The prevalence of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants is very low: a retrospective cohort register study.

BACKGROUND: Current guidelines from Scandinavian Neuro Committee mandate a 24-hour observation for head trauma patients on anticoagulants, even with normal initial head CT scans, as a means not to miss delayed intracranial hemorrhages. This study aimed to assess the prevalence, and time to diagnosis, of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants. METHOD: Utilizing comprehensive two-year data from Region Skåne's emergency departments, which serve a population of 1.3 million inhabitants, this study focused on adult head trauma patients prescribed oral anticoagulants. We identified those with intracranial hemorrhage within 30 days, defining delayed intracranial hemorrhage as a bleeding not apparent on their initial CT head scan. These cases were further defined as clinically relevant if associated with mortality, any intensive care unit admission, or neurosurgery. RESULTS: Out of the included 2,362 head injury cases (median age 84, 56% on a direct acting oral anticoagulant), five developed delayed intracranial hemorrhages. None of these five cases underwent neurosurgery nor were admitted to an intensive care unit. Only two cases (0.08%, 95% confidence interval [0.01-0.3%]) were classified as clinically relevant, involving subdural hematomas in patients aged 82 and 87 years, who both subsequently died. The diagnosis of these delayed intracranial hemorrhages was made at 4 and 7 days following initial presentation to the emergency department. CONCLUSION: In patients with head trauma, on oral anticoagulation, the incidence of clinically relevant delayed intracranial hemorrhage was found to be less than one in a thousand, with detection occurring four days or later after initial presentation. This challenges the effectiveness of the 24-hour observation period recommended by the Scandinavian Neurotrauma Committee guidelines, suggesting a need to reassess these guidelines to optimise care and resource allocation. TRIAL REGISTRATION: This is a retrospective cohort study, does not include any intervention, and has therefore not been registered.

A Single High-Sensitivity Cardiac Troponin T Strategy for Ruling Out Myocardial Infarction.

Background: Ruling out acute myocardial infarction (AMI) in the emergency department (ED) is challenging. Studies have shown that a high-sensitivity cardiac troponin T (hs-cTnT) <5 ng/L or <6 ng/L at presentation (0 h) can be used to rule out AMI. The objective of this study was to identify whether an even higher hs-cTnT threshold can be used for a safe rule out of AMI in the ED. Methods: The derivation cohort consisted of 24,973 ED patients with a primary complaint of chest pain. In this cohort, we identified the highest concentration of 0 h hs-cTnT that corresponded to a negative predictive value (NPV) of ≥99.5% for the primary endpoint of AMI/all-cause death within 30 days and the secondary endpoint of all-cause death within one year. The results were validated in two cohorts consisting of 132,021 and 1167 ED chest pain patients. Results: The 0 h hs-cTnT threshold corresponding to a NPV of ≥99.5% for the primary endpoint was <9 ng/L (NPV: 99.6% and 95% CI: 99.5-99.7). This cutoff provided a sensitivity of 96.2% (95% CI: 95.2-97.1) and identified 59.7% of the patients as low risk compared to 35.8% and 43.9% with a 0 h hs-cTnT <5 ng/L and <6 ng/L, respectively. The results were similar in the validation cohorts and seemed to perform even better in patients where the 0 h hs-cTnT was measured >3 h after symptom onset and in those with a nonischemic ECG and nonhigh risk history. Conclusions: A 0 h hs-cTnT cutoff of <9 ng/L safely rules out AMI/death within 30 days in a majority of chest pain patients and is a more effective strategy than the currently recommended <5 ng/L and <6 ng/L cutoffs. This trial is registered with NCT03421873.

The skåne emergency medicine (SEM) cohort.

BACKGROUND: In the European Union alone, more than 100 million people present to the emergency department (ED) each year, and this has increased steadily year-on-year by 2-3%. Better patient management decisions have the potential to reduce ED crowding, the number of diagnostic tests, the use of inpatient beds, and healthcare costs. METHODS: We have established the Skåne Emergency Medicine (SEM) cohort for developing clinical decision support systems (CDSS) based on artificial intelligence or machine learning as well as traditional statistical methods. The SEM cohort consists of 325 539 unselected unique patients with 630 275 visits from January 1st, 2017 to December 31st, 2018 at eight EDs in the region Skåne in southern Sweden. Data on sociodemographics, previous diseases and current medication are available for each ED patient visit, as well as their chief complaint, test results, disposition and the outcome in the form of subsequent diagnoses, treatments, healthcare costs and mortality within a follow-up period of at least 30 days, and up to 3 years. DISCUSSION: The SEM cohort provides a platform for CDSS research, and we welcome collaboration. In addition, SEM's large amount of real-world patient data with almost complete short-term follow-up will allow research in epidemiology, patient management, diagnostics, prognostics, ED crowding, resource allocation, and social medicine.

Universal inter-molecular radical transfer reactions on metal surfaces.

On-surface synthesis provides tools to prepare low-dimensional supramolecular structures. Traditionally, reactive radicals are a class of single-electron species, serving as exceptional electron-withdrawing groups. On metal surfaces, however, such species are affected by conduction band screening effects that may even quench their unpaired electron characteristics. As a result, radicals are expected to be less active, and reactions catalyzed by surface-stabilized radicals are rarely reported. Herein, we describe a class of inter-molecular radical transfer reactions on metal surfaces. With the assistance of aryl halide precursors, the coupling of terminal alkynes is steered from non-dehydrogenated to dehydrogenated products, resulting in alkynyl-Ag-alkynyl bonds. Dehalogenated molecules are fully passivated by detached hydrogen atoms. The reaction mechanism is unraveled by various surface-sensitive technologies and density functional theory calculations. Moreover, we reveal the universality of this mechanism on metal surfaces. Our studies enrich the on-surface synthesis toolbox and develop a pathway for producing low-dimensional organic materials.

Comorbidities in women with polycystic ovary syndrome: a sibling study.

BACKGROUND: Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. METHODS: This total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors. RESULTS: Three thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally. CONCLUSION: Having been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.

Previous SARS-CoV-2 infections and their impact on the protection from reinfection during the Omicron BA.5 wave - a nested case-control study among vaccinated adults in Sweden.

Objectives: We evaluated the protection afforded by SARS-CoV-2 infection-induced immunity against reinfection among working-age vaccinated individuals during a calendar period from June to December 2022 when Omicron BA.5 was the dominating subvariant in Scania County, Sweden. Methods: The study cohort (n = 71,592) mainly consisted of health care workers. We analyzed 4144 infected cases during the Omicron BA.5 dominance and 41,440 sex- and age-matched controls with conditional logistic regression. Results: The average protection against reinfection was marginal (16%, 95% confidence interval [CI] 7-23%) during the study period but substantially higher for recent infections. Recent infection (3-6 months) with Omicron BA.2 and BA.5 offered strong protection (86%, 95% CI 68-94% and 78%, 95% CI 69-84%), whereas more distant infection (6-12 months) with Omicron BA.1, BA.2, and the variants before Omicron offered marginal or no protection. Conclusions: These findings suggest that infection-induced immunity contributes to short-term population protection against infection with the subvariant BA.5 among working-age vaccinated individuals but wanes considerably with time, independent of the virus variant.

A Capture-Recapture-based Ascertainment Probability Weighting Method for Effect Estimation With Under-ascertained Outcomes.

Outcome under-ascertainment, characterized by the incomplete identification or reporting of cases, poses a substantial challenge in epidemiologic research. While capture-recapture methods can estimate unknown case numbers, their role in estimating exposure effects in observational studies is not well established. This paper presents an ascertainment probability weighting framework that integrates capture-recapture and propensity score weighting. We propose a nonparametric estimator of effects on binary outcomes that combines exposure propensity scores with data from two conditionally independent outcome measurements to simultaneously adjust for confounding and under-ascertainment. Demonstrating its practical application, we apply the method to estimate the relationship between health care work and coronavirus disease 2019 testing in a Swedish region. We find that ascertainment probability weighting greatly influences the estimated association compared to conventional inverse probability weighting, underscoring the importance of accounting for under-ascertainment in studies with limited outcome data coverage. We conclude with practical guidelines for the method's implementation, discussing its strengths, limitations, and suitable scenarios for application.

Mechanistic insights into on-surface reactions from isothermal temperature-programmed X-ray photoelectron spectroscopy.

On-surface synthesis often proceeds under kinetic control due to the irreversibility of key reaction steps, rendering kinetic studies pivotal. The accurate quantification of reaction rates also bears potential for unveiling reaction mechanisms. Temperature-Programmed X-ray Photoelectron Spectroscopy (TP-XPS) has emerged as an analytical tool for kinetic studies with splendid chemical and sufficient temporal resolution. Here, we demonstrate that the common linear temperature ramps lead to fitting ambiguities. Moreover, pinpointing the reaction order remains intricate, although this key parameter entails information on atomistic mechanisms. Yet, TP-XPS experiments with a stepped temperature profile comprised of isothermal segments facilitate the direct quantification of rate constants from fitting time courses. Thereby, rate constants are obtained for a series of temperatures, which allows independent extraction of both activation energies and pre-exponentials from Arrhenius plots. By using two analogous doubly versus triply brominated aromatic model compounds, we found that their debromination on Ag(111) is best modeled by second-order kinetics and thus proceeds via the involvement of a second, non-obvious reactant. Accordingly, we propose that debromination is activated by surface supplied Ag adatoms. This hypothesis is supported by Density Functional Theory (DFT) calculations. We foresee auspicious prospects for this TP-XPS variant for further exploring the kinetics and mechanisms of on-surface reactions.

Two-dimensional materials by large-scale computations and chemical exfoliation of layered solids.

MXenes are a family of two-dimensional (2D) materials typically formed by etching the A element from a parent MAX phase. Computational screening for other 3D precursors suitable for such exfoliation is challenging because of the intricate chemical processes involved. We present a theoretical approach for predicting 2D materials formed through chemical exfoliation under acidic conditions by identifying 3D materials amenable for selective etching. From a dataset of 66,643 3D materials, we identified 119 potentially exfoliable candidates, within several materials families. To corroborate the method, we chose a material distinctly different from MAX phases, in terms of structure and chemical composition, for experimental verification. We selectively etched Y from YRu2Si2, resulting in 2D Ru2SixOy. The high-throughput methodology suggests a vast chemical space of 2D materials from chemical exfoliation.

Rescaling creatinine makes GFR estimation equations generally applicable across populations - validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry.

OBJECTIVES: To make glomerular filtration rate (GFR) estimating equations applicable across populations with different creatinine generation by using rescaled serum creatinine (sCr/Q) where sCr represents the individual creatinine level and Q the average creatinine value in healthy persons of the same population. METHODS: GFR measurements (mGFR, plasma clearance of 51Cr-EDTA) were conducted in 964 adult Black Europeans. We established the re-expressed Lund-Malmö revised equation (r-LMR) by replacing serum creatinine (sCr) with rescaled creatinine sCr/Q. We evaluated the r-LMR equation based on Q-values of White Europeans (r-LMRQ-white; Q-values females: 62 µmol/L, males: 80 µmol/L) and Black Europeans (r-LMRQ-Black; Q-values females: 65 µmol/L, males: 90 µmol/L), and the European Kidney Function Consortium equation (EKFCQ-White and EKFCQ-Black) regarding bias, precision (interquartile range, IQR) and accuracy (percentage of estimates within ±10 % [P10] and ±30 % [P30] of mGFR). RESULTS: Median bias of r-LMRQ-White/r-LMRQ-Black/EKFCQ-White/EKFCQ-Black were -9.1/-4.5/-6.3/-0.9 mL/min/1.73 m2, IQR 14.7/14.5/14.5/15.6 mL/min/1.73 m2, P10 25.1 %/34.8 %/30.3 %/37.2 % and P30 74.2 %/84.1 %/80.6 %/83.6 %. The improvement of bias and accuracy when using proper Q-values was most pronounced in men. Similar improvements were obtained above and below mGFR 60 mL/min/1.73 m2 and at various age and BMI intervals, except for BMI<20 kg/m2 where bias increased, and accuracy decreased. CONCLUSIONS: GFR estimating equations may be re-expressed to include rescaled creatinine (sCr/Q) and used across populations with different creatinine generation if population-specific average creatinine concentrations (Q-values) for healthy persons are established.

Extending the cystatin C based EKFC-equation to children - validation results from Europe.

BACKGROUND: A new cystatin C based European Kidney Function Consortium (EKFCCysC) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFCCrea). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor QCysC. METHODS: Rescaling factor QCysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex QCysC-age relationship based on 4th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFCCysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available. RESULTS: The EKFCCysC with the simple QCysC-value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFCCysC with the more complex 4th degree QCysC-value. The arithmetic mean of the EKFCCrea and EKFCCysC with the simple QCysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4th degree QCysC-polynomial. CONCLUSION: Using exactly the same QCysC of 0.83 mg/L, the adult EKFCCysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFCCrea and EKFCCysC results in bias closer to zero and P30 slightly over 90%.

Prior electrocardiograms not useful for machine learning predictions of major adverse cardiac events in emergency department chest pain patients.

At the emergency department (ED), it is important to quickly and accurately determine which patients are likely to have a major adverse cardiac event (MACE). Machine learning (ML) models can be used to aid physicians in detecting MACE, and improving the performance of such models is an active area of research. In this study, we sought to determine if ML models can be improved by including a prior electrocardiogram (ECG) from each patient. To that end, we trained several models to predict MACE within 30 days, both with and without prior ECGs, using data collected from 19,499 consecutive patients with chest pain, from five EDs in southern Sweden, between the years 2017 and 2018. Our results indicate no improvement in AUC from prior ECGs. This was consistent across models, both with and without additional clinical input variables, for different patient subgroups, and for different subsets of the outcome. While contradicting current best practices for manual ECG analysis, the results are positive in the sense that ML models with fewer inputs are more easily and widely applicable in practice.

Sociodemographic characteristics and COVID-19 testing rates: spatiotemporal patterns and impact of test accessibility in Sweden.

BACKGROUND: Diagnostic testing is essential for disease surveillance and test-trace-isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates. METHODS: We included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8-1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood. RESULTS: We observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5-69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5-14 years) ranging from 0.56 (95% CI 0.47-0.67) to 0.87 (95% CI 0.80-0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10-18% decrease in inhabitants 15-29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70-105, supporting an intervention effect. CONCLUSIONS: Ensuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.

Patterns of simultaneous contact allergies in patients with contact sensitization to oxidised linalool and oxidised limonene.

BACKGROUND: Contact allergy rates of linalool and limonene hydroperoxides (HPs) have increased. OBJECTIVES: To demonstrate the patterns of simultaneous positive patch test (PT) reactions and prevalences of multiple contact allergies (MCAs) in patients with contact allergy to linalool and/or limonene HPs. METHODS: A retrospective analysis of consecutive dermatitis patients in 2015-2020 was performed. RESULTS: Of all 4192 patients, 1851 had at least one positive PT reaction. Of these, 410 (22.2%) had MCAs, significantly related to a higher age (p-value = 0.003). Patients with an exclusively positive reaction to linalool HPs but not limonene HPs were shown to have MCAs (p-value <0.001, odds ratio (95% confidence interval) = 4.15 (3.01-5.73)). Patients with simultaneous contact allergies to both linalool and limonene HPs had contact allergies to many other screening and fragrance allergens. CONCLUSIONS: Simultaneous positive PT reactions to allergens in baseline series and fragrances are common in patients with the HPs contact allergy, especially linalool HPs. The pattern of simultaneous PT reactions principally suggested the co-sensitization of the cosmetic allergens.

Performance of the European Kidney Function Consortium (EKFC) creatinine-based equation in United States cohorts.

Estimating glomerular filtration rate (GFR) is important in daily practice to assess kidney function and adapting the best clinical care of patients with and without chronic kidney disease. The new creatinine-based European Kidney Function Consortium (EKFC) equation is used to estimate GFR. This equation was developed and validated mainly in European individuals and based on a rescaled creatinine, with the rescaling factor (Q-value) defined as the median normal value of serum creatinine in a given population. The validation was limited in Non-Black Americans and absent in Black Americans. Here, our cross-sectional analysis included 12,854 participants from nine studies encompassing large numbers of both non-Black and Black Americans with measured GFR by clearance of an exogenous marker (reference method), serum creatinine, age, sex, and self-reported race available. Two strategies were considered with population-specific Q-values in Black and non-Black men and women (EKFCPS) or a race-free Q-value (EKFCRF). In the whole population, only the EKFCPS equation showed no statistical median bias (0.14, 95% confidence interval [-0.07; 0.35] mL/min/1.73m2), and the bias for the EKFCRF (0.74, [0.51; 0.94] mL/min/1.73m2) was closer to zero than that for the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI2021) equation (1.22, [0.99; 1.47]) mL/min/1.73m2]. The percentage of estimated GFR within 30% of measured GFR was similar for CKD-EPI2021 (79.2% [78.5%; 79.9%]) and EKFCRF (80.1% [79.4%; 80.7%]), but improved for the EKFCPS equation (81.1% [80.5%; 81.8%]). Thus, our EKFC equations can be used to estimate GFR in the United States incorporating either self-reported race or unknown race at the patient's discretion per hospital registration records.

Role of chloride on the instability of blue emitting mixed-halide perovskites.

Although perovskite light-emitting diodes (PeLEDs) have seen unprecedented development in device efficiency over the past decade, they suffer significantly from poor operational stability. This is especially true for blue PeLEDs, whose operational lifetime remains orders of magnitude behind their green and red counterparts. Here, we systematically investigate this efficiency-stability discrepancy in a series of green- to blue-emitting PeLEDs based on mixed Br/Cl-perovskites. We find that chloride incorporation, while having only a limited impact on efficiency, detrimentally affects device stability even in small amounts. Device lifetime drops exponentially with increasing Cl-content, accompanied by an increased rate of change in electrical properties during operation. We ascribe this phenomenon to an increased mobility of halogen ions in the mixed-halide lattice due to an increased chemically and structurally disordered landscape with reduced migration barriers. Our results indicate that the stability enhancement for PeLEDs might require different strategies from those used for improving efficiency.

Atomic Scale Design of MXenes and Their Parent Materials─From Theoretical and Experimental Perspectives.

More than a decade after the discovery of MXene, there has been a remarkable increase in research on synthesis, characterization, and applications of this growing family of two-dimensional (2D) carbides and nitrides. Today, these materials include one, two, or more transition metals arranged in chemically ordered or disordered structures of three, five, seven, or nine atomic layers, with a surface chemistry characterized by surface terminations. By combining M, X, and various surface terminations, it appears that a virtually endless number of MXenes is possible. However, for the design and discovery of structures and compositions beyond current MXenes, one needs suitable (stable) precursors, an assessment of viable pathways for 3D to 2D conversion, and utilization or development of corresponding synthesis techniques. Here, we present a critical and forward-looking review of the field of atomic scale design and synthesis of MXenes and their parent materials. We discuss theoretical methods for predicting MXene precursors and for assessing whether they are chemically exfoliable. We also summarize current experimental methods for realizing the predicted materials, listing all verified MXenes to date, and outline research directions that will improve the fundamental understanding of MXene processing, enabling atomic scale design of future 2D materials, for emerging technologies.

The concurrent validity of the Lund University Checklist for Incipient Exhaustion and the Karolinska Exhaustion Disorder Scale: a replication study.

OBJECTIVE: As part of our research on Swedish school principals, we examined the concurrent validity between the Karolinska Exhaustion Disorder Scale (KEDS) and the Lund University Checklist for Incipient Exhaustion (LUCIE) in a cross-sectional study sample (N = 2670). Specifically, we examined: (a) to what extent LUCIE and KEDS identified the same individuals and their level of agreement, and (b) to what extent the present observations among school-principals agreed with previous observations made in a highly educated and healthy study sample drawn from the general population. RESULTS: Depending on established cut-points on LUCIE, the Kappa agreement (K) between LUCIE and KEDS varied between fair (K = 0.34 [95% Confidence Interval = 0.30-0.38]) and moderate (K = 0.54 [95% Confidence Interval = 0.51-0.58]). While the instruments did not always identify the same individuals, the most reasonable comparison between KEDS and LUCIE was achieved when the cut-off on LUCIE was made between step two and step three. The results essentially replicated our previous results observed in a highly educated and healthy study sample drawn from the general population. The level of agreement suggests that KEDS and LUCIE scores are supplementary rather than interchangeable. Thus, individual result from KEDS and LUCIE are probably best understood in dialogue with the person screened.

Early Life Factors and Polycystic Ovary Syndrome in a Swedish Birth Cohort.

Polycystic ovary syndrome (PCOS) is a medical condition with important consequences for women's well-being and reproductive outcomes. Although the etiology of PCOS is not fully understood, there is increasing evidence of both genetic and environmental determinants, including development in early life. We studied a population of 977,637 singleton women born in in Sweden between 1973 and 1995, followed sometime between the age 15 and 40. The incidence of PCOS was measured using hospital register data during 2001-2012, complemented with information about the women's, parents' and sisters' health and social characteristics from population and health care registers. Cox regression was used to study how PCOS is associated with intergenerational factors, and a range of early life characteristics. 11,594 women in the study sample were diagnosed with PCOS during the follow-up period. The hazard rate for PCOS was increased 3-fold (HR 2.98, 95% CI 2.43-3.64) if the index woman's mother had been diagnosed with PCOS, and with 1.5-fold (HR 1.51, 95% CI 1.39-1.63) if their mother had diabetes mellitus. We found associations of PCOS with lower (<7) one-minute Apgar score (HR 1.19, 95% CI 1.09-1.29) and with post-term birth (HR 1.19, 95% CI 1.13-1.26). Furthermore, heavy (10+ cigarettes/day) maternal smoking (HR 1.30, 95% CI 1.18-1.44) and maternal obesity (HR 1.90, 95% CI 1.62-2.36) were strongly associated with PCOS. This study finds support for the heritability and fetal origins of PCOS. Risk of PCOS could be reduced by further emphasizing the importance of maternal and early life health.