Fetal Screening Research Articles

Abstract 4122486: Multicenter Study of Primary Fetal Cardiomyopathy: Clinical Outcomes And Genetic Etiologies, A Fetal Heart Society Research Collaborative Study

Background: Fetal cardiomyopathy (FCM) affects 8 per 100,000 live births, often with unknown etiology. Progress in fetal cardiac screening, genetic testing and management may have impacted historically poor outcomes. Aims: We sought to investigate genetic associations and clinical outcomes of FCM in the current era. Methods: This was a retrospective Fetal Heart Society Research Collaborative cohort study of FCM cases diagnosed from January 2017-December 2021 in 39 centers. Cases of fetal myocardial disease attributable to maternal diabetes, structural heart disease, arrhythmia or extra-cardiac conditions were excluded. Data including outcomes to 1 year after birth were collected. Significance of genetic testing results and FCM subtype were classified by each center. Results: There were 138 FCM cases diagnosed at a median gestational age of 27 +4 weeks (range 13-39 weeks). Suspected fetal heart disease (41%, 56/138) was the most common referral indication. There was a known family history of CM in 19% (26/138). FCM phenotypes included 38% (52/138) dilated, 24% (33/138) hypertrophic, 17% (24/138) non-compacted, 10% (14/138) mixed, 5% (7/138) restrictive, 3% (4/138) ventricular aneurysm, 3% (4/138) unspecified. Hydrops was present at diagnosis in 15% (20/138) and by delivery or at fetal demise in 26% (36/138). Of 128 continued pregnancies, 7% (9/128) had a fetal demise, 92% (118/128) a live birth and one was lost to follow-up. Among live births, 10% (12/118) received only palliative care. Of 106 actively treated, 75% (80/106) survived to 1 year; 7% (7/106) required ECMO, and 22% (23/106) were listed for transplant with 18 of these successfully transplanted. Of the cohort, a total of 80% (110/138) had genetic testing (including 30 with invasive prenatal testing), with 38% (52/138) having a confirmed genetic etiology and 28% (38/138) with a variant of uncertain significance (VUS) (Figure 1). Transplant-free survival to 1 year was similar for those with and without a genetic diagnosis (40%,21/52 vs 47%,40/86, p=0.48). Conclusion: Outcomes remain poor in FCM, with <50% 1-year survival overall. Confirmed genetic etiologies are now identified in nearly 40%, highlighting the importance of genetic testing.

Methodology Used in Studies Aimed at Measuring Fetal Soft Tissues by 2D Ultrasound for the Screening of Large for Gestational Age Fetuses: A Systematic Review.

Management of suspected large for gestational age (LGA) fetuses remains unclear because ultrasound-estimated fetal weight (EFW) is not accurate. This was a systematic review of observational studies on fetal soft tissues measurements used alone or in combination to create a new EFW formula, to improve the screening for LGA fetuses. Studies were scored using a predefined set of independently agreed methodological criteria and an overall quality score was assigned for study design, statistical analysis, and reporting methods. There is a need to standardize methodologies for soft fetal tissue measurements. We propose a set of suggestions for this purpose.

Evaluation of the clinical utility of NIPT-plus and analysis of adverse pregnancy outcomes.

To evaluate the performance of NIPT-plus in detecting fetal aneuploidies and CNVs and analyze the factors influencing adverse pregnancy outcomes. The retrospectively analyzed 8726 pregnant women who underwent NIPT-plus for fetal screening were classified into low- (who tested voluntarily) and high-risk (women with advanced age, abnormal ultrasound, abnormal serological screening, or a combination of indications) groups. Basic maternal information, prenatal findings, and pregnancy outcomes were recorded. NIPT-plus performance was assessed for various chromosomal abnormalities and the association between the fetal fraction and adverse pregnancy outcomes. Thirty-six (0.4%) patients had failed tests; 144 (1.65%) positive cases were detected, of which, 107 (74.31%) opted for invasive testing, and 51 were verified as true positives. The total positive predictive value was 45.45% and 48.65% in the low- and high-risk groups, respectively, and the difference was not significant. Among the subsequent cases with abnormal ultrasound monitoring, two false-negative cases were identified, and pathogenic CNV diagnosis was confirmed through amniocentesis, resulting in pregnancy termination. Fetal fraction was not associated with an increased adverse pregnancy outcome risk; however, ethnic differences may affect pregnancy outcomes. NIPT-plus technology use is no longer restricted to high-risk pregnant women, and it may produce false-positive results. The stakeholders should be aware of this limitation. The uncertainties and potential risks of the test results should be explained to the test takers to enable informed decision making and to minimize unnecessary anxiety and concerns. Ethnicity may influence adverse pregnancy outcomes in local multiracial settings.

Factors affecting the accuracy of fetal cardiac ultrasound screening in the first trimester of pregnancy.

Most studies on the performance of first-trimester cardiac screening have concentrated on comparing the detection rate between different protocols and not on the actual reason for false-negative results. Herein, we report the performance of first-trimester congenital heart disease (CHD) screening and factors that may affect the detection rate of CHDs. This retrospective observational study included patients who underwent first-trimester screening and subsequently gave birth at our facility. We analyzed the performance of first-trimester screening for CHD and major CHD (CHD requiring cardiac surgery or interventional catheterization within 12months of birth). Of the 6614 fetuses included, 53 had CHD and 35 had major CHD. For the prenatal diagnosis of CHD, the detection rate, specificity, positive predictive value, negative predictive value, and first-trimester detection rate for CHD were 64.1%, 99.9%, 94.4%, 99.7%, and 82.9%, respectively; the respective values for major CHD were 85.7%, 99.96%, 93.75%, 99.92%, and 85.7%. The detection rate was not significantly different when classified by crown-rump length or number of fetuses. A weak correlation was observed between low detection rate of major CHD and lower maternal body mass index (BMI) (correlation ratio: 0.17). The detection rate was significantly higher when the fetus was scanned with its spine at the 5-7 o'clock position (posterior spine) than at other positions (odds ratio: 3.82, 95% confidence interval: 1.16-12.5, p = 0.02). Posterior spine contributes to an improved diagnostic rate in first-trimester CHD screening. In addition, sonographers must recognize that low maternal BMI is a risk factor of false-negative results.

Antenatal anti-D prophylaxis and D antigen negativity in pregnant women of the UAE: a cross-sectional analysis from the Mutaba’ah Study

ObjectiveThis study aimed to determine the prevalence of the negative D antigen phenotype, adherence to routine antenatal anti-D immunoglobulin prophylaxis (RAADP) administration and D antigen sensitisation among pregnant women in...

Single-exon fetal RHD genotyping: a 31-month follow up in the obstetric population of Western Sweden.

The Rh blood group system is highly complex, polymorphic, and immunogenic. The presence of RHD gene variants in RhD negative pregnant women is a challenge in fetal RHD genotyping as it may influence the antenatal management of anti-D prophylaxis. The aim of this study was to determine the efficiency of a non-invasive single-exon approach in the obstetric population of Western Sweden in a 31-month follow up. The frequency and type of maternal RHD variants were explored and the relation to the ethnicity was elucidated. Discrepant results between fetal RHD genotyping and serological blood group typing of newborns were investigated and clarified. RHD exon 4 was analysed with quantitative real-time PCR technique in a total of 6,948 blood samples from RhD negative women in early pregnancy. All cases with suspected maternal RHD gene and discrepant results observed in newborn samples, were further investigated using both serological and molecular technologies. A total of 43 samples (0.6%) had inconclusive fetal genotyping result due the presence of a maternal RHD gene. These findings were in most cases (>66%) observed in pregnant women of non-European ancestry. Additionally, two novel RHD alleles were found. Seven discrepant results between fetal RHD genotype and serological RhD type of the newborns, were shown to be related to D antigen variants in newborns. Assay sensitivity was 99.95%, specificity 100%, and accuracy 99.97%. The single-exon approach for fetal RHD screening early in pregnancy is an appropriate choice in the population of Western Sweden, with a very low frequency of inconclusive results caused by the presence of maternal RHD gene variants. Due to the high sensitivity, specificity, and accuracy of the test, serological typing of neonates born to RhD negative women has no longer been performed at our laboratory since June 2023.

Comprehensive evaluation of fetal renal ultrasound parameters for fetal growth restriction

ObjectiveThis study aims to investigate variances in renal ultrasound parameters between fetuses experiencing fetal growth restriction (FGR) and those with normal intrauterine development, with the intent to offer actionable insights for clinical management. MethodForty-five pregnant women diagnosed with FGR between 28 and 36 weeks of gestation, who underwent examination at Wenzhou People's Hospital from September 2021 to June 2023, constituted the FGR group. Concurrently, 65 pregnant women with normal intrauterine development at matching gestational weeks formed the control group. Renal ultrasound parameters, encompassing renal artery peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), resistive indices (S/D, PI, RI), ratios of renal volume to gestational age (RV/WEEK) and estimated fetal weight (RV/EFW), vascular indices (VI, FI, VFI), were compared between the two groups. All parameters represented the mean values of bilateral kidneys. ResultIn the FGR group, fetal renal artery PSV (37.71 ± 9.93 cm/s), EDV (6.19 ± 1.50 cm/s), TAMX (15.10 ± 3.83 cm/s), RV/WEEK (0.45 ± 0.12), RV/EFW (7.53 ± 3.24), VI (22.19 ± 15.00), and VFI (5.53 ± 3.63) were significantly lower compared to the control group (PSV: 47.11 ± 11.24 cm/s, EDV: 7.13 ± 2.00 cm/s, TAMX: 17.85 ± 3.85 cm/s, RV/WEEK: 0.66 ± 0.19, RV/EFW:9.20 ± 3.17, VI: 28.67 ± 14.72, VFI: 7.40 ± 3.68). Conversely, fetal renal artery resistive indices (S/D: 9.09 ± 2.58, PI: 2.71 ± 0.56, RI: 0.92 ± 0.04) in the FGR group were notably higher than those in the control group (S/D: 6.22 ± 1.93, PI: 2.20 ± 0.73, RI: 0.87 ± 0.04), with statistical significance (P < 0.05). No significant difference was found in renal FI between the FGR group (26.78 ± 6.59) and the control group (26.89 ± 5.82) (P > 0.05). Receiver operating characteristic (ROC) curve analysis revealed higher diagnostic efficacy for RV/WEEK and RI among individual indicators, while combined parameter application yielded the highest diagnostic efficiency. ConclusionUtilizing a comprehensive evaluation of fetal kidney ultrasound parameters with multiple indices facilitates early screening and diagnosis of FGR fetuses, thereby aiding clinical decision-making and enhancing newborn birth outcomes.

The tip of the reproductive screening iceberg: ‘Every mother and every fetus matters’

Introduction: This commentary expands on the routine pregnancy screening recommended during pregnancy, with genomic diagnosis and treatment following a positive fetal screening test indicating possible morbidity. Materials and Methods: Evidenced-based review article. Results/Discussion: An evidenced-based tool is identified for preconception risk assessment for maternal education; clinical service prioritization is promoted allowing for the ethnic and effective care for reproductive and pediatric care services; tertiary fetal diagnostic and treatment options are summarized; fetal therapy, as a quaternary service, is reviewed; human resource training is discussed. Fiscal considerations and barriers for fetal genomic and congenital malformation treatment are discussed. Conclusion: Prioritized healthcare service, preconception risk estimate counselling, genomic diagnosis, and fetal therapy for congenital malformations can reduce the neonatal and childhood morbidity but there may be fiscal and access to care barriers for many families.

An effective ultrasound fetal palate screening software based on the “sequential sector scan through the oral fissure” and three-dimensional ultrasound

BackgroundOrofacial clefts are one of the most common congenital malformations of the fetal face and ultrasound is mainly responsible for its diagnosis. It is difficult to view the fetal palate, so there is currently no unified standard for fetal palate screening, and the diagnosis of cleft palate is not included in the relevant prenatal ultrasound screening guidelines. Many prenatal diagnoses for cleft palate are missed due to the lack of effective screening methods. Therefore, it is imperative to increase the display rate of the fetal palate, which would improve the detection rate and diagnostic accuracy for cleft palate. We aim to introduce a fetal palate screening software based on the “sequential sector scan though the oral fissure”, an effective method for fetal palate screening which was verified by our follow up results and three-dimensional ultrasound and to evaluate its feasibility and clinical practicability.MethodsA software was designed and programmed based on “sequential sector scan through the oral fissure” and three-dimensional ultrasound. The three-dimensional ultrasound volume data of the fetal face were imported into the software. Then, the median sagittal plane was taken as the reference interface, the anterior upper margin of the mandibular alveolar bone was selected as the fulcrum, the interval angles, and the number of layers of the sector scan were set, after which the automatic scan was performed. Thus, the sector scan sequential planes of the mandibular alveolar bone, pharynx, soft palate, hard palate, and maxillary alveolar bone were obtained in sequence to display and evaluate the palate. In addition, the feasibility and accuracy of the software in fetal palate displaying and screening was evaluated by actual clinical cases.ResultsFull views of the normal fetal palates and the defective parts of the cleft palates were displayed, and relatively clear sequential tomographic images and continuous dynamic videos were formed after the three-dimensional volume data of 10 normal fetal palates and 10 cleft palates were imported into the software.ConclusionsThe software can display fetal palates more directly which might allow for a new method of fetal palate screening and cleft palate diagnosis.

Mainstreaming genetics into Italian prenatal care: exploring the future implementation of non-invasive prenatal testing (NIPT) in the Italian National Healthcare System using stakeholder interviews

IntroductionNon-invasive prenatal testing (NIPT) has revolutionised the way prenatal testing is performed globally. Italy is one of the European countries considering incorporating NIPT nationwide into the publicly funded healthcare system....

Predictive capacity of fetal pancreatic circumference for gestational diabetes mellitus.

To assess the capacity of fetal pancreatic size, before standard blood glucose testing for screening and diagnosis, to predict maternal gestational diabetes mellitus (GDM). This was a retrospective cohort study of low-risk pregnant women recruited during routine second-trimester fetal anatomical screening at 20-25 weeks' gestation at two ultrasound units in Israel between 2017 and 2020. The predictive performance of fetal pancreatic circumference ≥ 80th and ≥ 90th centiles and glucose challenge test (GCT) was examined for the outcome of GDM. The independent-samples t-test was used to compare mean pancreatic circumference centile between pregnancies with GDM and those without GDM. Diagnostic performance was evaluated with 2 × 2 contingency tables and receiver-operating-characteristics (ROC) curves. Overall, 195 women were selected for statistical analysis. Twenty-four (12.3%) women were diagnosed subsequently with GDM. The mean ± SD fetal pancreatic circumference centile was significantly higher in the GDM group compared with the non-GDM group (82.4 ± 14.6 vs 62.8 ± 27.6; P < 0.001). The pancreatic circumference centile was correlated positively with the estimated fetal weight centile (Pearson's coefficient, 0.243; P = 0.001). The 80th centile cut-off for pancreatic circumference had the highest sensitivity (70.8%) and positive predictive value (23.3%) for future maternal GDM, with the best trade-off between sensitivity and specificity achieved at the 75th centile cut-off (sensitivity, 79%; specificity, 60%). The GCT had better specificity (90.2%) and negative predictive value (97.9%) compared with both cut-offs in pancreatic circumference. The area under the ROC curve was higher for pancreatic circumference compared with GCT (0.71 vs 0.64) and only the former was statistically significant (P = 0.001). Fetal pancreatic circumference has a higher positive predictive capacity compared with GCT. Measuring pancreatic circumference can identify pregnancies at high risk for maternal GDM, thereby promoting earlier diagnosis and treatment, decreasing the time period during which the fetus is exposed to high maternal glucose levels and improving infant outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perspectives of pregnant women on broadening the scope of noninvasive prenatal testing from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes: Aqualitative study.

To explore the perspectives of pregnant women on broadening the scope of noninvasive prenatal testing (NIPT) from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes. Four online focus groups (n=23 participants) and 14 individual semi-structured interviews were conducted. Participants included pregnant women with and without a history of adverse pregnancy outcomes. Both women at low and high risk of adverse pregnancy outcomes had a positive attitude towards using NIPT to predict adverse pregnancy outcomes. Perceived benefits included the possibility to potentially improve maternal and foetal outcomes by taking risk-reducing measures and/or intensified monitoring during pregnancy and the ability to mentally prepare for the potential adverse outcome. Perceived concerns included anxiety and stress caused by a high-risk test result, a false sense of control over pregnancy, and potential false reassurance. Additionally, women reasoned that broadening the scope of NIPT could increase the complexity of prenatal screening and raised concerns on the combined screening aims in one test (prediction of adverse pregnancy outcomes to improve foetal and maternal health vs. screening for foetal aneuploidies to increase reproductive autonomy). On a societal level, considerations on the risk of medicalising pregnancy and overall pressure to opt for NIPT were mentioned. In general, pregnant women have a positive attitude towards broadening the scope of NIPT to the prediction of pregnancy outcomes, although some concerns are acknowledged.

Infertility treatments and cyanotic congenital heart defects among livebirths in the USA: findings from a contemporary cohort.

Is there an elevated risk of cyanotic congenital heart defects (CCHD) among livebirths following infertility treatments? In this population-based study of single livebirths, infertility treatment (either ART or non-ART) was associated with a higher prevalence of CCHD among livebirths. The use of infertility treatment has been on the rise over the past few decades. However, there are limited studies assessing the risk of major cardiac defects following infertility treatments. A retrospective cohort study of livebirth data from the National Vital Statistics System (NVSS) was conducted, comprising of 9.6 million singleton livebirths among first-time mothers aged 15-49 years from 2016 to 2022. Information on infertility treatment use and CCHD was obtained from the health and medical information section of birth certificates, which was completed by healthcare staff after reviewing medical records. Logistic regression models were used to estimate odds ratios (OR) and 95% CI. Entropy balancing weighting analysis and probabilistic bias analysis were also performed. The proportion of births following infertility treatment increased from 1.9% (27116) to 3.1% (43510) during the study period. Overall, there were 5287 cases of CCHD resulting in a prevalence of 0.6 per 1000 livebirths. The prevalence was 1.2 per 1000 live births among infertility treatment users (ART: 1.1 per 1000 livebirths; non-ART: 1.3 per 1000 livebirths) while that for naturally conceived births was 0.5 per 1000 livebirths. Compared to naturally conceived births, the use of any infertility treatment (OR: 2.06, 95% CI: 1.82-2.33), either ART (OR: 2.02, 95% CI: 1.73-2.36) or other infertility treatments (OR: 2.12, 95% CI: 1.74-2.33), was associated with higher odds of CCHD after adjusting for maternal and paternal age, race and ethnicity, and education, as well as maternal nativity, marital status, source of payment, smoking status, and pre-pregnancy measures of BMI, hypertension and diabetes. This association did not differ by the type of infertility treatment (ART versus other infertility treatments) (OR: 1.04, 95% CI: 0.82-1.33, P = 0.712), and was robust to the presence of exposure and outcome misclassification bias and residual confounding. The findings are only limited to livebirths. We did not have the capacity to examine termination data, but differential termination by mode of conception has not been supported by previous studies designed to consider it. Infertility treatment use was self-reported, leading to the potential for selection bias and misclassification for infertility treatment and CCHD. However, the association persisted when systematic bias as well as exposure and outcome misclassification bias were accounted for in the analyses. Information on the underlying etiology of infertility relating to either maternal, paternal, or both factors, data on specific types of ART and other infertility treatments, as well as information on subtypes of CCHD, were all not available. In light of the increasing trend in the use of infertility treatment in the USA, and elsewhere, the finding of the current study holds significant importance for the clinical and public health of reproductive-aged individuals. The data show that the use of infertility treatment may expose offspring to elevated odds of severe congenital heart defects such as CCHD studied here. These findings cannot be interpreted causally. While our findings can assist in preconception counseling and prenatal care for pregnancies conceived by either ART or other infertility treatments, they also support some current recommendations that pregnancies resulting from infertility treatments undergo fetal echocardiography screening. No funding was sought for the study. The authors declare that they have no conflict of interest. N/A.

Which neonates should have a pre-operative echocardiography? Findings from a national survey and a retrospective tertiary single-centre analysis in the United Kingdom.

The detection of congenital heart disease (CHD) before neonatal surgery is crucial for anaesthetic and perioperative management. There are no established criteria for pre-operative echocardiography in neonates. We aimed to survey current practice in the United Kingdom and evaluate the reliability of antenatal screening and postnatal clinical assessment in detecting CHD before surgery. A 9-point questionnaire was sent to all paediatric surgical centres in the United Kingdom to assess their practice. Subsequently, a single-centre retrospective review of all neonatal surgery over 5years (2015-2020) was conducted in our tertiary paediatric/neonatal hospital. Data included pre-operative clinical assessment, performance of chest radiograph and echocardiography. Indications for echocardiography were categorised and assessed using sensitivity, specificity, positive predictive value and negative predictive value. All 26 paediatric surgical centres responded to our survey. 23/26 (88.5%) did not have established criteria or guidelines for pre-operative echocardiography. There was a large variation in which surgical conditions required a pre-operative scan and whether a normal clinical examination was considered sufficient to not require one. For the retrospective review, 454 patients were identified. There were 40 cases with CHDs (8.8%), 13 were classed as major or moderate. Indications for echocardiography were categorised into abnormal foetal cardiac screening, medical/surgical conditions associated with CHD and an abnormal cardiorespiratory examination. Sensitivity, specificity, positive predictive value and negative predictive value for major and moderate CHD were 46%, 99%, 67%, 98% for abnormal foetal screening, 46%, 97%, 35%, 98% for associated medical conditions, 62%, 66%, 6%, 98% for associated surgical conditions, and 100%, 66%, 9%, 100% for abnormal clinical examination. The use of pre-operative echocardiography in neonates is not standardised across the UK. The results from our cohort demonstrate that foetal echocardiography is not sufficient to capture all major and moderate CHDs, but the absence of abnormal clinical examination is highly reliable in ruling out them out. Specifying a list of medical/surgical of conditions associated with CHD warranting pre-operative echocardiography may improve yield, but this depends on the availability of resources and expertise.

P-769 Congenital heart defects in children born after assisted reproductive technology: A large cohort study from the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS)

Abstract Study question Are children conceived after assisted reproductive technology (ART) more likely to be born with congenital heart defects (CHDs) than those born after spontaneous conception (SC)? Summary answer Major CHDs and severe CHDs are associated with ART, with a higher risk in both ART-conceived singletons and multiples compared to singletons from SC. What is known already Children born after ART have higher risk of birth defects compared to children born after SC. Among these defects, CHDs hold the highest prevalence, accounting for about 50% of all major birth defects and affecting approximately 1-2% of children in the general population. Several cohort studies and systematic reviews, among these a recent review including 41 studies and in total 25,856 ART children, shows increased risk of CHDs in children born after ART. However, conflicting findings have been reported for specific CHDs. Study design, size, duration This Nordic registry-based cohort study included 7,747,637 liveborn children, with 171,735 conceived after ART. All liveborn children (singletons and multiples) in Denmark (1994–2014), Finland (1990–2014), Norway (1984–2015), and Sweden (1987–2015) were included. National data from ART registries, medical birth registries, patient registries, cause of death registries, and population registries were cross-linked. Participants/materials, setting, methods The International Classification of Diseases (ICD) versions 8, 9, 10 were used for selection of CHDs. Major and severe CHDs were defined according to European Concerted Action on Congenital Anomalies and Twins (EUROCAT). Outcomes were major CHDs, severe CHDs, six hierarchical CHD lesion groups, and ten selected major CHDs. CHD diagnoses were considered prenatally or within the first year of life in Denmark, Finland, Sweden, and prenatally or at birth in Norway. Main results and the role of chance Major CHDs occurred among 1.84% (n = 3159) children born after ART and among 1.15% (n = 86,824) children born after SC, with adjusted odds ratio (AOR) 1.36; 95% CI 1.31–1.41. Risk was highest in multiples, regardless of conception method. Severe CHDs were detected in 0.35% (n = 594) children born after ART and in 0.26% (n = 19,375) children born after SC; AOR 1.30; 95% CI 1.20–1.42. When analysing the risk of CHD for the specific groups of CHDs by the hierarchical classification, children born after ART had higher risk of CHDs than children born after SC for five of the six lesion groups: conotruncal defects, non-conotruncal defects, ventricular septal defect, atrial septal defects, and other CHDs. ART was further associated with an elevated risk in four of ten selected major CHDs. Major CHDs occurred among 1.62% (n = 2059) singletons born after ART and among 1.11% (n = 18,539) singletons born after SC; AOR 1.19; 1.14–1.24. The prevalence of severe CHDs was 0.31% (n = 399) among singletons born after ART and 0.25% (n = 18,539) among singletons born after SC; AOR 1.20; 95% CI 1.09–1.33. In singletons born after ART, no difference was seen between ICSI and IVF or between frozen and fresh embryo transfer for major CHDs or severe CHDs. Limitations, reasons for caution A main limitation in this study is the lack of information on CHDs in miscarriages, pregnancy terminations, and stillbirths. Another limitation is that information on specific techniques used in assisted reproduction was not available from Finland. Lastly, we did not have information on causes of infertility. Wider implications of the findings CHDs, although rare, imply severe risks. Our study reveals an association between ART and major CHDs. While most CHD-affected children survive to adulthood, high morbidity and mortality rates persist in childhood and adulthood. The potential benefit of fetal echocardiography screening in ART pregnancies, beyond routine obstetric ultrasound, remains uncertain. Trial registration number ISRCTN 11780826

A review of neonatal lupus syndrome.

This review article discusses neonatal lupus syndrome (NLS), an immune-mediated disease caused by maternal antibodies. Maternal antibodies in the fetal circulation are mostly but not always protective. NLS is a disease caused by pathogenic maternal autoantibodies in the fetal circulation. The passive immunization of the fetus by NLS-causing maternal antibodies may occur in the absence of a previously known maternal systemic autoimmune rheumatic disease (SARD). Screening for NLS-related antibodies in patients with related SARD or those in whom there is a risk of NLS including first-degree relatives should occur before pregnancy. This screening is best performed as part of a collaborative relationship between obstetrics and rheumatology. Pregnancy preparations in those with SARD include transitioning to pregnancy-safe medications. The symptoms of NLS range from minor skin rashes to fetal demise from heart block. Fetal screening allows for maternal therapeutic interventions that may be beneficial, as well as the use of fetal pacemakers in the more severe cases that include cardiac NLS.

Quantitative study of the ossification centers of the body of sphenoid bone in the human fetus

The aim of the present study was to examine the growth dynamics of the two ossification centers of the body of sphenoid bone in the human fetus, based on their linear, planar and volumetric parameters. The examinations were carried out on 37 human fetuses of both sexes aged 18–30 weeks of gestation, which had been preserved in 10% neutral formalin solution. Using CT, digital image analysis software, 3D reconstruction and statistical methods, we evaluated the size of the presphenoid and postsphenoid ossification centers. The presphenoid ossification center grew proportionately in sagittal diameter, projection surface area and volume, and logarithmically in transverse diameter. The postsphenoid ossification center increased logarithmically in sagittal diameter, transverse diameter and projection surface area, while its volumetric growth followed proportionately. The numerical findings of the presphenoid and postsphenoid ossification centers may be considered age-specific reference values of potential relevance in monitoring the normal fetal growth and screening for congenital disorders in the fetus. The obtained results may contribute to a better understanding of the growing fetal skeleton, bringing new numerical information regarding its diagnosis and development.

Cross-modal interaction and multi-source visual fusion for video generation in fetal cardiac screening

To address the limitation of preserving data for dynamic visualization in fetal ultrasound screening, a novel framework is proposed to facilitate the generation of fetal four-chamber echocardiogram videos, incorporating multi-source visual fusion and understanding. The framework utilizes an effective spectrogram-ultrasound synchronizer to align the ultrasound images with time, ensuring the generated video matches the actual heartbeat rhythm. It further employs effective frame interpolation techniques to synthesize a video by incorporating a nonlinear bidirectional motion prediction. By integrating a Transformer model for the autoregressive generation of visual semantic sequence, the proposed framework demonstrates its capability to generate high-resolution frames. Experimental outcomes show the Clip-Similarity of 96.23% and DINOv2-Similarity of 99.77%. Furthermore, a multimodal dataset of fetal echocardiogram examinations has been constructed.

Interaction between clinicians and artificial intelligence to detect fetal atrioventricular septal defects on ultrasound: how can we optimize collaborative performance?

Artificial intelligence (AI) has shown promise in improving the performance of fetal ultrasound screening in detecting congenital heart disease (CHD). The effect of giving AI advice to human operators has not been studied in this context. Giving additional information about AI model workings, such as confidence scores for AI predictions, may be a way of further improving performance. Our aims were to investigate whether AI advice improved overall diagnostic accuracy (using a single CHD lesion as an exemplar), and to determine what, if any, additional information given to clinicians optimized the overall performance of the clinician-AI team. An AI model was trained to classify a single fetal CHD lesion (atrioventricular septal defect (AVSD)), using a retrospective cohort of 121 130 cardiac four-chamber images extracted from 173 ultrasound scan videos (98 with normal hearts, 75 with AVSD); a ResNet50 model architecture was used. Temperature scaling of model prediction probability was performed on a validation set, and gradient-weighted class activation maps (grad-CAMs) produced. Ten clinicians (two consultant fetal cardiologists, three trainees in pediatric cardiology and five fetal cardiac sonographers) were recruited from a center of fetal cardiology to participate. Each participant was shown 2000 fetal four-chamber images in a random order (1000 normal and 1000 AVSD). The dataset comprised 500 images, each shown in four conditions: (1) image alone without AI output; (2) image with binary AI classification; (3) image with AI model confidence; and (4) image with grad-CAM image overlays. The clinicians were asked to classify each image as normal or AVSD. A total of 20 000 image classifications were recorded from 10 clinicians. The AI model alone achieved an accuracy of 0.798 (95% CI, 0.760-0.832), a sensitivity of 0.868 (95% CI, 0.834-0.902) and a specificity of 0.728 (95% CI, 0.702-0.754), and the clinicians without AI achieved an accuracy of 0.844 (95% CI, 0.834-0.854), a sensitivity of 0.827 (95% CI, 0.795-0.858) and a specificity of 0.861 (95% CI, 0.828-0.895). Showing a binary (normal or AVSD) AI model output resulted in significant improvement in accuracy to 0.865 (P < 0.001). This effect was seen in both experienced and less-experienced participants. Giving incorrect AI advice resulted in a significant deterioration in overall accuracy, from 0.761 to 0.693 (P < 0.001), which was driven by an increase in both Type-I and Type-II errors by the clinicians. This effect was worsened by showing model confidence (accuracy, 0.649; P < 0.001) or grad-CAM (accuracy, 0.644; P < 0.001). AI has the potential to improve performance when used in collaboration with clinicians, even if the model performance does not reach expert level. Giving additional information about model workings such as model confidence and class activation map image overlays did not improve overall performance, and actually worsened performance for images for which the AI model was incorrect. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cost-Effectiveness of the Prenatal Detection of Congenital Heart Diseases: A Systematic Literature Review

Background: Congenital heart disease is the most common congenital condition worldwide, with a prevalence of 80 cases per 10 000 live births. In addition to perinatal morbidity and mortality, it entails long-term consequences such as multiple surgeries, prolonged hospitalizations, lifelong cardiac follow-up, reduced quality of life, risk of heart failure, and premature mortality in adulthood. This significant health and economic burden on healthcare systems and families highlights the relevance of evaluating the cost-effectiveness of methods for early detection of this condition. Objective: To conduct a systematic literature review (SLR) to identify and analyze existing economic evaluations on prenatal detection of congenital heart diseases through ultrasound, focusing on the reported cost-effectiveness results and the methodological quality of the evaluated studies according to established criteria. Methods: An SLR of economic evaluations was conducted following PRISMA guidelines. A quantitative synthesis of key methodological components of each economic evaluation was performed. The incremental medical costs, effectiveness measures, and cost-effectiveness ratios reported in each study were compiled and compared. The methodological quality was assessed according to compliance with the 24 CHEERS criteria. Results: We found 785 articles, of which only 7 met all inclusion criteria. Most were cost-effectiveness analyses, with the most common outcome being number of cases detected. Screening with only 4-chamber views interpreted by general practitioners or cardiologists were dominant strategies compared with screening with 4-chamber plus outflow views interpreted by a general practitioner. Fetal echocardiography was most effective but most expensive. Screening with 4-chamber and outflow view, followed by referral to a specialist, were recommended as the least expensive strategy per defect detected. On average, articles met 17 of the 24 CHEERS criteria. Discussion: While recent cost-effectiveness analyses demonstrated improved methodological quality, there was a lack of homogeneity due to differences in comparators and population subgroups analyzed. Despite this heterogeneity, fetal ultrasonography screening was consistently identified as a cost-effective strategy, with its cost-effectiveness heavily influenced by the expertise of the interpreting physician. Conclusion: Most studies recommend implementing obstetric ultrasonography screening, without routine fetal echocardiography, for detecting congenital heart diseases.