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Introduction: Invasive prenatal testing with chromosomal microarray analysis after first-trimester screening is a relevant option but there is still debate regarding the indications. Therefore, we evaluated the prevalence of numerical chromosomal aberrations detected by classic karyotype and clinically relevant copy number variants (CNVs) in prenatal samples using array comparative genomic hybridization (aCGH) stratified to NT thickness: 4.5 mm, and by the presence/absence of associated structural anomalies detected by ultrasonography. Materials and Methods: Retrospective cohort study carried out at two tertiary Polish centers for prenatal diagnosis (national healthcare system) in central and south regions from January 2018 to December 2021. A total of 1746 prenatal samples were received. Indications for invasive prenatal testing included high risk of Down syndrome in the first-trimester combined test (n = 1484) and advanced maternal age (n = 69), and, in 193 cases, other reasons, such as parental request, family history of congenital defects, and genetic mutation carrier, were given. DNA was extracted directly from amniotic fluid (n = 1582) cells and chorionic villus samples (n = 164), and examined with classic karyotype and aCGH. Results: Of the entire cohort of 1746 fetuses, classical karyotype revealed numerical chromosomal aberrations in 334 fetuses (19.1%), and aCGH detected CNV in 5% (n = 87). The frequency of numerical chromosomal aberrations increased with NT thickness from 5.9% for fetuses with NT < p95th to 43.3% for those with NT > 4.5 mm. The highest rate of numerical aberrations was observed in fetuses with NT > 4.5 mm having at least one structural anomaly (50.2%). CNVs stratified by NT thickness were detected in 2.9%, 2.9%, 3.5%, 4.3%, 12.2%, and 9.0% of fetuses with NT < 95th percentile, 95th percentile–2.9 mm, 3.0–3.4 mm, 3.5–3.9 mm, 4.0–4.5 mm, and >4.5 mm, respectively. After exclusion of fetuses with structural anomalies and numerical aberrations, aCGH revealed CNVs in 2.0% of fetuses with NT < 95th percentile, 1.5% with NTp95–2.9 mm, 1.3% with NT 3.0–3.4 mm, 5.4% with NT 3.5–3.9 mm, 19.0% with NT 4.0–4.5 mm, and 14.8% with NT > 4.5 mm. Conclusions: In conclusion, our study indicates that performing aCGH in samples referred to invasive prenatal testing after first-trimester screening provides additional clinically valuable information over conventional karyotyping, even in cases with normal NT and anatomy. [ABSTRACT FROM AUTHOR]

There are limited data on how neighborhood-level risk factors affect the likelihood of having prenatal diagnosis. Neighborhood social vulnerability can be quantified and ranked using the social vulnerability index (SVI), a tool that measures the cumulative effect of external stressors in the local environment that may affect health outcomes. The objective of the study was to determine the relationship between SVI and prenatal diagnosis among pregnant patients who received genetic counseling. Retrospective cohort study of all pregnant patients who had genetic counseling at two hospitals in New York between January 2019 and December 2022. For each patient, the address of residence was linked to an SVI score (primary exposure) based on census tract. SVI scores were subdivided into fifths and analyzed categorically. The primary outcome was prenatal diagnosis (yes/no). Multivariable logistic regression was performed. A total of 5,935 patients were included for analysis and 231 (3.9 %) had prenatal diagnosis. On regression analysis, no association between SVI and prenatal diagnosis was observed. Patients who had a diagnostic procedure were more likely to be English speaking (aOR 1.80; 95 % CI 1.13–2.87), carriers of a genetic disorder (aOR 1.94; 95 % CI 1.32–2.86), had increased NT (aOR 6.89; 95 % CI 3.65–13.00), abnormal NIPS (aOR 9.58; 95 % CI 5.81–15.80), or had fetal structural anomalies (aOR 10.60; 95 % CI 6.62–16.96). No differences were seen based on race and ethnicity group, insurance type, or marital status. SVI score does not affect rate of prenatal diagnosis. Findings may differ in other geographic regions and populations. [ABSTRACT FROM AUTHOR]

This article presents a case series of 14 pregnant patients who received abnormal results from noninvasive prenatal testing (NIPT) and were subsequently evaluated and treated at a specific institution. The study found that abnormal NIPT results can indicate the presence of maternal malignancy, particularly when they do not align with the fetal karyotype. The patients in the study had various types of cancer, such as Hodgkin lymphoma and triple-negative breast cancer. The article emphasizes the importance of a multidisciplinary approach to managing cancer during pregnancy and highlights the use of noncontrast whole-body magnetic resonance imaging (WBMRI) as an effective initial diagnostic tool. The study concludes that treatment during and after pregnancy is feasible and can lead to positive outcomes for both the mother and the fetus. [Extracted from the article]

A 31‐year‐old primiparous woman underwent non‐invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t‐statistics (Z‐score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development. [ABSTRACT FROM AUTHOR]

After in vitro fertilization with a single embryo, the parents learned about being pregnant with twins in the 10th week with various indications that an embryonic mix-up could have taken place. The affected couple thus expressed the urgent desire for a clarification of parenthood considering an abortion. However, the prenatal test results would not have been available until the 14/15th week of pregnancy. Legally, then, severe physical or mental distress of the pregnant woman must be claimed by physicians to justify an abortion after the twelfth week. However, a lack of genetic relatedness could lead to serious psychological distress for the parents, making a pregnancy termination possible even after the twelfth week, which is discussed in this case study alongside the interdisciplinary team's ethical, legal, and medical considerations. For the invasive relationship testing, cultivated chorionic villi samples (CVS) from both unborn and saliva samples from the putative parents were genetically analyzed using classical short tandem repeats (STR) analysis. The perfect match of both CVS profiles suggested the occurrence of an unusual late twin shaft, for which, fortunately, parenthood could be confirmed. To our knowledge, this is the first report on a prenatal investigation of a suspected embryo mix-up after assisted reproductive technology (ART), in which parenthood should be fixed. We want to draw attention to this unthinkable scenario, which may increase in the future with ART-induced rising multiple pregnancies. [ABSTRACT FROM AUTHOR]

Background: Fetal sex and placental development impact pregnancy outcomes and fetal–maternal health, but the critical timepoint of placenta establishment in first trimester is understudied in human pregnancies. Methods: Pregnant subjects were recruited in late first trimester (weeks 10–14) at time of chorionic villus sampling, a prenatal diagnostic test. Leftover placenta tissue was collected and stored until birth outcomes were known, then DNA and RNA were isolated from singleton, normal karyotype pregnancies resulting in live births. DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip array (n = 56). Differential methylation analysis compared 25 females versus 31 males using a generalized linear model on 743,461 autosomal probes. Gene expression sex differences were analyzed with RNA-sequencing (n = 74). An integrated analysis was performed using linear regression to correlate gene expression and DNA methylation in 51 overlapping placentas. Results: Methylation analysis identified 151 differentially methylated probes (DMPs) significant at false discovery rate < 0.05, including 89 (59%) hypermethylated in females. Probe cg17612569 (GABPA, ATP5J) was the most significant CpG site, hypermethylated in males. There were 11 differentially methylated regions affected by fetal sex, with transcription factors ZNF300 and ZNF311 most significantly hypermethylated in males and females, respectively. RNA-sequencing identified 152 genes significantly sexually dimorphic at false discovery rate < 0.05. The 151 DMPs were associated with 18 genes with gene downregulation (P < 0.05) in the direction of hypermethylation, including 2 genes significant at false discovery rate < 0.05 (ZNF300 and CUB and Sushi multiple domains 1, CSMD1). Both genes, as well as Family With Sequence Similarity 228 Member A (FAM228A), showed significant correlation between DNA methylation and sexually dimorphic gene expression, though FAM228A DNA methylation was less sexually dimorphic. Comparison with other sex differences studies found that cg17612569 is male-hypermethylated across gestation in placenta and in human blood up to adulthood. Conclusions: Overall, sex dimorphic differential methylation with associated differential gene expression in the first trimester placenta is small, but there remain significant genes that may be regulated through methylation leading to differences in the first trimester placenta. Plain language summary: Fetal sex and placenta development affect pregnancy outcomes for both the fetus and mother throughout pregnancy, including risk of miscarriages, preterm birth, preeclampsia, and other outcomes. Epigenetics, the "overlay" of regulatory signals on DNA which affects how DNA is read, is not well understood in early pregnancy when critical placenta developments are happening that affect the rest of pregnancy. Here, we use leftover placenta biopsy samples (n = 56) donated by Cedars-Sinai patients with informed consent to learn about first trimester human placenta DNA methylation differences due to fetal sex. Out of the total 743,461 sites analyzed, we identified 151 sites significantly affected by fetal sex after correcting p-values to reduce false positives (false discovery rate < 0.05). We also performed an analysis to look at multiple sites and identified 11 regions across the genome with significant DNA methylation changes due to fetal sex. Furthermore, because DNA methylation is a regulatory mark on DNA which typically dampens gene expression, we also compared the DNA methylation sex differences to placental RNA-sequencing gene expression analysis using the same tissue from a mostly overlapping patient group (n = 74 total sequenced, n = 51 overlap). We identify 18 genes which show both significant DNA methylation differences and gene expression changes. The most significant gene was transcription factor ZNF300 with higher DNA methylation in males and reduced gene expression in males (and thus higher gene expression in females). This study identifies some sex differences that continue until later pregnancy and others that are unique to first trimester. Highlights: We identify sex differences in first trimester human placenta DNA methylation (n = 56) and total RNA-sequencing (n = 74), with a sample overlap of n = 51. At late first trimester, there are 151 differentially methylated probes (DMPs), significantly different between female and male placenta at false discovery rate < 0.05. These encompass 11 differentially methylated regions. The gene with placental DNA methylation most affected by fetal sex is transcription factor ZNF300, hypermethylated in males, and with significantly female upregulated gene expression in first trimester placenta, consistent with previous third trimester studies. In addition to ZNF300, other genes in significantly differentially methylated regions at first trimester include GABPA/ATP5J (hypermethylated in males); ZNF311, CCDC178, ATP5G2, FOXG1 (females); ZNF175 (males); SGCE (females); C6orf47-AS1/C6orf47, REC8, and FOXA1 (females). We identify 18 genes with significant fetal sex-associated changes in both placenta DNA methylation and placenta gene expression. The most significant are ZNF300, tumor suppressor CSMD1, and transcription factor ZNF311. [ABSTRACT FROM AUTHOR]

Since the 1950s, invasive prenatal diagnostics have played an integral role in perinatal management. However, its significance extends beyond detecting genetic abnormalities. This paper comprehensively reviews the indications for amniocentesis and chorionic villus sampling. Additionally, it examines various methods of genomic, infectious, and biochemical analysis, with a particular emphasis on the achievements of the last decade. [ABSTRACT FROM AUTHOR]

Fetal ventriculomegaly (VM) is a defect of the central nervous system, typically diagnosed during the second-trimester ultrasound in fetuses with an atrial diameter (AD) of >10 mm. Non-isolated ventriculomegaly (NIVM) is heterogeneous in nature, coexisting with additional intracranial and/or extracranial malformations and genetic syndromes, resulting in an unfavorable prognosis for the further development of the child. Both the pregnancy management and counseling are dependent on the findings of combined ultrasound/MRI, genetic testing, and gestational age at diagnosis. The purpose of this review is to propose a hypothesis that diagnostic advancements allow to define the process of identification of the isolated forms of VM (IVM). Based on the evidence presented in the literature, we consider whether prenatal decompression for severe isolated VM (ISVM) is supported by the experimental trials and whether it might be implemented in clinical practice. Also, we describe the evolution of the diagnostic methods and expert opinions about the previously used prenatal decompression techniques for ISVM. In conclusion, we introduce the idea that fetal surgery centers have either reached or nearly reached the necessary level of expertise to perform such procedures. Endoscopic cystoventriculostomy (ETV) appears to be the most promising, as it is associated with minimal perinatal complications and favorable neurological outcomes in the neonatal period. Randomized trials with long-term neurodevelopmental follow-up of children who underwent prenatal decompression due to ISVM are necessary. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is a group of motor neuron diseases. In 95% of SMA patients, the telomeric copy of the SMN gene (SMN1) is homozygously deleted. Due to the autosomal recessive pattern of SMA inheritance, individuals with a family history of SMA are at risk of being carriers. A total of 622 individuals from SMA families, including parents, siblings, and first, second, and third-degree relatives, were recruited to the neuro-genetic clinic of Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. SMA cases and suspected carriers were referred to the genetic laboratory. Pregnant women underwent amniocentesis and chorionic villi sampling at 12–14 gestational weeks. RFLP-PCR and real-time PCR were performed for symptomatic and asymptomatic individuals (possible carriers), respectively. RFLP and real-time PCR were performed for amniotic fluid and chorionic villi samples. Results: The study enrolled 622 subjects from SMA-affected families, including 159 fetuses and 463 non-fetuses. Two samples were missing. A total of 268 individuals (43.2%) were healthy (wild type), 187 individuals (30.1%) were heterozygous for exon deletion of SMN1, and 143 individuals (23%) were homozygous for exon deletion of SMN1. Four individuals (0.6%) showed three copies of the SMN1 gene. Conclusion: The frequency of carriers with two SMN1 copies on a single chromosome (cis) was estimated at 2.9% (18/622), and the total rate of carriers was approximately 21.8%. Considering the high rate of SMA carriers in this study, genetic counseling and definitive prenatal diagnosis are of utmost importance for reducing the psychosocial burden of the SMA disease among Iranian families. [ABSTRACT FROM AUTHOR]

Background: Classic vitrification methods are not appropriate when there are minimal numbers of viable sperm, and the new methods emphasize the low semen volumes in these cases. The aim was to assess the efficacy of the cryotech as a device for freezing low sperm volume, through the two methods of open (OVS) and closed (CVS) vitrification systems. Methods: Testicular biopsy samples from 30 men with obstructive azoospermia (OA) were assigned to three groups fresh control (FC), OVS, and CVS. Testicular sperms were selected using an ICSI injection pipette and vitrified on the cryotech straws, containing one droplet of freezing medium. After warming, sperm head morphometric characterizations were evaluated with the MSOME technique. Sperm motility, membrane integrity, chromatin quality assessment including DNA fragmentation, Chromomycine A3 staining (CMA3), and Aniline Blue (AB) were assessed. Fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) was done to examine sperm acrosome integrity. Results: The mean sperm motility, viability, and sperm with intact acrosome reduced after vitrification, in both methods of CVS, and OVS, but the results were more promising in the closed method (p < 0.05). However, the variations were not significant between the two methods of cryopreservation, the OVS undergoes significant head dimensions changes compared to the control group (p < 0.05). The results also showed higher membrane, and chromatin abnormality after OVS (p < 0.05). Conclusions: The overall post-thaw recovery of human testicular sperm proposes that CVS is more efficient for single sperm cryopreservation, while higher sperm viability, and lower alterations in chromatin, acrosome, and sperm head morphometry were seen compared to OVS. [ABSTRACT FROM AUTHOR]

Background: For women in the first trimester, amniocentesis or chorionic villus sampling is recommended for screening. Machine learning has shown increased accuracy over time and finds numerous applications in enhancing decision-making, patient care, and service quality in nursing and midwifery. This study aims to develop an optimal learning model utilizing machine learning techniques, particularly neural networks, to predict chromosomal abnormalities and evaluate their predictive efficacy. Methods/ design: This cross-sectional study will be conducted in midwifery clinics in Mashhad, Iran in 2024. The data will be collected from 350 pregnant women in the high-risk group who underwent screening tests in the first trimester (between 11-14 weeks) of pregnancy. Information collected includes maternal age, BMI, smoking habits, history of trisomy 21 and other chromosomal disorders, CRL and NT levels, PAPP-A and B-HCG levels, presence of insulin-dependent diabetes, and whether the pregnancy resulted from IVF. The study follows up with the women during their clinic visits and tracks the results of amniocentesis. Sampling is based on Convenience Sampling, and data is gathered using a checklist of characteristics and screening/amniocentesis results. After preprocessing, feature extraction is conducted to identify and predict relevant features. The model is trained and evaluated using K-fold cross-validation. Discussion: There is a growing interest in utilizing artificial intelligence methods, like machine learning and deep learning, in nursing and midwifery. This underscores the critical necessity for nurses and midwives to be well-versed in artificial intelligence methods and their healthcare applications. It can be beneficial to develop a machine learning model, specifically focusing on neural networks, for predicting chromosomal abnormalities. Ethical code: IR.MUMS.NURSE.REC. 1402.134 Plain English Summary: Approximately 3% of newborns are affected by congenital abnormalities and genetic diseases, leading to disability and death. Among live births, around 3000 cases of Down syndrome (trisomy 21) can be expected based on the country's birth rate. Pregnant women carrying fetuses with Down syndrome face an increased risk of pregnancy complications. Artificial intelligence methods, such as machine learning and deep learning, are being used in nursing and midwifery to improve decision-making, patient care, and research. Nurses need to actively participate in the development and implementation of AI-based decision support systems. Additionally, nurses and midwives should play a key role in evaluating the effectiveness of artificial intelligence-based technologies in professional practice. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the efficacy of α-thalassemia gene testing as a part of an antenatal intervention program over a 10-year period. Methods: All patients underwent α-thalassemia gene testing, which included the analysis of three types of deletions and mutations. Rare α-thalassemia gene testing was performed using Sanger sequencing, multiplex ligation-dependent probe amplification, and sequencing techniques. Prenatal diagnosis was performed in high-risk couples using chorionic villus sampling or amniocentesis. Results: From 2010 to 2019, among the 91,852 patients examined, α-thalassemia mutations were identified in 41.78% of patients. The most frequent α0 gene mutation was--SEA, followed by--THAI. Two rare α0 -thalassemia gene mutations at --32.8 and --230, were also observed. A total of 2,235 high-risk couples were identified, of which 562 were affected, including three with the--SEA/--THAI genotype and one with the--SEA/--230 genotype. Additionally, prenatal diagnosis revealed four cases of fetal anemia and/or mild edema, along with two cases of severe fetal edema. Chromosome and gene chip results were normal. Thalassemia gene testing showed an αCSα/αCSα genotype in four patients with anemia and/or mild edema, while two patients with severe fetal edema had one--SEA/αCSα genotype and one--SEA/--GX genotype. Using the cut-off points of 74.6 fL and 24.4 pg as criteria for identifying α0 -thalassemia carriers and HbH disease, the detection rate of missed diagnoses in high-risk couples is consistent with national guidelines for standards, potentially saving 10,217,700 ¥. Conclusion: Routine molecular testing for α-thalassemia in high-risk prenatal populations effectively prevented severe α-thalassemia births. Despite the high cost, the cutoff points proposed by this study suggest that implementing screening using a new parameter has the potential to reduce current expenses. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia–eclampsia–HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia–eclampsia–HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83–0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99–1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90–1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96–1.22), or preeclampsia–eclampsia–HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97–1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy. [ABSTRACT FROM AUTHOR]

This article discusses the identification of partial hydatidiform mole (PHM) using non-invasive single-cell sequencing of fetal circulating extravillous trophoblasts (cEVTs) isolated from maternal blood. PHM is a condition that is typically triploid and associated with risks such as pre-eclampsia and gestational trophoblastic disease. The article presents a case study where a novel cell-based non-invasive prenatal testing (CB-NIPT) platform was used to accurately diagnose PHM. The study found that the number of cEVTs recovered from maternal blood was significantly higher in the PHM case compared to healthy controls, suggesting the potential for cEVTs as an early marker for associated hypertensive disorders and pre-eclampsia. Early diagnosis of PHM is crucial for optimal management and this study demonstrates the potential of CB-NIPT technology for early blood-based detection of PHM. [Extracted from the article]

Studying human placental development and function presents significant challenges due to the inherent difficulties in obtaining and maintaining placental tissue throughout the course of an ongoing pregnancy. Here, we provide a detailed protocol for generating trophoblast organoids from chorionic villi obtained during ongoing pregnancy. Our method results in efficient generation of trophoblast organoids from chorionic villus sampling, does not require preselection of chorionic villi, and controls contamination of decidual gland organoids. The resulting trophoblast organoids spontaneously form syncytiotrophoblasts that start secreting hCG hormone amongst other placenta-specific factors. Our approach facilitates the generation of trophoblast organoids from a variety of genetic backgrounds, including trisomies and gene mutations, and can be aligned with prenatal diagnostic routines. The protocol requires up to 14 days and can be carried out by users with expertise in cell culture.

Some studies have suggested a link between celiac disease (CD) and adverse maternal, obstetrical, and neonatal outcomes. Using a large database, we evaluated the effect of CD on pregnancy outcomes. We conducted a retrospective cohort study using the National Inpatient Sample (NIS) of all deliveries from 2015 to 2019 in the United States. Using ICD-10 codes, we identified pregnant patients who had CD and those who did not. A multivariate logistic regression was used to generate odds ratios (ORs) with 95% confidence intervals (CIs) for maternal, obstetrical, and neonatal outcomes. Of 12,039,222 deliveries between 2015 and 2019, there were 10,555 births in women with CD. Pregnant women with CD were more likely to be white and older compared to those without CD. Pregnant women with CD were significantly more likely to carry a diagnosis of gestational hypertension (OR 1.26; 95% CI 1.04–1.52), preeclampsia (1.28; 1.08–1.53), and severe preeclampsia (1.62; 1.25–2.09). They were less likely to have a full-term uncomplicated delivery (OR 0.11; 95% CI, 0.05–0.20), while being more likely to require device-assisted delivery (1.25; 1.04–1.50) and sustain 3rd or 4th degree vaginal lacerations (1.56; 1.21–2.02). Babies of pregnant women with CD were more likely to be small for gestational age (SGA) (OR 1.29; 95% CI 1.03–1.61). CD in pregnancy appears to be associated with increased adverse maternal, obstetrical, and neonatal outcomes. Clinicians should discuss these increased risks with CD patients who are planning to conceive. [ABSTRACT FROM AUTHOR]

Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes. We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation. We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences. Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3. This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes. • Fetal and maternal health outcomes due to the placenta are sexually dimorphic, therefore sequencing was performed. • Sex differences were more prevalent in first trimester, and derived mostly from sex chromosomes. • Genes common to both sexes were identified, as well as genes exclusive to each sex. • This is the largest normative placenta transcriptome atlas stratified by sex across gestation. • Genes identified may account for changes during placentation or overall outcomes based on sex. [ABSTRACT FROM AUTHOR]

Background & Objective: Prenatal invasive procedures are used for diagnostic and therapeutic purposes. The present study aimed to assess the indications and early complications of invasive diagnostic tests. Materials & Methods: This retrospective descriptive study was conducted on 708 pregnant women who were referred for prenatal invasive tests in Tehran, Iran from May 2018 to April 2022. All medical records of the participants were reviewed and entered into the study. According to the implemented procedures, medical records were categorized into two chorionic villus sampling (CVS) and amniocentesis groups. The primary outcome was determining the frequent indications of invasive diagnostic tests and post-procedure complications. Results: Six hundred and sixty-eight medical records were included. Amniocentesis procedure was performed for 624 (93.7%) and 44 cases (6.3%) underwent CVS. The most frequent indication for invasive prenatal procedures was a history of abnormal findings related to the first trimester biomarkers followed by the abnormal findings of the second trimester biochemical markers, a history of high nuchal translucency>99th percentile, and abnormal biomarkers of sequential test. Comparing post-procedure complications, the results showed no significant difference between the CVS and amniocentesis groups (P=0.845). In the amniocentesis group, 2 cases had shown spontaneous abortion and 3 leakage of amniotic fluid, as well as two cases in the CVS group, had reported vaginal bleeding. Conclusion: Our results delineated that positive fetal aneuploidy screening tests together with increased nuchal translucency were the main indications of the invasive prenatal tests. Amniotic fluid leakage, vaginal bleeding, and spontaneous abortion should be considered as procedure-related complications. [ABSTRACT FROM AUTHOR]

Background: Male sperm DNA fragmentation (SDF) may be associated with assisted reproductive technology (ART) outcomes, but the impact of SDF on the occurrence of aneuploid-related miscarriage remains controversial. Methods: Genome-wide single-nucleotide polymorphism-based chromosomal microarray analysis was performed on 495 miscarried chorionic villus samples undergone IVF/ICSI treatment from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University. SDF was assessed using sperm chromatin structure assay. Patients were divided into four groups according to embryo transfer cycle type and maternal age, and the correlation between SDF and chromosome aberration was analyzed. A receiver operating characteristic (ROC) curve was utilized to find the optimal threshold. Results: Total chromosomal aneuploidy rate was 54.95%, and trisomy was the most common abnormality (71.32%). The chromosomally abnormal group had higher SDF than the normal group (11.42% [6.82%, 16.54%] vs. 12.95% [9.61%, 20.58%], P = 0.032). After grouping, elevated SDF was significantly correlated with an increasing chromosome aneuploidy rate only in women of advanced age who underwent fresh embryo transfer (adjusted odds ratio:1.14 [1.00–1.29], adjusted-P = 0.045). The receiver operating characteristic curve showed that SDF can predict the occurrence of chromosomal abnormality of miscarried conceptus in this group ((area under the curve = 0.76 [0.60–0.91], P = 0.005), and 8.5% was the optimum threshold. When SDF was ≥ 8.5%, the risk of such patients increased by 5.76 times (adjusted odds ratio: 6.76 [1.20–37.99], adjusted-P = 0.030). Conclusion: For women of advanced maternal age undergoing fresh embryo transfer, older oocytes fertilized using sperm with high SDF in IVF/ICSI treatment might increase the risk of chromosomal abnormality in miscarried conceptus. [ABSTRACT FROM AUTHOR]

Introduction: In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine. Methods: A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD. Results: Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion: Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi 'an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0-2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus. Results: Overall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures. Conclusion: Using MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS. [ABSTRACT FROM AUTHOR]

Purpose: The hypothesis was fetal sex determination by ultrasound at 11–14 weeks' gestation has sufficient accuracy to be clinically relevant. Methods: Fetal sex assessment by transabdominal ultrasound was performed in 567 fetuses at 11–14 weeks' gestation (CRL: 45–84 mm). A mid-sagittal view of the genital region was obtained. The angle of the genital tubercle to a horizontal line through the lumbosacral skin surface was measured. The fetus was assigned male sex if the angle was > 30°, and female sex if the genital tubercle was parallel or convergent (< 10°). At an intermediate angle of 10–30°, the sex was not assigned. The results were divided into three categories based on gestational age: 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks' gestation. To establish its accuracy, the first trimester fetal sex determination was compared to fetal sex determined on a mid-second trimester ultrasound. Results: Sex assignment was successful in 534/683 (78%) of the cases. The overall accuracy of fetal sex assignment across all gestational ages studied was 94.4%. It was 88.3%, 94.7%, and 98.6% at 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks' gestation, respectively. Conclusion: Prenatal sex assignment at the time of first trimester ultrasound screening has a high accuracy rate. The accuracy improved with increasing gestational age, which suggests that if clinically important decisions, such as chorionic villus sampling, are to be made based on fetal sex, they should be delayed until the latter part of the first trimester. [ABSTRACT FROM AUTHOR]

This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended. [ABSTRACT FROM AUTHOR]

Objective: In children, interhemispheric arachnoid cysts (IHACs) are rare lesions often associated with corpus callosum dysgenesis. It is still controversial about surgical treatments for IHACs. We aim to report our experience with pediatric IHAC patients and evaluate surgical courses and neurological developments. Methods: Pediatric IHACs treated between 2001 and 2021 were reviewed retrospectively. IHAC was observed until they represented rapid cyst enlargement or neurological symptoms. Cyst fenestration was done by microscope or endoscope, depending on the IHAC's location. Cyst size and corpus callosum dysgenesis were evaluated with neuroimaging. Neurological development was assessed from medical records at the last follow-up. Results: Fifteen children received cyst fenestration surgery (mean age 11.4 months). Eleven patients (73.3%) under observation showed rapid cyst enlargement in a short period (median 5 months). Cysto-ventriculostomy (CVS) and cysto-cisternostomy (CCS) regressed the cyst size significantly (p = 0.003). The median follow-up duration was 51 months (range 14–178 months). Corpus callosum dysgenesis was observed in eleven patients (73.3%, complete = 5, partial = 6). Among eight patients (53.3%) having developmental delay, five patients (33.3%) showed speech delay, including one patient with intractable seizures. Conclusion: Pediatric IHACs frequently present within 1 year after birth, with rapid cyst enlargement. CVS and CCS were effective in regressing the cyst size. Corpus callosum dysgenesis accompanied by IHAC might have a risk of language achievement; however, development delay could rely on multifactorial features, such as epilepsy or other brain anomalies. [ABSTRACT FROM AUTHOR]

Trisomy 18 (T18) and trisomy 21 (T21) are caused by chromosomal abnormalities, leading to intellectual disabilities and various health complications. T18 is caused by an extra chromosome 18, while T21 is caused by an extra chromosome 21. Both conditions cause abnormalities in the genes, which can lead to physical abnormalities and other health complications. Prenatal screening is a critical aspect of prenatal care that aims to identify potential inherited disorders early in pregnancy. Prenatal screening can help in detecting inherited abnormalities, such as T18 and T21, by testing for a certain genetic material in the mother's blood or amniotic fluid. If the genetic material is detected, it can be further tested and, if necessary, a prenatal diagnosis can be made. This allows for early planning, including DNA counseling, to prepare for any potential health complications associated with the disorder. In recent years, microRNAs have emerged as promising candidates for biomarkers in prenatal screening. Traditional screening methods, such as ultrasound, amniocentesis, and chorionic villus sampling, have played a crucial role in identifying trisomy pregnancies, but their accuracy is limited. In this review, we explore some of the anticipated future technological advancements and their anticipated influence on these screening methods. [ABSTRACT FROM AUTHOR]

• The risk of vertical transmission is higher in primary compared to non-primary infection, but there are no differences in terms of long-term sequelae once congenital infection has been established. • Ultrasound is the primary imaging modality to evaluate fetuses with congenital CMV infection. However, the positive predictive value of ultrasound is poor in the absence of confirmed fetal infection with amniocentesis. • MRI should be used to detect anomalies not easily identified by ultrasound and should be recommended in all pregnant women with positive amniocentesis at 28–32 weeks of gestation. • Early gestational age at maternal infection is one of the main determinants of post-natal adverse outcome in fetuses with congenital CMV infection. • Maternal therapy with high dose valacyclovir (2 g every 6 h, 8 g/day) can reduce the risk of vertical transmission, the symptomatic status and other adverse outcomes associated with congenital CMV infection, while HIG is not recommended. Although the clinical work-up of CMV in pregnancy has gradually become more accurate, counseling for CMV is still challenging. Despite the potential feasibility of universal prenatal serological screening, its introduction in prenatal diagnosis continues to raise concerns related to its real cost-effectiveness. Contextually, anticipating the confirmation of fetal infection earlier in pregnancy is one of the most pressing issues to reduce the parental psychological burden. Amniocentesis is still the gold standard and recent data have demonstrated that it could be performed before 20 weeks of gestation, provided that at least 8 weeks have elapsed from the presumed date of maternal seroconversion. New approaches, such as chorionic villus sampling (CVS) and virome DNA, even if not yet validated as confirmation of fetal infection, have been studied alternatively to amniocentesis to reduce the time-interval from maternal seroconversion and the amniocentesis results. Risk stratification for sensorineural hearing loss (SNHL) and long-term sequelae should be provided according to the prognostic predictors. Nevertheless, in the era of valacyclovir, maternal high-dose therapy, mainly for first trimester infections, can reduce the risk of vertical transmission and increase the likelihood of asymptomatic newborns, but it is still unclear whether valacyclovir continues to exert a beneficial effect on fetuses with positive amniocentesis. This review provides updated evidence-based key counseling points with GRADE recommendations. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the prevalence of computer vision syndrome (CVS) and its associated factors among undergraduate college students. Methodology: An analytical cross-sectional study was conducted from April 2022 to October 2022 using a web-based survey. A sample of 415 undergraduate college students was included through convenience sampling. Data collection utilized a self-structured questionnaire for socio-demographic information and a validated questionnaire (CVS-Q). Data entry and analysis were performed using SPSS version 23. Chi-square test and logistic regression were employed to identify associations and predictors, respectively, with statistical significance set at p = 0.05. Results: The mean age of the participants was 21.3 ± 2.8 years. Among 415 participants, the prevalence of CVS was 60.9%, with headache being the most commonly reported symptom (73.2%). Female gender (p < 0.001), presence of refractive error (p < 0.001), use of video display terminal (VDT) devices (p = 0.007), daily average screen time (p = 0.006), and lighting conditions while using VDT devices (p = 0.05) were significantly associated with CVS. Conclusion: A high frequency of computer vision syndrome was observed among undergraduate college students. Female gender, refractive error, type of VDT used, average screen time, and lighting conditions during VDT device use were significantly associated with CVS. [ABSTRACT FROM AUTHOR]

Congenital ichthyosis represents a wide spectrum of diseases. This article reviews prenatal testing for ichthyosis. We used pubmed.ncbi.nlm.nih.gov to search for 38 types of congenital ichthyosis combined with 17 words related to prenatal testing. Search resulted in 408 publications covering 13 types of ichthyoses and four types of tests. Biochemical testing is diagnostic in trichothiodystrophy, but nonspecific in X-linked ichthyosis and Refsum syndrome. Except in X-linked ichthyosis, biochemical testing requires invasive procedures to obtain fetal skin biopsy, amniocytes, or chorionic villus samples. It is superior to histological and cytological examination of fetal skin biopsy or amniocytes because keratinization occurs later in pregnancy and microscopy cannot differentiate between ichthyosis types. Imaging is more acceptable due to noninvasiveness and routine use, although ultrasonography is operator-dependent, nonspecific, and captures abnormalities at late stage. Molecular tests are described in at-risk pregnancies but testing of free fetal DNA was not described. [ABSTRACT FROM AUTHOR]

Study design: Cross sectional Background: Computers and visual display terminals are now an essential part of both our personal and professional lives thanks to phenomenal advancements in technology. Universities make substantial use of computers as a teaching and learning tool. Medical professionals can now access tools like medication formularies and medical calculators on their smart phones while holding textbooks. This necessitates reflection on the possible harmful health conditions that digital natives' increased screen time. Methods: Data for this cross-sectional study were gathered using a specially designed questionnaire that included demographic questions as well as questions about CVS and sleep disorders. After the group of experts had several conversations, a questionnaire was created. A language expert, a researcher, and a subject specialist made up this panel. Result: We had 60% prevalence of CVS, we did not observe any significant differences while comparing gender with 20-20 rules. Conclusion: In summary, a significant number of college students have both poor sleep quality and CVS. This is a serious public health concern that requires consideration. [ABSTRACT FROM AUTHOR]

Study Design: Cross sectional Background: Computer vision syndrome (CVS) is defined as a collection of vision-related symptoms and musculoskeletal symptoms that happen due to continuous and improper use of electronic devices, such as computers, tablets, and smart phones. It causes eye problems and muscular complaints, which may lead to a decreased efficiency and quality of life. The aim of this study is to estimates the prevalence, knowledge, and associated factors of CVS among electronic device users in the Asser region, Kingdom of Saudi Arabia. Methods: A Descriptive cross-sectional study was conducted to All Saudi and non-Saudi population of Aseer region except People who can’t read or understand Arabic. The sample size required for this study is calculated as 700 participants for 95% confidence level and a margin of error of 5%. The participants received electronic self-administered questionnaire distributed via social media platforms during 2022. The tool covers the following three parts: bio demographic data, knowledge and associated factors related questions and prevalence of the CVS symptoms. Informed consent will be obtained from all participants. Furthermore, the questionnaire is anonymous. Results: A total of 700 participants who met the inclusion criteria completed the study questionnaire. The age of the responders varied from less than 20 years to older than 60 years. A total of 367 (53.71%) responses were females. Eye problems after the use of electronic devices were experienced by 393 (56.14%) of the responders. Neck and shoulder pain being the most common symptom (79.95%), followed by blurred vision (71.07%), burning eye sensation (61.68%) and headache (60.41%). The more spent time with less taking breaks on electronic devices increasing the incidence of CVS symptoms. Back bent position was correlate with CVS symptoms . Conclusion: Computer vision syndrome (CVS) is very common among the study participants, with neck and shoulder pain being the most common symptoms. This study has shown that the development of CVS is associated significantly with the longer duration of electronic devices use(more than 5 hours daily), no taking breaks while using electronic devices, short distance (less than 40cm)from the electronic devices and sitting with back bent. We found in our study that the computer vision syndrome (CVS) is a growing public health problem, resulting in variety of complaints and symptoms. Thus, preventive measures and community education about the burden of such lifestyle, and the proper handling of devices must be addressed. [ABSTRACT FROM AUTHOR]

Studying human placental development and function presents significant challenges due to the inherent difficulties in obtaining and maintaining placental tissue throughout the course of an ongoing pregnancy. Here, we provide a detailed protocol for generating trophoblast organoids from chorionic villi obtained during ongoing pregnancy. Our method results in efficient generation of trophoblast organoids from chorionic villus sampling, does not require preselection of chorionic villi, and controls contamination of decidual gland organoids. The resulting trophoblast organoids spontaneously form syncytiotrophoblasts that start secreting hCG hormone amongst other placenta-specific factors. Our approach facilitates the generation of trophoblast organoids from a variety of genetic backgrounds, including trisomies and gene mutations, and can be aligned with prenatal diagnostic routines. The protocol requires up to 14 days and can be carried out by users with expertise in cell culture. [ABSTRACT FROM AUTHOR]

Background: Omphalocele and gastroschisis are the most frequent congenital developmental abdominal wall defects. Prenatal diagnosis of omphalocele and gastroschisis is critical in the management of the pregnancy, affording patients the option of termination. This study aims to evaluate the prenatal diagnosis and postnatal outcomes of omphalocele and gastroschisis cases. Materials and Methods: The cases of gastroschisis and omphalocele diagnosed prenatally and followed up at our university were evaluated retrospectively between January 2019 and January 2022. Maternal demographic and clinical characteristics and perinatal outcomes were compared between the cases. Results: This study evaluated 42 omphalocele and nine gastroschisis cases. All gastroschisis cases were isolated (p =.001). Additional anomalies were present in 61.9% of omphalocele cases. While two patients with gastroschisis refused the invasive procedure, the genetic results of the others were normal. The karyotype was abnormal in 42.9% of omphalocele cases (p =.008). Half of the omphalocele cases were terminated, and 38.1% (n = 8) of the terminated omphalocele cases were trisomy 18. The coexistence of multiple system anomalies and cystic hygroma was high in the terminated cases. In all cases of gastroschisis, only the intestines protruded from the abdominal wall into the amniotic fluid. The number of survivors of omphalocele was 23.8%. The median hospital stay was 25 and 14 days for gastroschisis and omphalocele, respectively. Conclusion: Prenatal diagnosis of omphalocele and gastroschisis is critical in pregnancy management. The presence of associated anomalies determines the prognosis of omphalocele and gastroschisis. [ABSTRACT FROM AUTHOR]

BackgroundThe risks of invasive prenatal tests are reported in previous studies such as miscarriage, fetal anomalies, and bleeding. However, few compare short-term and long-term outcomes between invasive tests. This study aims to investigate obstetric, perinatal, and children’s neurodevelopmental outcomes following chorionic villus sampling (CVS) or amniocentesis in singleton pregnancy.MethodsThis retrospective cohort study included healthy singleton pregnancies underwent transabdominal CVS (gestational age [GA] at 10–13 weeks) or amniocentesis (GA at 15–21 weeks) at a single medical center between 2012 and 2022. Only cases with normal genetic results were eligible. Short-term and long-term neurodevelopmental outcomes were evaluated.ResultsThe study included 200 CVS cases and 498 amniocentesis cases. No significant differences were found in body mass index, parities, previous preterm birth, conception method, and cervical length (CL) before an invasive test between the groups. Rates of preterm labor, preterm premature rupture of the membranes, preterm birth, neonatal survival, neonatal short-term morbidities, and long-term neurodevelopmental delay were similar. However, the CVS group had a higher rate of cervical cerclage due to short CL before 24 weeks (7.0%) compared to the amniocentesis group (2.4%). CVS markedly increased the risk of cervical cerclage due to short CL (adjusted odd ratio [aOR] = 3.17, 95%CI [1.23–8.12], p = 0.016), after considering maternal characteristics.ConclusionPerforming CVS resulted in a higher incidence of cerclage due to short cervix or cervical dilatation compared to amniocentesis in singleton pregnancies. This highlights the importance of cautious selection for CVS and the necessity of informing women about the associated risks beforehand.

Purpose Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was performed to investigate the clinical utility of prenatal diagnosis of 21-OHD using molecular genetic testing in families at risk. Methods This study included 27 pregnant women who had previously borne a child with 21-OHD. Fetal tissues were obtained using chorionic villus sampling (CVS) or amniocentesis. After the genomic DNA was isolated, Sanger sequencing of CYP21A2 and multiplex ligation-dependent probe amplification were performed. The clinical and endocrinological findings were reviewed retrospectively. Results A total of 39 prenatal genetic tests was performed on 27 pregnant women and their fetal tissues. The mean gestational age at the time of testing was 11.7 weeks for CVS and 17.5 weeks for amniocentesis. Eleven fetuses (28.2%) were diagnosed with 21-OHD. Among them, 10 fetuses (90.9%) harbored the same mutation as siblings who were previously diagnosed with 21-OHD. Among these, 4 fetuses (3 males and 1 female) identified as affected were born alive. All 4 patients have been treated with hydrocortisone, 9α-fludrocortisone, and sodium chloride since a mean of 3.7 days of life. The male patients did not show hyponatremia and dehydration, although they harbored pathogenic variants associated with the salt-wasting type of 21-OHD. Conclusions This study demonstrated the diagnostic efficacy and clinical consequences of diagnosis by prenatal genetic testing in families at risk for 21-OHD. All patients identified as affected were treated with hydrocortisone and 9α-fludrocortisone early after birth, which can prevent a life-threatening adrenal crisis.

This document is a Clinical Practice Update developed by the American College of Obstetricians and Gynecologists. It provides guidance on the use of paternal and fetal genotyping in the management of alloimmunization in pregnancy. The update recommends determining the paternal genotype to assess fetal risk and suggests molecular testing for accurate determination of RHD zygosity. It also discusses the use of noninvasive fetal red blood cell antigen genotyping using cell-free DNA as an alternative to invasive testing. The document emphasizes the importance of discussing testing options with pregnant patients and acknowledges the diversity of gender identities and family structures. [Extracted from the article]

We introduce two rare obstetric entities. They show very similar image findings, but the prognosis is different. Prognosis is generally favorable for complete hydatidiform mole with coexisting fetus (CHMCF), but placental mesenchymal dysplasia (PMD) has high fetal and neonatal mortality. Differential diagnosis is essential to management of pregnancy. Twin pregnancies with CHMCF are characterized by the coexistence of complete mole (diploid without fetal parts) and a normal live fetus with a normal placenta. US Findings: 1. Normal fetus and normal placenta with umbilical cord insertion 2. Separated molar placenta, vesicular sonographic pattern Differential Diagnosis: Partial mole (Triploid) Hematoma in placenta (normal β-hCG level) Placental mesenchymal dysplasia Biochemistry: β-hCG concentrations are extremely high • Chorionic villus sampling can be useful to differentiate in early pregnancy between CHMCF and partial hydatidiform mole • Amniocentesis or fetal blood sampling • Genotype of a CHM is entirely of paternal origin • Management of pregnancies with CHMCF has not been standardized • Continuation of CHMCF is an acceptable option: Intensive maternal follow up ultrasonography and β-hCG level monitoring • The chance of a live birth is 7 - 37%. • Complications: Fetal death, vaginal bleeding, preeclampsia, hyperthyroidism, gestational trophoblastic neoplasia Case 1: A 31-year old woman, gravida 2, para 0 CC: IUP at 17 weeks with abnormal placenta. Serum β-hCG levels: 234,358 mIU/mL (elevated) Fetal US: IUP at 17 weeks Twin pregnancy with complete H-mole and coexisting fetus Emergency Cesarian section for fetal distress at 27 wks Delivery: Boy, Apgar score 1'-1, 5'-1 Cytogenetic report: 46, XY, normal Pathological Diagnosis: Complete hydatidiform mole with coexisting fetus Case 2: A 32-year old woman, gravida 1, para 0 CC: IVF pregnancy follow up Serum β-hCG levels: 1,873,485 mIU/mL (elevated) Fetal US: IUP at 8 weeks Twin pregnancy with complete H-mole and coexisting fetus Dilatation and evacuation for vaginal bleeding at 10 weeks Pathological Diagnosis: Complete hydatidiform mole with coexisting fetus Part I: multiple fragments of placental tissue (about 5cc) with variable sized cysts (up to 0.7cm) Part II: multiple fragments of placental tissue (5 × 3cm) without grape like cystic change Developed persistent trophoblastic disease and 18 cycle chemotherapy Case 3: A 34-year old woman, gravida 1, para 0 CC: IVF pregnancy follow up fetus Serum β-hCG levels: 306,645 mIU/mL (elevated) Fetal US: IUP at 17 weeks Twin pregnancy with complete H-mole and coexisting fetus Rare placental lesion estimated to occur in 0.02% of pregnancies. Placental enlargement, dilated and tortuous chorionic vessels, and a focal distribution of cystically enlarged villi. US Findings: Typical large and thickened with multicystic, hypoechoic areas Differential Diagnosis: Partial mole, complete hydatidiform mole with coexisting fetus (CHMCF), chorangioma, intervillous hematoma, infarct or nonspecific hydropic changes • Characteristic morphologic features • Lack of trophoblastic hyperplasia –> maternal serum β-hCG levels are not elevated or only slightly elevated • No known risk of persistent gestational trophoblastic disease • No other specific maternal serum markers • Perinatal demise: not certain, but high as 43% • Cause of fetal death: Massive fetal hemorrhage secondary to rupture of delated periumbilical chorionic vessels Case 4: A 34-year old woman, gravida 1, para 0 CC: IUP at 12 weeks weeks Twin pregnancy with complete H-mole and coexisting fetus Serum β-hCG levels: 39,249 mIU/mL Fetal US: IUP at 12 weeks Twin pregnancy with complete H-mole and coexisting fetus Chorionic Villus Sampling (12 weeks) • Normal appearing placenta: 46, XX Normal • Abnormal appearing placenta: 46, XX Normal QF-PCR: placental mesenchymal dysplasia Pathological Diagnosis: Placental mesenchymal dysplasia Case 5: A 35-year old woman, gravida 2, para 1 CC: IUP 19 weeks, abnormal enlarged and honeycomb shaped placenta Serum β-hCG levels: none Fetal US: IUP at 20 weeks Twin pregnancy with complete H-mole and coexisting fetus R/O Placental mesenchymal dysplasia Amniocenthesis: Mosaicism 47,XY +15[3]/46,XX[31] Pathological Diagnosis: Placental mesenchymal dysplasia Complete Hydatidiform Mole with Coexisting Fetus vs Placental Mesenchymal Dysplasia We proposed two differential diagnosis points 1. Proportion of two patterns of placenta - CHMCF: similar size of two patterns of placenta - PMD: dominant vesicular pattern placenta 2. Umbilical cord insertion - CHMCF: center of normal placenta - PMD: junction of two different patterns of placenta → finally insert into abnormal placenta [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic hypertension in women of reproductive age is on the rise mainly due to delayed childbearing. Maternal chronic hypertension, prevailing prior to conception or manifesting within the early gestational period, poses a substantial risk for the development of preeclampsia with adverse maternal and fetal outcomes, specifically as a result of placental dysfunction. We aimed to investigate whether chronic hypertension is associated with placenta-mediated complications regardless of the development of preeclampsia in pregnancy. Methods: This was a population-based, retrospective cohort study from 'Soroka' university medical center (SUMC) in Israel, of women who gave birth between 1991 and 2021, comparing placenta-mediated complications (including fetal growth restriction (FGR), placental abruption, preterm delivery, and perinatal mortality) in women with and without chronic hypertension. Generalized estimating equation (GEE) models were used for each outcome to control for possible confounding factors. Results: A total of 356,356 deliveries met the study's inclusion criteria. Of them, 3949 (1.1%) deliveries were of mothers with chronic hypertension. Women with chronic hypertension had significantly higher rates of all placenta-mediated complications investigated in this study. The GEE models adjusting for preeclampsia and other confounding factors affirmed that chronic hypertension is independently associated with all the studied placental complications except placental abruption. Conclusions: Chronic hypertension in pregnancy is associated with placenta-mediated complications, regardless of preeclampsia. Therefore, early diagnosis of chronic hypertension is warranted in order to provide adequate pregnancy follow-up and close monitoring for placental complications, especially in an era of advanced maternal age. [ABSTRACT FROM AUTHOR]

Introduction: Chorionic villus sampling (CVS) remains essential for first-trimester genetic diagnosis, yet clinical volume may be insufficient to train new clinicians in the technique. Available simulation models are expensive, require animal parts or specialized resins, and cannot be stored for repeated use. Methods: We present a model for trans-abdominal CVS (TA-CVS) which is constructed from readily available materials costing less than $10 and can be refrigerated and re-used to train maternal-fetal medicine fellows in CVS. Results: All three attending physicians performing TA-CVS at our institution described the model as an accurate visual and tactile simulation, prompting its integration into our fellowship curriculum. To date, two senior fellows have achieved competency on the simulator and begun to perform clinical CVS under supervision, one of whom is an author on this paper. Both fellows and attendings indicated that the simulator provided a valuable tool for repeated practice prior to clinical CVS. Simulators are now maintained on the unit and have been re-used for 3 months and dozens of simulated procedures each without any apparent qualitative degradation in performance. Discussion/Conclusion: We describe a low-cost easily constructed, durable, high-fidelity simulator for TA-CVS. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between human chorionic gonadotropin and adverse pregnancy outcomes. Medline, Embase, PubMed, and Cochrane were searched in November 2021 using Medical Subject Headings (MeSH) and relevant key words. This analysis included published full-text studies of pregnant women with serum human chorionic gonadotropin testing between 8 and 28 weeks of gestation, investigating fetal outcomes (fetal death in utero, small for gestational age, preterm birth) or maternal factors (hypertension in pregnancy: preeclampsia, pregnancy-induced hypertension, placental abruption, HELLP syndrome, gestational diabetes mellitus). Studies were extracted using REDCap software. The Newcastle–Ottawa scale was used to assess for risk of bias. Final meta-analyses underwent further quality assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. A total of 185 studies were included in the final review, including the outcomes of fetal death in utero (45), small for gestational age (79), preterm delivery (62), hypertension in pregnancy (107), gestational diabetes mellitus (29), placental abruption (17), and HELLP syndrome (2). Data were analyzed separately on the basis of categorical measurement of human chorionic gonadotropin and human chorionic gonadotropin measured on a continuous scale. Eligible studies underwent meta-analysis to generate a pooled odds ratio (categorical human chorionic gonadotropin level) or difference in medians (human chorionic gonadotropin continuous scale) between outcome groups. First-trimester low human chorionic gonadotropin levels were associated with preeclampsia and fetal death in utero, whereas high human chorionic gonadotropin levels were associated with preeclampsia. Second-trimester high human chorionic gonadotropin levels were associated with fetal death in utero and preeclampsia. Human chorionic gonadotropin levels are associated with placenta-mediated adverse pregnancy outcomes. Both high and low human chorionic gonadotropin levels in the first trimester of pregnancy can be early warning signs of adverse outcomes. Further analysis of human chorionic gonadotropin subtypes and pregnancy outcomes is required to determine the diagnostic utility of these findings in reference to specific cutoff values. [ABSTRACT FROM AUTHOR]

Purpose Multiple endocrine neoplasia types 1 (MEN1) and 2 (MEN2) are inherited endocrine tumor syndromes caused by mutations in the MEN1 or RET genes. This study aimed to investigate clinical outcomes and molecular characteristics among children with MEN. Methods This study included eight patients from seven unrelated families. Data on clinical course, biochemical findings, and radiologic studies were collected by retrospective chart review. All diagnoses were genetically confirmed by Sanger sequencing of MEN1 in three MEN1 patients and RET in four patients with MEN2A and one patient with MEN2B. Results Three patients with MEN1 from two families presented with hypoglycemia at a mean age of 11±2.6 years. Four patients with MEN2A were genetically diagnosed at a mean of 3.0±2.2 years of age by family screening; one of them was prenatally diagnosed by chorionic villus sampling. Three patients with MEN2A underwent prophylactic thyroidectomy from 5 to 6 years of age, whereas one patient refused surgery. The patient with MEN2B presented with a tongue neuroma and medullary thyroid carcinoma at 6 years of age. Subsequently, he underwent a subtotal colectomy because of bowel perforation and submucosal ganglioneuromatosis at 18 years of age. Conclusion This study described the relatively long clinical course of pediatric MEN with a mean follow-up duration of 7.5±3.8 years. Insulinoma was the first manifestation in children with MEN1. Early diagnosis by family screening during the asymptomatic period enabled early intervention. The patient with MEN2B exhibited the most aggressive clinical course. [ABSTRACT FROM AUTHOR]

Rapid improvements in the field of prenatal medicine have been achieved due to the technological advancement of ultrasonography that has allowed recognition of various ultrasonographic findings and their combination with biochemical results and demographic characteristics in order to estimate a final individual risk for a chromosomal anomaly of the fetus and analysis of short fragments of fetal DNA released into the mother's bloodstream through a natural process of cell death. Invasive testing still remains the main clinically available diagnostic modality for the definite diagnosis of both chromosomal anomalies and many single-gene disorders. Amniocentesis is performed between 15 and 20 weeks of pregnancy to obtain fetal cells for genetic testing. This method is performed almost in the middle of pregnancy, and waiting for the results of the analysis may indicate termination of pregnancy in the second trimester. Chorionic villus sampling (CVS), usually performed between 11+0 and 13+6 weeks of gestation, is one of the invasive diagnostic methods used to diagnose chromosomal, genetic, and metabolic diseases in the embryonic period. Invasive procedures such as CVS and amniocentesis still remain the only definitive diagnostic tests for aneuploidy in pregnancy. CVS, as an invasive procedure carried out with experienced physicians in specialist centers, is not associated with a significant increase in fetal loss rate, with a risk rate below 0.5%, and the possible background risk for miscarriage is significantly higher in the presence of fetal anomaly and abnormal karyotype. Ultrasound-guided transabdominal (TA) CVS is a useful outdoor procedure and is considered the method of choice for fetal sampling and accurate early prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the use of Exome Sequencing (ES) for the detection of genome-wide Copy Number Variants (CNVs) and the frequency of SNVs-InDels in selected genes related to developmental disorders in a cohort of consecutive pregnancies undergoing invasive diagnostic procedures for minor or simple ultrasound findings with no indication of ES. Methods: Women undergoing invasive diagnostic testing (chorionic villus sampling or amniocentesis) for QF-PCR and chromosomal microarray analysis (CMA) due to prenatal ultrasound findings without an indication for ES were selected over a five-month period (May–September 2021). ES was performed to compare the efficiency of genome-wide CNV detection against CMA analysis and to detect monogenic disorders. Virtual gene panels were selected to target genes related to ultrasound findings and bioinformatic analysis was performed, prioritizing variants based on the corresponding HPO terms. The broad Fetal Gene panel for developmental disorders developed by the PAGE group was also included in the analysis. Results: A total of 59 out of 61 women consented to participate in this study. There were 36 isolated major fetal anomalies, 11 aneuploidy markers, 6 minor fetal anomalies, 4 multiple anomalies, and 2 other ultrasound signs. Following QF-PCR analysis, two uncultured samples were excluded from this study, and six (10%) common chromosome aneuploidies were detected. In the remaining 51 cases, no pathogenic CNVs were detected at CMA, nor were any pathogenic variants observed in gene panels only targeting the ultrasound indications. Two (3.9%) monogenic diseases, apparently unrelated to the fetal phenotype, were detected: blepharo-cheilo-odontic syndrome (spina bifida) and Duchenne muscular dystrophy (pyelocaliceal dilation). Conclusions: In our series of pregnancies with ultrasound findings, common aneuploidies were the only chromosomal abnormalities present, which were detected in 10% of cases. ES CNV analysis was concordant with CMA results in all cases. No additional findings were provided by only targeting selected genes based on ultrasound findings. Broadening the analysis to a larger number of genes involved in fetal developmental disorders revealed monogenic diseases in 3.9% of cases, which, although apparently not directly related to the indications, were clinically relevant. [ABSTRACT FROM AUTHOR]

Background: 3M syndrome is a rare autosomal recessive developmental disorder characterized by pre and postnatal growth deficiency, dysmorphic facial features, and normal intelligence. 3M syndrome should be suspected in a proband with a combination of characteristic or recognizable dysmorphic features. The diagnosis of 3M syndrome could be confirmed by identifying biallelic variants in CUL7, OBSL1, or CCDC8. Methods: Whole‐exome sequencing (WES) was performed to identify genetic causes. Reverse‐transcription polymerase chain reaction (RT‐PCR) was performed to detect aberrant splicing events. Haplotypes were constructed using multiplex PCR and sequencing. Variants of the parental haplotype and target likely pathogenic variants were detected by PCR and Sanger sequencing from the embryos. Copy number variant (CNV) detection was performed by next‐generation sequencing. Results: We present the case of a nonconsanguineous Chinese couple with one abnormal pregnancy, where the fetus showed 3M phenotypes of shortened long bones. WES identified two novel heterozygous mutations in CUL7: NM_014780.5:c.354del (p.Gln119ArgfsTer52) and NM_014780.5:c.1373‐15G>A. RT‐PCR from RNA of the mother's peripheral blood leucocytes showed that c.1373‐15G>A caused the insertion of a 13‐bp extra intron sequence and encoded the mutant p.Leu459ProfsTer25. Both variants were classified as likely pathogenic according to ACMG/AMP guidelines and Clinical Genome Resource specifications. During genetic counseling, the options of prenatal diagnosis through chorionic villus sampling or amniocentesis, adoption, sperm donation, and electing not to reproduce, as well as preimplantation genetic testing for monogenic disorders (PGT‐M), were discussed. The couple hopes to conceive a child of their own and refused to accept the 25% risk during the next pregnancy and opted for PGT‐M. They finally successfully delivered a healthy baby through PGT‐M. Conclusion: This study expanded the mutation spectrum of CUL7, detected the aberrant splicing event of CUL7 via RT‐PCR, constructed the haplotype for PGT‐M, and demonstrated the successful delivery of a healthy baby using PGT‐M. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the prevalence, risk factors, symptoms, and awareness of computer vision syndrome (CVS) among medical students during the coronavirus disease 2019 (COVID-19) pandemic. Methods: A cross-sectional observational study was conducted among 283 undergraduate medical students at a tertiary healthcare center. An electronic survey was conducted to collect the data. Data were analyzed using Statistical Package for Social Sciences (SPSS version 23). The Chi-square test (Fisher's exact test when required) was used to study the significance of associations. A P value <0.05 was considered statistically significant. Results: A high prevalence of CVS was observed in which 92% reported at least one symptom while using a digital device, the most frequent being eye strain (49%). Among extraocular complaints, joint pain in the wrist and fingers was most frequent. Significant association (P < 0.05) of CVS was found with increased duration of digital device usage, refractive error, use of glasses or contact lens, preexisting dry eye disease, and use of topical eye drops. 37% of the participants were aware of the 20-20-20 rule, while only 11% followed it. Conclusion: CVS is a common health concern among medical students. Hence, to increase the productivity of work, significant risk factors need to be addressed and awareness must be raised. [ABSTRACT FROM AUTHOR]

The need to determine the sex of the fetus in early pregnancy is usually based on medical indications for early implementation of appropriate therapeutic procedures, and is sometimes driven by parental curiosity. Medicine has made tremendous progress in early diagnosis of fetal sex in the last decades. The diagnostic methods described in the literature are characterized by varying degrees of accuracy, cost, and potential risk to the fetus. For these reasons, there is an ongoing debate about when and in which cases a particular method should be used. This paper presents an overview of the current methods of fetal sex determination. [ABSTRACT FROM AUTHOR]