Genetic counseling practices among outpatient obstetric providers in the Northeast.

BACKGROUND: 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. OBJECTIVE: This study aimed to describe how patient, provider, and practice demographics influence the offering of diagnostic prenatal genetic testing by outpatient prenatal care providers. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Prenatal Screening for Microdeletions and Rare Autosomal Aneuploidies.

Noninvasive prenatal screening with cell-free DNA is now considered a first-line screening for common aneuploidies. Advancements in existing laboratory techniques now allow to interrogate the entirety of the fetal genome, and many commercial laboratories have expanded their screening panels to include screening for rare autosomal aneuploidies and copy number variants. Here, we review the currently available data on the performance of fetal cell-free DNA to detect rare autosomal aneuploidies and copy number variants that are associated with clinically significant microdeletion and microduplication syndromes and the current position of medical societies on routine screening for these syndromes.

Impact of introducing cell-free DNA screening into clinical care on first trimester ultrasound.

OBJECTIVE: First-trimester ultrasound is an important component of prenatal care. We investigated the impact of introducing cell-free DNA (cfDNA) aneuploidy screening into routine care, on performance of first-trimester ultrasound. METHODS: Retrospective study of patients who had prenatal care at a tertiary referral center. We compared the performance of any first-trimester ultrasound between three different aneuploidy screening protocols, used consecutively during the study period: (1) combined first-trimester screening (FTS); (2) FTS and cfDNA offered together; (3) patients requested to choose between FTS and cfDNA. Secondary outcomes included performance of nuchal translucency (NT), aneuploidy screens and diagnostic genetic procedures. RESULTS: The number of patients undergoing first-trimester ultrasound remained similar with the second protocol but decreased in the third (68.7% vs. 40.9%, OR 0.32, 95% CI 0.25-0.4, p < 0.001). Diagnostic procedures decreased between protocol 1 and 2 (7.6% vs. 4.4%, OR 0.59, 95% CI 0.37-0.93, p = 0.02) while NT scans decreased between protocol 2 and 3 (6.8% vs. 1.3%, OR 0.18, 95% CI 0.09-0.4, p < 0.001). The rate of FTS decreased over the study period and less women had cfDNA when they had to choose one method (p < 0.001). CONCLUSIONS: Introducing cfDNA screening as an alternative to FTS, resulted in fewer patients receiving ultrasound in the first-trimester.

Fetal Screening for Chromosomal Abnormalities.

With more and more reproductive-aged women opting to pursue genetic screening during pregnancy, health care professionals must understand the variety of testing options available as well as the advantages and limitations of each testing option. Presently, no single screening test is universally believed to be superior because the combination of the specific test and the population being tested determines the range of potential identifiable conditions as well as the positive predictive values. As a result, pre- and posttest counseling are not always straightforward and may require discussions with multiple specialists including genetic counselors, obstetricians, and pediatricians/neonatologists. The purpose of this review is to summarize the screening options currently available to pregnant women to determine their risk of having a child affected by a chromosomal disorder. Screening for chromosomal abnormalities using ultrasonography, maternal serum analytes, cell-free DNA, and preimplantation genetic testing will be discussed here. Advances in the field, including the possible future use of cell-based noninvasive prenatal screening (NIPS) as a more accurate method for genetic screening and the incorporation of screening for copy number variants (microdeletions and duplications) into traditional cell-free NIPS will also be reviewed.

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota.

Understanding what happens at the time of embryo implantation has been the subject of significant research. Investigators from many differing fields including maternal fetal medicine, microbiology, genetics, reproductive endocrinology and immunology have all been studying the moment the embryo interacts with the maternal endometrium. A perfect relationship between the uterus and the embryo, mediated by a tightly controlled interaction between the embryo and the endometrium, is required for successful implantation. Any factors affecting this communication, such as altered microbiome may lead to poor reproductive outcomes. Current theories suggest that altered microbiota may trigger an inflammatory response in the endometrium that affects the success of embryo implantation, as inflammatory mediators are tightly regulated during the adhesion of the blastocyst to the epithelial endometrial wall. In this review, we will highlight the various microbiome found during the periconceptual period, the microbiomes interaction with immunological responses surrounding the time of implantation, its effect on implantation, placentation and ultimately maternal and neonatal outcomes.

Uterine structural abnormality and intrauterine device malposition: analysis of ultrasonographic and demographic variables of 517 patients.

BACKGROUND: Intrauterine devices are currently one of the leading forms of reversible contraception in the world. However, in approximately 10-25% of women, intrauterine devices can become malpositioned, leading to consequences including pain, bleeding, as well as possible decreased contraceptive efficacy. OBJECTIVE: We sought to determine whether certain reproductive and uterine characteristics are associated with an increased risk of intrauterine device malposition. We hypothesized that anatomical characteristics such as the presence of any uterine anomalies, particularly congenital anomalies and fibroids that may lead to cavitary distortion, would be associated with a higher incidence of intrauterine device malposition. MATERIALS AND METHODS: We conducted a retrospective case-control study in an academic medical center. All patients presenting for scheduled ultrasound appointments for gynecologic indication between June 2004 and February 2016 were included (1,253 ultrasound reports identified). Of these, 236 demonstrated malpositioned intrauterine devices. With a control group of 281 patients with normal intrauterine device location, a total of 517 patients were included in the study. Transabdominal and transvaginal ultrasounds were performed followed by 3-dimensional rendering (as per our institution's protocol for patients with intrauterine devices) using Voluson 730 and Voluson E8 ultrasound machines. Demographic and reproductive characteristics, indication for ultrasound, intrauterine device, and uterine characteristics were all extrapolated from the electronic medical record. χ2 Tests were performed for categorical variables. Generalized linear models for Poisson distributed variables, and multiple logistic regression were used to ascertain significant independent predictors of IUD malposition. Ninety-five percent confidence intervals and effect sizes were calculated, and P < .05 was considered statistically significant. RESULTS: In this study, we found a cumulative IUD malposition rate of 19%. In patients with malpositioned intrauterine devices, there was increased incidence of retroflexed uterine positions (7.6% vs 1.8%, P = .001), and all uterine anomalies (this includes septate and bicornuate uteri and fibroids, 31.9% vs 23.5%, P = .02) compared with controls. The anterior midline uterine position was more commonly noted in controls (28.5% vs 11%, P < .001). A higher total number of fibroids was noted in the malpositioned group (3.7 vs 1.8, P = .01); however, fibroid size was not statistically significant. In particular, there was an increased incidence of submucosal fibroids in women with malpositioned intrauterine devices (P = .01). Multivariable logistic regression revealed that anterior midline position (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.20-0.57) and absence of uterine anomalies (OR, 0.59; 95% CI, 0.38-0.93) were factors associated with a lower risk of IUD malposition; whereas vaginal bleeding (OR, 2.25; 95% CI, 1.38-3.67), pain (OR, 2.85; 95% CI, 1.84-4.44), or missing IUD strings at time of presentation (OR, 3.58; 95% CI, 1.88-6.82) were associated with an increased risk of malposition. CONCLUSION: Retroflexed uterine positions and all uterine malformations are associated with higher incidence of malpositioned intrauterine devices. Presence of increased number of fibroids and specifically submucosal fibroids showed a positive association with intrauterine device malposition, as did symptoms of bleeding, pain, and missing IUD strings at time of presentation. These findings pertain to women presenting for gynecologic ultrasound evaluation and may not be generalizable to all women with IUDs.

The Labor Games.

OBJECTIVE: To develop and evaluate a simulation laboratory designed to stimulate learning and increase medical students' preparedness for an obstetrics and gynecology clinical clerkship. METHODS: Ninety-seven medical students participated in the games during their obstetrics and gynecology clerkship in 1 year. Using the resident-as-teacher model, students rotated through seven stations, each with a simulated obstetric task. Points were awarded at each station, and the student with the highest score won. Self-perceived proficiency level and general preparedness for the clerkship were evaluated through paired pregame and postgame assessments. RESULTS: Postassessment results showed statistically significant (P<.001) increases in self-perceived competence performing all tested skills including reading fetal heart tracings, knot-tying, measuring cervical dilation, amniotomy, estimating fetal weight, and estimating blood loss. Approximately 97% enjoyed The Labor Games, 97.9% reported increased knowledge, and 96.9% learned valuable skills. Students also reported feeling more prepared for the obstetrics and gynecology rotation (2.6 compared with 3.3, P<.001). DISCUSSION: The Labor Games improved medical students' self-confidence and self-perceived skill level on obstetric tasks. Students also felt more prepared for the obstetrics and gynecology clerkship. This study creates a low-cost and reproducible simulation laboratory that is identified as effective by medical students in teaching skills, knowledge, and preparedness for an obstetrics and gynecology clerkship.

Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria.

Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.