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Objective: To investigate the association of agenesis of the ductus venosus (ADV) with genetic abnormalities using genetic studies—Chromosomal Microarray Analysis (CMA) and Exome Sequencing (ES). Design: Retrospective study of all fetuses diagnosed with ADV between January 2013 and December 2022 in a tertiary center. Results: ADV was diagnosed in 33 fetuses. The diagnosis was made at a mean gestational age of 21.2 ± 8.4 weeks. Conventional karyotype was applied in a single fetus (3.0%), CMA was applied in 21 fetuses (66.7%), and five fetuses (22.8%) were additionally tested with ES. ADV was isolated in eight fetuses (24%), whereas in 25 (76%) it was associated with abnormal ultrasound findings, including increased nuchal translucency (NT), intrauterine growth restriction (IUGR) and variable structural malformations, mostly cardiac (42%) followed by central nervous system (CNS) and skeletal malformations (24%). Genetic abnormalities were found in six fetuses out of 22 investigated (27%), of which 3 were detected by ES, 3 by CMA and 1 by conventional karyotype. A higher incidence of genetic aberrations was evident among ADVs associated with abnormal ultrasound findings. Genetic abnormalities were indicative of Prader Willi/Angelman syndrome, Noonan syndrome, CASK related disorder, 16q24.3 microdeletion syndrome and Trisomy 21. Conclusion: ADV associated with abnormal ultrasound findings is commonly correlated with genetic abnormalities and consequently unfavorable pregnancy outcomes. Our study emphasizes the value of genetic studies chiefly among cases associated with abnormal ultrasound findings, enabling early diagnosis of fetal pathologies associated with ADV, and providing better parental counseling. [ABSTRACT FROM AUTHOR]

Objective: To investigate how many novel pathogenic (P) and likely pathogenic (LP) nonprotein‐truncating or noncanonical splicing variants would be classified as variants of unknown significance (VUS) if they were detected in fetuses without abnormalities. Methods: The study included 156 patients with neurodevelopmental disorders diagnosed through postnatal exome sequencing. Causative P/LP nonprotein‐truncating and noncanonical splicing variants were retrospectively reclassified in cases without specific prenatal manifestations, disregarding postnatal symptoms. Results: Of the 156 patients, 72 had a nontruncating or noncanonical splicing variant. Six patients were excluded for having more than one possible causative variant. Twelve patients had prenatal malformations known to be associated with the diagnosed disorder; therefore, variant interpretation remained unchanged. In 33 of the 54 remaining cases, the variant had been previously reported as P/LP. Reclassification of the other 21 LP/P variants revealed that 16 would have been classified as VUS if detected prenatally. Conclusion: In our cohort, ∼24% (16/66) of causative nonprotein‐truncating/noncanonical splicing variants would have been classified as VUS if sequencing had been conducted during pregnancy. The potential for false‐negative results, stemming from limitations in the phenotypic information available prenatally, should be discussed with prospective parents. The criteria for classifying and reporting variants in the prenatal setting may require adjustment. [ABSTRACT FROM AUTHOR]

Objective: Significant discrepancy exists between laboratories in classification and reporting of copy number variants (CNVs). Studies exploring factors affecting prenatal CNV management are rare. Our "virtual fetus" pilot study examines these factors. Method: Ten prenatally diagnosed CNVs of uncertain significance (VUS) > 1Mb, encompassing OMIM‐morbid genes, inherited from healthy parents, were classified by 15 MD geneticists from laboratory, prenatal, and preimplantation genetic testing (PGT) units. Geneticists addressed factors affecting classification, obligation to report, and recommendation for invasive testing or PGT. Results: CNVs were classified likely benign (10.7%), VUS (74.7%), likely pathogenic (8.7%), or pathogenic (6.0%). Classification discrepancy was higher for losses versus gains. Classifying pathogenic/likely pathogenic was more common for losses (adjusted odds ratio [aOR] 10.9, 95% CI 1.55–76.9), and geneticists specializing in gynecology (aOR 4.9, 95% CI 1.03–23.3). 84.0% of respondents would report CNVs, depending on classification and family phenotype. Invasive testing in pregnancies was recommended for 29.3% of CNVs, depending on the classification and geneticist's specialization. PGT was recommended for 32.4%, depending on classification, experience years, and family's phenotype (38.0% for patients undergoing in vitro fertilization irrespectively, 26.7% otherwise). Conclusion: Factors affecting CNV classification/reporting are mainly dosage, family phenotype, geneticist specialization and experience. Understanding factors from our pilot study may facilitate developing an algorithm for clinical consensus and optimal management. Key points: What's already known about this topic?Chromosomal Microarray Analysis (CMA) currently constitutes the first‐tier test in genetic evaluation of fetuses. Although the utilization of CMA is well established, the clinical dilemmas it causes remain complex since the phenotype of many copy number variants (CNVs) cannot be accurately estimated prenatally. CNVs with scarce data and variants of uncertain significance (VUS) frequently cause patient stress. Despite constant guideline updates, significant inconsistency exists in CNV classification and reporting by different laboratories. What does this study add?In our "virtual fetus" model we found large variability in interpreting prenatal CMA results. Copy number losses versus gains, familial phenotype of variants, and clinician's background (medical field, years of experience) were found to have a major impact on how variants are interpreted and reported, and recommendations given for preimplantation/prenatal testing in subsequent pregnancies. Awareness of variation in interpretation and complexity in clinical decisions regarding CNVs may standardize optimal prenatal management. [ABSTRACT FROM AUTHOR]

Purpose: Women carriers of FMR1 premutation are at increased risk of early ovarian dysfunction and even premature ovarian insufficiency. The aim of this study was to examine a possible association between FMR1 permutation and numeric sex chromosome variations. Methods: A retrospective case-control study conducted in the reproductive center of a university-affiliated medical center. The primary outcome measure was the rate of sex chromosomal numerical aberrations, as demonstrated by haplotype analyses, in FMR1 premutation carriers compared to X-linked preimplantation genetic testing for monogenic/single gene defect (PGT-M) cycles for other indications that do not affect the ovarian follicles and oocytes. Results: A total of 2790 embryos with a final genetic analysis from 577 IVF PGT-M cycles were included in the final analysis. Mean age was similar between the groups, however, FMR1 carriers required more gonadotropins, and more women were poor responders with three or less oocytes collected. The ratio of embryos carrying a numeric sex chromosome variation was similar: 8.3% (138/1668) of embryos in the FMR1 group compared to 7.1% (80/1122) in the controls. A subgroup analysis based on age and response to stimulation has not demonstrated a significant difference either. Conclusions: Although carriers of FMR1 premutation exhibit signs of reduced ovarian response, it does not seem to affect the rate of numeric sex chromosomal variation compared to women undergoing PGT-M for other indications. This suggests that the mechanism for chromosomal number aberrations in women at advanced maternal age are different to those FMR1 premutation carriers with poor ovarian reserve. [ABSTRACT FROM AUTHOR]

Objectives: Phacomatoses are a group of neuro-oculo-cutaneous syndromes/ neurocutaneous disorders, involving structures arising from the embryonic ectoderm. Most of phacomatoses including the most common ones:, neurofibromatosis type I and type II (NF1, NF2) and tuberosclerosis complex (TSC), are autosomal dominant genetic disorders with full penetrance and variable expression. As no effective treatment exists, the only way to prevent the disease, is by prenatal genetic diagnosis (either chorionic villus sampling-CVS or amniocentesis-AC) and termination of pregnancy or performing preimplantation genetic testing (PGT). As the risk for an affected offspring is 50% in every pregnancy of an affected parent, prenatal, and preimplantation testing are of great importance. However, those procedures are associated with technical and ethical concerns. This chapter shortly reviews the common phacomatoses emphasizes their genetics and inheritance. We will review the common methods for prenatal and preimplantation diagnoses and discuss its use in common phacomatoses. Conclusion: Phacomatoses are common autosomal dominant genetic conditions with variable expression. Ante-natal genetic diagnosis is an appropriate approach for family planning in individuals affected by phacomatosis or parents of an affected child. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to evaluate the incidence of chromosomal aberration (both microscopic and submicroscopic) and the clinical outcome of fetuses with isolated muscular ventricular septal defect (VSD). Material and methods: The study included 40 pregnant women whose fetuses were diagnosed with isolated muscular ventricular septal defect (mVSD). Of these, 30 patients underwent amniocentesis and 10 declined. All samples were tested by chromosomal microarray analysis (CMA). Of the 40 women in the study, 32 gave birth and the clinical outcome of the children was retrieved from the patients' medical records. Results: Of the 30 patients who underwent amniocentesis, one was detected with mosaic Klinefelter syndrome and one was detected with a pathogenic copy number variant unrelated to the VSD. Clinical follow-up was performed on 26 children after birth. The first postnatal echocardiography did not detect a VSD in 13 (50%) of the followed-up children. Spontaneous closure occurred in another eight (30.8%) children during the postnatal follow-up period. In only five children (19.2%) VSD was still detected by echocardiography after the first year of life. Discussion: Isolated muscular VSD diagnosed prenatally does not appear to be a significant risk factor for chromosomal abnormalities and has a favorable clinical outcome. [ABSTRACT FROM AUTHOR]

Purpose: Meconium-stained amniotic fluid (MSAF) is rarely observed in preterm pregnancies, and its clinical significance is undetermined. We evaluated the correlation between MSAF and obstetrical and perinatal complications prior to 34 weeks' gestation.Materials and Methods: Pregnancies complicated with MSAF between 24 and 34 weeks of gestation were compared with same gestational age-matched controls. The variables measured were: obstetrical complications: clinical chorioamnionitis, Intrahepatic Cohlestasis of Pregnancy - ICP, Intra Uterine Growth Restriction - IUGR, preeclampsia, gestational diabetes; nonobstetrical complications; and perinatal complications: cord around neck/body, Apgar <7 at 5 min, cord pH, Neonatal Intensive Care Unit - NICU admission, complications during NICU hospitalization, and composite outcome.Results: Higher incidence of clinical chorioamnionitis (15% versus 4.3%; p = 0.041) and higher incidence of cord around the neck/body were found in the MSAF group in comparison with the clear AF group (27.4% versus 18.4%; p = 0.04). No significant differences between the study's groups were found in nonobstetrical complications or other perinatal complications investigated in our study.Conclusion: MSAF in preterm pregnancy is an ominous sign for the occurrence of chorioamnionitis and for in utero cord compression. Therefore, MSAF in preterm pregnancies should be considered as a non-reassuring sign. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study is to evaluate the incidence of chromosomal aberration (both microscopic and sub-microscopic) in fetuses with an aberrant right subclavian artery (ARSA) detected by ultrasonographic anomaly scan. Methods The study included 62 pregnant women whose fetuses were diagnosed with ARSA who were referred for genetic counseling. Of these, 55 patients underwent amniocentesis and 7 declined invasive testing. All 55 amniocentesis samples were tested by standard G-banding and chromosomal microarray, except for 2 samples for which only karyotype and fluorescence in situ hybridization for 22q11.2 deletions were performed. Results Of the 55 women who underwent amniocentesis, 5 were detected with trisomy 21 (9.1%), all of whom had additional ultrasound findings. Among the 14 fetuses with ARSA and additional ultrasound findings, the incidence of trisomy 21 was 35.7%. In fetuses with isolated ARSA, no chromosomal aberrations were detected by standard cytogenetic analysis and only one (1.9%) deleterious copy number variants (CNV) was detected by chromosomal microarray. Conclusion Aberrant right subclavian artery with additional ultrasound findings constitute a strong predictor for aneuploidy. However, when ARSA is found in isolation, it confers no increased risk for aneuploidy or pathogenic CNVs. © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An excerpt from the book "The Teacher Wars: A History of America's Most Embattled Profession" by Dana Goldstein is presented which focuses on the issues of public school teachers and teaching as a career profession in the U.S.

Objective The aim of this study is to examine the hypothesis that prolonged rupture of membranes (PROM) is associated with increased cord blood erythropoietin (EPO) concentrations, proportional to the duration of ruptured membranes. Study Design This study is a prospective, cross-sectional, observational (noninterventional) cohort study of mother-infant pairs. Criteria for inclusion were as follows: active labor with or without ruptured membranes and vaginally delivered neonates. Excluded were infants with major factors known to be associated with a potential increase in fetal erythropoiesis. Results A total of 40 mother-infant pairs were recruited. EPO was not influenced by duration of ruptured membranes and significantly correlated only with maternal body mass index. Conclusion Cord blood concentrations of EPO do not appear to be significantly affected by the duration of ruptured membranes. We speculate that erythropoiesis is upregulated in PROM by mechanisms that involve the production of cytokines and are not EPO driven. [ABSTRACT FROM AUTHOR]

The article reports on 26 adolescent boys and adult men who describe having been sexually abused by Catholic priests as children or adolescents. The length of time that it takes boys and men to report this abuse; the characteristics of priests' abuse; psychological sequelae, including psychiatric diagnosis; sexual concerns such as fantasies and questioning orientation; sexual abuse of others; and impact on spirituality has been discussed. All of the men described anger regarding the impact of the abuse on their sexual lives. They felt robbed and also felt unable to talk about it with anyone.

Transabdominal sonogram performed at 15 weeks of gestation. The white arrows demonstrate an aberrant right subclavian artery behind the fetal trachea. From Svirsky et al., Prenatal Diagnosis 37: 808‐811, DOI: 10.1002/pd.5092. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to evaluate the incidence of chromosomal aberration (both microscopic and sub-microscopic) in fetuses with an aberrant right subclavian artery (ARSA) detected by ultrasonographic anomaly scan.Methods: The study included 62 pregnant women whose fetuses were diagnosed with ARSA who were referred for genetic counseling. Of these, 55 patients underwent amniocentesis and 7 declined invasive testing. All 55 amniocentesis samples were tested by standard G-banding and chromosomal microarray, except for 2 samples for which only karyotype and fluorescence in situ hybridization for 22q11.2 deletions were performed.Results: Of the 55 women who underwent amniocentesis, 5 were detected with trisomy 21 (9.1%), all of whom had additional ultrasound findings. Among the 14 fetuses with ARSA and additional ultrasound findings, the incidence of trisomy 21 was 35.7%. In fetuses with isolated ARSA, no chromosomal aberrations were detected by standard cytogenetic analysis and only one (1.9%) deleterious copy number variants (CNV) was detected by chromosomal microarray.Conclusion: Aberrant right subclavian artery with additional ultrasound findings constitute a strong predictor for aneuploidy. However, when ARSA is found in isolation, it confers no increased risk for aneuploidy or pathogenic CNVs. © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article focuses on the author's travel to Israel and Palestine to discover whether food could possibly help to instill trust in an atmosphere of increasing hatred. She expresses her disappointment over the current governmental policies attempt to erase Palestinians from the historical narrative. She believes that food can open dialogue by helping build a common cultural identity between Israelis and Palestinians.