Normal Fetuses Research Articles

Twin Pregnancy Coexisting with Partial Mole and Normal Fetus: A Case Report

This case report highlights the rare occurrence of a twin pregnancy coexisting with a partial mole, presenting a unique set of challenges in management and outcome. A 20-year-old woman with primary subfertility conceived twins following ovulation induction, experiencing hyperemesis gravidarum and subsequently developing severe preeclampsia. Despite efforts to control her condition, termination of the pregnancy was necessary due to maternal safety concerns. Both twins, without anomalies, succumbed to early neonatal death. Histopathological examination revealed a partial mole. The case emphasizes the importance of vigilant monitoring and individualized treatment in such complex pregnancies, with a focus on maternal well-being. Continued follow-up is crucial to detect and manage potential gestational trophoblastic disease. This report underscores the need for informed decision-making and patient-centered care in managing twin pregnancies coexisting with molar tissue.

Auricular Deformational Anomalies Detected in Human Fetal Cadavers.

The aim of the study was to investigate the incidence and diversity of deformational auricular anomalies in human fetuses based on their morphologic appearances. A total of 100 auricles from 56 formalin-fixed fetuses (32 female and 24 male), gestational ages ranging from 17 to 36 weeks, were examined. The auricles were categorized according to the morphologic deformities outlined in existing literature. Of the samples analyzed, 67% exhibited auricular deformities, while the remaining 33% showed no auricle anomalies. Among the auricles with deformities, 73% displayed a single type of deformity: Conchal crus, 22%; Stahl's ear, 13%; inverted conchal bowl, 13%; lidding ear, 12%; cup ear, 7%; and constricted ear, 6%. In addition, 27% of the auricles exhibited 2 different deformities on the same side: Conchal crus with lidding ear, 10%; conchal crus with Stahl's ear, 5%; conchal crus with the antihelix 3rd crus, 3%; constricted ear with lidding ear, 5%; constricted ear with cup ear, 2%; and constricted ear with inverted conchal bowl, 2%. The most prevalent deformity was conchal crus, whereas cup ear was the least. Among the fetuses, 10 had bilaterally normal auricles, 8 had unilaterally normal auricles, 12 exhibited the same deformity bilaterally, and 14 displayed different deformities on each side. Auricular deformational variations can vary in shape and symmetry, even in morphologically normal fetuses. Identifying these deformities can contribute to accurate diagnosis and treatment planning for such anomalies in newborns.

Stillbirth in women with Type 1 Diabetes mellitus—still a current topic

PurposeCompared to the general stillbirth rate in Germany for term deliveries of 0.12% the risk in type 1 diabetes mellitus is reported to be up to ten times higher. The reasons for this excess risk of intrauterine demise are still not fully elucidated. Risk factors named in the literature include poor glycemic control before and during pregnancy and the occurrence of ketoacidosis. Additionally there might be a diabetes related type of placental dysfunction leading to organ failure in late pregnancy. Understanding the underlying causes is mandatory to develop strategies to reduce the incidences. The Purpose of this publication is to point out the difficulties in prediction of intrauterine death in pregnant type 1 diabetes patients and thus emphasizing the necessity of constant awareness to all caregivers.MethodsWe present a case series of four cases of stillbirth that occurred in patients with type 1 diabetes mellitus at our tertiary care obstetric unit during a five-year period.ResultsIn all four presented cases the underlying cause of intrauterine demise was different and we could not find a common mechanism or risk profile. Furthermore, established monitoring tools did not become peculiar to raise awareness. We compared our cases to published data. Underlying causes of intrauterine death in type 1 diabetes are discussed in the light of the current literature.ConclusionsThe main risk factors of stillbirth in diabetic pregnancies are high maternal blood glucose levels including pre-conceptional HbA1c and diabetic ketoacidosis. Late acute placental insufficiency are associated with intrauterine death in type 1 diabetes. Despite the elevated risk of near term intrauterine demise there are currently no guidelines on how to monitor pregnancies in type 1 diabetes for fetal distress during the third trimester. Established thresholds for fetal Doppler data indicating fetal distress in normal and growth restricted fetuses may not be applicable for overgrown fetuses. Future research on how to monitor the diabetic fetus needs to be initiated.

Evaluation of fetal cardiac morphology and function by fetal heart quantification technique in the normal second and third trimesters.

The study of fetal heart is receiving increasing attention. Fetal heart quantification (Fetal HQ) technology is a new speckle tracking technology that can analyze the 24-segment morphology and function of fetal ventricles. This study aims to use Fetal HQ to assess the changes in the structure and function of the fetal heart in normal mid to late pregnancy, providing a foundation for the clinical application of fetal cardiac speckle tracking technology. The heart size, global sphericity index (GSI), left ventricular [stroke volume (SV)], cardiac output (CO), ejection fraction (EF), global longitudinal strain (GLS), fractional area change (FAC), 24-segment end-diastolic diameter (EDD), sphericity index (SI) and fractional shortening (FS) of the two ventricles of 500 normal pregnant fetuses were evaluated by Fetal HQ. The subjects were divided into 5 groups according to gestational weeks (GA), and the changes of fetal heart morphology and function were observed. P<0.05 indicated the statistically significant difference. The fetal heart rate decreased gradually with the increase of GA (P<0.05). The size parameters of the fetal heart and two ventricles gradually increased with increasing GA (P<0.05). The 24 segments EDD of both ventricles increased with increasing GA (P<0.05), while the EDD increased first and then decreased from the ventricle base to the apex. The GSI and the 24 segments SI of two ventricles were basically not significantly different among the groups (P>0.05). The EF, GLS, FAC of the left ventricle and the GLS, FAC of the right ventricle decreased with the increase of GA (P<0.05), and SV and CO increased with increasing GA (P<0.05). The 24 segments FS of the left ventricle showed a downward trend with the increase of GA and gradually increased from the base to the apex. The FS of most segments of the right ventricle decreased with the increase of the GA and increased first and then decreased from the base to the apex. The whole and segmental size parameters of fetal heart can quantitatively evaluate the growth and development of fetal heart; the GSI and segmental SI are reliable morphological indexes for evaluating fetal heart; fetal ventricular function parameters EF, FAC, GLS and segmental FS can evaluate fetal cardiac function. The Fetal HQ technique can help us to evaluate the heart growth and development of normal fetuses in the second and third trimester of pregnancy.

Efficacy of Transcerebellar to Abdominal Circumference versus Head Circumference to Abdominal Circumference Ratio in Predicting Asymmetrical Intrauterine Growth Restriction

Background: Fetal growth restriction (FGR) is when a fetus is not able to achieve its genetic growth potential. The high incidence of FGR in the general obstetric population and its low recognition together lead to increased perinatal morbidity and mortality, and its early detection is useful in deciding the frequency of antenatal surveillance and optimizing the time of delivery to improve the neonatal outcome. The transverse cerebellar diameter/abdominal circumference (TCD/AC) ratio is a gestational age-independent parameter, which may be helpful in the early detection of FGR. Objectives: To compare the accuracy of transcerebellar to AC with head circumference (HC) to AC in predicting asymmetrical FGR after 20 weeks of gestation and to determine the significance of TCD and TCD/AC relationship in predicting fetal outcome as expressed by perinatal morbidity and mortality. Study Design: A prospective observational study. Materials and Methods: This prospective observational study was conducted in the Postgraduate Department of Obstetrics and Gynaecology. A total of 300 patients were taken and divided into two groups: Group A (patients of suspected FGR clinically) and Group B (healthy women with morphologically normal fetuses) in the age group of 18–35 years. Subjects with singleton, nonanomalous pregnancy, reliable dates, favorable lie to visualize posterior fossa, and gestation of 20 weeks or more, were taken from the said age group and followed for maternal and neonatal outcome. Results: The difference in TCD/AC ratio between patients with FGR (14.8 ± standard deviation [SD]) and without FGR (13.10 ± SD) is statistically significant with a P &lt; 0.0001 with good sensitivity (93%), specificity (94%), and diagnostic accuracy (93.66%) in predicting asymmetrical FGR when compared to HC/AC ratio with sensitivity 83%, specificity 93%, and diagnostic accuracy of 89.66%. Conclusion: The TCD/AC ratio is constant throughout pregnancy and is increased in FGR compared to normal pregnancy and can be used as a screening test to diagnose FGR.

Evaluation of fetal cerebral microvascular status and its relationship with fetal growth and development using microvascular imaging technique

The study conducted retrospective analysis design, aiming to explore the use of Microvascular Imaging Technique (MVFI) to assess fetal cerebral microcirculation and analyze the relationship between Microvascular Index (MVI) and fetal growth and development. 100 pregnant women who met the criteria for fetal growth restriction (FGR) provided in the Expert Consensus on Fetal Growth Restriction (2019 Edition) and underwent routine prenatal examinations at the Obstetrics and Gynecology Department of Peking University Third Hospital from January 2021 to June 2023 were selected as the study subjects. A normal fetus with a fetal weight less than 10 % can be classified as FGR, Pregnant women with fetal umbilical artery (UA) systolic and diastolic (S/D) values ≥3 were included in the observation group, while 200 pregnant women with normal fetuses were selected as the control group during the same period. The fetuses’ change in both groups were measured using color Doppler ultrasound, including bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The cerebral microcirculation of the fetuses in both groups was evaluated using MVFI, and the MVI values were compared. The clinical characteristics of FGR fetuses with umbilical artery S/D ratio ≥ 3 were summarized, and the correlation between fetal cerebral microvascular status and fetal growth and development was analyzed using Pearson correlation analysis. The outcomes told that the BPD, HC, AC, and FL values of the fetuses in the control group were lower the other’s value (P < 0.05), and the MVI and peak systolic velocity of the middle cerebral artery (MCA-PSV) values were also lower in the control group (P < 0.05). Pearson correlation analysis revealed a positive correlation between fetal growth and development and MVI and MCA-PSV values in FGR fetuses. In conclusion, MVFI can monitor and quantitatively analyze fetal intracranial microcirculation, visualize slow blood flow in microvascular structures, and this study provides preliminary evidence of the close relationship between fetal cerebral microcirculation and intrauterine growth and development.

Fetal 24-Segment Sphericity Index and Ventricular Fractional Shortening Between 12 and 20 Weeks of Gestation.

Although the fetal sphericity index (SI) and fractional shortening (FS) of 24 transverse segments have been previously reported after the 20th gestational week, there have been no reports during the first and early second trimester. This study aimed to clarify the SI and FS of 24 transverse segments in normal fetuses before the 20th gestational week. A total of 101 normal fetuses aged between 12 and 20 gestational weeks were examined. The displacement of the ventricular endocardium during the cardiac cycle was computed using speckle-tracking software (GE Healthcare, Milwaukee, WI). We analyzed the length of 24 end-diastolic lateral segments and the end-diastolic basal (seg1-6)- middle (Seg7-15)-apical (Seg16-24) distribution from the base to the apex of each ventricle, according to the method described by DeVore et al. The SI and FS were computed for each of the 24 segments by dividing the mid-basal-apical length by the transverse size. The SI for each segment was independent of the gestational age. The SI of the right ventricle was significantly lower than that of the left ventricle for segments 1-14, suggesting that the right ventricle was more spherical than the left ventricle in the basal segment only. The FS of the right ventricle was significantly lower than that of the left ventricle in segments 1 to 2 and 13 to 24. The morphology of the ventricles before 20 weeks of gestation differs from that between 20 and 40 weeks of gestation. This difference may be related to myocardial densification or performance.

Role of Transcerebellar Diameter and Transcerebellar Diameter/Abdominal Circumference Ratio in Assessing Fetal Growth and Diagnosing Intrauterine Growth Restriction.

Background In obstetrics, accurately determining gestational age (GA) is a critical aspect of managing pregnancy and evaluating fetal growth and development. Intrauterine growth restriction (IUGR) is characterized by the failure of the fetus to reach its potential growth. Early detection of IUGR is crucial for optimal obstetric care to reduce fetal complications and neonatal morbidity and mortality. The purpose of the current research is to determine the role of transcerebellar diameter (TCD) and the TCD/abdominal circumference (AC) ratio in assessing fetal growth and diagnosing IUGR. Methods In the sample, there were 600 expectant mothers with GA exceeding 28 weeks. We measured TCD and AC and then calculated the TCD/AC ratio. We used IBM SPSS Statistics for Windows, V. 22.0 (IBM Corp., Armonk, NY), for statistical analysis. The data was subjected to statistical tests, including Pearson's correlation coefficient, coefficient of determination, and tests of validity. Results The current research demonstrates a strong linear correlation between TCD and GA. Additionally, there was no notable disparity in TCD measurements between normal and IUGR fetuses with the same GA. There was an insignificant relationship between the TCD/AC ratio and GA, with a constant TCD/AC ratio in the third trimester of pregnancy in normal fetuses. The mean TCD/AC ratio was 14.72±0.89 (mean±standard deviation), and a cut-off value of 16.5 was determined to diagnose IUGR. Conclusion TCD can serve as a reliable measure for GA estimation during the third trimester in pregnant women with uncertain last menstrual period (LMP) or no dating scan and IUGR fetuses. In diagnosing IUGR, the TCD/AC ratio has demonstrated greater sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The TCD/AC ratio is a GA-independent measure that can be used to diagnose IUGR.

Prenatal exome sequencing for morphologically normal fetus: Should we be doing it?

We aimed to investigate the yield of prenatal exome sequencing (pES) in morphologically normal fetuses. This retrospective study analyzed 254 families with morphologically normal fetuses who underwent prenatal trio exome sequencing based on parental request between September 2020 and October 2023. Overall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES. Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant conditions), while 2 families (0.8%, 2/254) were incidentally found to be couples at risk of having a future pregnancy with a recessive condition. Among the six fetuses detected with monogenic disorders, two fetuses carried a de novo variant in OPA1 and NF1, which are known to cause Optic atrophy 1 and Neurofibromatosis, respectively. One fetus was detected with a maternally inherited variant in PKD2 related to polycystic kidney disease 2 (not known to the mother until then). One fetus was detected with a maternally inherited variant in SDHB associated with Pheochromocytoma. Two fetuses carried compound heterozygous variants in NAGLU and GJB2 associated with Mucopolysaccharidosis type IIIB and Deafness, respectively. In the 2 families where parents were found to be carriers but the fetuses were unaffected, heterozygous variants in the GJB2 and SERPINB7 genes were detected in the parents, respectively, which are associated with deafness and palmoplantar keratoderma. Our research indicated that pES can provide significant critical information for families with morphologically normal fetuses. Prenatal screening with exome sequencing requires careful management and detailed pre-test and post-test genetic counseling.

Pustular Psoriasis of Pregnancy Successfully Managed with Steroid and Cyclosporine – A Case Report

Pustular psoriasis of pregnancy is a well-known dermatosis of pregnancy. Erythematous plaques with pustular rings and central erosions affecting the intertriginous regions are one of the most common presentations. It can be severe during pregnancy and may impact both the mother and the foetus if not treated. It typically disappears quickly after birth, but there is a chance of recurrence with increased severity in consecutive pregnancies. Systemic corticosteroids are the treatment of choice in generalised pustular psoriasis of pregnancy (GPPP). Cyclosporine also plays a role in the management. We present a case of GPPP in a 30-year-old woman who was treated with systemic corticosteroids and cyclosporine with an uneventful childbirth and a normal foetus.

How automated techniques ease functional assessment of the fetal heart: Applicability of two-dimensional speckle-tracking echocardiography for comprehensive analysis of global and segmental cardiac deformation using fetalHQ®.

Prenatal echocardiographic assessment of fetal cardiac function has become increasingly important. Fetal two-dimensional speckle-tracking echocardiography (2D-STE) allows the determination of global and segmental functional cardiac parameters. Prenatal diagnostics is relying increasingly on artificial intelligence, whose algorithms transform the way clinicians use ultrasound in their daily workflow. The purpose of this study was to demonstrate the feasibility of whether less experienced operators can handle and might benefit from an automated tool of 2D-STE in the clinical routine. A total of 136 unselected, normal, singleton, second- and third-trimester fetuses with normofrequent heart rates were examined by targeted ultrasound. 2D-STE was performed separately by beginner and expert semiautomatically using a GE Voluson E10 (FetalHQ®, GE Healthcare, Chicago, IL). Several fetal cardiac parameters were calculated (end-diastolic diameter [ED], sphericity index [SI], global longitudinal strain [EndoGLS], fractional shortening [FS]) and assigned to gestational age (GA). Bland-Altman plots were used to test agreement between both operators. The mean maternal age was 33 years, and the mean maternal body mass index prior to pregnancy was 24.78kg/m2. The GA ranged from 16.4 to 32.0weeks (average 22.9weeks). Averaged endoGLS value of the beginner was -18.57%±6.59 percentage points (pp) for the right and -19.58%±5.63 pp for the left ventricle, that of the expert -14.33%±4.88 pp and -16.37%±5.42 pp. With increasing GA, right ventricular endoGLS decreased slightly while the left ventricular was almost constant. The statistical analysis for endoGLS showed a Bland-Altman-Bias of -4.24 pp±8.06 pp for the right and -3.21 pp±7.11 pp for the left ventricle. The Bland-Altman-Bias of the ED in both ventricles in all analyzed segments ranged from -.49mm±1.54mm to -.10mm±1.28mm, that for FS from -.33 pp±11.82 pp to 3.91 pp±15.56 pp and that for SI from -.38±.68 to -.15±.45. Between both operators, our data indicated that 2D-STE analysis showed excellent agreement for cardiac morphometry parameters (ED and SI), and good agreement for cardiac function parameters (EndoGLS and FS). Due to its complexity, the application of fetal 2D-STE remains the domain of scientific-academic perinatal ultrasound and should be placed preferably in the hands of skilled operators. At present, from our perspective, an implementation into clinical practice "on-the-fly" cannot be recommended.

Prenatal diagnosis of a skeletal disorder characterized by rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene: Case report and literature review.

The protein kinase domain containing cytoplasmic (PKDCC) gene (OMIM#618821) is associated with bone development. Biallelic variants in the PKDCC gene can cause rhizomelic limb shortening with dysmorphic features. A fetus was found to be rhizomelic limb shortening at 16 weeks of gestation and amniocentesis was performed at 19 weeks of gestation. Genomic DNA extracted from the amniotic fluid was subjected to chromosomal microarray analysis (CMA), and Trio-total whole-exome sequencing (Trio-WES). Sanger sequencing was used to verify the candidate pathogenic variants. CMA was normal, while Trio-WES identified two compound heterozygous variants in the PKDCC gene, namely c.417_c.423delCGGCGCG insTCATGGGCTCAGTACAC(p.G140fs*35) and c.345G>A (p.W115*,379). Then the fetus was aborted and the development of its bone cells were compared with that of a normal fetus of similar gestational age by histopathological examination. Clinical findings of the fetus were shortening humerus and femur, synophrys, much hair on the side face, simian line on the right palm, etc. Histopathological examination showed that the affected fetus had increased proliferative chondrocytes, widened proliferative bands, and delayed bone mineralization. We reported a prenatal case of rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene, which emphasized the important role of Trio-WES for diagnosis of skeletal dysplasia in fetuses.

Hepatic arterial buffer response in monochorionic twins with selective fetal growth restriction.

Monochorionic twins (MC) have higher risk ofperinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus. sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses. We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was-0.16 (±0.97). Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.

Relationship between diagnosis of conus arteriosus malformation and genetic diagnosis results in fetal cardiac axis abnormalities by echocardiography during middle pregnancy.

To explore the clinical value of echocardiography in detecting fetal cardiac axis abnormalities during middle pregnancy for diagnosing conus arteriosus malformation, and to compare and analyze the genetic diagnosis results, in order to provide evidence for clinical diagnosis and intervention. Four hundred twenty-one fetuses with conus arteriosus malformation from January 2020 to October 2023 were included as the conus arteriosus malformation group, and 917 healthy fetuses (all single fetuses) matched at the same gestational age were selected as the healthy group. There was no significant difference in gestational weeks between two groups (P > 0.05). The age of pregnant women in conus arteriosus malformation group was lower compared to healthy group (P < 0.05), and the fetal cardiac axis in conus arteriosus malformation group was significantly higher compared to healthy group (P < 0.05). Among the fetuses with conus arteriosus malformation, tetralogy of Fallot (TOF), transposition of the great arteries (TGA) and double outlet right ventricle (DORV) had the highest proportions, accounting for 38.00%, 18.29% and 17.58%, respectively. Among all types of conus arteriosus malformations, atresia pulmonary valve syndrome associated with TOF, persistent truncus arteriosus and DORV exhibited higher proportions of fetal cardiac axis abnormalities, at 75.00%, 36.84% and 27.03%, respectively, while TGA and interrupted aortic arch associated with B-type interruption had lower proportions of fetal cardiac axis abnormalities, at 2.60% and 4.55%, respectively. Genetic testing was conducted on 73 cases (17.34%) of fetuses with conus arteriosus malformation in this study. Among them, fetal cardiac axis abnormalities were considered positive for genetic results due to factors such as aneuploidy, copy number abnormalities, and single-gene pathogenicity. A total of 31 cases tested positive for genetic anomalies, with a positive rate of approximately 42.47%. In the middle pregnancy, the fetal cardiac axis in cases of conus arteriosus malformation was significantly higher than in normal fetuses. Moreover, there were variations in fetal cardiac axis among different types of conus arteriosus malformations, and these differences were notably associated with genetic diagnostic results.

Increased risk of fetal left–right asymmetry disorders associated with maternal SARS-CoV-2 infection during the first trimester

Our center has observed a substantial increase in the detection rate of fetal left–right(LR) asymmetry disorders between March and May 2023. This finding has raised concerns because these pregnant women experienced the peak outbreak of SARS-CoV-2 in China during their first trimester. To explore the relationship between maternal SARS-CoV-2 infection and fetal LR asymmetry disorders. A retrospective collection of clinical and ultrasound data diagnosed as fetal LR asymmetry disorders was conducted from January 2018 to December 2023. The case–control study involved fetuses with LR asymmetry disorders and normal fetuses in a 1:1 ratio. We evaluated and compared the clinical and fetal ultrasound findings in pregnant women with SARS-CoV-2 infection and pregnant women without infection. The Student t-test was utilized to compare continuous variables, while the chi-squared test was employed for univariable analyses. The incidence rate of LR asymmetry disorders from 2018 to 2023 was as follows: 0.17‰, 0.63‰, 0.61‰, 0.57‰, 0.59‰, and 3.24‰, respectively. A total of 30 fetuses with LR asymmetry disorders and 30 normal fetuses were included. This case–control study found that SARS-CoV-2 infection (96.67% vs 3.33%, P = .026) and infection during the first trimester (96.55% vs 3.45%, P = .008) were identified as risk factors. The odds ratio values were 10.545 (95% CI 1.227, 90.662) and 13.067 (95% CI 1.467, 116.419) respectively. In cases of SARS-CoV-2 infection in the first trimester, the majority of infections (88.1%, 37/42) occurred between 5 and 6 weeks of gestation. We found that 43.7% (66/151) of fetuses with LR asymmetry disorder had associated malformations, 90.9% (60/66) exhibited cardiac malformations. SARS-CoV-2 infection during the first trimester significantly increases the risk of fetal LR asymmetry disorders, particularly when the infection occurs between 5 and 6 gestation weeks. The most common associated malformation is heart malformation.

Antenatal visualization of the caudo-thalamic groove at expert fetal neurosonography.

to describe the normal features of the caudo-thalamic groove at antenatal brain ultrasound in a group of structurally normal fetuses at third trimester and to report a small series of cases with abnormal appearance of the caudothalamic groove at antenatal brain ultrasound. This was an observational study conducted at two referral Fetal Medicine units. A non-consecutive cohort of pregnant women with a singleton non anomalous pregnancy were prospectively recruited and underwent 3D ultrasound of the fetal brain at 28-32 weeks. At offline analysis the ultrasound volumes were adjusted in the multiplanar mode according to a standardized methodology, until the caudothalamic groove was visible on the parasagittal plane. To evaluate the inter-observer agreement, two operators were independently asked to indicate if the caudothalamic groove was visible unilaterally or bilaterally on each volume. The digital archives of the two Centres were also retrospectively searched to retrieve cases with abnormal findings at the level of the caudothalamic groove at antenatal brain ultrasound which were postnatally confirmed. 180 non-consecutive cases fulfilling the inclusion criteria were prospectively included. At offline analysis of the 3D US volumes the caudo-thalamic groove was identified on the parasagittal plane by both operators at least unilaterally in 176 cases (97.8%) and bilaterally in 174 cases (96.6%). The K-coefficient for the agreement between the two independent operators in recognizing the caudo-thalamic groove was 0.89 and 0.83 on one and both hemispheres respectively. At the retrospective search of our archives 5 cases with abnormal appearance of the groove at antenatal brain ultrasound (2 haemorrhage and 3 cyst) were found. Our study has demonstrated that the caudo-thalamic groove is consistently seen among normal fetuses at third trimester submitted to multiplanar neurosonography and that abnormal findings at this level may be antenatally detected. This article is protected by copyright. All rights reserved.

Prenatal Screening and Diagnosis: Time for a Paradigm Shift.

Recent advances in genetics and imaging have ushered substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is imperative that health care providers caring for pregnant individuals should reexamine established practices in prenatal screening and diagnosis. In the past, screening for chromosomal abnormalities was based almost entirely on Down syndrome. Pregnant individuals aged > 35 years were considered at "high risk" or of "advanced maternal age" based on age alone; however, the advent of tests with high sensitivity for prenatal detection of chromosomal abnormalities should lead to abandoning that concept, at least from the perspective of chromosomal abnormalities. Given that first-trimester and second-trimester screenings will fail to detect between 5 and 20% of Down syndrome, in most situations, noninvasive testing with cell-free DNA should be the first-line screen for Down syndrome. The fact that over 99% of fetuses with Down syndrome will be detected prenatally with cell-free DNA gives other fetal chromosomal and structural abnormalities increasing prominence. Chromosomal microarray analysis (CMA) permits prenatal detection of several clinically important chromosomal aberrations that cannot be detected by karyotype and may exist in structurally normal fetuses with low-risk cell-free DNA screening. As such, CMA should be more readily conducted when invasive testing is performed, regardless of the presence of a structural abnormality. Isolated sonographic "soft markers" have no clinical significance in patients who have normal cell-free DNA screening, can cause unwarranted anxiety and a negative impact on pregnancy, and perhaps it is time to stop discussing them. Detailed first-trimester ultrasound allows early detection of several severe fetal anomalies and, therefore, in settings with adequately trained personnel and resources, should be used more frequently. This opinion traces the evolution of prenatal screening and diagnosis and advocates for a paradigm shift that aligns with recent developments in prenatal screening and diagnostic capabilities. KEY POINTS: · Noninvasive prenatal testing with cell-free DNA should be available to all pregnant individuals.. · Chromosomal microarray should be available to all pregnant individuals undergoing amniocentesis.. · Patients >35 years with low-risk screening are not at "high risk" for chromosomal abnormalities..

Exome sequencing in every pregnancy? Results of trio exome sequencing in structurally normal fetuses.

This study aimed to assess the detection rate of clinically significant results of prenatal exome sequencing (pES) in low-risk pregnancies and apparently normal fetuses in non-consanguineous couples. A retrospective analysis of pES conducted at a single center from January 2020 to September 2023 was performed. Genetic counseling was provided, and detailed medical histories were obtained. High-risk pregnancies were excluded due to major ultrasound anomalies, sonographic soft markers, abnormal maternal biochemical screening, or family history suggestive of monogenic diseases as well as cases with pathogenic and likely pathogenic (P/LP) chromosomal microarray results. Exome analysis focused on ∼2100 genes associated with Mendelian genetic disorders. Variant analysis and classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. Among 1825 pES conducted, 1020 low-risk cases revealed 28 fetuses (2.7%) with potentially clinically significant variants indicating known monogenic diseases, primarily de novo dominant variants (64%). Among these 28 cases, 9 fetuses (0.9%) had the potential for severe phenotypes, including shortened lifespan and intellectual disability, and another 12 had the potential for milder phenotypes. Seven cases were reported with variants of uncertain significance (VUS) that, according to the ACMG criteria, leaned toward LP, constituting 0.7% of the entire cohort. Termination of pregnancy was elected in 13 out of 1020 cases (1.2%) in the cohort, including 7/9 in the severe phenotypes group, 2/12 in the milder phenotype group, and 4/7 in the VUS group. The 2.7% detection rate highlights the significant contribution of pES in low-risk pregnancies. However, it necessitates rigorous analysis, and comprehensive genetic counseling before and after testing.

Machine learning in prenatal MRI predicts postnatal ventricular abnormalities in fetuses with isolated ventriculomegaly.

To evaluate the intracranial structures and brain parenchyma radiomics surrounding the occipital horn of the lateral ventricle in normal fetuses (NFs) and fetuses with ventriculomegaly (FVs), as well as to predict postnatally enlarged lateral ventricle alterations in FVs. Between January 2014 and August 2023, 141 NFs and 101 FVs underwent 1.5 T balanced steady-state free precession (BSSFP), including 68 FVs with resolved lateral ventricles (FVM-resolved) and 33 FVs with stable lateral ventricles (FVM-stable). Demographic data and intracranial structures were analyzed. To predict the enlarged ventricle alterations of FVs postnatally, logistic regression models with 5-fold cross-validation were developed based on lateral ventricle morphology, blended-cortical or/and subcortical radiomics characteristics. Validation of the models' performance was conducted using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Significant alterations in cerebral structures were observed between NFs and FVs (p < 0.05), excluding the maximum frontal horn diameter (FD). However, there was no notable distinction between the FVM-resolved and FVM-stable groups (all p > 0.05). Based on subcortical-radiomics on the aberrant sides of FVs, this approach exhibited high efficacy in distinguishing NFs from FVs in the training/validation set, yielding an impressive AUC of 1/0.992. With an AUC value of 0.822/0.743 in the training/validation set, the Subcortical-radiomics model demonstrated its ability to predict lateral ventricle alterations in FVs, which had the greatest predictive advantages indicated by DCA. Microstructural alterations in subcortical parenchyma associated with ventriculomegaly can serve as predictive indicators for postnatal lateral ventricle variations in FVs. It is critical to gain pertinent information from a solitary fetal MRI to anticipate postnatal lateral ventricle alterations in fetuses with ventriculomegaly. This approach holds the potential to diminish the necessity for recurrent prenatal ultrasound or MRI examinations. Fetal ventriculomegaly is a dynamic condition that affects postnatal neurodevelopment. Machine learning and subcortical-radiomics can predict postnatal alterations in the lateral ventricle. Machine learning, applied to single-fetal MRI, might reduce required antenatal testing.

Ultrasound-based horizontal ranging in the localization of fetal conus medullaris.

Currently, there are a variety of methods for ultrasound to localize the conus medullaris. A concern is that measured values can be influenced by variations in spinal flexion and extension. To overcome this limitation, the present study measures the horizontal distance (HD) between the end of the conus medullaris and the caudal edge of last vertebral body ossification in normal fetus at different gestational weeks, and analyzes the relationship between the measured value and fetal growth, as well as the utility of these measurements in assessing the position of the conus medullaris. A total of 655 fetuses at gestational weeks 18-40, who underwent routine prenatal ultrasound, were selected in the study. We measured the distance between the end of the cone of the fetal spinal cord and the caudal end of the final vertebral ossification center (Distance1, D1), the distance between the end of the spinal cord cone and the intersection of the extension of D1 with the caudal skin (Distance2, D2), and HD. We analyzed the correlation between the measurements and gestational weeks, established normal reference values, the ratio of D1, D2 and HD to the commonly used growth parameters was calculated. The ratios of D1, D2, HD and the application value of each ratio phase were analyzed, and the reliability analysis of repeated measurement results among physicians was performed. D1, D2 and HD exhibited strong linear correlations with gestational weeks. Among the ratios of D1, D2 and HD to common growth parameters, D2/FL stabilized after 20 weeks of gestation and consistently exceeded 1. Repeatability tests between D1, D2 and HD showed good reliability (P> 0.05). D1, D2 and HD are significantly correlated with gestational age. Horizontal distance measurement can effectively determine the position of fetal conus medullaris, enabling rapid prenatal evaluation of low position of conus medullaris and excluding the possibility of tethered cord.