. Objective: We aimed to investigate the benefits and cost-effectiveness of NIPT as primary or contingent strategies limited to the high-risk population of trisomy 21 (T21). Methods: Referring to parameters from publications or on-site verification, a theoretical model involving 1,000,000 single pregnancies was established. We presented five screening scenarios, primary NIPT (Strategy 1), contingent NIPT after traditional triple serum screening higher than 1/300 or 1/1,000 (Strategy 2-1 or 2-2), and age-based Strategy 3. Strategy 3 was stratified, with the following options: (1) for advanced maternal age (AMA) of 40 years and more, diagnostic testing was offered, (2) for AMA of 35-39 years, NIPT was introduced, (3) if younger than 35 years of age, contingent NIPT with risk higher than 1:300 (Strategy 3-1) or 1:1,000 (Strategy 3-2) will be offered. The primary outcome was an incremental cost analysis on the baseline and alternative assumptions, taking aging society, NIPT price, and compliance into consideration. The strategy was "appropriate" when the incremental cost was less than the cost of raising one T21 child (0.215 million US$). The second outcome included total cost, cost-effect, cost-benefit analysis, and screening efficiency. Results: Strategy1 was costly, while detecting most T21. Strategy 2-1 reduced unnecessary prenatal diagnosis (PD) and was optimal in total cost, cost-effect, and cost-benefit analysis, nevertheless, T21 detection was the least. Strategy 3 induced most of the PD procedures. Then, setting Strategy2-1 as a baseline for incremental cost analysis, Strategy 3-1 was appropriate. In sensitivity analysis, when the NIPT price was lower than 47 US$, Strategy 1 was the most appropriate. In a society with more than 20% of people older than 35 years of age, the incremental cost of Strategy 3-2 was proper. Conclusion: Combined strategies involving NIPT reduced unnecessary diagnostic tests. The AMA proportion and NIPT price played critical roles in the strategic decision. The age-based strategy was optimal in incremental cost analysis and was presented to be prominent as AMA proportion and NIPT acceptance increased. The primary NIPT was the most effective, but only at a certain price, it became the most cost-effective strategy.

Prediction of Pregnancy Complications With Maternal Biochemical Markers Used in Down Syndrome Screening.

OBJECTIVE: To determine whether first- and second-trimester maternal serum biomarkers are useful for the prediction of pregnancy complications like preterm birth, intrauterine growth restriction (IUGR), and macrosomia. METHODS: We conducted a retrospective analysis of 353 women having first- or second-trimester combined test for Down syndrome screening who delivered at our institution between January 2018 and December 2020. Associations between first- and second-trimester serum markers and adverse pregnancy outcomes among those who underwent prenatal screening for Down syndrome in our clinic were studied. The adverse pregnancy outcomes, serum levels of pregnancy-associated plasma protein-A (PAPP-A), ß-human chorionic gonadotropin (ß-hCG), and maternal serum alpha-fetoprotein (ms-AFP) were recorded and analyzed. Correlation analyses of PAPP-A, free ßhCG, and ms-AFP with pregnancy outcomes were studied. We sought to predict the risks of preterm delivery (PTD, <37 weeks gestational age), low birth weight (LBW, <2500 grams) and macrosomia (>4000 grams). RESULTS: A total of 353 women who had first- and second-trimester screening test for Down syndrome were included. Two hundred fifty (70.08%) of them had first-trimester and 103 (41.2%) had second-trimester test. Mean age of the patients who underwent screening test for Down syndrome was 29.3±5.9, mean maternal weight was 67.3±13.6, mean gestational weeks at birth was 38.6±2.1 weeks and mean birth weight was 3260.9±511.1, preterm birth rate was 40/353 (11.3%), IUGR rate was 21/353 (5.9%), macrosomia rate was 17/353 (4.8%), stillbirth rate was 3/353 (0.8%). When laboratory and clinical parameters affecting birth weight and birth weeks were analysed in correlation analysis, both birth week and birth weight were found to be positively correlated with maternal weight. Of first-trimester markers Papp-A MoM (Multiples of Median) was found to be positively correlated with fetal birth weight (p = 0.044). Of second-trimester biochemical parameters ms-AFP was found to be negatively correlated with fetal birth weight (p = 0.039). CONCLUSION: The study concluded that there is a relationship between serum markers and adverse pregnancy outcomes. Significant associations were found between the levels of first- and second-trimester serum markers PAPP-A, AFP and IUGR, macromia and additionally significant association was found between maternal weight and both delivery week and fetal weight. These results can highlight the pregnancies at risk and follow-up intervals may be arranged according to risk scala which may help at antenatal follow-up of high-risk patients.

First trimester serum matrix metalloproteinase-7 is a poor predictor of late-onset preeclampsia.

OBJECTIVES: This study aims to evaluate matrix metalloproteinase-7 as a first trimester biomarker for late-onset preeclampsia, both alone and in combination with mean arterial pressure, uterine artery pulsatility index, and maternal characteristics. STUDY DESIGN: We conducted a nested case-control study from a prospective cohort consisting of 416 pregnant women who attended a routine first trimester scan. Baseline variables were obtained at inclusion and analysed subsequently to formation of case and control groups. The study was designed to detect a mean difference of > 15% in matrix metalloproteinase-7 concentrations between groups with a statistical power of 80%. MAIN OUTCOME MEASURES: The primary outcome was preeclampsia with delivery after 34 weeks of pregnancy. RESULTS: The median matrix metalloproteinase-7 concentration in cases of late-onset preeclampsia (n = 27) was marginally lower compared to normotensive controls but this difference was not statistically significant. Matrix metalloproteinase-7 predicted 14.8% of cases at a 10% false-positive rate. Addition of matrix metalloproteinase-7 to any combination of variables did not significantly improve their performance. CONCLUSIONS: Matrix metalloproteinase-7 is not a useful biomarker for late-onset preeclampsia, neither alone nor in combination with mean arterial pressure, uterine artery pulsatility index, or maternal characteristics.

The impact of prenatal screening tests on prenatal diagnosis in Taiwan from 2006 to 2019: a regional cohort study.

BACKGROUND: The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019. METHODS: The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website. RESULTS: This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively. CONCLUSION: During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.

Effectiveness of alpha-fetoprotein variants L2 and L3 as substitutes of alpha-fetoprotein in screening for fetal Trisomy 18.

OBJECTIVE: To evaluate the effectiveness of alpha-fetoprotein variants (AFP-L2, AFP-L3) in fetal screening for Trisomy 18 in place of alpha fetoprotein (AFP). METHODS: A retrospective case-control study was conducted. Collectively, 39 pregnant women bearing Trisomy 18 fetuses and 48 pregnant women with clinically normal and healthy fetuses were included. The serum AFP-L2 and AFP-L3 concentrations were detected by enzyme-linked immunosorbent assays. The likelihood ratio method and Python software were used to construct the risk model with AFP, free ß-hCG, AFP-L2, and AFP-L3 to predict Trisomy 18. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value, while the area under the curve (AUC) was used to assess the screening performance of AFP-L2 and AFP-L3 for fetal Trisomy 18. RESULTS: Compared to values observed for the control group, AFP-L2 and AFP-L3 concentrations which were significantly higher (both p< .001) in pregnant women with Trisomy 18 fetuses were 7.95 ± 3.57 ng/mL and 2.53 ± 1.80 ng/mL, respectively. Comparisons across multiple modeling methods showed that the highest AUC of screened Trisomy 18 fetuses (0.992, 0.986, and 0.976) was yielded by AFP-L2 + AFP-L3 + free ß-hCG, AFP-L2 + free ß-hCG, and AFP-L3 + free ß-hCG, with a sensitivity of 1.000 indicated in both instances. In different modeling methods, the order of AUC values was AFP-L2 + AFP-L3 + free ß-hCG > AFP-L2 + free ß-hCG > AFP-L3 + free ß-hCG > AFP + free ß-hCG. CONCLUSIONS: AFP-L2 and AFP-L3 showed higher sensitivity and specificity as substitutes for AFP in screening Trisomy 18. These two markers indeed improved the screening efficiency and reduced the false positive rate, when compared with AFP only.

Early warning of low maternal unconjugated estriol level by prenatal screening for fetus with X-linked ichthyosis / 中华妇产科杂志

Objective:To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE 3) levels and XLI. Methods:A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE 3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results:Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE 3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant ( Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions:The decrease levels of uE 3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE 3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.