Fetal Structural Abnormalities Research Articles

Genetic diagnosis of fetal microcephaly at a single tertiary center in China.

Background: Microcephaly is common in patients with neuropsychiatric problems, and it is usually closely related to genetic causes. However, studies on chromosomal abnormalities and single-gene disorders associated with fetal microcephaly are limited. Objective: We investigated the cytogenetic and monogenic risks of fetal microcephaly and evaluated their pregnancy outcomes. Methods: We performed a clinical evaluation, high-resolution chromosomal microarray analysis (CMA), and trio exome sequencing (ES) on 224 fetuses with prenatal microcephaly and closely followed the pregnancy outcome and prognosis. Results: Among 224 cases of prenatal fetal microcephaly, the diagnosis rate was 3.74% (7/187) for CMA and 19.14% (31/162) for trio-ES. Exome sequencing identified 31 pathogenic or likely pathogenic (P/LP) single nucleotide variants (SNVs) in 25 genes associated with fetal structural abnormalities in 37 microcephaly fetuses; 19 (61.29%) of which occurred de novo. Variants of unknown significance (VUS) was found in 33/162 (20.3%) fetuses. The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3. The live birth rate of fetal microcephaly in the syndromic microcephaly group was significantly higher than that in the primary microcephaly group [62.9% (117/186) vs 31.56% (12/38), p = 0.000]. Conclusion: We conducted a prenatal study by conducting CMA and ES for the genetic analysis of fetal microcephaly cases. CMA and ES had a high diagnostic rate for the genetic causes of fetal microcephaly cases. In this study, we also identified 14 novel variants, which expanded the disease spectrum of microcephaly-related genes.

Brain cortical maturation assessed by magnetic resonance imaging in unaffected or mildly affected fetuses with cytomegalovirus infection.

To assess by magnetic resonance imaging (MRI) the cortical maturation pattern in fetuses with cytomegalovirus (CMV) infection with mild or no abnormalities on ultrasound (US) and MRI, and to establish possible differences compared with healthy controls. This was a retrospective case-control study of consecutive pregnancies with a CMV-infected fetus undergoing prenatal MRI as a complementary diagnostic tool in two centers, and a control group of singleton low-risk pregnancies without fetal structural abnormalities, with normal fetal growth and with healthy newborns. CMV infection was confirmed by extraction of CMV-DNA from fetal and neonatal samples. Only fetuses with mild (mildly affected) or no (unaffected) neuroimaging abnormalities on US and MRI were included. MRI measurements of fetal parieto-occipital sulcus, cingulate sulcus and calcarine sulcus depth, Sylvian fissure depth and Sylvian fissure angles were performed and cortical development grading of specific cortical areas and sulci were assessed by one operator who was blinded to CMV infection status. Data were compared between controls and fetuses with CMV infection, using linear regression and non-parametric trend analysis. Twenty-four CMV-infected fetuses (seven unaffected and 17 mildly affected) and 24 healthy controls that underwent fetal MRI between 27 and 36 weeks' gestation were included. Compared with controls, CMV-infected fetuses showed significantly larger median lateral ventricular width (right side, 7.8 (interquartile range (IQR), 5.9-9.9) mm vs 3.9 (IQR, 2.6-5.3) mm; left side, 7.5 (IQR, 6.0-10.9) mm vs 4.2 (IQR, 3.2-5.3) mm), significantly decreased parieto-occipital sulcus depth (right side, 12.6 (IQR, 11.3-13.5) mm vs 15.9 (IQR, 13.5-17.3) mm; left side, 12.3 (IQR, 10.6-13.5) mm vs 16.0 (IQR, 13.3-17.5) mm) and calcarine sulcus depth (right side, 15.4 (IQR, 14.4-16.3) mm vs 17.5 (IQR, 16.1-18.7) mm; left side, 14.6 (IQR, 14.1-15.6) mm vs 16.7 (IQR, 15.6-18.9) mm) (P < 0.001 for all). Compared with controls, CMV-infected fetuses also had significantly smaller upper (right side, 42.8° (IQR, 35.8-45.8°) vs 48.9° (IQR, 38.4-64.7°); left side, 40.9° (IQR, 34.2-45.8°) vs 48.2° (IQR, 41.9-60.7°)) and lower (right side, 41.6° (IQR, 34.4-49.2°) vs 48.9° (IQR, 40.6-60.9°); left side, 42.2° (IQR, 38.8-46.9°) vs 48.9° (IQR, 39.5-57.5°)) Sylvian fissure angles (P < 0.05 for all). In addition, the mildly affected CMV-infected fetuses had a significantly lower cortical development grading in the temporal and parietal areas, and the parieto-occipital and calcarine sulci compared with healthy fetuses (P < 0.05). These differences persisted when adjusting for gestational age, ipsilateral atrium width, fetal gender and when considering small-for-gestational age as a confounding factor. Unaffected and mildly affected CMV-infected fetuses showed delayed cortical maturation compared with healthy controls. These results suggest that congenital CMV infection, even in non-severely affected fetuses that are typically considered of good prognosis, could be associated with altered brain cortical structure. Further research is warranted to better elucidate the correlation of these findings with neurodevelopmental outcomes. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Timing of Diagnosis of Fetal Structural Abnormalities After the Introduction of Universal Cell-Free DNA in the Absence of First-Trimester Anatomical Screening

ABSTRACT Cell-free DNA (cfDNA) screens are now widely used for trisomy 21, 18, and 13 (and less often for sex-chromosome aberrations). In 2017, the Netherlands became the first country to implement genome-wide cfDNA as a first-tier screening test for chromosomal abnormalities. The use of this test for first-trimester screening subsequently increased from 32% to 45%, with 2% of women still choosing to have the combined test. Although the official purpose of these tests is for aneuploidy screening, studies demonstrate that at least one-fourth of structural abnormalities in fetuses can be detected during nuchal translucency (NT) measurement. Whether the routine addition of first-trimester anatomy screening (FTAS) would be effective in detecting severe fetal structural anomalies with low rates of false-positive results was felt to be important to address, to determine whether this should be an integral component of prenatal screening program. This study aimed to determine the gestational age at which fetal anomalies were detected and which anomalies detected by second-trimester anatomical screening could have theoretically been diagnosed via FTAS had this been performed on all women in the cohort. The data for this retrospective observational study were collected from pregnant women referred to the University Medical Center of Groningen Fetal Medicine Unit from 2017 through 2020. Women in the cohort were referred based on suspicion of fetal structural abnormalities following a dating ultrasound, or first- or second-trimester anatomy survey. First-trimester anatomy surveys were performed only in women with high-risk indications, including monochorionic twin pregnancy (or greater multiple pregnancy), first-degree relative of the fetus with structural abnormalities, more than 1 more distant relative with similar abnormalities, preexisting diabetes mellitus or first-trimester diagnosis of diabetes mellitus, high-titer thyroid-stimulating hormone receptor antibodies, or high radiation exposure of &gt;0.50 Gy. In the study, all information was collected regarding additional examinations, invasive testing, and pregnancy outcomes, including postpartum follow-up to confirm the diagnosis. Cases with an abnormal cfDNA result or increased risk for aneuploidy based on serum screening were not included, nor were “soft markers” for aneuploidy or variations of normal anatomy such as persistent left superior vena cava. In all, 547 pregnancies had second-trimester anomalies and were included in the analysis. A total of 13 pregnancies underwent FTAS, whereas the other 534 (97.6%) underwent only the dating ultrasound scan and second-trimester anatomy scanning. Average maternal age was 29 years, with a median body mass index of 25.1 kg/m2, and the mean gestational age at the time of the anatomical survey of 21.4 weeks. Of the 13 pregnancies that underwent FTAS, anomalies were confirmed in 12 fetuses, whereas 1 had edema that resolved. Overall, 492 fetuses (92.1%) had structural anomalies that were confirmed, and analysis was done to determine whether these would have been diagnosable in the first trimester. In all, 66 (13.4%) were classified as “always detectable” in the first trimester, 303 (61.6%) as “sometimes detectable,” and 123 (25.0%) as “never detectable.” The mean gestational age at diagnosis was 22.8 weeks. Limitations of the study include its hypothetical classification of abnormalities as “always,” “sometimes,” and “never,” based on the literature. However, the authors concluded that the introduction of an early anatomical survey together with noninvasive screening for aneuploidies is appropriate based on these results.

Postmortem Evaluation of First Trimester Fetal Heart.

Due to rapid technology advancement and increasing diagnostic expertise, fetal medicine is rapidly improving. Prenatal diagnostic advancements made it possible to identify structural abnormalities in fetuses as early as the first trimester of pregnancy. However, to validate the echocardiographic diagnosis that led to the pregnancy termination, the termination of pregnancy owing to severe fetal deformities should be audited in accordance with a correct anatomic diagnosis. Following the PRISMA declaration, a systematic literature search was done to find articles on post-mortem first trimester human fetal heart evaluation. Thirteen suitable studies were found using the search method. It is theoretically possible to examine the human fetal heart after death in early pregnancy however these methods are not widely available due the costs associated with the procedure and the equipment, the effects of tissue coloration and distortion brought on by the fixation and contrasting processes (for micro-CT), the current requirement for a skilled operator to acquire, reconstruct, and process the images, and data storage requirements greater than those of conventional clinical scans.

In Utero Mapping and Development Role of CFTR in Lung and Gastrointestinal Tract of Cystic Fibrosis Patients.

In cystic fibrosis (CF) the ability of the CF transmembrane conductance regulator (CFTR) protein to mediate chloride and water transport is disrupted. While much progress has been made in CF research leading to effective treatments to improve CFTR function, including small molecule modulators, patients present with varying disease manifestations and responses to therapy. For many CF-affected organs, disease onset is known to occur during in utero development before treatments can be administered and progresses over time leading to irreversible damage to these organs. Thus, the role of functional CFTR protein, in particular, during early development needs to be further elucidated. Studies have detected CFTR proteins at very early gestational stages and revealed temporally and spatially variable CFTR expression patterns in fetuses, suggesting a potential role of CFTR in fetal development. However, the actual mechanisms of how defective CFTR in CF results in fetal morphogenetic abnormalities are yet to be established. This review aims to summarize fetal CFTR expression patterns specifically in the lung, pancreas, and gastrointestinal tract (GIT), as compared to adult patterns. Case studies of structural abnormalities in CF fetuses and newborns and the role of CFTR in fetal development will also be discussed.

Organ-specific learning curves of sonographers performing first-trimester anatomical screening and impact of score-based evaluation on ultrasound image quality.

First-trimester anatomical screening (FTAS) by ultrasound has been introduced in many countries as screening for aneuploidies, but also as early screening for fetal structural abnormalities. While a lot of emphasis has been put on the detection rates of FTAS, little is known about the performance of quality control programs and the sonographers' learning curve for FTAS. The aims of the study were to evaluate the performance of a score-based quality control system for the FTAS and to assess the learning curves of sonographers by evaluating the images of the anatomical planes that were part of the FTAS protocol. Between 2012-2015, pregnant women opting for the combined test in the North-Netherlands were also invited to participate in a prospective cohort study extending the ultrasound investigation to include a first-trimester ultrasound performed according to a protocol. All anatomical planes included in the protocol were documented by pictures stored for each examination in logbooks. The logbooks of six sonographers were independently assessed by two fetal medicine experts. For each sonographer, logbooks of examination 25-50-75 and 100 plus four additional randomly selected logbooks were scored for correct visualization of 12 organ-system planes. A plane specific score of at least 70% was considered sufficient. The intra-class correlation coefficient (ICC), was used to measure inter-assessor agreement for the cut-off scores. Organ-specific learning curves were defined by single-cumulative sum (CUSUM) analysis. Sixty-four logbooks were assessed. Mean duration of the scan was 22 ± 6 minutes and mean gestational age was 12+6 weeks. In total 57% of the logbooks graded as sufficient. Most sufficient scores were obtained for the fetal skull (88%) and brain (70%), while the lowest scores were for the face (29%) and spine (38%). Five sonographers showed a learning curve for the skull and the stomach, four for the brain and limbs, three for the bladder and kidneys, two for the diaphragm and abdominal wall and one for the heart and spine and none for the face and neck. Learning curves for FTAS differ per organ system and per sonographer. Although score-based evaluation can validly assess image quality, more dynamic approaches may better reflect clinical performance.

ISUOG Practice Guidelines (updated): performance of fetal magnetic resonance imaging.

ISUOG Practice Guidelines (updated): performance of fetal magnetic resonance imaging.

Prenatal diagnostic testing decisions in twin pregnancies in the era of cell-free DNA screening

Rates of diagnostic procedures in singleton pregnancies have declined since cell-free DNA (cfDNA) became commercially available. However, the impact of cfDNA on the uptake of diagnostic testing in twin gestations is unclear. We aimed to describe the rate of invasive diagnostic procedures in twin pregnancies after cfDNA screening with and without fetal structural abnormalities. This is a secondary analysis of data from a multicenter retrospective cohort study from 12/2011- 02/2020 that aimed to evaluate cfDNA screening performance in twin pregnancies. For this analysis, we excluded cases with a vanishing twin. cfDNA results were reported as positive, negative, or non-reportable. Structural abnormalities were defined as a major or minor anomaly, including an increased nuchal translucency >3mm. Rates of diagnostic testing were analyzed via chi-squared with odds ratio calculated by logistic regression. A total of 112 (6.6%) of 1,696 patients with twin pregnancies had cfDNA results and diagnostic procedures performed: 82 amniocenteses and 29 chorionic villus samplings (CVS). Diagnostic procedures were more frequent in patients that were older, had private insurance and conceived via IVF (Table 1). Patients with diagnostic testing were more likely to have positive or non-reportable cfDNA results compared to those without diagnostic testing. As noted in Figure 1A, 50% of positive cfDNA, 4.8% of negative cfDNA and 20% of non-reportable cfDNA ultimately had diagnostic testing. Figure 1B details the frequency of diagnostic procedures performed for each combination of cfDNA result and the presence of a structural abnormality. Diagnostic testing was more common if a structural abnormality was present (15.0% vs 4.5%, aOR 4.30 95% CI 2.71-6.83) and if there was an abnormal cfDNA result (32.8% vs 4.7%, aOR 8.72 95% CI 5.16-14.74), when adjusted for demographic factors. Cell-free DNA results and the presence of structural abnormalities greatly impact the decision to pursue diagnostic testing in patients with twin gestations.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Does the Presence of Extended Jugular Lymphatic Sacs Add More Risk to Nuchal Thickness for Genetic and Structural Abnormality?

The risks added by extended jugular lymphatic sacs (EJLS) to increased nuchal translucency (NT) including genetic and structural abnormalities and pregnancy outcomes have not been previously investigated, which this study aims to investigate. The data of 155 singleton pregnancies with increased fetal NT (≥95th percentile) of these 20 with fetal EJLS were evaluated retrospectively. Patients were stratified according to NT thickness such that ≥95th percentile - 3.5 mm, 3.6-4.4 mm, 4.5-5.4 mm, 5.5-6.4 mm, ≥6.5 mm, and grouped according to the presence of EJLS. Pregnancy outcomes, genetic and structural abnormalities were assessed by comparing EJLS with non-EJSL cases (n-EJLS). Associated with NT, the incidence of the presence of EJLS increased with NT, from 4.5% at the ≥95th percentile - 3.5 mm to 30.8% when NT ≥5.5 mm. In the n-EJLS group, the proportion of fetuses with structural and genetic abnormalities increased as the measurement of NT increased. This correlation was not observed in the EJLS group. Compared to n-EJLS, cases with EJLS had a higher rate of fetal structural (38.5% vs. 75%, P = 0.003) and genetic (18.5% vs. 45%, P = 0.005) anomalies and a lower term live birth rate (59.3% vs. 15%, P < 0.001). The increasing rate of EJLS was seen as NT increased. Compared to n-EJLS, the EJLS cases had a higher rate poor pregnancy outcomes and fetal genetic and structural abnormalities.

Application of Complete Prenatal Diagnosis in Fetal Ultrasound Abnormalities.

To investigate the value of prenatal diagnosis in fetal ultrasound abnormalities. Amniotic fluid samples of pregnant women who underwent invasive amniocentesis for ultrasound examination suggestive of fetal ultrasound structural abnormalities and soft markers of abnormalities during pregnancy from January 2016 to June 2021 at the Prenatal Diagnostic Center of Putian College Hospital were collected for amniotic fluid cell culture and G manifest band karyotype analysis. (1) Most pregnant women with ultrasound abnormalities were delivered at the age of 23 to 32 years. (2) There were 66 cases of abnormal karyotype with an abnormal incidence of 9.64% (66/685), with chromosomal number abnormalities predominating. (3) Fetal ultrasound abnormalities are mainly soft markers of abnormalities. (4) The comparison of ultrasound abnormalities in the low and high maternal-fetal age groups was not statis-tically significant. (1) Fetal ultrasound abnormalities are mainly soft markers of abnormalities. (2) The rate of fetal chromosomal abnormalities was the highest among the soft ultrasound indicators with NT thickening. (3) The incidence of fetal ultrasound abnormalities did not increase with increasing age. There was no statistical difference in the incidence of chromosomal abnormalities between the low age group and the high age group. (4) Fetal ultrasound testing provides a scientific and accurate basis for clinical heritage counseling and rebirth counseling, especially for chromosomal aneuploidy number abnormalities.

The successful pregnancy in patient with Wolff-Parkinson-White syndrome type B

Background: An aberrant accessory route is a hallmark of the rare heart rhythm condition called Wolff-Parkinson-White (WPW) syndrome. The onset of tachyarrhythmias, which can result in hemodynamic instability and even maternal mortality, is considered to be triggered by a variety of physiological changes that occur during pregnancy. Therefore, it is anticipated that effective management options for pregnant women who have WPW syndrome will be able to regulate tachyarrhythmias and give healthy pregnancies for both the mother and the fetus. Case Report: A 32-year-old pregnant woman with 34 weeks of gestational age arrived complaining of palpitations and breathing difficulties. The results of the ECG test revealed left branch bundle block (LBBB), a Wolff-Parkinson-White (WPW) type B pattern, and sinus tachycardia. Both an NST assessment and an echocardiographic evaluation revealed no fetal distress or structural abnormalities of the heart. The patient was treated with 300 mg of Propafenone, which was administered on a regular basis whenever the patient experienced palpitations. Due to a history of prior caesarean deliveries, the pregnancy had progressed to 40 weeks of gestation and caesarean birth under spinal anaesthesia was performed in this point. The infant was born healthy, full-term, and free from birth problems. Conclusion: One of the causes of tachyarrhythmias in WPW syndrome is pregnancy. Arrhythmias that could develop in women with WPW syndrome can be controlled with good pregnancy planning and management.

Application of Prenatal Whole Exome Sequencing for Structural Congenital Anomalies-Experience from a Local Prenatal Diagnostic Laboratory.

Fetal structural congenital abnormalities (SCAs) complicate 2-3% of all pregnancies. Whole-exome sequencing (WES) has been increasingly adopted prenatally when karyotyping and chromosomal microarray do not yield a diagnosis. This is a retrospective cohort study of 104 fetuses with SCAs identified on antenatal ultrasound in Hong Kong, where whole exome sequencing is performed. Molecular diagnosis was obtained in 25 of the 104 fetuses (24%). The highest diagnostic rate was found in fetuses with multiple SCAs (29.2%), particularly those with involvement of the cardiac and musculoskeletal systems. Variants of uncertain significance were detected in 8 out of the 104 fetuses (7.7%). Our study shows the utility of WES in the prenatal setting, and the extended use of the technology would be recommended in addition to conventional genetic workup.

Prioritizing Fetal Structural Abnormalities Over Risk for Pre-Eclampsia and Fetal Growth Restriction in the 20-24 Gestation Week Assessment in India: Missing the Woods for the Trees?

Aim To compare the magnitude of fetuses with congenital anomalies, pregnant women identified at high risk for preterm pre-eclampsia (PE) or with preterm PE, and with early fetal growth restriction (FGR) or high risk for FGR at the second trimester assessment at 20 to 24 weeks of gestation. Methods A standardized trimester-specific protocol that included clinical and demographic details, fetal biometry, estimated fetal weight (EFW), fetal abdominal circumference (FAC), mean arterial blood pressure and fetal Doppler studies was used to identify high risk for preterm PE and FGR. The Targeted Imaging for Fetal Anomalies (TIFFA) scan was used to identify congenital anomalies. In addition, 95% confidence intervals of the point estimates were derived, and the p -value was estimated to assess the statistical significance of the difference in proportions. Results Analysis of the data of 4,572 pregnant women screened between 20 and 24 gestation weeks showed a significantly lower prevalence ( p < 0.001) of congenital abnormalities (3.81%) compared to women diagnosed with early PE (2.71%) or with a high risk for PE (4.00%) and women (6.80%) with early FGR or at higher risk for fetal growth restriction with both EFW and FAC < 10th percentile. Conclusion The data on prevalence from Samrakshan show that the second-trimester assessment of pregnant women in India must expand its scope from the TIFFA scan to also focus on screening to identify women at high risk for preterm PE and FGR.

Intrauterine Transmission of Hepatitis C Virus Concomitant with Isolated Severe Fetal Ascites.

Perinatal Hepatitis C Virus (HCV) transmission occurs in 4-7% of the cases with detectable viremia at delivery. HCV testing in pregnancy is recommended. The fetal infection was previously described as asymptomatic although there are two cases, including this one, to report the presence of isolated fetal ascites in HCV infected fetuses. A 42-year-old patient, 3G, 3P, presented in the Emergency Room for painful uterine contraction. The third-trimester ultrasound examination noted severe fetal ascites, accompanied by hyperechoic bowels and polyhydramnios. The diagnosis required a detailed ultrasound exam, invasive testing (amniocentesis, cordocentesis, and fetal paracentesis), and a complete workup. The mother tested positive for HCV antibodies, and the fetal cord blood tested positive for HCV RNA. The ascites resolved after paracentesis, and the gastrointestinal and respiratory functions markedly improved. The fetus was delivered at term in good condition. The etiology of isolated fetal ascites is broad. This case may indicate that intrauterine HCV transmission is a potential cause of isolated fetal ascites in the absence of other explanation, and isolated fetal ascites can be the only sign revealed on a routine examination. We suspected, having no other detected cause for ascites, the intrauterine transmission of HCV. Invasive procedures, such as paracentesis, are required for abdominal decompression to manage isolated fetal ascites, as it may be a saving procedure. A genetic investigation is needed, and a good neonatal outcome is expected in the absence of fetal structural or genetic abnormalities, as in our case.

Highlights from the International Twins Congress 2021

Highlights from the International Twins Congress 2021

EP11.03: Structural and chromosomal abnormalities in fetuses with lateral ventricular atrium width between 9 and 10mm

EP11.03: Structural and chromosomal abnormalities in fetuses with lateral ventricular atrium width between 9 and 10mm

Timing of diagnosis of fetal structural abnormalities after the introduction of universal cell-free DNA in the absence of first-trimester anatomical screening.

IntroductionSince 2021, first‐trimester anatomical screening (FTAS) is offered in the Netherlands alongside genome‐wide cell‐free DNA (cfDNA). Previously, only second‐trimester anatomical screening (STAS) was offered. This study identifies structural abnormalities amenable to first‐trimester diagnosis detected at/after STAS in the period following cfDNA implementation and preceding FTAS introduction.MethodsThis retrospective cohort includes 547 fetuses referred between 2017 and 2020 because of suspected structural abnormalities before/at/after STAS. Additional prenatal investigations and postnatal follow‐up were searched. Abnormalities were classified into “always”, “sometimes”, and “never” detectable in the first‐trimester based on a previously suggested classification.ResultsOf the 547 pregnancies, 13 (2.6%) received FTAS and 534 (97.6%) received a dating ultrasound and STAS. In 492/534 (92.1%) anomalies were confirmed; 66 (13.4%) belonged to the “always detectable” group in the first trimester, 303 (61.6%) to the “sometimes detectable”, and 123 (25.0%) to the never detectable. Of the “always detectable” anomalies 29/66 (44%) were diagnosed during dating ultrasounds and 37 (56%) during STAS. The rate of termination of pregnancy for anomalies detected during FTAS and at/after STAS was 84.6% (n = 11/13) and 29.3% (n = 144/492) (p < 0.01).ConclusionWhen FTAS is not part of screening paradigms, most fetal anomalies remain undetected until the second trimester or later in pregnancy, including 56% of anomalies “always detectable” in the first trimester.

Holding a baby after stillbirth: the impact of fetal congenital and structural abnormalities.

ObjectiveStillbirth can result in numerous adverse psychosocial sequelae. Recommendations vary with regard to holding the baby after a stillbirth. Few studies have addressed the impact of fetal abnormalities on these outcomes.Study designAnalyses of singleton stillbirths within the Stillbirth Collaborative Research Network were conducted. Patient and stillbirth characteristics were compared between those who did and did not hold their baby. Results from psychometric surveys were compared between cases with and without visible fetal anomalies.ResultThere were no significant differences between those who held and those who did not hold in any patient or stillborn characteristics. Visible fetal abnormalities were not associated with adverse psychological outcomes.ConclusionFetal abnormalities, including congenital and post-demise changes, do not differ between those who held and did not hold their baby after stillbirth. This suggests that patients should not be discouraged from holding their stillborn infant in the presence of visible abnormalities.

The effect of gestational diabetes mellitus on fetal right heart growth in late-term pregnancy: A prospective study.

Gestational diabetes mellitus (GDM) is a complication of pregnancy strongly associated with an increased risk of structural fetal abnormalities. As the fetal heart grows quickly during the late-term pregnancy period, it is important to understand fetal heart growth before birth. This study explored how GDM affects fetal heart growth by evaluating basic echocardiography indicators during late pregnancy. This prospective, longitudinal study included 63 GDM patients (GDM group) and 67 healthy pregnant women (control group). All subjects underwent fetal echocardiography scans at gestational weeks 28-32, 32-36, and 36-40. Twelve echocardiographic indicators were assessed at each observation and analyzed by using a mixed model. The left atrial diameter (LA) and left ventricular end-diastolic diameter (LV) similarly increased from the first to the third observation. The right ventricular end-diastolic diameter (RV) was significantly different between the groups, and a group × time interaction was detected. The tricuspid annular peak systolic velocity (s') increased more rapidly in the GDM than the control group during the first to second observations, and the group × time interaction was significant. The increase in the tricuspid annular plane systolic excursion (TAPSE) of the GDM group was "slow-fast", while that of the control group was "fast-slow", during three observations. After adjusting covariates, the group difference and interaction effect of TAPSE and RV remained significant. The differences in fetal right heart indicators between the GDM and control groups suggest that GDM may affect the structure and functional growth of the fetal right heart during late-term pregnancy.

Prenatal Diagnosis Using Chromosomal Microarray Analysis in High-Risk Pregnancies.

Background: To assess the value of chromosomal microarray analysis (CMA) during the prenatal diagnosis of high-risk pregnancies. Methods: Between January 2016 and November 2021, we included 178 chorionic villi and 859 amniocentesis samples from consecutive cases at a multiple tertiary hospital. Each of these high-risk singleton pregnancies had at least one of the following indications: (1) advanced maternal age (AMA; ≥35 years; 546, 52.7%); (2) fetal structural abnormality on ultrasound (197, 19.0%); (3) high-risk first- or second-trimester Down syndrome screen (189, 18.2%), including increased nuchal translucency (≥3.5 mm; 90, 8.7%); or (4) previous pregnancy, child, or family history (105, 10.1%) affected by chromosomal abnormality or genetic disorder. Both G-banding karyotype analysis and CMA were performed. DNA was extracted directly and examined with oligonucleotide array-based comparative genomic hybridization. Results: Aneuploidies were detected by both G-banding karyotyping and CMA in 42/1037 (4.05%) cases. Among the 979 cases with normal karyotypes, 110 (10.6%) cases had copy number variants (CNVs) in CMA, including 30 (2.9%) cases with reported pathogenic and likely pathogenic CNVs ≥ 400 kb, 37 (3.6%) with nonreported VOUS, benign, or likely benign CNVs ≥ 400 kb, and 43 (4.1%) with nonreported CNVs < 400 kb. Of the 58 (5.6%) cases with aneuploidy rearrangements, 42 (4.1%) were diagnosed by both G-banding karyotyping and CMA; four inversions, six balanced translocations, and six low mosaic rates were not detected with CMA. Conclusions: CMA is an effective first step for the prenatal diagnosis of high-risk pregnancies with fetal structural anomalies found in ultrasonography or upon positive findings.