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

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case-series.

OBJECTIVES: To characterize a suggestive prenatal imaging pattern of Aicardi syndrome using ultrasound and MR imaging. METHODS: Based on a retrospective international series of Aicardi syndrome cases from tertiary centers encountered over a 20-year period (2000-2020), we investigated the frequencies of the imaging features in order to characterize an imaging pattern highly suggestive of the diagnosis. RESULTS: Among 20 cases included, arachnoid cysts associated with a distortion of the interhemispheric fissure were constantly encountered associated with complete or partial agenesis of the corpus callosum (19/20, 95%). This triad in the presence of other CNS disorganization, such as polymicrogyria (16/17, 94%), heterotopias (15/17, 88%), ventriculomegaly (14/20, 70%), cerebral asymmetry [14/20, 70%]) and less frequently extra-CNS anomaly (ocular anomalies [7/11, 64%], costal/vertebral segmentation defect [4/20, 20%]) represent a highly suggestive pattern of Aicardi syndrome in a female patient. CONCLUSION: Despite absence of genetic test to confirm prenatal diagnosis of AS, this combination of CNS and extra-CNS fetal findings allows delineation of a characteristic imaging pattern of AS, especially when facing dysgenesis of the corpus callosum.

Special Report of the Society for Maternal-Fetal Medicine Placenta Accreta Spectrum Ultrasound Marker Task Force: Consensus on definition of markers and approach to the ultrasound examination in pregnancies at risk for placenta accreta spectrum.

Placenta accreta spectrum includes the full range of abnormal placental attachment to the uterus or other structures, encompassing placenta accreta, placenta increta, placenta percreta, morbidly adherent placenta, and invasive placentation. The incidence of placenta accreta spectrum has increased in recent years, largely driven by increasing rates of cesarean delivery. Prenatal detection of placenta accreta spectrum is primarily made by ultrasound and is important to reduce maternal morbidity associated with the condition. Despite a large body of research on various placenta accreta spectrum ultrasound markers and their screening performance, inconsistencies in the literature persist. In response to the need for standardizing the definitions of placenta accreta spectrum markers and the approach to the ultrasound examination, the Society for Maternal-Fetal Medicine convened a task force with representatives from the American Institute of Ultrasound in Medicine, the American College of Obstetricians and Gynecologists, the American College of Radiology, the International Society of Ultrasound in Obstetrics and Gynecology, the Society for Radiologists in Ultrasound, the American Registry for Diagnostic Medical Sonography, and the Gottesfeld-Hohler Memorial Ultrasound Foundation. The goals of the task force were to assess placenta accreta spectrum sonographic markers on the basis of available data and expert consensus, provide a standardized approach to the prenatal ultrasound evaluation of the uterus and placenta in pregnancies at risk of placenta accreta spectrum, and identify research gaps in the field. This manuscript provides information on the Placenta Accreta Spectrum Task Force process and findings.

Interobserver Reliability of the Antenatal Consensus Classification System for Urinary Tract Dilatation.

OBJECTIVES: The consensus classification system for urinary tract dilatation (UTD) was designed to be more objective and reproducible than previously used systems. We sought to evaluate interobserver reliability of UTD components and overall scores in a prenatal population undergoing third-trimester ultrasound examinations. METHODS: We retrospectively identified patients who underwent antenatal ultrasound examinations for UTD between 28 and 40 weeks' gestation. All images from individual studies of 300 fetuses were reviewed independently by 5 experienced sonologists (1 maternal-fetal medicine specialist and 4 radiologists). Urinary tract dilatation scores (normal, A1, or A2/3) and Society for Fetal Urology (SFU) scores were assigned. Interobserver agreement between raters was evaluated with the Fleiss κ statistic. RESULTS: Overall interobserver agreement for the antenatal UTD risk score showed substantial agreement among all 5 readers (κ = 0.657 [95% confidence interval, 0.632, 0.683]; P < .001). All 5 readers applied the same UTD risk score in 53.7% of cases. Some variability in the antenatal UTD score and individual elements was observed. At least 2 UTD risk scores were assigned to a specific individual patient in 46.3% of cases (139 of 300), and all 3 UTD risk scores were assigned to a specific individual patient in 1.7% of cases (5 of 300). In 18.0% of cases (54 of 300), at least 2 readers assigned a UTD score different from that assigned by the other readers. Agreement was lowest for parenchymal appearance (κ = 0.225). Agreement for the SFU system was fair (κ = 0.368; P < .001). CONCLUSIONS: Interobserver agreement for the antenatal UTD grading system was substantial. Compared to the SFU system, the antenatal UTD system showed better agreement among readers.

Proceedings: Beyond Ultrasound First Forum on improving the quality of ultrasound imaging in obstetrics and gynecology.

The Beyond Ultrasound First Forum was conceived to increase awareness that the quality of obstetric and gynecologic ultrasound can be improved, and is inconsistent throughout the country, likely due to multiple factors, including the lack of a standardized curriculum and competency assessment in ultrasound teaching. The forum brought together representatives from many professional associations; the imaging community including radiology, obstetrics and gynecology, and emergency medicine among others; in addition to government agencies, insurers, industry, and others with common interest in obstetric and gynecologic ultrasound. This group worked together in focus sessions aimed at developing solutions on how to standardize and improve ultrasound training at the resident level and beyond. A new curriculum and competency assessment program for teaching residents (obstetrics and gynecology, radiology, and any other specialty doing obstetrics and gynecology ultrasound) was presented, and performance measures of ultrasound quality in clinical practice were discussed. The aim of this forum was to increase and unify the quality of ultrasound examinations in obstetrics and gynecology with the ultimate goal of improving patient safety and quality of clinical care. This report describes the proceedings of this conference including possible approaches to resident teaching and means to improve the inconsistent quality of ultrasound examinations performed today.

When ultrasound anomalies are present: An estimation of the frequency of chromosome abnormalities not detected by cell-free DNA aneuploidy screens.

OBJECTIVES: This study characterizes cytogenetic abnormalities with ultrasound findings to refine counseling following negative cell-free DNA (cfDNA). METHODS: A retrospective cohort of pregnancies with chromosome abnormalities and ultrasound findings was examined to determine the residual risk following negative cfDNA. Cytogenetic data was categorized as cfDNA detectable for aneuploidies of chromosomes 13, 18, 21, X, or Y or non-cfDNA detectable for other chromosome abnormalities. Ultrasound reports were categorized as structural anomaly, nuchal translucency (NT) ≥3.0 mm, or other "soft markers". Results were compared using chi squared and Fishers exact tests. RESULTS: Of the 498 fetuses with cytogenetic abnormalities and ultrasound findings, 16.3% (81/498) had non-cfDNA detectable results. In the first, second, and third trimesters, 12.4% (32/259), 19.5% (42/215), and 29.2% (7/24) had non-cfDNA detectable results respectively. The first trimester non-cfDNA detectable results reduced to 7.7% (19/246) if triploidy was detectable by cfDNA testing. For isolated first trimester NT of 3.0-3.49 mm, 15.8% (6/38) had non-cfDNA detectable results, while for NT ≥3.5 mm, it was 12.3% (20/162). For cystic hygroma, 4.3% (4/94) had non-cfDNA detectable results. CONCLUSIONS: Counseling for residual risk following cfDNA in the presence of an ultrasound finding is impacted by gestational age, ultrasound finding, and cfDNA detection of triploidy.

Proceedings: Beyond Ultrasound First Forum on Improving the Quality of Ultrasound Imaging in Obstetrics and Gynecology.

The Beyond Ultrasound First Forum was conceived to increase awareness that the quality of obstetric and gynecologic ultrasound can be improved, and is inconsistent throughout the country, likely due to multiple factors, including the lack of a standardized curriculum and competency assessment in ultrasound teaching. The forum brought together representatives from many professional associations; the imaging community including radiology, obstetrics and gynecology, and emergency medicine among others; in addition to government agencies, insurers, industry, and others with common interest in obstetric and gynecologic ultrasound. This group worked together in focus sessions aimed at developing solutions on how to standardize and improve ultrasound training at the resident level and beyond. A new curriculum and competency assessment program for teaching residents (obstetrics and gynecology, radiology, and any other specialty doing obstetrics and gynecology ultrasound) was presented, and performance measures of ultrasound quality in clinical practice were discussed. The aim of this forum was to increase and unify the quality of ultrasound examinations in obstetrics and gynecology with the ultimate goal of improving patient safety and quality of clinical care. This report describes the proceedings of this conference including possible approaches to resident teaching and means to improve the inconsistent quality of ultrasound examinations performed today.

The influence of noninvasive prenatal testing on gestational age at time of abortion for aneuploidy.

OBJECTIVE: The objective of this study is to compare the gestational age at termination for trisomy 13, 18, or 21 (aneuploidy) before and after the introduction of noninvasive prenatal testing (NIPT). METHODS: A retrospective cohort of women undergoing termination for aneuploidy at two academic institutions and one private clinic. We compared two time periods: before and after the introduction of NIPT (2006-2011 and 2012-2014, respectively). Maternal demographics and clinical characteristics were abstracted from the medical record. Nonparametric statistical methods were used to compare the two cohorts. RESULTS: Our cohort included 93 women: 41 prior to NIPT and 52 post-NIPT. Maternal age (38 post-NIPT vs 37 pre-NIPT; p = 0.17) did not differ between the time periods. Women in the post-NIPT were less likely to undergo diagnostic testing (82.7% vs 97.6%; p < 0.01) before proceeding to abortion after a positive screening result. In the post-NIPT period, there was a significant decrease in the gestational age at time of invasive testing (13.0 vs 15.7 weeks; p < 0.01) and women were more likely to undergo chorionic villous sampling (CVS) (59.6% vs 41.5%; p < 0.01). There was a significant decrease in the gestational age at termination (14.2 vs 17.2; p < 0.01). Women in the post-NIPT group were less likely to have terminations after 16 weeks (25.0% vs 61.0%; p < 0.01), 18 weeks (7.7% vs 39.0%; p < 0.01), or 20 weeks (3.9% vs 12.2%; p = 0.23). CONCLUSION: With the introduction of NIPT, the median gestational age at diagnosis and termination for women with Trisomy 13, 18, or 21 was 3 weeks earlier. Women were four times less likely to have a termination after 18 weeks and three times less likely to have a termination after 20 weeks. © 2017 John Wiley & Sons, Ltd.

Fetal Anatomic Imaging Between 11 and 14 Weeks Gestation.

Fetal imaging between 11 and 14 weeks is a standard component of prenatal risk assessment for aneuploidy. Evaluating the fetus during this gestational age window provides the opportunity to reliably examine anatomic structures. Using a defined imaging protocol, approximately 50% of major abnormalities can be detected. Some abnormalities should almost always be detected, some may be detected on occasion and others are not currently detectable. Imagers must be familiar with embryologic patterns of development and natural history of anomalies. Patients must be informed of the limitations of early anatomic evaluation. Currently, early anatomic evaluation does not replace the standard second trimester evaluation.

What is the role of the 11- to 14-week ultrasound in women with negative cell-free DNA screening for aneuploidy?

OBJECTIVE: This study aimed to examine the role of the 11- to 14-week ultrasound in women with negative cell-free DNA screening. METHODS: A retrospective cohort study of women at increased risk for aneuploidy based on age or medical history and negative cell-free DNA screening between March 2012 and March 2014 was conducted. Patients were included if they had an 11- to 14-week ultrasound and obstetrical care at our center(s). Primary outcome was an unexpected finding at ultrasound. Imaging findings were compared with obstetrical outcome by medical record review. RESULTS: Study group was composed of 1739 patients. An unexpected finding was identified in 60/1739 (3.5%). An abnormal fetal finding occurred in 37 living fetuses (2.1%); 33 had a nuchal translucency (NT) ≥ 3 mm, including four 'isolated' cystic hygroma and three with a structural abnormality. Four fetuses had a structural anomaly without a thick NT. Karyotype confirmed euploidy in 98.7% of available cases. Pregnancy termination was chosen by 63.6% of those with cystic hygroma or anomaly at the 11- to 14-week scan. Unexpected multiples were identified in 13 (0.7%) women and a fetal demise in 10 (0.6%). CONCLUSION: Unexpected findings at the 11- to 14-week scan occur in 3.5% of patients with negative cell-free DNA. Recognition provides options for comprehensive testing, consultation, and management.

Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA).

OBJECTIVE: Evaluate patient choices and outcomes following positive cfDNA. METHOD: Retrospective cohort study of women with positive cfDNA through two academic centers between March 2012 and December 2014. Patients were screened based on ACOG indications. Medical records reviewed for counseling, ultrasound findings, diagnostic testing, karyotype and outcome. RESULTS: CfDNA was positive in 114 women; 105 singletons and 9 twin pairs. CfDNA was positive for autosomal trisomy (21, 18, 13) in 96 (84.2%) and sex chromosome aneuploidy in 18 (15.8%). Certified genetic counselors performed 95% of post-cfDNA counseling. Prenatal diagnostic testing was pursued by 71/114 (62%). Karyotype was available in 91/105 (86.7%) singletons and confirmed aneuploidy in 75/91 (82.4%); the PPV of cfDNA with any ultrasound finding was 93.6% versus 58.6% without a finding. An abnormal sonographic finding was seen in 4/16 (25%) singletons with false positive cfDNA. Fetal termination occurred in 53/79 (67%) singletons and 3/5 (60%) twins with prenatal abnormal or unknown karyotype for autosomal trisomy. Eleven fetuses (11/56, 19.6%) were terminated for suspected autosomal trisomy without karyotype confirmation. CONCLUSION: Patient choices following positive cfDNA are varied. Ultrasound modifies the PPV of cfDNA. Termination rates for aneuploidy are not higher than historical controls. Recommendation for karyotype confirmation prior to termination is not universally followed. © 2016 John Wiley & Sons, Ltd.

Consider ultrasound first for imaging the female pelvis.

Ultrasound technology has evolved dramatically in recent years and now includes applications such as 3-dimensional volume imaging, real-time evaluation of pelvic organs (simultaneous with the physical examination), and Doppler blood flow mapping without the need for contrast, which makes ultrasound imaging unique for imaging the female pelvis. Among the many cross-sectional imaging techniques, we should use the most informative, less invasive, and less expensive modality to avoid radiation when possible. Hence, ultrasound imaging should be the first imaging modality used in women with pelvic symptoms.

Deep infiltrating endometriosis of the bowel wall: the comet sign.

The purpose of this study was to evaluate the appearance of deep infiltrating endometriosis of the bowel wall in the cul-de-sac and determine the characteristic appearance of these lesions. We searched our database between January 1, 2011, and December 31, 2013, for all patients who had sonographic findings of suspected deep infiltrating endometriosis of the bowel with obliteration of the cul-de-sac. The medical record of each patient was examined retrospectively for evidence of surgical confirmation of disease. The sonographic appearance, shape, and size of the bowel wall lesions were evaluated to develop criteria for deep infiltrating endometriosis of the rectosigmoid and cul-de-sac. The search of our database revealed 35 patients with sonographic findings of pelvic bowel wall endometriosis associated with obliteration of the cul-de-sac. Ten of these patients had surgical confirmation of bowel wall endometriosis after the scan, and another 4 patients had surgical evidence of endometriosis from prior surgery. All of the patients who underwent surgery subsequent to sonography had confirmation of their bowel wall infiltrative endometriosis. Sonographically, the bowel lesions were solid, focal, and tubular with slightly irregular margins and in most cases a thinner section or a "tail" at one end, resembling a comet. This study confirms that bowel wall implants have a very characteristic appearance, and extending the transvaginal examination to include an evaluation of the rectosigmoid seeking these bowel lesions is valuable, especially in any patient presenting with a history of pelvic pain.

Sonographic Findings in Fetal Renal Vein Thrombosis.

We present the sonographic findings of fetal renal vein thrombosis in a series of 6 patients. The mean gestational age at diagnosis was 31.2 weeks. Four cases were unilateral, and 2 were bilateral. The most common findings were renal enlargement and intrarenal vascular calcifications, followed by increased renal parenchymal echogenicity. Inferior vena cava thrombosis was found in 4 patients and common iliac vein thrombosis in 2. Fetal renal vein thrombosis is an uncommon diagnosis with characteristic sonographic findings. The presence of these findings should prompt Doppler interrogation of the renal vein and inferior vena cava to confirm the diagnosis.