Prenatal Diagnosis of Omphalocele and Soft Markers of Chromosomal Abnormalities In The First Trimester

Twin Reversed Arterial Perfusion Sequence.

Ultrasound was introduced in clinical practice in obstetrics and gynecology in 19581 and has completely changed the way obstetric care is provided, allowing for antenatal detection of major fetal abnormalities and placenta-related disorders. This rapidly evolving field has led to the description of a series of sonographic signs of fetal abnormalities in the second trimester2. Following the technological advances and improvements in imaging resolution in recent years, a clear shift toward early detection of fetal malformations and pregnancy complications at 11–14 weeks' gestation was seen, to the point that a detailed morphology assessment of the fetus at this early stage has now become routine practice and has high detection rates for the majority of major structural defects3-6. Traditionally, early first-trimester pregnancy ultrasound is performed to confirm a viable intrauterine pregnancy, to identify the number of embryos and to rule out ectopic pregnancy. In multiple pregnancy, chorionicity can be determined accurately at an early stage based on the number of gestational sacs seen; however, determination of amnionicity in monochorionic pregnancy may be challenging7 due to the difficulty in visualizing the thin intertwin membrane, particularly before 8 weeks' gestation. Due to the increasing uptake of transvaginal ultrasound, the development of high-frequency transvaginal probes and our improved understanding of embryological pathophysiology, it is now possible to detect fetal malformations before 11 weeks' gestation. In addition, acquisition of three-dimensional (3D) volume blocks facilitates visualization of a growing number of major embryonic and early fetal defects. Recent data also suggest that early markers of aneuploidy at 8–10 weeks, including increased nuchal fluid, skin edema, hydrops and hydrothorax, may prove valuable in identifying fetuses at risk of both chromosomal and structural abnormalities8. The unprecedented uptake and rapid clinical introduction of cell-free DNA (cfDNA) analysis, which has very high accuracy in screening for trisomies 21, 18 and 13, have led to an ever increasing uptake of pretest ultrasound scans performed at 6–10 weeks of gestation. The purpose of such a scan is, first, to confirm the gestational age, and second, to rule out situations in which the test should not be performed, namely miscarriage and the presence of a vanishing twin. This shift in the algorithm of antenatal screening now creates a window of opportunity for early screening and diagnosis of fetal anatomical defects by experienced ultrasound specialists. Early suspicion of lethal or severe fetal abnormalities allows not only for change in the diagnostic pathway (e.g. invasive genetic testing in preference to cfDNA), but also for timely reproductive choices and optimized clinical management. In these patients, early decision-making has the additional benefit of being associated with lower long-term psychological morbidity9. In this Opinion, we illustrate two-dimensional (2D) and 3D ultrasound images of pregnancies with fetal abnormality identified between 6 + 0 and 10 + 6 weeks of gestation. The detection of fetal abnormalities before 11 weeks of gestation relies not only on the experience of the operator but also on using high-resolution probes and transvaginal imaging. Use of different modalities of 3D ultrasound may also increase the diagnostic accuracy. Here, images of normal embryonic (up to 9 + 6 weeks' gestation) and fetal (from 10 + 0 weeks' gestation onwards) development and of suspected defects were acquired in early pregnancy by experienced ultrasound specialists, using both transabdominal and transvaginal ultrasound. In most cases, the diagnosis was either suspected or established at transvaginal examination. In almost all cases, 3D volumes were obtained and either immediately analyzed or stored for later offline analysis. All images were obtained by one of the authors during routine viability examinations or pre-cfDNA testing ultrasound, in specialized ultrasound clinics in Melbourne, Australia, in Nice, France, or in the Principality of Monaco. All ultrasound images were obtained using Voluson E8 or E10 (GE Healthcare, Zipf, Austria) ultrasound systems, equipped with real-time high-frequency transabdominal curvilinear probes (4–8 MHz and 5–9 MHz), linear probes (9 MHz) and high-frequency transvaginal 3D/4D volumetric probes (5–9 MHz and 6–12 MHz). In cases of suspected fetal abnormality, the fetal anatomy was reassessed thoroughly by the same professional at 11–14 weeks in most cases, and the clinical management regarding the method of screening for chromosomal abnormalities often changed (e.g. from cfDNA testing to chorionic villus sampling or amniocentesis). In all cases, the findings were confirmed by follow-up ultrasound examinations later in pregnancy or postnatally by visual inspection of the newborn or postmortem examination. Between 7 and 11 weeks' gestation, the embryo undergoes rapid development and growth (Figure 1), and organogenesis is largely complete by 10 weeks. At 7 weeks of gestational age, the embryo is approximately 10 mm in length, the amnion around it becomes visible, and the head is strongly flexed anteriorly10. By 8 weeks' gestation, the embryo measures around 16 mm and individual body parts can be identified on ultrasound; the head can be distinguished from the trunk and the limb buds can be delineated clearly10, 11. The cranial vesicles and cleavage of the prosencephalon can be appreciated. At 9 weeks, the fetal trunk elongates and straightens, the extremities protrude ventrally and a midgut herniation into the base of the umbilical cord becomes apparent. By 10 weeks, the crown–rump length (CRL) is between 30 and 35 mm, the fetus is distinctly human-appearing, the frontal bones of the skull are ossified, the physiological midgut herniation is evident, the hands and feet are relatively opposed and the digits can be seen10. With the availability of higher-resolution ultrasound probes and improvement of 3D multiplanar techniques of image acquisition, early first-trimester assessment of normal anatomic structures has heralded the development of exciting methods of sonoembryology, allowing evaluation of selected patients at risk for embryonic/fetal malformations and early detection of defects10, 11. Some severe embryonic/fetal abnormalities can be seen as early as 7–8 weeks of gestation. Figure 2 shows 3D sonographic images with rendering mode of conjoined craniopagus twins at 7 and 8 weeks of gestation. Early recognition of this type of severe abnormality allows early reproductive choices and avoids the risks related to late recognition, such as delivery of a large fetal volume which is associated with increased maternal morbidity. Cases of early amniotic rupture that are likely to evolve to amniotic band sequence with fetal disruption and limb amputations can also present in early pregnancy (Figure 3). In the setting of monochorionic twin pregnancy, the occurrence of twin reversed arterial perfusion (TRAP) sequence can at times be detected (Figure 4) facilitating early treatment options including cord occlusion of the acardiac twin. In a recent series from our group, comprising 104 cases of nuchal or subcutaneous edema and fetal hydrops diagnosed in early pregnancy (unpublished data), the condition resolved in approximately 80% of the cases by the time of the 11–14-week scan. However, the incidence of chromosomal abnormalities and major structural defects in this group was 21.5%, necessitating detailed sonographic examination at 11–14 weeks and changing the screening or diagnostic pathway in many cases. This high rate of adverse pregnancy outcome in cases of early subcutaneous edema is similar to that reported by Votino et al.8. Figure 5 shows cases of nuchal and generalized subcutaneous edema at 10 weeks of gestation. Major abnormalities of the central nervous system can be detected as early as 8 weeks of gestation. High-resolution transvaginal ultrasound imaging and good knowledge of the normal development of the brain cavities between 6 and 10 weeks are key prerequisites for the detection of abnormal brain anatomy in early pregnancy. Figure 6 shows the normal development of the brain cavities (telencephalon, diencephalon, mesencephalon and rhombencephalon) at 8 weeks of gestational age. Since ossification of the frontal bones occurs at 10 weeks' gestation, abnormal and irregular head shape may suggest early stages of acrania-exencephaly-anencephaly sequence (Figure 7)12. In these cases, the amniotic fluid often appears more echogenic than the extracelomic space. The cerebral falx can be seen in its entirety at 8–10 weeks. Other major brain abnormalities, such as alobar holoprosencephaly with fusion of the thalami and of the anterior horns of the lateral ventricles, can be identified at this stage (Figure 8) and early detection has been previously reported13. The association of alobar holoprosencephaly with trisomy 13 and poor neonatal outcomes may change the screening and diagnostic options for the woman, altering the management of the pregnancy. Similarly, in some cases, encephalocele with meningocele can also be detected before 11 weeks (Figure 9). Previous studies have shown an important association between dilated fourth ventricle in the first trimester and chromosomal defects14, and high-resolution transvaginal ultrasound now allows visualization of the posterior fossa spaces and structures. Using 3D rendering with transparency mode, dilatation of the brain cavities can be well visualized, especially dilatation of the fourth ventricle (Figure 10) and lateral cranial ventricles. Before 10 weeks of gestational age, the fetal spine can be seen on ultrasound as hypoechoic parallel lines (Figure 11); after this stage, the ossification process begins. Ossified vertebrae can be identified on ultrasound in coronal view of the spine after 10 weeks, but early diagnosis of spinal dysraphism before 16 weeks through direct visualization of the spine is challenging. The diagnosis of open spina bifida can be suggested by abnormalities of the posterior fossa in both sagittal and axial views of the fetal head5, 15. If a myelomeningocele is prominent in early pregnancy, the defect can be potentially visualized as early as 9–10 weeks (Figure 11), mainly with the use of high-resolution transvaginal ultrasound. Fetal heart activity can be first identified at 5–6 weeks of pregnancy. The four-chamber view of the heart and the right and left cardiac outflows can be visualized between 8 and 10 weeks' gestation in a large proportion of cases8, particularly in the hands of experienced operators, with the use of high-resolution transvaginal probes and 4D ultrasound modalities, such as spatiotemporal image correlation (STIC) (Figure 12). Major heart defects, such as hypoplastic left heart syndrome, can potentially be seen as early as 10 weeks (Figure 12). Between 9 and 11 weeks of gestational age, physiologic bowel herniation through the base of the umbilical cord is evident and occurs because the growth rate of the intestines is higher than that of the abdominal wall in the embryonic period. This herniation usually resolves by 12 weeks (CRL of 54 mm). The stomach can be visualized by 8 weeks in approximately 80% of the pregnancies8. When the bowel herniation measures more than 7 mm in its largest diameter, or if it persists at the end of 12 weeks, a ventral-wall defect can be suspected16, 17. In the case of omphalocele (or exomphalos), the protruding mass is typically smooth and has a rounded contour since the abdominal contents are contained by the peritoneal membrane. An irregular protrusion is highly suggestive of gastroschisis, in which the bowel loops are not contained by peritoneal membrane and are floating freely in the amniotic cavity. Figure 13 shows a normal fetus with midgut herniation at 10 weeks, along with different abdominal-wall defects including omphalocele, cloacal exstrophy and body-stalk anomaly. The fetal kidneys can be visualized at 9 weeks in approximately 50% of the pregnancies8 and appear as oval echogenic structures on either side of the spine in a coronal view. Utilizing 3D modalities, such as volume contrast imaging (VCI) and glass rendering with transparent minimal mode, may facilitate visualization of the kidneys. The bladder is seen as a small anechoic area within the pelvis and its longitudinal length should measure less than 6 mm in its largest diameter. Gross abnormalities of the abdominal wall and bladder exstrophy can be identified at these early stages (Figure 13). Figure 14 demonstrates a case of patent urachus connecting the bladder with the umbilicus. The limb buds are first seen at approximately 7–8 weeks, though visualization of the digits is difficult at this stage. Evaluation of the digits of the feet is challenging given that the soles of the feet are apposed 'en-face' by 9 to 10 weeks, whereas the fingers of the hands are readily identified as the arms are held in a fixed flexed position across the fetal chest and hands are separated at this stage. At times, polydactyly may be evident in early pregnancy (Figure 15). All long bones are identifiable by 10 weeks. Major limb abnormalities, such as ectrodactyly, fusion of the inferior limbs (sirenomelia) and limb absence can be suspected between 9 and 10 weeks of gestational age (Figure 16). With the advent of cfDNA testing, women are increasingly opting for pretest ultrasound assessment. High-frequency transvaginal ultrasound screening with 3D/4D technology can provide a definitive diagnosis in cases with certain fetal defects, such as acrania and conjoined twins. In others, a diagnosis may be suspected at 6–10 weeks and subsequently confirmed at 11–14 weeks or later in pregnancy. In patients with a suspected diagnosis of a fetal defect, it may be more appropriate that counseling is in favor of discouraging cfDNA testing and potentially proceeding with re-evaluation of the fetal anatomy at 11–14 weeks with consideration of definitive genetic testing via chorionic villus sampling or amniocentesis. In a study by Vora et al., ultrasound examination prior to cfDNA testing offered to women of ≥ 35 years of age identified findings that could have changed management in 16% of the cases18. Similarly, in a recent review of over 6000 pre-cfDNA scans, we concluded that findings that could potentially lead to change in management are observed in one in 10 pregnancies, and this proportion is even higher in women with advanced maternal age (unpublished data). An additional benefit of screening before 11 weeks of gestation is the identification of cases with increased nuchal fluid, subcutaneous edema or hydrops fetalis, which comprised 1% of cases in our cohort. Indeed, our data suggest that this group of patients is at high risk of adverse pregnancy outcome and have a 1/5 probability of having an underlying aneuploidy or fetal malformation (unpublished data). Therefore, the introduction of routine early ultrasound screening for all patients may herald a new tier of fetal-malformation and aneuploidy screening in the future. It is best to obtain maternal blood for cfDNA analysis at 10 weeks' gestation, rather than at 8 or 9 weeks, as the fetal fraction is greater at this time, which lowers the rate of test failure and increases its accuracy. This correlates well with the timing for identification of increased nuchal fluid, subcutaneous edema, fetal hydrops and fetal malformation, which is better at 10 weeks than at 6–9 weeks' gestation in our experience. The proportion of fluid in the amniotic and celomic cavities to fetus is greatest at 6–10 weeks' gestation compared to any other time in pregnancy, and this provides an ideal setting for 3D and 4D volume acquisition and analysis. Furthermore, the fetus is relatively inactive at this early stage when compared to the later stages of pregnancy, which facilitates anatomical review using both 2D and 3D analysis. However, screening for aneuploidies and fetal abnormalities at 8–10 weeks' gestation needs to be considered with caution, as to date there is limited evidence regarding the detection rate, and many of the organ systems are still undeveloped or too difficult to visualize at this early stage. Moreover, there is no evidence that early pregnancy screening is cost-effective, and future research needs to evaluate carefully whether detection of fetal abnormalities before 11 weeks' gestation is cost-beneficial on a population level. Caution is recommended when a diagnosis is made at a very early gestational age and confirmation of fetal abnormalities later in pregnancy is frequently required, which is of importance as we progress through the learning curve in sonoembryology, just as occurred in the history of ultrasound diagnosis in the mid-trimester and, more recently, in the first trimester at 11–14 weeks. Given that patients may choose surgical termination of pregnancy if a fetal malformation is detected, other grounds for urging caution are that antenatal screening and diagnosis at this early stage may become difficult to audit. Due to concerns regarding the possible biological effects of ultrasound and tissue heating, practitioners should observe the 'as low as reasonably achievable' (ALARA) principle. Although the increase in temperature seems negligible during first-trimester ultrasonography19, 20, exposure should be kept to the minimum necessary and the output display system should be monitored, aiming to maintain the thermal index below 1.0 (thermal index for soft tissue before 10 weeks and thermal index for bone thereafter)20, 21. Finally, patients should be counseled with due care, as early identification of a suspected anomaly which requires later confirmation may prolong patient anxiety until a firm diagnosis is achieved in the first or second trimester. S.M. and B.B. are invited speakers by and received in-kind contributions from GE (GE Healthcare, Zipf, Austria).

Background: Abnormal insertion of the umbilical cord (UC) into the placenta may initiate fetal growth restriction and potentially complicates labor with intrapartum hemorrhage. The aim of this study was to sonographically determine the relationship between umbilical cord insertion types and estimated fetal weight (EFW). Methods: This prospective cross-sectional study was done in a 7-month period and recruited 220 pregnant women with 27 to 37 weeks gestation attending the antenatal clinic of the Hospital. Ultrasound scan was done on the women to determine UC insertion and EFW. Data was analyzed using SPSS 23.0. Results: Peripheral UC had significantly higher EFW, age and BMI (P=0.000), (P=0.009) and (P=0.003). The difference in EFW between peripheral UC and central UC in BMI ≥ 30 kg/m2 was significant within the 31st – 32nd week of gestation (P=0.001) and 33rd – 34th week of gestation (P=0.034). EFW was least in velamentous UC subtype (1.385±0.12 kg) compared to central UC type (1.95±0.65 kg), eccentric UC subtype (2.29±0.77 kg) and marginal UC subtype (2.47±0.83 kg). Peripheral UC was significantly associated with BMI (P=0.000), employment status (P=0.048), past history of CS (P=0.000) and placental location (P=0.001). Conclusion: Fetal weight, in the third trimester, is greater in obese pregnant women with peripheral umbilical cord insertion, except with velamentous cord insertion, and this is significant between 31st and 34th weeks of gestation. Peripheral umbilical cord insertion is significantly associated with high maternal BMI, posterior placental location, past history of cesarean section and being employed.

To investigate the functional link between the velocity flow waveforms and the placental vascular resistance resulting from the umbilical arteries and the primary and secondary arterial branches as they enter into the placenta. Doppler ultrasound measurements of the placental FVW from 19 normal pregnancies from 20–40 weeks of gestation were carried. Measurements of PS, ED, S/D, PI, and RI were performed in the artery in the umbilical cord insertion into the placenta, in the first generation of the blood vessels on the chorion plate, and at the half width of the placenta below the insertion (intraplacental vessels). The data were analyzed according to the week of gestation, where a linear trend line was drawn in order to evaluate the general pattern. The results indicated that the normal variation of the flow in the placental vessels correlated well to the umbilical cord flow elsewhere. The flow in the chorionic blood vessels decreased as it entered the intraplacental vessels, both lower than the flow in umbilical cord insertion as expected. The velocities at PS and ED increased towards the end of the pregnancy. The indices PS, ED, S/D, PI, RI in the insertion of the umbilical cord yielded similar patterns along the week of gestation, although higher values, than in the intraplacental blood vessels. The values measured in the chorionic blood vessels were close to those of the intraplacental vessels at 20 week of gestation while later, towards the 40 week of gestational age, the values of the chorionic blood vessels were close to these at cord insertion into the placenta. The blood flow velocity along the placental vascular tree is reduced when moving to smaller blood vessels, due to increase in the resistance of the vessels. The PS and ED were the most sensitive parameters. Changes in the flow in the intraplacental vessels may reflect peripheral damage within the placenta prior to changes in the umbilical arteries.

Various soft markers can be detected in the ultrasonography of foetuses, which can be related to chromosomal abnormalities and increases the risk of abnormalities, or they can be considered as normal variations that can disappear due to the pregnancy progress. There are different tools to detect chromosomal abnormalities like conventional karyotyping, chromosomal microarray analysis (CMA), single nucleotide polymorphism (SNP) array, non-invasive prenatal test (NIPT), and non-invasive prenatal screening (NIPS). Therefore, in the present study, we aim to assess the accuracy of ultrasonic soft markers in the diagnosis of chromosomal abnormalities such as chromosomal structural abnormalities, aneuploidy, and triploidy, especially Trisomy 21 and Trisomy 18. A systemic literature search was performed using PubMed, Scopus, Google Scholar, and Web of Science. We gathered all articles published before August 2023. We selected English studies such as retrospective and cross-sectional ones that assessed the relationship between ultrasonic soft markers and foetal chromosomal abnormalities. A total of 10 articles with 18,580 cases were included in our systematic review article that assessed the foetal abnormalities and aneuploidies by using conventional karyotyping, SNP array, CMA, and NIPT (or NIPS). Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common abnormalities related to ultrasonic soft markers by karyotyping; however, Trisomy 13, 47, XXY, 45, X, and mosaic chromosomal abnormalities were other abnormalities detected. Results by CMA showed Trisomy 21 and Trisomy 18 as the most common abnormalities in the foetuses also with ultrasonic soft markers, and other abnormalities were pathogenic copy-number variations, Turner (XO), polyploidy, 22q11.2deletion, and Trisomy13, respectively. It was discovered that there is a greater possibility of having pathogenic copy number variations (CNVs) in the groups with multiple ultrasonic soft markers, while foetuses with ultrasonic soft markers have a decreased prevalence of CMA abnormality compared to those who had significant abnormalities or abnormal nuchal translucency. Trisomy 21 was the only abnormality found by NIPT in the groups with 1 and 2 soft markers, while groups with multiple soft markers were all normal. By using SNP array, it was identified that the rate of chromosomal abnormalities such as aneuploidy and triploidy, LOH, and CNVs was lower in the group with a single ultrasonic soft marker compared to the group with structural abnormalities in multiple systems. Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common chromosomal abnormalities that ultrasound soft markers could diagnose. Therefore, it is recommended to employ soft markers besides CMA, SNP array, and NIPS (or NIPT) for greater accuracy in detecting foetus abnormalities.

Objective To investigate the value of first-trimester ultrasound parameters in predicting complicated monochorionic diamniotic (MCDA) twins. Methods In this retrospective study, pregnant women diagnosed as MCDA twins by ultrasound in the First Affiliated Hospital of Sun Yat-sen University from January 2013 to January 2018 were recruited and divided into the following four groups: non-complicated MCDA twins group, twin-twin transfusion syndrome (TTTS) group, selective intrauterine growth restriction (sIUGR) group and twin anemia-polycythemia sequence (TAPS) group. Thickness of nuchal translucency (NT), crown-rump length (CRL), umbilical cord insertion (UCI) and ductus venosus (DV) flow at 11-14 weeks of gestation were recorded. The predictive value for complicated MCDA twins was analyzed using t-test, Chi-square (or Fisher's exact) test, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve. Results (1) A total of 430 MCDA twin pregnancies were included in this study with 152 in the TTTS group, 142 in the sIUGR group, seven in the TAPS group and 129 in the normal MCDA twins group. No further analysis was performed on the TAPS group due to the small sample size. (2) NT discordance in twins of the TTTS group was significantly greater than that in the normal MCDA twins group[(21.5±16.0)% vs (14.6±13.5)%, t=-3.533, P<0.001]. The area under ROC curve (AUC) of TTTS predicted by NT discordance was 0.649. Stratified analysis showed that TTTS was best predicted when NT discordance was 20% with the sensitivity of 57.9% and specificity of 70.6%. (3) The sIUGR group had greater discordance in CRL and NT and higher UCI discordance than the normal MCDA twins group [NT: (27.8±21.3)% vs (14.6±13.5)%, t=-5.556, P<0.001; CRL: (8.6±6.9)% vs (5.4±4.4)%, t=-3.144, P=0.002; UCI: 47.9% (68/142) vs 13.9% (18/129), χ2=35.929, P<0.001]. The AUC of sIUGR was 0.675 predicted by NT discordance and 0.649 by CRL discordance. Stratified analysis showed that NT discordance of 20% and CRL discordance of 10% were the best prediction for sIUGR with the sensitivity of 53.1% and 34.7% and specificity of 72.1% and 83.8%, respectively. Multivariate logistic regression analysis suggested that UCI discordance was the risk factor for sIUGR (OR=7.165, 95%CI: 2.637-19.472). Conclusions MCDA twins with NT discordance greater than 20% during early pregnancy are at increased risk for TTTS. CRL discordance greater than 10%, NT discordance greater than 20% and abnormal UCI are risk factors for sIUGR. Key words: Twins, monozygotic; Pregnancy trimester, first; Ultrasonography, prenatal; Nuchal translucency measurement; Fetofetal transfusion; Fetal growth retardation; Forecasting

This study aimed to evaluate and compare the clinical utility of chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES) in a consecutive cohort of high-risk pregnant women who underwent chorionic villus sampling (CVS), as well as to develop a stratified diagnostic strategy based on first-trimester pregnancy indications. This single-center retrospective cohort study included 338 singleton pregnancies that underwent CVS during the first trimester (11+ 0-13+ 6 weeks of gestation) between December 2023 and April 2025. High-risk pregnancies were defined by the presence of at least one of the following criteria: (1) advanced maternal age (AMA); (2) ultrasound detection of one or more soft markers or structural fetal anomalies; (3) abnormal first-trimester serum screening results; or (4) a history of adverse obstetric outcomes. Each chorionic villus sample underwent CMA using the Affymetrix CytoScan 750 K chip following DNA extraction, and 25 cases presenting with ultrasound abnormalities were subsequently analyzed using trio-WES on the MGISEQ-2000/DNBSEQ-T7 platform. Pregnancy outcomes and management decisions were prospectively monitored. Among the 338 patients, CMA identified chromosomal abnormalities in 56 cases (16.6%), including 23 cases of aneuploidy and 33 cases of copy number variation (CNV). The detection rate was significantly higher in the ultrasound abnormality group compared to the high-risk group identified through first-trimester serum screening (25.3% vs. 7.1%, p < 0.001). Within the ultrasound abnormality group, chromosomal abnormalities were most frequently observed in fetuses exhibiting both soft markers and structural anomalies (9/20, 45%). Moreover, the incidence of chromosomal abnormalities was higher among fetuses with nuchal translucency (NT) ≥ 4.5 mm and choroid plexus cystic hygroma (CH) (42.9% and 35.7%, respectively), though these differences were not statistically significant. Among CMA-negative cases with abnormal ultrasound findings, trio-WES identified an additional 5 of 22 (22.7%) genetic abnormalities, with a single-gene disease detection rate of 37.5% (3/8) in cases of multisystem malformations. The likelihood of single-gene disorders was significantly increased in pregnancies with NT ≥ 4.5 mm or multisystem malformations. Genetic findings had a substantial impact on clinical decision-making: termination rates were 95.7% (22/23) for aneuploidy, 50.0% (6/12) for pathogenic/likely pathogenic (P/LP) CNVs, and 100% (5/5) for P/LP monogenic variants identified by WES. Conversely, pregnancies with normal results had an 80.4% live birth rate, representing 94.4% of followed-up cases with normal findings. CMA remains essential for first-trimester prenatal diagnosis, while trio-WES provides a significant advantage in detecting single-gene disorders, particularly in fetuses with severe ultrasound anomalies. The strong association between genetic results and clinical decision-making highlights the clinical value of the proposed stratified diagnostic approach, offering evidence-based recommendations for optimizing first-trimester prenatal diagnostic strategies.

Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester: (Replaces Consults #10, Single umbilical artery, October 2010; #16, Isolated echogenic bowel diagnosed on second-trimester ultrasound, August 2011; #17, Evaluation and management of isolated renal pelviectasis on second-trimester ultrasound, December 2011; #25, Isolated fetal choroid plexus cysts, April 2013;

Uterine artery Doppler is an effective screening tool to identify high risk pregnancies in the second trimester. However, diagnosis at 22 weeks of gestation is too late to take therapeutic measures to influence trophoblastic invasion. Uterine artery Doppler at 20–23 weeks of gestation was compared to uterine artery Doppler at 12 and 13 weeks. 1524 singleton pregnancies were screened with uterine artery Doppler at 12 or 13 weeks (early) and at 20–23 weeks of gestation (late). The sum of right and left uterine artery pulsatility index was calculated. Cut-off was a PI of 2.6 at 20–23 weeks of gestation. The cut-off at early screening was calculated necessary to detect all pathological cases at late screening (PI > 2.6). 31 of the 1524 cases showed an added PI of > = 2.6 at early and late screening. Only two cases (0.13%) showed a PI higher than 2.6 at late screening after normal early screening. 934 (60.6%) tested normal at early and late screening and 567 (37.2%) showed high resistance at early, but normal resistance at late screening. Low resistance in the uterine arteries at early screening is very reassuring and results in a very low rate of pathological uterine artery Doppler results at late screening. However, the test-positive rate at early screening is rather high. A higher threshold at early screening leads to a lower detection rate of pathological cases. Additional parameters may be necessary, e.g. notch or notchindex, to lower the very high false-positive rate at early uterine artery Doppler screening.

A 35-year-old women, G4P2, was referred to our clinic after abnormal findings in a routine prenatal check-up at 28 weeks of gestation. Ultrasound examination revealed a highly vascularised mass with arteriovenous malformations arising from the umbilical cord insertion and polyhydramnios. There was a mostly well-defined hyperechoic mass of heterogeneous structure with a diameter about 76x71mm. At that moment Doppler indices were normal. After 1 week ultrasound revealed a progressive expansion of the mass and a blood flow pattern similar to umbilical artery. 31 gestational age ultrasound showed for the first time moderate cardiomegaly, mild pericardial effusion and an altered E/A Ratio from 0,57. At that point the mass diameter was about 129x96mm. After reviewing all mentioned findings and clinical state of the fetus and the mother a programmed misgav ladach Caesarean section was performed yielding a preterm female weighing 1680g with warning signs of heart failure, cardiomegaly, IRDS, hepatomegaly and tricuspidal insufficiency. The placenta weighed 1187g with a 150x100x50mm tumour at the umbilical cord insertion. Histologically there were mainly thin-walled variable sized and dilated vascular channels without endothelian atypia or multilayering. These vessels are distributed in a myxoid matrix, characteristic of a true hemangioma of the umbilical cord. Mother and baby did well. The child did not require any further surgical interventions. True hemangiomas of the umbilical cord are extremely rare, after reviewing the literature less than 50 cases have been reported, they are strongly associated with fetal morbimortality, a causal relationship has not been definitely established. There is no apparent association between cord hemangiomas and maternal age, race or gravidity nor does one sex predominate.

Seven cases of ultrasound diagnosis of velamentous insertion (VCI) of the umbilical cord at singleton pregnancies on 21–34 weeks of gestation are presented. The ultrasound picture two of the VIC types is presented: fixed in 5 cases and free in 2 cases. In one case the VCI was in the lower third of the uterus and the wound has been diagnosed the vasa previa. In other cases, the VCI was in middle third of the uterus. In all cases delivery was at 37–39.1 weeks of gestation. In 4 cases Cesarean sections were performed. In two of the VCI cases elective Ce sarean sections were performed for the following indications: previous Cesarean section and vasa previa. VCI can reliably be detected prenatally by gray-scale and color Doppler ultrasound. For fixed VCI located in the middle-upper of the uterus, no change in standard obstetrical management seems to be required.

Loss of Wharton's jelly and fibrosis in umbilical cord stricture area: A case report

We hereby reported a case of false negative non-invasive prenatal screening (NIPS) for trisomy 18. The fetus with increased nuchal translucency (3.2 mm) detected by ultrasound scan at 13+4 gestational weeks received NIPS and the result was negative in chromosomes 21, 18 and 13. A routine ultrasound examination at 22 weeks of gestation revealed multiple anomalies and a second NIPS was offered, which showed a negative result again. The pregnancy was terminated at 22+3 weeks. Multiple fetal and placental biopsies were collected for chromosome analysis using copy number variation sequencing based on high-throughput sequencing and fluorescence in situ hybridization. The fetal karyotype was shown to be 47,XY,+18 in fetal tissues (skin and liver) and umbilical cord, while no chromosomal abnormalities was detected at or near the center of the fetal and maternal surface of the placenta. Results of the chromosomal analysis along the edges of the fetal and maternal surfaces of the placenta were Chr18:47,XY,+18[60]/46,XY[40] and Chr18:47,XY,+18[35]/46,XY[65], respectively. We inferred that placental mosaicism was the cause of the false negative NIPS result. Therefore, genetic counseling before and after NIPS is necessary. Follow-up ultrasound is important for NIPS-negative patients. Invasive prenatal diagnosis is recommended when abnormal ultrasound markers with possible genetic etiology were recognized. Key words: Trisomy 18 syndrome; Ultrasonography, prenatal; False negative reactions; Nuchal translucency measurement

First reported by Chudleigh and colleagues in 1984 and considered ‘benign transient findings with no harmful sequelae’, an association between choroid plexus cysts and trisomy 18 was described by several following publications. Later on further studies have also suggested a significant risk for other chromosomal abnormalities, trisomy 21 in particular, so that literature data report an association between choroid plexus cysts and chromosomal abnormalities in about 8% of cases, more specifically in 1% if isolated and in 46% if associated with other malformations. As a consequence there are now different opinions on clinical significance and management, with some authors advocating karyotyping and others not. The aim of this study was to define the incidence of choroid plexus cysts in an unselected population and describe their association with aneuploidy. In the years 1993–99 a total of 10743 women from an unselected population attending a routine second‐trimester scanning were studied. Everyone underwent a detailed assessment of fetal anatomy by transabdominal sonography. In this period there were 27 fetuses in which choroid plexus cysts were the only sonographic abnormality, giving an incidence of 0.25% (in literature between 0.2 and 3.6%). Karyotyping was performed in only 12 cases, 11 normal and one trisomy 18. At birth the other 15 fetuses were normal. The incidence of aneuploidy was 3.70% (in according with literature review). We did not found association with other chromosomal abnormalities, trisomy 21 in particular. In the majority of cases the final risk remains small, but the presence of choroid plexus cysts increases the risk for aneuploidy, mainly trisomy 18. A need for further and wide studies about soft morphologic sonographic markers it’s necessary to better define their association with chromosomal abnormalities and as a consequence to better select the patients who need karyotyping, not underestimating that they appear in a large percentage of normal fetuses.To combine all the well‐known parameters (maternal and gestational age, serum biochemical screening, soft markers and nuchal translucency) seems to be the better way to adjust the risk of trisomy 21 and that of other chromosomal abnormalities, taking their different natural history into consideration.

Background: Nuchal Translucency Thickness (NTT) is a hypo-echoic region of subcutaneous fluid accumulation in the posterior neck region at the level of the cervical spine between the skin and soft tissues and is mostly found at 11–13 weeks of fetal gestation. It is visualised with a mid-sagittal ultrasound view of the fetus in a neutral position. The NTT provides a risk assessment for chromosomal abnormalities which has been used as a marker of possible fetal abnormalities. Hence, the justification to conduct the present study.&#x0D; Aim: To establish the mean fetal nuchal translucency thickness with corresponding gestational age (GA) and to assess the correlation between Crown Rump Length (CRL), GA, and NTT among apparently healthy pregnant women.&#x0D; Methods: A cross-sectional study was conducted among 150 apparently normal consenting pregnant women in their late first trimester in the Radiology department of Muhammad Abdullahi Wase Teaching Hospital, Kano from February 2021 to May 2021. Ultrasonographic measurements of the crown-rump length (CRL), gestational age (GA), and NTT were performed on pregnancies within 11 to 13 weeks of gestation. Their 2.5th, 25th, median and 97.5th percentiles of the NTT, GA, and CRL were determined using SPSS version 23 (IBM, 2017). Indicate correlation… as part of the analysis.&#x0D; Results: Median NTT at 11-13+6 weeks of gestation was found as 3.0±0.10mm. The NT thickness increased with increasing CRL and gestational week in the first trimester. The correlation coefficient between NTT and CRL as well as GA were 0.472 and 0.451, respectively.&#x0D; Conclusion: The overall mean NTT in Kano fetuses was determined. These should be useful for first-trimester screening in ruling out potential fetal chromosomal abnormalities in Kano, Nigeria.