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1.
  • Bergman, Lina, et al. (author)
  • Multi-Fetal Pregnancy, Preeclampsia, and Long-Term Cardiovascular Disease
  • 2020
  • In: Hypertension. - 0194-911X .- 1524-4563. ; 76:1, s. 167-175
  • Journal article (peer-reviewed)abstract
    • This Swedish register-based cohort study determined the separate and joint contribution of preeclampsia and multi-fetal pregnancy on a woman's risk of cardiovascular disease (CVD) later in life. The study included 892 425 first deliveries between 1973 and 2010 of women born 1950 until 1971, identified in the Swedish Medical Birth Register. A composite outcome of CVD was retrieved through linkage with the National Patient and Cause of Death Registers. Cox proportional hazard regression was used to assess the risk of CVD in women who had preeclampsia in a singleton or multi-fetal pregnancy, adjusting for potential confounders, and presented as adjusted hazard ratios. Compared with women who had a singleton pregnancy without preeclampsia (the referent group), women with preeclampsia in a singleton pregnancy had an increased risk of CVD (adjusted hazard ratio 1.75 [95% CI, 1.64-1.86]). Women who had a multi-fetal pregnancy without or with preeclampsia did not have an increased risk of future CVD (adjusted hazard ratios 0.94 [95% CI, 0.79-1.10] and 1.25 [95% CI, 0.83-1.86], respectively). As opposed to preeclampsia in a first singleton pregnancy, preeclampsia in a first multi-fetal pregnancy was not associated with increased risk of future CVD. This may support the theory that preeclampsia in multi-fetal pregnancies more often occurs as a result of the larger pregnancy-related burden on the maternal cardiovascular system and excessive placenta-shed inflammatory factors, rather than the woman's underlying cardiovascular phenotype.
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2.
  • Gunnerbeck, Anna, et al. (author)
  • Maternal Snuff Use and Smoking and the Risk of Oral Cleft Malformations - A Population-Based Cohort Study
  • 2014
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e84715-
  • Journal article (peer-reviewed)abstract
    • Objective: To determine if maternal use of snuff (containing high levels of nicotine, low levels of nitrosamines and no combustion products) is associated with an increased risk of oral cleft malformations in the infant and whether cessation of snuff use or smoking before the antenatal booking influences the risk. Method: A population-based cohort study was conducted on all live born infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic regression analyses (using adjusted odds ratios, with 95% confidence intervals [CI]). Results: Among 975 866 infants that had information on maternal tobacco use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who used snuff or smoked three months prior pregnancy stopped using before the antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users, the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who continued to use snuff or to smoke were 1.48 [1.00-2.21] and 1.19 [1.01-1.41], respectively. In contrast, in infants of mothers who stopped using snuff or stopped smoking before the antenatal booking, the corresponding risks were not increased (adjusted odds ratios [95% CI] were 0.71 [0.44-1.14] and 0.88 [0.73-1.05], respectively). Conclusion: Maternal snuff use or smoking in early pregnancy is associated with an increased risk of oral clefts. Infants of mothers who stopped using snuff or stopped smoking before the antenatal booking had no increased risk of oral cleft malformations. Oral snuff or other sources of nicotine should not be recommended as an alternative for smoke-cessation during pregnancy.
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3.
  • Gunnerbeck, Anna, et al. (author)
  • Relationship of Maternal Snuff Use and Cigarette Smoking With Neonatal Apnea
  • 2011
  • In: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 128:3, s. 503-509
  • Journal article (peer-reviewed)abstract
    • Background: Maternal smoking is associated with disturbed cardiorespiratory control in the infant. Despite lacking knowledge of whether the harmful effects of smoking are caused by combustion products in tobacco smoke or by nicotine, it has been argued that nicotine-replacement therapy during pregnancy is safer than smoking. Objective: The goal of this study was to investigate if the disturbances in cardiorespiratory control associated with maternal smoking are also seen in infants prenatally exposed to snuff. We hypothesized that prenatal nicotine exposure (via moist snuff) causes disturbances in autonomic control and thereby increases the risk of apnea in the newborn. Methods: In a nationwide Swedish cohort study, we studied associations between maternal tobacco use during pregnancy and neonatal apnea. Of 609 551 live-born singleton infants, 7599 were born to snuff-using mothers, 41 391 and 16 928 were born to light (1-9 cigarettes per day) and heavy (≥10 cigarettes per day) smokers, respectively. Logistic regression was used to calculate odds ratios, using 95% confidence intervals. Results: Compared with infants of nontobacco users, infants with prenatal exposure to snuff were at an increased risk of apnea even after adjustment for differences in gestational age (odds ratio: 1.96 [95% confidence interval: [1.30-2.96]) Smoking was associated with increased risk of apnea before, but not after, adjusting for gestational age. Conclusions: Snuff use during pregnancy is associated with a higher risk of neonatal apnea than smoking. Maternal use of snuff or nicotine-replacement therapy cannot be regarded as an alternative to smoking during pregnancy.
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4.
  • Kårehed, Karin, et al. (author)
  • Fibrinogen and histidine-rich glycoprotein in early-onset preeclampsia
  • 2010
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 89:1, s. 131-139
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To determine whether plasma levels of fibrinogen and the placental tissue distributions of fibrinogen and histidine-rich glycoprotein (HRG) differ between early- and late-onset preeclampsia. DESIGN: The study comprised 18 women with early-onset (gestational weeks 24-32) and 19 women with late-onset (gestational weeks 35-42) preeclampsia. As controls concerning the plasma levels of fibrinogen, we used samples from non-pregnant fertile women, healthy pregnant women at gestational weeks 24-32 and healthy pregnant women at gestational weeks 35-42. Placental samples from women with healthy pregnancies at gestational weeks 35-42 served as controls in the immunohistochemical staining. SETTING: Uppsala University Hospital, Uppsala. METHODS: Plasma fibrinogen levels were analyzed and the placental tissue expression of fibrinogen and HRG determined by immunohistochemistry. RESULTS: Plasma level of fibrinogen was increased in early-onset, but not late-onset, preeclampsia. Levels of fibrinogen were significantly lower, and that of HRG significantly higher, in placentas from women with early-onset preeclampsia as compared with control placentas (p = 0.01 and 0.001). CONCLUSIONS: HRG and fibrinogen might be involved in the hypercoagulability and the angiogenic imbalance seen in early-onset preeclampsia.
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6.
  • Altman, Maria, et al. (author)
  • Cause-specific infant mortality in a population-based Swedish study of term and post-term births : the contribution of gestational age and birth weight
  • 2012
  • In: BMJ Open. - : BMJ. - 2044-6055. ; 2:4
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE:To investigate infant mortality and causes of infant death in relation to gestational age (GA) and birth weight for GA in non-malformed term and post-term infants.DESIGN:Observational, retrospective nationwide cohort study.SETTING:Sweden 1983-2006.PARTICIPANTS:2 152 738 singleton non-malformed infants born at 37 gestational weeks or later.MAIN OUTCOME MEASURES:Infant, neonatal and postneonatal mortality and causes of infant death.RESULTS:Infant mortality rate was 0.12% (n=2687). Compared with infants born at 40 weeks, risk of infant mortality was increased among early term infants (37 weeks, adjusted OR 1.70, 95% CI 1.43 to 2.02). Compared with infants with normal birth weight for GA, very small for gestational age (SGA; <3rd percentile) infants faced a doubled risk of infant mortality (adjusted OR 2.13, 95% CI 1.80 to 2.53), and corresponding risk was also increased among moderately SGA infants (3rd to <10th percentile; adjusted OR 1.46, 95% CI 1.26 to 1.68). Sudden infant death syndrome (SIDS) was the most common cause of death, accounting for 39% of all infant mortality. Compared with birth at 40 weeks, birth at 37 weeks was associated with increased risks of death by infections, cardiovascular disorders, SIDS and malignant neoplasms. Very and moderately SGA were associated with increased risks of death by neonatal respiratory disorders, infections, cardiovascular disorders, SIDS and neuromuscular disorders. High birth weight for GA was associated with increased risks of death by asphyxia and malignant neoplasms.CONCLUSION:Early term birth and very to moderately low birth weight for GA are independent risk factors for infant mortality among non-malformed term infants.
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7.
  • Bolin, Marie, et al. (author)
  • Prediction of Preeclampsia by Combining Serum Histidine-Rich Glycoprotein and Uterine Artery Doppler
  • 2012
  • In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 25:12, s. 1305-1310
  • Journal article (peer-reviewed)abstract
    • BackgroundPreeclampsia is associated with both maternal and perinatal morbidity and mortality. Histidine-rich glycoprotein (HRG) is a protein interacting with angiogenesis, coagulation, and inflammatory responses, processes known to be altered in preeclamptic pregnancies. Significantly lower levels of HRG have been demonstrated as early as in the first trimester in women later developing preeclampsia compared with normal pregnancies. The aim of this study was to investigate whether the combination of HRG and uterine artery Doppler ultrasonography can be used as a predictor of preeclampsia.MethodsA total of 175 women were randomly selected from a case-control study; 86 women had an uncomplicated pregnancy and 89 women later developed preeclampsia. Blood samples and pulsatility index (PI) were obtained from both cases and controls in gestational week 14.ResultsHRG levels were significantly lower in women who developed preterm preeclampsia compared with controls, but not for women developing preeclampsia in general. PI was significantly higher in the preeclampsia group compared with controls, especially in preterm preeclampsia. The combination of HRG and PI revealed a sensitivity of 91% and a specificity of 62% for preterm preeclampsia.ConclusionsThe combination of HRG and uterine artery Doppler may predict preterm preeclampsia in early pregnancy.
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8.
  • Cnattingius, Sven, et al. (author)
  • Maternal Obesity and Risk of Preterm Delivery
  • 2013
  • In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:22, s. 2362-2370
  • Journal article (peer-reviewed)abstract
    • Importance Preterm birth is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age. Obesity increases the risk of preterm delivery, but the associations between overweight and obesity and subtypes of preterm delivery are not clear. Objective To study the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. Design, Setting, and Participants Population-based cohort study of women with live singleton births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. Main Outcomes and Measures Risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor). Risk estimates were adjusted for maternal age, parity, smoking, education, height, mother's country of birth, and year of delivery. Results Among 1 599 551 deliveries with information on early pregnancy BMI, 3082 were extremely preterm, 6893 were very preterm, and 67 059 were moderately preterm. Risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Among normal-weight women (BMI 18.5-<25), the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs [95% CIs]) of extremely preterm delivery were as follows: BMI 25 to less than 30 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to less than 35 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to less than 40 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92). Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI >= 30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women. Conclusions and Relevance In Sweden, maternal overweight and obesity during pregnancy were associated with increased risks of preterm delivery, especially extremely preterm delivery. These associations should be assessed in other populations.
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10.
  • Hesselman, Susanne, 1973-, et al. (author)
  • Time matters—a Swedish cohort study of labor duration and risk of uterine rupture
  • 2021
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:10, s. 1902-1909
  • Journal article (peer-reviewed)abstract
    • IntroductionUterine rupture is an obstetric emergency associated with maternal and neonatal morbidity. The main risk factor is a prior cesarean section, with rupture occurring in subsequent labor. The aim of this study was to assess the risk of uterine rupture by labor duration and labor management.Material and methodsThis is a Swedish register-based cohort study of women who underwent labor in 2013–2018 after a primary cesarean section (n = 20 046). Duration of labor was the main exposure, calculated from onset of regular labor contractions and birth; both timepoints were retrieved from electronic medical records for 12 583 labors, 63% of the study population. Uterine rupture was calculated as events per 1000 births at different timepoints during labor. Risk estimates for uterine rupture by labor duration, induction of labor, use of oxytocin and epidural analgesia were calculated using Poisson regression, adjusted for maternal and birth characteristics. Estimates were presented as adjusted rate ratios (ARR) with 95% confidence intervals (CI).ResultsThe prevalence of uterine rupture was 1.4% (282/20 046 deliveries). Labor duration was 9.88 hours (95% CI 8.93–10.83) for women with uterine rupture, 8.20 hours (95% CI 8.10–8.31) for women with vaginal delivery, and 10.71 hours (95% CI 10.46–10.97) for women with cesarean section without uterine rupture. Few women (1.0/1000) experienced uterine rupture during the first 3 hours of labor. Uterine rupture occurred in 15.6/1000 births with labor duration over 12 hours. The highest risk for uterine rupture per hour compared with vaginal delivery was observed at 6 hours (ARR 1.20, 95% CI 1.11–1.30). Induction of labor was associated with uterine rupture (ARR 1.54, 95% CI 1.19–1.99), with a particular high risk seen in those induced with prostaglandins and no risk observed with cervical catheter (ARR 1.19, 95% CI 0.83–1.71). Labor augmentation with oxytocin (ARR 1.60, 95% CI 1.25–2.05) and epidural analgesia (ARR 1.63, 95% CI 1.27–2.10) were also associated with uterine rupture.ConclusionsLabor duration is an independent factor for uterine rupture among women attempting vaginal delivery after cesarean section. Medical induction and augmentation of labor increase the risk, regardless of maternal and birth characteristics.
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11.
  • Nilvér, Helena, et al. (author)
  • Women's childbirth experiences in the Swedish Post-term Induction Study (SWEPIS) : a multicentre, randomised, controlled trial
  • 2021
  • In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:4
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To compare childbirth experiences in women randomly assigned to either induction of labour at 41 weeks or to expectant management until 42 weeks, in the Swedish Post-term Induction Study.DESIGN: A register-based, multicentre, randomised, controlled, superiority trial.SETTING: Women were recruited at 14 hospitals in Sweden, 2016-2018.PARTICIPANTS: Women with an uncomplicated singleton pregnancy were recruited at 41 gestational weeks.INTERVENTIONS: The women were randomly assigned to induction of labour at 41 weeks (induction group, n=1381) or expectant management until 42 weeks (expectant management group, n=1379).OUTCOME MEASURES: As main outcome, women's childbirth experiences were measured using the Childbirth Experience Questionnaire version 2 (CEQ2), in 656 women, 3 months after the birth at three hospitals. As exploratory outcome, overall childbirth experience was measured in 1457 women using a Visual Analogue Scale (VAS 1-10) within 3 days after delivery at the remaining eleven hospitals.RESULTS: The total response rate was 77% (2113/2760). There were no significant differences in childbirth experience measured with CEQ2 between the groups (induction group, n=354; expectant management group, n=302) in the subscales: own capacity (2.8 vs 2.7, p=0.09), perceived safety (3.3 vs 3.2, p=0.06) and professional support (3.6 vs 3.5, p=0.38) or in the total CEQ2 score (3.3 vs 3.2, p=0.07), respectively. Women in the induction group scored higher in the subscale participation (3.6 vs 3.4, p=0.02), although with a small effect size (0.19). No significant difference was observed in overall childbirth experience according to VAS (8.0 (n=735) vs 8.1 (n=735), p=0.22). CONCLUSIONS: There were no differences in childbirth experience, according to CEQ2 or overall childbirth experience assessed with VAS, between women randomly assigned to induction of labour at 41 weeks or expectant management until 42 weeks. Overall, women rated their childbirth experiences high.TRIAL REGISTRATION NUMBER: ISRCTN26113652.
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12.
  • Sederholm Lawesson, Sofia, 1973-, et al. (author)
  • Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.
  • 2023
  • In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 329:5, s. 393-404
  • Journal article (peer-reviewed)abstract
    • Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.Cross-sectional study of a population-based cohort of women in Sweden (n=10528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected.Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures.Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100.A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.
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13.
  • Thorgeirsdottir, Lilja, et al. (author)
  • Study protocol: establishment of a multicentre pre-eclampsia database and biobank in Sweden: GO PROVE and UP MOST, a prospective cohort study
  • 2021
  • In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
  • Journal article (other academic/artistic)abstract
    • 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).
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14.
  • Yang, Fen, et al. (author)
  • Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries
  • 2022
  • In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:11
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE An association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited. OBJECTIVE To investigate (1) the association between maternal preeclampsia and risks of ischemic heart disease (IHD) and stroke in the offspring, (2) whether the association varies by severity or timing of onset of preeclampsia, and (3) the role of preterm birth and small for gestational age (SGA) birth, both of which are related to preeclampsia and cardiovascular diseases, in this association. DESIGN, SETTING, AND PARTICIPANTS This multinational population-based cohort study obtained data from Danish, Finnish, and Swedish national registries. Live singleton births from Denmark (1973-2016), Finland (1987-2014), and Sweden (1973-2014) were followed up until December 31, 2016, in Denmark and December 31, 2014, in Finland and Sweden. Data analyses were performed between September 2020 and September 2022. EXPOSURES Preeclampsia and its subtypes, including early onset (<34 gestational weeks) and late onset (>= 34 gestational weeks), severe and mild or moderate, and with and without SGA birth. MAIN OUTCOMES AND MEASURES Diagnoses of IHD and stroke were extracted from patient and cause-of-death registers. Cox proportional hazards regression models and flexible parametric survival models were used to analyze the associations. Sibling analyses were conducted to control for unmeasured familial factors. RESULTS The cohort included of 8 475 819 births (2 668 697 [31.5%] from Denmark, 1636 116 [19.3%] from Finland, and 4171006 [49.2%] from Sweden, comprising 4350 546 boys [51.3%]). Of these offspring, 188 670 (2.2%) were exposed to maternal preeclampsia, 7446 (0.1%) were diagnosed with IHD, and 10 918 (0.1%) were diagnosed with stroke during the median (IQR) follow-up of 19.3 (9.0-28.1) years. Offspring of individuals with preeclampsia had increased risks of IHD (adjusted hazard ratio [HR], 1.33; 95% CI, 1.12-1.58) and stroke (adjusted HR, 1.34; 95% CI, 1.17-1.52). These associations were largely independent of preterm or SGA birth. Severe forms of preeclampsia were associated with a higher stroke risk than less severe forms (severe vs mild or moderate: adjusted HR, 1.81[95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]; early vs late onset: adjusted HR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]; with vs without SGA birth: adjusted HR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]). Sibling analyses suggested that the associations were partially explained by unmeasured familial factors. CONCLUSIONS AND RELEVANCE Results of this study suggest that offspring born to individuals with preeclampsia had increased IHD and stroke risk that were not fully explained by preterm or SGA birth, and that the associated risks for stroke were higher for severe forms of preeclampsia.
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15.
  • Akhter, Tansim, 1967-, et al. (author)
  • Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia
  • 2017
  • In: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 50, s. 93-99
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.
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16.
  • Akhter, Tansim, 1967-, et al. (author)
  • Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.
  • 2017
  • In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 241, s. 417-422
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.
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17.
  • Alkmark, Mårten, et al. (author)
  • Efficacy and safety of oral misoprostol vs transvaginal balloon catheter for labor induction : An observational study within the SWEdish Postterm Induction Study (SWEPIS)
  • 2021
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:8, s. 1463-1477
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Induction of labor is increasing in the world. A common indication for Induction of labor is late term and postterm pregnancy at 41 gestational week and thereafter. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41+0 to 42+0-1 gestational weeks.MATERIAL AND METHODS: In this observational study, based on data from Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1 213 women with a low-risk singleton pregnancy at 41 to 42 gestational weeks were induced with oral misoprostol (n=744) or transvaginal balloon catheter (n=469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 hours and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time-to-vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analogue scale. We present crude and adjusted mean differences and relative risks (RR) with 95% confidence interval (CI). Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score.RESULTS: Vaginal delivery within 24 hours was significantly lower in the misoprostol compared with the balloon catheter group (46.5% [346/744] vs 62.7% [294/469]; adjusted RR 0.76 [95% CI 0.64; 0.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31; 1.89]; maternal composite (2.3% [17/744] vs 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58; 4.97]). Adjusted mean time-to-vaginal delivery was increased by 3.8 hours (95% CI 1.3; 6.2) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups.CONCLUSION: Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 hours and a longer time-to-vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.
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18.
  • Belachew, Johanna, 1976-, et al. (author)
  • Risk of retained placenta in women previously delivered by caesarean section : a population-based cohort study.
  • 2014
  • In: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 121:2, s. 224-229
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To evaluate whether women with a caesarean section at their first delivery have an increased risk of retained placenta at their second delivery.DESIGN: Population-based cohort study.SETTING: Sweden.POPULATION: All women with their first and second singleton deliveries in Sweden during the years 1994-2006 (n = 258 608). Women with caesarean section or placental abruption in their second pregnancy were not included in the study population.METHODS: The risk of retained placenta at second delivery was estimated for women with a first delivery by caesarean section (n = 19 458), using women with a first vaginal delivery as reference (n = 239 150). Risks were calculated as odds ratios by unconditional logistic regression analysis with 95% confidence intervals (95%) after adjustments for maternal, delivery, and infant characteristics.MAIN OUTCOME MEASURES: Retained placenta with normal (≤1000 ml) and heavy (>1000 ml) bleeding.RESULTS: The overall rate of retained placenta was 2.07%. In women with a previous caesarean section and in women with previous vaginal delivery, the corresponding rates were 3.44% and 1.96%, respectively. Compared with women with a previous vaginal delivery, women with a previous caesarean section had an increased risk of retained placenta (adjusted OR 1.45; 95% CI 1.32-1.59), and the association was more pronounced for retained placenta with heavy bleeding (adjusted OR 1.61; 95% CI 1.44-1.79).CONCLUSIONS: Our report shows an increased risk for retained placenta in women previously delivered by caesarean section, a finding that should be considered in discussions of mode of delivery.
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19.
  • Bergman, Lina, 1982- (author)
  • Cerebral biomarkers in women with preeclampsia
  • 2017
  • Doctoral thesis (other academic/artistic)abstract
    • Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
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20.
  • Bergman, Lina, et al. (author)
  • Investigating Maternal Brain Alterations in Preeclampsia : the Need for a Multidisciplinary Effort
  • 2019
  • In: Current Hypertension Reports. - : Springer Science and Business Media LLC. - 1522-6417 .- 1534-3111. ; 21:9
  • Journal article (peer-reviewed)abstract
    • PURPOSE OF REVIEW: To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia.RECENT FINDINGS: The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.
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21.
  • Bergman, Lina, et al. (author)
  • Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects
  • 2014
  • In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 27:8, s. 1105-1111
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.METHODS:A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.RESULTS:Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).CONCLUSIONS:S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.
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22.
  • Bergman, Lina, et al. (author)
  • Preeclampsia and Increased Permeability Over the Blood–Brain Barrier : A Role of Vascular Endothelial Growth Receptor 2
  • 2021
  • In: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 34:1, s. 73-81
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.METHODS: The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert were exposed (12 h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in order to establish correlations with in vitro results.RESULTS: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.CONCLUSION: We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.
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23.
  • Bergman, Lina, 1982, et al. (author)
  • Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
  • 2020
  • In: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
  • Journal article (peer-reviewed)abstract
    • Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
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24.
  • Carlsson, Ylva, 1975, et al. (author)
  • Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.
  • 2023
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; :8, s. 1084-1091
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy.MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific.RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer  = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer  = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche  = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche  = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher  = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher  = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4).CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.
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25.
  • Carlsson, Ylva, 1975, et al. (author)
  • COVID-19 in Pregnancy and Early Childhood (COPE): study protocol for a prospective, multicentre biobank, survey and database cohort study.
  • 2021
  • In: BMJ open. - : BMJ. - 2044-6055. ; 11:9
  • Journal article (peer-reviewed)abstract
    • There is limited knowledge on how the SARS-CoV-2 affects pregnancy outcomes. Studies investigating the impact of COVID-19 in early pregnancy are scarce and information on long-term follow-up is lacking.The purpose of this project is to study the impact of COVID-19 on pregnancy outcomes and long-term maternal and child health by: (1) establishing a database and biobank from pregnant women with COVID-19 and presumably non-infected women and their infants and (2) examining how women and their partners experience pregnancy, childbirth and early parenthood in the COVID-19 pandemic.This is a national, multicentre, prospective cohort study involving 27 Swedish maternity units accounting for over 86000 deliveries/year. Pregnant women are included when they: (1) test positive for SARS-CoV-2 (COVID-19 group) or (2) are non-infected and seek healthcare at one of their routine antenatal visits (screening group). Blood, as well as other biological samples, are collected at different time points during and after pregnancy. Child health up to 4years of age and parent experience of pregnancy, delivery, early parenthood, healthcare and society in general will be examined using web-based questionnaires based on validated instruments. Short- and long-term health outcomes will be collected from Swedish health registers and the parents' experiences will be studied by performing qualitative interviews.Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (dnr 2020-02189 and amendments 2020-02848, 2020-05016, 2020-06696 and 2021-00870) and national biobank approval by the Biobank Väst (dnr B2000526:970). Results from the project will be published in peer-reviewed journals.NCT04433364.
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26.
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27.
  • de Brun, Maryam, 1991-, et al. (author)
  • Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden : A stepped wedge cluster randomised trial
  • 2024
  • In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 21:7
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.METHODS AND FINDINGS: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations.CONCLUSIONS: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term.TRIAL REGISTRATION: The trial is registered with ISRCTN (41918550).
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28.
  • Elden, Helen, 1959, et al. (author)
  • Study protocol of SWEPIS a Swedish multicentre register based randomised controlled trial to compare induction of labour at 41 completed gestational weeks versus expectant management and induction at 42 completed gestational weeks
  • 2016
  • In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 16:49
  • Journal article (peer-reviewed)abstract
    • Background: Observational data shows that postterm pregnancy (>= 42 gestational weeks, GW) and late term pregnancy (>= 41 GW), as compared to term pregnancy, is associated with an increased risk for adverse outcome for the mother and infant. Standard care in many countries is induction of labour at 42 GW. There is insufficient scientific support that induction of labour at 41 GW, as compared with expectant management and induction at 42 GW will reduce perinatal mortality and morbidity without an increase in operative deliveries, negative delivery experiences or higher costs. Large randomised studies are needed since important outcomes; such as perinatal mortality and hypoxic ischaemic encephalopathy are rare events. Methods/Design: A total of 10 038 healthy women >= 18 years old with a normal live singleton pregnancy in cephalic presentation at 41 GW estimated with a first or second trimester ultrasound, who is able to understand oral and written information will be randomised to labour induction at 41 GW (early induction) or expectant management and induction at 42 GW (late induction). Women will be recruited at university clinics and county hospitals in Sweden comprising more than 65 000 deliveries per year. Primary outcome will be a composite of stillbirth, neonatal mortality and severe neonatal morbidity. Secondary outcomes will be other adverse neonatal and maternal outcomes, mode of delivery, women's experience, cost effectiveness and infant morbidity up to 3 months of age. Data on background variables, obstetric and neonatal outcomes will be obtained from the Swedish Pregnancy Register and the Swedish Neonatal Quality Register. Data on women's experiences will be collected by questionnaires after randomisation and 3 months after delivery. Primary analysis will be intention to treat. The statistician will be blinded to group and intervention. Discussion: It is important to investigate if an intervention at 41 GW is superior to standard care in order to reduce death and lifelong disability for the children. The pregnant population, >41 GW, constitutes 15-20 % of all pregnancies and the results of the study will thus have a great impact. The use of registries for randomisation and collection of outcome data represents a unique and new study design.
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29.
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30.
  • Fadl, Helena, 1965-, et al. (author)
  • Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
  • 2019
  • In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
  • Journal article (peer-reviewed)abstract
    • Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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31.
  • Granfors, Michaela, et al. (author)
  • Placental location and pregnancy outcomes in nulliparous women : A population-based cohort study
  • 2019
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 98:8, s. 988-996
  • Journal article (peer-reviewed)abstract
    • Introduction: The impact of placenta previa on pregnancy, delivery and infant outcomes has been extensively studied. However, less is known about the possible association of placental location other than previa with pregnancy outcomes. The aim of this study was to investigate if placental location other than previa is associated with adverse pregnancy, delivery and infant outcomes.Material and methods: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The study population included 74 087 nulliparous women with singleton pregnancies resulting in live-born infants, with information about placental location from the second-trimester ultrasound screening. The association between placental location (fundal, lateral, anterior or posterior) and pregnancy outcomes was estimated using logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated, and adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, sex of the infant and in vitro fertilization. Main outcome measures were pregnancy, delivery and infant outcomes.Results: Compared with posterior placental location, fundal and lateral placental locations were associated with a number of adverse pregnancy outcomes, the most important being: very preterm birth (<32 weeks of gestation) (adjusted OR [aOR] 1.78, 95% CI 1.18-2.63 and aOR 2.12, 95% CI 1.39-2.25, respectively), moderate preterm birth (32-36 weeks of gestation) (aOR 1.23, 95% CI 1.001-1.51 and aOR 1.62, 95% CI 1.32-2.00, respectively), small-for-gestational-age birth (aOR 1.67, 95% CI 1.34-2.07 and aOR 1.77, 95% CI 1.39-2.25, respectively) and manual removal of the placenta in vaginal births (aOR 3.27, 95% CI 2.68-3.99 and aOR 3.27, 95% CI 2.60-4.10, respectively). Additionally, lateral placental location was associated with preeclampsia (aOR 1.30, 95% CI 1.03-1.65) and severe postpartum hemorrhage (aOR 1.42, 95% CI 1.27-1.82).Conclusions: Compared with posterior placental location, fundal and lateral placental locations are associated with a number of adverse pregnancy, delivery and infant outcomes.
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32.
  • Granfors, Michaela, et al. (author)
  • Placental location and risk of retained placenta in women with a previous cesarean section : A population-based cohort study.
  • 2020
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 99:12, s. 1666-1673
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Some studies have shown that women with a previous cesarean section, compared with women with a previous vaginal delivery, have an increased risk of retained placenta during a subsequent vaginal delivery. It is unknown whether this is mediated by anterior placental location, when the placenta might cover the uterine scar. The aim of this study was to evaluate whether the increased risk of retained placenta in women with a previous cesarean section is mediated by anterior placental location.MATERIAL AND METHODS: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The overall study population included 49 598 women with a vaginal second delivery, where adequate information about placental location from the second-trimester ultrasound scan was available. For the main analysis, including the 3921 women with a previous cesarean section, we calculated the relative risk of retained placenta in women with an anterior placental location, using women with non-anterior placental locations as reference. Relative risks were calculated as odds ratios (OR) with 95% CI. In a second model, adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, infant sex, and in vitro fertilization.RESULTS: In the overall study population, the rate of retained placenta at the second delivery was 2.0%. The proportion of women with a retained placenta was higher among women with a previous cesarean compared with those with a previous vaginal delivery (3.4% vs 1.9%; P < .0001). In the main analysis, including women with a previous cesarean section, the risk for retained placenta was not increased with anterior compared with non-anterior placental location (OR 0.84, 95% CI 0.60-1.20). Adjustments did not affect the estimates in a significant way.CONCLUSIONS: The increased risk of retained placenta in women with a previous cesarean section is not mediated by anterior placental location.
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33.
  • Granfors, Michaela, 1972-, et al. (author)
  • Thyroid Testing and Management of Hypothyroidism During Pregnancy : A Population-based Study
  • 2013
  • In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:7, s. 2687-2692
  • Journal article (peer-reviewed)abstract
    • Context: There are international guidelines on thyroid function testing and management of hypothyroidism during pregnancy. Few studies have evaluated how they are implemented into clinical practice. Objective: In this descriptive study, we assessed the implementation of international guidelines in this field into local guidelines and also into clinical practice. Design and Participants: In a nationwide survey, all guidelines in Sweden were collected (n = 29), and the adherence of the local guidelines to The Endocrine Society Guidelines 2007 was evaluated. In a follow-up in 1 district, 5254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included for subsequent review of their medical reports. Results: All but 1 district had guidelines on the subject. All local guidelines included fewer than the 10 listed reasons for thyroid testing recommended by The Endocrine Society Guidelines. Furthermore, most guidelines recommended additional types of thyroid function tests to TSH sampling and lower trimester-specific TSH upper reference limits for women on levothyroxine treatment (P < .001). In the follow-up, the thyroid testing rate was 20%, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More than half of the women (50.9%) who were on levothyroxine treatment at conception had an elevated TSH level at thyroid testing according to The Endocrine Society Guidelines. Conclusions: The local guidelines are variable and poorly compliant with international guidelines. Performance of thyroid testing is not optimal, and rates of elevated TSH at testing are extremely high in subgroups.
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34.
  • Hastie, Roxanne, et al. (author)
  • Aspirin use during pregnancy and the risk of bleeding complications : a Swedish population-based cohort study
  • 2021
  • In: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 224:1, s. 95.e1-95.e12
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Aspirin is offered to pregnant women to prevent preeclampsia, a severe obstetrical complication. Large studies of nonpregnant populations have consistently shown that aspirin prophylaxis increases the risk of hemorrhagic complications. However, there have not been any population-based studies investigating this in a pregnant population.OBJECTIVE: This study aimed to investigate whether aspirin use during pregnancy is associated with an increased risk of bleeding complications.STUDY DESIGN: We performed a register-based cohort study using the Swedish Pregnancy Register wherein we examined 313,624 women giving birth between January 2013 and July 2017. Logistic regression was used to assess the risk of antepartum, intrapartum, and postpartum hemorrhage. A propensity score and inverse probability treatment weighting was used to generate an odds ratio that corrects for differences in baseline characteristics.RESULTS: Aspirin use was registered in 4088 (1.3%) women during pregnancy. Compared with women who did not take aspirin, aspirin use was not associated with bleeding complications during the antepartum period (adjusted odds ratio, 1.22; 95% confidence interval, 0.97-1.54). However, aspirin users had a higher incidence of intrapartum bleeding (2.9% aspirin users vs 1.5% nonusers; adjusted odds ratio, 1.63; 95% confidence interval, 1.30-2.05), postpartum hemorrhage (10.2% vs 7.8%; adjusted odds ratio, 1.23; 95% confidence interval, 1.08-1.39), and postpartum hematoma (0.4% vs 0.1%; adjusted odds ratio, 2.21; 95% confidence interval, 1.13-4.34). The risk of a neonatal intracranial hemorrhage was also increased (0.07% vs 0.01%; adjusted odds ratio, 9.66; 95% confidence interval, 1.88-49.48). After stratifying by mode of birth, a higher incidence of bleeding among aspirin users was present for those who had a vaginal birth but not those who had a cesarean delivery.CONCLUSION: Using aspirin during pregnancy is associated with increased postpartum bleeding and postpartum hematoma. It may also be associated with neonatal intracranial hemorrhage. When offering aspirin during pregnancy, these risks need to be weighed against the potential benefits.
  •  
35.
  • Hastie, R., et al. (author)
  • Duration of labor among women with hypertensive disorders of pregnancy; A Swedish register cohort study
  • 2020
  • In: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 251, s. 114-118
  • Journal article (peer-reviewed)abstract
    • Objective: Preeclampsia is a severe obstetric complication affecting 2–8% of pregnancies. There is a common belief that women with preeclampsia experience a shorter duration of labor, where it is thought that increased inflammation that occurs with the disease facilitates labor. However, little evidence exists to support or refute this. Thus, we undertook a register-based cohort study investigating the association between hypertensive disorders of pregnancy and labor duration. Study design: This was a Swedish register-based cohort study of nulliparous women with spontaneous or induced onset of labor at >34 weeks of gestation with a singleton fetus in cephalic presentation. Information of duration of labor was retrieved from electronic birth records and compared between women with hypertensive disorders and normotensives pregnancies. Data was represented as mean adjusted difference in hours (adjusted for pre-gestational disorders, maternal characteristics and mode of delivery) and adjusted hazard ratios (aHR), with an event defined as vaginal birth and women with intrapartum caesarean section censored. An aHR >1 indicated shorter duration of labor. Results: Among 101,531 women, 5548 (5.5%) developed a hypertensive disorder of pregnancy. The overall mean duration of labor was 9.43 (SD 5.32) hours. Women with hypertensive disorders experienced a shorter duration of labor compared to normotensive women, with an adjusted mean difference of -0.68 h (95% CI −0.90, −0.47) for gestational hypertension and -1.53 h (95% CI −1.72, −1.35) for preeclampsia. This corresponded to an aHR of 1.05 (95% CI 1.01, 1.10) and 1.12 (95% CI 1.08, 1.17), respectively. However, when we confined the analysis to those who labored spontaneously, the presence of hypertensive disorders did not alter duration of labor (aHR 0.98, 95% CI 0.95,1.01). Only women who were induced and also had hypertensive disorders experienced a shorter duration of labor (aHR 1.07, 95% CI 1.04,1.09). Conclusions: Hypertensive disorders did not alter labor duration among women with spontaneous onset of labor, however an association was observed among women who were induced. © 2020 Elsevier B.V.
  •  
36.
  • Hastie, Roxanne, et al. (author)
  • Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women : A Swedish Population Register-Based Cohort Study
  • 2019
  • In: Hypertension. - 0194-911X .- 1524-4563. ; 73:5, s. 1097-1103
  • Journal article (peer-reviewed)abstract
    • Preeclampsia is a hypertensive disorder of pregnancy with a high rate of maternal and neonatal morbidity and mortality. The only definite treatment is delivery. Preclinical investigations have identified proton pump inhibitors (PPIs), which are commonly used to treat reflux during pregnancy, as a potential treatment for preeclampsia. The aim of this study was to determine the association between PPI use during pregnancy and preeclampsia risk in a population-based register cohort. Using the Swedish Pregnancy Register, we conducted a cohort study of nulliparous pregnant women delivering from January 2013 to July 2017. Associations between PPI use and preeclampsia were investigated using logistic regression analyses with risk estimates presented as crude and adjusted odds ratios (aOR) with 95% CI. Of 157 720 nulliparous pregnant women, 6051 (3.8%) reported PPI use during pregnancy. PPI use during any point of pregnancy was associated with an increased risk of overall preeclampsia (aOR of 1.17; 95% CI, 1.04-1.32) and preeclampsia at term (aOR of 1.20; 95% CI, 1.04-1.39). However, PPI use recorded after 28 gestational weeks was associated with a reduced risk of preterm (delivery <37 weeks) preeclampsia (aOR of 0.63; 95% CI, 0.41-0.96) and early (delivery <34 weeks) preeclampsia (aOR of 0.41; 95% CI, 0.20-0.82). These findings highlight the heterogeneity of this disease, with a potential role PPIs for preventing preterm preeclampsia when used in close proximity to disease onset. Targeting PPI use to women at greatest risk of preterm preeclampsia may help prevent this severe form of disease.
  •  
37.
  • Hesselman, Susanne, 1973-, et al. (author)
  • Duration of labor among women with thromboembolic events: A Swedish register study
  • 2021
  • In: European Journal of Obstetrics and Gynecology and Reproductive Biology: X. - : Elsevier BV. - 2590-1613. ; 11
  • Journal article (peer-reviewed)abstract
    • Introduction: Inflammation is central to initiation of labor and coagulation is closely interlinked with inflammation. Low-molecular-weight-heparin (LMWH) promotes inflammatory cervical remodeling, myometrium contractility and has been associated with shorter duration of labor. Material and methods: This was a cohort study of 136,661 deliveries 2013–2017, identified in the Swedish Pregnancy Register with prospectively collected pregnancy and labor characteristics. Information of duration of labor was retrieved from the electronic birth records and analyzed with Cox proportional hazard regressions according to previous or current thromboembolic disease (overall) with or without LMWH treatment with non-exposed as reference. Results: The crude hazard ratio for vaginal delivery was not different between women with thromboembolic disease and women without thromboembolic disease (HR 0.99, 95 % CI 0.91–1.09). A lower hazard ratio for vaginal delivery was observed among women with venous thromboembolism (VTE) with concomitant LMWH use/treatment (adjusted HR 0.86, 95 % CI 0.76−0.98) compared to non-exposed, implying a longer duration of labor in these cases. Conclusion: Thromboembolic disease was not associated with shorter duration of labor and in presence of LMWH these women experienced longer duration of labor. © 2021 The Authors
  •  
38.
  • Hesselman, Susanne, 1973-, et al. (author)
  • Neighborhood deprivation and adverse perinatal outcomes in Sweden : A population-based register study
  • 2019
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 98:8, s. 1004-1013
  • Journal article (peer-reviewed)abstract
    • Introduction: Neighborhood deprivation has been associated with adverse perinatal outcomes but it is unclear to what extent maternal and social risk factors explain the association and how a stressful environment per se contributes.Material and methods: A population-based register study including 218 030 deliveries in Sweden between January 2013 and July 2017 was conducted. Exposure was living in a deprived or severely deprived area defined by the National Operations Department of the Swedish Police Authority. Adverse perinatal outcomes included preterm births, small-for-gestational-age births and stillbirths. A propensity score-based method was used to control for individual baseline characteristics. Associations were investigated with logistic regression analyses and risk estimates are presented as crude (OR) and adjusted odds ratio (aOR) with 95% confidence interval (CI).Results: Living in a deprived neighborhood in Sweden was associated with extremely preterm births (deprived area OR 1.50, 95% CI 1.07-2.11, severely deprived OR 1.90, 95% CI 1.40-2.58), small-for-gestational-age birth (deprived OR 1.45, 95% CI 1.31-1.60, severely deprived OR 1.85, 95% CI 1.69-2.03) and stillbirth (deprived OR 1.62, 95% CI 1.17-2.26, severely deprived OR 1.56, 95% CI 1.11-2.19). After accounting for individual maternal and social risk factors, the risk of small for gestational age in severely deprived areas remained (aOR 1.45, 95% CI, 1.19-1.75).Conclusions: The contextual effect of living in a deprived neighborhood on the risk of extremely preterm births, small-for-gestational-age births and stillbirths was to a high extent explained by individual factors of women residing in exposed areas, yet remained for small-for-gestational-age births in severely deprived areas after adjustment for maternal and social risk factors.
  •  
39.
  • Lindam, Anna, et al. (author)
  • High Maternal Body Mass Index in Early Pregnancy and Risks of Stillbirth and Infant Mortality-A Population-Based Sibling Study in Sweden
  • 2016
  • In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 184:2, s. 98-105
  • Journal article (peer-reviewed)abstract
    • In a population-based case-control study, we investigated whether familial confounding influenced the associations between maternal overweight/obesity and risks of stillbirth and infant mortality by including both population and sister controls. Using nationwide data from the Swedish Medical Birth Register (1992-2011), we included all primiparous women with singleton births who also had a sister with a first birth during that time period. We used logistic regression analyses to calculate odds ratios (and 95% confidence intervals) adjusted for maternal age, height, smoking habits, education, and time period (5-year groups) of child's birth. Body mass index (BMI) was calculated as weight (kg)/height (m)(2). Compared with population controls with a normal BMI (18.5-24.9), stillbirth risk increased with increasing BMI (BMI 25-29.9: odds ratio (OR) = 1.51 (95% confidence interval (CI): 1.21, 1.89); BMI 30-34.9: OR = 1.77 (95% CI: 1.24, 2.50); BMI a parts per thousand yen35: OR = 3.16 (95% CI: 2.10, 4.76)). The sister case-control analyses revealed similar results. Offspring of obese women (BMI a parts per thousand yen30) had an increased risk of infant mortality when population controls were used (OR = 2.41, 95% CI: 1.83, 3.16), and an even higher risk was obtained when sister controls were used (OR = 4.04, 95% CI: 2.25, 7.25). We conclude that obesity in early pregnancy is associated with increased risks of stillbirth and infant mortality independently of genetic and early environmental risk factors shared within families.
  •  
40.
  • Lindberger, Emelie, et al. (author)
  • Association of maternal central adiposity measured by ultrasound in early mid pregnancy with infant birth size
  • 2020
  • In: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10
  • Journal article (peer-reviewed)abstract
    • We sought to investigate whether early mid pregnancy visceral and subcutaneous fat depths measured by ultrasound were associated with infant birth size, independent of early pregnancy BMI. A cohort study was performed at Uppsala University Hospital, Sweden, between 2015-2018. Visceral and subcutaneous fat depths were measured at the early second-trimester anomaly scan in 2498 women, giving birth to singleton, term infants. Primary outcomes were birthweight and LGA (birthweight standard deviation score>90th percentile in the cohort). Linear and logistic regression models were used, adjusted for BMI, age, smoking, parity, maternal country of birth, gestational age and infant sex. A 5-mm increase in visceral fat depth was associated with an increase in birthweight of 8.3 g [95% confidence interval (CI) 2.5-14.1 g], after adjustments, and a 6% increase in the adjusted odds of having an infant born LGA (OR 1.06, CI 1.02-1.11). There was no association between subcutaneous fat depth and birthweight or LGA after covariate adjustments. Hence, visceral fat depth measured by ultrasound in early mid pregnancy was associated with excessive fetal growth, independent of early pregnancy BMI, and may be useful in models for predicting LGA infants.
  •  
41.
  • Lindberger, Emelie, et al. (author)
  • Associations of ultrasound estimated early mid pregnancy visceral and subcutaneous fat depths and early pregnancy BMI with adverse neonatal outcomes
  • 2021
  • In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
  • Journal article (peer-reviewed)abstract
    • This study investigated whether maternal central adiposity and body mass index (BMI) were associated with neonatal hypoglycemia and adverse neonatal outcomes. A cohort study was performed at Uppsala University Hospital, Sweden, between 2015 and 2018. Visceral and subcutaneous fat depths were measured by ultrasound at the early second-trimester anomaly scan in 2771 women giving birth to singleton infants. Body mass index was assessed in early pregnancy. Logistic regression models were performed. Adjustments were made for age, BMI (not in model with BMI as exposure), smoking, maternal country of birth, and parity. Outcomes were neonatal hypoglycemia (blood glucose concentration < 2.6 mmol/l), a composite of adverse neonatal outcomes (Apgar < 7 at 5 min of age, or umbilical artery pH ≤ 7.0, or admission to neonatal intensive care unit), and the components of the composite outcome. Visceral and subcutaneous fat depths measured by ultrasound in early mid pregnancy were not associated with any of the outcomes in adjusted analyses. For every unit increase in BMI, the likelihood of neonatal hypoglycemia increased by 5% (aOR 1.05, 95% CI 1.01–1.10), the composite outcome by 5% (aOR 1.05, 95% CI 1.01–1.08), and admission to neonatal intensive care unit by 6% (aOR 1.06, 95% CI 1.02–1.10).
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42.
  • Lindberger, Emelie, et al. (author)
  • Maternal early mid-pregnancy adiponectin in relation to infant birth weight and the likelihood of being born large-for-gestational-age.
  • 2023
  • In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Journal article (peer-reviewed)abstract
    • This study aimed to evaluate the association of maternal adiponectin with infant birth size in 1349 pregnant women at Uppsala University Hospital, Sweden. The mean age of the women was 31.0 years, and 40.9% were nulliparous. Maternal early mid-pregnancy adiponectin was measured in microgram/mL. Linear regression models were performed to evaluate the association between adiponectin and infant birth weight. Logistic regression models were used to evaluate adiponectin in relation to the odds of giving birth to an infant large-for-gestational-age (LGA, infant birth weight standard deviation score > 90th percentile). Adjustments were made for early pregnancy BMI and diabetes mellitus. Prior adjustments, adiponectin was inversely associated with infant birth weight (β - 17.1, 95% confidence interval (CI) - 26.8 to - 7.4 g, P < 0.001), and one microgram/mL increase in adiponectin was associated with a 9% decrease in the odds of giving birth to an LGA infant (odds ratio 0.91, CI 0.85-0.97, P = 0.006). The associations did not withstand in the adjusted models. We found a significant interaction between adiponectin and infant sex on birth size. This interaction was driven by an inverse association between maternal adiponectin and birth size in female infants, whereas no such association was found in males.
  •  
43.
  • Liu, Can, et al. (author)
  • The association between postpartum hemorrhage and postpartum depression : A Swedish national register-based study
  • 2021
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8
  • Journal article (peer-reviewed)abstract
    • BackgroundPostpartum hemorrhage is an important cause of maternal death and morbidity. However, it is unclear whether women who experience postpartum hemorrhage are at an increased risk of postpartum depression.ObjectivesTo examine whether postpartum hemorrhage is associated with postpartum depression.MethodsWe conducted a national register-based cohort study of 486,476 Swedish-born women who had a singleton livebirth between 2007 and 2014. We excluded women with pre-existing depression or who filled a prescription for an antidepressant before childbirth. We classified postpartum depression up to 12 months after giving birth by the presence of an International Classification of Diseases, version 10 (ICD-10) diagnosis code for depression or a filled outpatient prescription for an antidepressant. We used Cox proportional hazard models, adjusting for maternal sociodemographic and obstetric factors.ResultsPostpartum depression was identified in 2.0% (630/31,663) of women with postpartum hemorrhage and 1.9% (8601/455,059) of women without postpartum hemorrhage. In our unadjusted analysis, postpartum hemorrhage was not associated with postpartum depression (unadjusted hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.97-1.15). After adjusting for maternal age, parity, education, cohabitation status, maternal smoking status, and early pregnancy maternal BMI, gestational age, and birthweight, the association did not appreciably change, with confidence intervals overlapping the null (adjusted HR = 1.08, 95% CI 0.99, 1.17).ConclusionsWithin a population-based cohort of singleton women in Sweden with no prior history of depression, postpartum hemorrhage was not associated with postpartum depression.
  •  
44.
  • Maack, Heidrun Petursdottir, et al. (author)
  • Maternal body mass index moderates antenatal depression effects on infant birthweight
  • 2019
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 6213-
  • Journal article (peer-reviewed)abstract
    • Obesity and depression are two common medical problems that pregnant women present with in antenatal care. Overweight and obesity at the beginning of the pregnancy, and excessive weight gain during pregnancy, are independent explanatory variables for fetal birthweight and independent risk factors for giving birth to a large for gestational age (LGA) infant. However, the effect of co-morbid depression has received little attention. This study set out to investigate if maternal body mass index (BMI) in early pregnancy moderates antenatal depression effects on infant birthweight. 3965 pregnant women participated in this longitudinal cohort study, where cases (n = 178) had Edinburgh Postnatal Depression Scale (EPDS) score ≥ 17 in gestational week 17 or 32, and remaining women (n = 3787) were used as controls. The influence of maternal BMI and antenatal depressive symptoms on standardized birthweight was evaluated by analysis of covariance, with adjustment for relevant confounders. Depressed women with BMI 25.0 kg/m2 or more gave birth to infants with significantly greater standardized birthweight than non-depressed overweight women, whereas the opposite pattern was noted in normal weight women (BMI by antenatal depressive symptoms interaction; F(1,3839) = 6.32; p = 0.012. The increased birthweight in women with co-prevalent overweight and depressive symptoms was not explained by increased weight gain during the pregnancy. Maternal BMI at the beginning of pregnancy seems to influence the association between antenatal depressive symptoms and infant birthweight, but in opposite directions depending on whether the pregnant women is normal weight or overweight. Further studies are needed to confirm our finding.
  •  
45.
  • Malmquist, Anna, 1981-, et al. (author)
  • ‘A daddy is the same as a mummy’ : Swedish children in lesbian households talk about fathers and donors
  • 2014
  • In: Childhood. - : Sage Publications. - 0907-5682 .- 1461-7013. ; 21:1, s. 119-133
  • Journal article (peer-reviewed)abstract
    • The present article discusses how 12 children (five to eight years) in planned lesbian familiestalk about families, parents and specifically ‘daddies’ as such and not having a father themselves.Findings from child interviews demonstrate that the children described daddies as ‘the same’ asmummies, i.e. as having the same functions. This contrasts with previous research showing howchildren of heterosexuals often describe mothers and fathers as different. The children varied interms of how they labelled donors. Some children adopted the denomination ‘daddy’, drawing ona paternity discourse, while others simply referred to him as ‘a man’.
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46.
  • Nelander, Maria, et al. (author)
  • Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI
  • 2018
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:10, s. 1212-1218
  • Journal article (peer-reviewed)abstract
    • BackgroundCerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. Still we do not know if the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty to examine the cerebral circulation.Material and methodsWe have used a non-invasive diffusion weighted magnetic resonance imaging (MRI) technique, intravoxel incoherent motion, to study cerebral perfusion on the capillary level and cerebral edema in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant women (n=16). Estimates of cerebral blood volume, blood flow and edema were measured in five different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and grey matter.ResultsExcept for the caudate nucleus, we did not detect any differences in cerebral perfusion measures on a group level. In the caudate nucleus we found lower cerebral blood volume  and lower blood flow in preeclampsia compared to both normal pregnancy (p=0.01 and p=0.03, respectively) and non-pregnant women (both p=0.02). No differences in edema were detected between study groups.ConclusionThe cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia compared to normal pregnancy and non-pregnant women. 
  •  
47.
  • Nelander, Maria, et al. (author)
  • Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study
  • 2017
  • In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 30:7, s. 667-672
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women.METHODS: This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test.RESULTS: Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy.CONCLUSIONS: Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms.
  •  
48.
  • Nelander, Maria, 1974-, et al. (author)
  • Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia : a proton magnetic resonance spectroscopy study
  • 2018
  • In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 31:7, s. 847-853
  • Journal article (peer-reviewed)abstract
    • Background: Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia.Method: We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant controls (n=16). Cerebral levels organic osmolytes were further correlated to plasma osmolality, and plasma levels of glutamate and sodium.Results: Compared to non-pregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes myo-inositol, choline and creatine (p=0.001 or less), and all these metabolites correlated with each other (p<0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (p<0.008), and cerebral myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (p<0.05).Conclusion: Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.
  •  
49.
  • Nelander, Maria, 1974- (author)
  • Preeclampsia and the Brain : Epidemiological and Magnetic Resonance Studies
  • 2018
  • Doctoral thesis (other academic/artistic)abstract
    • Preeclampsia is a pregnancy specific syndrome that causes substantial maternal and fetal morbidity and mortality. One major contributor to maternal deaths is eclampsia, i.e. when seizures arise in the context of preeclampsia. The pathophysiology of eclampsia is still incompletely chartered and the long-term cerebral consequences of preeclampsia are also largely unknown.This thesis consists of a register based cohort study (n=3232, study I), and a cross-sectional neuroimaging study of pregnant women with and without preeclampsia (n=78, studies II-IV).In paper I, we compared the incidence of dementia and cardiovascular disease (CVD) between women ≥65 years with a self-reported history of hypertensive pregnancy, and women with a normotensive pregnancy. No difference was found regarding dementia, but an increased risk of CVD persisted among these elderly women.In paper II, we used phosphorus magnetic resonance spectroscopy to measure cerebral magnesium levels (Mg2+). We found lower levels of Mg2+ in women with preeclampsia than in women with normal pregnancy and non-pregnant women. Further, which was novel, we showed that lower cerebral Mg2+levels correlated with visual disturbances. The findings are interesting, since magnesium sulfate is the most effective treatment and prophylaxis for eclampsia, but with a largely unknown mechanism of action.In paper III, we measured cerebral organic osmolytes with proton magnetic resonance spectroscopy and found lower levels of osmolytes in pregnancy. Cerebral osmolytes were positively correlated with a decreased plasma osmolality, indicating that there is a joint biological mechanism. The only osmolyte that differed between women with preeclampsia and healthy pregnant women was glutamate. Glutamate is an excitatory neurotransmitter, which also functions as an osmolyte. Thus, lower cerebral glutamate levels could have implications on the pathophysiology of seizures.In paper IV, cerebral perfusion and edema were assessed with magnetic resonance imaging using intravoxel incoherent motion technique. A reduced perfusion fraction was found in a part of the basal ganglia in women with preeclampsia. No difference in edema was detected.Our findings indicate Mg2+ metabolism, plasma hypoosmolality and possibly cerebral hypoperfusion to be involved in the pathophysiology of cerebral affection in preeclampsia.
  •  
50.
  • Nelander, Maria, et al. (author)
  • Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older : a cohort study
  • 2016
  • In: BMJ Open. - : BMJ. - 2044-6055. ; 6:1
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population.DESIGN: Cohort study.SETTING: Sweden.POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion.METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking.MAIN OUTCOME MEASURES: Dementia, CVD, stroke.RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81).CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population.
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Sundström Poromaa, I ... (8)
Naessén, Tord (8)
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Wikström, Johan, 196 ... (7)
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Hagberg, Henrik, 195 ... (7)
Högberg, Ulf, 1949- (7)
Wennerholm, Ulla-Bri ... (7)
Fadl, Helena, 1965- (7)
Saltvedt, Sissel (7)
Wennerholm, Ulla-Bri ... (7)
Lager, Susanne (7)
Hastie, Roxanne (7)
Åkerud, Helena, 1972 ... (7)
Lundgren, Maria (6)
Berntorp, Kerstin (6)
Larsson, Marita (6)
Christersson, Christ ... (6)
Strevens, Helena (6)
Bergman, Eva, 1959- (6)
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Simmons, David, 1959 ... (6)
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