UNASSIGNED: The 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.
UNASSIGNED: This 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.
UNASSIGNED: The 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.
UNASSIGNED: Performing 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.

Aim This study aims to assess the effect of implementing an enhanced prenatal genetic checklist to guide the provider\'s discussion on both screening and diagnostic options for fetal aneuploidy testing at the initial prenatal visit. Methods A retrospective quality improvement (QI) project was performed at a single, large, urban academic medical center. The implementation of this project was prospective; however, data was examined retrospectively after the QI initiative was implemented for three months. Patients were included if they were less than 24 weeks gestational age with a live intrauterine gestation at their initial obstetric (OB) visit. Patients less than 18 years old at the initial OB visit were excluded. The results were analyzed using the statistical software R. Chi-squared tests were used to examine proportional differences between the pre- and post-intervention groups with respect to demographic and clinical characteristics and documented genetic counseling discussions. Results A total of 416 patients were included in the final cohort. As measured by documentation, the rate of discussion of diagnostic prenatal genetic testing increased significantly from the pre-intervention proportion of 54% to the post-intervention proportion of 72% (p < 0.001). In the subgroup analysis of patients with advanced maternal age, the rate of discussion of diagnostic prenatal genetic testing increased significantly from the pre-intervention proportion of 53% to the post-intervention proportion of 83% (p = 0.003), and the rate of genetics counseling referrals made at the initial prenatal visit increased significantly from 4% pre-intervention to 38% post-intervention (p < 0.001). Conclusions The use of an enhanced prenatal genetic checklist led to increased discussion of diagnostic fetal aneuploidy testing and increased rates of referral to genetics counseling.

Developments in preconception and prenatal technologies have led to undeniable advances in how health-care providers screen and treat patients. Despite these advances, at any point errors can occur leading to misdiagnosis or a missed diagnosis. In some instances, the missed information can lead to the birth of a child with health issues where short of the error, the decision to avoid conception or terminate the pregnancy might have been made. When these lapses unfold, there exists the potential for a wrongful birth or wrongful life lawsuit to ensue. While these 2 actions are based on the same set of events, they are distinct legal claims with varying degrees of judicial permissibility. Global legal acceptability of wrongful birth and life lawsuits tends to resemble patterns in the United States. Analyzing prior wrongful birth and wrongful life claims can reveal common trends in events leading to these types of lawsuits, as well as an understanding of their potential outcomes. A familiarity with wrongful birth and wrongful life lawsuits demonstrates how these cases are unique from other forms of prenatal or birth injury tort lawsuits and can provide insights to common shortcomings in clinical practice. Applying these lessons to clinical practice highlights key approaches towards limiting the risk of certain errors leading to wrongful birth and wrongful life lawsuits, with the goal of health-care providers offering high quality health care.

Obesity rates are increasing world-wide with most of the increase in women of the reproductive age group. While recognised as an important contributor to non-communicable diseases, pregnant women with obesity are particularly at risk of not only maternal and pregnant complications but also have an increased risk of congenital malformations. Furthermore, pregnant obese women are more likely to be older and therefore at a greater risk of aneuploidy. Prenatal diagnosis in these women especially those who are morbidly obese is challenging due not only to their weight but the implications of the increase adiposity on biochemical markers of aneuploidy. In this review we discuss the current challenges in providing prenatal diagnosis for these women including those related to the ergonomics of ultrasound and those inherent in them because of their obesity. Appropriate counselling for these women should include the lower sensitivity of the tests, the difficulties in performing some of the procedures (imaging and invasive testing) as well as the increased risk of structural abnormalities related to their obesity.

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.

OBJECTIVE: 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.

Rupture of membranes in the first trimester is extremely rare. Generally at this gestational age, rupture is a complication of invasive genetic testing. Little is known about the complications or sequelae of such an occurrence and therefore the management options are limited. This article reports the case of a 35-year-old woman who had rupture of membranes after chorionic villus sampling in the first trimester; it describes her pregnancy course and eventual positive outcome. Regardless of gestational age at time of fluid loss, treatment options are limited. This article reviews the evidence regarding first-trimester rupture and the outcomes of expectant management.

BACKGROUND: 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.
CONCLUSIONS: We describe a low-cost easily constructed, durable, high-fidelity simulator for TA-CVS.

This retrospective case-controlled study analysed the outcome of pregnancies with first-trimester enlarged nuchal translucency (NT) and a normal karyotype. A total of 479 pregnancies with first-trimester NT measurements were grouped as control (370 cases; normal NT) and study (109 cases; enlarged NT, ≥95th percentile; with normal karyotype). Adverse outcomes included miscarriage, intrauterine foetal death, termination of pregnancy, neonatal death, and structural/chromosomal/genetic abnormalities. The study was conducted between June 2016 and June 2022 at the Foetal Maternal Unit of Kanad Hospital, UAE. Overall, the live birth rate in the study group was significantly lower (74.3%) compared to the control (94.1%, p < 0.001). All pregnancy outcomes of this group significantly differed compared to the control. The observed miscarriage level was 9.2% (vs. 1.1%, p < 0.001), intrauterine foetal death was 2.8% (vs. 0%, p = 0.001), spontaneous preterm birthwas 11% (vs. 4.9%, p = 0.020), and termination of pregnancy was 3.7% (vs. 0%, p < 0.001). The presence of foetal abnormalities was also significantly higher in the enlarged NT group at 21% (vs. 3.3%, p < 0.001). Results indicate that enlarged NT is associated with adverse pregnancy outcomes even when the karyotype is normal. Based on these results, a comprehensive review of the guidelines for counselling and managing pregnancies with enlarged NT and a normal karyotype is recommended.

The American College of Obstetricians and Gynecologists recommends all pregnant people be offered genetic screening and diagnostic testing regardless of risk factors. Previous studies have demonstrated disparities in referrals for genetic testing by race outside of pregnancy, but limited data exist regarding genetic counseling practices during pregnancy.
This study aimed to describe how patient, provider, and practice demographics influence the offering of diagnostic prenatal genetic testing by outpatient prenatal care providers.
This was a multicenter anonymous survey study conducted between October 2021 and March 2022. Outpatient prenatal care providers, including family medicine and obstetrics attendings, residents, maternal-fetal medicine fellows, nurse practitioners, physician assistants, and midwives, were surveyed about their genetic counseling practices and practice demographics. The primary outcome was the proportion of respondents who answered \"yes, all patients\" to the survey question \"Do you offer diagnostic genetic testing to all patients?\" The secondary outcomes included the association between patient and practice demographics and offering diagnostic testing. Diagnostic testing was defined as chorionic villus sampling or amniocentesis. Screening genetic tests were defined as sequential screen, quadruple screen, cell-free DNA screening, or \"other.\" The chi-square test or Fisher exact test was used as appropriate. For the outcome answers of diagnostic testing, logistic regression was performed to assess the association between the answer of diagnostic genetic testing and the current training level of providers, race and ethnicity, and insurance status variables. Multivariable analysis was performed to adjust for confounders.
A total of 635 outpatient prenatal care providers across 7 sites were sent the survey. Overall, 419 providers responded for a total response rate of 66%. Of the providers who responded, most were attendings (44.9%), followed by residents (37.5%). Providers indicated the race, insurance status, and primary language of their patient population. Screening genetic testing was offered by 98% of providers. Per provider report, 37% offered diagnostic testing to all patients, 18% did not offer it at all, and 44% only offered it if certain patient factors were present. Moreover, 54.8% of attendings reported universally offering diagnostic testing. On univariable analysis, residents were less likely to offer diagnostic testing than attendings (odds ratio, 0.18; 95% confidence interval, 0.11-0.30). Providers who serve non-Hispanic Black, Hispanic Black, and other Hispanic patients were less likely to report offering diagnostic testing than other patient populations. Providers who served non-Hispanic Whites were more likely to offer diagnostic testing (odds ratio, 2.26; 95% confidence interval, 1.51-3.39). Patient populations who were primarily privately insured were more likely to be offered diagnostic testing compared with primarily publicly insured patients (odds ratio, 6.25; 95% confidence interval, 3.60-10.85). Providers who served a primarily English-speaking population were more likely to offer diagnostic genetic testing than other patient populations (odds ratio, 0.43; 95% confidence interval, 0.26-0.69). On multivariable analysis, the factors that remained significantly associated with offering diagnostic testing included level of training (resident odds ratio, 0.33; 95% confidence interval, 0.17-0.62; P=.0006; advanced practice provider odds ratio, 0.34; 95% confidence interval, 0.15-0.82; P=.02), having at least one-third of the patient population identify as \"other Hispanic\" (odds ratio, 0.42; 95% confidence interval, 0.23-0.77; P=.005), and having private insurance instead of public insurance (primarily private insured odds ratio, 2.84; 95% confidence interval, 1.20-6.74; P=.02).
Although offering genetic screening and diagnostic testing to all patients is recommended, no provider group universally offers diagnostic testing. Providers who serve populations from a racial and ethnic minority, those with public insurance, and those whose primary language is not English are less likely to report universally offering diagnostic genetic testing.