Capacity to consent: a scoping review of youth decision-making capacity for gender-affirming care.

BACKGROUND: Transgender and gender expansive (TGE) youth often seek a variety of gender-affirming healthcare services, including pubertal suppression and hormone therapy requiring that TGE youth and their parents participate in informed consent and decision making. While youth must demonstrate the ability to understand and appreciate treatment options, risks, benefits, and alternatives as well as make and express a treatment choice, standardized approaches to assess the capacity of TGE youth to consent or assent in clinical practice are not routinely used. This scoping review identified the currently available data regarding adolescent capacity to consent to gender-affirming medical treatments. METHODS: Articles relevant to assessing adolescent capacity for clinical decision-making were identified using OVID Medline, Web of Science, and PubMed. Articles were reviewed and thematically analyzed. RESULTS: Eight relevant articles were identified using three tools for measuring adolescent clinical decision-making capacity: Measure of Understanding, Measure of Competence, and MacArthur Competence Assessment Tool (MacCAT). These studies explored hypothetical treatment decisions, mental health treatment decisions, HIV treatment decisions, genetic testing decisions, and gender-affirming medical decisions. Only one study specifically examines the capacity of TGE youth to consent to medical treatments. Age was correlated with capacity in most, but not all studies. Other studies found cognitive measures (IQ, literacy, numeracy) may impact important aspects of capacity (understanding and reasoning). CONCLUSIONS: For clinicians caring for TGE youth, tools such as the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) may prove useful, in conjunction with consideration of youth developmental abilities and utilization of shared decision-making practices. A standardized, collaborative approach to assessing TGE youth capacity would benefit TGE youth and their parents, and allow clinicians to more easily resolve ethical concerns.

Glucose Variability in People with Type 1 Diabetes: Associations with Body Weight, Body Composition, and Insulin Sensitivity.

The prevalence of overweight and obesity increases in people with type 1 diabetes (T1D). However, the impact of fat accumulation on glucose dynamics in T1D is poorly understood. We assessed continuous glucose monitoring (CGM) parameters in patients with T1D depending on their body weight, body composition, and insulin sensitivity. In 547 patients, including 238 overweight/obese individuals, CGM-derived time in range (TIR) and glucose variability (GV) were estimated. Body composition was assessed by DXA. Estimated glucose disposal rate (eGDR) was used as an indicator of insulin sensitivity. Overweight/obese patients, when compared to normal-weight ones, have a lower time below range (TBR) (<3 mmol/L), GV, and experienced fewer episodes of low glucose. In men, lower TIR, higher time above range (TAR), and GV reduction were associated with central adiposity assessed by total, trunk, and android fat mass. In women, gynoid fat mass only was associated with a lower TIR and higher TAR. The eGDR was a positive predictor of TIR and a negative predictor of TAR, TBR, and GV in men and women. In conclusion, adiposity in people with T1D is associated with a lower risk of CGM-confirmed hypoglycemia, higher TAR, and reduced GV. These features of daily glucose dynamics may be mediated by insulin resistance.

Utility of the 52-Gene Risk Score to Identify Patients with Idiopathic Pulmonary Fibrosis at Greater Risk of Mortality in the Era of Antifibrotic Therapy.

PURPOSE: We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy. METHODS: The 52-gene risk signature was implemented to classify patients as being at "high risk" or "low risk" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature. RESULTS: The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort. CONCLUSIONS: These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality.

Cross-species striatal hubs: Linking anatomy to resting-state connectivity.

Corticostriatal connections are essential for motivation, cognition, and behavioral flexibility. There is broad interest in using resting-state functional magnetic resonance imaging (rs-fMRI) to link circuit dysfunction in these connections with neuropsychiatric disorders. In this paper, we used tract-tracing data from non-human primates (NHPs) to assess the likelihood of monosynaptic connections being represented in rs-fMRI data of NHPs and humans. We also demonstrated that existing hub locations in the anatomical data can be identified in the rs-fMRI data from both species. To characterize this in detail, we mapped the complete striatal projection zones from 27 tract-tracer injections located in the orbitofrontal cortex (OFC), dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), ventrolateral PFC (vlPFC), and dorsal PFC (dPFC) of macaque monkeys. Rs-fMRI seeds at the same regions of NHP and homologous regions of human brains showed connectivity maps in the striatum mostly consistent with those observed in the tracer data. We then examined the location of overlap in striatal projection zones. The medial rostral dorsal caudate connected with all five frontocortical regions evaluated in this study in both modalities (tract-tracing and rs-fMRI) and species (NHP and human). Other locations in the caudate also presented an overlap of four frontocortical regions, suggesting the existence of different locations with lower levels of input diversity. Small retrograde tracer injections and rs-fMRI seeds in the striatum confirmed these cortical input patterns. This study sets the ground for future studies evaluating rs-fMRI in clinical samples to measure anatomical corticostriatal circuit dysfunction and identify connectional hubs to provide more specific treatment targets for neurological and psychiatric disorders.

Assessing the effects of "native speaker" status on classic findings in speech research.

It is common practice in speech research to only sample participants who self-report being "native English speakers." Although there is research on differences in language processing between native and nonnative listeners (see Lecumberri et al., 2010, for a review), the majority of speech research that aims to establish general findings (e.g., testing models of spoken word recognition) only includes native speakers in their sample. Not only is the "native English speaker" criterion poorly defined, but it also excludes historically underrepresented groups from speech perception research, often without attention to whether this exclusion is likely to affect study outcomes. The purpose of this study is to empirically test whether and how using different inclusion criteria ("native English speakers" vs. "nonnative English speakers") affects several well-known phenomena in speech perception research. Five hundred participants completed word (N = 200) and sentence (N = 300) identification tasks in quiet and in moderate levels of background noise. Results indicate that multiple classic findings in speech perception research-including the effects of noise level, lexical density, and semantic context on speech intelligibility-persist regardless of "native English" speaking status. However, the magnitude of some of these effects differed across participant groups. Taken together, these results suggest that researchers should carefully consider whether native speaker status is likely to affect outcomes and make decisions about inclusion criteria on a study-by-study basis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Foodprint 2.0: A computational simulation model that estimates the agricultural resource requirements of diet patterns.

Reducing the environmental pressures stemming from food production is central to meeting global sustainability targets. Shifting diets represents one lever for improving food system sustainability, and identifying sustainable diet opportunities requires computational models to represent complex systems and allow users to evaluate counterfactual scenarios. Despite an increase in the number of food system sustainability models, there remains a lack of transparency of data inputs and mathematical formulas to facilitate replication by researchers and application by diverse stakeholders. Further, many models lack the ability to model multiple geographic scales. The present study introduces Foodprint 2.0, which fills both gaps. Foodprint 2.0 is an updated biophysical simulation model that estimates the agricultural resource requirements of diet patterns and can be adapted to suit a variety of research purposes. The objectives of this study are to: 1) describe the new features of Foodprint 2.0, and 2) demonstrate model performance by estimating the agricultural resource requirements of food demand in the United States (US) using nationally representative dietary data from the National Health and Nutrition Examination Survey from 2009-2018. New features of the model include embedded functions to integrate individual-level dietary data that allow for variance estimation; new data and calculations to account for the resource requirements of food trade and farmed aquatic food; updated user interface; expanded output data for over 200 foods that include the use of fertilizer nutrients, pesticides, and irrigation water; supplementary files that include input data for all parameters on an annual basis from 1999-2018; sample programming code; and step-by-step instructions for users. This study demonstrates that animal-sourced foods consumed in the US accounted for the greatest share of total land use, fertilizer nutrient use, pesticide use, and irrigation water use, followed by grains, fruits, and vegetables. Greater adherence to the Dietary Guidelines for Americans was associated with lower use of land and fertilizer nutrients, and greater use of pesticides and irrigation water. Foodprint 2.0 is a highly modifiable model that can be a useful resource for informing sustainable diet policy discussions.

Volition and control in law and in brain science: neurolegal translation of a foundational concept.

The law assumes that healthy adults are generally responsible for their actions and have the ability to control their behavior based on rational and moral principles. This contrasts with some recent neuroscientific accounts of action control. Nevertheless, both law and neuroscience acknowledge that strong emotions including fear and anger may "trigger" loss of normal voluntary control over action. Thus, "Loss of Control" is a partial defense for murder under English law, paralleling similar defenses in other legal systems. Here we consider the neuroscientific evidence for such legal classifications of responsibility, particularly focussing on how emotional states modulate voluntary motor control and sense of agency. First, we investigate whether neuroscience could contribute an evidence-base for law in this area. Second, we consider the societal impact of some areas where legal thinking regarding responsibility for action diverges from neuroscientific evidence: should we be guided by normative legal traditions, or by modern understanding of brain functions? In addressing these objectives, we propose a translation exercise between neuroscientific and legal terms, which may assist future interdisciplinary research.

Splenic flexure adenocarcinoma: A national cohort analysis of extent of surgical resection and outcomes.

AIM: The optimal extent of resection for splenic flexure adenocarcinoma remains debated. These tumours straddle the left- and right-sided vasculature with lymphatic drainage in a watershed area; current guidelines recommend either segmental or extended colectomy. We analysed surgical management of splenic flexure tumours and compared outcomes between approaches. METHOD: The Surveillance, Epidemiology and End Results database was searched for adults with Stage I-III splenic flexure adenocarcinoma, 2004-2019. RESULTS: Of 5238 patients, 55% underwent extended colectomy. Compared to segmental colectomy, these patients were more likely to have advanced stage. On multivariable analysis, age ≤ 65 years remained independently associated with extended colectomy. Although fewer nodes were examined in segmental colectomy (median 14 vs. 16, p < 0.001), the number of positive nodes (both, median 0 [interquartile ratio 0-2], p = 0.20) and the lymph node ratio were similar between cohorts. Surgical approach was not significantly associated with increased positive nodal yield in adjusted analyses. Five-year overall and disease-specific survival were 73% and 84% for segmental and 72% and 83% for extended colectomy (p > 0.4); these remained comparable after adjustment. CONCLUSIONS: Nationally, we observed similar rates of segmental and extended colectomy for splenic flexure adenocarcinoma. Extended colectomy was not more common in Stage III disease, indicating lack of stage migration, and was not associated with better oncological outcomes. These observations support current practice involving either approach, which should be tailored to patient-related factors and preferences, while considering technical aspects and quality of life.

Systematic scoping review of cluster randomised trials conducted exclusively in low-income and middle-income countries between 2017 and 2022.

OBJECTIVE: Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time. DESIGN: A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews. DATA SOURCES: We searched MEDLINE between 1 January 2017 and 17 August 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022. DATA EXTRACTION AND SYNTHESIS: Data were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country's economic level or publication year. RESULTS: Among 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country's economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time. CONCLUSION: Our findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed.

Whole Body Physiologically Based Pharmacokinetic Model to Explain A Patient With Drug-Drug Interaction Between Voriconazole and Flucloxacillin.

BACKGROUND AND OBJECTIVES: Voriconazole administered concomitantly with flucloxacillin may result in subtherapeutic plasma concentrations as shown in a patient with Staphylococcus aureus sepsis and a probable pulmonary aspergillosis. After switching our patient to posaconazole, therapeutic concentrations were reached. The aim of this study was to first test our hypothesis that flucloxacillin competes with voriconazole not posaconazole for binding to albumin ex vivo, leading to lower total concentrations in plasma. METHODS: A physiologically based pharmacokinetic (PBPK) model was then applied to predict the mechanism of action of the drug-drug interaction (DDI). The model included non-linear hepatic metabolism and the effect of a severe infectious disease on cytochrome P450 (CYP) enzymes activity. RESULTS: The unbound voriconazole concentration remained unchanged in plasma after adding flucloxacillin, thereby rejecting our hypothesis of albumin-binding site competition. The PBPK model was able to adequately predict the plasma concentration of both voriconazole and posaconazole over time in healthy volunteers. Upregulation of CYP3A4, CYP2C9, and CYP2C19 through the pregnane X receptor (PXR) gene by flucloxacillin resulted in decreased voriconazole plasma concentrations, reflecting the DDI observations in our patient. Posaconazole metabolism was not affected, or was only limitedly affected, by the changes through the PXR gene, which agrees with the observed plasma concentrations within the target range in our patient. CONCLUSIONS: Ex vivo experiments reported that the unbound voriconazole plasma concentration remained unchanged after adding flucloxacillin. The PBPK model describes the potential mechanism driving the drug-drug and drug-disease interaction of voriconazole and flucloxacillin, highlighting the large substantial influence of flucloxacillin on the PXR gene and the influence of infection on voriconazole plasma concentrations, and suggests a more limited effect on other triazoles.

Anti-SARS-CoV-2 mRNA vaccination among patients living with SLE in Sweden: Coverage and clinical effectiveness.

OBJECTIVES: To describe the uptake of anti-SARS-CoV2 vaccination in 2021 and investigate vaccine effectiveness in systemic lupus erythematosus (SLE) patients in Sweden. METHODS: The cumulative incidence of first anti-SARS-CoV2 vaccination was estimated among SLE patients from the Swedish National Patient Register and matched comparators living in Sweden on January 1, 2021. To assess vaccine effectiveness, we included the individuals who received two doses of anti-SARS-CoV2 mRNA vaccines before year 2022, with no COVID-19 diagnosis code before the 2nd vaccine dose. Hospitalization rates with COVID-19 as main diagnosis during the year after second dose were compared between SLE patients and comparators in multivariable-adjusted marginal Cox models, overall and stratified by immunosuppressive treatment received during the year before second vaccine dose. RESULTS: Vaccination uptake was similar between SLE patients and comparators. By December 2021, 9% of both SLE and comparators had not received any vaccine doses. Among 5585 SLE patients and 37,102 comparators, 11 COVID-19 hospitalizations in the SLE group and 20 in the comparators occurred. SLE was associated with a higher risk of COVID-19 hospitalization (HR = 3.47, 95%CI 1.63-7.39). The HR was higher for immunosuppressive-treated SLE (7.03 95%CI 3.00-16.46) than for immunosuppressive-untreated (1.50 95%CI 0.34-6.60). Vaccination of immunosuppressive-untreated SLE patients had similar effectiveness as comparators. CONCLUSION: Anti-SARS-CoV2 vaccination coverage was similar between SLE patients and the general population in Sweden. Even though the incidence of post-vaccination COVID-19 hospitalization was very low, vaccine effectiveness was diminished in SLE patients compared to the general population and lowest in those treated with immunosuppressants.

The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results.

BACKGROUND: Olpasiran, a small interfering RNA (siRNA), blocks lipoprotein(a) (Lp(a)) production by preventing translation of apolipoprotein(a) mRNA. In phase 2, higher doses of olpasiran every 12 weeks (Q12W) reduced circulating Lp(a) by >95%. OBJECTIVES: This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety. METHODS: OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study) was a phase 2, dose-finding trial that enrolled 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L to 1 of 4 active doses of olpasiran vs placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W given subcutaneously). The last dose of olpasiran was administered at week 36; after week 48, there was an extended off-treatment follow-up period for a minimum of 24 weeks. RESULTS: A total of 276 (98.2%) participants entered the off-treatment follow-up period. The median study exposure (treatment combined with off-treatment phases) was 86 weeks (Q1-Q3: 79-99 weeks). For the 75 mg Q12W dose, the off-treatment placebo-adjusted mean percent change from baseline in Lp(a) was -76.2%, -53.0%, -44.0%, and -27.9% at 60, 72, 84, and 96 weeks, respectively (all P < 0.001). The respective off-treatment changes in Lp(a) for the 225 mg Q12W dose were -84.4%, -61.6%, -52.2%, and -36.4% (all P < 0.001). During the extension follow-up phase, no new safety concerns were identified. CONCLUSIONS: Olpasiran is a potent siRNA with prolonged effects on Lp(a) lowering. Participants receiving doses ≥75 mg Q12W sustained a ∼40% to 50% reduction in Lp(a) levels close to 1 year after the last dose. (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study [OCEAN(a)-DOSE]; NCT04270760).

Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.

Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS), the only backbone chemistry used clinically, may be insufficient for targeting extrahepatic tissues. To improve oligonucleotide stabilization, we report the discovery, synthesis and characterization of extended nucleic acid (exNA) consisting of a methylene insertion between the 5'-C and 5'-OH of a nucleoside. exNA incorporation is compatible with common oligonucleotide synthetic protocols and the PS backbone, provides stabilization against 3' and 5' exonucleases and is tolerated at multiple oligonucleotide positions. A combined exNA-PS backbone enhances resistance to 3' exonuclease by ~32-fold over the conventional PS backbone and by >1,000-fold over the natural phosphodiester backbone, improving tissue exposure, tissue accumulation and efficacy in mice, both systemically and in the brain. The improved efficacy and durability imparted by exNA may enable therapeutic interventions in extrahepatic tissues, both with siRNA and with other oligonucleotides such as CRISPR guide RNA, antisense oligonucleotides, mRNA and tRNA.

Culturing Osteochondral Explants Under Rotary Shaking or After Removing Bone Marrow Elements Increases Explant Cellular Viability.

BACKGROUND: Reduced viability in the deepest zones of osteochondral allografts (OCAs) can weaken the subchondral interface, potentially increasing the risk of failure. This reduction may result from nutritional imbalances due to uneven media distribution or interference from bone marrow elements. PURPOSE: To investigate whether culturing OCAs using a rotary shaker or removing the bone marrow elements would increase graft cellular viability. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine osteochondral explants were stored for 28 days at 4°C under 3 different conditions (n = 6 explants per group): static (control group), rotary shaker at 150 rpm (shaker group), and static after removal of bone marrow elements using a Waterpik device (Waterpik group). Chondrocyte viability was assessed using live/dead staining across the entire tissue and in each zone (superficial, middle, deep). Subchondral bone viability was assessed using TUNEL (terminal deoxynucleotidal transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling) staining to detect apoptotic cells. RESULTS: Both shaker (64.2%; P = .010) and Waterpik (65.6%; P = .005) conditions showed significantly higher chondrocyte viability compared with control (49.8%). When samples were analyzed by zone, the shaker and Waterpik groups displayed higher cellular viability at the middle zone (shaker = 60.6%, P < .001; Waterpik = 56.1%, P < .001) and deep zone (shaker = 63.1%, P = .018; Waterpik = 61.5%, P = .025) than the control group (25.6% at middle zone; 32.8% at deep zone). Additionally, shaker (56.7%; P = .018) and Waterpik (51.4%; P = .007) groups demonstrated a lower percentage of apoptotic cells in subchondral bone compared with control (88.0%). No significant differences were observed between the shaker and Waterpik groups in any of the analyses. CONCLUSION: Both rotary shaking and removal of bone marrow elements during storage of osteochondral explants led to higher chondrocyte viability at the middle and deep zones of the graft compared with the static storage condition. Enhancing nutrition delivery to the graft could improve its quality, potentially improving outcomes of OCA transplantation. CLINICAL RELEVANCE: The use of a rotary shaker or the removal of bone marrow elements may significantly improve the culture conditions, increasing graft viability and integrity after OCA storage.

A theoretical view on the stereochemistry of 1,3-benzoxazol-2-(3H)-ylidenes obtained from double vinylic substitution.

2-(1,3-Benzoxazol-2(3H)-ylidene)-3-oxo-3-phenylpropanenitrile (1) and methyl-2-(1,3-benzoxazol-2(3H)-ylidene)(cyano)acetate (2) are observed as single isomers by NMR spectroscopy. A theoretical study was carried out to investigate if this is due to the exclusive presence of the most stable diastereoisomer or if the ene moiety undergoes fast rotation, thereby allowing for the observation of an average conformer. Indeed, the pronounced stabilization of the E stereoisomer, attributed to intramolecular hydrogen bonding, makes it the single obtained product.

Increased Risk of Preterm Delivery Subtypes and Hypertensive Disorders of Pregnancy in First Deliveries of Patients With Systemic Vasculitis.

OBJECTIVE: The goal of this study was to investigate the risk of preterm birth subtypes and hypertensive disorders of pregnancy in patients with systemic vasculitis using large, statewide databases. METHODS: Births to nulliparous patients with prevalent systemic vasculitides (Takayasu arteritis [TAK], Behçet disease [BD], antineutrophil cytoplasmic antibody-associated vasculitis [AAV], and Kawasaki disease [KD]) were identified using International Classification of Diseases, Ninth Revision codes in linked administrative data and birth records from the California Department of Health Care Access and Information and California Vital Statistics from 1991 to 2012. Hypertensive disorders of pregnancy and preterm delivery (PTD) subtypes were identified. Multivariable-adjusted Poisson models estimated risk ratios (RRs) of these outcomes compared with the general birthing population without history of rheumatic disease. RESULTS: A total of 96 births to nulliparous patients with systemic vasculitis were identified (TAK, 14; AAV, 31; BD, 26; KD, 15) and compared with 4,191,900 births of the nulliparous general population. Adjusted RRs for all PTD types were elevated in patients with vasculitis (RR 3.21, 95% confidence interval [CI] 2.15-4.79), as were the RRs of all PTD subtypes including preterm premature rupture of membranes (RR 4.30, 95% CI 2.05-9.01) and spontaneous PTD (RR 4.99, 95% CI 3.01-8.28). Of the spontaneous PTDs among patients with vasculitis, 16.7% were early PTDs (20-31 weeks), with the remaining 83.3% occurring between 32 to 36 weeks. Patients with vasculitis also had an elevated risk of hypertensive disorders of pregnancy (RR 2.96, 95% CI 1.72-5.10). CONCLUSION: Among first-time births, we found that patients with systemic vasculitis have an elevated risk of PTD subtypes as well as hypertensive disorders of pregnancy.

A Counterfactual Analysis of Impact of Cesarean Birth in a First Birth on Severe Maternal Morbidity in the Subsequent Birth.

BACKGROUND: It is known that cesarean birth affects maternal outcomes in subsequent pregnancies, but specific effect estimates are lacking. We sought to quantify the effect of cesarean birth reduction among nulliparous, term, singleton, vertex (NTSV) births (i.e., preventable cesarean births) on severe maternal morbidity (SMM) in the second birth. METHODS: We examined birth certificates linked with maternal hospitalization data (2007-19) from California for NTSV births with a second birth (N = 779,382). The exposure was cesarean delivery in first birth and the outcome was SMM in the second birth. We used adjusted Poisson regression models to calculate risk ratios and population attributable fraction for SMM in the second birth and conducted a counterfactual impact analysis to estimate how lowering NTSV cesarean births could reduce SMM in second birth. RESULTS: The adjusted risk ratio for SMM in the second birth given a prior cesarean birth was 1.7 (95% CI 1.5-1.9); 15.5% (95% CI 15.3%-15.7%) of this SMM may be attributable to prior cesarean birth. In a counterfactual analysis where 12% of the California population least likely to get a cesarean birth instead delivered vaginally, we observed 174 fewer SMM events in a population of individuals with a low-risk first birth and a subsequent birth. CONCLUSIONS: In our counterfactual analysis, lowering primary cesarean birth among a NTSV population was associated with fewer downstream SMM events in subsequent births and overall. Additionally, our findings reflect the importance of considering the cumulative accrual of risks across the reproductive life-course.