Fetal Diagnosis Research Articles

Hybrid-FHR: a multi-modal AI approach for automated fetal acidosis diagnosis

BackgroundIn clinical medicine, fetal heart rate (FHR) monitoring using cardiotocography (CTG) is one of the most commonly used methods for assessing fetal acidosis. However, as the visual interpretation of CTG depends on the subjective judgment of the clinician, this has led to high inter-observer and intra-observer variability, making it necessary to introduce automated diagnostic techniques.MethodsIn this study, we propose a computer-aided diagnostic algorithm (Hybrid-FHR) for fetal acidosis to assist physicians in making objective decisions and taking timely interventions. Hybrid-FHR uses multi-modal features, including one-dimensional FHR signals and three types of expert features designed based on prior knowledge (morphological time domain, frequency domain, and nonlinear). To extract the spatiotemporal feature representation of one-dimensional FHR signals, we designed a multi-scale squeeze and excitation temporal convolutional network (SE-TCN) backbone model based on dilated causal convolution, which can effectively capture the long-term dependence of FHR signals by expanding the receptive field of each layer’s convolution kernel while maintaining a relatively small parameter size. In addition, we proposed a cross-modal feature fusion (CMFF) method that uses multi-head attention mechanisms to explore the relationships between different modalities, obtaining more informative feature representations and improving diagnostic accuracy.ResultsOur ablation experiments show that the Hybrid-FHR outperforms traditional previous methods, with average accuracy, specificity, sensitivity, precision, and F1 score of 96.8, 97.5, 96, 97.5, and 96.7%, respectively.ConclusionsOur algorithm enables automated CTG analysis, assisting healthcare professionals in the early identification of fetal acidosis and the prompt implementation of interventions.

Prenatal diagnosis of fetuses with ultrasound anomalies by whole-exome sequencing in Luoyang city, China.

Background: There is a great obstacle in prenatal diagnosis of fetal anomalies due to their considerable genetic and clinical heterogeneity. Whole-exome sequencing (WES) has been confirmed as a successful option for genetic diagnosis in pediatrics, but its clinical utility for prenatal diagnosis remains to be limited. Methods: A total of 60 fetuses with abnormal ultrasound findings underwent karyotyping or chromosomal microarray analysis (CMA), and those with negative results were further subjected to WES. The identified variants were classified as pathogenic or likely pathogenic (P/LP) and the variant of uncertain significance (VUS). Pregnancy outcomes were obtained through a telephone follow-up. Results: Twelve (20%, 12/60) fetuses were diagnosed to have chromosomal abnormalities using karyotyping or CMA. Of the remaining 48 cases that underwent WES, P/LP variants were identified in 14 cases (29.2%), giving an additional diagnostic yield of 23.3% (14/60). The most frequently affected organ referred for prenatal WES was the head or neck system (40%), followed by the skeletal system (39.1%). In terms of pathogenic genes, FGFR3 was the most common diagnostic gene in this cohort. For the first time, we discovered five P/LP variants involved in SEC24D, FIG4, CTNNA3, EPG5, and PKD2. In addition, we identified three VUSes that had been reported previously. Outcomes of pregnancy were available for 54 cases, of which 24 cases were terminated. Conclusion: The results confirmed that WES is a powerful tool in prenatal diagnosis, especially for fetuses with ultrasonographic anomalies that cannot be diagnosed using conventional prenatal methods. Additionally, newly identified variants will expand the phenotypic spectrum of monogenic disorders and greatly enrich the prenatal diagnostic database.

Umbilical–portal–systemic venous shunt and intrauterine growth restriction: an inquiry from a prospective study

BackgroundThe investigation of the fetal umbilical-portal venous system is based on the premise that congenital anomalies of this system may be related to adverse perinatal outcomes. Several retrospective small studies have reported a well-established association between umbilical–portal–systemic venous shunts and fetal growth restriction. However, the prevalence of portosystemic shunts in the fetal growth restricted population is yet to be determined. ObjectivesThe aims of this study were:1. To determine the prevalence of fetal umbilical–portal–systemic venous shunts in pregnancies complicated by fetal growth restriction.2. To compare the perinatal and neonatal outcome of fetal growth restriction pregnancies with and without umbilical–portal–systemic venous shunts. Study DesignA prospective cross-sectional study of pregnancies diagnosed with fetal growth restriction, as defined by the Society for Maternal-Fetal Medicine fetal growth restriction guidelines. All participants underwent a detailed anomaly scan supplemented with a targeted scan of the fetal portal system. Venous shunts were diagnosed using color Doppler mode. The perinatal outcomes of fetal growth restriction pregnancies with and without umbilical–portal–systemic venous shunts were compared. ResultsOne hundred and fifty cases of fetal growth restriction were recruited. The prevalence of umbilical–portal–systemic venous shunts in our cohort was 9.3% (n=14). Compared to the control group (fetal growth restriction without umbilical–portal–systemic venous shunts, n=136), the study group had a significantly lower mean gestational age at time of fetal growth restriction diagnosis [29.7 (±5.6) vs. 32.47 (±4.6) weeks of gestation, p=0.036] as well as an earlier gestational week at delivery [33.50 (±6.0) vs. 36.13 (±2.8), p=0.005]. The study group had a higher rate of fetal death (21.4% vs. 0.7%, p<0.001) and accordingly a lower rate of live births (71.4% vs. 95.6%, p=0.001). Associated additional fetal vascular anomalies were significantly more prevalent in the study group compared to controls (35.7% vs. 4.4%, respectively, p=<0.001). The rate of other associated anomalies was similar. The study group had a significantly lower rate of abnormal uterine artery Doppler indices (0% vs. 40.4% p=0.011) and a higher rate of abnormal ductus venosus Doppler indices (64.3% vs. 23% p=0.001). There were no cases of hypertensive disorders of pregnancy in the study group compared to 12.5% in the control group (p=0.16). Other perinatal and neonatal outcomes were comparable. ConclusionsUmbilical–portal–systemic venous shunt is a relatively common finding in growth restricted fetuses. Compared to fetal growth restriction pregnancies with a normal portal system, these pregnancies complicated by FGR and umbilical–portal–systemic venous shunt are associated with different Doppler flow pattern, increased risk for fetal death, earlier presentation of fetal growth restriction, lower gestational age at delivery, additional congenital vascular anomalies and a lower rate of pregnancy induced hypertensive disorders. Meticulous sonographic evaluation of the portal system should be considered in the prenatal workup of fetal growth restriction, as umbilical–portal–systemic venous shunts may have implications on perinatal outcome.

Prenatal diagnosis and outcomes in fetuses with duplex kidney.

Duplex kidney is a relatively frequent form of urinary system abnormality. This study aimed to elucidate the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) for duplex kidney and the perinatal outcomes of duplex kidney fetuses. This retrospective cohort study included 63 patients with duplex kidney diagnosed using antenatal ultrasound between August 2013 and January 2023. We reviewed the clinical characteristics, genetic test results, and pregnancy outcomes of the patients. Among the 63 cases based on the inclusion criteria, the CMA detected seven (11.1%) clinically significant variants and nine variants of uncertain significance (VUS), and the pathogenic/likely pathogenic (P/LP) copy number variations (CNVs) in the recurrent region that were associated with prenatal duplex kidney included 17q12, 17p13.3, and 22q11.2. No significant disparity was observed in the CMA detection rate between the unilateral and bilateral groups, or between the isolated and non-isolated groups. WES identified three (50%) P/LP single-gene variants in six fetuses with duplex kidney. We detected the following pathogenic genes in the duplex kidney fetuses: KMT2D, SMPD4, and FANCI. Pregnancy termination in cases where clinically significant variants were detected by genetic testing was different in statistical significance from that in cases with negative results (9/10, 90.0% vs 8/48, 16.7%, P < 0.001). This study elucidated the value of CMA and WES for fetal duplex kidney, proving that CMA and WES may be useful tools in prenatal diagnosis and genetic counseling.

Understanding perspectives on neural tube defect management: insights from Jordanian parents

Introduction Neural tube defects (NTDs) represent a spectrum of heterogeneous birth anomalies characterized by the incomplete closure of the neural tube. In Jordan, NTDs are estimated to occur in approximately one out of every 1000 live births. Timely identification of NTDs during the 18–22 weeks of gestation period offers parents various management options, including intrauterine NTD repair and termination of pregnancy (TOP). This study aims to assess and compare parental knowledge and perceptions of these management modalities between parents of affected children and those with healthy offspring. Materials and methods This retrospective case-control study was conducted at Jordan University Hospital (JUH) using telephone-administered questionnaires. Categorical variables were summarized using counts and percentages, while continuous variables were analyzed using mean and standard deviation. The association between exposure variables and outcomes was explored using binary logistic regression. Data analysis was performed using SPSS for Windows version 26 (SPSS Inc., Chicago, IL). Results The study sample comprised 143 participants, with 49.7% being parents of children with NTDs. The majority of NTD cases were associated with unplanned pregnancies, lack of folic acid supplementation, and postnatal diagnosis. Concerning parental knowledge of TOP in Jordan, 86% believed it to be legally permissible in certain situations. However, there was no statistically significant difference between cases and controls regarding attitudes toward TOP. While the majority of parents with NTD-affected children (88.7%) expressed a willingness to consider intrauterine surgery, this percentage decreased significantly (to 77.6%) after receiving detailed information about the procedure’s risks and benefits (p = .013). Conclusions This study represents the first case-control investigational study in Jordan focusing on parental perspectives regarding TOP versus intrauterine repair of myelomeningocele following a diagnosis of an NTD-affected fetus. Based on our findings, we urge the implementation of a national and international surveillance program for NTDs, assessing the disease burden, facilitating resource allocation toward prevention strategies, and promoting early diagnosis initiatives either by using newly suggested diagnostic biomarkers or early Antenatal ultrasonography.

Prenatal Diagnosis of Fetal Micrognathia at 11-20 Weeks of Gestation: A Prospective Observation Study.

To prospectively evaluate the prognosis of fetuses diagnosed with micrognathia using prenatal ultrasound screening. Between January 2019 and December 2022, a normal range of IFA to evaluate the facial profile in fetuses with micrognathia in a Chinese population between 11 and 20 gestational weeks was established, and the pregnancy outcomes of fetal micrognathia were described. The medical records of these pregnancies were collected, including family history, maternal demographics, sonographic findings, genetic testing results, and pregnancy outcomes. Ultrasound identified 25 patients with fetal micrognathia, with a mean IFA value of 43.6°. All cases of isolated fetal micrognathia in the initial scans were non-isolated in the following scans. A total of 78.9% (15/19) cases had a genetic cause confirmed, including 12 with chromosomal abnormalities and 3 with monogenic disorders. Monogenic disorders were all known causes of micrognathia, including two cases of campomelic dysplasia affected by SOX9 mutations and one case of mandibulofacial dysostosis with an EFTUD2 mutation. In the end, 19 cases were terminated, 1 live birth was diagnosed as Pierre Robin syndrome, and 5 cases were lost to follow-up. IFA is a useful indicator and three-dimensional ultrasound is a significant support technique for fetal micrognathia prenatal diagnosis. Repeat ultrasound monitoring and genetic testing are crucial, with CMA recommended and Whole exome sequencing performed when normal arrays are reported. Isolated fetal micrognathia may be an early manifestation of monogenic disorders.

Prenatal diagnosis of criss-cross heart – case series and review of the literature

Objective This study aimed to improve the accuracy of prenatal diagnosis by analyzing fetal echocardiographic features of criss-cross heart (CCH), to provide an effective basis for the development of management strategies and improve the prognosis of patients. Methods A retrospective analysis was performed on CCH cases diagnosed prenatally at our center between July 2016 and June 2022. Clinical data and prenatal fetal echocardiographic images were reviewed. Literature on prenatal diagnosis of CCH was searched from January 2000 to December 2023 in the PubMed database. Results Fourteen (0.03%) CCH cases were diagnosed from a database of fetal echocardiograms of 41354 cases at our center. The prenatal genetic testing results were normal in 10 cases and 4 cases didn’t check. All cases underwent termination of pregnancy. All cases showed crossed ventricular inflow tracts and combined with other cardiac structural abnormalities. A total of eight articles containing 25 cases were found in the literature review and all cases were associated with other cardiac structural abnormalities. Conclusion Prenatal echocardiography is the primary tool for fetal diagnosis of CCH. Continuous scanning helps avoid missing data and misdiagnosis.

Patient Survey Regarding Non-Medical Burdens of Care at a Parental Fetal Care Center.

Recognizing the paucity of literature describing the non-medical effects of care at a tertiary parental fetal care center upon families, the purpose of the study was to better examine the potential barriers that our patients face related to care in a parental fetal care center. An anonymous survey was sent via email to patients who received care from 2015 to 2021. The survey included questions regarding demographics, fetal diagnoses, non-medical expenses related to care, and the impact of care on patient relationships, employment, and other children. 453 patients (15.9%) responded out of the 2684 emails sent. 58.3% of patients traveled >100 miles to reach our referral center, with 20% traveling >300 miles. 42.6% of patients reported non-medical expenditures exceeding $1000, with nearly 1 in 10 reporting expenditures of >$5000 (8.6%). Overall, 38.2% of women reported moderate to severe financial burdens related to receiving care at the parental fetal care center. This study illuminates the financial and social burdens that care at a tertiary parental fetal care center imposes upon families. By acknowledging these barriers, we can strive to minimize them to best provide equitable access to high-quality fetal care services.

Diagnosis and postnatal prognosis of fetuses with myelomeningocele managed at our institution

Diagnosis and postnatal prognosis of fetuses with myelomeningocele managed at our institution

Chromosomal Microarray Analysis in Fetuses with Ultrasound Abnormalities.

To explore and evaluate the value of chromosomal microarray analysis (CMA) in prenatal diagnosis of fetuses with ultrasound abnormalities. A retrospective analysis was performed on 370 fetuses with ultrasound abnormalities received invasive prenatal diagnosis at Meizhou People's Hospital from October 2022 to December 2023. Fetal specimens were analyzed by CMA, and the detection rates of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) in ultrasound structural abnormalities (malformations of fetal anatomy) and non-structural abnormalities (abnormalities of fetal nonanatomical structure) were analyzed. There were 114 (30.8%) cases with isolated ultrasound structural abnormalities, 226 (61.1%) cases with isolated non-structural abnormalities (182 isolated ultrasound soft markers abnormalities, 30 isolated fetal growth restriction (FGR), and 8 isolated abnormalities of amniotic fluid volume), and 30 (8.1%) cases with both structural and non-structural abnormalities. The overall detection rate of aneuploidy and P/LP CNVs in isolated ultrasonic structural abnormalities was 5.3%, among which cardiovascular system abnormalities were the highest. In addition, the largest number of fetuses with non-structural abnormalities was nuchal translucency (NT) thickening (n = 81), followed by ventriculomegaly (n = 29), and nasal bone dysplasia (n = 24). The detection rate of chromosomal abnormalities of fetuses with abnormal ultrasound soft markers was 9.9%, and the detection rate in single abnormal ultrasound soft marker, and multiple ultrasound soft markers abnormalities was 9.7% (16/165) and 11.8% (2/17), respectively. Moreover, the detection rate of chromosomal abnormalities of fetuses with FGR and structural abnormalities combined with non-structural abnormalities was 6.7% (2/30), and 13.3% (4/30), respectively. The incidence of chromosomal abnormalities (aneuploidy and P/LP CNVs) varies among different fetal ultrasound abnormalities.

Influence of improved antenatal detection on the outcomes of complete atrioventricular block diagnosed in fetal-neonatal life and childhood periods - a single-centre experience in South Wales for 55 years.

This study aimed to analyse the influence of improved antenatal detection on the course, contemporary outcomes, and mortality risk factors of the complete atrioventricular block during fetal-neonatal and childhood periods in South Wales. The clinical characteristics and outcomes of complete atrioventricular block in patients without structural heart disease at the University Hospital of Wales from January 1966 to April 2021 were studied. Patients were divided into two groups according to their age at diagnosis: I-fetal-neonatal and II-childhood. Contemporary outcomes during the post-2001 era were compared with historical data preceding fetal service development and hence earlier detection. There were 64 patients: 26 were identified in the fetal-neonatal period and the remaining 38 in the childhood period. Maternal antibodies/systemic lupus erythematosus disease (anti-Ro/Sjögren's-syndrome-related Antigen A and/or anti-La/Sjögren's-syndrome-related Antigen B) were present in 15 (57.7%) of the fetal-neonatal. Fetal/neonatal and early diagnosis increased after 2001 with an incidence of 1:25000 pregnancies. Pacemaker implantation was required in 34 patients, of whom 13 were diagnosed in the fetal-neonatal group. Survival rates in cases identified before 2001 were at 96.3% (26/27), whereas it was 83.8% (31/37) in patients diagnosed after 2001 (P > 0.05). Other mortality risk factors comprised a lower gestational week at birth, maternal antibodies, and an average ventricular heart rate of < 55 bpm. Fetal diagnosis of complete atrioventricular block is still portends high fetal and neonatal mortality and morbidity despite significantly improved antenatal detection after 2001. Pacemaker intervention is needed earlier in the fetal-neonatal group. Whether routine antenatal medical treatment might alter this outcome calls for further prospective multicentre studies.

"I don't have a telephone to the fetus": Clinicians' conceptions of fetal patienthood in maternal-fetal surgery counseling

RationaleMaternal fetal surgery (MFS) has developed rapidly since the 1960s and centers for fetal diagnosis and therapy (CFDT) have proliferated. As a result, CFDT clinicians have intervened with fetuses through pregnant bodies for decades, yet the patienthood status of the fetus and its implications for the pregnant person's autonomy have been relatively unexamined. ObjectiveOur overall research aims were threefold: (1) to explore how clinicians train for and provide counseling for MFS; (2) to examine how clinicians assess fetal patienthood and its implications; and (3) to understand clinicians’ professed needs and their recommendations for education and training for the provision of MFS counseling. This focuses on aim two. MethodIn this qualitative study, conducted using in-depth interviews, we examined how 20 clinicians from 17 different sites understood fetal patienthood, how that affected their counseling of pregnant patients, and whether they drew on extant ethical frameworks for guidelines. ResultsWe identified three major themes: 1) Clinicians entered fetal surgery consultations with assumptions about fetal patienthood (frequently informed by beliefs about fetal viability, maternal attachment, and disciplinary perspectives); 2) they consciously assessed their pregnant patients' connections to their fetus to inform or re-calibrate their own understandings of fetal patienthood; and 3) they used a threshold -based conceptualization whereby the fetus achieved patienthood after crossing a symbolic boundary, often related to the clinician's ability to intervene. ConclusionsFew clinicians invoked an extant ethical framework to determine fetal patienthood; most asserted that they did not view directive counseling toward MFS as appropriate, instead working diligently to protect pregnant patients’ autonomy and rights to self-determination.

This birth is difficult but beautiful — parents’ experience of giving birth to a baby with a lethal foetal diagnosis

This birth is difficult but beautiful — parents’ experience of giving birth to a baby with a lethal foetal diagnosis

Clinical outcomes of fetuses with cardiac rhabdomyoma: A case series from a tertiary center.

The study aims to evaluate the genetic and clinical outcomes of fetal cardiac rhabdomyoma in our tertiary center. Data of cases with cardiac rhabdomyoma detected by fetal echocardiography during antenatal follow-up were analyzed retrospectively. Nine cases were included in the study. The incidence of cardiac rhabdomyoma was 0.003%. The median fetal diagnosis time was 26th weeks, the most common location was the LV. There was no hemodynamic disorder requiring cardiovascular intervention in any of the cases. Of the eight genetically tested cases, four were tuberous sclerosis complex (TSC) gene-negative, one hereditary TSC2, one de novo TSC1, and two de novo TSC2 gene mutants. Postnatal first-year survival rate of the cases was 88.8%. Cardiac rhabdomyoma is a rare fetal and pediatric pathology that generally is a remarkable finding in the clinical process of TSC. Therefore, cases should be evaluated multisystemically and genetic counseling should be given to the family.

Fetal cardiac magnetic resonance imaging of the descending aorta in suspected left-sided cardiac obstructions.

Severe left-sided cardiac obstructions are associated with high morbidity and mortality if not detected in time. The correct prenatal diagnosis of coarctation of the aorta (CoA) is difficult. Fetal cardiac magnetic resonance imaging (CMR) may improve the prenatal diagnosis of complex congenital heart defects. Flow measurements in the ascending aorta could aid in predicting postnatal CoA, but its accurate visualization is challenging. To compare the flow in the descending aorta (DAo) and umbilical vein (UV) in fetuses with suspected left-sided cardiac obstructions with and without the need for postnatal intervention and healthy controls by fetal phase-contrast CMR flow. A second objective was to determine if adding fetal CMR to echocardiography (echo) improves the fetal CoA diagnosis. Prospective fetal CMR phase-contrast flow in the DAo and UV and echo studies were conducted between 2017 and 2022. A total of 46 fetuses with suspected left-sided cardiac obstructions [11 hypoplastic left heart syndrome (HLHS), five critical aortic stenosis (cAS), and 30 CoA] and five controls were included. Neonatal interventions for left-sided cardiac obstructions (n = 23) or comfort care (n = 1 with HLHS) were pursued in all 16 fetuses with suspected HLHS or cAS and in eight (27%) fetuses with true CoA. DAo or UV flow was not different in fetuses with and without need of intervention. However, DAo and UV flows were lower in fetuses with either retrograde isthmic systolic flow [DAo flow 253 (72) vs. 261 (97) ml/kg/min, p = 0.035; UV flow 113 (75) vs. 161 (81) ml/kg/min, p = 0.04] or with suspected CoA and restrictive atrial septum [DAo flow 200 (71) vs. 268 (94) ml/kg/min, p = 0.04; UV flow 89 vs. 159 (76) ml/kg/min, p = 0.04] as well as in those without these changes. Adding fetal CMR to fetal echo predictors for postnatal CoA did not improve the diagnosis of CoA. Fetal CMR-derived DAo and UV flow measurements do not improve the prenatal diagnosis of left-sided cardiac obstructions, but they could be important in identifying fetuses with a more severe decrease in blood flow across the left side of the heart. The physiological explanation may be a markedly decreased left ventricular cardiac output with subsequent retrograde systolic isthmic flow and decreased total DAo flow.

Comparison of induction-to-expulsion interval during second-trimester medication abortion in pregnancies with anencephaly and other congenital anomalies compared to those without anomalies: A retrospective cohort study

To investigate whether induction to expulsion interval during second-trimester medication abortion in pregnancies complicated by anencephaly or other fetal anomalies is prolonged compared to pregnancies without fetal anomalies STUDY DESIGN: This was a retrospective cohort study of women who had second-trimester medication abortion at St. Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia). We assigned subjects to one of three groups based on fetal diagnosis: 1) anencephaly group 2) other congenital anomaly group 3) no anomaly group. Data were collected by reviewing patients' charts. We used SPSS version 23 to analyze the data. Simple descriptive analysis and Chi-squared test were performed as appropriate. A total of 303 women had second trimester medication at 14-28 weeks, of which 58 had anencephaly, 19 had congenital anomalies other than anencephaly, and the remaining 226 had no fetal anomalies. There was no difference in induction to expulsion interval among the groups. The mean induction to expulsion interval was 18.4 hours in the anencephaly group vs, 19.4 hours in the other congenital anomaly group vs. 19.2 hours in those without anomaly (p-value=0.924). The 24-hours non-expulsion rate was also comparable among the groups, with 5.25% rate of non-expulsion in the anencephaly group vs 15.8% in the other congenital anomaly group vs 11.15 % in the no anomaly group, (p-value=0.594). In multivariable regression analysis after controlling for parity, the 24-hour non-expulsion rate was not significantly different. In this study, pregnancies undergoing second-trimester medication abortion for fetal anomalies had comparable induction to expulsion interval and 24-hour expulsion rates compared to those who had the same procedure for other or no anomalies. Second-trimester medication abortion procedure length in pregnancies complicated by anencephaly is similar to those pregnancies without anomalies. All data generated or analyzed during this study are included in this published article.

Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Waardenburg syndrome type 4C due to heterozygous deletion of SOX10 gene

To explore the genetic basis for a Chinese pedigree featuring congenital profound syndromic deafness and chronic constipation, and provide prenatal diagnosis for a high-risk fetus. Whole-exome sequencing was carried out to analyze the sequences of genes associated with hereditary deafness, and multiplex ligation-dependent probe amplification (MLPA) was used to verify the candidate variant in the proband's parents and the fetus. The proband was found to have harbored a heterozygous deletion of SOX10, a pathogenic gene associated with Waardenburg syndrome type 4C (WS4C). The same deletion was found in her mother (with profound syndromic deafness and chronic constipation) and the fetus, but not in her father with normal hearing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the SOX10 gene deletion was predicted to be a pathogenic variant (PVS1+PM2_Supporting+PP1+PP4). The pedigree was diagnosed with WS4C, which has conformed to an autosomal dominant inheritance. Deletion of the entire SOX10 gene, as a loss-of-function variant, probably underlay its pathogenesis. Above finding has facilitated genetic counseling and prenatal diagnosis for this family.

Abstract 13374: The Intersection of Prenatal Clinical and Demographic Factors in Predicting Fetal Brain Volume and Neurodevelopmental Outcome in Single Ventricle CHD

Background: Fetuses with single ventricle (SV) CHD have small total brain volumes (TBV) which has been linked to neurodevelopmental impairment (NDI). Evidence suggests a prenatal origin of NDI for CHD. Our primary aim was to use machine learning methods to identify prenatal variables that predict fetal brain growth and in turn early NDI. Methods: This is a multi-center prospective cohort study of maternal-infant dyads with a fetal diagnosis of SV who underwent fetal brain MRI and in-depth prenatal clinical and sociodemographic data collection (self reported race/ethnicity, income, education, area deprivation index, maternal health, genetics, placental health). Infants had ND testing at 12-30 months with Bayley Scales of Infant and Toddler Development. Machine learning models used recursive partitioning to predict 1) gestational-age (GA) and sex-adjusted fetal TBV and 2) ND outcome while including fetal TBV in the models. Results: A total of 67 maternal-infant dyads were enrolled with a mean GA of 33.4 weeks (SD=3.4) at fetal MRI and male predominance (57%); 48 infants had follow-up at median age of 23.5 months (SD=6.3). Key predictors of fetal brain volume were race/ethnicity, maternal age, and cardiac anatomy (Figure 1A). For NDI, fetal brain volume was the strongest predictor of motor outcomes but was not associated with other domains (Figure 1D). Cardiac anatomy was the strongest predictor of cognitive outcome (Figure 1B), while race/ethnicity was the strongest predictor of language (Figure 1C). Cardiac anatomy, maternal age, and cerebral and placental hemodynamics (e.g., middle cerebral or umbilical artery pulsatility) each predicted multiple domains of neurodevelopment. Conclusions: In regression tree modeling, sociodemographic variables are the strongest predictors of fetal TBV, which in turn predicts motor outcome. Prenatal factors predicting NDI across all domains span sociodemographic, cardiac, and placental characteristics.

Family Counseling after the Diagnosis of Congenital Heart Disease in the Fetus: Scoping Review.

Congenital heart disease (CHD) is the leading cause of death from malformations in the first year of life and carries a significant burden to the family when the diagnosis is made in the prenatal period. We recognize the significance of family counseling following a fetal CHD diagnosis. However, we have observed that most research focuses on assessing the emotional state of family members rather than examining the counseling process itself. The objective of this study was to identify and summarize the findings in the literature on family counseling in cases of diagnosis of CHD during pregnancy, demonstrating gaps and suggesting future research on this topic. Eight databases were searched to review the literature on family counseling in cases of CHD diagnosis during pregnancy. A systematic search was conducted from September to October 2022. The descriptors were "congenital heart disease", "fetal heart", and "family counseling". The inclusion criteria were studies on counseling family members who received a diagnosis of CHD in the fetus (family counseling was defined as any health professional who advises mothers and fathers on the diagnosis of CHD during the gestational period), how the news is expressed to family members (including an explanation of CHD and questions about management and prognosis), empirical and qualitative studies, quantitative studies, no publication deadline, and any language. Out of the initial search of 3719 reports, 21 articles were included. Most were cross-sectional (11) and qualitative (9) studies, and all were from developed countries. The findings in the literature address the difficulties in effectively conducting family counseling, the strengths of family counseling to be effective, opportunities to generate effective counseling, and the main challenges in family counseling.

Prenatal Evaluation of a Fetal Cystic Hygroma: An Unexpected Finding of a De Novo Fetal BRCA1 Deletion Case Report

This case presents a novel occurrence of a de novo BRCA1 gene deletion in a fetus with a cystic hygroma. Chorionic villus sampling (CVS) was performed for chromosome G-banding analysis, demonstrating a normal karyotype: 46, XX. Chromosome microarray analysis performed as a reflex test revealed an 80 kb deletion on 17q21.31, encompassing the BRCA1 gene. Follow-up FISH analysis performed on parental blood samples yielded negative results, confirming that the deletion was de novo in the fetus. Subsequent anatomic ultrasound evaluation showed no identifiable structural defects, and it was concluded that the microdeletion was unlikely to be the cause of the cystic hygroma. Regardless, it will be imperative that the patient’s daughter be appropriately counseled regarding the implications of carrying a BRCA1 deletion and the need for heightened surveillance in adulthood. As BRCA1 genetic testing is traditionally performed on adult patients with informed consent, this case report highlights the need for ongoing conversations and research in the management of incidental fetal diagnosis discovered during routine prenatal testing, as well as the care and counseling of these patients and their families.