Normal Ultrasound Examination Research Articles

First-Trimester Ultrasound Screening in Routine Obstetric Practice.

Technologic advances and ultrasonographer-physician experience in fetal imaging have led to significant improvements in our ability to distinguish between normal and abnormal fetal structural development in the latter part of the first trimester. As a critical component of pregnancy care, assessment of fetal anatomy at the end of the first trimester with a standardized imaging protocol should be offered to all pregnant patients regardless of aneuploidy screening results because it has been demonstrated to identify approximately half of fetal structural malformations. Early identification of abnormalities allows focused genetic counseling, timely diagnostic testing, and subspecialist consultation. In addition, a normal ultrasound examination result offers some degree of reassurance to most patients. Use of cell-free DNA alone for aneuploidy screening while foregoing an accompanying early anatomic evaluation of the fetus will result in many anomalies that are typically detected in the first trimester not being identified until later in pregnancy, thus potentially diminishing the quality of obstetric care for pregnant individuals and possibly limiting their reproductive options, including pregnancy termination.

Evaluating the development of endometriosis and adenomyosis lesions over time: An ultrasound study of symptomatic women.

There is a gap in knowledge regarding development of endometriosis and adenomyosis lesions visible at transvaginal ultrasound. The objectives were to evaluate if women with symptoms suggestive of endometriosis or adenomyosis but normal ultrasound examination develop endometriosis or adenomyosis lesions visible at ultrasound over time and if alterations of symptoms over time are associated with ultrasound findings at follow-up. This was a prospective cohort study of 100 symptomatic women with normal initial ultrasound examination during 2014-2017 who underwent follow-up ultrasound examination in 2022. Symptoms suggestive of endometriosis were assessed using visual analog scale at both examinations and minimal clinically important difference of 10 mm was considered as a significant alteration. An examiner with expertise in advanced ultrasound examination of endometriosis performed transvaginal ultrasound examinations in accordance with the consensus protocol by the International Deep Endometriosis Analysis group. At follow-up ultrasound examination of 100 women, 13 (13% [95% CI 7.1-21.2]) had visible endometriosis or adenomyosis lesions, 8 (8% [95% CI 3.5-15.2]) had endometriosis lesions, and 6 (6% [95% CI 2.2-12.6]) had adenomyosis. At follow-up, women with endometriosis or adenomyosis lesions reported lower intensity of dysmenorrhea and chronic pelvic pain compared to women without lesions (48 mm [IQR 16-79] vs. 73 mm [IQR 46-85] and 45 mm [IQR 26-57] vs. 57 mm [IQR 36-75], p = 0.087 and p = 0.026, respectively). None of the women with endometriosis or adenomyosis lesions reported increased intensity of dysmenorrhea at follow-up, compared to 32/86 women (37%) without lesions (p = 0.008). Increased intensity of chronic pelvic pain tended to be less common in women with lesions compared to those without (3/13 [23%] vs. 35/86 [41%], p = 0.223). Our findings suggest that in symptomatic women, endometriosis and adenomyosis lesions visible at ultrasound may develop over time. However, majority of women remain having normal ultrasound examinations despite symptoms. Exacerbation of dysmenorrhea or chronic pelvic pain during follow-up was not associated with the development of endometriosis or adenomyosis lesions visible at ultrasound, suggesting that even women with less severe symptoms might benefit from a follow-up ultrasound when indicated.

Ultrasound as the first line investigation for midgut malrotation: a UK tertiary centre experience

To present the first 22-months experience of transitioning to an ultrasound-first pathway for suspected midgut malrotation. An "ultrasound-first" imaging pathway was initiated in October 2021. Twenty-two-months later, a search was undertaken of all <1-year-old patients with "bilious", "malrotation," or "volvulus" as the imaging indication. Reports and images from upper gastrointestinal fluoroscopy (UGI) and ultrasound were reviewed, and diagnoses and outcomes were documented. The search yielded 101 eligible cases between October 2021 and July 2023. Of the patients, 63/101 (62%) had both ultrasound and UGI: 47/63 (75%) ultrasound first, 16/63 (25%) UGI first. Thirty-one per cent (31/101) had ultrasound only and 7/70 (10%) UGI only. The pathway diagnosed 7/8 (88%) infants with midgut malrotation with or without volvulus and one infant who had an inconclusive ultrasound examination with a suspected an internal hernia and who was found to have malrotation volvulus at surgery. Twenty-one infants who had confidently normal ultrasound examinations and who also had UGI all had a normal duodenojejunal flexure position. Ultrasound detected alternative pathology in eight children. Duodenal visualisation improved with time: 6/15 (40%) in the first 6 months to 23/34 (68%) after the first year. The transition to ultrasound as the first diagnostic test for midgut malrotation can be done safely and effectively in a UK centre, which previously relied solely on UGI.

The role of first-trimester ultrasound screening for women with positive noninvasive prenatal testing results.

This study aimed to assess the utility of ultrasound screening for pregnancies with positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. We performed a retrospective analysis of positive noninvasive prenatal testing results and first-trimester ultrasound screening at our department between 2013 and 2019. Invasive genetic testing was performed if the patient had positive noninvasive prenatal testing results. Fetal ultrasound and cytogenetic data were collected. Noninvasive prenatal testing was performed in the women for advanced maternal age, nuchal translucency thickness, or history of abnormality in the previous child or relative. Forty-one pregnant women had positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. Twenty-three women had positive results for trisomy 21, 13 had positive results for trisomy 18, and 5 had positive results for trisomy 13 at 11 to 14 weeks of gestation. The positive predictive value of noninvasive prenatal testing was 100% for trisomy 21, 84.6% for trisomy 18, and 100% for trisomy 13. The positive predictive value of positive noninvasive prenatal testing results and fetal morphological abnormalities was 100% for trisomy 21, trisomy 18, and trisomy 13. Combining an ultrasound examination with noninvasive prenatal testing resulted in a higher positive predictive value for trisomy 18. Normal ultrasound examination results can help alleviate stress caused by false-positive noninvasive prenatal testing results. In contrast, the positive predictive value and negative predictive value for trisomy 21 were not altered by adding an ultrasound examination to noninvasive prenatal testing.

Prevalence of Sub-Clinical Hypothyroidism in Diagnosed Cases of Gallstone Disease

Thyroid issues have long been debated as a possible cause of gall stone disease. The link between hypothyroidism and gallstone disease could be explained in a variety of ways. The main objective of this study is to determine the prevalence of hypothyroidism in gallstone patients and to rule out hypothyroidism as a probable cause of gallstone formation. A prospective study was conducted in surgical wards of Department of surgery sree balaji medical college from 2016 to 2017. All patients were evaluated using a comprehensive clinical history and examination, as well as suitable investigations such as abdominal USG, thyroid function tests, and lipid profiles. Out of 22 patients 19 patients (86.4%) had normal TSH, 2 patients (9.1%) had increased TSH, 1 patient (4.5%) had decreased TSH. Raised TSH was more in the AGE Group of 61- 75 years, which is comparable to other studies. Out of 22 patients, (100%) had normal T3 levels. 19 patients (86.4%) had normal T4 levels and Ultrasound examination of neck, 2 patients (9.1%) had decreased T4 level and 1 patient (4.5%) had increased T4 levels and 3 patients (13.6%) had abnormal Ultrasound Neck findings. Hence In this Study Cholelithiasis is most commonly seen in Females of age group of 41-60 years and prevalence of raised TSH level in cholelithiasis patient was 9% and most were found in the age group of 61-80 years.

Practical approach for the diagnosis of biliary atresia on imaging, part 2: magnetic resonance cholecystopancreatography, hepatobiliary scintigraphy, percutaneous cholecysto-cholangiography, endoscopic retrograde cholangiopancreatography, percutaneous liver biopsy, risk scores and decisional flowchart.

We aim to present a practical approach to imaging in suspected biliary atresia, an inflammatory cholangiopathy of infancy resulting in progressive fibrosis and obliteration of extrahepatic and intrahepatic bile ducts. Left untreated or with failure of the Kasai procedure, biliary atresia progresses to biliary cirrhosis, end-stage liver failure and death within the first years of life. Differentiating biliary atresia from other nonsurgical causes of neonatal cholestasis is difficult as there is no single method for diagnosing biliary atresia and clinical, laboratory and imaging features of this disease overlap with those of other causes of neonatal cholestasis. In this second part, we discuss the roles of magnetic resonance (MR) cholecystopancreatography, hepatobiliary scintigraphy, percutaneous biopsy and percutaneous cholecysto-cholangiography. Among imaging techniques, ultrasound (US) signs have a high specificity, although a normal US examination does not rule out biliary atresia. Other imaging techniques with direct opacification of the biliary tree combined with percutaneous liver biopsy have roles in equivocal cases. MR cholecystopancreatography and hepatobiliary scintigraphy are not useful for the diagnosis of biliary atresia. We propose a decisional flowchart for biliary atresia diagnosis based on US signs, including elastography, percutaneous cholecysto-cholangiography or endoscopic retrograde cholangiopancreatography and liver biopsy.

Intracranial Hemorrhage

Intracranial Hemorrhage

Reference intervals and reliability of cavum septi pellucidi volume measurements by three-dimensional ultrasound between 19 and 24weeks' gestation.

A small or a large cavum septi pellucidi (CSP) during routine second trimester sonography may suggest abnormal cerebral development. Therefore, determination of CSP volume with three-dimensional (3D) ultrasound can be valuable. For this purpose, we sought to evaluate the reference ranges and measurement reliability of CSP volume by Virtual Organ Computer-aided AnaLysis (VOCAL). VOCAL software was used to calculate the CSP volume from transabdominal multiplanar datasets of 99 structurally normal fetal ultrasound examinations between 19 and 24weeks of gestation. Linear regression was utilized to determine reference intervals for CSP volumes as a function of gestational week (GW). Agreement among three evaluators with different proficiency levels (obstetrics and gynecology resident, perinatology fellow, and perinatologist) was assessed, using intraclass correlation coefficients (ICC) and 95% confidence intervals (CI). CSP volume and gestational age was positively correlated (r2=0.383, p=0.0001), represented by the following equation: 0.058-(1.016xGW). Interobserver agreement between perinatologist and fellow was relatively high (ICC, 0.78; 95% CI, 0.70-0.85), whereas limited ultrasound experience (resident) was associated with fair agreement with non-novice observers (ICC for resident and perinatologist, 0.50; 95% CI, 0.29-0.65 and ICC for resident and fellow, 0.57; 95% CI, 0.38-0.71). Reference ranges of CSP volumes using VOCAL from 19 0/6 through 24 6/7weeks of gestation were established. A first-degree model to estimate CSP volume as a function of gestational age was also constructed. CSP volumetry seems reliable when evaluated by an examiner with particular 3D sonography experience.

Systematic retrospective analysis of 13 cases of uterine arteriovenous fistula: Pathogeny, diagnosis, treatment and follow-up.

To analyze the causes, clinical manifestations, diagnosis and treatment of uterine arteriovenous fistula (UAVF). We retrospectively analyzed 13 patients with UAVF admitted to our hospital from October 2016 to April 2019. All patients had a history of intrauterine surgery (curettage for abortion, artificial removal of placenta, hysteroscopy, diagnostic curettage and intrauterine device removal). The main clinical manifestation of UAVF is paroxysmal massive vaginal bleeding; this involved a massive gush of vaginal blood that stopped suddenly. Sonographic images with typical features of UAVF were observed for 12 patients. Pelvic contrast-enhanced magnetic resonance imaging was performed as a noninvasive adjuvant examination method for diagnosis. Twelve patients underwent uterine arteriography and a diagnosis of UAVF was confirmed. Then, bilateral uterine artery embolization (UAE) was performed. One patient underwent laparoscopic hysterectomy directly instead of uterine arteriography because of unstable vital signs and one patient underwent laparoscopic hysterectomy 25 weeks after the second UAE. The median time until menstrual recovery was 33 days (range, 20-70 days) after UAE. The median time until normal ultrasound examination results was 10 weeks (range, 2-35 weeks). Acquired UAVF was associated with a history of previous intrauterine surgery. The ultrasound examination and pelvic contrast-enhanced MRI were noninvasive adjuvant examination method to effectively assist in diagnosis. Uterine arteriography is considered the gold standard for the diagnosis of UAVF, and UAE is considered an effective intervention for treating UAVF and maintaining reproductive function with less damage. Hysterectomy is an appropriate option when conservative measures have failed to prevent a life-threatening hemorrhage.

Which Metabolic Index is Appropriate for Predicting Non-alcoholic Steatohepatitis?

BACKGROUND There are controversial ideas about the application of metabolic indices for the prediction of nonalcoholic steatohepatitis (NASH). In this study, we evaluated some novel metabolic indices for the screening of NASH. METHODS This prospective case-control study was performed in a gastroenterology outpatient clinic. Consecutively selected patients with persistently elevated aminotransferase levels and evidence of fatty liver in ultrasonography were enrolled. Those with other etiologies of aminotransferase elevation were excluded. The remaining was presumed to have NASH. The control group consisted of age and sex-matched subjects with normal liver function tests and liver ultrasound examinations. RESULTS Finally, 94 patients with steatohepatitis and 106 controls were included in the project. The mean liver fat content (LFC), aspartate aminotransferase, and alanine aminotransferase levels were significantly lower in the control group than in the NASH group. LFC was independently associated with the presence of NASH in logistic regression analysis. LFC had a good area under the curve for the prediction of NASH in ROC (receiver operating characteristic curve) analysis. CONCLUSION LFC seems to be a reliable metabolic index for the detection of patients with NASH.

Information Women Choose to Receive About Prenatal Chromosomal Microarray Analysis.

To examine the choices of women with both high-risk and low-risk pregnancies who are undergoing prenatal chromosomal microarray analysis in a clinical setting regarding three challenging types of findings: variants of uncertain clinical significance, susceptibility loci for neurodevelopmental disorders, and copy number variants associated with risks for adult-onset conditions. We assessed whether women's choices were associated with indications for testing or with one-on-one pretest genetic counseling. In this cross-sectional study, medical records of women who underwent invasive prenatal chromosomal microarray analysis testing (N=1,070) at Hadassah Medical Center between June 2017 and February 2018 were examined for testing indications, choices regarding chromosomal microarray analysis findings, and type of pretest genetic counseling. Multivariable analyses to assess associations with testing indication and prior genetic counseling were carried out using logistic regression models. In total, 56% of women (n=593) chose to be informed of all three types of findings and 20% (n=218) chose not to be informed of any of the findings beyond high-penetrance childhood-onset pathogenic findings. Variants of uncertain clinical significance as a single choice was the least-selected finding (2.5%, n=27). Low-risk pregnancies (ie, those with normal biochemical screening and fetal ultrasound examinations) were associated with increased interest in receiving genetic information about adult-onset conditions (adjusted odds ratio [aOR] 1.7; 95% CI 1.18-2.33) and susceptibility loci (aOR 1.5; 95% CI 1.08-2.10). Women with both high-risk and low-risk pregnancies were generally more likely to choose to receive additional genetic information, albeit differences in preferences depend on testing indication and type of pretest counseling.

Usefulness and reliability of cell free fetal DNA screening for main trisomies in case of atypical profile on first trimester maternal serum screening

BackgroundPatients with atypical values of HCG and/or PAPP-A are at higher risk of chromosomal abnormality and vascular complications of pregnancy. The performance of cfDNA in this particular population has not yet been evaluated.ObjectivesThe primary objective was to evaluate the usefulness and reliability of cfDNA in screening for trisomy 21, 18 and 13 for patients with HCG < 0.25 multiple of median (MoM), HCG > 5.0 MoM and/or PAPP-A < 0.25 MoM, PAPP-A > 2.5 MoM. The secondary objective was to evaluate the contribution of cfDNA assay for the prediction of pregnancy’s vascular complications.MethodBetween June 2016 and July 2017, we analysed a women cohort from all over France who had at least one first trimester serum biomarker outside of normal range, in a retrospective, observational and multicentre study. Patients were included if they had a single pregnancy, normal first trimester ultrasound examination, whatever the result of the combined first trimester screening test was. The cfDNA was analysed by massive parallel sequencing technique. The accuracy of cfDNA assay was evaluated by calculation of sensitivity and specificity, and multivariate regression analysis was used to search for predictive factors for pregnancy’s vascular complications.ResultsAmong the 498 patients who underwent a cfDNA assay in this context, twenty-one (4.2%) were excluded because of loss to follow-up. Out of 477, test failure occurred for four patients initially, reduced to two patients (0.4%) after redrawn. CfDNA was positive for Trisomy 21 (n = 19), Trisomy 18 (n = 6) and Trisomy 13 (n = 1) and negative in 449. The sensitivity of cfDNA assay for trisomy 21 screening was 100% (19/19) (IC 95% 82.4–100) and specificity 100% (458/458) (IC 95% 99.2–100). Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was identified. Intra Uterine growth restriction under 5th percentile (n = 44, 9.8%) was significantly associated with a low fetal fraction (OR = 0.87, IC 95% 0.79–0.96, p = 0.006).ConclusioncfDNA assay is an effective and reliable tool for women with atypical profile of first trimester serum biomarkers.

Common Findings in Ultrasound Examination of the Liver and Kidney in Sokoto Metropolis

Objectives: To evaluate and document common findings in ultrasound examination of the liver and kidneys in Sokoto metropolis and to reveal gender and age distribution of the findings in these organs.&#x0D; Materials and Methods: The data was collected retrospectively from the hospital archives and records using a data capture sheet.&#x0D; Results: Total sample of 322 ultrasound reports of the liver and kidneys in which some patients had two findings, one in the liver and another in the kidney, some had liver findings only, some kidney findings only, while some had normal ultrasound examination. Liver findings recorded a dominant male gender with a frequency of 75 (70.1%). Findings in the liver reported were liver cirrhosis, hepatomegaly, fatty liver, primary liver cell carcinoma, hepatic metastasis, chronic liver disease (CLD), hepatitis, hepatoma and liver cyst. Liver cirrhosis had the highest frequency with 29 (27.1%), hepatomegaly with a frequency of 17 (15.9%) followed by fatty liver and plcc with a frequency of 13 (12.1%) each. The age range of 40-49 years had the highest frequency for the liver findings with 23 (21.5%), followed by 60-69 years with 18 (16.8%) while 10-19 years had the least frequency with 3 (2.8%). For the kidney findings, male gender also dominated the findings with a frequency of 107 (64.1%). The age range that had the highest frequency was 20-29 years with 43 (25.7%), followed by 30-39 years with a frequency of 27 (16.2%). The age range with the least frequency was 80-89 years with 6 (3.6%). The pathological kidney findings reported were pyelonephritis, renal parenchyma disease (grades I, II, III, and IV), hydronephrosis, renal calculi, renal cyst, ectopic kidney, renal mass, renal failure and nephrotic syndrome. Pyelonephritis was recorded as the commonest finding with a frequency of 67 (40.1%), followed by renal parenchymal disease with 35 (21.0%).&#x0D; Conclusion: The study revealed that male gender is at higher risk of having both liver and kidney diseases in Sokoto metropolis than the female and the age of those at higher risk ranged from 20-49 years.&#x0D; Liver cirrhosis and pyelonephritis are the commonest diseases of the liver and kidneys respectively.

A prospective study of high resolution ultrasound in brachial plexopathies – Correlation with electrophysiological measurements

ObjectivesTo evaluate the diagnostic role of ultrasound in brachial plexopathies. MethodsWe included 59 healthy subjects (HS) and 42 patients consecutively referred with clinical suspicion of brachial plexopathy from October 2015 to May 2016. Patients underwent routine electrodiagnostic testing (EDx) as reference standard and a blinded standardised ultrasound examination of the brachial plexus as index test with cross-sectional area (CSA) as the ultrasound parameter of choice. ResultsSeventeen patients were diagnosed by EDx with brachial plexopathy, ten with mononeuropathies, and ten had normal EDx. Five had a cervical radiculopathy. In 11 (64%) out of the 17 patients with EDx diagnosed plexopathy, we found at least one abnormal level on ultrasound. Six (60%) out of ten normal EDx patients had a normal ultrasound examination at all levels. Ultrasound identified the same abnormal level(s) as EDx in eight (73%) of the 11 patients who had both abnormal EDx and ultrasound results. Mean CSA was higher in the plexopathy group compared to HS at the level of the C6 root (p = .022), the middle trunk (p = .027), and the medial cord (p = .003). ConclusionUltrasound examination showed abnormalities in patients with brachial plexopathies in good agreement with EDx. SignificanceUltrasound may be an important supplement to electrodiagnostics in evaluating brachial plexopathies.

The rate of brain abnormalities on in utero MRI studies in fetuses with normal ultrasound examinations of the brain and calculation of indicators of diagnostic performance

To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS). A prospective cohort study of pregnant women whose fetus had no structural brain (or body) abnormalities recognised on antenatal ultrasonography. Women were recruited from 12 centres across the UK and underwent iuMRI at 18 gestational weeks or more in the [blinded for review]. The imaging studies were reviewed by an experienced neuroradiologist. The positive and negative predictive values of both USS and iuMRI have been calculated by combining the results of this study with the results from the main [blinded for review] study. One hundred and ninety-eight pregnant women were recruited and underwent iuMRI of 205 fetuses. Brain abnormalities were shown on iuMRI in two fetuses that were not recognised on USS (one case of a focal cortical abnormality and one case of mild ventriculomegaly). The negative predictive value for USS was 99.5% and 100% for iuMRI. To the authors' knowledge, this is the first study comparing USS and iuMRI in low-risk pregnancies. USS has a comparatively high rule-out for fetal brain abnormalities and should remain the screening tool of choice.

Lower limb volume in healthy individuals after walking with compression stockings

ObjectiveDespite the modern appeal of wearing compressive garments during physical activities, the literature is lacking in quality data and controversial in the investigations dealing with the pathophysiologic mechanism by which graduated compression stockings (GCS) affect the calf pump activation in healthy individuals. The aim of the investigation was to provide insight into the clinical effects of GCS use during a standardized walking exercise. MethodsTwenty physically active healthy volunteers (mean age, 34 ± 5 years; body mass index, 22 ± 2 kg/m2) underwent lower limb ultrasound scanning to exclude vascular impairment. All individuals performed continuous aerobic exercise, walking for 30 minutes on a treadmill, under cardiac monitoring, at 70% of individual estimated maximal heart rate according to the Tanaka equation. The study population performed the standardized walk without GCS (baseline) and at 1 week performed the same standardized walk wearing knee-length 20 to 30 mm Hg GCS (compression). All individuals underwent a lower limb volume assessment by truncated cone formula before and after the walk and a perceived exertion assessment by means of the validated Borg scale at the end of the exercise protocol. ResultsAll individuals had normal venous and arterial ultrasound examination findings. No significant postural defects were reported. Both legs were assessed in all 20 individuals for a total of 40 cases with and 40 cases without GCS. In the baseline group, the median (interquartile range) lower limb volume changed from 2496 (770) mL before exercise to 2512 (805) mL (P = .2597) after exercise. The compression group reported a significant lower limb volume change from 2466 (670) mL before exercise to 2276 (567) mL (P = .0001) after exercise. Mean perceived exertion was 13 (11) and 11 (1) in the baseline and compression groups, respectively (P = .0001). The interface pressure exerted by the GCS was 24 (2) mm Hg. No complaints in terms of discomfort were reported after use of GCS. ConclusionsIn healthy individuals, GCS (24 [2] mm Hg) use during a continuous standardized walk of 30 minutes is associated with a significant decrease in lower limb volume and a decrease in perceived exertion. The mechanism by which GCS impart their effect during physical activity may involve improved muscle pump function and reductions in inflammatory pathways. Further study will need to validate the mechanisms of the function of GCS used during physical exercise.

190: Optimal surveillance of monochorionic-diamniotic twins for twin-twin transfusion syndrome

Biweekly surveillance ultrasound (US) examination is a strategy recommended to detect early twin-twin transfusion syndrome (TTTS) in monochorionic-diamniotic (MCDA) twins. However, data to support this frequency of surveillance are scarce. Our objective was to determine whether a biweekly scanning paradigm can reliably detect TTTS at an early stage (i.e. < Quintero stage II). This is a retrospective cohort study of women with MCDA twin pregnancies whose first US exam occurred at our center between 2012 and 2018. Women with uncertain chorionicity, less than 2 serial US exams, or those followed outside of our healthcare system were excluded. Routine surveillance consisted of an US exam every 2 weeks starting at 16 weeks gestational age (GA). Univariate analysis of US exam patterns and pregnancy characteristics was performed comparing women that had TTTS to those who did not. For women diagnosed after at least one normal US examination, GA and Quintero stage at diagnosis and length of time since the last normal US exam was determined to assess whether the frequency of US examination was adequate. To assess whether the initial screening US was early enough to detect evolving TTTS, women diagnosed with TTTS on their first US were considered separately. Of 409 women with MCDA twins that met inclusion criteria, 46 (11.3%) developed TTTS. Women with TTTS had less time between scans (7.4 ± 7.6 vs. 12.7 ± 8.0 days, p < 0.01), but baseline characteristics were otherwise similar between the groups (Table 1). Among women with TTTS, 25 (54.4%) were diagnosed at their first US while 21 (46.6%) were diagnosed at a later US. Those diagnosed at the first US had similar GA (20.3 ± 3.8 vs. 22.3 ± 4.9, p = 0.16) and Quintero stage (median II vs. III, p = 0.34) as those diagnosed at a later US exam. The majority of TTTS detected after at a later US (i.e. >1 US) was diagnosed within 2 weeks of the last normal US (16/21, 76%). Most of these twins (9/16, 56%, p = 0.09) had stage II or greater disease on diagnosis (Figure 1). In this cohort of women that had biweekly ultrasounds, most cases of TTTS were detected at an advanced stage (Quintero stage > I). This suggests that biweekly US alone is not adequate to diagnose early TTTS. Further research is required to determine whether more frequent US screening may improve early detection. For women diagnosed on first US, it is unclear from this analysis whether earlier US would detect TTTS earlier.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

False-positive rates in screening for trisomies 18 and 13: a comparison between first-trimester combined screening and a cfDNA-based approach.

To determine the false-positive rates (FPR) associated with screening for trisomy 18/13 using first-trimester combined screening (FTCS) and an ultrasound plus cfDNA-based approach (US-cfDNA), which includes a detailed ultrasound examination, a cfDNA analysis and a FTCS reflex backup test for cases with uninformative results. This is a sub-analysis of a randomized controlled trial, which was performed between 2015 and 2016. Pregnant women with a normal first-trimester ultrasound examination at 11-13weeks' gestation (NT < 3.5mm, no anomalies) were randomized into two groups: FTCS and US-cfDNA screening. The overall FPR in screening for trisomies 18/13 and 21 was compared with the FPR in screening for trisomy 21 alone. Pregnancies were considered screen positive if the risk for trisomy 21 was 1:100 and for trisomy 18 and 13, 1:20 each. The study population consisted of 688 pregnancies in each study arm. In the FCTS group, median delta NT was 0.0mm, free beta-hCG and PAPP-A 0.96 and 1.11 MoM. In the US-cfDNA group, median delta NT was 0.0mm. In 10 pregnancies, the cfDNA analysis was uninformative. In the FTCS and in the US-cfDNA group, the FPR in screening for trisomy 21 was 2.5% and 0%. In both groups, the overall FPR was not increased by adding screening algorithms for trisomies 18 and 13. In conclusion, the addition of screening for trisomies 18 and 13 to screening for trisomy 21 does not significantly change FPR. This is true for both the FTCS and the US-cfDNA-based approach.

False-Positive Rate in First-Trimester Screening Based on Ultrasound and Cell-Free DNA versus First-Trimester Combined Screening with Additional Ultrasound Markers

Objective: To determine whether screening for trisomy 21 based on first-trimester combined screening (FTCS) with assessment of nasal bone (NB), tricuspid flow (TCF), and ductus venosus flow (DVF) results in similar false-positive rates compared to ultrasound and cell-free DNA (cfDNA) screening. Methods: This is a subanalysis of a prospective randomized controlled trial which was performed between October 2015 and December 2016. Pregnant women with a normal first-trimester ultrasound examination at 11 to 13 weeks’ gestation were randomized into two groups: (1) FTCS with assessment of the NB, TCF, and DVF (extended FTCS [eFTCS]), and (2) ultrasound + cfDNA screening. The false-positive rate in screening for trisomy 21 was defined as the primary outcome parameter. Results: The study population consisted of 688 women in each study arm. In the eFTCS group, the median delta fetal nuchal translucency thickness (NT) was 0.0 mm, free beta-hCG and PAPP-A were 0.96 and 1.11 MoM, and NB, TCF, and DVF PIV were abnormal in 0.9, 0.6, and 7.0% cases. In the ultrasound + cfDNA group, the median delta NT was 0.0 mm. In 10 pregnancies the cfDNA analysis was uninformative and the risk of trisomy 21 was based on eFTCS. There were no false-positive cases in the ultrasound + cfDNA group, whereas the false-positive rates were between 0.9 and 2.2% with eFTCS. Conclusion: Screening for trisomy 21 based on ultrasound + cfDNA has a lower false-positive rate than screening based on eFTCS.

First-trimester risk assessment based on ultrasound and cell-free DNA vs combined screening: a randomized controlled trial.

This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT)≤ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was >1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (> 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n= 87) and cases of fetal death and loss to follow-up (n= 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.