First-trimester Screening Research Articles

Pregnancy Through Assisted Conception After Radical Trachelectomy: A Case Report

Introduction: Trachelectomy, a conservative surgery in the early stages of cervical cancer, allows young women to keep their fertility. Infertility after such a surgery is frequent, and many couples should opt for assisted reproduction. Objectives: This case report aims to present a successful pregnancy in a woman with a history of cervical cancer and complete removal of the uterine cervix through trachelectomy. Case Presentation: A successful pregnancy is described after two failed attempts of embryo transfer (ET) in a 32-year-old woman with a history of trachelectomy due to stage IA invasive squamous cell carcinoma of the cervix. Before and after radical trachelectomy, she received adjuvant chemotherapy. In her second course of in-vitro fertilization, after a mock transfer at the time of ovum pickup with 11 oocytes and 7-day 3 embryos, her third ET cycle under ultrasound guide was successful. During pregnancy, in the first-trimester screening, nuchal translucency was reported to be 4.5 mm. Therefore, chorionic villous sampling and comparative genomic hybridization CGH-Array were performed before preparing for abdominal cerclage at 14 weeks. Further screening tests were normal. Finally, she delivered a 2430 g healthy baby girl through cesarean section at 37 weeks. Conclusions: The mock transfer and ultrasound-guided ET are suggested for women with a history of trachelectomy.

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.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin at 11-13 weeks' gestation.

To examine the performance of screening for preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of maternal serum glycosylated fibronectin (GlyFn), mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). This was a case-control study in which maternal serum GlyFn was measured using a point-of-care device in stored samples from a non-intervention screening study of singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation. In the same samples, PlGF was measured by time-resolved fluorometry. We used samples from women who delivered with PE at < 37 weeks' gestation (n = 100), PE at ≥ 37 weeks (n = 100), gestational hypertension (GH) at < 37 weeks (n = 100), GH at ≥ 37 weeks (n = 100) and 1000 normotensive controls with no pregnancy complications. In all cases, MAP and UtA-PI had been measured during the routine 11-13-week visit. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements of medical history. Similarly, the measured values of MAP, UtA-PI and PlGF were converted to MoMs. The competing-risks model was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE or GH at < 37 and ≥ 37 weeks' gestation. Screening performance was estimated by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at 10% fixed false-positive rate (FPR). The maternal characteristics and elements of medical history with a significant effect on the measurement of GlyFn were maternal age, weight, height, race, smoking status and history of PE. In pregnancies that developed PE, GlyFn MoM was increased and the deviation from normal decreased with increasing gestational age at delivery. The DR and AUC of screening for delivery with PE at < 37 weeks' gestation by maternal factors alone were 50% and 0.834, respectively, and these increased to 80% and 0.949, respectively, when maternal risk factors were combined with MAP, UtA-PI and PlGF (triple test). The performance of the triple test was similar to that of screening by a combination of maternal factors, MAP, UtA-PI and GlyFn (DR, 79%; AUC, 0.946) and that of screening by a combination of maternal factors, MAP, PlGF and GlyFn (DR, 81%; AUC, 0.932). The performance of screening for delivery with PE at ≥ 37 weeks' gestation was poor; the DR for screening by maternal factors alone was 35% and increased to only 39% with use of the triple test. Similar results were obtained when GlyFn replaced PlGF or UtA-PI in the triple test. The DR of screening for GH with delivery at < 37 and ≥ 37 weeks' gestation by maternal factors alone was 34% and 25%, respectively, and increased to 54% and 31%, respectively, with use of the triple test. Similar results were obtained when GlyFn replaced PlGF or UtA-PI in the triple test. GlyFn is a potentially useful biomarker in first-trimester screening for preterm PE, but the findings of this case-control study need to be validated by prospective screening studies. The performance of screening for term PE or GH at 11 + 0 to 13 + 6 weeks' gestation by any combination of biomarkers is poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal First-Trimester Alpha-Fetoprotein and Placenta-Mediated Pregnancy Complications.

Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers. Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption). A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]). Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.

SC4_3. Implementation of routine first-trimester combined screening for preeclampsia based on the gaussian algorithm: a clinical effectiveness study

SC4_3. Implementation of routine first-trimester combined screening for preeclampsia based on the gaussian algorithm: a clinical effectiveness study

OP09_4. Detection of false positives from first-trimester preeclampsia screening at the second-trimester of pregnancy (STOPPRE trial)

OP09_4. Detection of false positives from first-trimester preeclampsia screening at the second-trimester of pregnancy (STOPPRE trial)

The effect of cognitive behavioral counseling on anxiety and worry level of women with intermediate risk during first trimester screening for down syndrome: a randomized controlled trial: a randomized controlled trial

BackgroundAnxiety related to prenatal screening programs negatively affects maternal and child health.ObjectiveThe study aimed to determine the effect of Cognitive Behavioral Counseling on the anxiety and worry levels of women with intermediate risk during first-trimester screening for Down Syndrome.MethodsThe study was a randomized controlled trial conducted on 52 pregnant women with intermediate risk (1: 51 − 1:1500) during first-trimester screening for Down Syndrome and without additional structural anomalies that referred to three cities of Zanjan province in 2021. The eligible women were randomly assigned to intervention and control groups, with a block size of four. The intervention group received CBC in four sessions of 120 min two times a week by phone. Data were collected using Vandenberg Anxiety Questionnaire, and Cambridge Worry Questionnaire in three phases baseline, after the intervention, and 6 weeks follow-ups. Data were analyzed using independent t-test, chi-square, and repeated measures ANOVA at a 95% confidence level. (P < 0.05).ResultsIn the counselling group, the mean (SD) of a total score of anxiety before the intervention was 67.11 (20.68) which decreased to 32.50 (13.58) in six weeks after the intervention. Furthermore, the mean (SD) of a total score of worry before the intervention was 56.19 (16.76) which decreased to 32.96 (8.89) six weeks after the intervention. Based on the repeated measures ANOVA test, the mean total score of anxiety and worry were statistically significant 6 weeks after the intervention compared with the control group(p < 0.001).ConclusionBased on the study results, CBC can reduce the anxiety and worry levels of women with intermediate risk during first trimester screening for Down Syndrome.Trial registrationThe study was registered at the Iranian Registry of Clinical Trials website under the code IRCT20160608028352N8, (https://en.irct.ir/trial/49998). The first trial registration date was (29/08/2020).

OP19_5. First-trimester screening for preeclampsia and small-for-gestational-age: a comparison of the gaussian and FMF algorithms

OP19_5. First-trimester screening for preeclampsia and small-for-gestational-age: a comparison of the gaussian and FMF algorithms

Cost-effectiveness analysis of a first-trimester screening test for preterm preeclampsia in the Netherlands

ObjectivesThe risk of preterm preeclampsia (PT PE) can significantly be reduced by starting acetylsalicylic acid ≤ 16 weeks of gestational age. First trimester predictive models based on maternal risk factors to effectively start this therapy lacked sufficient power, but recent studies showed that these models can be improved by including test results of biochemical and/or -physical markers. To investigate whether testing a biochemical marker in the first trimester is cost-effective in the Netherlands, a cost-effectiveness analysis was performed in this study. Study designThe outcome of this study was expressed as an incremental cost-effectiveness ratio (ICER) with as effect prevented PT PE cases. To evaluate the impact of each model parameter and to determine model uncertainties, both univariate and probabilistic sensitivity analyses were performed. ResultsWhen compared to the baseline strategy, the test strategy is estimated to save almost 4 million euros per year on a national scale and at the same time this would prevent an additional 228 PT PE cases. The sensitivity analyses showed that the major drivers of the result are the costs to monitor a high-risk pregnancy and the specificity and that most of the model simulations were in the southeast quadrant: cost saving and more prevented complications. ConclusionsThis study showed that a first-trimester test strategy to screen for PT PE in the first trimester is potentially cost-effective in the Dutch healthcare setting. The fact that the specificity is a major driver of the ICER indicates the importance for a (new) screening model to correctly classify low-risk pregnancies.

Screening for Preeclampsia and Fetal Growth Restriction in the First Trimester in Women without Chronic Hypertension.

Nowadays, it is possible to identify a group at increased risk of preeclampsia (PE) and fetal growth restriction (FGR) using the principles of the Fetal Medicine Foundation (FMF). It has been established for several years that acetylsalicylic acid (ASA) reduces the incidence of PE and FGR in high-risk populations. This study aimed to evaluate the implementation of ASA use after the first-trimester screening in a Polish population without chronic hypertension, as well as its impact on perinatal complications. A total of 874 patients were enrolled in the study during the first-trimester ultrasound examination. The risk of PE and FGR was assessed according to the FMF guidelines, which include the maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtPI), pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PLGF). Among patients with a risk higher than >1:100, ASA was administered at a dose of 150 mg. Perinatal outcomes were assessed among the different groups. When comparing women in the high-risk group with those in the low-risk group, a statistically significantly higher risk of pregnancy complications was observed in the high-risk group. These complications included pregnancy-induced hypertension (PIH) (OR 3.6 (1.9-7)), any PE (OR 7.8 (3-20)), late-onset PE (OR 8.5 (3.3-22.4)), FGR or small for gestational age (SGA) (OR 4.8 (2.5-9.2)), and gestational diabetes mellitus type 1 (GDM1) (OR 2.4 (1.4-4.2)). The pregnancies in the high-risk group were more likely to end with a cesarean section (OR 1.9 (1.2-3.1)), while the newborns had significantly lower weights (<10 pc (OR 2.9 (1.2-6.9)), <3 pc (OR 10.2 (2.5-41.7))). The first-trimester screening test for PE and FGR is a necessary and effective tool in identifying high-risk pregnancies. ASA prophylaxis among high-risk patients may have the most beneficial effect. Furthermore, this screening tool may significantly reduce the incidence of early-onset PE (eo-PE).

Are Fetal Nuchal Translucency Thickness and Crown-rump Length Associated with Maternal Hematological and Biochemical Profile?

Background: Nuchal translucency (NT) and crown-rump length (CRL) measurements are useful fetal screening tests. The extent to which maternal hematological and biochemical profiles may impact these markers has not been evaluated. This study is designed to address this issue. Methods: Data from the first-trimester screening for aneuploidy and maternal laboratory results, including maternal fasting blood sugar (FBS), thyroid stimulating hormone (TSH), hemoglobin, hematocrit, vitamin D3, and ferritin, were collected at 11 - 13 weeks of gestational age. The association between NT/CRL and maternal laboratory tests was analyzed and reported. Results: 258 women with a mean ± SD age of 32.6 ± 5.2 years participated in the study. NT and CRL values were not correlated with maternal laboratory variables. Otherwise, CRL was positively correlated with increasing maternal age, and NT was associated with increasing gestational age. Conclusions: The results of this study indicate that NT and CRL values at 11 - 13 weeks of gestation are independent of maternal hemoglobin, FBS, vitamin D3, and ferritin status.

Aspirin Discontinuation at 24 to 28 Weeks’ Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial

ABSTRACT Preeclampsia affects up to 4% of pregnancies and is marked by the development of hypertension and proteinuria after 20 weeks of gestation. Complications associated with the disorder include preterm birth, fetal growth restriction, placental abruption, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, seizures, and other end organ damage. Aspirin has been shown to reduce the incidence of preterm preeclampsia by 62%. However, it can also lead to peripartum bleeding. Screening for preeclampsia in the first trimester (11 to 13 weeks' gestation) can help identify up to 60% of pregnant individuals who will develop preterm preeclampsia. If preeclampsia screening is conducted during this first trimester, aspirin can be initiated earlier and discontinued earlier to mitigate the risk of peripartum bleeding. In addition, increased soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio is associated with preeclampsia weeks before its clinical onset. An sFlt-1:PlGF of ≤38 has been shown to accurately exclude preeclampsia in pregnant individuals with suspected disease. The aim of this study was to compare the effect of discontinuing aspirin in pregnant individuals at 24 and 28 weeks' gestation with a normal sFlt-1:PlGF ratio of ≤38 against those who continued aspirin treatment until 36 weeks of gestation. This was an open-label, randomized, noninferiority trial conducted at 9 maternity hospitals in Spain. Included were adult individuals with singleton pregnancies who had live births, were found to be at high risk of preeclampsia at the first-trimester screening, and a normal sFlt-1:PlGF between 24 and 28 weeks of gestation. Participants were randomly assigned 1:1 to discontinue aspirin (intervention group) or continue aspirin treatment (control group). The primary outcome was delivery due to preterm preeclampsia (before 37 weeks' gestation). Noninferiority was met if the higher 95% confidence interval (CI) for the difference in the incidences of preterm preeclampsia between the 2 groups was &lt;1.9%. A total of 964 pregnant individuals, who were identified as high-risk for preterm preeclampsia and prescribed 150 mg of aspirin daily at bedtime, were eligible for the analysis. The rates of preterm preeclampsia in the intervention and control groups were 1.48% and 1.73%, respectively (absolute difference, −0.25% [95% CI, −1.86% to 1.36%]). In conclusion, the threshold for noninferiority was not met. In pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio of ≤38, discontinuing aspirin at 24 to 28 weeks' gestation was noninferior to continuing aspirin until 36 weeks to prevent preterm preeclampsia.

The role of ultrasound in first-trimester screening after the introduction of NIPT as a service of public health insurance - a consensus statement of the Fetal Medicine Foundation (FMF) Germany.

Combined first-trimester screening (FTS) and noninvasive prenatal testing (NIPT) have been proven to be reliable noninvasive procedures to detect the most common chromosomal abnormalities (trisomies 21, 18, 13) in the first trimester. The aim of this paper is to demonstrate the strengths and limitations of these two procedures and to give a consensus statement of the Fetal Medicine Foundation (FMF) Germany on how to use the two techniques in the first trimester after the introduction of NIPT as a service of the statutory health insurance companies in Germany.

Early Prediction of Gestational Diabetes Mellitus Using Placental Strain Elastography and Subcutaneous Adipose Tissue Thickness.

The aim of this study is to investigate the efficacy of placental strain ratio values measured by real-time sonoelastography and maternal subcutaneous adipose tissue thickness measured by two-dimensional ultrasonography in predicting gestational diabetes mellitus in the first trimester. The population of the study consisted of the first 210 consecutive singleton pregnant women who applied for routine first-trimester screening between the 11th and 14th week of gestation.B-mode subcutaneous adipose tissue thickness sonography and real-time placental strain elastography scanning were performed.All patients underwent 75 g oral glucose tolerance test between the 24th and 28th week of gestation. American Diabetes Association criteria were used in the diagnosis of gestational diabetes mellitus. It was observed that body mass index (p<0.001), first-trimester fasting blood sugar (p<0.001), subcutaneous adipose tissue thickness (p<0.001), and placental strain ratio value (p<0.001) affected the development of gestational diabetes mellitus statistically. The multivariate analysis shown that subcutaneous adipose tissue thickness (odds ratio=1.271, 95% CI=1.142-1.416, p<0.001) and placental strain ratio value (odds ratio=3.664, 95% CI=1.927-6.969, p<0.001) were the independent risk factors affecting the development of gestational diabetes mellitus. The findings of this study indicated a positive correlation between 75 g oral glucose tolerance test application and first trimester subcutaneous adipose tissue thickness and placental strain ratio. Using the cut-off values of>11.5 mm for subcutaneous adipose tissue and>0.986 for placental strain ratio, the development of gestational diabetes mellitus may be predicted in the early weeks of pregnancy.

What Should be the Thyroid Stimulating Hormone Cut-off Level in the First-Trimester Screening? A prospective Cohort Study and Mini Review of The Guidelines

Aim: Thyroid Stimulating Hormone (TSH) and Human Chorionic Gonadotropin (hCG) are glycoproteins that the alpha subunit common. As a consequence of this, hCG has intrinsic thyrotropic activity. Because of high levels of hCG, maternal serum thyrotropin level is seen to decrease in 80% of pregnancies. Novel investigation and several commission opinions recommend that the TSH cut-off value should be 2.5 mU/L in the first-trimester thyroid function screening.. We aimed to evaluate the contributions of the maternal serum TSH cut-off value of 2.5 mU/L to the development of maternal and fetal complications. Materials and Methods: We constructed the study with pregnancies in their first 12 weeks and planned to do only observation prospectively. We excluded pregnant women with systemic disease and any history of thyroid surgery or thyroid pathology. According to the TSH level, a case group(TSH level &amp;gt;2.5 mU/L) and a control group (TSH level&amp;lt;2.5 mU/L) were created through the pregnants with normal Thyroxine (T4) levels. The cohort group were divided into four subgroups according to whether they were anti-thyroid peroxidase (anti-TPO) positive or not. We observed the fetomaternal outcomes like pregnancy loss, hyperemesis gravidarum, hypertensive disorders, gestational diabetes, prelabour rupture of membranes, placental abruption, with routine prenatal visits until delivery; also delivery style, birth weight, shoulder dystocia, newborn intensive care needs, and postpartum hemorrhage were recorded. Results: The incidence of miscarriage in the subgroup with TSH &amp;gt;2.5 mU/L and anti-TPO (+) was significantly higher than in those with TSH &amp;lt;2.5 mU/L and anti-TPO (+) (p&amp;lt;0.05). All groups had no significant difference in other maternal or fetal/neonatal complications. Conclusion: If only the population-based nomograms are created, we may advise maternal serum TSH level as &amp;lt;2.5 mU/L for first-trimester screening. Single or multiple pregnancy status, gestational age, and the presence of thyroid peroxidase antibodies should also be taken into account when creating these nomograms.

Early Detection of Isolated Severe Congenital Heart Defects Is Associated with a Lower Threshold to Terminate the Pregnancy

Introduction: Early detection of isolated severe congenital heart defects (CHDs) allows extra time for chromosomal analysis and informed decision making, resulting in improved perinatal management and patient satisfaction. Therefore, the aim of this study was to assess the value of an additional first-trimester screening scan compared to only a second-trimester scan in fetuses diagnosed with isolated severe CHDs. Prenatal detection rate, time of prenatal diagnosis, and pregnancy outcome were evaluated in the Netherlands after implementation of a national screening program. Materials and Methods: We performed a retrospective geographical cohort study and included 264 pre- and postnatally diagnosed isolated severe CHD cases between January 1, 2007, and December 31, 2015, in the Amsterdam region. Severe CHD was defined as potentially life threatening if intervention within the first year of life was required. Two groups were defined: those with a first- and second-trimester anomaly scan (group 1) and those with a second-trimester anomaly scan only (group 2). A first-trimester scan was defined as a scan between 11 + 0 and 13 + 6 weeks of gestation. Results: Overall, the prenatal detection rate for isolated severe CHDs was 65%; 63% were detected before 24 weeks of gestation (97% of all prenatally detected CHDs). Prenatal detection rate was 70.2% in the group with a first- and second-trimester scan (group 1) and 58% in the group with a second-trimester scan only (group 2) (p < 0.05). Median gestational age at detection was 19 + 6 (interquartile range [IQR] 15 + 4 – 20 + 5) in group 1 versus 20 + 3 (IQR: 20 + 0 – 21 + 1) in group 2 (p < 0.001). In group 1, 22% were diagnosed before 18 weeks of gestation. Termination of pregnancy rate in group 1 and group 2 were 48% and 27%, respectively (p < 0.01). Median gestational age at termination did not differ between the two groups. Conclusion: Prenatal detection rate of isolated severe CHDs and termination of pregnancy rate was higher in the group with both a first- and second-trimester scan. We found no differences between timing of terminations. The additional time after diagnosis allows for additional genetic testing and optimal counseling of expectant parents regarding prognosis and perinatal management, so that well-informed decisions can be made.

First-Trimester Screening for Miscarriage or Stillbirth-Prediction Model Based on MicroRNA Biomarkers.

We evaluated the potential of cardiovascular-disease-associated microRNAs to predict in the early stages of gestation (from 10 to 13 gestational weeks) the occurrence of a miscarriage or stillbirth. The gene expressions of 29 microRNAs were studied retrospectively in peripheral venous blood samples derived from singleton Caucasian pregnancies diagnosed with miscarriage (n = 77 cases; early onset, n = 43 cases; late onset, n = 34 cases) or stillbirth (n = 24 cases; early onset, n = 13 cases; late onset, n = 8 cases; term onset, n = 3 cases) and 80 selected gestational-age-matched controls (normal term pregnancies) using real-time RT-PCR. Altered expressions of nine microRNAs (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-342-3p, and miR-574-3p) were observed in pregnancies with the occurrence of a miscarriage or stillbirth. The screening based on the combination of these nine microRNA biomarkers revealed 99.01% cases at a 10.0% false positive rate (FPR). The predictive model for miscarriage only was based on the altered gene expressions of eight microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p and miR-195-5p). It was able to identify 80.52% cases at a 10.0% FPR. Highly efficient early identification of later occurrences of stillbirth was achieved via the combination of eleven microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-145-5p, miR-210-3p, miR-342-3p, and miR-574-3p) or, alternatively, by the combination of just two upregulated microRNA biomarkers (miR-1-3p and miR-181a-5p). The predictive power achieved 95.83% cases at a 10.0% FPR and, alternatively, 91.67% cases at a 10.0% FPR. The models based on the combination of selected cardiovascular-disease-associated microRNAs had very high predictive potential for miscarriages or stillbirths and may be implemented in routine first-trimester screening programs.

Locating Multiple Standard Planes in First-Trimester Ultrasound Videos via the Detection and Scoring of Key Anatomical Structures

This study was aimed at developing a first-trimester standard plane detection (FTSPD) system that can automatically locate nine standard planes in ultrasound videos and investigating its utility in clinical practice. The FTSPD system, based on the YOLOv3 network, was developed to detect structures and evaluate the quality of plane images by using a pre-defined scoring system. A total of 220 videos from two different ultrasound scanners were collected to compare detection performance between our FTSPD system and sonographers with different levels of experience. The quality of the detected standard planes was quantitatively rated by an expert according to a scoring protocol. Kolmogorov-Smirnov analysis was used to compare the distributions of scores across all nine standard planes. The expert-rated scores indicated that the quality of the standard planes detected by the FTSPD system was on par with that of the planes detected by senior sonographers. There were no significant differences in the distributions of the scores across all nine standard planes. The FTSPD system performed significantly better than junior sonographers in five standard plane types. The results of this study suggest that our FTSPD system has significant potential for detecting standard planes in first-trimester ultrasound screening, which may help to improve the accuracy of fetal ultrasound screening and facilitate early diagnosis of abnormalities. The quality of the standard planes selected by junior sonographers can be significantly improved with the assistance of our FTSPD system.

Adverse pregnancy outcomes in women at increased risk of preterm pre-eclampsia on first-trimester combined screening.

Uteroplacental dysfunction may not only result in pre-eclampsia (PE) but also in preterm birth (PTB), small-for-gestational-age (SGA) birth and stillbirth. The aim of this study is to evaluate the positive predictive value (PPV) of first-trimester combined PE screening for all of these placenta-mediated adverse pregnancy outcomes. Retrospective cohort study. Tertiary referral maternity unit. A total of 13 211 singleton pregnancies. First-trimester combined screening for preterm PE using the Fetal Medicine Foundation (FMF) algorithm. Hypertensive disorders of pregnancy (HDP), PTB, SGA birth and stillbirth were combined to assess composite adverse and severe adverse pregnancy outcomes (CAPO and CAPO-S). The PPVs for CAPO and CAPO-S were calculated for women with a combined risk for preterm PE of ≥1 in 50 and ≥1 in 100. First-trimester combined screening identified 2215 women (16.8%) with a risk of ≥1 in 100 for preterm PE. The PPVs for a risk of ≥1 in 100 for CAPO and CAPO-S were 38.8% and 18.2%, respectively. The equivalent PPVs for a risk of ≥1 in 50 were 45.1% and 21.1%, respectively. Women identified at high risk of preterm PE are also at increased risk of other placenta-mediated adverse pregnancy outcomes, such as PTB, SGA birth and stillbirth. Women at high risk for preterm PE after first-trimester screening may benefit from a higher surveillance care pathway, with interventions to mitigate all the adverse outcomes associated with placental dysfunction.

The value of detailed first-trimester ultrasound in the era of noninvasive prenatal testing

In 2020, the American College of Obstetricians and Gynecologists recommended noninvasive prenatal testing be offered to all patients. However, current societal guidelines in the United States do not universally recommend a detailed first-trimester ultrasound. This study aimed to determine the additional findings identified through first-trimester ultrasound that would have otherwise been missed if noninvasive prenatal testing was used alone as a first-trimester screening method. This was a retrospective cohort study involving 2158 pregnant patients and 2216 fetuses that were seen at a single medical center between January 1, 2020, and December 31, 2022. All those included underwent both noninvasive prenatal testing and detailed first-trimester ultrasound between 11.0 and 13.6 weeks of gestation. Noninvasive prenatal testing results were categorized as low risk or high risk, and first-trimester ultrasound results were categorized as normal or abnormal. Abnormal first-trimester ultrasounds were further classified as first-trimester screening markers (increased nuchal translucency, absent nasal bone, tricuspid regurgitation, and ductus venosus reverse a-wave) or structural defects (the cranium, neck, heart, thorax, abdominal wall, stomach, kidneys, bladder, spine, and extremities). Descriptive statistics were used to report our findings. Of 2216 fetuses, 65 (3.0%) had a high-risk noninvasive prenatal testing result, whereas 2151 (97.0%) had a low-risk noninvasive prenatal testing result. Of those with a low-risk noninvasive prenatal testing result, 2035 (94.6%) had a normal first-trimester ultrasound, whereas 116 (5.4%) had at least 1 abnormal finding on first-trimester ultrasound. The most common screening marker detected within the low-risk noninvasive prenatal testing group was absent nasal bone (52/2151 [2.4%]), followed by reversed a-wave of the ductus venosus (30/2151 [1.4%]). The most common structural defect in this group was cardiac abnormality (15/2151 [0.7%]). Overall, 181 fetuses were identified as having "abnormal screening" through either a high-risk noninvasive prenatal testing result (n=65) or through a low-risk noninvasive prenatal testing result but abnormal first-trimester ultrasound (n=116). In summary, the incorporation of first-trimester ultrasound screening identified 116 additional fetuses (5.4%) that required further follow-up and surveillance than noninvasive prenatal testing alone would have identified. Detailed first-trimester ultrasound identified more fetuses with a potential abnormality than noninvasive prenatal testing alone. Therefore, first-trimester ultrasound remains a valuable screening method that should be used in combination with noninvasive prenatal testing.