Hybrid Quadrupole Mass Filter-Radial Ejection Linear Ion Trap and Intelligent Data Acquisition Enable Highly Multiplex Targeted Proteomics.

Targeted mass spectrometry (MS) methods are powerful tools for the selective and sensitive analysis of peptides identified in global discovery experiments. Selected reaction monitoring (SRM) is the most widely accepted clinical MS method due to its reliability and performance. However, SRM and parallel reaction monitoring (PRM) are limited in throughput and are typically used for assays with around 100 targets or fewer. Here we introduce a new MS platform featuring a quadrupole mass filter, collision cell, and linear ion trap architecture, capable of targeting 5000-8000 peptides per hour. This high multiplexing capability is facilitated by acquisition rates of 70-100 Hz and real-time chromatogram alignment. We present a Skyline external software tool for building targeted methods based on data-independent acquisition chromatogram libraries or unscheduled analysis of heavy labeled standards. Our platform demonstrates ∼10× lower limits of quantitation (LOQs) than traditional SRM on a triple quadrupole instrument for highly multiplexed assays, due to parallel product ion accumulation. Finally, we explore how analytical figures of merit vary with method duration and the number of analytes, providing insights into optimizing assay performance.

A Workflow for Improved Analysis of Cross-Linking Mass Spectrometry Data Integrating Parallel Accumulation-Serial Fragmentation with MeroX and Skyline.

Cross-linking mass spectrometry (XL-MS) has evolved into a pivotal technique for probing protein interactions. This study describes the implementation of Parallel Accumulation-Serial Fragmentation (PASEF) on timsTOF instruments, enhancing the detection and analysis of protein interactions by XL-MS. Addressing the challenges in XL-MS, such as the interpretation of complex spectra, low abundant cross-linked peptides, and a data acquisition bias, our current study integrates a peptide-centric approach for the analysis of XL-MS data and presents the foundation for integrating data-independent acquisition (DIA) in XL-MS with a vendor-neutral and open-source platform. A novel workflow is described for processing data-dependent acquisition (DDA) of PASEF-derived information. For this, software by Bruker Daltonics is used, enabling the conversion of these data into a format that is compatible with MeroX and Skyline software tools. Our approach significantly improves the identification of cross-linked products from complex mixtures, allowing the XL-MS community to overcome current analytical limitations.

Maternal and newborn outcomes in pregnancies complicated by Guillain-Barré syndrome.

OBJECTIVES: Guillain-Barré syndrome (GBS) is a rare autoimmune disorder that affects the peripheral nervous system. The purpose of our study was to evaluate maternal and fetal/neonatal outcomes among pregnancies complicated by GBS. METHODS: We performed a retrospective cohort study using the Healthcare Cost and Utilization Project - National Inpatient Sample from the United States. ICD-9 codes were used to identify all pregnant women who delivered between 1999 and 2015 and had a diagnosis of GBS. The remaining women without GBS who delivered during that time period constituted the comparison group. The associations between maternal GBS and obstetrical and fetal/neonatal outcomes were evaluated using multivariate logistic regression, while adjusting for the confounding effects of maternal characteristics. RESULTS: Of 13,792,544 births included in our study, 291 were to women with GBS, for an overall incidence of 2.1/100,000 births. A steady increase in maternal GBS was observed over the study period (from 1.26 to 3.8/100,000 births, p=0.02). Further, women with GBS were more likely to have pregnancies complicated by preeclampsia, OR 1.69 (95 % CI 1.06-2.69), sepsis, 9.30 (2.33-37.17), postpartum hemorrhage, 1.83 (1.07-3.14), and to require a transfusion, 4.39 (2.39-8.05). They were also at greater risk of caesarean delivery, 2.07 (1.58-2.72) and increased length of hospital stay, 4.48 (3.00-6.69). Newborns of women with GBS were more likely to be growth restricted, 2.50 (1.48-4.23). CONCLUSIONS: GBS in pregnancy is associated with maternal and newborn adverse outcomes. These patients would benefit from close follow-up throughout their pregnancy and in the postpartum period.

Incidence, Characteristics, and Outcomes of Robin Sequence: A Population-Based Analysis in the United States.

INTRODUCTION: While the literature is replete of clinical studies reporting on the Robin sequence (RS), population-based analyses are scarce with significant variability within the literature in terms of reported incidence, demographic parameters, and outcomes. The authors have conducted a 20-year population-based analysis to guide clinical practice. METHODS: A birth cohort was created from the available datasets in the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID; 2000-2019). Robin sequence patients were identified and further stratified by syndromic status. Incidence, demographic parameters, and outcomes including mortality and tracheostomy rates were computed. A subset analysis comparing the isolated and syndromic cohorts was conducted. Data was analyzed through a χ 2 or t test. RESULTS: The incidence of RS was 5.15:10,000 (95% CI: 4.99-5.31) from a birth cohort of 7.5 million. Overall, 63.3% of the cohort was isolated RS and 36.7% had syndromic RS. Robin sequence patients had a significantly higher rate of cardiac (25.9%) and neurological (8.6%) anomalies compared with the general birth cohort and were most commonly managed in urban teaching hospitals ( P <0.0001). The pooled mortality and tracheostomy rates were 6.6% and 3.6%, respectively. Syndromic status was associated with a longer length of hospital stay (27.8 versus 13.6 d), tracheostomy rate (6.2% versus 2.1%), and mortality (14.1% versus 2.2%) compared with isolated RS ( P <0.0001). CONCLUSIONS: The true incidence of RS is likely higher than previously reported estimates. Isolated RS patients have a low associated mortality and tracheostomy rate and are typically managed in urban teaching hospitals. Syndromic status confers a higher mortality rate, tracheostomy rate, and length of stay compared with nonsyndromic counterparts.

MSstats Version 4.0: Statistical Analyses of Quantitative Mass Spectrometry-Based Proteomic Experiments with Chromatography-Based Quantification at Scale.

The MSstats R-Bioconductor family of packages is widely used for statistical analyses of quantitative bottom-up mass spectrometry-based proteomic experiments to detect differentially abundant proteins. It is applicable to a variety of experimental designs and data acquisition strategies and is compatible with many data processing tools used to identify and quantify spectral features. In the face of ever-increasing complexities of experiments and data processing strategies, the core package of the family, with the same name MSstats, has undergone a series of substantial updates. Its new version MSstats v4.0 improves the usability, versatility, and accuracy of statistical methodology, and the usage of computational resources. New converters integrate the output of upstream processing tools directly with MSstats, requiring less manual work by the user. The package's statistical models have been updated to a more robust workflow. Finally, MSstats' code has been substantially refactored to improve memory use and computation speed. Here we detail these updates, highlighting methodological differences between the new and old versions. An empirical comparison of MSstats v4.0 to its previous implementations, as well as to the packages MSqRob and DEqMS, on controlled mixtures and biological experiments demonstrated a stronger performance and better usability of MSstats v4.0 as compared to existing methods.

TurnoveR: A Skyline External Tool for Analysis of Protein Turnover in Metabolic Labeling Studies.

In spite of its central role in biology and disease, protein turnover is a largely understudied aspect of most proteomic studies due to the complexity of computational workflows that analyze in vivo turnover rates. To address this need, we developed a new computational tool, TurnoveR, to accurately calculate protein turnover rates from mass spectrometric analysis of metabolic labeling experiments in Skyline, a free and open-source proteomics software platform. TurnoveR is a straightforward graphical interface that enables seamless integration of protein turnover analysis into a traditional proteomics workflow in Skyline, allowing users to take advantage of the advanced and flexible data visualization and curation features built into the software. The computational pipeline of TurnoveR performs critical steps to determine protein turnover rates, including isotopologue demultiplexing, precursor-pool correction, statistical analysis, and generation of data reports and visualizations. This workflow is compatible with many mass spectrometric platforms and recapitulates turnover rates and differential changes in turnover rates between treatment groups calculated in previous studies. We expect that the addition of TurnoveR to the widely used Skyline proteomics software will facilitate wider utilization of protein turnover analysis in highly relevant biological models, including aging, neurodegeneration, and skeletal muscle atrophy.

Evaluating the Performance of the Astral Mass Analyzer for Quantitative Proteomics Using Data-Independent Acquisition.

We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data-independent acquisition, the Thermo Scientific Orbitrap Astral mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific Orbitrap mass spectrometers, which have long been the gold standard for high-resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high-quality quantitative measurements across a wide dynamic range. We also use a newly developed extracellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5000 plasma proteins in a 60 min gradient with the Orbitrap Astral mass spectrometer.

Avant-garde: an automated data-driven DIA data curation tool.

Several challenges remain in data-independent acquisition (DIA) data analysis, such as to confidently identify peptides, define integration boundaries, remove interferences, and control false discovery rates. In practice, a visual inspection of the signals is still required, which is impractical with large datasets. We present Avant-garde as a tool to refine DIA (and parallel reaction monitoring) data. Avant-garde uses a novel data-driven scoring strategy: signals are refined by learning from the dataset itself, using all measurements in all samples to achieve the best optimization. We evaluate the performance of Avant-garde using benchmark DIA datasets and show that it can determine the quantitative suitability of a peptide peak, and reach the same levels of selectivity, accuracy, and reproducibility as manual validation. Avant-garde is complementary to existing DIA analysis engines and aims to establish a strong foundation for subsequent analysis of quantitative mass spectrometry data.

Obstetric outcomes in women with vulvodynia or vaginismus.

PURPOSE: Vulvodynia and vaginismus are common chronic vulvar pain disorders for which there is a paucity of literature on pregnancy outcomes of affected women. The study objective was to evaluate the associations between vulvodynia and vaginismus and obstetric outcomes. METHODS: We performed a retrospective cohort study including all birth-related admissions from 1999 to October 2015 extracted from the Healthcare Cost and Utilization Project-National Inpatient Sample from the United States. Women with vulvodynia or vaginismus were identified using the appropriate ICD-9 codes. Multivariate logistic regression models, adjusted for baseline maternal characteristics, were performed to evaluate the effect of vulvodynia and vaginismus on obstetrical and neonatal outcomes. RESULTS: A total of 879 obstetrical patients with vulvodynia or vaginismus were identified in our cohort of 13,792,544 patients admitted for delivery in US hospitals between 1999 and 2015, leading to an overall prevalence of 6 cases per 100,000 births. Between 1999 and 2015, the annual prevalence of vulvodynia or vaginismus rose from 2 to 16 cases per 100,000. Vulvodynia and vaginismus were associated with increased risks of eclampsia, chorioamnionitis, post-term pregnancy, cesarean delivery, instrumental vaginal delivery, blood transfusions, prolonged hospital stays, congenital anomalies and intrauterine growth restriction. CONCLUSION: Vulvodynia and vaginismus in pregnancy appears underreported in pregnancy compared to reported population rates. Prevalence of reporting seems to have increased in the last decades and is associated with increased risks of maternal and newborn morbidities. Obstetrical caregivers should be aware of the underreporting of these conditions and the associated adverse effects when counseling obstetrical patients.

Maternal and neonatal outcomes in women with a history of chemotherapy exposure: a population-based study of 8 million obstetric admissions.

PURPOSE: With improvement in cancer care and fertility preservation, increasing numbers of cancer survivors are requiring obstetrical care. The objective of our study was to evaluate the effect of history of chemotherapy exposure on maternal and neonatal outcomes. METHODS: A retrospective population-based cohort study was conducted using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) to obtain data on maternal and newborn outcomes in a cohort of births occurring between the years 2006 and 2015. The annual and overall prevalence of chemotherapy exposure was calculated among pregnant women, and multivariate logistic regression models were used to estimate the effect of history of exposure to chemotherapy on the risk of adverse maternal and newborn outcomes. RESULTS: Of 7,907,139 birth admissions, 613 had a history of chemotherapy exposure for an overall incidence of 7.75 per 100,000 admissions. The prevalence of chemotherapy exposure in pregnancy increased during the study period (P < 0.001). Women with a history of chemotherapy were more likely to suffer from obstetric and medical complications including pre-eclampsia, chorioamnionitis, postpartum hemorrhage, and venous thromboembolism as well as an increased risk in overall mortality (OR 9.39, 95% CI 1.31-67.32). No differences were observed in the incidence of adverse neonatal outcomes, including stillbirth, intra-uterine growth restriction, or preterm birth. CONCLUSION: Women with history of chemotherapy have higher incidence of pregnancy complications and maternal death, with no differences in fetal or newborn outcomes.

Incidence and risk factors of bladder injury during cesarean delivery: a cohort study.

PURPOSE: To identify risk factors associated with bladder injury during cesarean delivery, and to determine the frequency of associated morbidities. METHODS: Data obtained from the United States' Health Care Cost and Utilization Project-Nationwide Inpatient Sample were used to conduct a retrospective population-wide cohort study. ICD-9 codes were used to identify women who underwent a cesarean delivery between 1999 and 2015. Subsequently, women were classified based on whether or not they experienced a bladder injury during delivery. Multivariate logistic regression was used to determine predictors of bladder injury in cesarean deliveries and to examine the associated morbidities while adjusting for baseline maternal demographics and clinical characteristics. RESULTS: Of 4,169,681 cesarean deliveries identified, there were 7,627 (0.2%) bladder injuries for an overall incidence of 18 per 10,000. Women ≥ 35 years were at greater risk of bladder injury 1.5 (1.4-1.6), as were women with endometriosis 2.0 (1.5-2.7) and Crohn's disease 2.7 (1.7-4.2). Risk of bladder injury increased if the cesarean delivery was associated with placenta previa 2.2 (1.9-2.4), previous cesarean delivery 4.3 (4.1-4.6), failed instrumental delivery 4.1 (3.5-4.8), fetal distress 1.7 (1.6-1.8), failed trial of labor after cesarean delivery 1.3 (1.2-1.4), and labor dystocia 1.7 (1.6-1.8). Cesarean hysterectomies presented the greatest risk for bladder injury 37.0 (33.7-40.6). Bladder injury was associated with an increased frequency of sepsis, venous thromboembolism, peritonitis, blood transfusions and longer hospital stays. CONCLUSION: Bladder injury during cesarean deliveries is a rare outcome but it is more common among women with certain demographic and clinical characteristics. Among these cases, strategies to prevent sepsis and venous thromboembolism should be considered.

Development and Application of Multidimensional Lipid Libraries to Investigate Lipidomic Dysregulation Related to Smoke Inhalation Injury Severity.

The implication of lipid dysregulation in diseases, toxic exposure outcomes, and inflammation has brought great interest to lipidomic studies. However, lipids have proven to be analytically challenging due to their highly isomeric nature and vast concentration ranges in biological matrices. Therefore, multidimensional techniques such as those integrating liquid chromatography, ion mobility spectrometry, collision-induced dissociation, and mass spectrometry (LC-IMS-CID-MS) have been implemented to separate lipid isomers as well as provide structural information and increased identification confidence. These data sets are however extremely large and complex, resulting in challenges for data processing and annotation. Here, we have overcome these challenges by developing sample-specific multidimensional lipid libraries using the freely available software Skyline. Specifically, the human plasma library developed for this work contains over 500 unique lipids and is combined with adapted Skyline functions such as indexed retention time (iRT) for retention time prediction and IMS drift time filtering for enhanced selectivity. For comparison with other studies, this database was used to annotate LC-IMS-CID-MS data from a NIST SRM 1950 extract. The same workflow was then utilized to assess plasma and bronchoalveolar lavage fluid (BALF) samples from patients with varying degrees of smoke inhalation injury to identify lipid-based patient prognostic and diagnostic markers.

Cesarean delivery on maternal request in the United States from 1999 to 2015.

BACKGROUND: The rate of cesarean delivery has increased in the United States over the last several decades. However, the rate of cesarean delivery on maternal request remains undetermined, and recent data on cesarean delivery on maternal request are lacking. OBJECTIVE: This study aimed to describe the prevalence and temporal trends of cesarean delivery on maternal request in the United States and characterize the population of women who elect to undergo a cesarean delivery in the absence of fetal or maternal indications. Maternal outcomes between women who delivered by cesarean delivery on maternal request and those who did not were compared. STUDY DESIGN: A retrospective cohort study was conducted using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999 to 2015. An algorithm based on International Classification of Diseases, Ninth Revision codes was created to identify patients who underwent a primary elective cesarean delivery in the absence of fetal or maternal indications. Maternal characteristics and outcomes between women who delivered by cesarean delivery on maternal request and those who did not were compared using descriptive and logistic regression analyses. RESULTS: Of the 13,698,835 deliveries included throughout the study period, 228,586 were identified as cesarean delivery on maternal request. Rates of cesarean delivery on maternal request among all live births increased throughout the study period, from 1% in 1999 to 1.62% in 2015 (P<.0001). Women who delivered by cesarean delivery on maternal request were more likely to be >35 years of age, were in the highest income quartile, and have private insurance. Cesarean delivery on maternal request was associated with an increased risk of venous thromboembolism (odds ratio, 1.9; 95% confidence interval, 1.8-2.0), myocardial infarction (odds ratio, 6.3; 95% confidence interval, 3.8-10.4), sepsis (odds ratio, 5.6; 95% confidence interval, 4.7-6.6), disseminated intravascular coagulation (odds ratio, 2.9; 95% confidence interval, 2.3-3.7), death (odds ratio, 14.5; 95% confidence interval, 11.4-18.6), and prolonged hospital stay (odds ratio, 4.9; 95% confidence interval, 4.8-5.1) and a lower risk of postpartum hemorrhage (odds ratio, 0.7; 95% confidence interval, 0.7-0.7). CONCLUSION: Our findings indicated that cesarean delivery on maternal request accounts for a small but increasing proportion of all cesarean deliveries in the United States. Cesarean delivery on maternal request was more prevalent among women with certain demographic characteristics, indicating that the option of cesarean delivery on maternal request may be more appealing or more frequently offered to a certain population of women. Although the overall risk of adverse events is low for individual births, population effects can result in increased morbidity and mortality. Therefore, the rates of cesarean delivery on maternal request should be monitored on a national level. Study findings were limited by the absence of a specific diagnostic code for cesarean delivery on maternal request.

Perinatal outcomes in pregnancies complicated by acute pancreatitis.

OBJECTIVES: Acute pancreatitis is a rare condition that can be associated with significant complications. The objective of this study is to evaluate the maternal and newborn outcomes associated with acute pancreatitis in pregnancy. METHODS: A retrospective cohort study using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from the United States was performed. All pregnant patients with acute pancreatitis were identified using International Classification of Disease-9 coding from 1999 to 2015. The effect of acute pancreatitis on maternal and neonatal outcomes in pregnancy was evaluated using multivariate logistic regression, while adjusting for baseline maternal characteristics. RESULTS: From 1999 to 2015, there were a total of 13,815,919 women who gave birth. There were a total of 14,258 admissions of women diagnosed with acute pancreatitis, including 1,756 who delivered during their admission and 12,502 women who were admitted in the antepartum period and did not deliver during the same admission. Acute pancreatitis was associated with increased risk of prematurity, OR 3.78 (95% CI 3.38-4.22), preeclampsia, 3.81(3.33-4.36), postpartum hemorrhage, 1.90(1.55-2.33), maternal death, 9.15(6.05-13.85), and fetal demise, 2.60(1.86-3.62) among women diagnosed with acute pancreatitis. Among women with acute pancreatitis, delivery was associated with increased risk of requiring transfusions, 6.06(4.87-7.54), developing venous thromboembolisms, 2.77(1.83-4.18), acute respiratory failure, 3.66(2.73-4.91), and disseminated intravascular coagulation, 8.12(4.12-16.03). CONCLUSIONS: Acute pancreatitis in pregnancy is associated with severe complications, such as maternal and fetal death. Understanding the risk factors that may lead to these complications can help prevent or minimize them through close fetal and maternal monitoring.

Maternal and neonatal outcomes among pregnant women with inflammatory myopathies.

OBJECTIVES: Pregnancy outcomes in women with inflammatory myopathies (IM) are not well studied. The purpose of this study is to evaluate the effects of IM on maternal and neonatal outcomes. METHODS: We conducted a retrospective cohort study using data from the Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS) from 1999 to 2015. Among all pregnant women who delivered during this period, those with a diagnosis of IM were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding, which included all patients with dermatomyositis and polymyositis. Maternal and neonatal outcomes were compared in pregnant women with and without IM. Multivariate logistic regression analysis was used to estimate the adjusted effects of IM on these outcomes. RESULTS: A total of 13,792,544 pregnant women delivered between 1999 and 2015, of which 308 had a diagnosis of IM, for an overall prevalence of 2 per 100,000 pregnant women, with rates increasing over the study period. Pregnant women with IM were more likely to be older, African American and suffer from other autoimmune connective tissue diseases. IM in pregnancy was associated with greater risk of preeclampsia, caesarean delivery, major postpartum infections, urinary tract infections and longer hospital stay. Neonates born to mothers with IM had greater risk of prematurity, small for gestational age and intrauterine fetal demise. CONCLUSIONS: Pregnant women with IM are at higher risk of adverse maternal and neonatal outcomes and should be closely followed in specialized centers with collaboration between maternal-fetal medicine and rheumatology.

Hospital antenatal admissions for threatened preterm labor: how long should we be "observing"?

PURPOSE: We sought to describe temporal trends in hospital admissions for threatened preterm labor (TPTL) and to examine hospital admission duration among women delivered or discharged undelivered. METHODS: We carried out a cohort study on all TPTL admissions among pregnancies with a live singleton fetus and intact membranes between 1999 and 2015 using the United States' Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. ICD-9 codes were used to identify women with TPTL. Duration of antenatal admission length of stay was calculated in days following admission to hospital until delivery ("Delivery Admission") or undelivered discharge ("Observation Admission"). Analyses included evaluating trends of birth admissions over total admissions, identifying predictors of delivery using logistic regression, and measuring risk for delivery with increasing duration of antepartum hospitalization. RESULTS: Of 15,335,288 pregnancy admissions, 1,089,987 admissions were for TPTL, with 61.8% being 'Delivery Admissions". During the 16-year study period, overall rates of TPTL admissions declined with a rising proportion of admissions being "Delivery Admissions". "Delivery Admissions" were more common among patients who were older, non-Caucasian, obese, or who had placental abruption. "Observation Admissions" were more common among admissions for antepartum hemorrhage or antepartum spotting. Among all "Delivery Admissions" for TPTL, 89% had delivered within 2 days, 7% delivered within 3-6 days, and 5% delivered beyond 6 days. CONCLUSION: Overall admissions for TPTL declined over the study period with increasing proportions being "Delivery Admissions". Protocols taking into consideration declining risk of preterm birth among patients undelivered after 2 days may be helpful in reducing unnecessary prolonged observation admissions.

Audit logs to enforce document integrity in Skyline and Panorama.

SUMMARY: Skyline is a Windows application for targeted mass spectrometry method creation and quantitative data analysis. Like most graphical user interface (GUI) tools, it has a complex user interface with many ways for users to edit their files which makes the task of logging user actions challenging and is the reason why audit logging of every change is not common in GUI tools. We present an object comparison-based approach to audit logging for Skyline that is extensible to other GUI tools. The new audit logging system keeps track of all document modifications made through the GUI or the command line and displays them in an interactive grid. The audit log can also be uploaded and viewed in Panorama, a web repository for Skyline documents that can be configured to only accept documents with a valid audit log, based on embedded hashes to protect log integrity. This makes workflows involving Skyline and Panorama more reproducible. AVAILABILITY AND IMPLEMENTATION: Skyline is freely available at https://skyline.ms. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association between obsessive-compulsive disorder and obstetrical and neonatal outcomes in the USA: a population-based cohort study.

Obsessive-compulsive disorder (OCD) is a mental disorder linked to functional impairments and adverse health outcomes. We sought to examine the association between pregnant women with OCD and obstetrical and neonatal outcomes in the USA. A retrospective population-based cohort study was conducted using data provided by pregnant women from the Nationwide Inpatient Sample, a nationally representative database of hospitalizations in the USA, from 1999 to 2015. Using diagnostic and procedure codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), we identified births and classified women by OCD status. Demographic and clinical characteristics were compared for women with and without OCD and multivariate logistic regressions were used to obtain odds ratios (OR) to compare obstetrical and neonatal outcomes between the two groups, adjusting for relevant demographic and clinical variables. Between 1999 and 2015, there were 3365 births to women with OCD, corresponding to an overall prevalence of 24.40 per 100,000 births. Women with OCD were more likely to be older than 25, Caucasian, of higher socioeconomic status, smokers or used drugs and alcohol, and have other comorbid psychiatric conditions. In adjusted models, OCD was associated with a higher risk of gestational hypertension, preeclampsia, premature rupture of membranes, caesarean and instrumental deliveries, venous thromboembolisms and preterm birth. Pregnancies in women with OCD are at high risk of adverse obstetrical and neonatal outcomes. A multidisciplinary approach should be used to identify high risk behaviours and ensure adequate prenatal follow-up and care be available for those with high risk pregnancies.

Association Between First-Trimester Bleeding and Retained Placenta Requiring Dilatation and Curettage.

OBJECTIVE: Early subchorionic hemorrhage may lead to a disruption in the placental-uterine matrix, which may result in an adherence of the placenta to the endometrium. We evaluated the effect of a first-trimester bleed on the need for a post-vaginal delivery dilatation and curettage (D&C) for removal of retained placenta. METHODS: We conducted a case-control study at a tertiary care centre between 2012 and 2016. Patients identified through medical records as having required a post-vaginal delivery D&C for retained placenta were considered cases and were matched 1:5 with patients delivering vaginally within 1 week who did not require a D&C. History of first-trimester bleeding and subchorionic hemorrhage were identified through chart review. Conditional logistic regression analyses estimated the effect of a first-trimester bleed on the requirement for D&C for retained placenta. Models were adjusted for maternal age and previous uterine surgery. RESULTS: There were 68 cases of retained placenta requiring D&C, for an estimated 3 in 1000 deliveries. Patients requiring D&C were slightly older than controls but were otherwise comparable with respect to baseline demographic characteristics. In adjusted analyses, patients who required a postpartum D&C were more likely than controls to have had a first-trimester bleed at 11.8% and 0.6%, respectively (OR 25.3; 95% CI 4.7-135.4, P < 0.001). Postpartum D&C for retained placenta was associated with postpartum hemorrhage, need for blood transfusion, and manual removal of placenta. CONCLUSION: First-trimester bleeding should be considered a high-risk determinant for post-vaginal delivery D&C for retained placenta and for severe postpartum hemorrhage.

Maternal and fetal outcomes in pregnancies with obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is linked to many health comorbidities. We aimed to ascertain if OSA correlates with a rise in poor obstetrical outcomes. METHODS: Employing the United States' Healthcare Cost and Utilization Project - National Inpatient Sample, we performed our retrospective cohort study including all women who delivered between 2006 and 2015. ICD-9 codes were used to characterize women as having a diagnosis of OSA. Temporal trends in pregnancies with OSA were studied, baseline features were evaluated among gravidities in the presence and absence of OSA, and multivariate logistic regression analysis was utilized in assessing consequences of OSA on patient and newborn outcomes. RESULTS: Of a total 7,907,139 deliveries, 3,115 belonged to patients suffering from OSA, resulting in a prevalence of 39 per 100,000 deliveries. Rates rose from 10.14 to 78.12 per 100,000 deliveries during the study interval (p<0.0001). Patients diagnosed with OSA were at higher risk of having pregnancies with preeclampsia, OR 2.2 (95% CI 2.0-2.4), eclampsia, 4.1 (2.4-7.0), chorioamnionitis, 1.4 (1.2-1.8), postpartum hemorrhage, 1.4 (1.2-1.7), venous thromboembolisms, 2.7 (2.1-3.4), and to deliver by caesarean section, 2.1 (1.9-2.3). Cardiovascular and respiratory complications were also more common among these women, as was maternal death, 4.2 (2.2-8.0). Newborns of OSA patients were at elevated risk of being premature, 1.3 (1.2-1.5) and having congenital abnormalities, 2.3 (1.7-3.0). CONCLUSIONS: Pregnancies with OSA were linked to an elevated risk of poor maternal and neonatal outcomes. During pregnancy, OSA patients should receive attentive follow-up care in a tertiary hospital.