Preeclampsia and small for gestational age (SGA) births share pathophysiologic pathways involving the cardiovascular system, inflammation, and placentation. To evaluate their pathophysiological differences and similarities, we compared alterations in mid-pregnancy circulating protein levels in women with subsequent preeclampsia and/or SGA birth. We used the Olink cardiovascular panel II to measure 92 mid-pregnancy plasma proteins in healthy pregnant women with subsequent uncomplicated pregnancies (controls; n = 480), term (≥ 37 weeks) preeclampsia (n = 233), preterm (< 37 weeks) preeclampsia (n = 40), SGA birth (n = 106), or combined preeclampsia and SGA birth (n = 31). False discovery rate-adjusted Kruskal-Wallis and Dunn's post-hoc tests identified protein level differences between controls and each adverse outcome group. Compared with controls, mid-pregnancy protein alterations were most common in women with subsequent term preeclampsia, particularly involving the cardiovascular proteins angiotensin-converting enzyme 2 and B-type natriuretic peptide. Across all outcomes, matrix metalloproteinase-12 and placental growth factor were lower compared to controls, particularly in those with combined disorder. In summary, cardiovascular and inflammatory protein alternations were most common in women with subsequent preeclampsia. Shared dysregulation of matrix metalloproteinase-12 and placental growth factor, both known regulators of placentation and the vascular system, suggests their involvement in both preeclampsia and SGA births, albeit the pathways may differ.

Abstract Introduction Cerebral complications of preeclampsia pose a significant threat to pregnant women worldwide. The underlying pathophysiology is unclear, but impaired cerebral autoregulation may contribute to adverse maternal outcomes. Long‐term consequences of preeclampsia include cerebrovascular disease, and impairment of cerebral autoregulation could contribute to these outcomes. The aim of this study was to assess cerebral autoregulation in women with preeclampsia and normotensive pregnancies during pregnancy and 1‐year postpartum to quantify impairment during disease and evaluate its persistence or recovery over time. Methods This multicenter, prospective, observational cohort study included women from the UPMOST or GoPROVE studies. Women with preeclampsia were examined at diagnosis. Participants underwent transcranial Doppler examinations at inclusion and 1‐year postpartum. Women were categorized as having normotensive pregnancies or preeclampsia with or without maternal complications. Cerebral autoregulation was assessed by the autoregulation index (ARI). Differences in mean ARI between and within groups were analyzed using regression models for repeated measures. Results A total of 124 women were included in the analysis. During pregnancy, mean ARI was higher in normotensive pregnancies compared with preeclampsia (6.90 [SD, 0.77] vs. 6.12 [SD, 1.45]; mean difference 0.78 [95% CI, 0.37–1.19]), but no difference was observed 1‐year postpartum (6.11 [SD, 1.14] vs. 6.15 [SD, 1.10]; mean difference −0.03 [95% CI, −0.47 to 0.54]). Mean ARI did not differ between preeclampsia with or without severe features, either during pregnancy (6.24 [SD, 1.49] vs. 5.98 [SD, 1.40]; mean difference 0.27 [95% CI, −0.43 to 0.96]), or 1‐year postpartum (6.13 [SD, 1.23] vs. 6.18 [SD, 0.94]; mean difference −0.05 [95% CI, −0.64 to 0.54]). Conclusion Preeclampsia impairs the autoregulatory advantage offered by pregnancy. This renders the maternal brain more vulnerable to neurovascular injury. This impairment appears to resolve by 1‐year postpartum, suggesting that persistently depressed cerebral autoregulation is unlikely to account for long‐term cerebrovascular consequences of preeclampsia.

Fetal macrosomia is associated with adverse short- and long-term outcomes for the mother and the child. Present models to predict fetal macrosomia cannot be used in all settings, and their precision could be improved. We assessed if waist circumference could replace or outperform weight for early pregnancy prediction of macrosomia. We included 5827 women in this population-based cohort study and assessed the influence of early pregnancy waist circumference and weight on the prediction of macrosomia with logistic regression analysis. We generated receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC) to compare models, including waist circumference, weight, or neither of them. The odds of macrosomia increased with a larger waist circumference (adjusted odds ratio (AOR) 1.03 (95% Confidence Interval (CI) 1.02, 1.04)). For women with waist circumference between 80 and 88 cm the AOR was 1.41 (95% CI 1.09, 1.82) and women with waist circumference ≥ 88 cm had AOR 1.98 (95% CI 1.56, 2.53) for macrosomia. There was no difference in predictive capacity between waist circumference and weight in the macrosomia prediction model. The AUC was 0.75 (95% CI 0.72, 0.77) for waist circumference and 0.74 (95% CI 0.72, 0.77) for weight. The model that excluded waist circumference and weight had an AUC of 0.72 (95% CI 0.70, 0.75). The predictive capacity of the model including waist circumference was, however, higher than that of the model without waist circumference or weight ( p < 0.001). In conclusion, waist circumference can replace weight in an early pregnancy macrosomia prediction model.

ImportanceGestational hypertension, preeclampsia, and eclampsia are established risk factors for stroke and dementia later in life. Whether these pregnancy complications are associated with an increased risk of new-onset neurological disorders within months to years after giving birth is not known.ObjectiveTo explore whether gestational hypertension, preeclampsia, and eclampsia are associated with new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth.Design, Setting, and ParticipantsIn this register-based cohort study, exposures were identified in the Swedish Medical Birth Register from 2005 to 2018. Follow-up was conducted using the National Patient Register, containing diagnoses from specialized inpatient and outpatient care. Follow-up started 42 days after delivery and continued until the first event, death, emigration, or the end of the follow-up period (2019). The risk was calculated with Cox regression analysis and expressed as adjusted hazard ratio (aHR) with a 95% CI. Through the Swedish Medical Birth Register, 659 188 primiparous women with singleton pregnancies between 2005 and 2018 were identified. Women with a diagnosis of chronic hypertension (n = 4271) or a prepregnancy neurological disorder (n = 6532) were excluded. The final study population included 648 385 women. Data analyses were conducted in 2023.ExposuresGestational hypertension, preeclampsia, and eclampsia.Main outcomeThe primary outcome was a composite neurological outcome of migraine, headache, epilepsy, sleep disorder, or mental fatigue.ResultsThe study included 648 385 women with a mean age of 28.5 (SD, 5.0) years at the time of their first pregnancy. Women with gestational hypertension (n = 11 133), preeclampsia (n = 26 797), and eclampsia (n = 625) all had an association with increased risk for a new-onset neurological disorder compared with women with normotensive pregnancies. The aHR for gestational hypertension was 1.27 (95% CI, 1.12-1.45), 1.32 (95% CI, 1.22-1.42) for preeclampsia, and 1.70 (95% CI, 1.16-2.50) for eclampsia. When exploring individual outcomes, women with eclampsia were associated with more than a 5 times increased risk of epilepsy (aHR, 5.31; 95% CI, 2.85-9.89).Conclusion and RelevanceIn this study, gestational hypertension, preeclampsia, and eclampsia were associated with an increased risk of new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth. Guidelines recommend follow-up after delivery for women with gestational hypertension and preeclampsia for their increased risk of cardiovascular disease. At these visits, caregivers should also pay attention to persisting or new-onset of neurological symptoms, since this group of women appears to be vulnerable to developing or experiencing neurological disorders.

Improvement of prenatal identification of large-for-gestational-age (LGA) infants could lower the risk for adverse outcomes. Therefore, we sought to evaluate the association of a combination of maternal waist circumference (WC) and abdominal fat depths with infant birth size. A cohort study including 1240 women was performed between 2015 and 2018 at Uppsala University Hospital, Sweden. Maternal WC was measured at the first antenatal visit, and visceral (VF) and subcutaneous (SCF) fat depths by ultrasound at the second-trimester anomaly scan. Waist circumference, VF, and SCF were categorized as low or high (cut-offs WC ≥ 88 cm, VF ≥ 54 mm, SCF ≥ 21 mm). Outcomes were birth weight standard deviation score (BWSDS) and LGA (BWSDS > 90th and > 97th percentile). Secondary outcome was small-for-gestational-age (SGA, BWSDS < 10th and < 3rd percentile). Univariate analysis of variance and logistic regression analyses were performed adjusted for maternal weight, height, parity, smoking, country of birth, pregestational diabetes, and chronic hypertension. For both high and low WC, high VF was positively associated with BWSDS and LGA. There was no association with SGA. The results did not demonstrate any value of the combination of WC and fat depth measures in predicting infant birth size but suggested VF as a marker for large infants.

Prediction of women at high risk of preeclampsia is important for prevention and increased surveillance of the disease. Current prediction models need improvement, particularly with regard to late-onset preeclampsia. Preeclampsia shares pathophysiological entities with cardiovascular disease; thus, cardiovascular biomarkers may contribute to improving prediction models. In this nested case-control study, we explored the predictive importance of mid-pregnancy cardiovascular biomarkers for subsequent preeclampsia. We included healthy women with singleton pregnancies who had donated blood in mid-pregnancy (~ 18 weeks’ gestation). Cases were women with subsequent preeclampsia ( n = 296, 10% of whom had early-onset preeclampsia [< 34 weeks]). Controls were women who had healthy pregnancies ( n = 333). We collected data on maternal, pregnancy, and infant characteristics from medical records. We used the Olink cardiovascular II panel immunoassay to measure 92 biomarkers in the mid-pregnancy plasma samples. The Boruta algorithm was used to determine the predictive importance of the investigated biomarkers and first-trimester pregnancy characteristics for the development of preeclampsia. The following biomarkers had confirmed associations with early-onset preeclampsia (in descending order of importance): placental growth factor (PlGF), matrix metalloproteinase (MMP-12), lectin-like oxidized LDL receptor 1, carcinoembryonic antigen-related cell adhesion molecule 8, serine protease 27, pro-interleukin-16, and poly (ADP-ribose) polymerase 1. The biomarkers that were associated with late-onset preeclampsia were BNP, MMP-12, alpha-L-iduronidase (IDUA), PlGF, low-affinity immunoglobulin gamma Fc region receptor II-b, and T cell surface glycoprotein. Our results suggest that MMP-12 is a promising novel preeclampsia biomarker. Moreover, BNP and IDUA may be of value in enhancing prediction of late-onset preeclampsia.

INTRODUCTION:It is well known that both women with polycystic ovary syndrome (PCOS) and women with gestational diabetes mellitus (GDM) have increased risks of adverse pregnancy outcomes, but little is known whether the combination of these two conditions exacerbates the risks. We explored risk estimates for adverse pregnancy outcomes in women with either PCOS or GDM and the combination of both PCOS and GDM. MATERIAL AND METHODS:Nationwide register-based historical cohort study in Sweden including women who gave birth to singleton infants during 1997-2015 (N = 281 806). The risks of adverse pregnancy outcomes were estimated for women exposed for PCOS-only (n = 40 272), GDM-only (n = 2236), both PCOS and GDM (n = 1036) using multivariable logistic regression analyses. Risks were expressed as odds ratios with 95% confidence intervals (CIs) and adjusted for maternal characteristics, including maternal BMI. Women with neither PCOS nor GDM served as control group. Maternal outcomes were gestational hypertension, preeclampsia, postpartum hemorrhage, and obstetric anal sphincter injury. Neonatal outcomes were preterm birth, stillbirth, shoulder dystocia, born small or large for gestational age, macrosomia, low Apgar score, infant birth trauma, cerebral impact of the infant, neonatal hypoglycemia, meconium aspiration syndrome and respiratory distress. RESULTS:Based on non-significant PCOS by GDM interaction analyses, we found no evidence that having PCOS adds any extra risk beyond that of having GDM for maternal and neonatal outcomes. For example, the adjusted odds ratio for preeclampsia in women with PCOS-only were 1.18 (95% CI 1.11-1.26), for GDM-only 1.77 (95% CI 1.45-2.15), and for women with PCOS and GDM 1.86 (95% CI 1.46-2.36). Corresponding adjusted odds ratio for preterm birth in women with PCOS-only were 1.34 (95% CI 1.28-1.41), GDM-only 1.64 (95% CI 1.39-1.93), and for women with PCOS and GDM 2.08 (95% CI 1.67-2.58). Women with PCOS had an increased risk of stillbirth compared with the control group (aOR 1.52, 95% CI 1.29-1.80), whereas no increased risk was noted in women with GDM (aOR 0.58, 95% CI 0.24-1.39). CONCLUSIONS:The combination of PCOS and GDM adds no extra risk beyond that of having GDM alone, for a number of maternal and neonatal outcomes. Nevertheless, PCOS is still an unrecognized risk factor in pregnancy, exemplified by the increased risk of stillbirth.

BACKGROUND Preeclampsia in a first pregnancy is a strong risk factor for preeclampsia in a second pregnancy. Whether chronic hypertension developed after a first pregnancy (interpregnancy hypertension) affects the recurrence risk of preeclampsia is unknown. METHODS This is a population-based cohort study of 391,645 women with their first and second singleton births between 2006 and 2017. Exposure groups were women with preeclampsia in their first pregnancy, interpregnancy hypertension, or both risk factors. Women with neither risk factor were used as a reference group. We calculated the adjusted relative risk (aRR) with 95% confidence intervals (CIs) for overall preeclampsia in the second pregnancy as well as preterm (<37 gestational weeks) and term (>= 37 gestational weeks) subgroups of the disease. RESULTS Women with preeclampsia in their first pregnancy who did or did not develop interpregnancy hypertension had rates of preeclampsia in their second pregnancy of 21.5% and 13.6%, respectively. In the same population, the corresponding rates of preterm preeclampsia were 5.5% and 2.6%, respectively. After adjusting for maternal factors, women with preeclampsia in their first pregnancy who developed interpregnancy hypertension and those who did not have almost the same risk of overall preeclampsia in their second pregnancy (aRRs with 95% CIs: 14.51; 11.77-17.89 and 12.83; 12.09-13.62, respectively). However, preeclampsia in the first pregnancy and interpregnancy hypertension had a synergistic interaction on the outcome of preterm preeclampsia (aRR with 95% CI 26.66; 17.44-40.80). CONCLUSIONS Women with previous preeclampsia who developed interpregnancy hypertension had a very high rate of preterm preeclampsia in a second pregnancy, and the two risk factors had a synergistic interaction.

Background: More than two in five Swedish women are overweight or obese when becoming pregnant. Maternal overweight or obesity and excessive pregnancy weight gain are associated with several adverse pregnancy outcomes. The underlying mechanisms that link maternal adiposity, diet, exercise, pregnancy weight gain with pregnancy outcome are incompletely understood. Methods: We describe the design for a cross-sectional study of pregnant women at Uppsala University Hospital, Sweden. All participants delivered by elective cesarean section before the onset of labor. At inclusion, participants answered two questionnaires concerning their dietary and exercise habits. Fasting maternal blood samples (buffy coat, plasma, serum) were collected. During the cesarean section, biopsies of maternal subcutaneous and visceral adipose tissues were obtained. Placental tissue was collected after delivery. All biological samples were processed as soon as possible, frozen on dry ice, and stored at −70 °C. Pregnancy outcomes and supplementary maternal characteristics were collected from medical records. Results: In total, 143 women were included in the study. Of these women, 33.6% were primiparous, 46.2% had a pre-pregnancy body mass index (BMI) over 25 kg/m2, and 11.2% of the offspring were born large for gestational age (LGA). Complete collection, that is both questionnaires and all types of biological samples, was obtained from 81.1% of the participants. Conclusions: This study is expected to provide a resource for exploration of the associations between maternal weight, diet, exercise, pregnancy weight gain, and pregnancy outcome. Results from this study will be published in peer-reviewed, international scientific journals. This study was approved by the Regional Ethics Review Board in Uppsala (approval no 2014/353) and with an amendment by the Swedish Ethical Review Authority (approval no 2020-05844).

OBJECTIVE:To explore whether the association between polycystic ovary syndrome (PCOS) and pre-eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of pre-eclampsia. DESIGN:Nationwide register-based cohort study. SETTING:Sweden. POPULATION:Nulliparous women with PCOS (n = 22 947) and non-PCOS controls (n = 115 272) giving singleton birth at ≥22 gestational weeks during 1997-2015. Treated clinical hyperandrogenism was defined as filled prescriptions of anti-androgenic drugs during 2005-2017 (n = 2301 among PCOS women). METHODS:The risk of pre-eclampsia was estimated with conditional logistic regression, expressed as adjusted odds ratio (OR) with 95% confidence interval (CI). Adjustments were performed individually for confounders and predictors. MAIN OUTCOME MEASURES:Overall pre-eclampsia. Early/late (delivery <34/≥34 weeks) pre-eclampsia. Pre-eclampsia with or without a small-for-gestational-age (SGA) infant. RESULTS:Compared with controls, women with PCOS had a 29% increased risk of pre-eclampsia (predictor adjusted OR 1.29, 95% CI 1.20-1.39), with similar risk estimates for PCOS women with and without treated clinical hyperandrogenism. The association between PCOS and early pre-eclampsia seemed stronger than its association with late pre-eclampsia (predictor adjusted OR 1.64 (95% CI 1.33-2.02) and 1.26 (95% CI 1.17-1.37). Additionally, the association seemed slightly stronger between PCOS and pre-eclampsia in women with an SGA infant than without. CONCLUSIONS:Women with PCOS face an increased risk for pre-eclampsia, especially early pre-eclampsia and pre-eclampsia with an SGA infant. We were unable to determine on the basis of available data, whether hyperandrogenism is associated with pre-eclampsia.

Preeclampsia and cardiovascular disease (CVD) share multiple features and risk factors. Circulating angiotensin-converting enzyme 2 (ACE2) is increased in CVD and mediates SARS-CoV-2 entry into host cells, causing COVID-19 infection. The role of ACE2 in preeclampsia pathophysiology is unknown. We hypothesized that circulating ACE2 is increased in mid-pregnancy in women later developing preeclampsia. We included 296 women later developing preeclampsia (cases) and 333 women with a continuous healthy pregnancy (controls). Circulating ACE2 was measured with an immunoassay based on proximity extension assay technology, with levels being expressed as relative quantification on a log2 scale. Median (interquartile range) ACE2 levels were higher in cases than in controls; 3.84 (3.50–4.24) vs. 3.72 (3.45–4.04), p = 0.002. Adjusted logistic regression models showed a 60% increased risk for later development of preeclampsia with one unit elevation of ACE2 (adjusted odds ratio (aOR) 1.60, 95% confidence intervals (CI) 1.17–2.18). Preterm preeclampsia (diagnosis before 37 gestational weeks, n = 97) seemed to have a stronger ACE2 association than term preeclampsia, n = 199 (aORs, 95% Cis 2.14, 1.15–3.96 and 1.52, 1.04–2.23, respectively). Circulating ACE2 is increased at mid-pregnancy in women later developing preeclampsia, particularly preterm preeclampsia. Thus, our finding indicates a partly shared pathophysiological pathway between preeclampsia and CVD.

Abstract Background Identifying women at high risk for preeclampsia is essential for the decision to start treatment with prophylactic aspirin. Prediction models have been developed for this purpose, and these typically incorporate body mass index (BMI). As waist circumference (WC) is a better predictor for metabolic and cardiovascular outcomes than BMI in nonpregnant populations, we aimed to investigate if WC is a BMI-independent predictor for preeclampsia and if the addition of WC to a prediction model for preeclampsia improves its performance. Methods We used a population-based cohort of 4,696 women with WC measurements taken in the first trimester. The influence of WC on the risk of developing preeclampsia was evaluated by multivariable logistic regression. We generated receiver operating characteristic curves and calculated the area under the curve (AUC) to evaluate the usefulness of WC measurements for prediction of preeclampsia. Results Women who developed preeclampsia had greater early pregnancy WC than women who did not (85.8 ± 12.6 vs. 82.3 ± 11.3 cm, P < 0.001). The risk of preeclampsia increased with larger WC in a multivariate model, adjusted odds ratio 1.02 (95% confidence interval 1.01–1.03). However, when adding BMI into the model, WC was not independently associated with preeclampsia. The AUC value for preeclampsia prediction with BMI and the above variables was 0.738 and remained unchanged with the addition of WC to the model. Conclusions Large WC is associated with a higher risk of preeclampsia, but adding WC to a prediction model for preeclampsia that already includes BMI does not improve the model’s performance.

The objective of this study was to evaluate the associations of 92 maternal blood-based proteins with increased infant birth size. The study was performed at the Uppsala University Hospital, Sweden, and included 857 mother and child dyads. The mean age of the women was 30.3 years, and 53.2% were nulliparous. Blood samples were collected at mean 18 + 2 weeks’ gestation, and the Olink cardiovascular II panel was used to measure 92 proteins, either known to be or suspected to be markers of cardiovascular and inflammatory disease in humans. Multiple linear regression models adjusted for maternal age, parity, pre-conception BMI, height, and smoking were performed to evaluate the association of each individual protein with infant birth size. We also performed sex-stratified analyses. Eight proteins (Matrix metalloproteinase-12 (MMP-12), Prostasin (PRSS8), Adrenomedullin (ADM), Pappalysin-1 (PAPP-A), Angiotensin-converting enzyme 2 (ACE2), Sortilin (SORT1), Lectin-like oxidized LDL receptor 1 (LOX-1), and Thrombomodulin (TM)) were associated with infant birth size after false discovery rate adjustment. In the analyses including only female infants, ten proteins (MMP-12, Growth/differentiation factor 2 (GDF-2), PRSS8, SORT1, ADM, Interleukin-1 receptor antagonist protein (IL-1ra), Leptin (LEP), ACE2, TM, and Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A)) were associated with infant birth size. Two proteins (PAPP-A and PRSS8) were associated with infant birth size among male infants. Our study suggests several proteins as potential biomarkers for increased birth weight, and our findings could act as a base for future research to identify new potential markers that could be added to improve screening for large infants.

Our recent study demonstrates the beneficial effect of a combined supplementation of vitamin B12, folic acid, and docosahexaenoic acid in reducing the severity of pregnancy induced hypertension (PIH). It is also known to be associated with angiogenic imbalance and inflammation. The current study examines whether the individual/combined supplementation of folic acid, vitamin B12 and omega-3 fatty acid during pregnancy can ameliorate the inflammatory markers and restore the angiogenic balance in a rat model of PIH.There were total of six groups, control and five treatment groups: PIH Induced; PIH+vitamin B12; PIH+folic acid; PIH+Omega-3 fatty acids and PIH+combined micronutrient supplementation (vitamin B12+folic acid+omega-3 fatty acids). Hypertension during pregnancy was induced using L- Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day). Dams were dissected at d20 of gestation and placental tissues were collected for further analysis.Animals from the PIH induced group demonstrated lower (p<0.01 for both) IL-10 and VEGF levels as compared to control. However, PIH induction did not alter the protein levels of eNOS, IL-6, Flt and mRNA levels of VEGF and VEGFR-1/ Flt-1. Individual micronutrient supplementation of vitamin B12 and folate did not offer benefit. In contrast individual omega-3 fatty acid as well as combined micronutrient supplementation showed IL-10 and VEGF levels comparable to that of control.Omega 3 fatty acid supplementation plays a key role in reducing inflammation in pregnancy induced hypertension.

Early identification of high-risk pregnancies enables identification of those who would benefit from aspirin prophylaxis and increased surveillance for pre-eclampsia. A high body mass index (BMI) is a well-known predictor for pre-eclampsia. However, if abdominal adipose tissue distribution is associated with pre-eclampsia is limited investigated. Subcutaneous adipose tissue (SAT) thickness and visceral adipose tissue (VAT) thickness were measured by ultrasound on 3777 women at around 18 gestational weeks. SAT thickness was measured from the skin to linea alba and VAT from linea alba to the anterior aortic wall. The risk of developing pre-eclampsia (de novo hypertension at ≥ 20 gestational weeks in combination with proteinuria) was evaluated by logistic regression and expressed as odds ratio (OR) with 95% confidence intervals (CI). The risk of pre-eclampsia increased by 79% for every cm in SAT thickness (OR 1.79; 95% CI 1.48–2.17) and by 23% for every cm VAT thickness (OR 1.23; 95% CI 1.11–1.35). After adjustment for maternal age, parity, BMI, smoking and country of birth, the association between SAT thickness and pre-eclampsia remained (AOR 1.35; 95% CI 1.02–1.79). Greater SAT thickness measured with second trimester ultrasound is associated with increased risk of developing pre-eclampsia. The measurement may improve prediction models for pre-eclampsia.

Mucosal melanoma of paranasal sinuses is a rare disease with a challenging treatment and a poor prognosis. In this paper, we reported the successful multimodality treatment of malignant mucosal melanoma of frontal sinus.A 65-year-old female presented with a frequent nosebleed for one month before admission. Computed tomography and magnetic resonance imaging showed a mass in the right frontal and ethmoidal sinuses with adjacent bone erosion and right orbit invasion. Biopsy revealed malignant melanoma. No metastasis was found. The definitive diagnosis was malignant mucosal melanoma of paranasal sinuses AJCC stage IVb (T4bN0M0). We used right frontobasal craniotomy to resect tumor for local control of the disease. Immunohistochemical staining was Melan A(+), S100(+), and HMB45(+). A week postoperative, she received adjuvant radiotherapy and immunotherapy (pembrolizumab). For three months postoperative, the patient had no recurrence and metastasis, no headache and no new neurological deficits. She returned to her daily activities.Mucosal melanoma of paranasal sinuses is usually aggressive and diagnosed at an advanced stage. Management options are surgery, radiation therapy, chemotherapy, and immunotherapy. These options were performed on a case-by-case basis and depend on the extent and location of the tumor. Despite that, the prognosis remains very poor, with a high rate of local recurrences and distant metastases. Therefore, post-treatment lifetime and frequent follow-ups are highly recommended.The critical issues in management of mucosal melanoma are early diagnosis, multimodality treatment, and frequent follow-ups.

Introduction Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women’s and their partners’ experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia. The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care. Methods and analysis This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women’s and partner’s experiences are distributed at follow-up. Ethics and dissemination By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women’s personal identification number and pseudonymised after identification in the biobank before analysis. This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309). Results from the study will be published in international peer-reviewed journals. Trial registration number ISRCTN13060768

Junus, K. 2018. Preeclampsia – Studies on the Placenta and B-type Natriuretic Peptide. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1487. 68 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0411-3. Preeclampsia has several pathophysiological pathways, but the placenta has a central role. The pathophysiology appears to differ between the two subtypes – earlyand late-onset preeclampsia. In clinically evident preeclampsia, maternal circulatory levels of the cardiac peptide B-type natriuretic peptide (BNP) and its cleavage fragment NT-proBNP are elevated, but whether or not the peptides are involved in the pathophysiology of preeclampsia is unknown. The overall aim of the current work was to expand knowledge of preeclampsia pathophysiology, with a main focus on the relationship between BNP and NT-proBNP, and earlyand late-onset preeclampsia. In Paper I, the placental transcriptional profiles of earlyand late-onset preeclampsia were compared by using microarrays and bioinformatics. A total of 196 transcripts were differently regulated in the two groups. Using qRT-PCR, mRNA levels of the two angiogenesis-related transcripts ACVRL1 and EGFL7 were confirmed to be lower in early-onset preeclampsia than in both late-onset preeclampsia and early controls. In Paper II, the circulatory levels of NT-proBNP were higher in both earlyand late-onset preeclampsia than in gestational age-matched controls. BNP mRNA and protein were detected by qRT-PCR and immunohistochemistry in placentas from both women with preeclampsia and controls. In Paper III, circulatory levels of NT-proBNP were measured in the early second-trimester in women who later developed early-onset preeclampsia and in women who continued to have normal pregnancies. No differences were found between the two groups of women. In Paper IV, the secretion of NT-proBNP, and the mRNA levels of BNP and BNP receptors were investigated in cultured primary trophoblasts. Low levels of NT-proBNP were found in the supernatants of term but not first-trimester trophoblasts. BNP and BNP-receptor mRNA were detected in term trophoblasts. The results of this work strengthen the concept of the two subtypes of preeclampsia (earlyand late-onset) having partly different pathophysiological pathways. The results also indicate that the placenta releases BNP and that BNP may have receptor-mediated effects on the placenta.