Appendectomy during pregnancy: rates, safety, and outcomes over a five-year period. A hospital-based follow-up study.

INTRODUCTION: Appendicitis is the most common acute abdominal complication during pregnancy. If appendix perforation occurs there is an increasing risk of preterm delivery and other pregnancy complications. OBJECTIVE: To assess the outcome of pregnancy after appendectomy, the mode of surgery used, appendectomy rates, and complications. METHODS: A prospective cohort study of pregnant women with, or without, appendectomy at South Stockholm General Hospital, December 2015 to February 2021 in a setting where pregnant women are prioritized for surgery and laparoscopic surgery was standard of care in first half of pregnancy. Data on preoperative imaging, surgical method, intraoperative findings, microscopic findings, hospital stay, pregnancy, and 30-day complications were prospectively recorded in a local appendectomy register. A non-pregnant control group was gathered comprising women of fertile age in the same study interval. RESULTS: During the study period 50 pregnant women, of whom 44 gave birth, underwent appendectomy of 38 199 women giving birth. There were no differences between women with or without appendectomy in proportion of preterm delivery (4.5% vs. 5.6%), small-for-gestational age (2.3% vs. 6.2%), or Cesarean delivery (18.2% vs. 20.4%). The rate of appendix perforation was 19% in non-pregnant control group compared to 12% among pregnancy. There was no case of perforated appendix in the second half of pregnancy. However, women with gestational age > 20 weeks more frequently had an unaffected appendix compared to those operated ≤ 20 gestational weeks (4/11 vs. 2/39, p = .005). Laparoscopic surgery was used in 97% of non-pregnant control group, 92% of appendectomies ≤ 20 weeks gestation, and in 27% >20 weeks. As compared to first half, the appendectomy rate was three times lower during the second half of pregnancy. Pregnant women had priority for surgery < 6 h compared to < 24 h among non-pregnant women, this resulted in a shorter time-to-surgery among pregnant women (p < .001). CONCLUSION: Routine laparoscopic surgery and time priority for pregnant surgery is associated with a low risk of perforation, preterm birth and other complications. However, a low threshold for surgery may increase the risk of a negative exploration.

Combination of Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) with sonographic and demographic characteristics in preoperative prediction of recurrence or progression of endometrial cancer.

OBJECTIVE: To evaluate the ability of demographic and sonographic variables and the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) classification to predict preoperatively tumor recurrence or progression in women with endometrial cancer. METHODS: The study included 339 women with histologically confirmed endometrial cancer who underwent expert transvaginal ultrasound in a single center before surgery as part of the prospective International Endometrial Tumor Analysis 4 study or who were evaluated using the same protocol. The tumors were classified according to histotype, FIGO (International Federation of Gynecology and Obstetrics) grade and FIGO stage. In addition, molecular analysis was performed for classification into the four ProMisE subtypes: polymerase-ϵ exonuclease domain mutations (POLE EDM), mismatch repair proteins deficiency (MMR-D), protein 53 wild type (p53 wt) and protein 53 abnormal (p53 abn). Demographic and preoperative sonographic characteristics, tumor recurrence or progression and survival were compared between the ProMisE subgroups. Cox regression analysis was used to identify prognostic factors associated with recurrence or progression, using univariable models to study crude associations and multivariable models to study adjusted associations. Logistic regression and receiver-operating-characteristics (ROC)-curve analysis were used to assess the predictive ability of the preoperative prognostic factors regarding recurrence or progression of cancer within 3 years after surgery, and to compare their predictive ability to that of the European Society for Medical Oncology (ESMO) preoperative (based on depth of myometrial invasion, histotype and grade) and postoperative (based on histotype, grade, surgical stage and lymphovascular space invasion) risk classifications. In a separate subanalysis, cases were stratified according to ProMisE p53 abn status (present vs absent) and sonographic tumor size (anteroposterior (AP) diameter < 2 cm vs ≥ 2 cm). RESULTS: Median follow-up time from surgery was 58 months (interquartile range, 48-71 months; range, 0-102 months). Recurrence or progression of cancer occurred in 51/339 (15%) women, comprising 14% of those with MMR-D, 8% of those with POLE EDM, 9% of those with p53 wt and 45% of those with p53 abn ProMisE subtype. On multivariable analysis, age, waist circumference, ProMisE subtype and tumor extension and AP diameter on ultrasound were associated with tumor recurrence or progression. A multivariable model comprising ProMisE subtype, age, waist circumference and sonographic tumor extension and size (area under the ROC curve (AUC), 0.89 (95% CI, 0.85-0.93)) had comparable ability to predict tumor recurrence/progression to that of a multivariable model comprising histotype, grade, age, waist circumference and sonographic tumor extension and size (AUC, 0.88 (95% CI, 0.83-0.92)), and better predictive ability than both the preoperative (AUC, 0.74 (95% CI, 0.67-0.82); P < 0.01) and postoperative (AUC, 0.79 (95% CI, 0.72-0.86); P < 0.01) ESMO risk classifications. Women with a combination of non-p53 abn subtype and tumor size < 2 cm (164/339 (48%)) had a very low risk (1.8%) of tumor recurrence or progression. CONCLUSIONS: The combination of demographic characteristics, sonographic findings and ProMisE subtype had better preoperative predictive ability for tumor recurrence or progression than did the ESMO classification, supporting their use in the preoperative risk stratification of women with endometrial cancer. The combination of p53 status with ultrasound tumor size has the potential to identify preoperatively a large group of women with a very low risk of recurrence or progression. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Validation of ultrasound strategies to assess tumor extension and to predict high-risk endometrial cancer in women from the prospective IETA (International Endometrial Tumor Analysis)-4 cohort.

OBJECTIVES: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). METHODS: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. RESULTS: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver-operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. CONCLUSIONS: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound-based risk model for preoperative prediction of lymph-node metastases in women with endometrial cancer: model-development study.

OBJECTIVE: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. METHODS: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). RESULTS: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68-0.78), the calibration slope was 1.06 (95% CI, 0.79-1.34) and the calibration intercept was 0.06 (95% CI, -0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. CONCLUSIONS: Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Massive blood transfusion in relation to delivery: incidence, trends and risk factors: a population-based cohort study.

OBJECTIVE: To estimate incidence, trends over time, and risk factors for massive blood transfusions in obstetric patients. A secondary aim was to evaluate transfusion ratios in relation to massive transfusion. DESIGN: Population-based cohort. SETTING: Five hospitals, in the Stockholm County, Sweden, from 1990 to 2011. POPULATION: All women that gave birth in Stockholm county, Sweden, and who received blood transfusions postpartum between 1990 and 2011. METHODS: Data on pregnancies and deliveries from the Swedish National Medical Birth Registry was cross-linked to the Stockholm transfusion database. Massive blood transfusion was defined as the transfusion of ≥10 units of red blood cells from partus through the next day. MAIN OUTCOME MEASURES: Main primary outcome was massive blood transfusion postpartum. RESULTS: Our cohort comprised 517 874 deliveries. Massive blood transfusion occurred in 277 women, for an incidence of 5.3 per 10 000 deliveries, and increased by 30% (P < 0.001) between the first and the second half of the study period. Major risk factors apparent before delivery were abnormal placentation (odds ratio [OR] 41; 95% CI 29.3-58.1), pre-eclampsia/placental abruption (OR 4; 95% CI 2.8-5.6), and previous caesarean delivery (OR 4; 95% CI 3.1-6.0). Risk factors at time of delivery were uterine rupture, atonic uterus, and caesarean delivery (OR 38, 17, and 3, respectively). CONCLUSION: We found an increasing trend in the postpartum rate of massive transfusion. Women with abnormal placentation were found to have the highest increased risk. Improved antenatal awareness of these women at risk might improve management and reduce the rate of massive transfusion. TWEETABLE ABSTRACT: Risk of massive blood transfusion in obstetric patients increases with placental complications and prior caesarean section.

The International Network of Obstetric Survey Systems study of uterine rupture: a descriptive multi-country population-based study.

OBJECTIVE: International comparison of complete uterine rupture. DESIGN: Descriptive multi-country population-based study. SETTING: International. POPULATION: International Network of Obstetric Survey Systems (INOSS). METHODS: We merged individual data, collected prospectively in nine population-based studies, of women with complete uterine rupture, defined as complete disruption of the uterine muscle and the uterine serosa, regardless of symptoms and rupture of fetal membranes. MAIN OUTCOME MEASURES: Prevalence of complete uterine rupture, regional variation and correlation with rates of caesarean section (CS) and trial of labour after CS (TOLAC). Severe maternal and perinatal morbidity and mortality. RESULTS: We identified 864 complete uterine ruptures in 2 625 017 deliveries. Overall prevalence was 3.3 (95% CI 3.1-3.5) per 10 000 deliveries, 22 (95% CI 21-24) in women with and 0.6 (95% CI 0.5-0.7) in women without previous CS. Prevalence in women with previous CS was negatively correlated with previous CS rate (ρ = -0.917) and positively correlated with TOLAC rate of the background population (ρ = 0.600). Uterine rupture resulted in peripartum hysterectomy in 87 of 864 women (10%, 95% CI 8-12%) and in a perinatal death in 116 of 874 infants (13.3%, 95% CI 11.2-15.7) whose mother had uterine rupture. Overall rate of neonatal asphyxia was 28% in neonates who survived. CONCLUSIONS: Higher prevalence of complete uterine ruptures per TOLAC was observed in countries with low previous CS and high TOLAC rates. Rates of hysterectomy and perinatal death are about 10% following complete uterine rupture, but in women undergoing TOLAC the rates are extremely low (only 2.2 and 3.2 per 10 000 TOLACs, respectively.) TWEETABLE ABSTRACT: Prevalence of complete uterine rupture is higher in countries with low previous CS and high TOLAC rates.

Postpartum blood transfusion and hemorrhage as independent risk factors for venous thromboembolism.

INTRODUCTION: Profuse postpartum hemorrhage (PPH) and red blood cell (RBC) transfusion have been suggested to be associated with venous thromboembolic events (VTE). However, it is not fully clear if they are independent major risk factors. METHODS: Women who gave birth in the Stockholm area between 1999 and 2002 were those studied, i.e., before the implementation of guidelines for thromboprophylaxis in pregnancy. In this population-based cohort study the Swedish Medical Birth Registry was linked to the National Discharge Registry and to the transfusion database. Cases with VTE were identified as well as the patient's transfusion history. The main outcome was an assessment of RBC transfusion and PPH as independent risk factors for postpartum thrombosis, analyzed in logistic regression models. RESULTS: Out of the 82,376 deliveries, 56 cases of postpartum VTE were identified (0.7‰). Compared to the control group, the risk of VTE increased with the number of RBC transfusions: 1 to 3 units (OR = 3.3, 95% CI 1.2-8.9) and >3 units (OR = 5.2, 95%CI 1.7-16.1), but PPH was not found to be a major risk factor (OR = 1.4, 95% CI 0.5-3.5). Surprisingly, the small group treated with plasma in addition to RBC transfusion were not at a significantly increased risk (OR = 1.8, 95% CI 0.2-14.0). Preeclampsia and placental abruption were major risk factors. CONCLUSION: We found RBC transfusion, but not PPH alone, to be an independent risk factor for postpartum VTE and propose that it should be included in the thromboprophylaxis algorithm for implementation during pregnancy.

Ultrasound characteristics of endometrial cancer as defined by International Endometrial Tumor Analysis (IETA) consensus nomenclature: prospective multicenter study.

OBJECTIVE: To describe the sonographic features of endometrial cancer in relation to tumor stage, grade and histological type, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective multicenter study of 1714 women with biopsy-confirmed endometrial cancer undergoing standardized transvaginal grayscale and Doppler ultrasound examination according to the IETA study protocol, by experienced ultrasound examiners using high-end ultrasound equipment. Clinical and sonographic data were entered into a web-based database. We assessed how strongly sonographic characteristics, according to IETA, were associated with outcome at hysterectomy, i.e. tumor stage, grade and histological type, using univariable logistic regression and the c-statistic. RESULTS: In total, 1538 women were included in the final analysis. Median age was 65 (range, 27-98) years, median body mass index was 28.4 (range 16-67) kg/m2 , 1377 (89.5%) women were postmenopausal and 1296 (84.3%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage of tumor. High-risk tumors, compared with low-risk tumors, were less likely to have regular endometrial-myometrial junction (difference of -23%; 95% CI, -27 to -18%), were larger (mean endometrial thickness; difference of +9%; 95% CI, +8 to +11%), and were more likely to have non-uniform echogenicity (difference of +7%; 95% CI, +1 to +13%), a multiple, multifocal vessel pattern (difference of +21%; 95% CI, +16 to +26%) and a moderate or high color score (difference of +22%; 95% CI, +18 to +27%). CONCLUSION: Grayscale and color Doppler sonographic features are associated with grade and stage of tumor, and differ between high- and low-risk endometrial cancer. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Low maternal circulating levels of vitamin D as potential determinant in the development of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM), defined as any glucose intolerance with the onset or first recognition during pregnancy, is characterized by rising incidence, fostered by the worldwide increase of pathological nutritional status from young age. Clinical research has intended to identify potential risk factors, suggested improvements in screening strategies, and recommended the combination between promotion of an appropriate lifestyle before and during pregnancy and selected therapeutic approaches. Preventing pathological hyperglycemia could have several benefits, ranging from clinical side (reduction in the risk of adverse perinatal and long-term sequelae) to financial side (cost reduction to healthcare systems). Among risk factors recognized, deficiency in 25-hydroxyvitamin D [25(OH)D], already acknowledged as involved in calcium homeostasis, pathogenesis of cardiovascular, oncological, infective and immunity diseases, could predispose to the development of both type 1 and 2 diabetes, modifying the activity of pancreatic ß-cells vitamin D (VD) receptor. In pregnant women, lower 25(OH)D concentrations have been suggested to present an inverse association with maternal glycaemia, insulin resistance, and increased risk of GDM. In spite of growing body of evidence, there is not full agreement on the therapeutic association between GDM based on VD deficiency and 25(OH)D supplementation. In the attempt to bring up-to-date the role of low VD levels on subsequent development of GDM, this narrative review, based on medium-high-quality randomized clinical trials, systematic reviews, and meta-analysis published in last decade, has a twofold purpose: firstly, to elucidate the relationship between maternal VD status and GDM; and secondly, to illuminate the impact of VD supplementation on GDM onset.

Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort.

OBJECTIVE: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. METHODS: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. RESULTS: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. CONCLUSION: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.

Abnormally invasive placenta-prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries.

OBJECTIVE: The objective was to investigate prevalence, estimate risk factors, and antenatal suspicion of abnormally invasive placenta (AIP) associated with laparotomy in women in the Nordic countries. DESIGN: Population-based cohort study. SETTING AND POPULATION: A 3-year Nordic collaboration among obstetricians to identify and report on uterine rupture, peripartum hysterectomy, excessive blood loss, and AIP from 2009 to 2012 The Nordic Obstetric Surveillance Study (NOSS). METHODS: In the NOSS study, clinicians reported AIP cases from maternity wards and the data were validated against National health registries. MAIN OUTCOME MEASURES: Prevalence, risk factors, antenatal suspicion, birth complications, and risk estimations using aggregated national data. RESULTS: A total of 205 cases of AIP in association with laparotomy were identified, representing 3.4 per 10 000 deliveries. The single most important risk factor, which was reported in 49% of all cases of AIP, was placenta praevia. The risk of AIP increased seven-fold after one prior caesarean section (CS) to 56-fold after three or more CS. Prior postpartum haemorrhage was associated with six-fold increased risk of AIP (95% confidence interval 3.7-10.9). Approximately 70% of all cases were not diagnosed antepartum. Of these, 39% had prior CS and 33% had placenta praevia. CONCLUSION: Our findings indicate that a lower CS rate in the population may be the most effective way to lower the incidence of AIP. Focused ultrasound assessment of women at high risk will likely strengthen antenatal suspicion. Prior PPH is a novel risk factor associated with an increased prevalence of AIP. TWEETABLE ABSTRACT: An ultrasound assessment in women with placenta praevia or prior CS may double the awareness for AIP.

On the evolutionary advantage of coagulation factor V Leiden (FVL).

Carriership of coagulation factor V Leiden (FVL) is by far the most common thrombophilia in Western populations. FVL is caused by a single point mutation in the gene coding for coagulation factor V (FV) causing a lifelong procoagulatory state with an increased risk of venous thromboembolism (VTE) which might be fatal. It is believed that the mutation occurred in one person 21,000 years ago and today 3% to 15% of the Western populations are carriers. A potentially dangerous mutation such as FVL ought to be rare and should have been reduced, if not eradicated, by selection during the course of human evolution. Thus, FVL must confer the carriers with an evolutionary advantage in order to be so prevalent. Lower risk of profuse bleeding and increased fecundity might give carriers an advantage. In this paper we give an updated short background and discuss possible evolutionary advantages and disadvantages.

Transvaginal ultrasound assessment of myometrial and cervical stromal invasion in women with endometrial cancer: interobserver reproducibility among ultrasound experts and gynecologists.

OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynecologists in the prediction by transvaginal ultrasound of deep myometrial and cervical stromal invasion in women with endometrial cancer. METHODS: Sonographic videoclips of the uterine corpus and cervix of 53 women with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated into a digitalized survey. Nine ultrasound experts and nine gynecologists evaluated presence or absence of deep myometrial and cervical stromal invasion. Histopathology from hysterectomy specimens was used as the gold standard. RESULTS: Compared with gynecologists, ultrasound experts showed higher sensitivity, specificity and agreement with histopathology in the assessment of cervical stromal invasion (42% (95% CI, 31-53%) vs 57% (95% CI, 45-68%), P < 0.01; 83% (95% CI, 78-86%) vs 87% (95% CI, 83-90%), P = 0.02; and kappa, 0.45 (95% CI, 0.40-0.49) vs 0.58 (95% CI, 0.53-0.62), P < 0.001, respectively) but not of deep myometrial invasion (73% (95% CI, 66-79%) vs 73% (95% CI, 66-79%), P = 1.0; 70% (95% CI, 65-75%) vs 69% (95% CI, 63-74%), P = 0.68; and kappa, 0.48 (95% CI, 0.44-0.53) vs 0.52 (95% CI, 0.48-0.57), P = 0.11, respectively). Though interobserver reproducibility (in the context of test proportions 'good' and 'very good', according to kappa) regarding deep myometrial invasion did not differ between the groups (experts, 34% vs gynecologists, 22%, P = 0.13), ultrasound experts assessed cervical stromal invasion with significantly greater interobserver reproducibility than did gynecologists (53% vs 14%, P < 0.001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial and cervical stromal invasion in endometrial cancer is best performed by ultrasound experts, as, compared with gynecologists, they showed a greater degree of agreement with histopathology and greater interobserver reproducibility in the assessment of cervical stromal invasion.

Selective serotonin reuptake inhibitor use during pregnancy increases the risk of postpartum hemorrhage and anemia: a hospital-based cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are known to increase the risk of gastrointestinal bleeding. OBJECTIVE: Study the risk of bleeding-related complications in relation to SSRI in pregnancy. PATIENTS/METHODS: This was a hospital-based cohort study. All women who gave birth at Karolinska University Hospital in Stockholm over a 5-year period (2007 to 2011) were included in the study. Those women who the electronic maternal health record indicated were using SSRI (n = 500) were considered exposed, and all other women formed a control population (n = 39,594). The main outcome measures were blood loss, postpartum hemorrhage (PPH), PP anemia and length of hospitalization. RESULTS: The absolute risk of PPH and PP anemia for the 1.2% exposed to SSRI were 18.0% and 12.8%, respectively. Women with a vaginal non-surgical delivery who reported use of SSRI during pregnancy had approximately a 2-fold increased risk of both PPH (OR, 2.6; 95% CI, 2.0-3.5) and PP anemia (OR, 2.1; 95% CI, 1.5-2.9), as compared with controls. Blood loss and length of hospitalization were significantly higher among women using SSRI than non-users (arithmetic mean 484 mL vs. 398 mL, 3.8 days vs. 2.4 days, respectively). CONCLUSION: The use of SSRI during pregnancy increases blood loss and doubles the risk of PPH and PP anemia in a setting where SSRI had not been considered a risk factor for increased blood loss. Because PPH is a leading cause of maternal mortality and morbidity, the awareness of bleeding-related complications is important, both in relation to pregnancy and to surgery in general.

Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort.

BACKGROUND: Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels. METHODS: We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data. RESULTS: There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%. CONCLUSION: The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.

Routine ultrasound examination at 41 weeks of gestation and risk of post-term severe adverse fetal outcome: a retrospective evaluation of two units, within the same hospital, with different guidelines.

OBJECTIVE: To study whether a routine with a routine ultrasound examination (routine scan) at 41 gestational weeks as compared with ultrasound on clinical indication (indicated scan), lowered the risk of severe adverse fetal outcome in post-term period. DESIGN: A retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. POPULATION: Eight years of deliveries, 2002-2009. METHOD: One of the two delivery units at Karolinska University Hospital used a routine scan at 41 week of gestation and the other unit used an indicated scan. Severe adverse fetal outcome were defined: severe asphyxia, death or cerebral damage. The study was analysed using logistic regression with adjustment for potential confounders. MAIN OUTCOME MEASURES: Differences in post-term severe adverse fetal outcome. RESULTS: No increased risk of post-term severe adverse fetal outcome was seen at the unit using a routine scan; conversely, a 48% significantly increased risk was seen at the unit using an indicated scan (OR 0.89, 95% confidence interval, CI, 0.5-1.5 and OR 1.48, 95% CI 1.06-2.1, respectively). Comparing post-term periods, there was no significantly increased risk at the unit using indicated scans (OR 1.6, 95% CI 0.9-3.0). There was a 60% increased prevalence of small-for-gestational age (SGA) newborns in the post-term period at the unit using indicated scans (OR 1.6, 95% CI 1.1-2.4), but no differences in operative delivery. CONCLUSION: A policy to use routine scans at 41 weeks of gestation seems to normalise an increased post-term risk of severe adverse fetal outcome, possible due to increased awareness of SGA and/or oligohydramniosis.

Umbilical artery Doppler in relation to placental pathology and FV Leiden in pregnant women and their offspring.

OBJECTIVE: Abnormal umbilical artery blood flow has been implicated in pregnancy complications and fetal demise. Its relation to histopathological changes in the placenta and to maternal or fetal thrombophilia is less well understood. The aim of this study was to evaluate the relation between umbilical artery Doppler findings, placental histopathology, and maternal and fetal coagulation factor V Leiden (FVL) status. METHODS: Two previous studies on FVL in pregnancy made the placentas of 25 women with maternal FVL carriership and 43 randomly selected non-carriers available for a histopathological examination. Umbilical artery Doppler velocimetry was performed on 54 women in late pregnancy. RESULTS: Abnormal umbilical artery Doppler velocimetry was associated with an approximately sevenfold increased risk of fetoplacental thrombotic vasculopathy (odds ratio [OR]: 7.5, 95% confidence intervals [CI]: 1.3-44.3), ischemic lesions (OR: 7.5, 95% CI: 1.2-46.1) and fetal carriership of FVL (OR: 8.2, 95% CI: 1.5-43.5), but not maternal FVL. Fetal FVL carriership was also associated with a sevenfold increased risk of ischemic lesions (OR: 6.7, 95% CI: 1.3-35). CONCLUSIONS: Our results indicate that the fetal - not the maternal - FVL carriership matters regarding the umbilical artery blood flow and placental pathology, which might explain some of the heterogeneity of studies.