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Backgroud: A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes. Methods: In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes. Results: Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed. Conclusions: This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P. [ABSTRACT FROM AUTHOR]

Background: Ultrasound serves as a valuable tool for the early detection of fetal bowel dilatation, yet the correlation between fetal bowel dilatation and gastrointestinal malformations remains to be further investigated. This study aims to explore the relationship by conducting a follow-up and analysis of fetuses with bowel dilation. Methods: A retrospective analysis was conducted on 113 fetuses with bowel dilatation at our center from July 2014 to December 2019. The location and degree of bowel dilatation were analyzed. ROC curves were constructed based on the diameter of the bowel and its ratio to fetal gestational age. Results: In total, 40 of 41 cases (97.6%) with upper gastrointestinal dilatation (double-bubble sign) and 46 of 72 cases (63.9%) with lower gastrointestinal dilatation were diagnosed with gastrointestinal malformations postnatally. The AUC of the dilatation diameter was 0.854 with a cutoff value of 18.05 mm in patients with lower gastrointestinal dilatation. The ratio of the diameter to gestational age (D/GA) showed a higher AUC of 0.906 with a cutoff value of 0.4931. Conclusions: The presence of the double-bubble sign in fetuses indicates a close association with duodenal obstruction. The risk of gastrointestinal malformations increases when the bowel diameter exceeds 18.05 mm, particularly when the D/GA surpasses 0.4931. [ABSTRACT FROM AUTHOR]

Background: Deep learning (DL) is a new technology that can assist prenatal ultrasound (US) in the detection of congenital heart disease (CHD) at the prenatal stage. Hence, an economic-epidemiologic evaluation (aka Cost-Utility Analysis) is required to assist policymakers in deciding whether to adopt the new technology. Methods: The incremental cost-utility ratios (CUR), of adding DL assisted ultrasound (DL-US) to the current provision of US plus pulse oximetry (POX), was calculated by building a spreadsheet model that integrated demographic, economic epidemiological, health service utilization, screening performance, survival and lifetime quality of life data based on the standard formula: CUR = Increase in Intervention Costs - Decrease in Treatment costs Averted QALY losses of adding DL to US & POX US screening data were based on real-world operational routine reports (as opposed to research studies). The DL screening cost of 145 USD was based on Israeli US costs plus 20.54 USD for reading and recording screens. Results: The addition of DL assisted US, which is associated with increased sensitivity (95% vs 58.1%), resulted in far fewer undiagnosed infants (16 vs 102 [or 2.9% vs 15.4%] of the 560 and 659 births, respectively). Adoption of DL-US will add 1,204 QALYs. with increased screening costs 22.5 million USD largely offset by decreased treatment costs (20.4 million USD). Therefore, the new DL-US technology is considered "very cost-effective", costing only 1,720 USD per QALY. For most performance combinations (sensitivity > 80%, specificity > 90%), the adoption of DL-US is either cost effective or very cost effective. For specificities greater than 98% (with sensitivities above 94%), DL-US (& POX) is said to "dominate" US (& POX) by providing more QALYs at a lower cost. Conclusion: Our exploratory CUA calculations indicate the feasibility of DL-US as being at least cost-effective. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. Methods: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. Results: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD‐flow combined with STIC than that in the 2D combined with HD‐flow. Conclusion: HD‐flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the local incidence of orofacial cleft (OFC) encountered in fetal morphology scan and prenatal diagnosis, genetic etiology of fetuses with or without other structural abnormalities, and their pregnancy outcomes. Design: Retrospective cohort study. Setting: Two maternal fetal medicine units, tertiary hospitals, Hong Kong. Participants: All pregnant women with antenatal diagnosis of fetal OFC between January 2016 and December 2020 (N = 66). Results: OFC has an incidence of 0.13% among pregnancies in Hong Kong and 28.8% (19/66) were syndromic cleft that exhibited other fetal structural anomalies. There were 55 cases (84.6%) who opted for invasive prenatal diagnostic testing. Genetic defects were identified in 25.8% (17/66) of this cohort, including 14 pathogenic variants. The detection rate in the syndromic cases is 68.4% (13/19) which was significantly higher than 8.5% (4/47) among non-syndromic cases. Aneuploidies would be the most common cause, accounting for 9.1% (6/66). Chromosomal microarray analysis (CMA) provided an incremental diagnostic yield of 6.1% compared to conventional karyotyping. A total of 29 live births including 3 cases of a variant of uncertain significance and 26 cases without genetic abnormalities detected have continued pregnancy to birth. There were 87.5% (21/24) without detectable pathogenic genetic abnormality reported good long-term outcomes. The chance of OFC fetuses having a good long-term outcome was significantly higher if no genomic variant was detected (P <.001). Conclusions: Invasive prenatal tests with CMA should be offered to pregnancies with OFC regardless of the type. It has provided incremental diagnostic yield over conventional karyotyping and helped in prenatal and genetic counseling. A negative result in non-syndromic OFC favors couples to keep the pregnancy. [ABSTRACT FROM AUTHOR]

Medical imaging in pregnancy (antenatal imaging) is routine. However, the effect of seeing fetal images on the parent–fetal relationship is not well understood, particularly for fathers or partners, or when using advanced imaging technologies. This review aimed to explore how parent experience and prenatal attachment is impacted by antenatal imaging. Database searches were performed between September 2020 and April 2021 Inclusion criteria were English language primary research studies published since 2000, describing or reporting measures of attachment after antenatal imaging in expectant parents. The Pillar Integration Process was used for integrative synthesis. Twenty-three studies were included. Six pillar themes were developed: 1) the scan experience begins before the scan appointment; 2) the scan as a pregnancy ritual; 3) feeling actively involved in the scan; 4) parents' priorities for knowledge and understanding of the scan change during pregnancy; 5) the importance of the parent–sonographer partnership during scanning; and 6) scans help to create a social identity for the unborn baby. Antenatal imaging can enhance prenatal attachment. Parents value working collaboratively with sonographers to be actively involved in the experience. Sonographers can help facilitate attachment by delivering parent-centred care tailored to parents' emotional and knowledge needs. [ABSTRACT FROM AUTHOR]

The phenotypes of Xp22.33 or Yp11.32 microdeletions comprising the short-stature homeobox (SHOX) gene have been extensively described in adults and children. Herein, the prenatal ultrasound phenotype and pregnancy outcomes of fetuses with Xp22.33/Yp11.32 microdeletions were analyzed to improve our understanding, diagnosis, and monitoring of this genetic condition in the fetal stage. A total of 9,100 pregnant women referred to tertiary units for prenatal diagnosis were evaluated by chromosomal microarray analysis(CMA). Seven (0.08 %) fetuses had Xp22.33/Yp11.32 microdeletions, ranging from 243 kb to 1.1 Mb, that comprised SHOX. The ultrasonic phenotypes differed among these fetuses, with three fetuses presenting abnormal bone development, one had labial-palatal deformity and strawberry head, two had an abnormal ultrasonic soft marker, and one had no abnormalities. After genetic counseling, only one couple underwent pedigree assessment, which confirmed the paternal origin of the microdeletion. This infant presented delayed speech development, whereas other three infants showed a typical postnatal development. In three cases, the parents chose to terminate the pregnancy. The ultrasonic phenotype of fetuses with Xp22.33/Yp11.32 microdeletions resulting in SHOX heterozygosity loss is variable. Prenatal CMA can quickly and effectively diagnose Xp22.33/Yp11.32 microdeletions and SHOX loss, which may help prenatal counseling. [ABSTRACT FROM AUTHOR]

Background: Combined first‐trimester screening (cFTS) for fetal anomalies involves maternal serum screening for biochemical markers and measurement of the nuchal translucency (NT) by ultrasound. Noninvasive prenatal screening (NIPS) analyses cell‐free DNA present in a maternal blood sample for presence of fetal chromosomal aneuploidies. Aims: To compare NIPS with cFTS as frontline screening in a public hospital in Australia. Materials and methods: Women were offered NIPS in addition to the usual cFTS routinely offered to all women at a public hospital in NSW, Australia. The cFTS sample was collected at ten weeks' gestation and the NIPS sample at 12 weeks' gestation at the ultrasound appointment. Results: In a low‐risk population of 997 women, frontline NIPS had a screen‐positive rate of 0.5% (5/997) vs 4.2% (42/997) with cFTS. cFTS correctly identified one trisomy 21 case and one trisomy 18 case; however, there were two trisomy 18 false negatives. Of five positive NIPS calls, four were correctly identified as trisomy 21 (one) and trisomy 18 (three); there were no NIPS false negatives. Overall, the false‐positive rate with NIPS was 0.1% vs 4.0% by cFTS. Conclusions: The lower screen‐positive rate with NIPS for common trisomies was a result of the significantly lower false‐positive rate with NIPS. Consequently, NIPS as first‐line screening, even if funded by the hospital, may provide cost savings. We believe NIPS should be used from ten weeks' gestation in conjunction with morphology ultrasound for routine first‐trimester prenatal management. [ABSTRACT FROM AUTHOR]

Aim: This retrospective study aimed to investigate the value of exome sequencing (ES) in fetuses with isolated first‐trimester increased nuchal translucency (NT) and normal chromosomes. Methods: ES was performed on 103 fetuses with isolated first trimester increased NT and normal chromosomes. The detection rate of monogenic conditions was analyzed. Results: Diagnostic variants were detected in nine cases in which phenotypes and genotypes correlated well, two positive cases were Thanatophoric dysplasia type I, and one case was Kabuki syndrome, which had been detected in previous studies. Eight of the nine cases with diagnostic variants developed additional structural malformations later in pregnancy. Among the nine positive cases, six had a NT thickness between 95th percentile (95th–3.4 mm), and three cases with an increased NT of 3.5 mm or greater. Also, there was no statistical difference in the diagnosis of diagnostic variants in cases with or without a thickened nuchal fold (NF). Conclusions: The diagnostic yield of prenatal ES is low for fetuses with an isolated increased NT. In addition to Noonan syndrome, there are additional genetic syndromes such as Kabuki syndrome and Thanatophoric dysplasia type I that are potentially associated with an increased NT. A cut‐off of greater than the 95th percentile may be useful in case selection for ES. Whether it is clinically meaningful to monitor NF values for fetuses with isolated increased NT and normal chromosomes worth considering. [ABSTRACT FROM AUTHOR]

Introduction: Routine prenatal screening ultrasounds primarily serve to diagnose major fetal anomalies which may prompt further testing and inform clinical decision-making, including possible pregnancy termination. Meanwhile, expectant parents may view the ultrasound experience and information gained differently from their clinicians. In this setting, how to best counsel patients, especially regarding the increasing findings of indeterminant clinical significance, is unclear. Greater understanding of women's views before undergoing their ultrasound may help to guide anticipatory counseling about the purpose of screening and interpretation of results. Methods: We surveyed 289 patients presenting for scheduled prenatal ultrasounds at an academic tertiary care center. Discrete and open-ended questions assessed views surrounding the receipt of abnormal results and management of the pregnancy once fetal anomalies are detected. Qualitative responses were analyzed using thematic analysis. Results: Most (95%) desired information about abnormal sonographic findings, although only half would consider pregnancy termination for anomalies. Reasons for wanting return of abnormal results included preparedness, valuing knowledge, and to a lesser extent, informing decision-making. When considering potential termination as a result of ultrasound findings, participants' rationales demonstrated deontological (seeing termination as inherently impermissible or permissible), relational (duties arising from the role of being a mother), and consequentialist (weighing harms and benefits) reasoning. Conclusion: This study highlights women's perceptions of prenatal ultrasounds as an inherently valuable source of information and preparedness, beyond their role in informing clinical decision-making. Identifying the ethical constructs underpinning patients' perspectives may help direct development of counseling tools responsive to individual needs and values regarding prenatal ultrasound findings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Severe environmental pollution and contaminants left in the environment due to the abuse of chemicals, such as methylmercury, are associated with an increasing number of embryonic disorders. Ultrasound imaging has been widely used to investigate embryonic development malformation and dysorganoplasia in both research and clinics. However, this technique is limited by its low contrast and lacking functional parameters such as the ability to measure blood oxygen saturation (SaO2) and hemoglobin content (HbT) in tissues, measures that could be early vital indicators for embryonic development abnormality. Herein, we proposed combining two highly complementary techniques into a photoacoustic-ultrasound (PA-US) dual-modality imaging approach to noninvasively detect early mouse embryo abnormalities caused by methylmercury chloride (MMC) in real time. OBJECTIVES: This study aimed to assess the use of PA-US dual-modality imaging for noninvasive detection of embryonic toxicity at different stages of growth following prenatal MMC exposure. Additionally, we compared the PA-US imagining results to traditional histological methods to determine whether this noninvasive method could detect early developmental defects in utero. METHODS: Different dosages of MMC were administrated to pregnant mice by gavage to establish models of different levels of embryonic malformation. Ultrasound, photoacoustic signal intensity (PSI), blood oxygen saturation (SaO2), and hemoglobin content (HbT) were quantified in all experimental groups. Furthermore, the embryos were sectioned and examined for pathological changes. RESULTS: Using PA-US imaging, we detected differences in PSI, SaO2, HbT, and heart volume at embryonic day (E)14.5 and E11.5 for low and high dosages of MMC, respectively. More important, our results showed that differences between control and treated embryos identified by in utero PAUS imaging were consistent with those identified in ex vivo embryos using histological methods. CONCLUSION: Our results suggest that noninvasive dual-modality PA-US is a promising strategy for detecting developmental toxicology in the uterus. Overall, this study presents a new approach for detecting embryonic toxicities, which could be crucial in clinics when diagnosing aberrant embryonic development. [ABSTRACT FROM AUTHOR]

Objective: To examine the performance of a model combining maternal risk factors, uterine artery pulsatility index (UtA-PI) and estimated fetal weight (EFW) at 19-24 weeks' gestation, for predicting all antepartum stillbirths and those due to impaired placentation, in a training dataset used for development of the model and in a validation dataset.Methods: The data for this study were derived from prospective screening for adverse obstetric outcome in women with singleton pregnancy attending for routine pregnancy care at 19 + 0 to 24 + 6 weeks' gestation. The study population was divided into a training dataset used to develop prediction models for placental dysfunction-related antepartum stillbirth and a validation dataset to which the models were then applied. Multivariable logistic regression analysis was used to develop a model based on a combination of maternal risk factors, EFW Z-score and UtA-PI multiples of the normal median. We examined the predictive performance of the model by, first, the ability of the model to discriminate between the stillbirth and live-birth groups, using the area under the receiver-operating-characteristics curve (AUC) and the detection rate (DR) at a fixed false-positive rate (FPR) of 10%, and, second, calibration by measurements of calibration slope and intercept.Results: The study population of 131 514 pregnancies included 131 037 live births and 477 (0.36%) stillbirths. There are four main findings of this study. First, 92.5% (441/477) of stillbirths were antepartum and 7.5% (36/477) were intrapartum, and 59.2% (261/441) of antepartum stillbirths were observed in association with placental dysfunction and 40.8% (180/441) were unexplained or due to other causes. Second, placental dysfunction accounted for 80.1% (161/201) of antepartum stillbirths at < 32 weeks' gestation, 54.2% (52/96) at 32 + 0 to 36 + 6 weeks and 33.3% (48/144) at ≥ 37 weeks. Third, the risk of placental dysfunction-related antepartum stillbirth increased with increasing maternal weight and decreasing maternal height, was 3-fold higher in black than in white women, was 5.5-fold higher in parous women with previous stillbirth than in those with previous live birth, and was increased in smokers, in women with chronic hypertension and in parous women with a previous pregnancy complicated by pre-eclampsia and/or birth of a small-for-gestational-age baby. Fourth, in screening for placental dysfunction-related antepartum stillbirth by a combination of maternal risk factors, EFW and UtA-PI in the validation dataset, the DR at a 10% FPR was 62.3% (95% CI, 57.2-67.4%) and the AUC was 0.838 (95% CI, 0.799-0.878); these results were consistent with those in the dataset used for developing the algorithm and demonstrate high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 1.029 and the intercept was -0.009, demonstrating good agreement between the predicted risk and observed incidence of placental dysfunction-related antepartum stillbirth. The performance of screening was better for placental dysfunction-related antepartum stillbirth at < 37 weeks' gestation compared to at term (DR at a 10% FPR, 69.8% vs 29.2%).Conclusions: Screening at mid-gestation by a combination of maternal risk factors, EFW and UtA-PI can predict a high proportion of placental dysfunction-related stillbirths and, in particular, those that occur preterm. Such screening provides poor prediction of unexplained stillbirth or stillbirth due to other causes. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Birth defects are responsible for approximately 7% of neonatal deaths worldwide by World Health Organization in 2004. Many methods have been utilized for examining the congenital anomalies in fetuses. This study aims to investigate the efficiency of simultaneous CNV-seq and whole-exome sequencing (WES) in the diagnosis of fetal anomaly based on a large Chinese cohort.Methods: In this cohort study, 1800 pregnant women with singleton fetus in Hubei Province were recruited from 2018 to 2020 for prenatal ultrasonic screening. Those with fetal structural anomalies were transferred to the Maternal and Child Health Hospital of Hubei Province through a referral network in Hubei, China. After multidisciplinary consultation and decision on fetal outcome, products of conception (POC) samples were obtained. Simultaneous CNV-seq and WES was conducted to identify the fetal anomalies that can compress initial DNA and turnaround time of reports.Results: In total, 959 couples were finally eligible for the enrollment. A total of 227 trios were identified with a causative alteration (CNV or variant), among which 191 (84.14%) were de novo. Double diagnosis of pathogenic CNVs and variants have been identified in 10 fetuses. The diagnostic yield of multisystem anomalies was significantly higher than single system anomalies (32.28% vs. 22.36%, P  = 0.0183). The diagnostic rate of fetuses with consistent intra- and extra-uterine phenotypes (172/684) was significantly higher than the rate of these with inconsistent phenotypes (17/116, P  = 0.0130).Conclusions: Simultaneous CNV-seq and WES analysis contributed to fetal anomaly diagnosis and played a vital role in elucidating complex anomalies with compound causes. [ABSTRACT FROM AUTHOR]

Objective: To examine the potential value of maternal ophthalmic artery Doppler at 35-37 weeks' gestation in combination with the established biomarkers of pre-eclampsia (PE), including mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE.Methods: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at any time and at < 3 weeks after assessment by a combination of maternal demographic characteristics and medical history with biomarkers. The area under the receiver-operating-characteristics curve and detection rate (DR) of delivery with PE, at a 10% false-positive rate (FPR), in screening by combinations of maternal factors with ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio), MAP, UtA-PI, serum PlGF and serum sFlt-1 were determined. The modeled performance of screening for PE was also estimated.Results: The study population of 2287 pregnancies contained 60 (2.6%) that developed PE, including 19 (0.8%) that delivered with PE at < 3 weeks after assessment. The PSV ratio improved the prediction of PE with delivery at any stage after assessment provided by maternal factors alone (from 25.4% to 50.6%), maternal factors and MAP (54.3% to 62.7%), maternal factors, MAP and PlGF (68.3% to 70.8%) and maternal factors, MAP, PlGF and sFlt-1 (75.7% to 76.7%), at a FPR of 10%. The PSV ratio also improved the prediction of PE with delivery at < 3 weeks after assessment provided by maternal factors alone (from 31.0% to 69.4%), maternal factors and MAP (74.1% to 83.4%), maternal factors, MAP and UtA-PI (77.1% to 85.0%) and maternal factors, MAP and PlGF (84.8% to 88.6%). The empirical results for DR at a 10% FPR were consistent with the modeled results. Screening by a combination of maternal factors with MAP and PSV ratio also detected 59.4% (95% CI, 58.6-82.5%) of cases of gestational hypertension with delivery at any stage after assessment, and 86.7% (95% CI, 82.4-100%) of those with delivery at < 3 weeks after assessment.Conclusion: Ophthalmic artery Doppler could potentially improve the performance of screening for PE at 35-37 weeks, especially imminent PE with delivery within 3 weeks after assessment, but further studies are needed to validate this finding. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To investigate cerebral anomalies other than Chiari type 2 malformation in fetuses with myelomeningocele (MMC).Design: A retrospective cohort study in a single tertiary centre.Setting: A review of associated cerebral anomalies in cases with prenatal diagnosis of myelomeningocele.Population: Seventy cases of fetal myelomeningocele.Methods: Ultrasound and MRI images were blindly reviewed. Postnatal imaging and results of the postmortem results were also reviewed. The association between cerebral anomalies and the following ultrasound findings was measured: level of the defect, ventriculomegaly, microcephaly and fetal talipes.Main Outcome Measures: A microcephaly was observed in 32/70 cases (46%) and a ventriculomegaly was observed in 39/70 cases (56%). Other cerebral anomalies were diagnosed in 47/70 (67%).Results: Other cerebral anomalies were represented by 42/70 cases with abnormal CC (60%), 8/70 cases with perinodular heterotopia (PNH; 11%), 2/70 cases with abnormal gyration (3%). MRI performed only in fetal surgery cases confirmed the ulltrasound findings in all cases and provided additional findings in two cases (PNH). Risk ratios of fetal cerebral anomalies associated with MMC did not reach significance for microcephaly, ventriculomegaly, talipes or the level of the defect There was an overall good correlation between pre- and postnatal findings with a Kappa value of 0.79 [95% CI 0.57-1] and 82% agreement.Conclusion: Fetal brain anomalies other than Chiari type 2 malformation are frequently observed in fetuses with myelomeningocele, predominantly represented by CC anomalies. Whether these associated cerebral anomalies have an impact on selecting cases eligible for fetal surgery needs further evaluation.Tweetable Abstract: Fetal cerebral anomalies other than Chiari type 2 malformation, microcephaly, and ventriculomegaly may be associated with MMC in up to 67% of the cases. [ABSTRACT FROM AUTHOR]

Aims: Excessive placental invasion is a life-threatening obstetric disease. Determining the extent of placental villi invasion prenatally is crucial for formulating a surgical plan for pregnant women. The objective of this study was to explore the diagnostic accuracy of the Crystal Vue technique combined with two-dimensional (2D) ultrasound in detecting the degree of placenta accreta spectrum (PAS) located in the C-section scar area.Materials and Methods: Twenty-seven pregnant women with a strong suspicion of PAS underwent 2D ultrasound combined with a Crystal Vue examination. The diagnosis of 2D ultrasound alone and Crystal Vue combined with 2D ultrasound was statistically calculated, respectively. Cohen's kappa (k) was used to measure the consistency between these two ultrasound diagnosis and the postoperative diagnosis.Results: The postoperative diagnosis of 27 pregnant women was as follows: 6 cases of placental accreta, 11 cases of placental increta, 2 cases of placental percreta, 2 cases of placental accrete and placental increta, 2 cases of placental accreta and placental percreta, and 4 cases without PAS. Compared with the postoperative diagnosis, 20 cases (74.07%) were correctly diagnosed by 2D ultrasound alone, 6 cases were misdiagnosed, and one case the diagnosis was incomplete, which were substantially consistent with the postoperative diagnosis (k=0.612, p<0.01). Twenty-six cases (96.30%) were correctly diagnosed by Crystal Vue combined with 2D ultrasound; only one case was incomplete diagnosed which was  almost perfectly consistent with the postoperative diagnosis (k=0.934, p<0.01).Conclusions: Combining the Crystal Vue technique with 2D ultrasound can improve the diagnostic accuracy of ultrasound for detecting all types of PAS located in C-section scar area. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS).Methods: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial.Results: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher).Conclusions: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Applying whole-exome sequencing (WES) for the diagnosis of diseases in children has shown significant diagnostic strength compared with chromosomal microarray. WES may also have the potential of adding clinically relevant prenatal information in cases where a fetus is found to have structural anomalies. We present results from the first fetal exomes performed in a tertiary center in Denmark.Material and Methods: Couples/expectant parents were included in Central Denmark Region from July 2016 to March 2019. Inclusion was not systematic, but where one or more fetal malformations or severe fetal hydrops were detected, and a specific diagnosis had not been obtained by chromosomal microarray. WES was performed in ongoing pregnancies (N = 11), after intrauterine demise (N = 5), or after termination of pregnancy based on ultrasound findings (N = 19). In most cases, a trio format was applied comprising fetal and parental DNA.Results: WES was performed in 35 highly selected fetal cases. Pathogenic variants, or variants likely to explain the phenotype, were detected in 9/35 (26%). Variants of uncertain significance were detected in 7/35 (20%) and there was one secondary finding (3%). Out of the 11 ongoing pregnancies, four reached a genetic diagnosis (36%). Detection rate was highest in cases of multisystem anomalies (7/13, 54%). WES was completed in all three trimesters and both autosomal dominant, autosomal recessive and X-linked inheritance were revealed.Conclusions: We present data from 35 cases of exome sequencing applied in a setting of fetal malformations. Importantly, though, we wish to share our personal experiences with implementing WES into a prenatal setting. As a medical society, we must continue to share what we do not understand, what went wrong, what is difficult, and what we do not agree upon. A common understanding and language are warranted. We also advocate that more research is needed concerning the clinical value, as well as costs and patient perspectives, of using WES in pregnancy. We believe that WES will lead to improved prenatal and perinatal care. [ABSTRACT FROM AUTHOR]

Introduction: Currently fetal nuchal translucency (NT) ≥3.5 mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with an NT 3.0-3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non-invasive prenatal test (NIPT) results.Material and Methods: A retrospective study and meta-analysis of literature cases with NT between 3.0 and 3.4 mm and 2 cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0 and 3.4 mm) tested in the period July 2012 to June 2019 and Central Denmark region (with a risk >1:300 and NT between 3.0 and 3.4 mm) tested between September 2015 and December 2018.Results: A total of 522 fetuses were referred for invasive testing and chromosomal microarray. Meta-analysis indicated that in 1:7.4 (13.5% [95% CI 8.2%-21.5%]) fetuses a chromosomal aberration was diagnosed. Of these aberrant cases, 47/68 (69%) involved trisomy 21, 18, and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and is highest if NIPT was performed only for common trisomies-1:21 (4.8% [95% CI 3.2%-7.3%]). However, it may be substantially lowered if a genome-wide 10-Mb resolution NIPT test was offered (~1:464).Conclusions: Based on these data, we suggest that the NT cut-off for invasive testing could be 3.0 mm (instead of 3.5 mm) because of the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay because all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of 1:21 to 1:464 for chromosome aberrations other than common trisomies, dependent on the NIPT approach, should be raised. If a pregnant woman declines invasive testing, but still wants a test with a broader coverage of clinically significant conditions then the genome-wide >10-Mb resolution NIPT test, which detects most aberrations, could be proposed. [ABSTRACT FROM AUTHOR]

Introduction: A common concern regarding the introduction of chromosomal microarray in prenatal testing is the concomitant identification of an uncertain copy number variant (CNV) where significance and clinical implication for the unborn child can be difficult or impossible to predict. Following the identification of an uncertain CNV, prospective parents may decide to continue the pregnancy. The aim of this study was to explore how prospective parents manage uncertainty and experience pregnancy in light of an uncertain CNV result.Material and Methods: Qualitative interviews with 16 women and 10 partners who had received a prenatally diagnosed, uncertain CNV. Participants were recruited from the Aarhus University Hospital, Denmark and most were interviewed in their homes 1-14 weeks after birth. Data were analyzed using thematic analysis.Results: Following the CNV diagnosis, some couples focused on the severe syndromes ruled out by the result, whereas others were more concerned with the new potential risks, for example, learning disabilities. Most couples did not remember the actual diagnosis, but all described a number of attention points generated by the CNV result. During pregnancy, the couples used various strategies to limit worry and enjoy their pregnancy, such as limiting information seeking, reducing talk of the CNV, and deferring thoughts of potential consequences. Furthermore, ultrasound was considered a valuable resource for reducing worry as it provided reassurance about the development of the baby. Inherited CNVs caused relief on one hand, but also feelings of responsibility for the child's potential challenges. After birth, worry decreased considerably, but all couples paid some extra attention to the child's development, while also being alert to the risk of wrongfully interpreting the child's development in terms of the CNV. Eleven couples expressed satisfaction with knowing about the child's CNV, whereas five couples would rather not have known.Conclusions: The results indicate that health professionals should be mindful of terminology, remember to point out what has been ruled out by the CNV result, and discuss potential coping strategies with the couple. Furthermore, these couples may have a higher need for ultrasound during pregnancy to help reduce worry. More research is needed on the families' long-term coping. [ABSTRACT FROM AUTHOR]

Objectives: To examine the performance of the routine 11-13-week scan in detecting fetal defects in twin pregnancies and to examine if, in pregnancies with a fetal defect, compared to those with normal fetuses, there is increased incidence of nuchal translucency thickness (NT) ≥ 95th and ≥ 99th percentiles or intertwin discordance in crown-rump length (CRL) ≥ 10% and ≥ 15%.Methods: This was a retrospective analysis of prospectively collected data in twin pregnancies undergoing routine ultrasound examination for fetal anatomy, according to standardized protocols, at 11-13 weeks' gestation between 2002 and 2019. Pregnancies with known chromosomal abnormality were excluded. The final diagnosis of fetal defect was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal defects was determined.Results: The study population of 6366 twin pregnancies with two live fetuses at 11-13 weeks' gestation included 4979 (78.2%) dichorionic (DC) and 1387 (21.8%) monochorionic (MC) twin pregnancies. The main findings were: first, the overall incidence of fetal defects was higher in MC than in DC twins (2.8% vs 1.3%); second, the proportion of defects diagnosed in the first trimester was higher in MC than in DC twins (52.6% vs 27.1%); third, the pattern of defects in relation to detectability at the 11-13-week scan (always detectable, sometimes detectable and never detectable) was similar to that reported previously in singleton pregnancies; fourth, always-detectable defects included acrania, alobar holoprosencephaly, encephalocele, pentalogy of Cantrell, exomphalos, body-stalk anomaly, twin reversed arterial perfusion sequence and conjoined twins; fifth, the incidence of fetal NT ≥ 95th percentile was higher in those with than in those without a defect (16.5% vs 4.5% in DC twins and 19.2% vs 5.9% in MC twins) and this was also true for NT ≥ 99th percentile (8.3% vs 1.0% in DC twins and 15.4% vs 2.0% in MC twins); and sixth, the incidence of CRL discordance ≥ 10% was higher in those with than in those without a defect (20.2% vs 7.9% in DC twins and 33.8% vs 9.3% in MC twins) and this was also true for CRL discordance ≥ 15% (10.1% vs 1.9% in DC twins and 28.2% vs 2.8% in MC twins).Conclusions: First, fetal defects are more common in MC than in DC twin pregnancies. Second, first-trimester detection of fetal defects in DC twin pregnancies is similar to that in singleton pregnancies. Third, first-trimester detectability of defects in MC twins is higher than in DC twins. Fourth, in twin pregnancies with a fetal defect, there is higher intertwin discordance in CRL and incidence of increased NT, but the predictive performance of screening by these markers is poor. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to explore the utility of rapid medical trio exome sequencing (ES) for prenatal diagnosis using the skeletal dysplasia as an exemplar.Method: Pregnant women who were referred for genetic testing because of ultrasound detection of fetal abnormalities suggestive of a skeletal dysplasia were identified prospectively. Fetal samples (amniocytes or cord blood), along with parental blood, were send for rapid copy number variations testing and medical trio ES in parallel.Results: Definitive molecular diagnosis was made in 24/27 (88.9%) cases. Chromosomal abnormality (partial trisomy 18) was detected in one case. Sequencing results had explained the prenatal phenotype enabling definitive diagnoses to be made in 23 cases. There were 16 de novo dominant pathogenic variants, four dominant pathogenic variants inherited maternally or paternally, two recessive conditions with pathogenic variants inherited from unaffected parents, and one X-linked condition. The turnaround time from receipt of samples in the laboratory to reporting sequencing results was within 2 weeks.Conclusion: Medical trio ES can yield very timely and high diagnostic rates in fetuses presenting with suspected skeletal dysplasia. These definite diagnoses aided parental counseling and decision making in most of cases. [ABSTRACT FROM AUTHOR]

Objectives: To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy.Methods: This was a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling.Results: First, in pregnancies with a vanishing twin, median free β-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling.Conclusions: First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To develop enhanced prediction models to update the QUiPP App prototype, a tool providing individualized risk of spontaneous preterm birth (sPTB), for use in women with symptoms of threatened preterm labor (TPTL), incorporating risk factors, transvaginal ultrasound assessment of cervical length (CL) and cervicovaginal fluid quantitative fetal fibronectin (qfFN) test results.Methods: Participants were pregnant women between 23 + 0 and 34 + 6 weeks' gestation with symptoms of TPTL, recruited as part of four prospective cohort studies carried out at 16 UK hospitals between October 2010 and October 2017. The training set comprised all women whose outcomes were known in May 2017 (n = 1032). The validation set comprised women whose outcomes were gathered between June 2017 and March 2018 (n = 506). Parametric survival models were developed for three combinations of predictors: risk factors plus qfFN test results alone, risk factors plus CL alone, and risk factors plus both qfFN and CL. The best models were selected using the Akaike and Bayesian information criteria. The estimated probability of sPTB < 30, < 34 or < 37 weeks' gestation and within 1 or 2 weeks of testing was calculated and receiver-operating-characteristics (ROC) curves were created to demonstrate the diagnostic ability of the prediction models.Results: Predictive statistics were similar between the training and the validation sets at most outcome time points and for each combination of predictors. Areas under the ROC curves (AUC) demonstrated that all three algorithms had good accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1 and 2 weeks' post-testing in the validation set, particularly the model combining risk factors plus qfFN alone (AUC: 0.96 at < 30 weeks; 0.85 at < 34 weeks; 0.77 at < 37 weeks; 0.91 at < 1 week from testing; and 0.92 at < 2 weeks from testing).Conclusions: Validation of the new prediction models suggests that the QUiPP App v.2 can reliably calculate risk of sPTB in women with TPTL. Use of the QUiPP App in practice could lead to better targeting of intervention, while providing reassurance and avoiding unnecessary intervention in women at low risk. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Accurate mid-pregnancy prediction of spontaneous preterm birth (sPTB) is essential to ensure appropriate surveillance of high-risk women. Advancing the QUiPP App prototype, QUiPP App v.2 aimed to provide individualized risk of delivery based on cervical length (CL), quantitative fetal fibronectin (qfFN) or both tests combined, taking into account further risk factors, such as multiple pregnancy. Here we report development of the QUiPP App v.2 predictive models for use in asymptomatic high-risk women, and validation using a distinct dataset in order to confirm the accuracy and transportability of the QUiPP App, overall and within specific clinically relevant time frames.Methods: This was a prospective secondary analysis of data of asymptomatic women at high risk of sPTB recruited in 13 UK preterm birth clinics. Women were offered longitudinal qfFN testing every 2-4 weeks and/or transvaginal ultrasound CL measurement between 18 + 0 and 36 + 6 weeks' gestation. A total of 1803 women (3878 visits) were included in the training set and 904 women (1400 visits) in the validation set. Prediction models were created based on the training set for use in three groups: patients with risk factors for sPTB and CL measurement alone, with risk factors for sPTB and qfFN measurement alone, and those with risk factors for sPTB and both CL and qfFN measurements. Survival analysis was used to identify the significant predictors of sPTB, and parametric structures for survival models were compared and the best selected. The estimated overall probability of delivery before six clinically important time points (< 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks after testing) was calculated for each woman and analyzed as a predictive test for the actual occurrence of each event. This allowed receiver-operating-characteristics curves to be plotted, and areas under the curve (AUC) to be calculated. Calibration was performed to measure the agreement between expected and observed outcomes.Results: All three algorithms demonstrated high accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks of testing, with AUCs between 0.75 and 0.90 for the use of qfFN and CL combined, between 0.68 and 0.90 for qfFN alone, and between 0.71 and 0.87 for CL alone. The differences between the three algorithms were not statistically significant. Calibration confirmed no significant differences between expected and observed rates of sPTB within 4 weeks and a slight overestimation of risk with the use of CL measurement between 22 + 0 and 25 + 6 weeks' gestation.Conclusions: The QUiPP App v.2 is a highly accurate prediction tool for sPTB that is based on a unique combination of biomarkers, symptoms and statistical algorithms. It can be used reliably in the context of communicating to patients the risk of sPTB. Whilst further work is required to determine its role in identifying women requiring prophylactic interventions, it is a reliable and convenient screening tool for planning follow-up or hospitalization for high-risk women. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Preterm birth is a major cause of neonatal morbidity and mortality. There is an urgent need to accurately predict imminent delivery to enable necessary interventions such as tocolytic, glucocorticoid, and magnesium sulfate administration. We aimed to evaluate placental α-macroglobulin-1 as a new diagnostic marker in the prediction of preterm birth.Material and Methods: We performed a prospective observational trial in women with intact membranes between 24+0 and 36+6 weeks of gestation. We included both women with and without threatened preterm labor symptoms. We evaluated the test performance of placental α-macroglobulin-1 measurements in cervicovaginal fluid regarding three different presentation-to-delivery intervals: ≤2, ≤7, ≤14 days. In addition, we calculated placental α-macroglobulin-1 performance in combination with other prognostic factors such as ultrasonographic cervical length measurements.Results: We included 126 women in the study. We detected high specificity (97%-98%) and negative predictive value (89%-97%) for placental α-macroglobulin-1 at all time intervals. We assessed placental α-macroglobulin-1 in combination with cervical length measurements (≤15 mm) in the sub-group of women presenting with threatened preterm labor symptoms (n = 63) and detected high positive predictive values (100%) for 7- and 14-day presentation-to-delivery intervals.Conclusions: Our study provides evidence that placental α-macroglobulin-1 testing in cervicovaginal fluid, in combination with cervical length measurements, accurately predicts preterm birth in women with preterm labor symptoms. This novel test combination may be used clinically to triage women presenting with threatened preterm labor, avoiding overtreatment and unnecessary hospitalizations. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential value of routine ultrasound examination at 35-37 weeks' gestation in the diagnosis of previously unknown fetal abnormalities.Methods: This was a prospective study of 52 400 singleton pregnancies attending for a routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation; all pregnancies had a previous scan at 18-24 weeks and 47 214 also had a scan at 11-13 weeks. We included pregnancies resulting in live birth or stillbirth but excluded those with known chromosomal abnormality. Abnormalities were classified according to the affected major organ system, and the type and incidence of new abnormalities were determined.Results: In the study population, the incidence of fetal abnormality was 1.9% (995/52 400), including 674 (67.7%) that had been diagnosed previously during the first and/or second trimester, 247 (24.8%) that were detected for the first time at 35-37 weeks and 74 (7.4%) that were detected for the first time postnatally. The most common abnormalities that were diagnosed during the first and/or second trimester and that were also observed at 35-37 weeks included ventricular septal defect, talipes, unilateral renal agenesis and/or pelvic kidney, hydronephrosis, duplex kidney, unilateral multicystic kidney, congenital pulmonary airway malformation, ventriculomegaly, cleft lip and palate, polydactyly and abdominal cyst or gastroschisis. The most common abnormalities first seen at 35-37 weeks were hydronephrosis, mild ventriculomegaly, ventricular septal defect, duplex kidney, ovarian cyst and arachnoid cyst. The incidence of abnormalities first seen at 35-37 weeks was 0.5% and those that were detected exclusively for the first time at this examination were ovarian cyst, microcephaly, achondroplasia, dacryocystocele and hematocolpos. The incidence of abnormalities first seen postnatally was 0.1% and the most common were isolated cleft palate, polydactyly or syndactyly and ambiguous genitalia or hypospadias; prenatal examination of the genitalia was not a compulsory part of the protocol.Conclusions: A high proportion of fetal abnormalities are detected for the first time during a routine ultrasound examination at 35-37 weeks' gestation. Such diagnosis and subsequent management, including selection of timing and place for delivery and postnatal investigations, could potentially improve postnatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Aim: To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS).Materials and Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: To assess trends in ultrasound-indicated prenatal diagnostic testing performed over the past two decades in the Australian state of Victoria, in the context of rapidly changing practices in aneuploidy screening and chromosome analysis.Methods: This was a retrospective analysis of all ultrasound-indicated prenatal diagnostic testing (amniocentesis and chorionic villus sampling) performed in the state of Victoria between 1994 and 2016. Ultrasound indications for testing included: fetal structural abnormality, fetal death, fetal growth restriction, abnormal amniotic fluid volume, genetic 'soft marker' and unspecified ultrasound abnormality. Maternal age, indication for testing, type of diagnostic procedure, gestational age, type of chromosome analysis (G-banded karyotyping or chromosomal microarray (CMA)) and test results were obtained. Diagnostic yield (i.e. percentage of tests yielding a major abnormality) was analyzed by year, maternal age and gestational age. Statistical analysis was performed using the χ2 tests for trend or difference in proportions, as appropriate.Results: During the 23-year study period, 1 533 317 births were recorded and 16 152 diagnostic procedures were performed for the primary indication of ultrasound abnormality. In recent years, ultrasound abnormality became the most common indication for prenatal invasive testing (29.4% of diagnostic tests between 2013 and 2016) due to a steep decline in testing for other indications such as positive result on combined first-trimester screening or advanced maternal age alone. In 2016, over 95% of ultrasound-indicated procedures were performed with CMA; among these, pathogenic copy number variant (CNV) was the most common (3.5%) abnormality detected, followed by trisomy 21 (2.8%). The diagnostic yield of ultrasound-indicated tests performed < 16 weeks was significantly higher than that of tests performed after 20 weeks (31.5% vs 9.0%).Conclusions: Ultrasound-indicated invasive testing is contributing to prenatal diagnosis in new ways in the genomic era. A pathogenic CNV is now the most likely diagnosis after ultrasound-indicated testing, rather than trisomy 21 or other whole-chromosome aneuploidy. Despite steady improvements in first-trimester screening for aneuploidy, the diagnostic yield of ultrasound-indicated tests > 20 weeks has remained stable due to increased utilization of CMA. Procedures performed for structural abnormalities < 16 weeks continue to have the highest diagnostic yield, supporting the benefits of early fetal structural assessment at 11-13 weeks. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To define current obstetric opinion and clinical practice regarding the prenatal diagnosis of vasa previa in Australia and New Zealand.Methods: A population-based cross-sectional survey of Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted from April to May, 2016. Descriptive analysis was used to define factors influencing opinion and practice regarding definition of vasa previa, attributable risk factors, and the value of screening.Results: Overall, 453 respondents were included in the study. Two-thirds (304/453; 67.1%) defined vasa previa as exposed fetal vessel(s) running over or within 2 cm of the internal os. A higher proportion of ultrasound specialists (30/65; 46.2%) preferred a broader definition as compared with generalists (115/388; 29.6%; P<0.001). Overall, Fellows were supportive (342/430; 79.5%) of both reporting ultrasound-based risk factors at the 20-week anomaly scan and targeted screening (298/430; 69.3%). Only 77/453 (17.0%) respondents recognized all five "known" risk factors for vasa previa.Conclusions: There was a lack of consensus regarding the definition and diagnosis process for vasa previa. There was also a knowledge gap in risk factors for vasa previa that would inform a targeted screening policy. Nevertheless, support for targeted screening was strong from obstetricians who responded. [ABSTRACT FROM AUTHOR]

Objective: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13, contingent on the results of the first-trimester combined test in twin pregnancy.Methods: Screening for trisomies 21, 18 and 13 was carried out in 959 twin pregnancies by assessment of a combination of maternal age, fetal nuchal translucency thickness, and serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-13 weeks' gestation in two UK NHS hospitals. Women in the high-risk group (risk ≥ 1 in 100) were offered the option of invasive testing, cfDNA testing or no further testing, and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates.Results: In 42 (4.4%) of the 959 pregnancies, there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow-up. The 917 pregnancies with known trisomic status of both twins included six that were discordant for trisomy 21, four that were discordant for trisomy 18 and 907 with no trisomy 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.1%) and 667 (72.7%) of the pregnancies were classified as high risk, intermediate risk and low risk, respectively. The high-risk group included five (83.3%) cases of trisomy 21 and three (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included six pregnancies with trisomy 21, three with trisomy 18 and 206 with no trisomy 21, 18 or 13. The cfDNA test classified correctly as screen positive all six cases of trisomy 21 and two of the three with trisomy 18, and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening led to prenatal detection of all cases of trisomy 21 and three of four with trisomy 18.Conclusion: This study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To assess the performance of non-invasive prenatal testing (NIPT) for achondroplasia using high-resolution melting (HRM) analysis, and to propose an optimal diagnostic strategy combining ultrasound examination and cell-free fetal DNA (cffDNA) analysis.Methods: In this prospective multicenter study, cffDNA was extracted from blood of pregnant women at risk for fetal achondroplasia (owing to paternal achondroplasia, previous affected child or suspected rhizomelic shortening) and of pregnant low-risk controls. The presence of either one of the two main fibroblast growth factor receptor 3 gene (FGFR3) mutations was determined using HRM combined with confirmation by SNaPshot minisequencing. Results were compared with phenotypes obtained using three-dimensional computed tomography or postnatal examination, and/or molecular diagnosis by an invasive procedure. Fetal biometry (head circumference and femur length) was analyzed in order to develop a strategy in which cffDNA analysis for diagnosis of achondroplasia is offered only in selected cases.Results: Eighty-six blood samples from women at risk for fetal achondroplasia and 65 from controls were collected. The overall sensitivity and specificity of NIPT were 1.00 (95% CI, 0.87-1.00) and 1.00 (95% CI, 0.96-1.00), respectively. Critical reduction in femur length of affected fetuses could be observed from 26 weeks' gestation.Conclusions: HRM combined with SNaPshot minisequencing is a reliable method for NIPT for achondroplasia. Its implementation in routine clinical care combined with ultrasonography is an efficient strategy for the non-invasive diagnosis of achondroplasia. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background Fetal megacystis is a sonographic feature that may be indicative of several underlying pathologies. Despite advances in diagnosis and management, the overall prognosis of affected fetuses remains poor and about 50% of such pregnancies are terminated. Aims To define the frequency, management, survival and renal outcomes of fetal megacystis over nine years at Wellington Hospital, New Zealand. Materials and Methods A nine-year retrospective review of fetuses with an antenatal diagnosis of megacystis was undertaken. Results Sixteen cases were identified (nine live births, five terminations and two perinatal deaths). This gives an observed frequency of one per 940 fetuses scanned. Two-thirds of the live births have survived and been followed for a mean of 5.3 years. None have required renal dialysis or transplantation to date. Conclusions The current series contributes to our knowledge of fetal megacystis and helps to inform antenatal counselling. Improved prognostic criteria are urgently required to accurately differentiate between fetuses with favourable versus poor outcomes. [ABSTRACT FROM AUTHOR]

Background: A paucity of evidence regarding the natural history of congenital pulmonary airway malformations (CPAMs) and pulmonary sequestration (PS) has resulted in a divergence in management strategy of asymptomatic cases.Methods: We describe the long-term clinical course of 119 children diagnosed with these lesions treated at Great Ormond Street Hospital (GOSH). Cases were identified via the GOSH patient database. Study entry required the identification of a cystic lung lesion on prenatal ultrasound and confirmation of CPAM/PS on postnatal CT imaging. Patients followed up for at least 5 years were included.Results: 51 (43%) patients were managed surgically; 8 (6.7%) as an emergency during the neonatal period, 6 (5.1%) electively due to concerning features on CT scan, 20 (17%) following medical advice, 1 (0.8%) following a severe respiratory infection and in 5 (4.2%) the indication was unclear. The indication in 11 (9.2%) was recurrent respiratory infection and median age at surgery was 1.6 years (range 0.4 to 4.6 years). No cases of malignancy were identified on histological examination of resected lesions. 68 (57%) patients were managed conservatively for a median period of 9.9 years (range 5.2 years to 18 years). Seven (10%) were discharged, one was followed-up elsewhere (1.5%) and eight (11%) were lost to follow-up. In four patients (5.9%), the lesion resolved spontaneously. 52 (76%) continue to be followed-up and remain asymptomatic.Conclusions: This is one of the largest case series documenting the natural history of CPAMs and PS following a prenatal diagnosis and demonstrates that conservative management is a reasonable option in selected cases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart in generating standard fetal echocardiography views.Methods: In this prospective cohort study of patients with normal fetal hearts (19-30 gestational weeks), one or more STIC volume datasets were obtained of the apical four-chamber view. Each STIC volume successfully obtained was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates for standard fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated.Results: One or more STIC volumes (total n = 463) were obtained from 246 patients. A single STIC volume per patient was analyzed using the FINE method. In normal cases, FINE was able to generate nine fetal echocardiography views using: (1) diagnostic planes in 76-100% of the cases, (2) VIS-Assistance® in 96-100% of the cases, and (3) a combination of diagnostic planes and/or VIS-Assistance® in 96-100% of the cases.Conclusion: FINE applied to STIC volumes can successfully generate nine standard fetal echocardiography views in 96-100% of cases in the 2nd and 3rd trimesters. This suggests that the technology can be used as a method of screening for congenital heart disease. [ABSTRACT FROM AUTHOR]

Background: Congenital pulmonary airway malformation (CPAM) is an increasingly recognized disease with potential mortality. Owing to limited published studies, the true incidence is yet to be determined. We carried out this prospective study with the aim to estimate its true incidence on a population basis.Methods: An antenatal ultrasonography program was implemented since 2009. Fetuses with suspected intra-thoracic lesions were monitored by regular follow-ups. Antenatal course, postnatal outcomes, and other demographics were compared to those of patients with CPAM in the previous decades (1989-2008). The incidence of CPAM was calculated in different periods.Results: 66 CPAM patients were identified between 2009 and 2014 with 62 patients being detected by antenatal scan. In contrast, 45 patients were identified between 1989 and 2008 with 27 patients being detected antenatally. The incidence rate during the past and recent period was estimated as ~1 in 27,400 and ~1 in 7200 live births, respectively (p = 0.024).Conclusion: With increasing awareness of clinicians and the universal use of latest ultrasound technology, it is likely that more CPAM cases will be detected in the future. Here, we presented our best estimated incidence rate of CPAM, yet only a larger scale study can reveal its true incidence. [ABSTRACT FROM AUTHOR]

Background: Maternal and neonatal mortality figures remain unacceptably high worldwide and new approaches are required to address this problem. This paper evaluates the impact on maternal and neonatal mortality of a pregnancy care package for rural areas of developing countries with portable ultrasound and blood/urine tests. Methods: An observational study was conducted, with intervention and control groups not randomly assigned. Setting: Rural areas of the districts of Senahu, Campur and Carcha, in Alta Verapaz Department (Guatemala). The control group is composed by 747 pregnant women attended by the community facilitator, which is the common practice in rural Guatemala. The intervention group is composed by 762 pregnant women attended under the innovative Healthy Pregnancy project. That project strengthens the local prenatal care program, providing local nurses training, portable ultrasound equipment and blood and urine tests. The information of each pregnancy is registered in a medical exchange tool, and is later reviewed by a gynecology specialist to ensure a correct diagnosis and improve nurses training. Results: No maternal deaths were reported within the intervention group, versus five cases in the control group. Regarding neonatal deaths, official data revealed a 64 % reduction for neonatal mortality. A 37 % prevalence of anemia was detected. Non-urgent referral was recommended to 70 pregnancies, being fetal malpresentation the main reported cause. Conclusion: Impact data on maternal mortality (reduction to zero) and neonatal mortality (NMR was reduced to 36 %) are encouraging, although we are aware of the limitations of the study related to possible biasing and the small sample size. The major reduction of maternal and neonatal mortality provides promising prospects for these low-cost diagnostic procedures, which allow to provide high quality prenatal care in isolated rural communities of developing countries. [ABSTRACT FROM AUTHOR]

The aim of this article was to explore whether expectant parents' attitudes to termination or continuation of pregnancy, both in general and in case of fetal abnormality, are affected by previous experiences of miscarriage and whether attitudes change after ultrasound screening with normal findings. It was also of interest to investigate differences in attitudes in relation to age, parity and gender. A prospective one-year cohort study was carried out. Questionnaires were administered before and after the ultrasound examination. Analyses included 1258 women and 925 men. A comparison between the results pre- and post-ultrasound showed that after the ultrasound examination, there were significant changes towards a more positive attitude to give birth to a baby with an abnormality. Men were significantly more willing to terminate for a fetal abnormality and significantly less hesitant towards abortion in general than women. Women aged 35 years or older were significantly less willing to give birth to a baby with an abnormality and significantly more positive to termination for fetal abnormality than younger women. Parents showed understanding attitudes towards other parents' decisions no matter what these were. We conclude that parents need individualized information and support in connection with prenatal diagnosis, due to parental hesitancy. Midwives play an important role in this. [ABSTRACT FROM AUTHOR]

Objective: To identify whether preterm surveillance clinics (PSCs) risk-stratify high-risk women accurately by comparing outcomes of those admitted to hospital on the basis of asymptomatic testing with those not admitted.Methods: We performed a subanalysis from a larger prospective cohort study on sonographic cervical length, quantitative fetal fibronectin (qfFN) and risk of spontaneous preterm birth. We identified 1130 asymptomatic singleton pregnancies at high risk of preterm birth, screened between 23 and 28 weeks of gestation at a PSC in a tertiary hospital in London, UK. Gestational age at delivery, the proportion of preterm births that delivered < 30 weeks and neonatal outcomes were compared between women admitted electively when asymptomatic as a consequence of screening-test results and those who were not routinely admitted.Results: In total, 66 (6%) women attending the PSC were admitted to hospital following asymptomatic screening (inpatient group). The mean gestational age at delivery for those not admitted electively (outpatient group) was at term and was significantly higher than that of those admitted from PSC (38.4 vs 31.2 weeks; P < 0.0001). Preterm birth < 30 weeks' gestation was rare in the outpatient group relative to those admitted (1.32% vs 36.4%; P < 0.0001). Neonatal mortality was 0.188% in the outpatient group compared with 4.55% in those admitted electively (P < 0.0001). The incidence of other complications such as neonatal death, 5-min Apgar score < 7, special care baby unit/neonatal intensive care unit admission, respiratory distress syndrome, intraventricular hemorrhage and low birth weight were significantly lower in those managed as outpatients than in those admitted electively.Conclusion: PSCs measuring cervical length and qfFN accurately triage asymptomatic high-risk pregnant women, enabling those at highest risk of adverse outcome to be identified for elective admission to hospital and appropriate management. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart.Methods: In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated.Results: One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance.Conclusions: In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of fetal growth and cerebrovascular resistance at different periods in gestation with neurodevelopment (ND) at 14 months in the univentricular subject.Methods: We reviewed serial prenatal ultrasound (US) examinations from 133 infants enrolled in the Pediatric Heart Network's Single Ventricle Reconstruction or Infants with Single Ventricle trials, including a subset of 82 infants in whom ND was assessed at 14 months using mental (MDI) and psychomotor (PDI) developmental indices. US examinations were assigned to one of four gestational time periods: (1) 20-23 weeks, (2) 24-29 weeks, (3) 30-33 weeks and (4) ≥ 34 weeks. Middle cerebral artery (MCA) flow velocity was measured and pulsatility index (PI), a measure of downstream resistance, was calculated. Data on fetal head circumference (HC), femur length, abdominal circumference (AC) and estimated fetal weight (EFW) were collected and their Z-scores were calculated. We evaluated the rate of change of these parameters over time within individuals, tested correlations between fetal growth and ND and assessed predictors of ND using linear regression.Results: The mean prenatal HC Z-score was < 0 at each gestational-age period and became more negative later in pregnancy. There was less growth in HC from time period 3 to period 4 compared with from period 2 to 3 (Δ HC Z-score, -0.07 ± 0.1 vs 0.11 ± 0.22, P = 0.03). Though ND did not correlate with HC, HC Z-score or MCA-PI Z-score, HC growth from period 2 to period 3 correlated with MDI (r = 0.45, P = 0.047). AC Z-score in period 4 predicted MDI (β = 4.02, P = 0.04). EFW Z-score and AC Z-score in period 2 predicted PDI (β = 10.6, P = 0.04 and β = 3.29, P = 0.047, respectively). Lower MCA-PI at initial US predicted higher PDI (β = -14.7, P = 0.03).Conclusion: In univentricular fetuses, lower cerebrovascular resistance may be protective for ND. Decreased fetal somatic growth may predict developmental abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background Fetal interrupted aortic arch (IAA) is a rare cardiac anomaly and its prenatal diagnosis is challenging. The purpose of our report is to evaluate the use of two-dimensional echocardiography (2 DE) and 4D echocardiography with B-flow imaging and spatiotemporal image correlation (4D BF- STIC) in detecting IAA type A ( IAA-A). Materials & Methods Twenty-three cases of confirmed IAA-A identified by fetal echocardiography were involved in the study. The fetal echocardiography image data were reviewed to analyze the ratio of right ventricle to left ventricle ( RV/ LV) diameter, the ratio of main pulmonary artery to ascending aorta ( MPA/ AAO) diameter, and the correlation of RV/ LV diameter ratio and size of ventricular septal defect ( VSD). 4D BF- STIC was performed in 21 fetuses using the sagittal view (4D BF- STIC-sagittal) and the four-chamber view (4D BF- STIC-4 CV) as initial planes of view. An additional 183 normal fetuses were also included in our study. RV/ LV and MPA/ AAO ratios were calculated and compared with that of IAA-A fetuses. Fetal 2 DE, 4D BF- STIC-sagittal, and 4D BF- STIC-4 CV were used to visualize the aortic arch and its associated neck vessels. Six subgroups were evaluated according to gestational age. Results Fetal 2 DE, 4D BF- STIC-sagittal, and 4D BF- STIC-4 CV made the correct prenatal diagnosis of IAA-A in 19/23 (82.6%), 14/21 (66.7%), and 19/21 (90.5%) of patients, respectively. A significantly enlarged MPA combined with symmetric ventricles was found in the IAA-A fetuses, while the size of the VSD was negatively correlated with RV/ LV ratio. 4D BF- STIC-sagittal and 4D BF- STIC-4 CV were better than traditional 2D ultrasound in detecting the aortic arch and neck vessels between 17 and 28 gestational weeks and 29 to 40 gestational weeks in normal fetuses. Conclusion It is demonstrated that IAA-A could be diagnosed by traditional fetal echocardiography, while 4D technique could better display the anatomic structure and the spatial relationships of the great arteries. Use of volume reconstruction may promote its clinical usage and help prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Multiple first trimester aneuploidy sonomarkers have been introduced recently. Objective: To evaluate the efficacy of first trimester sonomarkers in fetal aneuploidy detection without serum markers. Methods: There were entirely 280 fetuses with 11-13+6 weeks' gestation (crown-rump -length between 45-84 mm) enrolled to assess nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow. The performance of each single marker and multiple markers for major fetal aneuploidy screening were determined. Results: Totally, 190 fetuses (67.85%) underwent invasive prenatal diagnosis with 14 major chromosome abnormalities identified including 4 cases of trisomy 21, 4 cases of trisomy 18, 3 cases of trisomy 13 and 3 cases of 45, XO. NT was the most accurate single marker with sensitivity of 71.43% and false-positive rate (FPR) of 4.14% while NB or TR was the most specific marker (99.6%) but lacked sensitivity. Among multiple first trimester-screening sonomarkers, NT plus TR evaluation were the most sensitive test (78.57%) with FPR of 4.76%. Conclusion: NT was the most accurate first trimester-screening marker for fetal aneuploidy. NT plus TR assessment as double-screening markers could improve the sensitivity by 7% leading to the lower number of unnecessary invasive prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The study aim was to determine the frequency of prenatal ultrasound diagnosis of congenital anomalies in Newborns (NB) with birth defects hospitalized in two Neonatal Intensive Care Units (NICU) of Cali (Colombia) and to identify socio-demographic factors associated with lack of such diagnosis. Methods: It was an observational cross-sectional study. NB with congenital defects diagnosable by prenatal ultrasound (CDDPU), who were hospitalized in two neonatal intensive care units (NICU), were included in this study. A format of data collection for mothers, about prenatal ultra-sonographies, socio-demographic data and information on prenatal and definitive diagnosis of their conditions was applied. Multiple logistic and Cox regressions analyses were done. Results: Were included 173 NB, 42.8% of cases had no prenatal diagnosis of CDDPU; among them, 59.5% had no prenatal ultrasound (PNUS). Lack of PNUS was associated with maternal age, 25 to 34 years (Odds Ratio [OR]: 4.41) and 35 to 47 years (OR: 5.24), with low levels of maternal education (OR: 8.70) and with only a PNUS compared to having two or more PNUS (OR: 4.00). Mothers without health insurance tend to be delayed twice the time to access the first PNUS in comparison to mothers with payment health insurance (Hazard Ratio [HR]: 0.51). Among mothers who had PNUS, screening sensitivity of CDDPU after the 19th gestational week was 79.2%. Conclusions: The frequency of prenatal diagnosis is low and is explained by lack of PNUS, or by lack of diagnostic in the PNUS. An association between lack of PNUS and late age pregnancy and low level of maternal education was found. In addition, uninsured mothers tend to delay twice in accessing to the first PNUS in comparison to mothers with health insurance. It is necessary to establish national policies which ensure access to appropriate, timely and good quality prenatal care for all pregnant women in Colombia. [ABSTRACT FROM AUTHOR]

Background: Since 2007, the American College of Obstetricians and Gynecologists (ACOG) has recommended that all pregnant women be offered prenatal screening for fetal aneuploidy (i.e., trisomies 21, 18, 13). Current screening options include tests with sub-optimal sensitivity and specificity rates, while diagnostic procedures are invasive and create risk of procedure related miscarriage. The verifi™ test, a non-invasive test using circulating cell-free DNA (cfDNA), extracted from a maternal blood sample as early as 10 weeks gestation has demonstrated comparable sensitivity and superior specificity to invasive diagnostics in detecting fetal aneuploidy in chromosomes 21, 18, and 13. Methods: A cost-model was developed to evaluate the impact of incorporating this prenatal test into routine high-risk maternal screening practice. The multi-stage transition probability model leveraged published cost estimates from Medicare as well as practice patterns and disease rates from published literature. Results: The model demonstrates that inclusion of the verifi™ prenatal test provides clear clinical benefits. These include a 66 percent reduction in invasive diagnostic induced miscarriages and 38 percent more women receiving a T21 diagnosis. Total costs for prenatal screening and diagnosis for fetal aneuploidies are reduced by 1 percent annually. Conclusion: Significant clinical and cost advantages are likely to occur when novel non-invasive prenatal screening tests with high sensitivity and specificity are incorporated into routine high-risk screening practice. [ABSTRACT FROM AUTHOR]

Abstract: Children with hypoplastic left heart syndrome (HLHS) are at risk for neurodevelopmental dysfunction; prenatal factors may play a role in this predilection. Cerebral blood flow profiles are abnormal in fetuses with HLHS, raising the possibility that cerebral hemodynamics in utero may be related to neurodevelopmental abnormalities. Prenatal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is technically feasible and improves left heart hemodynamics. This study aimed to assess the effects of prenatal intervention on cerebral blood flow profiles and head circumference in fetuses with evolving HLHS. Seventy fetuses underwent prenatal aortic valvuloplasty for evolving HLHS (median 23 weeks gestation). Among 46 fetuses that had successful valvuloplasty and available data, middle cerebral artery (MCA) pulsatility (PI) and resistive (RI) indices were abnormal (Z-scores –1.7±1.1 and –2.2±1.4, p <0.001). Early post-valvuloplasty (n =33) and at late gestation follow-up (n =28), MCA PI and RI Z-scores remained low with no difference from pre- or early postintervention. Fetal head circumference was normal, as were umbilical artery PI and RI Z-scores. Cerebral blood flow characteristics are abnormal in mid-gestation fetuses with evolving HLHS, suggesting low cerebral vascular impedance. The mechanisms and significance of these abnormalities are unknown. Prenatal aortic valvuloplasty did not have a major impact on these indices. (E-mail: doff.mcelhinney@cardio.chboston.org) [Copyright &y& Elsevier]

Abstract: The objective of this study was to determine if very early ultrasonographic measurements obtained from human and baboon are comparable. For this purpose, the gestational, amniotic and yolk sacs, embryonic crown rump length (CRL) and heart rate were measured ultrasonographically between 35 and 47 days from the mean day of a three-day mating period in baboons (n = 18) and between 42 to 58 days from fertilization as calculated from the CRL measurements in human pregnancies (n = 82). Ultrasonographic measurements from both species were then plotted in the same graph using Carnegie stages of embryonic development as the independent variable to allow for visual comparisons. Mean gestational age at ultrasonographic studies was significantly different for humans and baboons (50.4 vs. 41 days, respectively; p > 0.01). Significant correlations (p > 0.01) were noted between ultrasonographic measurements and Carnegie stages of development in both humans and baboons. Only the gestational and the yolk sacs were significantly smaller in baboons than in humans (p > 0.05). The findings that embryonic CRL, extra-embryonic space and heart rate are very similar between the 17th and 23rd Carnegie developmental stages make the baboon a promising surrogate of human pregnancy for investigations using celocentesis. (E-mail: jsantolaya@partners.org) [Copyright &y& Elsevier]