Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis.

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Have there been changes in the application of mechanical ventilation in relation to scientific evidence? A multicenter observational study in Mexico. / ¿Se han producido cambios en la aplicación de la ventilación mecánica en relación con la evidencia científica? Estudio multicéntrico en México.

OBJECTIVE: The main study objectives were to describe the practice of mechanical ventilation over an 18-year period in Mexico, and estimate changes in mortality among critical patients subjected to invasive mechanical ventilation (IMV). DESIGN: A retrospective subanalysis of a prospective observational study conducted in 1998, 2004, 2010 and 2016 was carried out. SETTING: Intensive Care Units (ICUs) in Mexico. PARTICIPANTS: Adult patients consecutively enrolled in the ICU during one month and who underwent IMV for more than 12hours or noninvasive mechanical ventilation for more than one hour. Follow-up was performed up to a maximum of 28 days after inclusion. INTERVENTIONS: None. PRINCIPAL VARIABLES OF INTEREST: Age, sex, severity upon admission as estimated by SAPS II, parameters of daily arterial blood gases, treatment and complication variables, date and status at discharge from the ICU and from hospital. RESULTS: A total of 959 patients were included in 81 ICUs. Tidal volume (vt) decreased significantly both in patients with acute respiratory distress syndrome (ARDS) criteria (estimated 8.5ml/kg b.w. in 1998 to 6ml/kg in 2016; P<0.001) and in patients without ARDS (estimated 9ml/kg b.w. in 1998 to 6ml/kg in 2016; P<0.001). The ventilatory protective strategy (defined as vt < 6ml/kg or < 8ml/kg and a plateau pressure < 30cmH2O) was: 19% in 1998, 44% in 2004, 58% in 2010 and 75% in 2016 (P<0.001). The adjusted mortality rate in ICU over the 4 periods was: in 2004, odds ratio (OR) 1.05 (95% confidence interval, 95%CI: 0.73-1.72; P=0.764); in 2010, OR 1.68 (95%CI: 1.13-2.48; P=0.009); in 2016, OR 0.85 (95%CI: 0.60-1.20; P=0.368). CONCLUSIONS: The clinical practice of IMV in Mexican ICUs has been modified over a period of 18 years. The most significant change is the ventilatory strategy based on low vt. These changes have not been associated with significant changes in mortality.

Non-conventional graphene superlattices as electron band-pass filters.

Electron transmission through different non-conventional (non-uniform barrier height) gated and gapped graphene superlattices (GSLs) is studied. Linear, Gaussian, Lorentzian and Pöschl-Teller superlattice potential profiles have been assessed. A relativistic description of electrons in graphene as well as the transfer matrix method have been used to obtain the transmission properties. We find that it is not possible to have perfect or nearly perfect pass bands in gated GSLs. Regardless of the potential profile and the number of barriers there are remanent oscillations in the transmission bands. On the contrary, nearly perfect pass bands are obtained for gapped GSLs. The Gaussian profile is the best option when the number of barriers is reduced, and there is practically no difference among the profiles for large number of barriers. We also find that both gated and gapped GSLs can work as omnidirectional band-pass filters. In the case of gated Gaussian GSLs the omnidirectional range goes from -50° to 50° with an energy bandwidth of 55 meV, while for gapped Gaussian GSLs the range goes from -80° to 80° with a bandwidth of 40 meV. Here, it is important that the energy range does not include remanent oscillations. On the light of these results, the hole states inside the barriers of gated GSLs are not beneficial for band-pass filtering. So, the flatness of the pass bands is determined by the superlattice potential profile and the chiral nature of the charge carriers in graphene. Moreover, the width and the number of electron pass bands can be modulated through the superlattice structural parameters. We consider that our findings can be useful to design electron filters based on non-conventional GSLs.

Encefalopatía traumática crónica, definición, diagnóstico y prevención: revisión de la literatura / Chronic traumatic encephalopathy, definition, diagnosis and prevention: review of literature

La encefalopatía traumática crónica (ETC) es una enfermedad neurodegenerativa que se produce como consecuencia traumatismos cerebrales repetitivos; concusiones, que son un síndrome clínico que se caracteriza por una alteración de la función cerebral. Una concusión, bajo su estricta definición, no debiese causar cambios estructurales en el cerebro por lo que no sería visible a través de imágenes, sí existen cambios a nivel microscópicos, bioquímicos y biomecánicos. La mayoría de los pacientes tienen completa resolución de sus síntomas dentro de 10 días (90 por ciento), pero existe un pequeño porcentaje que persiste con estos, pudiendo presentarse como un síndrome postconcusional, síndrome de segundo impacto o una encefalopatía traumática crónica. La ETC se caracteriza por la acumulación de prot-tau hiperfosforilada en neuronas y astrocitos. Estas se van a presentar en forma de ovillos o hilos neurofibrilares. En etapas iniciales las encontraremos de forma focalizada en la corteza frontal y en las formas más severas su distribución será más generalizada, distribuyéndose en la mayoría de las regiones del cerebro. Su diagnóstico se realiza a través de histopatología, por lo que hasta el momento sólo se ha logrado post-mortem. Se está trabajando en nuevas tecnologías asociadas a biomarcadores y PET para lograr una diagnostico premortem. El mayor énfasis en el manejo de esta taupatía es la prevención y adecuado manejo de las concusiones.

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease which is produced as a consequence of repeated brain trauma: concussions, which are a clinical syndrome characterized by an alteration in brain functions. A concussion, understrict definition, should not cause structural changes to the brain. Therefore, it would not be possible to see through images if there were changes at a microscopic, biochemical level. Most patients see their symptoms completely resolved within 10 days (90 percent), but there is a small percentage which persists, and these might cause a post-concussional syndrome, second impact syndrome of chronic traumatic encephalopathy. CTE is characterized by the accumulation of hyper-phosphorylated Tau protein in neurons and astrocytes. These appear in the form of neurofibrillary tangles. During the initial stages they are focalized in the frontal cortex and, in more severe cases, their distribution is more generalized, spreading through the majority of the regions in the brain. It is diagnosis is done through histopathology. Thus, it has only been possible to do post mortem. New technologies associated with bio-markers and PET are being worked on to achieve a pre-mortem diagnosis. The greatest emphasis in the handling of this tauopathy lies in the prevention and the adequate handling of concussions.

Crisis asmática grave asociada con infección viral / Severe asthmatic crisis related to viral infection

Resumen ANTECEDENTES: 50% de las crisis asmáticas son desencadenadas por infecciones virales, su relación con parámetros clínicos no se ha descrito en los adultos. OBJETIVO: determinar la prevalencia de crisis asmáticas de acuerdo con el espectro viral y su asociación con características clínicas y mecánica respiratoria. MATERIAL Y MÉTODO: estudio clínico, prospectivo y observacional en el que se incluyeron pacientes con crisis asmática grave del 1 de diciembre de 2010 al 31 de diciembre de 2011. Se excluyeron los pacientes con sospecha de infección bacteriana. Se aplicó cuestionario de síntomas, se determinó panel viral por hisopado nasal, espirometría y estudios de laboratorio. Se obtuvo el consentimiento informado de los participantes. RESULTADOS: se incluyeron en el estudio 100 pacientes. La edad promedio fue de 39±14 años, IMC 27±4 kg/m2, escala de Borg 6.2±1.2, escala mMRC 2.6±0.6, tiempo de los síntomas 7±7 días, FEV1 de 42±14%, oximetría de pulso 88±3% y estancia de 4.5±1.7 días. El 47% de los pacientes tenía rinitis alérgica. Se aisló virus en 36% (rinovirus 15% y coronavirus 6%). Al comparar la causa viral vs no viral, se observó que los pacientes eran menores en el primer grupo (36±13 vs 43±17 años, p=0.014); no hubo diferencia entre grado de obstrucción y síntomas. A mayor severidad del asma hubo más aislamientos de virus. CONCLUSIÓN: las crisis asmáticas asociadas con virus respiratorios tienen comportamiento clínico similar al de las no asociadas. En los pacientes con menor edad y con comportamiento más grave se aíslan virus con más frecuencia.

Abstract BACKGROUND: 50% of asthma attacks are triggered by viral in fections; its relationship with clinical parameters has not been described in adults. OBJECTIVE: To determine the prevalence of asthma attacks according to viral spectrum and its association with clinical features and respiratory mechanics. MATERIAL AND METHOD: A clinical, prospective and observational study with patients with severe asthma attended from December 1st 2010 to December 31st 2011. We excluded patients with suspected bacterial infection. Symptom questionnaire was applied, it was determined by nasal swab viral panel, spirometry and laboratory studies. Informed consent was obtained. RESULTS: One hundred patients were included. Mean age was 39±14 years, BMI 27±4 kg/m2, Borg 6.2±1.2, mMRC 2.6±0.6, length of symptoms 7±7 days and FEV1 of 42±14%, pulse oximetry 88±3% and stay 4.5±1.7 days; 47% of patients had allergic rhinitis. Virus was isolated in 36% (15% rhinovirus and 6% coronavirus). Comparing the non-viral vs viral etiology, patients were younger (36±13 vs 43±17 years, p=0.014) there was no difference between the degree of obstruction and symptoms. A greater severity of asthma was related to more isolation. CONCLUSION: Asthma attacks associated with respiratory viruses have similar clinical behavior to not associated ones. In younger patients with more severe behavior virus are isolated more frequently.

Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma.

BACKGROUND: The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus. METHODS: Patients with clinical stage II or III SCC of the esophagus received cisplatin 30 mg/m2/week (days 1, 8, 15), LDCI-FU 300 mg/m2/day (days 1-21), and concomitant RT to a dose of 45 Gy (150 cGy/fraction, 2 fractions/day) on tumor and affected lymph nodes, followed by radical esophagectomy. RESULTS: From 1997 to 2012, 64 patients were treated with this regimen. Twenty-four patients (37 %) had grade 3 esophagitis, 18 (28 %) of whom required hospitalization. The risk of hospitalization was reduced by placement of a jejunostomy tube before starting induction chemoradiotherapy. Six patients (9 %) had grade 3-4 neutropenia. Fifty-three patients (83 %) underwent esophageal resection and complete resection was achieved in 45 (70 %). The overall median survival was 28 months (95 % CI: 20.4-35.6) and 5-year survival was 38 %. In the 18 patients attaining a pathological complete response, median survival was 132 months and 5-year survival was 72 %. Positron emission tomography standardized uptake values (PET SUVmax) post-chemoradiotherapy were associated with pathological response (p = 0.03) and survival (p = 0.04). CONCLUSIONS: Intensive preoperative hyperfractionated RT concomitant to low-dose cisplatin and LDCI-FU is effective in patients with locally advanced SCC of the esophagus, with good pathological response and survival and manageable toxicities. Post-chemoradiotherapy PET SUVmax shows promise as a potential prognostic factor.

One-shot phase stepping with a pulsed laser and modulation of polarization: application to speckle interferometry.

For applications involving time varying optical phase distributions, fast cameras and/or pulsed lasers have to be used. To apply phase-shifting interferometry techniques (PSI) as well, single shot capture is required. Among others, modulation of polarization and phase grating interferometry is a possible technique to be considered. In this paper, a report about the use of this technique based on a double pulse laser system is presented. Single-pulse and twin-pulse operations are considered both in optical interferometers as well as in ESPI systems (mainly in subtraction mode). In ESPI a reduction of the degree of polarization appears due to scattering, so some measures have to be taken to prevent such deletereous effect. To show the feasibility of the proposed variants some experimental results are presented.

Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl ß-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

Aromatase and estrogen receptor alpha mRNA expression as prognostic biomarkers in patients with astrocytomas.

Estrogens are oncogenic hormones at a high level in breast, prostate, endometrial and lung cancer. Estrogens are synthesized by aromatase which has been used as a biomarker both in breast and lung cancer. Estrogen biological activities are executed by their classic receptors (ERα and ERß). ERα has been described as a cancer promoter and ERß, as a possible tumor suppressor. Both receptors are present at low levels in primary multiforme glioblastoma (GBM). The GBM frequency is 50 % higher in men than in women. The GBM patient survival period ranges from 7 to 18 months. The purpose of this pilot study was to evaluate aromatase and estrogen receptor expression, as well as 17ß-estradiol concentration in astrocytoma patients biopsies to obtain a prognosis biomarker for these patients. We analyzed 36 biopsies of astrocytoma patients with a different grade (I-IV) of malignity. Aromatase and estrogen receptor mRNA expression were analyzed by semiquantitative RT-PCR, and the E2 levels, by ELISA. E2 concentration was higher in GBM, compared to grade II or III astrocytomas. The number of cells immunoreactive to aromatase and estrogen receptors decreased as the grade of tumor malignity increased. Aromatase mRNA expression was present in all biopsies, regardless of malignity grade or patient age or gender. The highest expression of aromatase mRNA in GBM patients was associated to the worst survival prognostic (6.28 months). In contrast lowest expression of ERα mRNA in astrocytoma patients had a worst prognosis. In conclusion, aromatase and ERα expression could be used as prognosis biomarkers for astrocytoma patients.

Economic evaluation of Cardio inCode®, a clinical-genetic function for coronary heart disease risk assessment.

BACKGROUND: A clinical­genetic function (Cardio inCode®) was generated using genetic variants associated with coronary heart disease (CHD), but not with classical CHD risk factors, to achieve a more precise estimation of the CHD risk of individuals by incorporating genetics into risk equations [Framingham and REGICOR (Registre Gironí del Cor)]. OBJECTIVE: The objective of this study was to conduct an economic analysis of the CHD risk assessment with Cardio inCode®, which incorporates the patient's genetic risk into the functions of REGICOR and Framingham, compared with the standard method (using only the functions). METHODS: A Markov model was developed with seven states of health (low CHD risk, moderate CHD risk, high CHD risk, CHD event, recurrent CHD, chronic CHD, and death). The reclassification of CHD risk derived from genetic information and transition probabilities between states was obtained from a validation study conducted in cohorts of REGICOR (Spain) and Framingham (USA). It was assumed that patients classified as at moderate risk by the standard method were the best candidates to test the risk reclassification with Cardio inCode®. The utilities and costs (€; year 2011 values) of Markov states were obtained from the literature and Spanish sources. The analysis was performed from the perspective of the Spanish National Health System, for a life expectancy of 82 years in Spain. An annual discount rate of 3.5 % for costs and benefits was applied. RESULTS: For a Cardio inCode® price of €400, the cost per QALY gained compared with the standard method [incremental cost-effectiveness ratio (ICER)] would be €12,969 and €21,385 in REGICOR and Framingham cohorts, respectively. The threshold price of Cardio inCode® to reach the ICER threshold generally accepted in Spain (€30,000/QALY) would range between €668 and €836. The greatest benefit occurred in the subgroup of patients with moderate­high risk, with a high-risk reclassification of 22.8 % and 12 % of patients and an ICER of €1,652/QALY and €5,884/QALY in the REGICOR and Framingham cohorts, respectively. Sensitivity analyses confirmed the stability of the study results. CONCLUSIONS: Cardio inCode® is a cost-effective risk score option in CHD risk assessment compared with the standard method.

Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder.

Biotin is the prosthetic group of carboxylases that have important roles in the metabolism of glucose, fatty acids and amino acids. Biotinidase has a key role in the reutilization of the biotin, catalyzing the hydrolysis of biocytin (ε-N-biotinyl-l-lysine) and biocytin-containing peptides derived from carboxylase turnover, thus contributing substantially to the bioavailability of this vitamin. Deficient activity of biotinidase causes late-onset multiple carboxylase in humans, whose pathogenic mechanisms are poorly understood. Here we show that a knock-out biotinidase-deficient mouse from a C57BL/6 background that was fed a low biotin diet develops severe ATP deficit with activation of the energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK), inhibition of the signaling protein mTOR, driver of protein synthesis and growth, and affecting the expression of central-carbon metabolism genes. In addition, sensitivity to insulin is augmented. These changes are similar to those observed in nutritionally biotin-starved rats. These findings further our understanding of the pathogenesis of human biotinidase deficiency.

Dietary glycemic index/load and peripheral adipokines and inflammatory markers in elderly subjects at high cardiovascular risk.

BACKGROUND AND AIMS: Epidemiological and clinical studies suggest that low-glycemic index diets could protect against weight gain. However, the relationship between these diets and adipokines or inflammatory markers is unclear. In the present study we examine how the dietary glycemic index (GI) and dietary glycemic load (GL) are associated with several adipokines and related metabolic risk markers of obesity and diabetes in a cross-sectional and longitudinal manner. METHODS AND RESULTS: 511 elderly community-dwelling men and women at high cardiovascular risk were recruited for the PREDIMED trial. Dietary data were collected at baseline and after 1 year of follow-up. The GI and GL were calculated. Plasma leptin, adiponectin and other metabolic risk markers were measured at baseline and after 1 year. At baseline, subjects in the highest quartiles of GI showed significantly higher levels of TNF and IL-6 than those in the lowest quartiles. Dietary GI index was negatively related to plasma leptin and adiponectin levels. After 1 year of follow-up, subjects with a higher increase in dietary GI or GL showed a greater reduction in leptin and adiponectin plasma levels. There was no association between GI or GL and the other metabolic markers measured. CONCLUSION: Our results suggest that the consumption of high-GI or high-GL diets may modulate plasma concentrations of leptin and adiponectin, both adipostatic molecules implicated in energy balance and cardiometabolic risk.

"Estilos de vida en adolescentes de nivel medio superior de una comunidad semiurbana" / "Lifestyles in teen top-middle level of a semi-urban comunity"

Se propuso identificar los estilos de vida en adolescentes de una comunidad semiurbana, buscando respuesta a la pregunta: ¿Cuáles son los factores que se identifican en el instrumento Fantastic, en los estudiantes de la comunidad de Ixtlahuaca? Se trabajó con la variable de estilos de vida, ocupando el instrumento FANTASTIC. La muestra la conforman 1088 estudiantes, 603 hombres y 485 mujeres. La religión de mayor prevalencia es la católica con 844. Del instrumento se obtuvo una fiabilidad de .79, con 6 factores identificados: sentimientos negativos y estrés, satisfacción y pensamiento positivo, alimentación dañina, relajación y sueño, alcohol y tabaco, cafeína. Se concluye que se requiere manejo de hábitos saludables, prevención de adicciones y alimentación.

The proposal was to identify lifestyles among adolescents in a semi-urban community, seeking answers to the question: What are the factors that are identified in the Fantastic instrument in students Ixtlahuaca community? We worked with the lifestyle variable, holding the instrument FANTASTIC. The sample is formed by 1088 students, 603 men and 485 women. The most prevalent religion is Catholic with 844. The instrument yielded a reliability of .79, with 6 factors identified: negative feelings and stress, satisfaction and positive thinking, harmful food, relaxation and sleep, alcohol and snuff, caffeine. It is concluded that it is required management of healthy habits, addictions and alimentation prevention.

Thrombophilias and adverse pregnancy outcomes: results from the Danish National Birth Cohort.

BACKGROUND: Inherited thrombophilias have inconsistently been linked to adverse pregnancy outcomes. Differences in study design, size and population could explain this heterogeneity. OBJECTIVE: The aim of the present study was to evaluate if factor (F)V Leiden G1691A, prothrombin mutation G20210A (PTM) and methylenetetrahydrofolate reductase C677T (MTHFR) increased the risk of severe preeclampsia, fetal growth restriction, very preterm delivery, placental abruption and a composite of these outcomes also including stillbirth. PATIENTS AND METHODS: In a nested case-cohort study of pregnant women in Denmark, we genotyped 2032 cases and 1851 random controls. Each of the medical records of the cases was validated. We calculated both genomic and allelic models, and present both models. We also performed sensitivity analyses adjusting for parity, age, smoking, body mass index and socioeconomic status. RESULTS: In the allelic models, FV Leiden increased the risk of the composite outcome (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1-1.8), severe preeclampsia (OR 1.6, 95% CI 1.1-2.4), fetal growth restriction (OR 1.4, 95% CI 1.1-1.8) and placental abruption (OR = 1.7 (95% CI 1.2-2.4). In the sensitivity analyses, adjustment diminished these estimates slightly. PTM was not significantly associated with any of the outcomes, and MTHFR was only significantly associated with severe preeclampsia (OR 1.3, 95% CI 1.1-1.6). CONCLUSION: FV Leiden predisposes to adverse pregnancy outcomes in a setting of Scandinavian women.