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Hypertensive disorders of pregnancy (HDP), especially preeclampsia, and diabetes during pregnancy pose significant risks for both maternal and infant health, extending to long-term outcomes such as early-onset cardiovascular disease and metabolic disorders. Current strategies for managing HDP focus on screening, prevention, surveillance, and timely intervention. No disease-modifying therapies exist so far for established preeclampsia; delivery remains the definitive resolution. Preventive measures-including early pregnancy screening, exercise, and low-dose aspirin-show promise. Antihypertensive treatments reduce severe hypertension risks, whereas magnesium sulfate remains the standard for preventing eclampsia. Planned delivery from gestational week 37 can balance maternal benefits and neonatal risks in women with established preeclampsia. Delivery between 34 and 37 weeks gestation in women with preeclampsia has to balance risks for mother and infant. Lifestyle interventions-particularly diet and physical activity-are pivotal in managing gestational diabetes mellitus and type 2 diabetes. The oral antidiabetic metformin has shown benefits in glycaemic control and reducing maternal weight gain, although its long-term effects on offspring remain uncertain. The safety of other peroral antidiabetics in pregnancy is less studied. Advancements in glucose monitoring and insulin administration present encouraging prospects for enhancing outcomes in women with diabetes types 1 and 2. Both HDP and diabetes during pregnancy necessitate vigilant management through a combination of lifestyle modifications, pharmacological interventions, and timely obstetric care. Although certain treatments such as low-dose aspirin and metformin show efficacy in risk reduction, further research is ongoing to ensure safety for both mothers and their offspring to reduce short- and long-term adverse effects.
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Antihipertensivos , Diabetes Gestacional , Hipoglucemiantes , Humanos , Embarazo , Femenino , Diabetes Gestacional/prevención & control , Hipoglucemiantes/uso terapéutico , Antihipertensivos/uso terapéutico , Recién Nacido , Hipertensión Inducida en el Embarazo/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Metformina/uso terapéuticoRESUMEN
OBJECTIVE: Simultaneous activation of ß2- and ß3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of ß1-ARs - and thus inducing cardiovascular complications - are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel ß2-and ß3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models. METHODS: In the developmental phase, we assessed the impact of ATR-127's on cAMP accumulation in relation to the non-selective ß-AR agonist isoprenaline across various rodent ß-AR subtypes, including neonatal rat cardiomyocytes. Following these experiments, L6 muscle cells were stimulated with ATR-127 to assess the impact on GLUT4-mediated glucose uptake and intramyocellular cAMP accumulation. Additionally, in vitro, and in vivo assessments are conducted to measure ATR-127's effects on BAT glucose uptake and thermogenesis. Finally, diet-induced obese mice were treated with 5 mg/kg ATR-127 for 21 days to investigate the effects on glucose homeostasis, body weight, fat mass, skeletal muscle glucose uptake, BAT thermogenesis and hepatic steatosis. RESULTS: Exposure of L6 muscle cells to ATR-127 robustly enhanced GLUT4-mediated glucose uptake despite low intramyocellular cAMP accumulation. Similarly, ATR-127 markedly increased BAT glucose uptake and thermogenesis both in vitro and in vivo. Prolonged treatment of diet-induced obese mice with ATR-127 dramatically improved glucose homeostasis, an effect accompanied by decreases in body weight and fat mass. These effects were paralleled by an enhanced skeletal muscle glucose uptake, BAT thermogenesis, and improvements in hepatic steatosis. CONCLUSIONS: Our results demonstrate that ATR-127 is a highly effective, novel ß2- and ß3-ARs agonist holding great therapeutic promise for the treatment of obesity and its comorbidities, whilst potentially limiting cardiovascular complications. As such, the therapeutic effects of ATR-127 should be investigated in more detail in clinical studies.
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Tejido Adiposo Pardo , Ratones Endogámicos C57BL , Músculo Esquelético , Animales , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Ratones , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Masculino , Ratas , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Hígado Graso/metabolismo , Hígado Graso/tratamiento farmacológico , Termogénesis/efectos de los fármacos , Agonistas Adrenérgicos/farmacologíaRESUMEN
OBJECTIVE: To investigate the effect of vacuum extraction (VE) or caesarean section (CS), compared with expectant management, on pelvic floor dysfunction (PFD) 1-2 years postpartum in primiparous women with a prolonged second stage of labour. DESIGN: A population-based questionnaire and cohort study. SETTING: Stockholm, Sweden. POPULATION: A cohort of 1302 primiparous women with a second stage duration of ≥3 h, delivering from December 2017 to November 2018. METHODS: The 1-year follow-up questionnaire from the Swedish National Perineal Laceration Register was distributed 12-24 months postpartum. Exposure was VE or CS at 3-4 h or 4-5 h, compared with expectant management. MAIN OUTCOME MEASURES: Pelvic floor dysfunction was defined as at least weekly symptoms of urinary incontinence, pelvic organ prolapse or a Wexner score of ≥4. The risk of PFD was calculated using Poisson regression with robust variance estimation, presented as crude and adjusted relative risks (RRs and aRRs) with 95% confidence intervals (95% CIs). The implication of obstetric anal sphincter injury (OASI) on pelvic floor disorders was investigated through mediation analysis. RESULTS: In total, 35.1% of women reported PFD. Compared with expectant management, the risk of PFD was increased after VE at 3-4 h (aRR 1.33, 95% CI 1.06-1.65) and 4-5 h (aRR 1.34, 95% CI 1.05-1.70), but remained unchanged after CS. The increased risk after VE was not mediated by OASI. CONCLUSIONS: Pelvic floor dysfunction was common in primiparous women after a prolonged second stage, and the risk of PFD increased after VE but was unaffected by CS, compared with expectant management. If a spontaneous vaginal delivery eventually occurred, allowing an extended duration of labour did not increase the risk of PFD.
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Cesárea , Segundo Periodo del Trabajo de Parto , Trastornos del Suelo Pélvico , Extracción Obstétrica por Aspiración , Espera Vigilante , Humanos , Femenino , Embarazo , Adulto , Trastornos del Suelo Pélvico/etiología , Trastornos del Suelo Pélvico/epidemiología , Trastornos del Suelo Pélvico/terapia , Suecia/epidemiología , Extracción Obstétrica por Aspiración/efectos adversos , Extracción Obstétrica por Aspiración/estadística & datos numéricos , Encuestas y Cuestionarios , Cesárea/estadística & datos numéricos , Cesárea/efectos adversos , Estudios de Cohortes , Complicaciones del Trabajo de Parto/epidemiología , Complicaciones del Trabajo de Parto/etiología , Prolapso de Órgano Pélvico/epidemiología , Prolapso de Órgano Pélvico/terapia , Prolapso de Órgano Pélvico/etiología , Incontinencia Urinaria/etiología , Incontinencia Urinaria/epidemiologíaRESUMEN
OBJECTIVE: To investigate the risk of recurrent maternal red-cell transfusion in delivery. DESIGN: Nationwide long-standing retrospective cohort study. SETTING: Swedish medical birth register. POPULATION: All registered births from 2000 to 2017 in Sweden. METHODS: We included all women with between one and three consecutive registered births from 22 weeks of gestation onwards and all maternal red-cell transfusions in the peripartum period within the defined period of study. Information on gestational and non-gestational comorbidity was collected and we identified any female siblings. In our analyses we compared the risk of red-cell transfusion in delivery in relation to transfusion history and gestational and non-gestational comorbidity. MAIN OUTCOME MEASURES: Maternal peripartum red-cell transfusion, defined as a recorded transfusion in the period from 1 day before and 7 days after delivery. RESULTS: We included 825 451 women with a total 1 419 909 deliveries, including 786 097 (55.4%) first, 511 398 (36.0%) second and 122 414 (8.6%) third deliveries. Of women with previous obestric transfusion, 8.7% were transfused in a second delivery, compared with 1.7% of women without transfusion or diagnosis of haemorrhage. A previous diagnosis of haemorrhage did not affect the odds ratio of transfusion recurrence. Among women who were transfused in their first two deliveries, 15.5% were transfused in third delivery, corresponding to an 11-fold increase, compared with non-transfused women (adjusted odds ratio aOR 11.5, 95% CI 7.9-16.6). Women with a sister transfused in delivery were at increased risk of transfusion in a second delivery (aOR 1.8, 95% CI 1.6-2.1). CONCLUSIONS: Women with previous red-cell transfusion are at an increased risk of red-cell transfusion in a subsequent delivery, compared with women without a history of red-cell transfusion.
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Transfusión de Eritrocitos , Hemorragia , Femenino , Humanos , Estudios Longitudinales , Estudios Retrospectivos , Transfusión de Eritrocitos/efectos adversos , Transfusión Sanguínea , Factores de RiesgoRESUMEN
OBJECTIVE: To quantify temporal trends and regional variation in severe maternal morbidity (SMM) in Sweden. DESIGN: Cohort study. POPULATION: Live birth and stillbirth deliveries in Sweden, 1999-2019. METHODS: Types and subtypes of SMM were identified, based on a standard list (modified for Swedish clinical setting after considering the frequency and validity of each indicator) using diagnoses and procedure codes, among all deliveries at ≥22 weeks of gestation (including complications within 42 days of delivery). Contrasts between regions were quantified using rate ratios (RRs) and 95% confidence intervals (95% CIs). Temporal changes in SMM types and subtypes were described. MAIN OUTCOME MEASURES: Types and subtypes of SMM. RESULTS: There were 59 789 SMM cases among 2 212 576 deliveries, corresponding to 270.2 (95% CI 268.1-272.4) per 10 000 deliveries. Composite SMM rates increased from 236.6 per 10 000 deliveries in 1999 to 307.3 per 10 000 deliveries in 2006, before declining to 253.8 per 10 000 deliveries in 2019. Changes in composite SMM corresponded with temporal changes in severe haemorrhage rates, which increased from 94.9 per 10 000 deliveries in 1999 to 169.3 per 10 000 deliveries in 2006, before declining to 111.2 per 10 000 deliveries in 2019. Severe pre-eclampsia, eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome (103.8 per 10 000 deliveries), severe haemorrhage (133.7 per 10 000 deliveries), sepsis, embolism, disseminated intravascular coagulation, shock and severe mental health disorders were the most common SMM types. Rates of embolism, disseminated intravascular coagulation and shock, acute renal failure, cardiac complications, sepsis and assisted ventilation increased, whereas rates of surgical complications, severe uterine rupture and anaesthesia complications declined. CONCLUSIONS: The observed spatiotemporal variations in composite SMM and SMM types provide substantive insights and highlight regional priorities for improving maternal health.
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Coagulación Intravascular Diseminada , Embolia , Complicaciones del Embarazo , Sepsis , Embarazo , Femenino , Humanos , Estudios de Cohortes , Sepsis/epidemiología , Sepsis/etiología , Hemorragia , Morbilidad , Complicaciones del Embarazo/epidemiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: The impact of first stage labour duration on maternal outcomes is sparsely investigated. We aimed to study the association between a longer active first stage and maternal complications in the early postpartum period. DESIGN: A population-based cohort study. SETTING: Regions of Stockholm and Gotland, Sweden, 2008-2020. POPULATION: A cohort of 159 459 term, singleton, vertex pregnancies, stratified by parity groups. METHODS: The exposure was active first stage duration, categorised in percentiles. Poisson regression analysis was performed to estimate the adjusted relative risk (aRR) and the 95% confidence interval (95% CI). To investigate the effect of second stage duration on the outcome, mediation analysis was performed. MAIN OUTCOME MEASURES: Severe perineal lacerations (third or fourth degree), postpartum infection, urinary retention and haematoma in the birth canal or ruptured sutures. RESULTS: The risks of severe perineal laceration, postpartum infection and urinary retention increased with a longer active first stage, both overall and stratified by parity group. The aRR increased with a longer active first stage, using duration of <50th percentile as the reference. In the ≥90th percentile category, the aRR for postpartum infection was 1.64 (95% CI 1.46-1.84) in primiparous women, 2.43 (95% CI 1.98-2.98) in parous women with no previous caesarean delivery (CD) and 2.33 (95% CI 1.65-3.28) in parous women with a previous CD. The proportion mediated by second stage duration was 33.4% to 36.9% for the different outcomes in primiparous women. The risk of haematoma or ruptured sutures did not increased with a longer active first stage. CONCLUSIONS: Increasing active first stage duration is associated with maternal complications in the early postpartum period.
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Laceraciones , Infección Puerperal , Retención Urinaria , Embarazo , Femenino , Humanos , Laceraciones/epidemiología , Laceraciones/etiología , Parto Obstétrico/efectos adversos , Estudios de Cohortes , Retención Urinaria/epidemiología , Retención Urinaria/etiología , Periodo Posparto , Perineo/lesiones , Hematoma/complicacionesRESUMEN
ß2-Adrenergic receptor (ß2AR) agonists have been reported to stimulate glucose uptake (GU) by skeletal muscle cells and are therefore highly interesting as a possible treatment for type 2 diabetes (T2D). The chirality of compounds often has a great impact on the activity of ß2AR agonists, although this has thus far not been investigated for GU. Here we report the GU for a selection of synthesized acyclic and cyclic ß-hydroxy-3-fluorophenethylamines. For the N-butyl and the N-(2-pentyl) compounds, the (R) and (R,R) (3d and 7e) stereoisomers induced the highest GU. When the compounds contained a saturated nitrogen containing 4- to 7-membered heterocycle, the (R,R,R) enantiomer of the azetidine (8a) and the pyrrolidine (9a) had the highest activity. Altogether, these results provide pivotal information for designing novel ß2AR agonist for the treatment of T2D.
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Agonistas de Receptores Adrenérgicos beta 2 , Diabetes Mellitus Tipo 2 , Humanos , Agonistas Adrenérgicos , Agonistas de Receptores Adrenérgicos beta 2/química , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/farmacología , Aminas , Transporte Biológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa , Receptores Adrenérgicos beta 2/metabolismoRESUMEN
BACKGROUND: We aimed to investigate the associations of pre-existing maternal cardiovascular disease (CVD) with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) in offspring. METHODS: This population-based cohort study included singletons live-born without major malformations in Sweden (n = 2â699â675) and British Columbia (BC), Canada (n = 887â582) during 1990-2019, with follow-up from age 1 year until the outcome, death, emigration or December 2020, whichever came first. The primary exposure was defined as a composite CVD diagnosed prior to conception: cerebrovascular disease, arrhythmia, heart failure, valvular and congenital heart diseases. The incidences of ADHD, ASD and ID, comparing offspring of mothers with versus without CVD, were calculated as adjusted hazard ratios (aHRs). These results were compared with models using paternal CVD as negative control exposure. RESULTS: Compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD [95% confidence interval (CI): 1.10-1.20] and ASD (95% CI 1.07-1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (HR 1.31, 95% CI 1.02-1.61), cerebrovascular disease (HR 1.20, 95% CI 1.08-1.32), congenital heart disease (HR 1.18, 95% CI 1.08-1.27), arrhythmia (HR 1.13, 95% CI 1.08-1.19) and valvular heart disease (HR 1.12, 95% CI 1.00-1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (HR 1.25, 95% CI 1.04-1.46), congenital heart disease (HR 1.17, 95% CI 1.01-1.33) and arrythmia (HR 1.12, 95% CI 1.01-1.21). Paternal CVD did not show associations with ADHD, ASD or ID, except for cerebrovascular disease which showed associations with ADHD and ASD. CONCLUSIONS: In this large cohort study, pre-existing maternal CVD was associated with increased risk of ADHD and ASD in offspring.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Enfermedades Cardiovasculares , Trastornos Cerebrovasculares , Cardiopatías Congénitas , Insuficiencia Cardíaca , Trastornos del Neurodesarrollo , Efectos Tardíos de la Exposición Prenatal , Masculino , Femenino , Humanos , Lactante , Estudios de Cohortes , Trastorno del Espectro Autista/epidemiología , Colombia Británica/epidemiología , Enfermedades Cardiovasculares/epidemiología , Suecia/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Cardiopatías Congénitas/epidemiología , Arritmias Cardíacas/complicaciones , Trastornos Cerebrovasculares/epidemiología , Trastornos Cerebrovasculares/complicaciones , Efectos Tardíos de la Exposición Prenatal/epidemiología , Trastornos del Neurodesarrollo/epidemiologíaRESUMEN
Background: Severe perineal lacerations (SPLs), common worldwide, are associated with short- and long-term complications: pelvic floor disorders, fecal incontinence, fistula, and profound psychological impacts. Limited research suggests that experiencing SPL may influence future reproductive intentions, but research on outcomes is lacking. Methods: We analyzed the effect of experiencing SPL during a first delivery among a large cohort of Swedish births between 1992 and 2013. We used linear and multinomial logistic regression to estimate the associations between SPL and four reproductive outcomes: subsequent total birth number, probability of a second birth, interpregnancy interval (IPI), and subsequent scheduled cesarean birth. Results: Among 947,035 singleton live-born first-births, we found that experiencing SPL was associated with slightly fewer overall births in fully adjusted models (a decrease of -0.020 births; 95% confidence interval [CI]: -0.028 to -0.012), but no difference in the probability of a second birth (risk ratio [RR]: 1.00; 95% CI: 0.99 to 1.00) or IPI. Scheduled cesarean was increased in births after SPL (adjusted RR: 4.57; 95% CI: 4.42 to 4.73). A secondary comparison of SPL to severe postpartum hemorrhage suggests that some of these observed differences may be related to experiencing any severe outcome, and some specifically to perineum disruption. Conclusion: This study provides a deeper understanding of the long-term impacts of SPL, which may be useful in informing best clinical practices for supporting women who have experienced SPL.
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The nationwide Swedish Medical Birth Register (MBR) includes more than 98% of all births in Sweden since 1973. The MBR is updated annually, and is based on information from antenatal, obstetric, and neonatal records. Maternal information includes self-reported medical history, socio-demographic factors, smoking and snuff use, medication use, height and measured weight. Birth and neonatal/postpartal data include birth date, mode of delivery, singleton or multiple birth, gestational age, stillbirth, birth weight, birth length, head circumference, infant sex, Apgar scores, and maternal and infant diagnoses/procedures. The overall quality of the MBR is very high, partly due to the semi-automated data extraction from the standardized regional electronic health records. The MBR can be linked to other health registers through the unique personal identity numbers of mothers and live-born offspring. More than 1000 scientific publications have used MBR as a data source.
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Madres , Nacimiento Prematuro , Recién Nacido , Embarazo , Humanos , Femenino , Suecia/epidemiología , Peso al Nacer , Fumar , Edad GestacionalRESUMEN
Prior evidence evaluating the benefits and harms of expectant labour duration during active first stage is inconclusive regarding potential consequences for the neonate. Population-based cohort study in Stockholm-Gotland region, Sweden, including 46,040 women (Robson 1), between October 1st, 2008 and June 15th, 2020. Modified Poisson regression was used for the association between active first stage of labour duration and adverse neonatal outcomes. 94.2% experienced a delivery with normal neonatal outcomes. Absolute risk for severe outcomes increased from 1.9 to 3.0%, moderate outcomes increased from 2.8 to 6.2% (> 10.1 h). Compared to the reference, (< 5.1 h; median), the adjusted relative risk (aRR) of severe neonatal outcome significantly increased beyond 10.1 h (> 90th percentile) (aRR 1.53, 95% CI 1.26, 1.87), for moderate neonatal outcome the aRR began to slowly increase beyond 5.1 h (≥ 50 percentile; aRR 1.40, 95% CI 1.24, 1.58). Mediation analysis indicate that most of the association was due to a longer active first stage of labour, 13% (severe neonatal outcomes) and 20% (moderate neonatal outcomes) of the risk was mediated (indirect effect) by longer second stage of labour duration. We report an association between increasing active first stage duration and increased risk of adverse neonatal outcomes. We did not observe a clear labour duration risk threshold.
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Trabajo de Parto , Humanos , Femenino , Recién Nacido , Resultado del Embarazo , Factores de Tiempo , Factores de Riesgo , Adulto Joven , Adulto , SueciaRESUMEN
BACKGROUND: Acute pancreatitis in pregnancy (APIP) is a rare but potentially life-threatening condition, affecting women at any gestation. The aim of this review is to investigate the demographics, etiology, management, and outcomes of pancreatitis in pregnant women in a major tertiary hospital in Queensland. METHODS: Data was collected from the hospital medical records of all patients diagnosed with APIP from 01/01/2012 until 30/04/2021 at the Mater Hospital, Brisbane. Descriptive statistical measures were employed. Spearman's rank correlation was used to challenge different risk factors for readmission. RESULTS: 26 patients met the inclusion criteria, with 38 admissions during the study period. Biliary pancreatitis was the most common etiology (n = 14, 53.8%). 42.5% of admissions were managed operatively (n = 15). 38.5% of patients had more than one admission (n = 10). Undergoing a laparoscopic cholecystectomy on index admission correlated with a significantly lower chance of repeat admission (rs= -.48, p = .013, CI = - .737 to -.102). CONCLUSION: This is the first study of this condition in an Australian institution. It demonstrates that in patients with acute biliary pancreatitis, operative management can be safely employed at any trimester and laparoscopic cholecystectomies should be performed in the index admission to reduce the risk of readmission to hospital.
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Objective: To study the association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy. Design: Prospective, population based cohort study. Setting: All singleton pregnancies after 22 completed gestational weeks registered in the Swedish Pregnancy Register and the Medical Birth Registry of Norway, from 1 March 2020 to 24 May 2022. Participants: 312 456 individuals available for analysis (201 770 in Sweden and 110 686 in Norway), with pregnancies that reached 42 completed gestational weeks by the end of follow-up in the pregnancy registries, excluding individuals with SARS-CoV-2 infection before pregnancy and those with a diagnosis of pre-existing hypertension or onset of hypertension before 20 gestational weeks. Main outcome measures: Newly diagnosed hypertension during pregnancy was defined as a composite outcome of a diagnosis of gestational hypertension, pre-eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, or eclampsia, from gestational week 20 to one week after delivery. The association between SARS-CoV-2 infection and hypertension during pregnancy was investigated with a stratified Cox proportional hazard model, adjusting for maternal age, body mass index, parity, smoking, region of birth, education, income, coexisting medical conditions, previous hypertension during pregnancy, number of healthcare visits during the past year, and vaccination against SARS-CoV-2. Pre-eclampsia was also analysed as a separate outcome. Results: Of 312 456 individuals available for analysis, 8% (n=24 566) had SARS-CoV-2 infection any time during pregnancy, 6% (n=18 051) had a diagnosis of hypertension during pregnancy, and 3% (9899) had pre-eclampsia. SARS-CoV-2 infection during pregnancy was not associated with an increased risk of hypertension during pregnancy (adjusted hazard ratio 0.99, 95% confidence interval 0.93 to 1.04) or pre-eclampsia (0.98, 0.87 to 1.10). The results were similar for SARS-CoV-2 infection in all gestational trimesters and in different time periods that corresponded to dominance of different variants of the SARS-CoV-2 virus. Conclusions: This population based study did not find any evidence of an association between SARS-CoV-2 infection during pregnancy and an increased risk of hypertension during pregnancy or pre-eclampsia.
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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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Preeclampsia , Proteínas Gestacionales , Femenino , Humanos , Embarazo , Biomarcadores , Inmunoensayo , Factor de Crecimiento Placentario , Preeclampsia/diagnóstico , Primer Trimestre del Embarazo , Suecia , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Physical activity is a useful means to improve symptoms and memory performance to some extent in individuals with stress-induced exhaustion disorder. Individuals in this group commonly do not need to reach the recommended levels of physical activity. Developing methods to support physical activity as a lasting behaviour is important. OBJECTIVE: The aim of the study was to explore the processes involved when using physical activity prescription as part of rehabilitation in a group context for individuals with stress-induced exhaustion disorder. METHOD: A total of 27 individuals with stress-induced exhaustion disorder participated in six focus groups. The informants underwent a multimodal intervention including prescription of physical activity. The physical activity prescription had a cognitive behaviour approach and included information about physical activity, home assignments and goal setting. The data was analysed with grounded theory method using constant comparison. RESULTS: The analysis of the data was developed into the core category 'trying to integrate physical activity into daily life in a sustainable way', and three categories: 'acceptance of being good enough', 'learning physical activity by doing' and 'advocation for physical activity in rehabilitation'. The informants identified that during the physical activity prescription sessions they learned what physical activity was, what was 'good enough' in terms of dose and intensity of physical activity, and how to listen to the body's signals. These insights, in combination with performing physical activity during home assignments and reflecting with peers, helped them incorporate physical activity in a new and sustainable way. A need for more customised physical activity with the ability to adjust to individual circumstances was requested. CONCLUSION: Prescription of physical activity in a group context may be a useful method of managing and adjusting physical activity in a sustainable way for individuals with stress-induced exhaustion disorder. However, identifying people who need more tailored support is important.
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Terapia Cognitivo-Conductual , Pacientes , Humanos , Ejercicio Físico , Grupos Focales , PrescripcionesRESUMEN
'Doing science together' collaborations are a more intense form of university-industry interactions and are characterized by a mutual involvement and active participation of academic and company scientists in scientific research. Here, we examine the successful approach that AstraZeneca and its internationally renowned academic partners, Karolinska Institutet and Uppsala University, implemented to fully unlock the potential of all parties in long-term, explorative, truly collaborative research programs. The underlying premises of these successful research programs are three collaborative governance mechanisms (3MCs) that are required that leverage the strengths of each organization: mutual collaboration; mutually beneficial science; and a mutual governance model with senior management involvement.
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Industrias , Humanos , UniversidadesRESUMEN
BACKGROUND: Although adverse pregnancy outcomes are associated with an increased risk of cardiovascular disease, studies on timing and subtypes of heart failure after a hypertensive pregnancy are lacking. OBJECTIVES: The goal of this study was to assess the association between pregnancy-induced hypertensive disorder and risk of heart failure, according to ischemic and nonischemic subtypes, and the impact of disease characteristics and the timing of heart failure risks. METHODS: This was a population-based matched cohort study, comprising all primiparous women without a history of cardiovascular disease included in the Swedish Medical Birth Register between 1988 and 2019. Women with pregnancy-induced hypertensive disorder were matched with women with normotensive pregnancies. Through linkage with health care registers, all women were followed up for incident heart failure, classified as ischemic or nonischemic. RESULTS: In total, 79,334 women with pregnancy-induced hypertensive disorder were matched with 396,531 women with normotensive pregnancies. During a median follow-up of 13 years, rates of all heart failure subtypes were more common among women with pregnancy-induced hypertensive disorder. Compared with women with normotensive pregnancies, adjusted HRs (aHRs) with 95% CIs were as follows: heart failure overall, aHR: 1.70 (95% CI: 1.51-1.91); ischemic heart failure, aHR: 2.28 (95% CI: 1.74-2.98); and nonischemic heart failure, aHR: 1.60 (95% CI: 1.40-1.83). Disease characteristics indicating severe hypertensive disorder were associated with higher heart failure rates, and rates were highest within the first years after the hypertensive pregnancy but remained significantly increased thereafter. CONCLUSIONS: Pregnancy-induced hypertensive disorder is associated with an increased short-term and long-term risk of incident ischemic and nonischemic heart failure. Disease characteristics indicating more severe forms of pregnancy-induced hypertensive disorder amplify the heart failure risks.
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Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Hipertensión Inducida en el Embarazo , Embarazo , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Insuficiencia Cardíaca/epidemiología , Estudios de Cohortes , Suecia/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Little is known about the latent phase of labor, including whether its duration influences subsequent labor processes or birth outcomes. OBJECTIVE: This study aimed to describe the duration of the latent phase of labor from self-report of the onset of painful contractions to a cervical dilation of 5 cm in a large, Swedish population and evaluate the association between the duration of the latent phase of labor and perinatal processes and outcomes that occurred during the active phase of labor, second stage of labor, birth and immediately after delivery, stratified by parity. STUDY DESIGN: This was a population-based cohort study of 67,267 pregnancies with deliveries between 2008 and 2020 in the Stockholm-Gotland Regions, Sweden. Nulliparous and parous women without a history of cesarean delivery in spontaneous labor with a term (≥37 weeks of gestation), singleton, live, and vertex fetus without major malformations were included. Imputation was used if the notation of the end of the latent phase of labor (ie, cervical dilation of 5 cm) was missing in the partograph. Multivariable logistic regression was used to estimate the association with adjusted odds ratios and 95% confidence intervals, controlling for potential covariates. RESULTS: Including the time from painful contraction onset to a cervical dilation of 5 cm, the median durations of the latent phase of labor were 16.0 (interquartile range, 10.0-26.6) hours for nulliparous women and 9.4 (interquartile range, 5.9-15.3) hours for multiparous women. The durations of the latent phase of labor beyond the median were associated with increased odds of labor dystocia diagnosis during the first stage active phase or second stage of labor and interventions commonly associated with dystocia (amniotomy, oxytocin augmentation, epidural, and cesarean delivery). The duration of the latent phase of labor of ≥90th percentile vs less than the median in nulliparous women demonstrated an increased risk of adverse neonatal outcomes (Apgar score of <7 at 5 minutes and neonatal intensive care unit admission), chorioamnionitis, and fetal occiput posterior. In multiparous women, longer duration of the latent phase of labor was associated with an increased risk of neonatal intensive care unit admission and chorioamnionitis but was not associated with an Apgar score of <7 at 5 minutes. The duration of the latent phase of labor was not associated with additional markers of maternal risk. CONCLUSION: The duration of the latent phase of labor in nulliparous women was longer than that of multiparous women at each point of distribution. A longer duration of the latent phase of labor was associated with more frequent dystocia diagnoses and related interventions during the first stage active phase or second stage of labor, including cesarean delivery, nulliparous fetal occiput posterior position, chorioamnionitis, and markers of neonatal morbidity. More research is needed to identify potential mediating paths between the duration of the latent phase of labor and neonatal morbidity.
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Corioamnionitis , Distocia , Recién Nacido , Embarazo , Femenino , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Paridad , Distocia/epidemiología , Presentación en Trabajo de PartoRESUMEN
Importance: Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown. Objective: To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening. Design, Setting, and Participants: Cross-sectional study of a population-based cohort of women in Sweden (n = 10â¯528) 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. Exposures: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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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Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria , Complicaciones del Embarazo , Resultado del Embarazo , Anciano , Femenino , Humanos , Persona de Mediana Edad , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/epidemiología , Constricción Patológica/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Transversales , Diabetes Gestacional/epidemiología , Hipertensión Inducida en el Embarazo/epidemiología , Preeclampsia/epidemiología , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Factores de Riesgo , Suecia/epidemiología , Complicaciones del Embarazo/epidemiologíaRESUMEN
Pregnancy-related factors are important for short- and long-term health in mothers and offspring. The nationwide population-based Swedish Medical Birth Register (MBR) was established in 1973. The present study describes the content and quality of the MBR, using original MBR data, Swedish-language and international publications based on the MBR.The MBR includes around 98% of all births in Sweden. From 1982 onwards, the MBR is based on prospectively recorded information in standardized antenatal, obstetric, and neonatal records. When the mother and infant are discharged from hospital, this information is forwarded to the MBR, which is updated annually. Maternal data include information from first antenatal visit on self-reported obstetric history, infertility, diseases, medication use, cohabitation status, smoking and snuff use, self-reported height and measured weight, allowing calculation of body mass index. Birth and neonatal data include date and time of birth, mode of delivery, singleton or multiple birth, gestational age, stillbirth, birth weight, birth length, head circumference, infant sex, Apgar scores, and maternal and infant diagnoses/procedures, including neonatal care. The overall quality of the MBR is very high, owing to the semi-automated data extraction from the standardized regional electronic health records, Sweden's universal access to antenatal care, and the possibility to compare mothers and offspring to the Total Population Register in order to identify missing records. Through the unique personal identity numbers of mothers and live-born offspring, the MBR can be linked to other health registers. The Swedish MBR contains high-quality pregnancy-related information on more than 5 million births during five decades.