First-trimester Screening Research Articles

Learning Curve of First-Trimester Detailed Cardiovascular Ultrasound Screening by Moderately Experienced Obstetricians in 3509 Consecutive Unselected Pregnancies with Fetal Follow-Up

Our primary objective was to assess the effectiveness of detailed cardiovascular ultrasound screening during the first trimester, which was performed by obstetricians with intermediate experience. We collected first-trimester fetal cardiac screening data from an unselected pregnant population at RMC-Fetal Medicine Center during a study period spanning from 1 January 2010, to 31 January 2015, in order to analyze our learning curve. A pediatric cardiologist performed a follow-up assessment in cases where the examining obstetrician determined that the fetal cardiac screening results were abnormal or high-risk. Overall, 42 (0.88%) congenital heart abnormalities were discovered prenatally out of 4769 fetuses from 4602 pregnant women who had at least one first-trimester cardiac ultrasonography screening. In total, 89.2% of the major congenital heart abnormalities (27 of 28) in the following fetuses were discovered (or at least highly suspected) at the first-trimester screening and subsequent fetal echocardiography by the pediatric cardiology specialist. Of these, 96.4% were diagnosed prenatally. According to our results, the effectiveness of first-trimester fetal cardiovascular ultrasound screening conducted by moderately experienced obstetricians in an unselected (’routine’) pregnant population may reach as high as 90% in terms of major congenital heart defects, provided that equipment, quality assurance, and motivation are appropriate.

Role of routine uterine artery Doppler at 18-22 and 24-28 weeks' gestation following routine first-trimester screening for pre-eclampsia.

To assess the performance of mean uterine artery pulsatility index (UtA-PI) at 18-22 and 24-28 weeks of gestation in the prediction of pre-eclampsia (PE) and small-for-gestational age (SGA), and its role in reassessing the risk of PE and SGA in pregnancies screened for PE in the first trimester. This was a retrospective observational cohort study of 4464 women with singleton pregnancy screened routinely for PE in the first trimester, using the Gaussian algorithm, from March 2019 to May 2021, and who underwent UtA-PI assessment at 18-22 gestational weeks. Women were categorized as low risk or high risk based on the risk index obtained after first-trimester screening for PE. In high-risk patients, UtA-PI was also assessed at 24-28 weeks of gestation. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio and area under the receiver-operating-characteristics curve were calculated to assess the performance of UtA-PI at 18-22 and 24-28 weeks in predicting PE and SGA in the high-risk group. In all participants, different UtA-PI percentiles at 18-22 or 24-28 weeks, or their combination, were analyzed to explore their role in reassessing the risk of PE and SGA following first-trimester PE screening. The performance of UtA-PI at 18-22 and 24-28 weeks in the high-risk group was good for predicting preterm PE and preterm SGA, and excellent for predicting early-onset PE and early-onset SGA, with an NPV of > 97% for all outcomes. In the low-risk group, UtA-PI ≥ 95th percentile at 18-22 weeks' gestation identified a subgroup of pregnancies with a significantly higher risk of preterm SGA compared to the low-risk group. In the high-risk group, UtA-PI < 60th percentile at 18-22 weeks' gestation, UtA-PI < 85th percentile at 24-28 weeks' gestation, and UtA-PI < 85th percentile at 24-28 weeks' gestation in women with UtA-PI ≥ 60th percentile at 18-22 weeks, identified subgroups of pregnancies with a risk of PE and SGA comparable to that of the low-risk group. The performance of UtA-PI at 18-22 and 24-28 gestational weeks in high-risk pregnancies identified during first-trimester screening for PE is similar to that in the general population. The risk of PE and SGA in a high-risk cohort can be reassessed by measuring UtA-PI at 18-22 weeks, 24-28 weeks or both, allowing adjustment of follow-up, particularly de-escalation of care. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Abnormal microRNA expression profile at early stages of gestation in pregnancies destined to develop placenta previa

BackgroundPlacenta previa is the abnormal implantation of the placenta into the lower segment of the uterus, is associated with adverse maternal and fetal outcomes such as placenta accreta spectrum disorders, antepartum and postpartum hemorrhage, fetal growth restriction, prematurity, stillbirth and neonatal death, thrombophlebitis, and septicemia. The aim of the study was to assess retrospectively how the later onset of placenta previa affects the microRNA expression profile in the whole peripheral blood during the first trimester of gestation.MethodsRegarding the occurrence of the association between aberrant microRNA expression profiles at early stages of gestation and later onset of various pregnancy-related complications, we selected for the study pregnancies developing placenta previa as the only pregnancy-related disorder. In total, 24 singleton pregnancies diagnosed with placenta previa that underwent first-trimester prenatal screening and delivered on-site within the period November 2012–May 2018 were included in the study. Overall, 80 normal pregnancies that delivered appropriate-for-gestational age newborns after completing 37 weeks of gestation were selected as the control group based on the equality of the length of biological sample storage.ResultsDownregulation of multiple microRNAs (miR-20b-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-103a-3p, miR-130b-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-210-3p, miR-342-3p, and miR-574-3p) was observed in pregnancies destined to develop placenta previa. The combination of seven microRNAs (miR-130b-3p, miR-145-5p, miR-155-5p, miR-181a-5p, miR-210-3p, miR-342-3p, and miR-574-3p) showed the highest accuracy (AUC 0.937, p &amp;lt; 0.001, 100.0% sensitivity, 83.75% specificity) to differentiate, at early stages of gestation, between pregnancies with a normal course of gestation and those with placenta previa diagnosed in the second half of pregnancy. Overall, 75% of pregnancies destined to develop placenta previa were correctly identified at 10.0% FPR.ConclusionConsecutive large-scale analyses must be performed to verify the reliability of the proposed novel early predictive model for placenta previa occurring as the only pregnancy-related disorder.

False-Positive Diagnosis of Congenital Heart Defects at First-Trimester Ultrasound: An Italian Multicentric Study.

Objective. Our objective was to assess the proportion of false-positive CHD cases at the first-trimester evaluation of the fetal heart, performed by experienced operators. Methods. This multicenter retrospective study included of pregnant women with suspicion of CHDs during first-trimester screening for aneuploidies. In all cases, the fetal heart assessments were performed by obstetricians with extensive experience in first-trimester scanning, following an extended protocol proposed by SIEOG national guidelines, which included an axial view of the fetal abdomen and chest to assess visceral situs and evaluation of the four-chamber view (4CV) and three-vessel trachea view (3VTV) with color Doppler. In all suspected cases, fetal echocardiography was offered within 16 and/or at 19-22 weeks' gestation. Results. From a population of 4300 fetuses, 46 CHDs were suspected. Twenty-four cases were excluded from this analysis because the parents opted for early termination of the pregnancies due to associated structural and/or genetic anomalies. For the remaining 22, echocardiography was performed by 16 weeks in 14 cases (64%) and after 16 weeks in 8 cases. In 19 cases (86.4%), a fetal cardiologist confirmed the presence of a CHD. In three cases (13%), the cardiac anatomy was found to be normal at the fetal echocardiography and postnatally. Conclusions. This study shows that the proportion of false-positive cases at the first-trimester ultrasound examination of the fetal heart, performed by experienced operators, may carry a higher risk of false-positive diagnosis than expected. Therefore, this issue must be discussed in instances where a CHD is suspected at the first-trimester screening.

Factors affecting the accuracy of fetal cardiac ultrasound screening in the first trimester of pregnancy.

Most studies on the performance of first-trimester cardiac screening have concentrated on comparing the detection rate between different protocols and not on the actual reason for false-negative results. Herein, we report the performance of first-trimester congenital heart disease (CHD) screening and factors that may affect the detection rate of CHDs. This retrospective observational study included patients who underwent first-trimester screening and subsequently gave birth at our facility. We analyzed the performance of first-trimester screening for CHD and major CHD (CHD requiring cardiac surgery or interventional catheterization within 12months of birth). Of the 6614 fetuses included, 53 had CHD and 35 had major CHD. For the prenatal diagnosis of CHD, the detection rate, specificity, positive predictive value, negative predictive value, and first-trimester detection rate for CHD were 64.1%, 99.9%, 94.4%, 99.7%, and 82.9%, respectively; the respective values for major CHD were 85.7%, 99.96%, 93.75%, 99.92%, and 85.7%. The detection rate was not significantly different when classified by crown-rump length or number of fetuses. A weak correlation was observed between low detection rate of major CHD and lower maternal body mass index (BMI) (correlation ratio: 0.17). The detection rate was significantly higher when the fetus was scanned with its spine at the 5-7 o'clock position (posterior spine) than at other positions (odds ratio: 3.82, 95% confidence interval: 1.16-12.5, p = 0.02). Posterior spine contributes to an improved diagnostic rate in first-trimester CHD screening. In addition, sonographers must recognize that low maternal BMI is a risk factor of false-negative results.

Prediction of Fetal Death in Preterm Preeclampsia Using Fetal Sex, Placental Growth Factor and Gestational Age.

Preeclampsia (PE) is a systemic disease that affects 4.6% of pregnancies. Despite the existence of a first-trimester screening for the prediction of preterm PE, no consensus exists regarding neither the right moment to end the pregnancy nor the appropriate variables to estimate the prognosis. The objective of this study was to obtain a prediction model for perinatal death in patients with preterm PE, useful for clinical practice. Singleton pregnant women with PE and preterm delivery were included in an observational retrospective study. Multiple maternal and fetal variables were collected, and several multivariable logistic regression analyses were applied to construct models to predict perinatal death, selecting the most accurate and reproducible according to the highest area under the curve (AUC) and the lowest Akaike Information Criteria (AIC). A group of 148 pregnant women were included, and 18 perinatal deaths were registered. Univariable logistic regression selected as statistically significant variables the following: gestational age (GA) at admission, fetal sex, poor response to antihypertensive drugs, PlGF, umbilical artery (UA) pulsatility index (PI), cerebroplacental ratio (CPR), and absent/reversed ductus venosus (DV). The multivariable model, including all these parameters, presented an AUC of 0.95 and an AIC of 76.5. However, a model including only GA and fetal sex presented a similar accuracy with the highest simplicity (AUC 0.93, AIC 67.6). Finally, in fetuses with a similar GA, fetal death became dependent on PlGF and fetal sex, underlying the role of fetal sex in all circumstances. Female fetal sex and low PlGF are notorious predictors of perinatal death in preterm PE, only surpassed by early GA at birth.

Screening Characteristics of Hemoglobin and Mean Corpuscular Volume for Detection of Iron Deficiency in Pregnancy.

Iron deficiency in pregnancy remains underdiagnosed despite professional society recommendations for first-trimester complete blood count (CBC) screening. To determine the effectiveness of the CBC hemoglobin and mean corpuscular volume (MCV) to identify iron deficiency in pregnancy, we conducted a retrospective analysis of 20,550 pregnancies from 2009 to 2022 at the University of California, San Francisco, obstetrics clinics. A total of 16,547 (80.5%) pregnant individuals had first-trimester screening CBC; 345 (2.1%) had a coincident ferritin test. Hemoglobin level less than 11 g/dL and MCV level less than 80 fL each had sensitivity of only 30% (95% CI, 20-41%) to detect first-trimester iron deficiency (ferritin level less than 30), corresponding to a negative likelihood ratio of 0.90 (95% CI, 0.77-1.05) and 0.85 (95% CI, 0.73-0.99), respectively. More than 50% of the 1,749 women with documented iron deficiency anytime during pregnancy were neither anemic nor microcytic at the time of diagnosis.

First-Trimester Preeclampsia-Induced Disturbance in Maternal Blood Serum Proteome: A Pilot Study.

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11-13 weeks of gestation were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6-40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE.

Dépistage et prévention de la prééclampsie par l’algorithme de la Fetal Medicine Foundation : une étude avant-après

ObjectiveIn order to identify women at high risk of pre-eclampsia and offer them aspirin prophylactic treatment, the Fetal Medicine Foundation (FMF) recommends a first-trimester screening test. The commonly used threshold for aspirin administration is a risk >1/100, which implies treating an important number of patients. We aimed to assess the use of this strategy with a more restrictive threshold: risk >1/70 and evaluate the impact of this strategy on the prevalence of pre-eclampsia with premature delivery in nulliparous women. MethodsA before-and-after cohort study conducted from 01/09/2014 to 01/12/2018, including nulliparous women undergoing first-trimester ultrasound at the University Hospital of Toulouse. Between 09/2014 and 09/2016 (“before cohort”), women did not undergo pre-eclampsia screening. Between 01/2017 and 12/2018 (“after cohort”), women underwent targeted pre-eclampsia screening using the FMF algorithm, and those with a risk >1/70 received 100mg aspirin. The primary outcome was pre-eclampsia with premature delivery. A univariate and then a multivariate analysis were performed to take into account potential confounding factors. ResultsAmong the 1030 women of the before cohort, 17 women (1.7%) experienced pre-eclampsia with premature delivery, compared to 8 women (1.3%) among the 629 of the after cohort, with no significant difference between the two groups (Adjusted Odd Ratio (95%CI)=0.73 [0.31–1.74]). In the after cohort, 18 women (2.9%) had a risk greater than 1/70 and therefore received aspirin. According to the FMF screening test, 89 women (14.1%) had a risk>1/100, which is the usual threshold for prescribing aspirin for prophylaxis. This means that 71 women had a risk greater than 1/100 but less than 1/70 and therefore did not receive aspirin in this study, even though they would have received aspirin at the usual threshold. ConclusionsThe screening and prevention strategy for pre-eclampsia using restrictive thresholds did not decrease the rate of preeclampsia with premature delivery.

First-trimester uterine artery pulsatility index and preeclampsia risk in pregnancies after artificial frozen embryo transfer: analysis of over 27,000 pregnancies

Accumulating evidence indicates that pregnancies after Artificial Cycle Frozen Embryo Transfer are associated with an increased risk of preeclampsia. Uterine Artery Doppler, along with maternal factors and serum biomarkers, is a crucial biomarker for first-trimester preeclampsia screening, aiding in identifying "high-risk" patients. Guidelines strongly recommend administering aspirin (150mg/day) in these women, owing to robust evidence demonstrating a 62% reduction in the incidence of preeclampsia. Although previous studies suggested lower Uterine Artery Pulsatility Index after Frozen Embryo Transfer, no previous studies explored the impact of the type of endometrial preparation in Uterine Artery Doppler or its influence on estimating 1st-trimester preeclampsia risk. The study aims to evaluate the possible impact of endometrial preparation for frozen embryo transfer on the Uterine Artery Pulsatility Index during the first-trimester preeclampsia screening. This is a retrospective single-center study including 27289 singleton pregnancies (naturally conceived or after assisted reproductive treatment) who underwent the 1st-trimester ultrasound screening at our University Hospital between January 2010 and May 2023. Overall, 27289 pregnancies were included: 23410 naturally conceived and 3879 following assisted reproductive technologies including 391 after ovulation induction and intrauterine insemination, 888 in-vitro fertilization and fresh embryo transfer, and 2600 natural or artificial frozen embryo transfer cycles. An Analysis of covariance (ANCOVA) was conducted to assess if there is an association between the UtAPI value and the mood of conception, adjusting for confounding factors (age, weight, smoking, and oocyte donation). Overall, pregnancies after artificial frozen embryo transfer demonstrated significantly lower 1st-trimester Uterine Artery Pulsatility Index as compared with all other modes of conception in a multivariable regression analysis adjusted for age, weight, smoking, and oocyte donation. The percent difference was 22.6 [CI95%: 20,6; 24,5] compared to naturally conceived pregnancy, 24.5 [CI95%:20,7; 28,1] to Ovulation Induction or intrauterine insemination, 24.8 [CI95%: [22,9; 27,6] to fresh Embryo Transfer and 21.7 [CI95%: [17,6; 25,5] compared to Natural Cycle Frozen Embryo Transfer. When calculating the risk for initiating preventive aspirin administration, the number of patients with increased risk (>1/100) who initiated prophylactic aspirin was significantly lower in the artificial cycle frozen embryo transfer group (7.8% vs 16.0% in natural cycle p<0.001 vs. 11.0% in Fresh embryo transfer p=0.01 vs. 10.5% in ovulation induction or intrauterine insemination p=0.14 vs. 9,3% in naturally conceived pregnancy p=0.03). Surprisingly although significantly fewer patients were considered at high risk for preeclampsia in the Artificial Cycle Frozen Embryo Transfer group, analysis of the actual incidence of preeclampsia demonstrated three times higher preeclampsia incidence in Artificial Cycle group 5.3% (122/2284) as compared with naturally conceived 1.4 % (321/23410), Ovulation Induction and intrauterine insemination 1.3 % (5/391) or Natural Cycle pregnancies 1.6 % (5/316) and more than two times higher when compared to fresh Embryo Transfer pregnancies 2.3 % (20/888), p<0.001. Pregnancies following frozen embryo transfer in artificial cycle are associated with significantly lower Uterine Artery Pulsatility Index during 1st-trimester preeclampsia screening. This results in a significantly lower number of patients being classified as high-risk for developing preeclampsia, despite accumulating evidence that artificial cycles are linked to an increased risk of preeclampsia. Therefore, the first-trimester preeclampsia risk algorithm should be adjusted to accurately assess risk for those undergoing Artificial Cycle Frozen Embryo Transfer, to prevent the under-treatment of patients who are at very high risk of developing preeclampsia and may benefit from prophylactic aspirin.

First-Trimester Ultrasound Screening in Routine Obstetric Practice.

First-Trimester Ultrasound Screening in Routine Obstetric Practice.

Can maternal inflammatory and nutritional status, evaluated by the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI) in the first trimester, predict late-onset fetal growth restriction?

ObjectiveThe aim of this study was to evaluate the potential of immunonutritional markers, specifically the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI), in predicting late-onset fetal growth restriction (LO-FGR) during the first trimester.Materials and methodsThis retrospective study was conducted at a tertiary care center between October 2022 and August 2023. The study included a total of 213 singleton pregnancies, with 99 women in the LO-FGR group and 114 in the healthy control group, matched by maternal age and gestational age at delivery. All blood samples were collected between 11 and 14 weeks of gestation (during the first-trimester screening test). We analyzed first-trimester laboratory parameters, specifically focusing on hemoglobin levels, white blood cells (WBCs), lymphocytes, platelets, and albumin levels. Afterwards, we calculated the HALP score and PNI, and then compared the values of both groups.ResultsBoth HALP score (3.58 ± 1.31 vs. 4.19 ± 1.8, p = 0.012) and PNI (36.75 ± 2.9 vs. 39.37 ± 3.96, p < 0.001) were significantly lower in the FGR group than in the control group. The HALP score cut-off value of < 3.43 in predicting FGR had a sensitivity of 62.3% and specificity of 54.5% (AUC = 0.600, 95% CI: 0.528–0.672, p = 0.012). The PNI cut-off value of < 37.9 in predicting FGR had a sensitivity of 65.8% and specificity of 62.9% (AUC = 0.707, 95% CI: 0.632–0.778, p < 0.001). While the HALP score was not a significant predictor of composite adverse neonatal outcomes in the FGR group, PNI showed a cut-off value of < 37.7 with a sensitivity of 60.9% and specificity of 59.7% (AUC = 0.657, 95% CI: 0.581–0.733, p < 0.001).ConclusionThe HALP score and PNI are valuable prognostic tools for predicting the risk of FGR in the first trimester. Low PNI values are also associated with composite adverse neonatal outcomes in pregnancies complicated by FGR.

Array Comparative Genomic Hybridization (aCGH) Results among Patients Referred to Invasive Prenatal Testing after First-Trimester Screening: A Comprehensive Cohort Study.

Introduction: Invasive prenatal testing with chromosomal microarray analysis after first-trimester screening is a relevant option but there is still debate regarding the indications. Therefore, we evaluated the prevalence of numerical chromosomal aberrations detected by classic karyotype and clinically relevant copy number variants (CNVs) in prenatal samples using array comparative genomic hybridization (aCGH) stratified to NT thickness: <the 95th percentile, the 95th percentile-2.9 mm, 3.0-3.4 mm, 3.5-3.9 mm, 4.0-4.5 mm, and >4.5 mm, and by the presence/absence of associated structural anomalies detected by ultrasonography. Materials and Methods: Retrospective cohort study carried out at two tertiary Polish centers for prenatal diagnosis (national healthcare system) in central and south regions from January 2018 to December 2021. A total of 1746 prenatal samples were received. Indications for invasive prenatal testing included high risk of Down syndrome in the first-trimester combined test (n = 1484) and advanced maternal age (n = 69), and, in 193 cases, other reasons, such as parental request, family history of congenital defects, and genetic mutation carrier, were given. DNA was extracted directly from amniotic fluid (n = 1582) cells and chorionic villus samples (n = 164), and examined with classic karyotype and aCGH. Results: Of the entire cohort of 1746 fetuses, classical karyotype revealed numerical chromosomal aberrations in 334 fetuses (19.1%), and aCGH detected CNV in 5% (n = 87). The frequency of numerical chromosomal aberrations increased with NT thickness from 5.9% for fetuses with NT < p95th to 43.3% for those with NT > 4.5 mm. The highest rate of numerical aberrations was observed in fetuses with NT > 4.5 mm having at least one structural anomaly (50.2%). CNVs stratified by NT thickness were detected in 2.9%, 2.9%, 3.5%, 4.3%, 12.2%, and 9.0% of fetuses with NT < 95th percentile, 95th percentile-2.9 mm, 3.0-3.4 mm, 3.5-3.9 mm, 4.0-4.5 mm, and >4.5 mm, respectively. After exclusion of fetuses with structural anomalies and numerical aberrations, aCGH revealed CNVs in 2.0% of fetuses with NT < 95th percentile, 1.5% with NTp95-2.9 mm, 1.3% with NT 3.0-3.4 mm, 5.4% with NT 3.5-3.9 mm, 19.0% with NT 4.0-4.5 mm, and 14.8% with NT > 4.5 mm. Conclusions: In conclusion, our study indicates that performing aCGH in samples referred to invasive prenatal testing after first-trimester screening provides additional clinically valuable information over conventional karyotyping, even in cases with normal NT and anatomy.

Detection Rate of Fetal Anomalies in Early Mid-Trimester Compared to Late Mid-Trimester Detailed Scans: Possible Implications for First-Trimester Sonography.

Objective: A late mid-trimester fetal organ scan (lMTS) is recommended between 18 and 22 weeks of pregnancy. Evidence has been accumulating on the effectiveness of first-trimester anatomy scans. Early mid-trimester fetal scans (eMTSs; 14-17 weeks) may have the advantage of visualization of most organs, hence allowing earlier genetic assessment and decision making. Our aim is to examine the effectiveness of eMTSs in identifying fetal anomalies compared to lMTSs. Methods: A retrospective study was conducted based on data from the multidisciplinary prenatal diagnosis clinic in a tertiary center. During the study period (2011-2021), an out-of-pocket eMTS in a community setting was offered routinely to the general population. Women who had previously undergone an eMTS and were later assessed due to a fetal anomaly in our clinic were included in the study. The cohort was divided into two groups according to whether the anomaly had been detected during the eMTS. We then compared the groups for factors that may be associated with anomaly detection in eMTSs. We used t-tests and chi-square tests, for quantitative and qualitative variables, respectively, to determine variables related to eMTS anomaly detection, and logistic regression for multivariate analysis. Results: Of 1525 women assessed in our multidisciplinary clinic, 340 were included in the study. The anomaly detection rate of the eMTS compared to the lMTS was 59.1% The eMTS detection rates for specific organ systems were as follows: skeletal, 57%; cardiac, 52%; congenital anomalies of the kidneys and urinary tract (CAKUT), 44%; central nervous system, 32.4%; chest, 33%; and abdominal, 28%. In multivariate analysis, abnormal first-trimester screening (aOR 3.2; 95%CI 1.26-8.08) and multiple anomalies (aOR 1.86; 95%CI 1.02-3.37) were found to be associated with eMTS anomaly detection. Conclusions: The eMTS detection rate was nearly 60% and was most accurate in detecting skeletal, cardiac, and CAKUT anomalies. Since the eMTS was community-based, this rate likely reflects a "real-world" scenario. Our findings support consideration of performing an eMTS or first-trimester scan routinely for earlier diagnosis and decision making, as an adjunctive to lMTSs. Future studies will examine the cost-effectiveness of early scans.

Placental mosaicism for autosomal trisomies: comprehensive follow-up of 528 Danish cases (1983–2021)

BackgroundMosaicism, characterized by the presence of two or more chromosomally distinct cell lines, is detected in 2% to 4% of chorionic villus samples (CVSs). In these cases, the aberration may be confined to the placenta or additionally present in the fetus. Fetal involvement may manifest as fetal malformations, while confined placental mosaicism (CPM) poses risks such as preterm birth and low birth weight. Differentiating between true fetal mosaicism and CPM at the time of the chorionic villus sampling is challenging and requires follow-up by an amniocentesis and ultrasonography. ObjectiveTo estimate the risk of fetal involvement or adverse pregnancy outcomes for specific chromosomes after detecting mosaicism for an autosomal trisomy in a CVS and identify high (red), intermediate (yellow), and low (green) risk chromosomes. Further, to explore possible associations with level of mosaicism and screening parameters. Study DesignA retrospective descriptive study of all singleton pregnancies with mosaicism detected in CVSs from 1983 to 2021 identified in the Danish Cytogenetic Central Registry and the Danish Fetal Medicine Database. ResultsOf 90,973 CVSs, 528 cases had mosaicism involving an autosomal trisomy and where genetic follow-up had been performed. The overall risk of fetal involvement was 13% (69/528) with extensive variations depending on which chromosome was involved (eg, trisomy 7: 0% [0/55] or trisomy 21: 46% [19/41]). Higher levels of mosaicism in the CVS suggested fetal involvement as mean mosaic level was 55% in true fetal mosaics vs 28% in cases confined to the placenta (P=.0002). In cases with CPM (459/528), the risk of delivering small-for-gestational-age neonates was 14% (48/341). The risk of preterm birth (before 37 weeks) was 15% (51/343). The collective risk of adverse outcome was 22% (76/343) in pregnancies that continued and where information on birth weight and gestational age at birth was available. Adverse outcomes varied substantially between chromosomes. Also, multiple-of-the-median (MoM) values of pregnancy-associated plasma protein A was predictive of these issues as it was significantly lower in cases with adverse outcome compared to cases with a normal outcome (small for gestational age: 0.23 MoM vs 0.47 MoM, P<.0001) or preterm birth: 0.25 MoM vs 0.47 MoM, P<.0001). After the introduction of combined first-trimester screening (cFTS) in 2004, the detection of cases with fetal involvement seemed to increase as the risk before 2004 was 9% (16/174) compared to 15% (53/354) after 2004 (risk ratio: 1.7 [95% CI: 1.0; 2.8]). The risk of adverse outcome in CPM pregnancies increased from 16% (22/139) before 2004 to 27% (55/204) after 2004 (risk ratio 1.7 [95% CI: 1.1; 2.7]). ConclusionIntroducing cFTS increased the detection of placental mosaicism with fetal involvement and CPM with adverse outcome. In cases of mosaicism in CVSs, the risk of fetal involvement and adverse outcomes varied considerably between chromosomes. Importantly, adverse outcomes were seen in CPM for many trisomies besides trisomy 16.

Awareness of down syndrome screening among educated Muslim women is associated with a favorable attitude toward testing

ObjectiveThere is a general assumption that Muslim women refuse Down syndrome screening, and therefore, many health practitioners do not offer it or briefly discuss it with their participants. This study aims to objectively assess women’s awareness, knowledge, and attitudes toward Down Syndrome screening (D.S.S) in a Muslim-majority population.MethodsWe conducted a cross-sectional study among attendees of antenatal clinics at a major university hospital in Saudi Arabia, aiming for a sample size of at least 385 Muslim women. A semi-structured questionnaire assessed awareness of different D.S.S. options and the source of that information (2 items), specific knowledge of D.S.S. (14 items), and attitudes (4 items). The knowledge and attitudes scores were calculated using a five-level agreement Likert-type scale.ResultsAmong 434 participants, with an even distribution among all age groups and a majority of a college degree holder or higher (71%), 178 (41.0%) reported awareness of D.S.S. Factors associated with increased awareness were maternal age above 40 or those under 30, nulliparity, and extended family history of fetal congenital anomalies (P-value = 0.03,0.015, and 0.017, respectively). Recognized tests were ultrasound measurement of nuchal translucency (71.9%) and first-trimester serum screening (58.4%). The sources of knowledge were obstetricians (53.9%), followed by family and friends (27.0%). The overall mean ± SD knowledge score was 53.9 ± 8.7 out of 70, and the mean attitude score was 17.4 ± 2.9 out of 20. Having 1 or 2 children is associated with a higher knowledge score, and most participants who reported awareness of D.S.S. (51.7%) had a favorable attitude toward screening.ConclusionAwareness of D.S.S. among Muslim women is associated with favorable attitudes towards testing, contradicting the general assumption and highlighting the need for systematic education to increase awareness and subsequent testing uptake.

First-trimester predictive models for adverse pregnancy outcomes-a base for implementation of strategies to prevent cardiovascular disease development.

This study aimed to establish efficient, cost-effective, and early predictive models for adverse pregnancy outcomes based on the combinations of a minimum number of miRNA biomarkers, whose altered expression was observed in specific pregnancy-related complications and selected maternal clinical characteristics. This retrospective study included singleton pregnancies with gestational hypertension (GH, n = 83), preeclampsia (PE, n = 66), HELLP syndrome (n = 14), fetal growth restriction (FGR, n = 82), small for gestational age (SGA, n = 37), gestational diabetes mellitus (GDM, n = 121), preterm birth in the absence of other complications (n = 106), late miscarriage (n = 34), stillbirth (n = 24), and 80 normal term pregnancies. MiRNA gene expression profiling was performed on the whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time reverse transcription polymerase chain reaction (RT-PCR). Most pregnancies with adverse outcomes were identified using the proposed approach (the combinations of selected miRNAs and appropriate maternal clinical characteristics) (GH, 69.88%; PE, 83.33%; HELLP, 92.86%; FGR, 73.17%; SGA, 81.08%; GDM on therapy, 89.47%; and late miscarriage, 84.85%). In the case of stillbirth, no addition of maternal clinical characteristics to the predictive model was necessary because a high detection rate was achieved by a combination of miRNA biomarkers only [91.67% cases at 10.0% false positive rate (FPR)]. The proposed models based on the combinations of selected cardiovascular disease-associated miRNAs and maternal clinical variables have a high predictive potential for identifying women at increased risk of adverse pregnancy outcomes; this can be incorporated into routine first-trimester screening programs. Preventive programs can be initiated based on these models to lower cardiovascular risk and prevent the development of metabolic/cardiovascular/cerebrovascular diseases because timely implementation of beneficial lifestyle strategies may reverse the dysregulation of miRNAs maintaining and controlling the cardiovascular system.

Combined first-trimester screening and invasive diagnostics for atypical chromosomal aberrations: Danish nationwide study of prenatal profiles and detection compared with NIPT.

Our aim was to examine the prenatal profiles of pregnancies affected by an atypical chromosomal aberration, focusing on pathogenic copy-number variants (pCNVs). We also wanted to quantify the performance of combined first-trimester screening (cFTS) and a second-trimester anomaly scan in detecting these aberrations. Finally, we aimed to estimate the consequences of a policy of using non-invasive prenatal testing (NIPT) rather than invasive testing with chromosomal microarray analysis (CMA) to manage pregnancies identified as high risk by cFTS. This was a retrospective review of the Danish Fetal Medicine Database of all pregnant women who underwent cFTS and a risk assessment for trisomy 21 between 1 January 2008 and 31 December 2018. Chromosomal aberrations diagnosed prenatally, postnatally or from fetal tissue following pregnancy loss or termination of pregnancy were identified. Chromosomal aberrations were grouped into one of six categories: triploidy; common trisomy (13, 18 or 21); monosomy X; other sex-chromosome aberration (SCA); pCNV; and rare autosomal trisomy (RAT) or mosaicism. The prevalence of each aberration category was stratified by the individual cFTS markers and trisomy 21 risk estimate, and the size of each pCNV diagnosed by CMA was calculated. We retrieved data on 565 708 pregnancies, of which 3982 (0.70%) were diagnosed with a fetal chromosomal aberration. cFTS identified 87% of the common trisomies, but it also performed well in identifying triploidies (86%), monosomy X (92%), atypical SCAs (58%) and RATs or mosaicisms (70%). pCNVs comprised 27% (n = 1091) of the chromosomal aberrations diagnosed overall, and the prevalence increased during the study period, as prenatal CMA was increasingly being performed. In pregnancies with a maternal age < 30 years, nuchal translucency (NT) thickness ≤ 95th centile, pregnancy-associated plasma protein-A (PAPP-A) ≥ 1 multiple of the median, or trisomy 21 risk of ≤ 1 in 1000, the prevalence of pCNVs exceeded significantly the prevalence of trisomies 21, 18 and 13. Pregnancies affected by a pCNV had significantly increased NT and decreased levels of the maternal biomarkers PAPP-A and β-human chorionic gonadotropin compared with unaffected pregnancies. However, only 23% of these pregnancies screened positive on cFTS and 51% of pCNVs were not detected until after birth. Among high-risk pregnancies, pCNVs comprised 14% of diagnosed aberrations, and when other atypical aberrations were considered, conventional NIPT (screening for trisomies 21, 18 and 13 and monosomy X) would miss 27% of all pathogenic aberrations diagnosed from invasive testing following a high-risk cFTS result. Thus, 1 in 26 pregnancies at high risk following cFTS would be affected by a chromosomal aberration despite a normal result from conventional NIPT. In a contingent screening model using NIPT for the 'intermediate'-risk group (trisomy 21 risk of 1 in 100-299), 50% of the aberrations would be missed. In our cohort, 79% of the pCNVs diagnosed were < 5Mb and therefore not detectable using current forms of 'genome-wide' NIPT. As a by-product of screening for trisomies 21, 18 and 13, most triploidies and the majority of atypical SCAs, RATs and mosaicisms are detected before birth. However, only 23% of pCNVs are associated with a high-risk result according to cFTS and only half are diagnosed before birth. Replacing invasive testing with NIPT for high-risk pregnancies would substantially decrease the first-trimester detection of pathogenic chromosomal anomalies. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

"It Empowers You to Empower Them": Health Professional Perspectives of Care for Hyperglycaemia in Pregnancy Following a Multi-Component Health Systems Intervention.

The Northern Territory (NT) and Far North Queensland (FNQ) have a high proportion of Aboriginal and Torres Strait Islander women birthing who experience hyperglycaemia in pregnancy. A multi-component health systems intervention to improve antenatal and postpartum care in these regions for women with hyperglycaemia in pregnancy was implemented between 2016 and 2019. We explored health professional perspectives on the impact of the intervention on healthcare. The RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance) underpinned this mixed-methods evaluation. Clinicians were surveyed before (n = 183) and following (n = 137) implementation. The constructs explored included usual practice and satisfaction with care pathways and communication between services. Clinicians, policymakers and the implementation team were interviewed (n = 36), exploring the impact of the health systems intervention on practice and systems of care. Survey and interview participants reported improvements in clinical practice and systems of care. Self-reported glucose screening practices improved, including the use of recommended tests (72.0% using recommended first-trimester screening test at baseline, 94.8% post-intervention, p < 0.001) and the timing of postpartum diabetes screening (28.3% screening at appropriate interval after gestational diabetes at baseline, 66.7% post-intervention, p < 0.001). Health professionals reported multiple improvements to care for women with hyperglycaemia in pregnancy following the health systems intervention.

Limited Role of MSAFP Screening for Prenatal Omphalocele Detection.

Although serum screening for aneuploidies has become less prevalent, maternal-serum alpha-fetoprotein (MSAFP) screening for body-wall defects remains widespread. We explored whether MSAFP screening is associated with earlier omphalocele detection than ultrasound alone. This is a retrospective cohort study of prenatally detected omphalocele cases at our center from 2007 to 2023. We explored the association between MSAFP screening, gestational age at omphalocele detection, and clinical outcomes. Among 101 pregnancies with prenatally diagnosed omphalocele, 27 (26.7%) had MSAFP screening. The median gestational age at MSAFP screening was 17 weeks 4 days. Of those who received MSAFP screening, 11 (41%) had values ≥2.5 multiples of the median (MoM) and 16 (59%) were not elevated. MSAFP results did not correlate with omphalocele size and were not associated with prenatal or postnatal outcomes. MSAFP screening did not result in earlier suspicion for or confirmation of omphalocele (P = .97 and P = .87, respectively). In contrast, first-trimester ultrasound screening was associated with earlier suspicion for and confirmation of omphalocele (P < .01 and P = .01, respectively). There were no clinical or demographic differences between those who received MSAFP screening and those who did not (including body mass index or commute distance to an urban center). MSAFP screening is not associated with earlier omphalocele detection. Furthermore, in pregnancies with prenatally diagnosed omphalocele, the results of MSAFP screening are not predictive of clinical outcomes.