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.

Amniotic fluid embolism: 20-year incidence and case-fatality trends in the United States.

OBJECTIVE: To estimate incidence and case-fatality rates of amniotic fluid embolism (AFE) and to examine their temporal trends. STUDY DESIGN: Population-based retrospective cohort study using the 2000-2019 Health Care Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS). Annual population rates were estimated using HCUP-NIS specific weighting. Descriptive analyses and logistic regression described trends within the cohort. RESULTS: Over the study period, AFE incidence rate remained stable (mean 4.9 cases/100,000 deliveries) and the case-fatality rate declined (mean 17.7 %,95 % CI 16.40-10.09). Highest AFE incidence rates and fatality rates were in women ≥ 35 years, African-Americans, and in urban-teaching hospitals. AFE mortality rates decreased among Hispanics. CONCLUSION: AFE rates remained stable and fatality rates declined over time. Highest rates of AFE occurrence and death were in women who typically have greater risk of experiencing adverse obstetrical outcomes. Continued research into early diagnostic methods and effective treatments are needed to further improve AFE incidence and mortality rates.

Obstetrical and neonatal outcomes in women with gestational Lyme disease.

OBJECTIVE: The incidence of Lyme disease (LD) infections has risen in recent decades. Gestational LD has been associated with adverse pregnancy outcomes; however, the results have been contradictory. The study objective was to examine the effects of gestational LD on obstetrical and neonatal outcomes. METHODS: Using the Healthcare Cost & Utilization Project National (Nationwide) Inpatient Sample from the United States, we conducted a retrospective cohort study of pregnant patients admitted to the hospital between 2016 and 2019. The exposed group consisted of pregnant patients with gestational LD infection (International Classification of Diseases, Tenth Revision [ICD-10] code A692x), while the comparison group consisted of pregnant patients without gestational LD. Descriptive statistics and multivariate logistic regression models, adjusted for baseline maternal characteristics, were used to determine the associations between gestational LD and obstetrical and neonatal outcomes. RESULTS: The cohort included 2 943 575 women, 226 of whom were diagnosed with LD during pregnancy. The incidence of LD was 7.67 per 100 000 pregnancy admissions. The incidence of gestational LD was stable over the study period. Pregnant patients with LD were more likely white, older, to have private health insurance, and to belong to a higher income quartile. Gestational LD was associated with an increased risk of placental abruption (adjusted odds ratio [aOR], 3.45 [95% confidence interval (CI), 1.53-7.80]) and preterm birth (aOR, 1.58 [95% CI, 1.03-2.42]). CONCLUSION: Gestational LD is associated with a higher risk of placental abruption and preterm birth. Pregnancies complicated by LD, while associated with a higher risk of certain adverse outcomes, can be followed in most healthcare settings.

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.

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.

Targeted proteomics data interpretation with DeepMRM.

Targeted proteomics is widely utilized in clinical proteomics; however, researchers often devote substantial time to manual data interpretation, which hinders the transferability, reproducibility, and scalability of this approach. We introduce DeepMRM, a software package based on deep learning algorithms for object detection developed to minimize manual intervention in targeted proteomics data analysis. DeepMRM was evaluated on internal and public datasets, demonstrating superior accuracy compared with the community standard tool Skyline. To promote widespread adoption, we have incorporated a stand-alone graphical user interface for DeepMRM and integrated its algorithm into the Skyline software package as an external tool.

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 extra-cellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5,000 plasma proteins in a 60-minute gradient with the Orbitrap Astral mass spectrometer.

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.

Obstetrical and neonatal outcomes among pregnancies complicated by hyperparathyroidism.

PURPOSE: Severe hypercalcemia resulting from hyperparathyroidism may result in adverse perinatal outcomes. The objective of this study was to evaluate maternal and neonatal outcomes among pregnant women with hyperparathyroidism using a population database. METHODS: A retrospective cohort study was conducted using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999-2015. ICD-9 codes were used to identify women diagnosed with hyperparathyroidism during pregnancy. Perinatal outcomes between pregnant women with and without hyperparathyroidism were compared. Multivariate logistic regression, controlling for age, race, income, insurance type, hospital location, and comorbidities, evaluated the effect of hyperparathyroidism on perinatal outcomes. RESULTS: Of 13,792,544 deliveries included over the study period, 368 were to women with hyperparathyroidism. The overall incidence of hyperparathyroidism was 2.7/100,000 births, increasing from 1.6 to 5.2/100,000 births over the study period (p < 0.0001). Women with hyperparathyroidism were older and had more comorbidities, such as obesity, and pre-gestational hypertension and diabetes. Relative to the comparison group, women with hyperparathyroidism were more likely to deliver preterm, OR 1.69 (95% CI 1.24-2.29), to develop preeclampsia, 3.14 (2.30-4.28), and to deliver by cesarean, 1.69 (1.36-2.09). Infants born to mothers with hyperparathyroidism were more likely to be growth restricted, 1.83 (1.08-3.07), and to be diagnosed with a congenital anomaly, 4.21 (2.09-8.48). CONCLUSION: Hyperparathyroidism during pregnancy is associated with a significant increase in adverse perinatal outcomes, including preeclampsia, preterm delivery, fetal growth restriction, and congenital anomalies. As such, pregnancies among women with hyperparathyroidism should be considered high-risk, and specialized care is recommended in order to minimize maternal and neonatal morbidity.

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.

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.

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.

Utilizing Skyline to analyze lipidomics data containing liquid chromatography, ion mobility spectrometry and mass spectrometry dimensions.

Lipidomics studies suffer from analytical and annotation challenges because of the great structural similarity of many of the lipid species. To improve lipid characterization and annotation capabilities beyond those afforded by traditional mass spectrometry (MS)-based methods, multidimensional separation methods such as those integrating liquid chromatography, ion mobility spectrometry, collision-induced dissociation and MS (LC-IMS-CID-MS) may be used. Although LC-IMS-CID-MS and other multidimensional methods offer valuable hydrophobicity, structural and mass information, the files are also complex and difficult to assess. Thus, the development of software tools to rapidly process and facilitate confident lipid annotations is essential. In this Protocol Extension, we use the freely available, vendor-neutral and open-source software Skyline to process and annotate multidimensional lipidomic data. Although Skyline ( https://skyline.ms/skyline.url ) was established for targeted processing of LC-MS-based proteomics data, it has since been extended such that it can be used to analyze small-molecule data as well as data containing the IMS dimension. This protocol uses Skyline's recently expanded capabilities, including small-molecule spectral libraries, indexed retention time and ion mobility filtering, and provides a step-by-step description for importing data, predicting retention times, validating lipid annotations, exporting results and editing our manually validated 500+ lipid library. Although the time required to complete the steps outlined here varies on the basis of multiple factors such as dataset size and familiarity with Skyline, this protocol takes ~5.5 h to complete when annotations are rigorously verified for maximum confidence.

Menopausal Hormone Therapy Formulation and Breast Cancer Risk.

OBJECTIVE: To evaluate whether the increased risk of breast cancer is dependent on the formulation of menopausal hormone therapy (HT) used. METHODS: We performed a population-based case-control study of women aged 50 years or older using data from the U.K. Clinical Practice Research Datalink. Women with incident cases of breast cancer were age-matched (1:10) with a control group of women with comparable follow-up time with no history of breast cancer. Exposures were classified as ever or never for the following menopausal HT formulations: bioidentical estrogens, animal-derived estrogens, micronized progesterone, and synthetic progestin. Logistic regression analyses were performed to estimate the adjusted effect of menopausal HT formulation on breast cancer risk. RESULTS: Between 1995 and 2014, 43,183 cases of breast cancer were identified and matched to 431,830 women in a control group. In adjusted analyses, compared with women who never used menopausal HT, its use was associated with an increased risk of breast cancer (odds ratio [OR] 1.12, 95% CI 1.09-1.15). Compared with never users, estrogens were not associated with breast cancer (bioidentical estrogens: OR 1.04, 95% CI 1.00-1.09; animal-derived estrogens: OR 1.01, 95% CI 0.96-1.06; both: OR 0.96, 95% CI 0.89-1.03). Progestogens appeared to be differentially associated with breast cancer (micronized progesterone: OR 0.99, 95% CI 0.55-1.79; synthetic progestin: OR 1.28, 95% CI 1.22-1.35; both OR 1.31, 0.30-5.73). CONCLUSION: Although menopausal HT use appears to be associated with an overall increased risk of breast cancer, this risk appears predominantly mediated through formulations containing synthetic progestins. When prescribing menopausal HT, micronized progesterone may be the safer progestogen to be used.

Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain.

RING-between-RING (RBR) E3 ligases mediate ubiquitin transfer through an obligate E3-ubiquitin thioester intermediate prior to substrate ubiquitination. Although RBRs share a conserved catalytic module, substrate recruitment mechanisms remain enigmatic, and the relevant domains have yet to be identified for any member of the class. Here we characterize the interaction between the auto-inhibited RBR, HHARI (AriH1), and its target protein, 4EHP, using a combination of XL-MS, HDX-MS, NMR, and biochemical studies. The results show that (1) a di-aromatic surface on the catalytic HHARI Rcat domain forms a binding platform for substrates and (2) a phosphomimetic mutation on the auto-inhibitory Ariadne domain of HHARI promotes release and reorientation of Rcat for transthiolation and substrate modification. The findings identify a direct binding interaction between a RING-between-RING ligase and its substrate and suggest a general model for RBR substrate recognition.

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.

Effect of hidradenitis suppurativa on obstetric and neonatal outcomes.

PURPOSE: Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease with an often-unsatisfactory response to treatment. The objective was to evaluate the association between HS and pregnancy, delivery and neonatal outcomes. METHODS: The United States' Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database was used to conduct a retrospective cohort study among all women who delivered between 1999 and 2015. ICD-9 code 705.83 identified those with HS, with the remaining deliveries composing the comparison group. Multivariate logistic regression compared maternal and neonatal outcomes between these two groups, while adjusting for baseline maternal variables. RESULTS: The study included 13,792,544 deliveries, of which 1021 were associated with an HS diagnosis (7.4/100,000 deliveries). During the observation period, there was an upward trend in the prevalence of HS among pregnant women (<0.0001). Pregnant women with HS were more likely to be African-American, to belong to a lower income quartile, and to be insured by Medicaid. They were also more likely to smoke, to be morbidly obese, and to be hypertensive. Compared with women without HS, those with HS had a greater likelihood of developing preeclampsia (OR 1.36, 95% CI 1.08-1.71), delivering by cesarean section (OR 1.78, 95% CI 1.56-2.02), and having a baby with congenital anomalies (OR 2.00, 95% CI 1.10-3.62). CONCLUSIONS: Although HS is a complex skin disorder, pregnancies complicated by HS had comparable outcomes to non-HS pregnancies, with the exception of a greater risk of preeclampsia, cesarean sections, and congenital anomalies. Health-care providers and women should be aware of these HS associated risks.

Maternal and neonatal outcomes of births to women with psoriasis: a population-based cohort of 13 million births.

PURPOSE: Psoriasis is a common auto-immune disease affecting the skin and joints for which the current literature remains limited and contradictory in the context of pregnancy. The purpose of our study was to evaluate the association between psoriasis in pregnancy and maternal and newborn outcomes. METHODS: A population based retrospective cohort study was conducted using the 1999-2015 United States' Healthcare Cost and Utilization Project Nationwide Inpatient Sample. ICD-9 codes were used to identify delivery admissions to women with or without psoriasis, as well as maternal and fetal outcomes. Adjusting for baseline characteristics, multivariate logistic regression models were performed to estimate the effects of psoriasis on maternal and newborn outcomes. RESULTS: The cohort consisted of 3737 women with psoriasis, among a total of 13,792,544 pregnancy admissions in US hospitals between the years 1999 and 2015, for a period prevalence of 27.1 cases per 100,000 pregnant women. Psoriasis was associated with preeclampsia, OR 1.4 (95% CI 1.2-1.6), gestational diabetes, 1.27 (1.13-1.42), myocardial infarction, 13.4 (3.3-54.6), chorioamnionitis, 1.3 (1.0-1.6), delivery by cesarean section, 1.2 (1.1-1.3), anemia, 1.74 (1.18-2.57), and requiring blood transfusions, 1.4 (1.0-1.8). Their newborns were at higher risk of being born preterm, 1.2 (1.1-1.4), congenital anomalies, 1.7 (1.2-2.4), and intra-uterine growth restriction, 1.5 (1.2-1.7). CONCLUSION: Women with psoriasis and their newborns appear more prone to adverse outcomes of pregnancy. It would be prudent for these women to be followed closely during pregnancy by their obstetrical caregiver and dermatologist. Further investigation is warranted regarding the management of psoriasis during pregnancy.

Pregnancy outcomes in women with Ehlers-Danlos Syndrome.

PURPOSE: Ehlers-Danlos Syndrome (EDS) is an inherited connective tissue disorder caused by abnormal collagen synthesis. Little is known about its effects on pregnancy. The purpose of this study was to evaluate the pregnancy outcomes in women with EDS. MATERIALS AND METHODS: We conducted a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database from the United States. The study included women who delivered between 1999 and 2014. We measured the prevalence of EDS over time, and compared the baseline, obstetrical, and neonatal outcomes among women with EDS to the general obstetrical population without EDS. Unconditional logistic regression models were used to calculate the adjusted effect of EDS on maternal and neonatal outcomes. RESULTS: The overall prevalence of EDS in pregnancy was 7 per 100,000 births, with the trend increasing over the 16 year study period (p < .0001). Women with EDS were more likely to be Caucasian, belong to a higher income quartile, and smoke. Pregnancies in women with EDS were associated with prematurity, 1.47 (1.18-1.82), cervical incompetence, 3.11 (1.99-4.85), antepartum hemorrhage, 1.71 (1.16-2.50), placenta previa, 2.26 (1.35-3.77) and maternal death, 9.04 (1.27-64.27). Pregnant women with EDS were more likely to be delivered by cesarean section, 1.55 (1.36-1.76), have longer postpartum stays (>7 days), 2.82 (2.08-3.85), and have a neonate with intra-uterine growth restriction, 1.81 (1.29-2.54). CONCLUSIONS: EDS in pregnancy is a high-risk condition with increased maternal morbidity and mortality, as well as newborn morbidity. Consideration should be given to prematurity preventative measures and high-risk pregnancy consultation.