Fetal Structural Abnormalities Research Articles

Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Chromosomal microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism array, are widely applied in the diagnostic evaluation for both constitutional and neoplastic disorders. In a constitutional setting, this technology is accepted as the first-tier test for the evaluation of chromosomal imbalances associated with intellectual disability, autism, and/or multiple congenital anomalies. Furthermore, chromosomal microarray analysis is recommended for patients undergoing invasive prenatal diagnosis with one or more major fetal structural abnormalities identified by ultrasonographic examination, and in the evaluation of intrauterine fetal demise or stillbirth when further cytogenetic analysis is desired. This technology also provides important genomic data in the diagnosis, prognosis, and therapy of neoplastic disorders, including both hematologic malignancies and solid tumors. To assist clinical laboratories in the validation of chromosomal microarray methodologies for constitutional and neoplastic applications, the American College of Medical Genetics and Genomics (ACMG) Laboratory Quality Assurance Committee has developed these updated technical laboratory standards, which replace the ACMG technical standards and guidelines for microarray analysis in constitutional and neoplastic disorders previously published in 2013.

Euploid First-Trimester Cystic Hygroma: A More Benign Entity than Previously Thought?

Objective: Studies summarizing the outcome of first-trimester septated cystic hygroma are generally based on small studies or from multiple centers with limited ascertainment. We reviewed the natural history of a large cohort of such cases from a single tertiary referral center, with the aim being to establish contemporary outcome data, particularly in the setting of normal karyotype. Methods: A retrospective cohort study from 2007 to 2017 was conducted at a single tertiary referral prenatal diagnosis center. Data were analyzed from a prospectively collated fetal anomaly database. Search terms were “increased nuchal translucency (NT),” “cystic hygroma,” and “septated cystic hygroma.” All cases were confirmed to have NT >3 mm with septations. Cases of simple increased NT without septations were excluded. Results: During the study period, over 110,000 pregnancies were delivered at our center, resulting in 410 cases of septated cystic hygroma diagnosed prior to 14 weeks’ gestation. Pregnancy outcome was obtained in 99% (405/410) of cases, with detailed pathology outcome available in 92% (378/410). A total of 87% (351/405) underwent invasive prenatal testing, and postnatal chromosome status was established in further 27 cases. A total of 61% (230/378) had abnormal chromosomal status. Of the 39% (148/378) with normal chromosomal status, only 13% (19/148) had a significant structural fetal abnormality, which included 7 cardiac and 12 noncardiac abnormalities. Overall, the perinatal loss was 62% (253/405). The total survival rate in the setting of euploid cystic hygroma without structural abnormality was 84% (108/129). Conclusions: Counseling regarding outcomes in the setting of first-trimester septated cystic hygroma initially focuses on the strong likelihood of an abnormal karyotype, which occurs in 61% of cases. However, once fetal chromosomal abnormality is excluded, our results demonstrate only a 13% incidence of major structural fetal abnormality, which appears significantly less than previously reported. Normal fetuses have a 77% survival rate. These data represent the largest single-center study of first-trimester cystic hygroma with complete outcome data and therefore will be useful for contemporary patient counseling. Such counseling can be more positive than previously expected, once chromosomal abnormality is first excluded.

Overview of Inception and Viability of Genetic Amniocentesis

Clinical procedures that took both time and effort in terms of prior diagnosis are being aided by technology and significant advancements in recognizing and predicting outcomes long before they actually take place. The aim of prenatal diagnosis is to detect fetal structural and genetic abnormalities. That is why it is possible to talk in the unborn fetus about preventing and detecting inherited and congenital illnesses. The most comprehensive and intrinsic makeup shared by all and therefore a vital subject to comparative analysis even before birth is the unmistakable nucleotide sequence that directs all physical and chemical changes. Amniocentesis involves taking out a small sample of amniotic fluid from the sac surrounding the fetus and analysis of its composition, so in essence genetic amniocentesis refers to examination of genetic abnormalities that might be prevalent in the developing fetus This permits taking decisions concerning about the progress of pregnancy to be made before viability. Comparatively less commonly, amniocentesis is performed in the beginning of third trimester instead of earlier testing. Advanced genomic study technologies such as Chromosomal Microarray Analysis (CMA) provide much more accurate and detailed information about the fetus. The ideal site for amniocentesis for localization should be determined by an ultrasound scan but in the absence of this facility, a site may be selected after careful palpation of the gravid uterus. Trisomy, Micro deletions/ micro substitutions can be detected by genetic amniocentesis. Fluorescence in Situ Hybridization is a dependable and brief technique for identifying maximum chromosomal variations and has now been carried out as a routine symptomatic strategy for the discovery of fetal irregularities.

Effects of E-Cigarette Exposure on Prenatal Life and Childhood Respiratory Health: A Review of Current Evidence.

In the last decade, widespread use of E-cigarettes (EC) has occurred all over the world. Whereas, a large amount of evidence on harm to children from conventional cigarette exposure is available, data on health effects in this population throughout different vulnerability windows are still a matter of concern. Exposure to EC during pregnancy may compromise placental function, resulting in fetal structural abnormalities. Specifically, this may cause physio-pathologic changes in the developing lung, which in turn may impair respiratory health later in life. Furthermore, there is evidence that using EC can cause both short- and long-term respiratory problems in the pediatric population and there is great concern for future young people with nicotine addiction. The low parental perception of the risks connected to EC exposure for children increases their susceptibility to harmful effects from passive vaping. This minireview aims to summarize the current evidence focusing on: (i) prenatal effects of EC passive exposure; (ii) post-natal respiratory effects of EC exposure in youth; (iii) parental attitudes toward EC use and perception of children's health risks connected to EC exposure; and (iv) addressing gaps in our current evidence.

Association of fetal cardiac structural abnormalities and chromosomal aneuploidies and copy number variations

To investigate the association of fetal cardiac structural abnormalities with chromosomal aneuploidies and copy number variations (CNVs) in amniocytes. 328 pregnant women were subjected to fetal ultrasonography and chromosomal microarray analysis (CMA). Based on the fetal heart structure, the subjects were divided into normal (n=273) and abnormal groups (n=55). The detection rates of chromosomal aneuploidies and CNVs were compared between the two groups. Spearman method was used to assess the association between the results and fetal cardiac structural abnormalities. The detection rates for chromosomal aneuploidies and CNVs in the abnormal group were significantly higher than that in the normal group (P< 0.05), and the incidence of fetal cardiac structural abnormalities was strongly associated with chromosomal aneuploidies and CNVs (P< 0.05). Fetal chromosomal aneuploidies and CNVs are strongly associated with cardiac structural abnormalities.

OUTCOME OF SECOND BABY OF TWIN IN A RURAL TEACHING HOSPITAL OF WEST BENGAL, INDIA

Background: Multiple pregnancies are a high-risk situation because of its inherent risks to mother and the fetus. Twin or multiple pregnancies are gaining importance worldwide because of the attributable rise in treatment of infertility including assisted reproductive technologies. Twin pregnancies are associated with increased fetal loss, prematurity, structural abnormalities, and fetal growth restriction. Complications associated with twin pregnancy. The conduct of a twin delivery remains one of the most challenging events in the current obstetric practice. This Methods: study was an Hospital-based cross-sectional descriptive study conducted in the Department of Obstetrics &amp; Gynaecology of Bankura Sammilani Medical College and Hospital, Bankura, West Bengal from January 2020 to December 2020. 238 patients were included in the study after informed consent from the patient about being a part of this study. Template was generated in MS excel sheet and analysis was done on SPSS software. Results: Majority 154 (64.7%) of women belonged to age group 21-30 years. Gestational age of 159 (66.8%) mothers were &lt; 37 weeks. Perinatal outcome of second twin was highest in the maternal age group 20 years. Perinatal outcome of second twin was highest in the birth weight of the 2nd twin &lt; 2500 grams. Delivery time interval between the babies was maximum 175 (73.5%) is &lt; 10 minutes. Gestational age, Conclusions: presentation, mode of delivery, and birth weight are the signicant determinants of perinatal outcome of the second twin. The second twin is at higher risk of perinatal morbidity and mortality than the rst twin. Frequent antenatal care should be advised to the mothers.

Diagnostic accuracy of ultrasound screening for fetal structural abnormalities during the first and second trimester of pregnancy in low-risk and unselected populations

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: The main objectives of this review are to assess the diagnostic accuracy of first‐ and second‐trimester fetal anomaly screening in low‐risk pregnant women, and to compare overall performance of single‐ and two‐stage screening approaches with regards to the number of cases detected before birth, as well as the proportion of false positive diagnoses. Secondary objectives Our secondary objective is to identify potential sources of heterogeneity between studies by investigating the effect of clinical factors (i.e. prior testing, factors related to the conduct of the ultrasound examination, and healthcare setting of the study) and methodological factors (i.e. related to the study design, such as methods used for postnatal ascertainment of cases) on screening performance.

Application of Combined Ultrasound and Maternal Serum Biochemical Indexes in the Detection of Fetal Structural Abnormalities and Chromosomal Abnormalities

By exploring different prenatal diagnosis indications of fetal chromosomal abnormalities, it can provide a theoretical basis and reference value for clinical consultation of pregnant women with similar high-risk factors. In this paper, 1800 pregnant women undergoing amniotic fluid aspiration chromosomal examination in the prenatal diagnosis center were selected as the object of this study. Amniocentesis, fetal cell culture, and karyotype analysis were performed on pregnant women who were 14-20 weeks pregnant and had signed an informed consent. After amniocentesis fetal chromosome analysis, the type of fetal chromosomal abnormality was determined, and the detection rate of chromosomal abnormality was statistically described. Chi-square test was used for comparison between groups, P &lt; 0.05. This study shows that the use of ultrasound screening combined with maternal serum indicators is effective in screening fetal structural abnormalities and chromosomal abnormalities in early pregnancy, and significantly improves the detection rate of chromosomal abnormalities. The detection of fetal structural malformations is also very high, but it should be combined with ultrasound screening of mid-to-late pregnancy. The tricuspid regurgitation and umbilical vein a-wave reversal in the soft ultrasound index can be used as predictors of fetal congenital heart disease in early pregnancy.

Role of Imaging in Obstetric Interventions: Criteria, Considerations, and Complications.

US has an established role in the prenatal detection of congenital and developmental disorders. Many pregnant women undergo US at 18-20 weeks of gestation for assessment of fetal anatomy and detection of structural anomalies. With advances in fetoscopy and minimally invasive procedures, in utero fetal interventions can be offered to address some of the detected structural and physiologic fetal abnormalities. Most interventions are reserved for conditions that, if left untreated, often cause in utero death or a substantially compromised neonatal outcome. US is crucial for preprocedural evaluation and planning, real-time procedural guidance, and monitoring and assessment of postprocedural complications. Percutaneous needle-based interventions include in utero transfusion, thoracentesis and placement of a thoracoamniotic shunt, vesicocentesis and placement of a vesicoamniotic shunt, and aortic valvuloplasty. Fetoscopic interventions include myelomeningocele repair and tracheal balloon occlusion for congenital diaphragmatic hernia. In rare cases, open hysterotomy may be required for repair of a myelomeningocele or resection of a sacrococcygeal teratoma. Monochorionic twin pregnancies involve specific complications such as twin-twin transfusion syndrome, which is treated with fetoscopic laser ablation of vascular connections, and twin reversed arterial perfusion sequence, which is treated with radiofrequency ablation. Finally, when extended placental support is necessary at delivery for repair of congenital high airway obstruction or resection of lung masses, ex utero intrapartum treatment can be planned. Radiologists should be aware of the congenital anomalies that are amenable to in utero interventions and, when necessary, consider referral to centers where such treatments are offered. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2021.

The Value of Prenatal Systematic Ultrasonic Examination of Fetal Structural Abnormality in Diagnosing Fetal Structural Abnormality

In order to explore the value of prenatal systematic ultrasound examination of fetal structural abnormality in the diagnosis of fetal structural abnormality, this paper retrospectively analyzed 200 cases of fetal abnormality referrals from December 2017 to December 2019 in the prenatal systematic ultrasound examination of the designated hospital in this study of pregnant women. By sorting, summarizing and summarizing the actual conditions of the systematic ultrasound examination of each prenatal fetal abnormal section, this study calculated, recorded and analyzed the detection rate, missed diagnosis rate, sensitivity, and specificity of the systematic ultrasound examination of structural abnormality, and then discussed the value of prenatal systematic ultrasound in the diagnosis of fetal structural abnormality. The results showed that, 185 cases were detected out of 200 fetal abnormality with the detection rate of 92.5%; missed diagnosis rate is 7.3%; detection sensitivity is 87.43%; and specificity is 76.58%. Among them, the detection rate of malformations of different diseases from high to low is cardiovascular system (97.54%), nervous system (93.16%), respiratory system (90.62%), facial system (87.54%), and urinary system (85.47%). Therefore, the prenatal systematic ultrasound fetal structural abnormality examination for pregnant women can achieve good diagnostic results, can provide pregnant women with fetal structural abnormality the opportunity to terminate pregnancy early, and effectively reduce the birth of structural abnormal fetuses and the burden of family and society, having important clinical significance and reducing.

We Need to Improve Prenatal Screening Practices in Primary Obstetric Care: A Representative Data from a Fetal Medicine Unit in Coastal Karnataka

BackgroundThe present observational data from the fetal medicine unit aim to identify gaps in prenatal screening modalities employed in the primary obstetric care population in coastal Karnataka.MethodsA retrospective observational study of all referrals to Fetal Medicine unit is over 2 years. For each fetal abnormality, we reviewed the literature to note the range of gestational age at which the abnormality should almost always be diagnosed. Taking this as standard, the gestational age at which each of these problems was diagnosed and referred was noted down. They were compared and analysed to understand the efficiency of prenatal screening practices in the referral population. The final perinatal outcome was also noted down in order to assess the impact on perinatal mortality/morbidity.ResultsA total of 277 cases were referred to fetal medicine unit. Two hundred twenty-eight cases (82.31%) were low risk pregnancies. Among 277 cases, 200 (72.2%) had structural abnormalities, 7 (2.5%) chromosomal/ genetic abnormalities, 61 (22.02%) isolated soft markers, and 9 (3.2%) twin-related problems. Detection rate of structural abnormalities was 33% at 14 weeks and 52.22% at 20 weeks, considering those anomalies usually diagnosed by these gestational age windows. The primary reason for delayed diagnosis was non-performance of ultrasound “on time”, rather than missed diagnosis. Fifty-three per cent (106 out of 200) of all the fetal structural abnormalities were diagnosed beyond 20 weeks. Average gestational age at mid-trimester anomaly scan in this group was between 20 and 24 weeks. Sixty-one patients were referred due to isolated soft markers, 30 beyond 20 weeks. Eighty per cent of them did not have any aneuploidy screening in pregnancy.ConclusionPractice of fetal medicine hugely depends upon appropriate prenatal screening practices in the referral population. There is an urgent need to bring in standard protocols for Prenatal Screening across all the primary obstetric care providers, both in the public and private sectors. Considering the huge burden of delayed prenatal diagnosis in our country, the proposed revision of MTP bill is a welcome change in fast-growing field of fetal diagnosis and therapy.

527 Is there an association between postoperative cervical length after cerclage and gestational age at delivery?

Ultrasound (US) surveillance of cervical length after US and physical exam (PE) indicated cerclage has been used to attempt to identify women at highest risk for spontaneous preterm birth (PTB). Data is limited regarding the change in cervical length (CL) after cerclage placement and timing of delivery. The objectives of this study were to determine if there is an association between change in CL (difference in CL measurement prior to and post cerclage placement) and gestational age (GA) at delivery in women undergoing US or PE indicated cerclage and if there is a cutoff in CL change predictive of delivery at term. This was a retrospective study of singleton pregnancies who underwent US or PE indicated cerclage between 7/2017 and 6/2019. Patients were excluded if there was history of prior PTB, multiple gestation, placenta or vasa previa, history indicated cerclage, known fetal chromosomal or structural abnormality, or incomplete records. The Spearman correlation coefficient was used to evaluate the relationship between the change in CL and GA at delivery and the change in CL and weeks gained in pregnancy. A ROC curve was generated to determine if there was a change in CL predictive of delivery at term. 43 patients met inclusion criteria. 77% (n=33) delivered at term and 23% (n=10) delivered preterm. There was no significant correlation between change in CL and GA at delivery (Spearman correlation coefficient = 0.16, p<0.32) or between change in CL and weeks gained in pregnancy (Spearman correlation coefficient = 0.05, p<0.76). A gain in CL of ≥1.4 cm after cerclage placement was associated with delivery at term (Figure 1). The change in CL after cerclage placement was not associated with GA at delivery or prolongation of pregnancy. The majority of patients who received US or PE indicated cerclage delivered at term. A gain in CL of ≥1.4 cm was associated with delivery at term. This information may be used to appropriately counsel patients undergoing US or PE indicated cerclage.

A report on the impact of rapid prenatal exome sequencing on the clinical management of 52 ongoing pregnancies: a retrospective review.

Studies have shown that prenatal exome sequencing (PES) improves diagnostic yield in cases of fetal structural malformation. We have retrospectively analysed PES cases from two of the largest fetal medicine centres in the UK to determine the impact of results on management of a pregnancy. A retrospective review of clinical case notes. Two tertiary fetal medicine centres. Pregnancies with fetal structural abnormalities referred to clinical genetics via a multidisciplinary team. We retrospectively reviewed the notes of all patients who had undergone PES. DNA samples were obtained via chorionic villus sampling or amniocentesis. Variants were filtered using patient-specific panels and interpreted using American College of Medical Genetics guidelines. A molecular diagnosis was made in 42% (18/43) ongoing pregnancies; of this group, there was a significant management implication in 44% (8/18). A positive result contributed to the decision to terminate a pregnancy in 16% (7/43) of cases. A negative result had a significant impact on management in two cases by affirming the decision to continue pregnancy. We demonstrate that the results of PES can inform pregnancy management. Challenges include variant interpretation with limited phenotype information. These results emphasise the importance of the MDT and collecting phenotype and variant data. As this testing is soon to be widely available, we should look to move beyond diagnostic yield as a measure of the value of PES. Prenatal exome sequencing can aid decision-making in pregnancy management; review ahead of routine implementation in NHS.

Psychological outcomes, knowledge and preferences of pregnant women on first-trimester screening for fetal structural abnormalities: A prospective cohort study.

IntroductionThe primary aim of this study is to investigate the impact of a 13-week anomaly scan on the experienced levels of maternal anxiety and well-being. Secondly, to explore women’s knowledge on the possibilities and limitations of the scan and the preferred timing of screening for structural abnormalities.Material and methodsIn a prospective-cohort study conducted between 2013–2015, pregnant women in the North-Netherlands underwent a 13-week anomaly scan. Four online-questionnaires (Q1, Q2, Q3 and Q4) were completed before and after the 13- and the 20-week anomaly scans. In total, 1512 women consented to participate in the study and 1118 (74%) completed the questionnaires at Q1, 941 (64%) at Q2, 807 (55%) at Q3 and 535 (37%) at Q4. Psychological outcomes were measured by the state-trait inventory-scale (STAI), the patient’s positive-negative affect (PANAS) and ad-hoc designed questionnaires.ResultsNine-nine percent of women wished to be informed as early as possible in pregnancy about the absence/presence of structural abnormalities. In 87% of women levels of knowledge on the goals and limitations of the 13-week anomaly scan were moderate-to-high. In women with a normal 13-week scan result, anxiety levels decreased (P < .001) and well-being increased over time (P < .001). In women with false-positive results (n = 26), anxiety levels initially increased (STAI-Q1: 39.8 vs. STAI-Q2: 48.6, P = 0.025), but later decreased around the 20-week anomaly scan (STAI-Q3: 36.4 vs. STAI-Q4: 34.2, P = 0.36).ConclusionsThe 13-week scan did not negatively impact the psychological well-being of pregnant women. The small number of women with screen-positive results temporarily experienced higher anxiety after the scan but, in false-positive cases, anxiety levels normalized again when the abnormality was not confirmed at follow-up scans. Finally, most pregnant women have moderate-to-high levels of knowledge and strongly prefer early screening for fetal structural abnormalities.

Pilot study of fetal brain development and morphometry in prenatal opioid exposure and smoking on fetal MRI

PurposeThe purpose of this study was to assess for any differences in brain maturation, structure and morphometry in fetuses exposed to opioids in utero, compared to non-opioid exposed fetuses on fetal MRI. MethodsWe performed a prospective study in pregnant women using opioids and healthy pregnant women without prenatal opioid use. We evaluated brain maturation, structure, and morphometry on second or third trimester fetal MRI and assessed group differences. Results28 pregnant women were enrolled, 12 with opioid exposure (average gestational age 33.67, range 28–39 w), 9 of whom also smoked, and 16 without opioid exposure (average gestational age 32.53, range 27–38 w). There was a significant difference in the anteroposterior diameter of the fetal cerebellar vermis in the opioid exposed fetuses compared to non-opioid exposed fetuses (p = 0.004). There were no significant differences in brain biparietal diameter, fronto-occipital diameter, transverse cerebellar diameter and anteroposterior dimension of the pons in opioid exposed fetuses compared to non-opioid exposed fetuses. There were no abnormalities in brain maturation and no major brain structural abnormalities in the opioid exposed fetuses. ConclusionSmaller fetal anteroposterior cerebellar vermian dimension was associated with in utero opioid exposure. There were no abnormalities in brain maturation or major structural abnormalities in fetuses exposed to opioids.

Prenatal array comparative genomic hybridization in a well-defined cohort of high-risk pregnancies. A 3-year implementation results in a public tertiary academic referral hospital.

To find out whether the diagnostic yield of prenatal array comparative genomic hybridization (aCGH) can be improved by targeting preselected high-risk pregnancies. All the in-house arrays ordered by the Fetomaternal Medical Center from February 2016 until December 2018 were retrospectively analyzed. The indications for array analysis included fetal structural abnormalities, increased nuchal translucency ≥3.5mm and a chromosomal abnormality in a parent or a sibling. Common aneuploidies were excluded. Diagnostic yield was 15.1% in the entire patient cohort and as high as 20% in fetuses with multiple structural anomalies. The diagnostic yield was lowest in the group with isolated growth retardation. A total of 76 copy number variants (CNVs) were reported from a total of 65 samples, including 16 CNVs associated with a well-described microdeletion/microduplication syndrome, six autosomal trisomies in mosaic form, and three pathogenic single-gene deletions with dominant inheritance and 12 CNVs known to be risk factors for eg developmental delay. The diagnostic yield of aCGH was higher than what has previously been reported in less defined patient cohorts. However, the number of CNVs with unclear correlation to the fetal ultrasound findings was still relatively high. The importance of adequate pre- and posttest counseling must therefore be emphasized.

Application of chromosome microarray analysis in prenatal diagnosis

BackgroundTo explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis.MethodsThe results of chromosome karyotype analysis and CMA of 477 cases undergoing amniocentesis were analyzed. The results of the no ultrasound abnormality group and the ultrasound abnormality group were compared separately. Within the ultrasound abnormality group, the results of the ultrasound structural malformation group, the ultrasound soft index abnormality group, and other ultrasound abnormality (including abnormal amniotic fluid volume and fetal growth restriction) groups were compared.ResultsAbnormal chromosome and CMA results were found in a total of 71 cases (15.88%, 71/447), which can be broken down into a total of 23 karyotype abnormalities (5.15%, 23/447), consisting of 18 cases of aneuploidy (4.03%, 18/447), 2 cases of unbalanced chromosome rearrangements (0.44%, 2/447), and 3 cases of chimerism (0.67%, 3/447); 17 cases with detection of pathogenic copy number variations (pCNVs) (3.80%, 17/447); and 31 cases of detection of clinical variants of unknown significance (VOUS) (6.93%, 31/447). CMA detected 3.8% more genetic abnormalities than karyotype analysis (in addition to the abnormalities detected simultaneously by karyotype analysis). Between the no ultrasound abnormality group and the ultrasound abnormality group, there was an extremely significant difference in the detection rate of an abnormal chromosomal karyotype (P < 0.01) and of VOUS (P < 0.01), but there was no significant difference in the detection rate of pCNV (P > 0.05). Comparing the ultrasound structural malformation group, the ultrasound soft index abnormality group, and the other ultrasound abnormality group, there were no significant differences in the detection rate of abnormal chromosomal karyotypes (P > 0.05), pCNV (P > 0.05) or VOUS (P > 0.05).ConclusionsThe detection rate of chromosomal karyotype abnormalities in prenatal diagnosis in cases with no ultrasound abnormalities was higher. For cases with fetal ultrasound structural abnormalities, when compared with traditional karyotype analysis, CMA can improve the detection rate of fetal genetic abnormalities. However, the no ultrasound abnormality group also had a high VOUS abnormality detection rate, so it is necessary to strictly define the CMA indications.

Absent Cavum Septi Pellucidi

Absent Cavum Septi Pellucidi

Exploring the predicted yield of prenatal testing by evaluating a postnatal population with structural abnormalities using a novel mathematical model.

To determine the yield of prenatal testing and screening options after identification of fetal structural abnormalities using a novel mathematical model. A retrospective chart review was conducted to collect structural abnormality and genetic testing data on infants who were evaluated postnatally by a medical geneticist. A novel mathematical model was used to determine and compare the predicted diagnostic yields of prenatal testing and screening options. Over a quarter of patients with at least one structural abnormality (28.1%, n = 222) had a genetic aberration identified that explained their phenotype. Chromosomal microarray (CMA) had the highest predicted diagnostic yield (26.8%, P < .001). Karyotype (20.8%) had similar yields as genome wide NIPT (21.2%, P = .859) and NIPT with select copy number variants (CNVs) (17.9%, P = .184). Among individuals with an isolated structural abnormality, whole exome sequencing (25.9%) and CMA (14.9%) had the highest predicted yields. This study introduces a novel mathematical model for predicting the potential yield of prenatal testing and screening options. This study provides further evidence that CMA has the highest predicted diagnostic yield in cases with structural abnormalities. Screening with expanded NIPT options shows potential for patients who decline invasive testing, but only in the setting of adequate pre-test counseling.

Routine first-trimester ultrasound screening using a standardized anatomical protocol

First-trimester ultrasound scans were introduced to China for nearly 20 years. The ability of first-trimester ultrasound screening to detect different malformations was variable. A recent systematic review concluded that the use of a standardized anatomic protocol was the most crucial factor to improve the sensitivity of first-trimester ultrasound screening for anomalies. Standardized sectional scans have long been used for routine anatomy screening during the second trimester. However, during the first trimester, most of the previous studies have described the observation of anatomic structures but have not specified clearly the standard sectional views. We aimed to determine the performance of routine first-trimester scans using a standardized anatomic protocol for detecting structural abnormalities in China. This was a large retrospective study involving 59,063 sequential unselected pregnancies. Scans at 11 to 13+6 weeks were performed in a single center during a 7-year span. All fetuses were examined following a predefined protocol for standardized views. From October 2008 to December 2015, first-trimester scans were performed in 53,349 pregnant women with available outcome. Of these, there were 1578 (3%) pregnancies that presented with at least 1 fetal structural abnormality. The detection rate for first-trimester screening was 43.1% (95% confidence interval, 40.6%-45.5%). Routine first-trimester scans detected 95.6% of abdominal wall defects, 66.3% of nervous system defects, 33.8% of limbs and skeleton malformations, 30.8% of facial abnormalities, 21.2% of urogenital abnormalities, 18.4% of thoracic and lung abnormalities, and 4.1% of gastrointestinal tract abnormalities. During the first trimester, 37.7% of cardiac defects were identified and included 57.9% of major cardiac defects and 2.6% of mild cardiac defects. A robust high detection rate for anencephaly, exencephaly, cephalocele, holoprosencephaly, exomphalos, gastroschisis, Pentalogy of Cantrell, sirenomelia, and body stalk anomaly was achieved during routine first-trimester scans. A standardized anatomic protocol is advised when performing routine first-trimester ultrasound screening. It is recommended that screening for severe structural abnormalities should be extended to the first trimester.