Diagnostic Performance of Ultrasonography-Based Risk Models in Differentiating Between Benign and Malignant Ovarian Tumors in a US Cohort.

Importance: Ultrasonography-based risk models can help nonexpert clinicians evaluate adnexal lesions and reduce surgical interventions for benign tumors. Yet, these models have limited uptake in the US, and studies comparing their diagnostic accuracy are lacking. Objective: To evaluate, in a US cohort, the diagnostic performance of 3 ultrasonography-based risk models for differentiating between benign and malignant adnexal lesions: International Ovarian Tumor Analysis (IOTA) Simple Rules with inconclusive cases reclassified as malignant or reevaluated by an expert, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX), and Ovarian-Adnexal Reporting and Data System (O-RADS). Design, Setting, and Participants: This retrospective diagnostic study was conducted at a single US academic medical center and included consecutive patients aged 18 to 89 years with adnexal masses that were managed surgically or conservatively between January 2017 and October 2022. Exposure: Evaluation of adnexal lesions using the Simple Rules, ADNEX, and O-RADS. Main Outcomes and Measures: The main outcome was diagnostic performance, including area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Surgery or follow-up were reference standards. Secondary analyses evaluated the models' performances stratified by menopause status and race. Results: The cohort included 511 female patients with a 15.9% malignant tumor prevalence (81 patients). Mean (SD) ages of patients with benign and malignant adnexal lesions were 44.1 (14.4) and 52.5 (15.2) years, respectively, and 200 (39.1%) were postmenopausal. In the ROC analysis, the AUCs for discriminative performance of the ADNEX and O-RADS models were 0.96 (95% CI, 0.93-0.98) and 0.92 (95% CI, 0.90-0.95), respectively. After converting the ADNEX continuous individualized risk into the discrete ordinal categories of O-RADS, the ADNEX performance was reduced to an AUC of 0.93 (95% CI, 0.90-0.96), which was similar to that for O-RADS. The Simple Rules combined with expert reevaluation had 93.8% sensitivity (95% CI, 86.2%-98.0%) and 91.9% specificity (95% CI, 88.9%-94.3%), and the Simple Rules combined with malignant classification had 93.8% sensitivity (95% CI, 86.2%-98.0%) and 88.1% specificity (95% CI, 84.7%-91.0%). At a 10% risk threshold, ADNEX had 91.4% sensitivity (95% CI, 83.0%-96.5%) and 86.3% specificity (95% CI, 82.7%-89.4%) and O-RADS had 98.8% sensitivity (95% CI, 93.3%-100%) and 74.4% specificity (95% CI, 70.0%-78.5%). The specificities of all models were significantly lower in the postmenopausal group. Subgroup analysis revealed high performances independent of race. Conclusions and Relevance: In this diagnostic study of a US cohort, the Simple Rules, ADNEX, and O-RADS models performed well in differentiating between benign and malignant adnexal lesions; this outcome has been previously reported primarily in European populations. Risk stratification models can lead to more accurate and consistent evaluations of adnexal masses, especially when used by nonexpert clinicians, and may reduce unnecessary surgeries.

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.

FMR1 premutation frequency in a large, ethnically diverse population referred for carrier testing.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is caused by an expansion of cytosine-guanine-guanine (CGG) repeats in the FMR1 gene. Female premutation allele carriers (55-200 CGG repeats) are at risk to have an affected child. Currently, specific population-based carrier screening for FXS is not recommended. Previous studies exploring female premutation carrier frequency have been limited by size or ethnicity. This retrospective study provides a pan-ethnic estimate of the Fragile X premutation carrier frequency in a large, ethnically diverse population of women referred for routine carrier screening during a specified time period at Progenity, Inc. Patient ethnicity was self-reported and categorized as: African American, Ashkenazi Jewish, Asian, Caucasian, Hispanic, Native American, Other/Mixed/Unknown, or Sephardic Jewish. FXS test results were stratified by ethnicity and repeat allele category. Total premutation carrier frequency was calculated and compared against each ethnic group. A total of 134,933 samples were included. The pan-ethnic premutation carrier frequency was 1 in 201. Only the Asian group differed significantly from this frequency. Using the carrier frequency of 1 in 201, a conservative pan-ethnic risk estimate for a male fetus to have FXS can be calculated as 1 in 2,412. This risk is similar to the highest ethnic-based fetal risks for cystic fibrosis and spinal muscular atrophy, for which population-wide screening is currently recommended. This study adds to the literature and supports further evaluation into specific population-wide screening recommendations for FXS.

Clinical experience with multigene carrier panels in the reproductive setting.

OBJECTIVES: Expanded carrier testing is acknowledged as an acceptable strategy for carrier testing by the American College of Obstetrics and Gynecology. Limited studies have investigated positivity rates of expanded carrier panels. We describe our experience with 3 commercial laboratory panels varying in size from 3 to 218 disorders. METHODS: We reviewed outcomes for 3 multigene carrier screening panels: trio (3 diseases), standard (23 diseases), and global (218 diseases). All panels used targeted genotype analysis of preselected mutations via next-generation sequencing. We calculated positivity rates for each panel. RESULTS: Positivity rates were 7.2% for Preparent Trio, 13.2% for Preparent Standard, and 35.8% for Preparent Global. The most frequent positive results in the global panel were (in descending order): abnormal hemoglobin electrophoresis, familial Mediterranean fever, cystic fibrosis, fragile X, glucose-6-phosphate dehydrogenase deficiency, alpha-thalassemia, and nonsyndromic hearing loss. CONCLUSIONS: While genetic diseases are individually rare, they are cumulatively common. Our experience illustrates that, with a panel of 218 diseases, the likelihood of identifying a carrier can be as high as 36%. Understanding panel positivity rates is one important factor for providers when choosing the right test for their practice, setting appropriate expectations for patients, and planning for follow-up counseling.

Anesthetic Considerations for the Parturient After Solid Organ Transplantation.

Over the past 40 years, the success of organ transplantation has increased such that female solid organ transplant recipients are able to conceive and carry pregnancies successfully to term. Anesthesiologists are faced with the challenge of providing anesthesia care to these high-risk obstetric patients in the peripartum period. Anesthetic considerations include the effects of the physiologic changes of pregnancy on the transplanted organ, graft function in the peripartum period, and the maternal side effects and drug interactions of immunosuppressive agents. These women are at an increased risk of comorbidities and obstetric complications. Anesthetic management should consider the important task of protecting graft function. Optimal care of a woman with a transplanted solid organ involves management by a multidisciplinary team. In this focused review article, we review the anesthetic management of pregnant patients with solid organ transplants of the kidney, liver, heart, or lung.

Utility of magnetic resonance imaging for suspected appendicitis in pregnant women.

OBJECTIVE: The purpose of this study was to estimate the rate and risk of appendix nonvisualization and alternative diagnoses made with magnetic resonance imaging (MRI) for suspected appendicitis in pregnant women. STUDY DESIGN: We performed a retrospective cohort study of consecutive pregnant women who underwent MRI for suspected appendicitis at a single center from 2007-2012. Data on clinical presentation, imaging, and surgical pathologic evidence were extracted from electronic medical records. Odds ratios estimated risk factors for nondiagnosis. Radiologic diagnoses were identified, and rates of diagnoses were calculated. Subgroup analysis was performed among women who underwent initial imaging with ultrasound scanning. RESULTS: Over the 5-year period, 171 pregnant women underwent MRI for suspected appendicitis. The rate of nonvisualization was 30.9% (n = 53). Of the remaining 118 women with a visualized appendix, 18 women had imaging findings that were consistent with appendicitis and underwent appendectomy. Twelve cases of appendicitis were confirmed on pathologic evaluation (66.7%). Women with nonvisualization of the appendix on MRI were more likely to be beyond the first trimester (odds ratio, 2.1; 95% confidence interval, 1.0-4.5). Seventy-four women had disease diagnosed on MRI (43.3%). In the group of 43 women who had a nondiagnostic ultrasound scanning before the MRI, the rate of subsequent diagnostic MRI was 65% (n = 28). CONCLUSION: MRI yields a high diagnostic rate and accuracy in pregnant women with suspected appendicitis and provides alternative diagnoses to guide further management. Given the high rate of appendix nonvisualization on ultrasound scanning that has been reported in the literature, we recommend MRI as the imaging modality of choice for this population in settings in which MRI is readily available.

Infectious morbidity is higher after second-stage compared with first-stage cesareans.

OBJECTIVE: The objective of the study was to compare maternal and neonatal infectious morbidity following cesareans performed in the second and first stages of labor. STUDY DESIGN: We conducted a retropective cohort study of all consecutive, singleton, term, cesarean deliveries in laboring women in a single institution from 2005 to 2012. Second-stage cesareans were defined as those performed at complete cervical dilation (10 cm), and first-stage cesareans were those performed before 10 cm cervical dilation. The primary outcome was endometritis. Rates of infectious morbidity were compared in the 2 groups. Multivariable logistic regression was used to calculate adjusted risk estimates. RESULTS: Of 2505 cesareans meeting inclusion criteria, 400 (16.0%) were performed in the second stage, whereas 2105 (84.0%) were performed in the first stage of labor. The risk of endometritis was nearly 3-fold higher in second- compared with first-stage cesareans (4.25% vs 1.52%; crude odds ratio, 2.88; 95% confidence interval, 1.58-5.23). The risk remained significantly higher after controlling for confounders (adjusted odds ratio, 2.78; 95% confidence interval, 1.51-5.09). CONCLUSION: Second-stage cesarean is associated with an increased risk of endometritis compared with first-stage cesarean. Further studies will determine whether different infection preventive strategies are needed at second-stage cesareans to reduce endometritis.

An economic analysis of prenatal cytogenetic technologies for sonographically detected fetal anomalies.

When congenital anomalies are diagnosed on prenatal ultrasound, the current standard of care is to perform G-banded karyotyping on cultured amniotic cells. Chromosomal microarray (CMA) can detect smaller genomic deletions and duplications than traditional karyotype analysis. CMA is the first-tier test in the postnatal evaluation of children with multiple congenital anomalies. Recent studies have demonstrated the utility of CMA in the prenatal setting and have advocated for widespread implementation of this technology as the preferred test in prenatal diagnosis. However, CMA remains significantly more expensive than karyotype. In this study, we performed an economic analysis of cytogenetic technologies in the prenatal diagnosis of sonographically detected fetal anomalies comparing four strategies: (i) karyotype alone, (ii) CMA alone, (iii) karyotype and CMA, and (iv) karyotype followed by CMA if the karyotype was normal. In a theoretical cohort of 1,000 patients, CMA alone and karyotype followed by CMA if the karyotype was normal identified a similar number of chromosomal abnormalities. In this model, CMA alone was the most cost-effective strategy, although karyotype alone and CMA following a normal karyotype are both acceptable alternatives. This study supports the clinical utility of CMA in the prenatal diagnosis of sonographically detected fetal anomalies.

The role of ultrasound in the diagnosis of fetal genetic syndromes.

The use of ultrasound in the prenatal diagnosis of fetal genetic syndromes is rapidly evolving. Advancing technology and new research findings are aiding in the increased accuracy of ultrasound-based diagnosis in combination with other methods of non-invasive and invasive fetal testing. Ultrasound as a screening tool for aneuploidy and other anomalies is increasingly being used throughout pregnancy, beginning in the first trimester. Given the number of recorded syndromes, it is important to identify patterns and establish a strategy for identifying abnormalities on ultrasound. These syndromes encompass a wide range of causes from viral, substance-linked, chromosomal, and other genetic syndromes. Despite the ability of those experienced in ultrasound, it is important to note that not all fetal genetic syndromes can be identified prenatally, and even common syndromes often have no associated ultrasound findings. Here, we review the role of ultrasound in the diagnosis of fetal genetic syndromes.

Ovarian complete hydatidiform mole: case study with molecular analysis and review of the literature.

Ectopic complete molar pregnancy in the ovary is an exceptionally rare event. Here we present a case of ovarian complete hydatidiform mole in a 20-year-old gravida 2 para 1 woman. At presentation, the patient underwent excision of a hemorrhagic left ovarian cyst, with routine sections demonstrating a hemorrhagic corpus luteum with a single microscopic focus of detached atypical trophoblast, without chorionic villi. Subsequent left salpingo-oophorectomy for persistently elevated human chorionic gonadotropin led to a final diagnosis of complete hydatidiform mole arising in the ovary. The fallopian tube was unremarkable. Zygosity was determined using short tandem repeat analysis, confirming the diagnosis of monospermic complete mole. In the clinical setting of a markedly elevated human chorionic gonadotropin level and an ovarian mass, histopathologic examination is critical in distinguishing ectopic pregnancy from choriocarcinoma. Short tandem repeat analysis can be a useful adjunct to histologic diagnosis in challenging cases.

Impact of obesity on incision-to-delivery interval and neonatal outcomes at cesarean delivery.

OBJECTIVE: The purpose of this study was to test the hypothesis that increasing body mass index (BMI) is associated with increased time from skin incision to infant delivery and increased neonatal morbidity at cesarean delivery. STUDY DESIGN: We performed a retrospective cohort study of all cesarean deliveries that occurred at 1 institution from 2004-2008. Four comparison groups were defined by BMI of <30 kg/m(2) (n = 668 women), 30-39.9 kg/m(2) (n = 1002 women), 40-49.9 kg/m(2) (n = 403 women), or ≥50 kg/m(2) (n = 193 women). The primary outcome was time from skin incision to infant delivery. Secondary outcomes were a composite measure of neonatal morbidity and its individual components: 5-minute Apgar score <7, umbilical cord arterial pH <7.10 and <7.20, umbilical cord arterial base excess ≤8 mmol/L, special care nursery admission, and neonatal intensive care unit admission. RESULTS: Increasing BMI was associated with significantly increased time from skin incision to infant delivery, which demonstrated a dose-response pattern. Minutes from skin incision to delivery of the infant by BMI strata were 9.4 ± 5.9 for <30 kg/m(2), 11.0 ± 6.8 for 30-39.9 kg/m(2), 13.0 ± 8.0 for 40-49.9 kg/m(2), and 16.0 ± 11.3 for ≥50 kg/m(2) (P < .01). Composite neonatal morbidity was significantly higher with increasing BMI: 23.0% for <30 kg/m(2), 25% for 30-39.9 kg/m(2), 29.8% for 40-49.9 kg/m(2), and 32.1% for ≥50 kg/m(2) (P = .02). CONCLUSION: Increasing BMI is associated with a significantly increased time from skin incision to infant delivery and neonatal morbidity. Cesarean delivery technique remains to be optimized for obese women.

Fibroid tumors are not a risk factor for adverse outcomes in twin pregnancies.

OBJECTIVE: Uterine fibroid tumors have been associated with adverse outcomes in singleton pregnancies. We aimed to estimate risk for adverse obstetric outcomes that are associated with fibroid tumors in twin pregnancies. STUDY DESIGN: A retrospective cohort study of twin pregnancies with ≥1 fibroid tumor on second trimester ultrasound examination. Outcomes included small-for-gestational-age fetal growth, preterm delivery, preterm rupture of membranes, abruption, preeclampsia, and intrauterine fetal death. Univariable and multivariable analyses were used to evaluate the impact of fibroid tumors on outcomes in twin pregnancies compared with twin pregnancies without fibroid tumors. RESULTS: Of 2378 nonanomalous twin pregnancies, 2.3% had fibroid tumors. Twin pregnancies with fibroid tumors were no more likely to have small-for-gestational-age growth (40.0% vs. 36.0%; adjusted odds ratio, 1.1; 95% confidence interval, 0.7-2.0) or preterm delivery at <34 weeks' gestation (25.0% vs. 24.0%; adjusted odds ratio, 1.0; 95% confidence interval, 0.5-1.9) than twin pregnancies without fibroid tumors. Other adverse outcomes were no more likely to occur in twin pregnancies with fibroid tumors than in twin pregnancies without fibroid tumors. Post hoc power calculations suggested >97% power to detect 2-fold differences in small for gestational age and preterm delivery at <34 weeks' gestation. CONCLUSION: In contrast to data that suggest an increased risk for adverse outcomes in singleton pregnancies with fibroid tumors, twin pregnancies with fibroid tumors do not appear to be at increased risk for complications compared with those pregnancies without fibroid tumors.

Neural tube defects and associated low birth weight.

OBJECTIVE: To estimate the association between neural tube defects (NTDs) and low birth weight. STUDY DESIGN: This was a retrospective cohort study of women undergoing ultrasound from 17 to 22 weeks from 1990 to 2008. Presence or absence of fetal NTD defined the two study groups. The primary outcomes were intrauterine growth restriction (IUGR), birth weight <10th percentile, and severe IUGR <5th percentile. Subgroup analysis was performed to observe if the association with IUGR persisted. RESULTS: Of 66,956 women, 170 were found to have fetal NTD. Only the rate of advanced maternal age differed between the study groups. Fetuses with an NTD were at significantly increased risk for IUGR <10th percentile (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.8 to 3.9) and <5th percentile (aOR 2.8, 95% CI 1.9 to 4.3). The association persisted in subgroup analyses. CONCLUSION: Fetuses with NTD are at increased risk for IUGR, suggesting that a policy of serial growth scans in cases with isolated NTD is justified.

Risk of preterm delivery and growth restriction in twins discordant for structural anomalies.

OBJECTIVE: We sought to determine whether twin gestations with an anomalous fetus are at increased risk of preterm delivery or intrauterine growth restriction (IUGR) compared to twins with 2 normal fetuses. STUDY DESIGN: This was a retrospective cohort of twins undergoing ultrasound 15-22 weeks' gestation. Groups were defined by the presence of 1 twin with a major anomaly (discordant) or by twins with no major anomalies (normal). The primary outcomes were preterm delivery (<37 weeks) and IUGR (<10th percentile). RESULTS: Of 1977 twin pregnancies, 66 had a twin with a major anomaly. Preterm delivery occurred in 42 (63.6%) discordant twins, compared to 1271 (66.5%) normal twins (risk ratio, 1.0; 95% confidence interval, 0.8-1.2). IUGR was diagnosed in 15 (22.7%) normal co-twins, compared to 406 (21.3%) presenting twins in normal twins (risk ratio, 1.1; 95% confidence interval, 0.7-1.7). CONCLUSION: Twins discordant for major anomalies are not at increased risk of preterm delivery or IUGR compared to twins with no major anomalies.

Fetal congenital heart disease and intrauterine growth restriction: a retrospective cohort study.

OBJECTIVE: Fetal congenital heart disease may lead to abnormal fetal growth. Our objective was to estimate the association between fetal congenital heart disease (CHD) and intrauterine growth restriction (IUGR) in an effort to better inform clinical management of continuing pregnancies complicated by fetal congenital heart disease. METHODS: In a retrospective cohort study, outcome data was collected from singleton pregnancies undergoing routine anatomic survey at a tertiary medical center between 1990 and 2008. Dedicated research nurses collected information on delivery outcomes in an on-going manner. Subjects with a prenatal diagnosis of fetal CHD were compared to those without CHD. Stratified analyses for isolated fetal CHD and major CHD were performed. The primary outcome was IUGR less than 10th percentile by the Alexander growth standard. Logistic regression was used to adjust for confounding variables and refine the estimates of risk. RESULTS: Among 67,823 patients, there were 193 cases of fetal CHD (0.3%) and 5,669 cases of IUGR (8.4%). Prenatal diagnosis of CHD was associated with an increased risk of IUGR (23.8% vs. 8.5%, adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 2.4-4.6), and the risk was greatest in fetuses with major CHD (16.5% vs. 8.5%, aOR 2.1, 95% CI 1.3-3.2). Isolated CHD was also associated with an increased risk of IUGR (17.8% vs. 8.5%, aOR 2.2, 95% CI 1.4-3.7). CONCLUSION: Patients with a prenatal diagnosis of fetal CHD have a three-fold increase in risk of developing IUGR; patients with isolated fetal CHD are twice as likely to develop IUGR. Based on our findings, serial growth assessment may be a reasonable option for patients with fetal CHD diagnosed at routine anatomic survey.

Congenital uterine anomalies and adverse pregnancy outcomes.

OBJECTIVE: We sought to estimate whether the presence of a maternal uterine anomaly is associated with adverse pregnancy outcomes. STUDY DESIGN: This retrospective cohort study included singleton pregnancies undergoing routine anatomic survey from 1990 through 2008 at a major tertiary care medical center. Pregnancies with a diagnosis of uterine anomaly (uterine septum, unicornuate uterus, bicornuate uterus, uterine didelphys) were compared to those with normal anatomy. Primary outcomes of interest were spontaneous preterm birth (PTB), breech presentation, and cesarean delivery. RESULTS: The presence of an anomaly was associated with PTB <34 weeks (adjusted odds ratio [aOR], 7.4; 95% confidence interval [CI], 4.8-11.4; P < .01), PTB <37 weeks (aOR, 5.9, 95% CI, 4.3-8.1; P < .01), primary nonbreech cesarean delivery (aOR, 2.6; 95% CI, 1.7-4.0; P < .01), preterm premature rupture of membranes (aOR, 3.2; 95% CI, 1.8-5.6; P < .01), and breech presentation (aOR, 8.6; 95% CI, 6.2-12.0; P < .01). CONCLUSION: Women with a uterine anomaly are at risk for PTB, highlighting an at-risk population that needs additional study for possible interventions for PTB prevention.

Viral respiratory disease in pregnancy.

PURPOSE OF REVIEW: Recently there has been an increased concern over viral respiratory infections and their potential for a pandemic. This concern makes it important to review the most current guidelines for the management of viral respiratory diseases in pregnancy. RECENT FINDINGS: The topics covered are influenza, avian influenza, and severe acute respiratory syndrome. SUMMARY: Pregnant women have an increased susceptibility to viral respiratory diseases. The most common respiratory virus to infect pregnant women is influenza. All women who intend to become pregnant or are pregnant should receive the influenza vaccine. If a pregnant woman develops influenza she should be treated with supportive care. Antiviral medications should be reserved for cases where the benefits outweigh the risks. Avian influenza (H5N1) is a new emerging virus usually contracted from direct contact with diseased birds. There is no commercially available vaccine at this time to prevent infection. Pregnant women should be treated aggressively with supportive care and antiviral medications, as the significant risk of maternal mortality outweighs the potential fetal risks. Pregnant women diagnosed clinically with severe acute respiratory syndrome should be treated empirically, as a serologic diagnosis can take weeks to confirm. The treatment of pregnant women with severe acute respiratory syndrome should be without ribavirin.