Fetal Screening Research Articles

Clinical application of noninvasive prenatal testing in twin pregnancies: a single-centre experience

Objectives To evaluate the clinical efficiency of non-invasive prenatal testing (NIPT) for fetal chromosomal aneuploidy screening in twin pregnancies. Methods A total of 1650 women with twin pregnancies were enrolled in the study, which underwent NIPT at the Southwest Hospital, Army Medical University, Chongqing, China from January 2013 to June 2022. Fetal karyotyping analysis was conducted in high-risk patients, with subsequent follow-up on pregnancy outcomes. Results In 1650 pregnancies, NIPT results showed ten cases of the fetal chromosome aneuploidy, of which six cases were true positive and four cases were false positive. The sensitivity, specificity, positive predictive value (PPV), and false-positive rate (FPR) of trisomy 21 were 100%, 99.79%, 57.14%, and 0.18%, respectively. Sensitivity, specificity, PPV, and FPR of trisomy 18 were 100%, 99.94%, 50%, and 0.06%, respectively. The sensitivity, specificity, PPV, and FPR of trisomy 13 were 100%, 100%, 100%, and 0%, respectively. No false negatives were detected and the negative predictive value (NPV) was 100% of the total. Eleven pregnancies failed the NIPT test with no-call due to the low fetal fraction (< 4%). Conclusions NIPT is a high-performing routine primary prenatal screening test in twin pregnancies, with high sensitivity and specificity in screening for fetal aneuploidy.

Malignancy in pregnancy: Multimodality imaging and treatment.

The diagnosis of cancer is increasingly made in the pregnant population, thought to be from the increasing average age of pregnancy and the use of prenatal fetal noninvasive screening techniques, leading to incidental detection of cancer in the mother. Complex challenges are associated with imaging, diagnosis, staging, and treatment of cancers in this patient population, which require highly specialized interdisciplinary management. This report discusses the use of multimodality imaging and safety considerations in pregnant patients, reviews the current guidelines for ionizing radiation imaging techniques, and presents a series of commonly and uncommonly encountered cancers in pregnancy with current diagnostic imaging guidelines. The authors also discuss the role of multidisciplinary management and treatment options and provide an overview of therapy-related considerations in the age of novel anticancer therapies. PLAIN LANGUAGE SUMMARY: The diagnosis and management of pregnant patients who have cancer are actively evolving as novel imaging techniques and anticancer therapies are being developed. Radiologically, there are inherent difficulties in balancing the minimization of fetal ionization while acquiring diagnostic quality imaging necessary for the diagnosis, staging, and treatment of maternal disease. Standardized imaging protocols are still being developed, with evolving imaging guidelines coupled with rapidly expanding research and development of novel anticancer therapies, which come with their side effects and complications. Caring for this patient population is especially challenging and requires specialized multidisciplinary attention.

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.

Diabetes Mellitus in Pregnancy.

Diabetes mellitus (DM) in pregnancy imposes increased risks for the pregnant person, fetus, and infant, which includes miscarriage, congenital anomalies, accelerated fetal growth, iatrogenic prematurity, preeclampsia, delivery-related trauma, cesarean section, neonatal hypoglycemia, and respiratory distress syndrome. Preconceptual counseling for people with type 1 or type 2 DM who are contemplating pregnancy includes education about these risks, and optimization of glucose control. Fetal screening early in pregnancy in persons with type 1 or type 2 DM allows for early diagnosis and therapy optimization. In addition, screening for gestational DM in the late second trimester is routine given that such pregnancies are also affected. The overall perinatal morbidity and mortality of pregnancies complicated by DM is substantially higher than in the general obstetric population, proportionate to the level of glucose control.

African care for congenital central nervous system disorders: Falling far short of global management standards?

African care for congenital central nervous system disorders: Falling far short of global management standards?

Second Trimester Fetal Cardiac Screening - Current Opinion.

Congenital malformations are a major cause of miscarriage, perinatal mortality, prematurity, childhood death and disability worldwide. The well-being of each affected child with a birth defect depends primarily on which organ or body part is affected and how severely. The World Health Organization (WHO) estimates that approximately 295,000 newborns die each year as a result of congenital anomalies during the neonatal period.[1] The development of research in this area, the early diagnosis of birth defects, the promotion of prenatal screening programs, and the development of preventive public health strategies are important tools with great impact on the prognosis of these defects. The most common birth defects are cardiac anomalies, neural tube defects and trisomy 21.[1] [2]

Public Health England and Co-Production with the Fetal Anomaly Screening Programme

As the new Cell-free DNA (Cf-DNA) prenatal screening test for Down syndrome was being introduced into the UK’s fetal anomaly screening program, Down syndrome charities had an opportunity to participate. An experience of co-production where we were the minority voice then followed. This paper explores that process and our experience as a charity. Institutional and societal structures meant that it was difficult to be heard and a significant amount of bias was noted within the program. Consequently, our viewpoints were often considered and then dismissed. However, at times we were listened to, and feel that there were some valuable changes made resulting from our involvement. The end product was far from reflective of all that we stand for, and there are still lessons to be learned in England about the need to place a higher value on minority voices of lived experience in a co-production exercise.

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.

Cytogenetic outcomes following a failed cell-free DNA screen: a population-based retrospective cohort study of 35,146 singleton pregnancies

Cell-free fetal DNA screening is routinely offered to pregnant individuals to screen for aneuploidies. Although cell-free DNA screening is consistently more accurate than multiple-marker screening, it sometimes fails to yield a result. These test failures and their clinical implications are poorly described in the literature. Some studies suggest that a failed cell-free DNA screening result is associated with increased likelihood of cytogenetic abnormalities. This study aimed to assess the association between a failed cell-free DNA test and common aneuploidies. The objectives were to determine: (1) the proportion of test failures on first and subsequent attempts, and (2) whether a failed cell-free DNA screen on first attempt is associated with increased likelihood of common aneuploidies (trisomies 21, 18, and 13, and sex chromosome aneuploidies). This was a population-based retrospective cohort study using data from Ontario's prescribed maternal and child registry, Better Outcomes Registry and Network Ontario. The study included all singleton pregnancies in Ontario with an estimated date of delivery from September 1, 2016 to March 31, 2019 that had a cell-free DNA screening record in the registry. Specific outcomes (trisomies 21, 18, and 13, and sex chromosome aneuploidies) of pregnancies with a failed cell-free DNA screen on first attempt were compared with those of pregnancies with low-risk cell-free DNA-screening results using modified Poisson regression adjusted for funding status (publicly funded vs self-paid), gestational age at screening, method of conception, and maternal age for autosomal aneuploidies. Our cohort included 35,146 pregnancies that had cell-free DNA screening during the study period. The overall cell-free DNA screening failure rate was 4.8% on first attempt and 2.2% after multiple attempts. An abnormal cytogenetic result for trisomies 21, 18, and 13, or sex chromosome aneuploidies was identified in 19.4% of pregnancies with a failed cell-free DNA screening for which cytogenetic testing was performed. Pregnancies with a failed cell-free DNA screen on first attempt had a relative risk of 130.3 (95% confidence interval, 64.7-262.6) for trisomy 21, trisomy 18, or trisomy 13, and a risk difference of 5.4% (95% confidence interval, 2.6-8.3), compared with pregnancies with a low-risk result. The risk of sex chromosome aneuploidies was not significantly greater in pregnancies with a failed result compared with pregnancies with a low-risk result (relative risk, 2.7; 95% confidence interval, 0.9-7.9; relative difference, 1.2%; 95% confidence interval,-0.9 to 3.2). Cell-free DNA screening test failures are relatively common. Although repeated testing improves the likelihood of an informative result, pregnancies with a failed cell-free DNA screen upon first attempt remain at increased risk for common autosomal aneuploidies, but not sex chromosome aneuploidies.

Utility of fetal cardiac magnetic resonance imaging in assessing the cardiac axis in fetuses with congenital heart disease.

Fetal dedicated echocardiography is the standard to measure the fetal cardiac axis. However, fetal screening ultrasound (US) or fetal dedicated echocardiography may be technically limited. The purpose of this study was to explore the accuracy of fetal cardiac magnetic resonance imaging (MRI) to measure the cardiac axis in fetuses with congenital heart disease as an adjunct to fetal dedicated echocardiography and to assess the predictive value of fetal cardiac MRI measurements in distinguishing healthy fetuses from fetuses with congenital heart disease. This is a retrospective study of fetuses referred to our hospital for a fetal cardiac MRI from November 2019 to December 2021. Cardiac axes were measured in the 4-chamber view of the fetal heart using fetal cardiac MRI and dedicated echocardiography, or only using fetal cardiac MRI when screening US was technically limited. The fetuses were divided into a congenital heart disease group and a healthy control group. We used Bland-Altman analysis and the intraclass correlation coefficient (ICC) to assess the agreement of cardiac axis measurements in fetuses with congenital heart disease obtained by cardiac MRI and by fetal dedicated echocardiography. Receiver operating characteristic (ROC) curve analysis of the fetal cardiac axes in the congenital heart disease and healthy fetus groups assessed the predictive value of the cardiac axis measurements. This retrospective study included 431 women (162 carrying fetuses with congenital heart disease, 269 carrying healthy fetuses). Cardiac axes were measured in the 162 fetuses with congenital heart disease using fetal cardiac MRI and dedicated echocardiography. Cardiac axes were measured in the 269 healthy control fetuses using fetal cardiac MRI when fetal screening US was technically limited. The interobserver analysis and intraobserver analysis showed that the cardiac axis measured by fetal cardiac MRI and fetal dedicated echocardiography was repeatable (ICC>0.90). In 162 fetuses with congenital heart disease, Bland-Altman analysis showed a strong agreement between cardiac MRI and fetal dedicated echocardiography measurements for the cardiac axis. The ICC for the cardiac axis values between cardiac MRI and fetal dedicated echocardiography measurements was 0.99. In fetuses with congenital heart disease, 64.2% (104/162) had an abnormal cardiac axis. For the fetal cardiac axis in both the 162 fetuses with congenital heart disease and the 269 healthy fetuses, the area under the ROC curve reached 0.85 (95% confidence interval: 0.80-0.89; P<0.0001). The cardiac axis can be accurately measured using fetal cardiac MRI when fetal dedicated echocardiography/fetal screening US is technically limited. The cardiac axis measurements by fetal cardiac MRI are consistent with known cardiac axis measurements by fetal dedicated echocardiography. The frequency of abnormal cardiac axis depends on the type of congenital heart disease.

Explaining mothers’ experiences of performing fetal health screening tests in the first trimester of pregnancy: A qualitative study with content analysis approach

BackgroundThe only way to prevent the birth of infants with chromosomal disorders is prenatal diagnosis. Prenatal diagnosis of fetal abnormalities is a critical and stressful emotional event for pregnant women which is accompanied with worry and concern. The aim of the present study was to gain deeper insights into mothers’ experiences of performing fetal health screening tests. MethodsThis was a qualitative research using a conventional content analysis approach. The study population consisted of pregnant women referring to genetic diagnosis laboratories at 11–19 weeks of gestation who were currently in the third trimester of pregnancy. After selecting the participants, a text message was first sent to the mothers and they were asked about the most appropriate time for the interview. At the arranged time, a video call was made with the mother. The data collection method was discovery interviews (Semi-structured interviews). The analysis model used in this study was based on Granheim and Landman’s method. The manuscript was prepared based on Consolidated Criteria for Reporting Qualitative Studies check list for qualitative studies. ResultsFrom a total of 11 interviews, 145 initial codes were obtained which were organized into 3 main categories: Worry and stress; Multi-faceted support; and Conflict between fear and hope. These categories included nine subcategories, namely Concern about the child's disability, Fear of intentional termination of pregnancy, Financial costs, Need for medical support, Husband support, Educational support, Peer support, Fear-hope emotional conflict caused by confirmed diagnosis of fetal abnormalities, and Normal test results. ConclusionAccording to the results of this study, mothers who go for a fetal health screening test and receive suspicious results initially, live in a state of fear and hope until they receive a definitive answer. In order to get rid of their worries and concerns, they need external support such as social support and peer support in addition to the support of their husbands and family.

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

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. 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. 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. 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.

Relationship between False Positive Screening Results of Down Syndrome and Adverse Pregnancy Outcomes.

Maternal serum sample screening in the first and second trimesters has been commonly used to identify women who are at risk of fetal trisomy 21. In addition, these serum markers are associated with adverse perinatal outcomes. Hence, the present study was conducted to determine the relationship between false positive screening results of Down syndrome and adverse pregnancy outcomes. This prospective, two-group, cohort study was conducted on 608 pregnant women who had undergone fetal contingent screening. They were selected through convenience sampling in the twentieth week of pregnancy and were followed up until delivery. The raw Odd Ratios (OR), Relative Risk (RR), and adjusted OR of adverse pregnancy outcomes were calculated in the false positive and true negative groups. The adjusted OR of developing preeclampsia was 1.98 (95%CI: 1.14-3.42), and its RR was 2.13 (95%CI: 1.34-3.38) times higher in the false positive group. Moreover, the adjusted OR of Small for Gestational Age (SGA) was 2.80 (95%CI: 1.76-4.47), and its RR was 2.28 (95%CI: 1.54-3.36) times higher in the false positive group. The adjusted OR of Low Birth Weight (LBW) was 3.34 (95%CI: 1.97-5.64), and its RR was 2.65 (95%CI: 1.72-4.11) times higher in the false positive group. In addition, no significant difference was observed between false positive and true negative groups in terms of preterm birth. Women with a false positive fetal screening test result are more likely to suffer from preeclampsia, SGA, and LBW and require planned prenatal care.

Efficacy of late First-Trimester Fetal Cardiac Screening (Four Chamber View and Ventricular Outflow Tracts) for detection of cardiac anomalies in a Low-Risk Pregnant women

Efficacy of late First-Trimester Fetal Cardiac Screening (Four Chamber View and Ventricular Outflow Tracts) for detection of cardiac anomalies in a Low-Risk Pregnant women

Investigation of the Distribution of Fetal Nasal Bone Percentile Values in First-Trimester Fetal Anomaly Screening

Investigation of the Distribution of Fetal Nasal Bone Percentile Values in First-Trimester Fetal Anomaly Screening

Incidental Detection of Maternal Malignancy by Fetal Cell-Free DNA Screening

(Abstracted from Obstet Gynecol 2022;140:121–131) Early detection and targeted treatment of human disorders are the goal of precision medicine. The advancing technology of cell-free DNA (cfDNA) is increasingly being applied in screening, diagnosis, and treatment of several disease processes.

COMBINED FIRST TRIMESTER SCREENING FOR FETAL DOWN SYNDROME AT THE SPLIT UNIVERSITY HOSPITAL CENTER: A SEVEN-YEAR EXPERIENCE.

The aim of this study was to present the results and to explore the success of combined screening at the Split University Hospital Center. A cross-sectional retrospective study was performed, including all pregnant women who underwent combined screening at the Split University Hospital Center from 2011 to 2017. Data were collected from the hospital archives. During the research period, a total of 6898 pregnant women underwent combined screening. With the high risk cut-off value set at 1:250, the sensitivity of combined screening was 81.0% and specificity 96.8% (AUC 0.929, 95% CI 0.859-1.000; p<0.001). The mean value of a priori risk of Down syndrome based on age was higher than the one calculated by combined screening (1:487.57 vs. 1:13216.9; p<0.001). The number of women who were a priori at a high risk of Down syndrome was significantly higher than the number of those at a high risk based on combined screening results (1457 vs. 239; p<0.001). With the increase in women's age, a statistically significant increase was detected in the mean value of a priori risk of Down syndrome, as well as in the risk based on combined screening results (p<0.001). Combined screening detected a high risk in 8.09% (118/1457) of pregnant women a priori at a high risk of Down syndrome, as well as in 2.22% (121/5441) of pregnant women a priori at a low risk of it. Thus, combined screening placed 121 pregnant women a priori at a low risk in the high-risk group. Down syndrome was subsequently confirmed in 17 (14.05%) women. Analysis of the combined screening results confirmed the validity of using the said fetal Down syndrome screening method in the study population of pregnant women.

High fetal fraction on cell-free fetal DNA screening: is it associated with adverse perinatal outcomes?

High fetal fraction on cell-free fetal DNA screening: is it associated with adverse perinatal outcomes?

Fetal anatomy screening at 11–14 weeks’ ultrasonography, comparison of TAUSG and TVUSG

Fetal anatomy screening at 11–14 weeks’ ultrasonography, comparison of TAUSG and TVUSG

The Relationship Between the Full Biophysical Profile and Rapid Biophysical Profile in Antepartum Fetal Surveillance

Background: One of the best tests for the assessment of a fetus is the biophysical profile test which has a significant effect on the fetus’s health and the outcome of pregnancy. The present study was designed to determine the relationship between the full biophysical profile (FBP) and the rapid biophysical profile (RBP) tests in antepartum fetal surveillance. Methods: In this prospective study, Singleton pregnancies (n=209) with more than 34 weeks of gestational age were chosen. Both FBP and RBP tests were performed for all the patients. The main outcome is the Apgar score and neonatal intensive care unit admission analyzed by SPSS software, version 24. The sensitivity, specificity, positive predictive value, and negative predictive value of RBP were calculated. Findings: Out of 209 people who entered the study, 48 women (23.0%) had gestational diabetes, 84 women (40.2%) had hypertension pregnancy (preeclampsia), 45 people (21.5%) had intrauterine growth restriction, and 45 women (21.5%) had post-date pregnancy. For predicting adverse fetal outcomes of pregnancy, the sensitivity, specificity, positive predictive value, and negative predictive value of RBP were 95%, 73%, 52%, and 98%, respectively. Conclusion: According to the statistically significant positive correlation between RBP and FBP and its simple and rapid application, RBP might be an acceptable alternative method for primary antepartum fetal screening tests in overcrowded obstetrics centers.