Prenatal Aneuploidy Screening Research Articles

Prenatal cell-free DNA screening for chromosomal aneuploidies after euploid embryo transfer shows high concordance with preimplantation genetic testing for aneuploidy results and low positive predictive values

To evaluate the positive predictive value (PPV) of prenatal cell-free DNA screening for chromosomal aneuploidies in pregnancies achieved either after single euploid transfer in IVF/PGT cycles or transfer of single untested embryo, and to assess the concordance of prenatal-cfDNA-screening and PGT-A results. Single centre retrospective cohort study SUBJECTS: 2973 prenatal-cfDNA-screening results for the most common trisomies(T)(T13,T18,T21,X,Y) and microdeletions(1p36;4p16.3;5p15.2;15q11.2;22q11.2) from singleton pregnancies allocated into 2 groups: PGT-A group (n=1204) pregnancy after single euploid transfer and non-PGT-A group (n=1769) pregnancy after transfer of single untested embryo, between 2016 and 2023. Primary outcome measure was accuracy of prenatal-cell-free-DNA-screening. Positive and negative prenatal-cell-free-DNA-screening results, and subsequent prenatal or postnatal diagnostic testing were used to classify each positive prenatal-cell-free-DNA-screening result as a true or a false positive. Secondary endpoints were to evaluate the concordance of PGT-A and prenatal-cell-free-DNA-screening results and to assess the differences of the fetal fraction of cell-free-DNA used for prenatal-cell-free-DNA-screening report between the study groups. Prenatal-cell-free-DNA-screening was performed at mean 11.3±1.8weeks gestational age (GA) and yielded results in 99.9% of the patients (0.1% cancellation rate). There was no difference in the fetal fraction between PGT-A tested and not tested pregnancies (9.5%±4% vs 10.3%±4%). 13 positive prenatal-cell-free-DNA-screening results (2-T21,2-X0,4-XXX,1-XYY, 1-indeterminate sex, 2-22q11 del/dup, 1-15q11.2) were received for PGT-A group. Only one (22q11 dup) was confirmed with amniocentesis and fetal autopsy, giving a PPV for an abnormal prenatal-cfDNA-screening of 7.7%, the rest had results concordant with PGT-A. Sex chromosomes were 100% concordant between prenatal-cell-free-DNA-screening and PGT-A results, giving a 100% PPV for PGT-A for sex chromosomes and 100% NPV for aneuploidies. Positive prenatal-cell-free-DNA-screening results were received for 27 pregnancies from untested embryos (1.5%), follow up testing was electively performed for 21, and 8 had confirmed the prenatal-cell-free-DNA-screening result, giving a PPV for the non-PGT-A group of 38%. This study demonstrates that patients undergoing IVF/PGT and single euploid embryo transfer can reliably do prenatal-cell-free-DNA-screening during their first trimester. Fetal fraction in singleton pregnancies after PGT-A tested embryos is not different from pregnancies with untested embryos. PPV for an abnormal prenatal-cell-free-DNA-screening result after euploid embryo transfer was reassuringly low (7.7%). PGT-A reliably selects against aneuploidy with 100% concordance with fetal sex.

Prenatal screening for aneuploidies by analysis of circulating total free deoxyribonucleic acid in maternal plasma. Narrative review

The non-invasive prenatal test is a screening method for fetal aneuploidies and if the result is at high risk, it must be confirmed through diagnostic genetic test. It is the most sensitive and specific detection test for common fetal aneuploidies and minimizes the use of invasive techniques, only for pregnant women at high risk. Genetic counseling should be performed before and after screening. This study aims to describe the basic fundamentals of non-invasive prenatal testing by analyzing free circulating deoxyribonucleic acid in maternal plasma for aneuploidy screening, and the primary methods and advances in molecular biology, including next-generation sequencing technologies, which have facilitated it, considering its benefits and limitations when applying it in clinical practice, in this rapidly changing field.

Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies

ABSTRACT Background Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort. Research design and methods In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated. Results The sensitivity was 97.7% (95%CI, 87.7–99.9), 87.3% (95% CI, 76.5–94.4), 96.1% (95%CI, 86.5–99.5), and 95.7% (95% CI, 78.1–99.9), the PPV was 25.8% (95%CI, 19.2–33.2), 80.9% (95%CI, 69.5–89.4), 79.0% (95%CI, 66.8–88.3), and 53.7% (95%CI, 37.4–69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0–95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all. Conclusions NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.

Most Unusual Twin Pairs: A Look at Uterus Didelphys / Twin Research Reviews: Prenatal Aneuploidy Screening for Twin Pregnancies; Twin Conceptions by Same-Sex Male Couples; Legal Personality of Conjoined Twins; Twin Study of Cannabis Use / Human Interest and Importance: Being Taken for Twins Saved Sisters; Twin Children of Jailed Nobel Prize Winner; British 'Biracial' Twins; Triplets Born at Start

A review of an unusual twin type-twins born to women with two uteri (uterus didelphys)-is presented. This review is followed by summaries of recent research and perspectives concerning prenatal aneuploidy screening for twin pregnancies, twin conceptions by same-sex male couples, legal personality of conjoined twins, and a twin study of cannabis use. Interesting information about twins that has appeared in the media is also presented, namely how being taken for twins saved a pair of sisters; twin children of a jailed Nobel Prize winner, British 'biracial' twins, triplets born at the start of Russia's attack on Ukraine, and twins born in different years.

Parental refusal of prenatal screening for aneuploidies.

To analyze the reasons for refusal of aneuploidy screening in a multicultural Middle Eastern population. The study included patients delivering in a university hospital, who had refused aneuploidy screening during their pregnancy. We evaluated through a questionnaire submitted during the postpartum period the sociodemographic characteristics, beliefs, attitudes, and the main reason underpinning their choice. Religious, ethical, and financial factors, personal beliefs, medical information, perceived media information, and familial input were assessed through a Likert scale. Our pilot study included 70 patients. The main reason (33 %) was the refusal to terminate pregnancy if the screening tests ultimately led to a diagnosis of aneuploidy. Lack of adequate information on the availability and benefits of this screening method (28 %), religious beliefs (17 %), in addition to other minor reasons such as financial considerations, familial recommendations, late pregnancy follow-ups, and media influence were also identified as contributing factors. Aneuploidy screening is routinely offered to couples, with varying uptake rates observed worldwide. Sufficient information on prenatal screening and diagnosis should be provided to all pregnant women, presenting all available options, thus enabling them to make a free and informed choice during their pregnancy.

Применение неинвазивного пренатального ДНК-скрининга анеуплоидий при многоплодной беременности

Применение неинвазивного пренатального ДНК-скрининга анеуплоидий при многоплодной беременности

Cytogenetic Outcomes Following a Failed Cell-Free DNA Screen: A Population-Based Retrospective Cohort Study of 35,146 Singleton Pregnancies

(Abstracted from Am J Obstet Gynecol 2023;229:168.e1–e8) Cell-free DNA (cfDNA) screening is a form of prenatal genetic screening for aneuploidies. This method boasts lower false-positive rates than multiple-marker screening methods and is now commonly recommended.

A statistical investigation of parameters associated with low cell-free fetal DNA fraction in maternal plasma for noninvasive prenatal testing

Background 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. Methods 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. Results 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. Conclusion 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.

Evaluation of the incidence of anomaly in fetus and neonates of prenatal aneuploidy screening

Evaluation of the incidence of anomaly in fetus and neonates of prenatal aneuploidy screening

Cell-free DNA methylation-based preeclampsia prediction: Ajourney to improve maternal health.

Presymptomatic prediction of preeclampsia (PE) is crucial to enable early prophylactic treatment. Current screening tools are either complex or lack predictive value. We recently demonstrated that cell-free DNA methylation can be leveraged to predict early-onset PE in 57% at a 10% false positive rate. Importantly, this minimally invasive screening test can be implemented as an add-on to current widespread noninvasive prenatal aneuploidy screening. Here, we highlight the pitfalls and promising prospects of this research.

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

Background: In October 2015, the Massachusetts Medicaid program temporarily stopped reimbursing the ICD-10 code used by certain communities for serum aneuploidy screening. This change resulted in a substantial number of patients without aneuploidy screening for approximately three years.Objective: To determine the change in utilization 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 under 35 years of age receiving aneuploidy serum screening at a Massachusetts community health center. The study compared aneuploidy serum screening rates 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 versus non-reimbursed 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, compared to 9% (10/112) post-policy change. Traditional aneuploidy serum screening in a low-risk (aged <35 years) Hispanic population was considered cost-saving (i.e., resulted in lower incremental costs and higher incremental benefits compared to non-reimbursed or limited screening).Conclusions: From a U.S. healthcare payer perspective, aneuploidy serum screening for Hispanic pregnant individuals under 35 years of age is economically advantageous compared to limited screening.

Prenatal aneuploidy screening and its impact on stillbirth etiology evaluation.

Stillbirth impacts 1% of all pregnancies in the USA with the underlying cause often remaining unknown. The objective of this study was to identify if prenatal aneuploidy screening impacted patient agreement to stillbirth evaluation. We performed a retrospective cohort study of patients with a singleton stillbirth after 20 weeks of gestation between October 2017 and December 2021. Demographics and stillbirth evaluation were collected for all patients. Multivariable logistic regression was performed adjusting for variables that were significant in univariate analysis. A total of 81 persons experienced stillbirth during the study period. Approximately 59.3% of patients had prenatal aneuploidy screening: 39.5% integrated screening, 37.5% non-invasive prenatal testing (NIPT), and 22.9% quad screen. Prenatal genetic screening did not significantly impact patient agreement to placental pathology, serum laboratory evaluation, or fetal autopsy. Patients with NIPT were less likely to have genetic testing sent at the time of stillbirth compared to those with another aneuploidy screening (aOR 0.27, 95% CI 0.07-0.99). Prenatal aneuploidy screening was not associated with patient acceptance of stillbirth evaluation. However, patients with NIPT were less likely to pursue further genetic testing during stillbirth evaluation, so further education regarding the benefit of karyotype and microarray should be included in patient counseling.

Economic evaluation of prenatal screening for fetal aneuploidies in Thailand.

Historically, there has been a lack of cost-effectiveness data regarding the inclusion of universal non-invasive prenatal testing (NIPT) for trisomy 21, 18, and 13 in the benefit package of the Universal Health Coverage (UHC) in Thailand. Therefore, this study aimed to perform the cost-benefit analysis of prenatal screening tests and calculate the budget impact that would result from the implementation of a universal NIPT program. A decision-tree model was employed to evaluate cost and benefit of different prenatal chromosomal abnormalities screenings: 1) first-trimester screening (FTS), 2) NIPT, and 3) definitive diagnostic (amniocentesis). The comparison was made between these screenings and no screening in three groups of pregnant women: all ages, < 35 years, and ≥ 35 years. The analysis was conducted from societal and governmental perspectives. The costs comprised direct medical, direct non-medical, and indirect costs, while the benefit was cost-avoidance associated with caring for children with trisomy and the loss of productivity for caregivers. Parameter uncertainties were evaluated through one-way and probabilistic sensitivity analyses. From a governmental perspective, all three methods were found to be cost-beneficial. Among them, FTS was identified as the most cost-beneficial, especially for pregnant women aged ≥ 35 years. From a societal perspective, the definitive diagnostic test was not cost-effective, but the other two screening tests were. The most sensitive parameters for FTS and NIPT strategies were the productivity loss of caregivers and the incidence of trisomy 21. Our study suggested that NIPT was the most cost-effective strategy in Thailand, if the cost was reduced to 47 USD. This evidence-based information can serve as a crucial resource for policymakers when making informed decisions regarding the allocation of resources for prenatal care in Thailand and similar context.

SARS-CoV-2 in early pregnancy-does it affect the aneuploidy screening markers and cause pregnancy loss?

It is known that vertical transmission of various infections poses a potential risk to the fetus, especially in early pregnancy. Potential effects of SARS-CoV-2 infection on early pregnancy and placental formation and functions still remain unknown. To determine the alterations of prenatal aneuploidy screening markers in a group of pregnant women who were SARS-CoV-2 positive during the first trimester. The secondary goal was to assess pregnancy loss rates. The study group consisted of pregnant women who were diagnosed with mild forms of SARS-CoV-2 infection before the screening test at any time in early pregnancy. The control group included pregnant women who were not diagnosed with SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 infection was detected by RT-PCR in the nasopharyngeal swab samples. Multivariate linear regression analysis was performed due to evaluate effect of SARS-CoV-2 infection on NT and serum aneuploidy screening parameters taking maternal age and gestational age which the COVID-19 RT-PCR test result was positive into account. We did not find any significant difference between the COVID-19-positive and COVID-negative groups in gestational age at screening, sonographic measurements of CRL, NT, and serum levels of PAPP-A, free hCG, and triple test serum markers even after accounting for maternal age and gestational age which the COVID-19 RT-PCR test result was positive. There was no statistically significant difference in pregnancy loss. We did not find any evidence for unfavorable prenatal biochemical, ultrasound markers of fetal aneuploidy screening tests, and pregnancy loss rates in our study group.

Analysis of mid-trimester maternal serum β-hCG and AFP as markers of preterm and term adverse pregnancy outcomes form a tertiary care hospital, Morang, Nepal

Background: Mid-trimester maternal serum markers have been used for prenatal aneuploidy screening for a long time. The aim of the study was to assess the mid-term serum levels of β-human chorionic gonadotropin and alpha-fetoproteins for placenta-mediated adverse pregnancy outcomes (PMAPOs) in preterm and term pregnancies.&#x0D; Material and methods: A prospective cohort study involving nulliparous women with singletons without aneuploidy or fatal fetal abnormalities was carried out a tertiary care hospital, Morang, Nepal. AFP and β-hCG levels were estimated between 13 and 17 weeks of gestation in the mother's serum. All values were in multiples of the median (MoM) and compared between women with PMAPOs.&#x0D; Results: The serum levels of AFP and β-hCG were obtained in 176 out of 300 nulliparous women. The MoM of serum β-hCG (1.3 vs 1.1) and AFP (1.4 vs 1.1) were higher in PMAPOs-affected women than in controls.&#x0D; Conclusion:Preterm PMAPOs, but not term PMAPOs, are more likely in the present study when maternal serum AFP or β -hCG levels are more significant than 2.0 MoM. If fetal growth is within the normal range at 37 weeks of gestation, it is advisable that women with increased serum β-hCG or AFP receive regular prenatal care.

First and second trimester maternal serum markers for prenatal aneuploidy screening: An update on the adjustment factors for race, smoking, and insulin dependent diabetes mellitus

ObjectivesThe concentrations of maternal serum markers for aneuploidy screening are influenced by maternal characteristics such as race, smoking, insulin dependent diabetes mellitus (IDDM), and in vitro fertilization (IVF). Accurate risk estimation requires adjustment of initial values for these characteristics. This study aims to update and validate adjustment factors for race, smoking, and IDDM. MethodsThe study included singleton pregnancies that received multiple marker screening in Ontario, Canada between January 2012, and December 2018, and had their information collected in the Better Outcomes Registry & Network (BORN) Ontario. Serum markers assessed included first trimester pregnancy-associated plasma protein A (PAPP-A), free β and total human chorionic gonadotropin (hCG), placental growth factor (PlGF) and αlpha-fetoprotein (AFP); second trimester AFP, unconjugated estriol (uE3), total hCG and inhibin A. The Mann-Whitney U test was used to assess the differences in the median multiple of the median (MoM) of serum markers between study and reference groups. New adjustment factors were generated by dividing the median MoM of a particular race, individuals who smoke tobacco, or have IDDM by those of the reference groups. ResultsThe study included 624,789 pregnancies. There were statistically significant differences in serum marker concentrations among pregnant individuals who were Black, Asian, or First Nations compared to a White group, those who smoked compared to Non-smoking individuals, and those with IDDM compared to Non-IDDM group. New adjustment factors for race, smoking, and IDDM were validated by comparing median MoM of serum markers corrected using the current adjustment factors and new adjustment factors generated in this study. ConclusionThe adjustment factors generated in this study can adjust the effects of race, smoking, and IDDM on serum markers more accurately.

Obstetrical, perinatal, and genetic outcomes associated with nonreportable prenatal cell-free DNA screening results

The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes. This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes. This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. Obstetrical outcomes and neonatal genetic testing results were collected from 21 primary-care and referral centers in the United States, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction. In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 1.4-3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30]). Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications.

Association of maternal risk factors with fetal aneuploidy and the accuracy of prenatal aneuploidy screening: a correlation analysis based on 12,186 karyotype reports

BackgroundNIPT is becoming increasingly important as its use becomes more widespread in China. More details are urgently needed on the correlation between maternal risk factors and fetal aneuploidy, and how these factors affect the accuracy of prenatal aneuploidy screening.MethodsInformation on the pregnant women was collected, including maternal age, gestational age, specific medical history and results of prenatal aneuploidy screening. Additionally, the OR, validity and predictive value were also calculated.ResultsA total of 12,186 analysable karyotype reports were collected with 372 (3.05%) fetal aneuploidies, including 161 (1.32%) T21, 81 (0.66%) T18, 41 (0.34%) T13 and 89 (0.73%) SCAs. The OR was highest for maternal age less than 20 years (6.65), followed by over 40 years (3.59) and 35–39 years (2.48). T13 (16.95) and T18 (9.40) were more frequent in the over-40 group (P < 0.01); T13 (3.62/5.76) and SCAs (2.49/3.95) in the 35–39 group (P < 0.01). Cases with a history of fetal malformation had the highest OR (35.94), followed by RSA (13.08): the former was more likely to have T13 (50.65) (P < 0.01) and the latter more likely to have T18 (20.50) (P < 0.01). The sensitivity of primary screening was 73.24% and the NPV was 98.23%. The TPR for NIPT was 100.00% and the respective PPVs for T21, T18, T13 and SCAs were 89.92, 69.77, 53.49 and 43.24%, respectively. The accuracy of NIPT increased with increasing gestational age (0.81). In contrast, the accuracy of NIPT decreased with maternal age (1.12) and IVF-ET history (4.15).Conclusions①Pregnant patients with maternal age below 20 years had higher risk of aneuploidy, especially in T13; ②A history of fetal malformations is more risky than RSA, with the former more likely to have T13 and the latter more likely to have T18; ③Primary screening essentially achieves the goal of identifying a normal karyotype, and NIPT can accurately screen for fetal aneuploidy; ④A number of maternal risk factors may influence the accuracy of NIPT diagnosis, including older age, premature testing, or a history of IVF-ET. In conclusion, this study provides a reliable theoretical basis for optimizing prenatal aneuploidy screening strategies and improving population quality.

Cost-effectiveness of ultrasound before non-invasive prenatal screening for fetal aneuploidy.

To determine the cost-effectiveness of first-trimester ultrasound before fetal aneuploidy screening with cell-free DNA (cfDNA) compared with screening by cfDNA alone. A decision analytic model was constructed for 400 000 pregnant individuals with advanced maternal age who desired first-trimester aneuploidy screening with cfDNA in the USA, to compare two screening strategies: (1) cfDNA only and (2) ultrasound performed within 4 weeks before cfDNA. Input parameters included probability of fetal aneuploidy, cfDNA performance, desire for diagnostic testing, pregnancy outcomes, and pregnancy and lifetime costs and utilities. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), in terms of cost in 2020 US dollars (USD) per quality-adjusted life year (QALY) gained. Secondary outcomes included procedure-related loss, pregnancy termination, live birth with aneuploidy, live birth with structural anomaly and stillbirth. Discounting was performed at 3% per year with an estimated maternal lifespan of 81 years starting at the age of 35 years. One-way, multiway and Monte Carlo probabilistic sensitivity analyses were performed. All base-case estimates and ranges of uncertainty were derived from the literature. The willingness-to-pay threshold was set at 100 000 USD per QALY. In the base-case analysis, ultrasound before cfDNA screening was more cost-effective than cfDNA screening without pretest ultrasound, with an ICER of 12 588 USD and higher net monetary benefit (24 241 vs 20 466). The strategy involving ultrasound before cfDNA was more costly by 544 USD but also more effective (by 0.04 QALY) compared with cfDNA alone. Base-case results were robust in sensitivity analyses with the strategy involving ultrasound before cfDNA always remaining the most cost-effective approach with the highest net monetary benefit. First-trimester ultrasound before cfDNA is a more cost-effective strategy for non-invasive prenatal aneuploidy screening compared with cfDNA alone. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Non-invasive prenatal testing for everybody or contingent screening?

To compare the advantages and disadvantages of two main implementation strategies for non-invasive prenatal testing (NIPT) for the detection of trisomies 21, 13 and 18 in public healthcare settings. These concern NIPT as a first-tier screening test for all pregnant women, or NIPT contingent on an increased risk first-trimester combined test (FCT) result. Comparison based on (un)published data and literature. Despite the lower prevalence of trisomies in the low-risk population, data show that the positive predictive value (PPV) and detection-miscarriage ratio of first-tier NIPT are comparable to NIPT used as contingency test. Advantages of NIPT as a first-tier test compared to FCT with contingent NIPT are that there is no time-window for testing, sensitivity is higher, fewer women need follow-up testing (PPV of NIPT is higher than PPV of FCT), less anxiety for pregnant women and partners. When given the choice, pregnant women prefer first-tier NIPT. Although contingency testing still seems to be the cheaper option, the differences in costs are becoming increasingly smaller and might soon disappear. We argue that NIPT should preferably be offered as a first-tier test for the detection of fetal aneuploidies for all pregnant women, provided that women are supported to make informed decisions. This article is protected by copyright. All rights reserved.