Crown-rump Length Measurements Research Articles

Biparietal diameter vs crown-rump length as standard parameter for late first-trimester pregnancy dating.

To compare the precision of biparietal diameter (BPD) and crown-rump length (CRL) as predictors of gestational age in the human fetus in the late first and early second trimesters, using a population-based approach. We constructed term and gestational-age prediction curves for first-trimester dating, based on 11 041 pregnancies with 12 260 measurements of CRL and/or BPD from a population-based Norwegian clinical database. We used a population-based approach with local linear quantile regression, combined with a time-to-event strategy that compensates for induced births. Term prediction precision was assessed by estimating and comparing the prediction residual curves using a time-to-event analysis. Individual differences in gestational-age predictions from CRL and BPD were assessed using measurements performed on the same fetus on the same day. A sensitivity analysis was performed to evaluate the effect of not distinguishing between non-spontaneous and spontaneous births. CRL and BPD provided almost identical term prediction precision judged from the residual distribution. In about 51% of examinations, the difference in predicted gestational age was 1 day or less; 24% of examinations had a difference of 2 days, 14% had a difference of 3 days, 7% had a difference of 4 days and only 5% of all examinations had a difference of 5 days or more. Incorrectly removing induced births from the analysis, or treating them as spontaneous, would cause a substantial systematic prediction bias of about 2 days. Based on population data, using comparisons at an individual level, our study found that BPD is as precise as CRL when used for first-trimester dating. BPD has advantages from a clinical point of view, since it is technically less challenging and less time-consuming to measure compared with CRL, and can be measured and assessed throughout the entire pregnancy. © 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.

The impact of maternal vulnerability on stress biomarkers and first-trimester growth: the Rotterdam Periconceptional Cohort (Predict Study).

Is the degree of maternal vulnerability positively associated with stress biomarkers (stress hormones, C-reactive protein, tryptophan metabolites, and one-carbon metabolites), and does long-term exposure to stress hormones reduce first-trimester growth? The maternal vulnerability risk score is positively associated with concentrations of hair cortisol and cortisone and negatively with tryptophan, while higher hair cortisol concentrations are associated with reduced first-trimester growth without mediation of tryptophan. A high degree of maternal vulnerability during the periconception period is associated with impaired first-trimester growth and pregnancy complications, with consequences for long-term health of the child and future life course. However, due to the challenges of early identification of vulnerable women, the uptake of periconception care is low in this target group. Between June 2022 and June 2023, this study was conducted in a sub-cohort of 160 pregnant women participating in the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective tertiary hospital-based cohort. One hundred and thirty-two women with ongoing pregnancies and available stress biomarker data were included in the analysis. Data on periconceptional social, lifestyle, and medical risk factors were collected via self-administered questionnaires, and these factors were used for the development of a composite maternal vulnerability risk score. Stress biomarkers, including stress hormones (hair cortisol and cortisone) and inflammatory and oxidative stress biomarkers (C-reactive protein, total homocysteine, and tryptophan metabolites) were determined in the first trimester of pregnancy. First-trimester growth was assessed by crown-rump length (CRL) and embryonic volume (EV) measurements at 7, 9, and 11 weeks gestation by making use of an artificial intelligence algorithm and virtual reality techniques using 3D ultrasound data sets. The associations between the maternal vulnerability risk score and stress biomarkers were identified using linear regression models, and between stress hormones and CRL- and EV-trajectories using mixed models. A mediation analysis was performed to assess the contribution of tryptophan. All associations were adjusted for potential confounders, which were identified using a data-driven approach. Several sensitivity analyses were performed to check the robustness of the findings. The maternal vulnerability risk score was positively associated with concentrations of hair cortisol and cortisone (pg/mg) (β = 0.366, 95% CI = 0.010-0.722; β = 0.897, 95% CI = 0.102-1.691, respectively), and negatively with tryptophan concentrations (µmol/L) (β = -1.637, 95% CI = -2.693 to -0.582). No associations revealed for C-reactive protein and total homocysteine. Higher hair cortisol concentrations were associated with reduced EV-trajectories (3√EV: β = -0.010, 95% CI = -0.017 to -0.002), while no associations were found with CRL-trajectories. Mediation by tryptophan was not shown. Residual confounding cannot be ruled out, and the external validity may be limited due to the study's single-center observational design in a tertiary hospital. There is mounting evidence that a high degree of maternal vulnerability negatively affects maternal and perinatal health, and that of the future life course. The results of our study emphasize the need to identify highly vulnerable women as early as possible, at least before conception. Our findings suggest that the chronic stress response and alterations of the maternal tryptophan metabolism are involved in maternal vulnerability, affecting first-trimester growth, with potential impact on the long-term health of the offspring. This study was funded by the Departments of Obstetrics and Gynecology and Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and the Junior Award granted by the De Snoo-van 't Hoogerhuijs Foundation in March 2022. There are no conflicts of interest. N/A.

Diagnostic Accuracy of an Integrated AI Tool to Estimate Gestational Age From Blind Ultrasound Sweeps

Accurate assessment of gestational age (GA) is essential to good pregnancy care but often requires ultrasonography, which may not be available in low-resource settings. This study developed a deep learning artificial intelligence (AI) model to estimate GA from blind ultrasonography sweeps and incorporated it into the software of a low-cost, battery-powered device. To evaluate GA estimation accuracy of an AI-enabled ultrasonography tool when used by novice users with no prior training in sonography. This prospective diagnostic accuracy study enrolled 400 individuals with viable, single, nonanomalous, first-trimester pregnancies in Lusaka, Zambia, and Chapel Hill, North Carolina. Credentialed sonographers established the "ground truth" GA via transvaginal crown-rump length measurement. At random follow-up visits throughout gestation, including a primary evaluation window from 14 0/7 weeks' to 27 6/7 weeks' gestation, novice users obtained blind sweeps of the maternal abdomen using the AI-enabled device (index test) and credentialed sonographers performed fetal biometry with a high-specification machine (study standard). The primary outcome was the mean absolute error (MAE) of the index test and study standard, which was calculated by comparing each method's estimate to the previously established GA and considered equivalent if the difference fell within a prespecified margin of ±2 days. In the primary evaluation window, the AI-enabled device met criteria for equivalence to the study standard, with an MAE (SE) of 3.2 (0.1) days vs 3.0 (0.1) days (difference, 0.2 days [95% CI, -0.1 to 0.5]). Additionally, the percentage of assessments within 7 days of the ground truth GA was comparable (90.7% for the index test vs 92.5% for the study standard). Performance was consistent in prespecified subgroups, including the Zambia and North Carolina cohorts and those with high body mass index. Between 14 and 27 weeks' gestation, novice users with no prior training in ultrasonography estimated GA as accurately with the low-cost, point-of-care AI tool as credentialed sonographers performing standard biometry on high-specification machines. These findings have immediate implications for obstetrical care in low-resource settings, advancing the World Health Organization goal of ultrasonography estimation of GA for all pregnant people. ClinicalTrials.gov Identifier: NCT05433519.

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA. Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA. A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020. We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires. This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended. This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest. NTR4356.

Prenatal ultrasound diagnosis and quality control of fetal nuchal translucency.

In clinical ultrasound examinations, it is challenging to perform quality control on the images of each fetal nuchal translucency (NT) and crown-rump length (CRL). However, small measurement differences can increase the probability of false-positive or false-negative diagnosis. Therefore, it is necessary to establish a quality control system for fetal NT examination. This study aims to control the quality of fetal NT and CRL measurements, evaluate the accuracy of ultrasound physicians in early pregnancy NT measurements, and analyze the impact of increased fetal structure screening on the detection rate of chromosomal abnormalities. Data were collected from cases before and after 12 months of NT examination quality control, with 2 214 before quality control and 2 538 cases after quality control. Three quality control data metrics were analyzed: NT multiple of median (NT-MoM), standard deviation (SD) of log10MoM [(SD) log10MoM], and the slope of NT on CRL (SNC). The performance of NT measurements was monitored through the individual CRL NT-MoM within the 0.9-1.1 MoM range of the normal median curve, while grouped based on different years of experience (<3 years, 3-6 years, >6 years), and NT-MoM values among these groups were compared. Data on NT thickening, structural anomalies, and chromosomal abnormalities were retrospectively analyzed during the quality control period. According to the curve equation of the American NTQR project group, the NT-MoM value before quality control was 0.921 7 MoM, the (SD) log10MoM value was 0.091 92, and the SNC value was 12.20%. After quality control, the NT-MoM value was 0.948 3 MoM, the (SD) log10MoM value was 0.094 81, and the SNC value was 11.43%. The comparison of NT-MoM values before and after quality control showed a statistically significant difference (P<0.000 1). The comparison of NT-MoM values measured by ultrasound physicians with different years of experience before and after quality control also showed statistically significant differences (P<0.000 1). The NT-MoM values for the 3-6 years and >6 years groups were higher after quality control (P<0.05), while the <3 years group showed no significant difference before and after quality control (P>0.05). After quality control, cases of NT thickening without significant structural abnormalities accounted for 19.05%, NT thickening with structural abnormalities accounted for 47.62%, and NT normal with structural abnormalities accounted for 33.33%. There were 36 cases of fetal heart abnormalities, accounting for 20.34% of the total abnormality rate, with a positive rate of 36% in chromosome tests. After quality control, ultrasound physicians measure NT more accurately, but differences among measurements remain. Measurements by experienced ultrasound physicians are closer to expected values, usually lower than expected. Monitoring fetal NT and CRL measurements helps improve measurement accuracy. Increasing structural screening during NT examinations, especially for the fetal heart, enhances the detection rate of chromosomal abnormalities.

Comparison of Fetal Crown-Rump Length Measurements between Thawed and Fresh Embryo Transfer.

Background and Objectives: Neonates born from thawed embryo transfers tend to have a significantly higher birthweight compared to those from fresh embryo transfers. The aim of this study was to compare the crown-rump length (CRL) between thawed and fresh embryos to investigate the potential causes of different growth patterns between them. Materials and Methods: This was a retrospective study (July 2010-December 2023) conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. In total, 3082 assisted reproductive technology (ART) pregnancies (4044 embryos) underwent a routine scan at 11+0-13+6 gestational weeks and were included in the study. Maternal age, the type of embryo transfer (thawed vs. fresh, donor vs. their own oocytes), CRL, twin and singleton gestations were analyzed. Results: The mean maternal age in thawed was significantly higher than in fresh embryos (39.8 vs. 35.8 years, p-value < 0.001). The mean CRL z-score was significantly higher in thawed compared to fresh embryo transfers (0.309 vs. 0.199, p-value < 0.001). A subgroup analysis on singleton gestations showed that the mean CRL z-score was higher in thawed blastocysts compared to fresh (0.327 vs. 0.215, p-value < 0.001). Accordingly, an analysis on twins revealed that the mean CRL z-score was higher in thawed blastocysts (0.285 vs. 0.184, p-value: 0.015) and in oocytes' recipients compared to own oocytes' cases (0.431 vs. 0.191, p-value: 0.002). Conclusions: The difference in CRL measurements between thawed and fresh embryos may be a first indication of the subsequent difference in sonographically estimated fetal weight and birthweight. This finding highlights the need for additional research into the underlying causes, including maternal factors and the culture media used.

The role of the ratio of first trimester CRL (crown rump length) measurement to NT (nuchal translucency) measurements in predicting early-onset fetal growth restriction (FGR)

Objective: Our aim is to evaluate the role of the ratio of first-trimester CRL (crown rump length) measurement to NT (nuchal translucency) measurements in predicting early-onset fetal growth restriction (FGR) and to contribute to the existing literature.&#x0D; Methods: In the present case-control study, fetuses with early-onset FGR were compared to a frequency matched low risk control group. This study was conducted in the perinatology clinic of Ankara Bilkent City Hospital between 2020 and 2023. Maternal age, gravidity, parity, crown-rump length (CRL), and nuchal translucency (NT) measurements were compared between pregnant women with early onset FGR (n=39) and pregnant women without FGR (n=50).&#x0D; Results: The mean age of pregnant women with FGR who participated in the study was 27.1±0.8, and the mean age of pregnant women without FGR was 26.3±0.6, and no statistically significant difference was found between the two groups (p=0.4)). Mean CRL was 54.98±1.08 mm in the group with FGR and 56.99±1.11 mm in the group without FGR; there was no significant difference between the two groups (p=0.2). The NT value was 1.11 ± 0.04 mm in the FGR group and 1.13 ± 0.02 mm in the without FGR group, there was no significant difference between the two groups (p=0.73). The mean CRL/NT ratio was 52.00±2.33 in the group with early onset FGR and 51.46±1.48 in the group without FGR and there was no statistically significant difference between the two groups (p=0.83).&#x0D; When the early developing FGR group is evaluated within itself, the mean age at diagnosis was 31.7±0.3 weeks. EFW mean percentile at diagnosis was 4.5±0.6 and ac percentile was 2.9±0.4. The mean umbilical artery systole/diastole ratio (UA-SD) was 2.9±0.16 and the mean umbilical artery pulsatility index (UA-PI) was 1.02±0.05.&#x0D; Conclusion: Crown-rump length to nuchal translucency ratio is not clinically useful to predict early-onset FGR.

Accuracy of prenatal and postnatal biomarkers for estimating gestational age: a systematic review and meta-analysis

Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small for GA at a population level. Currently, the gold standard for pregnancy dating is measurement of the fetal crown rump length at 11-14 weeks of gestation. However, this is not possible for women first presenting in later pregnancy, or in settings where routine ultrasound is not available. A reliable, cheap and easy to measure GA-dependent biomarker would provide an important breakthrough in estimating the age of pregnancy. Therefore, the aim of this study was to determine the accuracy of prenatal and postnatal biomarkers for estimating gestational age (GA). Systematic review prospectively registered with PROSPERO (CRD42020167727) and reported in accordance with the PRISMA-DTA. Medline, Embase, CINAHL, LILACS, and other databases were searched from inception until September 2023 for cohort or cross-sectional studies that reported on the accuracy of prenatal and postnatal biomarkers for estimating GA. In addition, we searched Google Scholar and screened proceedings of relevant conferences and reference lists of identified studies and relevant reviews. There were no language or date restrictions. Pooled coefficients of correlation and root mean square error (RMSE, average deviation in weeks between the GA estimated by the biomarker and that estimated by the gold standard method) were calculated. The risk of bias in each included study was also assessed. Thirty-nine studies fulfilled the inclusion criteria: 20 studies (2,050 women) assessed prenatal biomarkers (placental hormones, metabolomic profiles, proteomics, cell-free RNA transcripts, and exon-level gene expression), and 19 (1,738,652 newborns) assessed postnatal biomarkers (metabolomic profiles, DNA methylation profiles, and fetal haematological components). Among the prenatal biomarkers assessed, human chorionic gonadotrophin measured in maternal serum between 4 and 9 weeks of gestation showed the highest correlation with the reference standard GA, with a pooled coefficient of correlation of 0.88. Among the postnatal biomarkers assessed, metabolomic profiling from newborn blood spots provided the most accurate estimate of GA, with a pooled RMSE of 1.03 weeks across all GAs. It performed best for term infants with a slightly reduced accuracy for preterm or small for GA infants. The pooled RMSEs for metabolomic profiling and DNA methylation profile from cord blood samples were 1.57 and 1.60 weeks, respectively. We identified no antenatal biomarkers that accurately predict GA over a wide window of pregnancy. Postnatally, metabolomic profiling from newborn blood spot provides an accurate estimate of GA, however, as this is known only after birth it is not useful to guide antenatal care. Further prenatal studies are needed to identify biomarkers that can be used in isolation, as part of a biomarker panel, or in combination with other clinical methods to narrow prediction intervals of GA estimation. The research was funded by the Bill and Melinda Gates Foundation (INV-000368). ATP is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre funding scheme. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, the Department of Health, or the Department of Biotechnology. The funders of this study had no role in study design, data collection, analysis or interpretation of the data, in writing the paper or the decision to submit for publication.

Incidence of neonatal morbidity in small-for-gestational-age twins based on singleton and twin charts.

To compare morbidity, as measured by length of stay in the neonatal intensive care unit (NICU), in twin and singleton gestations classified as small-for-gestational age (SGA) according to estimated fetal weight < 10th percentile on twin or singleton growth charts. NICU length of stay was compared in 1150 twins and 29 035 singletons that underwent ultrasound assessment between 35 + 0 and 36 + 6 weeks' gestation. Estimated fetal weight was obtained from measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Gestational age was derived from the first-trimester crown-rump length measurement, using the larger of the two twins. Singletons and twins were compared in terms of NICU admission rate and length of stay according to classification as SGA by the Fetal Medicine Foundation singleton and twin reference distributions. The overall proportions of twins and singletons admitted to NICU were similar (7.3% vs 7.4%), but twins tended to have longer lengths of stay in NICU (≥ 7 days: 2.4% vs 0.8%; relative risk (RR), 3.0 (95% CI, 1.6-4.4)). Using the singleton chart, a higher proportion of twins were classified as SGA compared with singletons (37.6% vs 7.0%). However, the proportion of SGA neonates entering NICU was similar (10.2% for twins and 10.1% for singletons) and the proportion of SGA neonates spending ≥ 7 days in NICU was substantially higher for twins compared with singletons (3.7% vs 1.4%; RR, 2.6 (95% CI, 1.4-4.7)). When singleton charts are used to define SGA in twins and in singletons, there is a greater degree of growth-related neonatal morbidity amongst SGA twins compared with SGA singletons. Consequently, singleton charts do not inappropriately overdiagnose fetal growth restriction in twins and they should be used for monitoring fetal growth in both twins and singletons. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Automating the Human Action of First-Trimester Biometry Measurement from Real-World Freehand Ultrasound

Objective: Automated medical image analysis solutions should closely mimic complete human actions to be useful in clinical practice. However, more often an automated image analysis solution only represents part of a human task which restricts its practical utility. In the case of ultrasound-based fetal biometry, an automated solution should ideally recognize key fetal structures in free-hand video guidance, select a standard plane from a video stream and perform biometry. A complete automated solution should automate all three sub-actions.Methods: This paper considers how to automate the complete human action of first-trimester biometry measurement from real-world freehand ultrasound. In the proposed hybrid Convolutional Neural Network (CNN) architecture design, a classification-regression-based guidance model detects and tracks fetal anatomical structures (using visual cues) in the ultrasound video. Several high-quality standard planes which contain the mid-sagittal view of the fetus are sampled at multiple timestamps (using a custom-designed confident-frame detector) based on the estimated probability values associated with predicted anatomical structures that define the biometry plane. Automated semantic segmentation is performed on the selected frames to extract fetal anatomical landmarks. A crown-rump length (CRL) estimate is calculated as the mean CRL from these multiple frames.Results: Our fully automated method shows a high correlation with clinical expert CRL measurement (Pearson ρ=0.92, R-Squared (R2)=0.84) and a low mean absolute error of 0.834 (weeks) for fetal age estimation on a test data set of 42 videos.Conclusion: A novel algorithm for standard plane detection employs a quality detection mechanism defined by clinical standards and ensuring precise biometric measurements.

Fetal Medicine Foundation charts for fetal growth in twins.

To derive reference distributions of estimated fetal weight (EFW) in twins relative to singletons. Gestational-age- and chorionicity-specific reference distributions for singleton percentiles and EFW were fitted to data on 4391 twin pregnancies with two liveborn fetuses from four European centers, including 3323 dichorionic (DC) and 1068 monochorionic diamniotic (MCDA) twin pregnancies. Gestational age was derived using the larger of the two crown-rump length measurements obtained during the first trimester of pregnancy. EFW was obtained from ultrasound measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Singleton percentiles were obtained using the Fetal Medicine Foundation population weight charts for singleton pregnancies. Hierarchical models were fitted to singleton Z-scores with autoregressive terms for serial correlations within the same fetus and between twins from the same pregnancy. Separate models were fitted for DC and MCDA twins. Fetuses from twin pregnancies tended to be smaller than singletons at the earliest gestational ages (16 weeks for MCDA and 20 weeks for DC twins). This was followed by a period of catch-up growth until around 24 weeks. After that, both DC and MCDA twins showed reduced growth. In DC twins, the EFW corresponding to the 50th percentile was at the 50th percentile of singleton pregnancies at 23 weeks, the 43rd percentile at 28 weeks, the 32nd percentile at 32 weeks and the 22nd percentile at 36 weeks. In MCDA twins, the EFW corresponding to the 50th percentile was at the 36th percentile of singleton pregnancies at 24 weeks, the 29th percentile at 28 weeks, the 19th percentile at 32 weeks and the 12th percentile at 36 weeks. In DC and, to a greater extent, MCDA twin pregnancies, fetal growth is reduced compared with that observed in singleton pregnancies. Furthermore, after 24 weeks, the divergence in growth trajectories between twin and singleton pregnancies becomes more pronounced as gestational age increases. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

IVF pregnancy dating: Comparative analysis of gestational age estimation based on embryo transfer date and ultrasound measurements of crown-rump length

Introduction. In in-vitro fertilization pregnancies, the precise date of conception is known. Relying solely on the embryo transfer date for pregnancy dating can lead to inaccuracies and mismanagement in prenatal care. This study aimed to compare gestational age estimated by first-trimester ultrasound measurements with gestational age determined by the known date of embryo transfer. Material and Methods. This retrospective study included 30 patients who conceived through in-vitro fertilization. Only patients with singleton pregnancies who underwent first-trimester ultrasound screening by a single sonographer between January 2008 and March 2024 were included. Gestational age was calculated for each patient based on ultrasound measurements of crown-rump length and the date of embryo transfer. Results. Gestational age estimated by ultrasound in our study was statistically significantly higher than that determined by the embryo transfer date. The mean difference was 0.9 days (?2.14, 95% confidence interval [0.1, 1.7]) (p&lt;0.05), and a median difference was 0.5 days (interquartile range 0-2.75) (p&lt;0.05). Conclusion. Gestational age estimated by crown-rump length was higher than that calculated by the known date of conception. For pregnancies conceived through in-vitro fertilization, it is advisable to consider both the date of embryo transfer and the gestational age calculated from ultrasound measurements for more accurate pregnancy dating.

The significance of a smaller than expected crown–rump length measurement for predicting the occurrence of subsequent miscarriage in a viable first trimester pregnancy

The significance of a smaller than expected crown–rump length measurement for predicting the occurrence of subsequent miscarriage in a viable first trimester pregnancy

Postconceptual Neonatal Dating by Transmastoid Ultrasound of Transcerebellar Diameter-Comparison to Crown Rump Length Measurement: A Proof of Concept Paper.

Transcerebellar diameter (TCD) has been utilized prenatally as a tool to estimate gestational age (GA) when fetal growth aberrations are suspected. Traditionally, first trimester ultrasound (1TUS) has been the gold standard of dating a pregnancy in spontaneous pregnancies. We sought to determine if neonatal TCD measurement was as accurate as 1TUS in the estimation of postconceptual gestational age (PCGA). A retrospective cohort from a registry of high-quality transmastoid views of consecutive patients from July 2019 to November 2020, delivered from 24 to 34 weeks GA, and with a 1TUS were included. The reference PCGA was the sum of the GA at delivery by 1TUS and day of life. The PCGA by TCD was calculated from Chang et al for GA by TCD. Reference and experimental values were compared by correlation, agreement within 7 days, and Bland-Altman analysis. Of the 154 individual patients in the registry of high-quality transmastoid views during the study period, 62 met inclusion and exclusion criteria. PCGA by 1TUS and TCD were highly correlated (r = 0.86, P < .001; κ = 47% agreement within 7 days of PCGA). The bias of PCGA by TCD was 4.6 days earlier than the PCGA by 1TUS (95% confidence interval of agreement: -29.2, 20). PCGA estimation by neonatal transmastoid TCD was highly correlated with that of 1TUS. It generally underestimates GA by 4.6 days. This relationship warrants further investigation to determine if this method of estimating PCGA in undated gestations is generalizable.

A-331 Prenatal Maternal First Trimester Screening and Establishing the Multiple of Medians of Double Marker Tests in Tertiary Care Hospital in India

Abstract Background Down's syndrome, Edwards syndrome, and Patau syndrome (trisomy 21, 18, 13 respectively) in a fetus can be screened by prenatal testing using the maternal serum. Prenatal testing can provide an accurate assessment of the patient's risk of carrying an affected fetus. Double marker testing which includes the levels of free β- Human Chorionic Gonadotropin and Pregnancy Associated Plasma Protein A in the maternal serum along with the measurement of Crown Rump Length and Nuchal Translucency helps in determining the risk of Trisomy 21. Prenatal testing prevents the need for invasive methods. Methods This is a study conducted in Kokilaben Dhirubhai Ambani Hospital and Research Centre, Mumbai, Maharashtra, India from January 2012 to December 2018 for 628 pregnant women. The data for 1st trimester was divided into 3 groups: 11 to 11.6 weeks(86 patients), 12 to 12.6 weeks (421 patients), and 13 to 13.6 weeks (121 patients) based on their gestational age. This study included the determination of levels of double markers like free β- Human Chorionic Gonadotropin and Pregnancy Associated Plasma Protein A using maternal serum along with the ultrasound studies which included the Crown Rump Length and Nuchal Translucency measurements. Additional factors like a history of chromosomal abnormalities, smoking habits, insulin-dependent diabetes, and other dichotomous markers like the presence of nasal bone, abnormal ductal flow, and tricuspid regurgitation are also considered in calculating the risk. The concentration of biochemical parameters was expressed in Multiple of Median (MOM) with respect to maternal age. The risk assessment was analyzed using SSDW 5 and SSDW 6 software and the cut-off was set at 1:250 for age as well as trisomy 21, 18, and 13. Results The total number of positive patients for trisomy 21 and trisomy 13/18 were represented in percentage which turned out to be 2.86% and 1.11% respectively in association with the gestational age, dichotomous markers, double marker test, and ultrasound studies. The MOM for β-HCG, PAPPA, and NT were compared in SSDW5 and SSDW6. The mean β-HCG MOM negative and positive patients (trisomy 21) were found to be 1.34 ± 0.945 and 2.74 ± 1.685 respectively indicating the levels increase above normal. The mean PAPPA MOM negative and positive patients (trisomy 21) were found to be 1.47 ± 0.9125 and 0.77 ± 7667 respectively indicating the levels decrease below the normal. The NT mom for negative and positive patients was 0.91 ± 1879 and 1.88 ± 1.6508 respectively which suggests that the thickness of nuchal translucency increases with the increased risk for trisomy 21. Conclusion 18 out of 628 patients tested positive for trisomy 21 which was assessed using double marker testing and ultrasound studies. The levels of free β-HCG were seen to be increased and the levels of PAPPA were decreased in the patients who showed higher risks. Prenatal testing provides an advantage for early detection of this disorder.

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.

Combining early pregnancy bleeding with ultrasound measurements to assess spontaneous abortion risk among infertile patients

Approximately 15% of all clinically recognized pregnancies in patients with infertility result in spontaneous abortion. However, despite its potential to have a profound and lasting effect on physical and emotional well-being, the natural history of spontaneous abortion in women with infertility has not been described. Although vaginal bleeding is a common symptom in pregnancies conceived via reproductive technologies, its prognostic value is not well understood. This study aimed to evaluate the combination of early pregnancy bleeding and first-trimester ultrasound measurements to determine spontaneous abortion risk. This was a retrospective cohort study of patients with infertility who underwent autologous embryo transfer resulting in singleton intrauterine pregnancy confirmed by ultrasound from January 1, 2017, to December 31, 2019. Early pregnancy symptoms of bleeding occurring before gestational week 8 and measurements of crown-rump length and fetal heart rate from ultrasounds performed during gestational week 6 (6 0/7 to 6 6/7 weeks of gestation) and gestational week 7 (7 0/7 to 7 6/7 weeks of gestation) were recorded. Modified Poisson regression with robust error variance was adjusted a priori for patient age, embryo transfer day, and transfer of a preimplantation genetic-tested embryo to estimate the relative risk and 95% confidence interval of spontaneous abortion for dichotomous variables. The relative risks and positive predictive values for early pregnancy bleeding combined with ultrasound measurements on the occurrence of spontaneous abortion were calculated for patients who had an ultrasound performed during gestational week 6 and separately for patients who had an ultrasound performed during gestational week 7. The primary outcome was spontaneous abortion in the setting of vaginal bleeding with normal ultrasound parameters. The secondary outcomes were spontaneous abortion with vaginal bleeding and (1) abnormal crown-rump length, (2) abnormal fetal heart rate, and (3) both abnormal crown-rump length and abnormal fetal heart rate. Of the 1858 patients who were included (359 cases resulted in abortions and 1499 resulted in live births), 315 patients (17.0%) reported vaginal bleeding. When combined with ultrasound measurements from gestational week 6, bleeding was significantly associated with increased spontaneous abortion only when accompanied by absent fetal heart rate (relative risk, 5.36; 95% confidence interval, 3.36-8.55) or both absent fetal heart rate and absent fetal pole (relative risk, 9.67; 95% confidence interval, 7.45-12.56). Similarly, when combined with ultrasound measurements from gestational week 7, bleeding was significantly associated with increased spontaneous abortion only when accompanied by an abnormal assessment of fetal heart rate or crown-rump length (relative risk, 5.09; 95% confidence interval, 1.83-14.19) or both fetal heart rate and crown-rump length (relative risk, 14.82; 95% confidence interval, 10.54-20.83). With normal ultrasound measurements, bleeding was not associated with increased spontaneous abortion risk (relative risk: 1.05 [95% confidence interval, 0.61-1.78] in gestational week 6 and 0.80 [95% confidence interval, 0.36-1.74] in gestational week 7), and the live birth rate was comparable with that in patients with normal ultrasound measurements and no bleeding. Patients with a history of infertility who present after embryo transfer with symptoms of vaginal bleeding should be evaluated with a pregnancy ultrasound to accurately assess spontaneous abortion risk. In the setting of normal ultrasound measurements, patients can be reassured that their risk of spontaneous abortion is not increased and that their live birth rate is not decreased.

Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins

Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Investigating the "Fetal Side" in Recurrent Pregnancy Loss: Reliability of Cell-Free DNA Testing in Detecting Chromosomal Abnormalities of Miscarriage Tissue.

(1) Background: The aim of our study is to evaluate whether cell-free DNA testing can overlap the genetic testing of miscarriage tissue in women with early pregnancy loss (EPL) and length of recurrent pregnancy loss (RPL); (2) Methods: We conducted a prospective cohort study at the Pregnancy Loss Unit of the Fondazione Policlinico Universitario A. Gemelli (IRCCS), Rome, Italy between May 2021 and March 2022. We included women with EPL and length of RPL. Gestational age was >9 weeks + 2 days and <12 weeks + 0 days of gestation corresponding to a crown rump length measurement of >25 and <54 mm. Women underwent both dilation and curettage for the collection of miscarriage tissue and for blood sample collection. Chromosomal microarray analysis (CMA) on miscarriage tissues was performed by oligo-nucleotide- and single nucleotide polymorphisms (SNP)-based comparative genomic hybridization (CGH+SNP). Maternal blood samples were analyzed by Illumina VeriSeq non-invasive prenatal testing (NIPT) to evaluate the cell-free fetal DNA (cfDNA) and the corresponding fetal fraction and the presence of genetic abnormalities; (3) Results: CMA on miscarriage tissues revealed chromosome aneuploidies in 6/10 cases (60%), consisting of trisomy 21 (5 cases) and monosomy X (one case). cfDNA analysis was able to identify all cases of trisomy 21. It failed to detect monosomy X. A large 7p14.1p12.2 deletion concomitant to trisomy 21 was, in one case, detected by cfDNA analysis but it was not confirmed by CMA on miscarriage tissue. (4) Conclusions: cfDNA largely reproduces the chromosomal abnormalities underlying spontaneous miscarriages. However, diagnostic sensitivity of cfDNA analysis is lower with respect to the CMA of miscarriage tissues. In considering the limitations when obtaining biological samples from aborted fetuses suitable for CMA or standard chromosome analysis, cfDNA analysis is a useful, although not exhaustive, tool for the chromosome diagnosis of both early and recurrent pregnancy loss.

Compensatory mechanisms in response to induced hypothyroidism in the late gestation pig fetus†.

To understand the effect of fetal thyroid gland disruption on development in swine, we evaluated thyroid hormone levels, growth and developmental characteristics, and gene expression associated with thyroid hormone metabolism in late gestation fetuses exposed to methimazole (MMI). Pregnant gilts were given either oral MMI or equivalent sham from gestation day 85-106 (n= 4/group), followed by intensive phenotyping of all fetuses (n= 120). Samples of liver (LVR), kidney (KID), fetal placenta (PLC), and the corresponding maternal endometrium (END) were collected from a subset of fetuses (n= 32). Fetuses exposed to MMI in utero were confirmed hypothyroid, with a significant increase in thyroid gland size, goitrous thyroid histology, and dramatically suppressed thyroid hormone in serum. In dams, no differences in temporal measurements of average daily gain, thyroid hormone, or rectal temperatures relative to controls suggests that MMI had little effect on maternal physiology. However, fetuses from MMI-treated gilts exhibited significant increases in body mass, girth, and vital organ weights, but no differences in crown-rump length or bone measurements suggesting non-allometric growth. The PLC and END showed a compensatory decrease in expression of inactivating deiodinase (DIO3). Similar compensatory gene expression was observed in fetal KID and LVR with a downregulation of all deiodinases (DIO1, DIO2, DIO3). Minor alterations in the expression of thyroid hormone transporters (SLC16A2 and SLC16A10) were observed in PLC, KID, and LVR. Collectively, MMI crosses the PLC of the late gestation pig, resulting in congenital hypothyroidism, alterations in fetal growth, and compensatory responses within the maternal fetal interface.