Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.

OBJECTIVES: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. METHODS: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. RESULTS: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. CONCLUSIONS: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

Diagnostic yield with exome sequencing in prenatal severe bilateral ventriculomegaly: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to determine the incremental diagnostic yield of prenatal exome sequencing after negative chromosomal microarray analysis results in prenatally diagnosed bilateral severe ventriculomegaly or hydrocephalus; another objective was to categorize the associated genes and variants. DATA SOURCES: A systematic search was performed to identify relevant studies published until June 2022 using 4 databases (Cochrane Library, Web of Science, Scopus, and MEDLINE). STUDY ELIGIBILITY CRITERIA: Studies in English reporting on the diagnostic yield of exome sequencing following negative chromosomal microarray analysis results in cases of prenatally diagnosed bilateral severe ventriculomegaly were included. METHODS: Authors of cohort studies were contacted for individual participant data, and 2 studies provided their extended cohort data. The incremental diagnostic yield of exome sequencing was assessed for pathogenic/likely pathogenic findings in cases of: (1) all severe ventriculomegaly; (2) isolated severe ventriculomegaly (as the only cranial anomaly); (3) severe ventriculomegaly with other cranial anomalies; and (4) nonisolated severe ventriculomegaly (with extracranial anomalies). To be able to identify all reported genetic associations, the systematic review portion was not limited to any minimal severe ventriculomegaly case numbers; however, for the synthetic meta-analysis, we included studies with ≥3 severe ventriculomegaly cases. Meta-analysis of proportions was done using a random-effects model. Quality assessment of the included studies was performed using the modified STARD (Standards for Reporting of Diagnostic Accuracy Studies) criteria. RESULTS: A total of 28 studies had 1988 prenatal exome sequencing analyses performed following negative chromosomal microarray analysis results for various prenatal phenotypes; this included 138 cases with prenatal bilateral severe ventriculomegaly. We categorized 59 genetic variants in 47 genes associated with prenatal severe ventriculomegaly along with their full phenotypic description. There were 13 studies reporting on ≥3 severe ventriculomegaly cases, encompassing 117 severe ventriculomegaly cases that were included in the synthetic analysis. Of all the included cases, 45% (95% confidence interval, 30-60) had positive pathogenic/likely pathogenic exome sequencing results. The highest yield was for nonisolated cases (presence of extracranial anomalies; 54%; 95% confidence interval, 38-69), followed by severe ventriculomegaly with other cranial anomalies (38%; 95% confidence interval, 22-57) and isolated severe ventriculomegaly (35%; 95% confidence interval, 18-58). CONCLUSION: There is an apparent incremental diagnostic yield of prenatal exome sequencing following negative chromosomal microarray analysis results in bilateral severe ventriculomegaly. Although the greatest yield was found in cases of nonisolated severe ventriculomegaly, consideration should also be given to performing exome sequencing in cases of isolated severe ventriculomegaly as the only brain anomaly identified on prenatal imaging.

Disparities in obstetric morbidity by maternal level of education.

BACKGROUND: Maternal race and socioeconomic status are predictors of obstetric morbidity and mortality in the U.S. A better understanding of the role that maternal education plays in these disparities could enable and target better interventions to improve obstetric outcomes. OBJECTIVE: This study aims to assess the impact of the level of education on morbidity. STUDY DESIGN: We conducted a retrospective nested cohort study from a multicenter observational cohort of women undergoing cesarean delivery. Nulliparous women with live, non-anomalous singleton gestations who underwent primary cesarean section and had education status recorded were included. Education level was categorized as none, elementary, high school, some college, and a college degree. The primary outcome was a composite of maternal cesarean complications including hysterectomy, uterine atony, blood transfusion, surgical injury, arterial ligation, infection, wound complication, and ileus. A composite of neonatal morbidity was evaluated as a secondary outcome. We then created a multivariable logistic regression model adjusting for selected demographic and obstetric variables that may influence the likelihood of the primary outcome. RESULTS: 10,344 women met inclusion criteria with a 20.3% incidence of the primary outcome. After adjusting for potential confounding variables including race and medical co-morbidities, the incidence of maternal cesarean complications was found to be higher for women with only elementary (OR 1.34, 95% CI 1.01-1.78) and high school (OR 1.24, 95% CI 1.03-1.48) education, compared to women with a college degree. There was also higher neonatal morbidity among women with high school (OR 1.39, 95% CI 1.20-1.62) and some college (OR 1.23, 95% CI 1.04-1.46) education, compared to women with a college degree. CONCLUSION: These findings suggest that efforts to alleviate adverse outcomes in obstetrics should target patient counseling and health literacy as differences in educational background are closely associated with disparities in maternal and neonatal morbidity.

Telehealth Uptake into Prenatal Care and Provider Attitudes during the COVID-19 Pandemic in New York City: A Quantitative and Qualitative Analysis.

OBJECTIVE: This study aimed to (1) determine to what degree prenatal care was able to be transitioned to telehealth at prenatal practices associated with two affiliated hospitals in New York City during the novel coronavirus disease 2019 (COVID-19) pandemic and (2) describe providers' experience with this transition. STUDY DESIGN: Trends in whether prenatal care visits were conducted in-person or via telehealth were analyzed by week for a 5-week period from March 9 to April 12 at Columbia University Irving Medical Center (CUIMC)-affiliated prenatal practices in New York City during the COVID-19 pandemic. Visits were analyzed for maternal-fetal medicine (MFM) and general obstetrical faculty practices, as well as a clinic system serving patients with public insurance. The proportion of visits that were telehealth was analyzed by visit type by week. A survey and semistructured interviews of providers were conducted evaluating resources and obstacles in the uptake of telehealth. RESULTS: During the study period, there were 4,248 visits, of which approximately one-third were performed by telehealth (n = 1,352, 31.8%). By the fifth week, 56.1% of generalist visits, 61.5% of MFM visits, and 41.5% of clinic visits were performed via telehealth. A total of 36 providers completed the survey and 11 were interviewed. Accessing technology and performing visits, documentation, and follow-up using the telehealth electronic medical record were all viewed favorably by providers. In transitioning to telehealth, operational challenges were more significant for health clinics than for MFM and generalist faculty practices with patients receiving public insurance experiencing greater difficulties and barriers to care. Additional resources on the patient and operational level were required to optimize attendance at in-person and video visits for clinic patients. CONCLUSION: Telehealth was rapidly implemented in the setting of the COVID-19 pandemic and was viewed favorably by providers. Limited barriers to care were observed for practices serving patients with commercial insurance. However, to optimize access for patients with Medicaid, additional patient-level and operational supports were required. KEY POINTS: · Telehealth uptake differed based on insurance.. · Medicaid patients may require increased assistance for telehealth.. · Quick adoption of telehealth is feasible..

Telehealth for High-Risk Pregnancies in the Setting of the COVID-19 Pandemic.

As New York City became an international epicenter of the novel coronavirus disease 2019 (COVID-19) pandemic, telehealth was rapidly integrated into prenatal care at Columbia University Irving Medical Center, an academic hospital system in Manhattan. Goals of implementation were to consolidate in-person prenatal screening, surveillance, and examinations into fewer in-person visits while maintaining patient access to ongoing antenatal care and subspecialty consultations via telehealth virtual visits. The rationale for this change was to minimize patient travel and thus risk for COVID-19 exposure. Because a large portion of obstetric patients had underlying medical or fetal conditions placing them at increased risk for adverse outcomes, prenatal care telehealth regimens were tailored for increased surveillance and/or counseling. Based on the incorporation of telehealth into prenatal care for high-risk patients, specific recommendations are made for the following conditions, clinical scenarios, and services: (1) hypertensive disorders of pregnancy including preeclampsia, gestational hypertension, and chronic hypertension; (2) pregestational and gestational diabetes mellitus; (3) maternal cardiovascular disease; (4) maternal neurologic conditions; (5) history of preterm birth and poor obstetrical history including prior stillbirth; (6) fetal conditions such as intrauterine growth restriction, congenital anomalies, and multiple gestations including monochorionic placentation; (7) genetic counseling; (8) mental health services; (9) obstetric anesthesia consultations; and (10) postpartum care. While telehealth virtual visits do not fully replace in-person encounters during prenatal care, they do offer a means of reducing potential patient and provider exposure to COVID-19 while providing consolidated in-person testing and services. KEY POINTS: · Telehealth for prenatal care is feasible.. · Telehealth may reduce coronavirus exposure during prenatal care.. · Telehealth should be tailored for high risk prenatal patients..

Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection.

OBJECTIVE: To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes. METHODS: Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19-related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described. RESULTS: Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26-6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26-9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down-level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated. CONCLUSION: One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down-level care.

Port Site Metastases: A Survey of the Society of Gynecologic Oncology and Commentary on the Clinical Workup and Management of Port Site Metastases.

STUDY OBJECTIVE: Laparoscopic port site metastases (PSMs) have an incidence of .5% to 2%. The management of an isolated PSM (iPSM), without evidence of recurrence elsewhere, remains unclear. The aim of this study was to elucidate practices regarding iPSMs. DESIGN: A 23-item survey was created using commercially available survey software. Over the course of January 2016 the survey was e-mailed to the members of the Society of Gynecologic Oncology with 2 follow-up reminder e-mails. (Canadian Task Force classification III.) SETTING: Online survey. MEASUREMENTS AND MAIN RESULTS: Of the 709 surveys sent, 132 were returned. Providers practicing for <5 years saw fewer PSMs and those who performed more minimally invasive surgeries (MISs) saw more PSMs. Comparing providers who have or have not seen PSMs, no differences in pneumoinsufflation pressure, the mode of delivery of the specimen, the use of local anesthesia at port site incisions, or the method of deflation were seen. If an iPSM was suspected, most providers indicated they would obtain imaging (computed tomography, 51%, or positron emission tomography/computed tomography, 43%) followed by an interventional radiology-guided biopsy (29%) or resection of the mass. Tendency for treatment is to surgically resect the lesion followed by adjuvant therapy. CONCLUSION: After controlling for time in practice, we did not find a strong risk factor for iPSMs other than performing >75% of oncologic surgeries by MIS. Most respondents performed imaging when suspecting iPSMs and use systemic adjuvant therapy after confirming iPSMs.

Improving quality of surgical care and outcomes: factors impacting surgical site infection after colorectal resection.

Surgical site infections (SSIs) result in patient morbidity and increased costs. The purpose of this study was to determine reasons underlying SSI to enable interventions addressing identified factors. Combining data from the American College of Surgeons National Surgical Quality Improvement Project with medical record extraction, we evaluated 365 patients who underwent colon resection from January 2009 to December 2012 at a single institution. Of the 365 patients, 84 (23%) developed SSI. On univariate analysis, significant risk factors included disseminated cancer, ileostomy, patient temperature less than 36°C for greater than 60 minutes, and higher glucose level. The median number of cases per surgeon was 36, and a case volume below the median was associated with a higher risk of SSI. On multivariate analysis, significant risks associated with SSI included disseminated cancer (odds ratio [OR], 4.31; P < .001); surgery performed by a surgeon with less than 36 cases (OR, 2.19; P = .008); higher glucose level (OR, 1.06; P = .017); and transfusion of five units or more of blood (OR, 3.26; P = .029). In this study we found both modifiable and unmodifiable factors associated with increased SSI. Identifying modifiable risk factors enables targeting specific areas to improve the quality of care and patient outcomes.