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This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.
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Nascimento Prematuro , Progesterona , Progestinas , Humanos , Nascimento Prematuro/prevenção & controle , Gravidez , Progesterona/administração & dosagem , Progesterona/uso terapêutico , Feminino , Progestinas/administração & dosagem , Progestinas/uso terapêutico , Administração Intravaginal , Fatores de Risco , Medida do Comprimento Cervical , Colo do ÚteroRESUMO
Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes1. Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation have resulted in similar clinical outcomes, as demonstrated by the GIPR-GLP-1R co-agonist tirzepatide2 and AMG-133 (ref. 3) combining GIPR antagonism with GLP-1R agonism. This underlines the importance of a better understanding of the GIP system. Here we show the necessity of ß-arrestin recruitment for GIPR function, by combining in vitro pharmacological characterization of 47 GIPR variants with burden testing of clinical phenotypes and in vivo studies. Burden testing of variants with distinct ligand-binding capacity, Gs activation (cyclic adenosine monophosphate production) and ß-arrestin 2 recruitment and internalization shows that unlike variants solely impaired in Gs signalling, variants impaired in both Gs and ß-arrestin 2 recruitment contribute to lower adiposity-related traits. Endosomal Gs-mediated signalling of the variants shows a ß-arrestin dependency and genetic ablation of ß-arrestin 2 impairs cyclic adenosine monophosphate production and decreases GIP efficacy on glucose control in male mice. This study highlights a crucial impact of ß-arrestins in regulating GIPR signalling and overall preservation of biological activity that may facilitate new developments in therapeutic targeting of the GIPR system.
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Fenótipo , Receptores dos Hormônios Gastrointestinais , beta-Arrestinas , Receptores dos Hormônios Gastrointestinais/genética , Receptores dos Hormônios Gastrointestinais/metabolismo , Animais , Camundongos , Humanos , beta-Arrestinas/metabolismo , Variação Genética , beta-Arrestina 2/metabolismo , beta-Arrestina 2/genética , Transdução de Sinais , Polipeptídeo Inibidor Gástrico/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Obesidade/metabolismo , Obesidade/genética , Masculino , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/genéticaRESUMO
INTRODUCTION: Pregnancy increases the risk of periodontitis due to the increase in progesterone and estrogen. Moreover, periodontitis during pregnancy is associated with development of pregnancy and birth related complications. The aim of this study is to determine, whether periodontal treatment during pregnancy can reduce systemic inflammation and lower the risk of adverse pregnancy and birth related outcomes. METHODS AND ANALYSIS: The PROBE study is a non-randomized controlled intervention study conducted among 600 pregnant women with periodontitis. The women will be recruited among all pregnant women at two Danish hospitals in Region Zealand during their nuchal translucency scan and will subsequently be screened for periodontitis. The intervention group includes 300 pregnant women, who will be offered state-of-the-art periodontal treatment during pregnancy. The control group includes additional 300 pregnant women, who will be offered periodontal treatment after giving birth. Outcome measures include periodontal measures, inflammatory, hormonal and glycaemic markers as well as the prevalence of preterm birth risk, low birth weight and risk markers of gestational diabetes mellitus (GDM) and preeclampsia that will be collected from all screened women and further during pregnancy week 20 and pregnancy week 35 for women enrolled in the intervention. ETHICS AND DISSEMINATION: The study's findings will be published in peer reviewed journals and disseminated at national and international conferences and through social media. The PROBE study is designed to provide important new knowledge as to whether periodontal treatment during pregnancy can reduce the prevalence of complications related to pregnancy and birth. CLINICAL TRIALS REGISTRATION: The study was registered on clinicaltrials.gov (NCT06110143).
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Periodontite , Resultado da Gravidez , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Diabetes Gestacional , Recém-Nascido de Baixo Peso , Periodontite/terapia , Periodontite/complicações , Pré-Eclâmpsia/prevenção & controle , Complicações na Gravidez/prevenção & controle , Nascimento Prematuro/prevenção & controleRESUMO
INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.
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Resultado da Gravidez , Gravidez em Diabéticas , Sistema de Registros , Humanos , Gravidez , Feminino , Dinamarca/epidemiologia , Estudos Prospectivos , Gravidez em Diabéticas/epidemiologia , Resultado da Gravidez/epidemiologia , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Recém-Nascido , Adulto , Fatores de Risco , Estado Pré-Diabético/epidemiologia , Projetos de Pesquisa , Peso ao NascerRESUMO
BACKGROUND: Cervical cancer is preventable. Screening is important for early detection. However, even in high-income countries, coverage is sub-optimal. We identified socioeconomic, lifestyle and biological determinants of cervical screening coverage. METHODS: In Denmark, women aged 23-64 are free of charge personally invited to screening. All cervical cell samples are registered centrally in the Patobank. We linked data from the Lolland-Falster Health Study (LOFUS) with Patobank data. LOFUS was a population-based health survey undertaken in 2016-2020. With logistic regression, coverage defined as ≥1 cervical sample registered within a 6-year period from 2015 to 2020 was compared across levels of risk factors expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Among 13â406 women of screening aged 23-64 and invited to LOFUS, 72% had ≥1 cervical sample registered. Non-participation in LOFUS was a strong predictor of low coverage; aOR 0.32; 95% CI 0.31-0.36. Among LOFUS participants, education was a strong predictor of coverage in univariate analysis, OR 0.58; 95% CI 0.48-0.71, but this association disappeared in multi-variate analysis, aOR 0.86; 95% CI 0.66-1.10. In multi-variate analysis, predictors of low coverage were high age, living without a partner, retired, current smoker, poor self-rated health, elevated blood pressure and elevated glycated haemoglobin. CONCLUSIONS: Women with low cervical screening coverage had limited contact to healthcare, exemplified by non-participation in LOFUS, and pertinent health and social problems, exemplified by elevated blood pressure and glycated haemoglobin, poor self-rated health, and retirement already in screening age. Structural changes in screening are needed to reach non-screened women.
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Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer , Hemoglobinas Glicadas , Programas de Rastreamento , Renda , DinamarcaRESUMO
BACKGROUND AND AIMS: The diagnosis of gestational diabetes mellitus (GDM) is based exclusively on glucose measurements, which are highly influenced by pre-analytical and analytical factors. Therefore, poor agreement across laboratories may affect the prevalence of GDM. We aimed to determine the inter-laboratory bias of glucose measurements and the impact on GDM prevalence. MATERIAL AND METHODS: A prospective cohort study of women (n = 110) referred for second-trimester GDM diagnostics using a 75 g oral glucose tolerance test. Maternal glucose was assessed from venous plasma at fasting, 1 h and 2 h. Venous blood were collected in Fluoride Citrate tubes and frozen. Samples were analyzed at five central laboratories using four different automated glucose Hexokinase methods and GDM prevalence was evaluated according to WHO2013 diagnostic criteria. RESULTS: Maximum inter-laboratory bias was 0.19, 0.30 and 0.27 mmol/L in fasting, 1 h and 2 h samples, respectively. GDM prevalence ranged 30.0-41.1% across laboratories. CONCLUSION: Inter-laboratory bias for mean venous glucose was low and within desirable limits. Nonetheless, the impact on GDM prevalence was considerable, which may inappropriately affect clinical practice.
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Diabetes Gestacional , Gravidez , Feminino , Humanos , Glicemia , Glucose , Estudos Prospectivos , LaboratóriosRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) complicates up to 10% of pregnancies and is a well-known risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Little is known about possible long-term risks of other diseases. BACKGROUND: The aim was to review the literature for evidence of associations with morbidity other than T2DM and cardiovascular disease and with long-term mortality. METHODS: A systematic review based on searches in Medline, Embase, and Cochrane Library until March 31, 2021, using a broad range of keywords. We extracted study characteristics and results on associations between GDM and disease occurrence at least 10 years postpartum, excluding studies on women with diabetes prior to pregnancy or only diabetes prior to outcome. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Newcastle-Ottawa Scale was used to assess risk of bias. RESULTS: We screened 3084 titles, 81 articles were assessed full-text, and 15 included in the review. The strongest evidence for an association was for kidney diseases, particularly in Black women. We found indication of an association with liver disease, possibly restricted to women with T2DM postpartum. The association between GDM and breast cancer had been studied extensively, but in most cases based on self-reported diagnosis and with conflicting results. Only sparse and inconsistent results were found for other cancers. No study on thyroid diseases was found, and no study reported on short-term or long-term mortality in women with a history of GDM. CONCLUSION: Given the frequency of GDM, there is a need for better evidence on possible long-term health consequences, in particular, studies based on comprehensive records of diagnosis of GDM and long-term health outcomes.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Feminino , Seguimentos , Humanos , Morbidade , GravidezRESUMO
PURPOSE: To test a non-pharmacological silicone patch for treatment of symptomatic hemorrhoids with focus on usability, safety, and self-reported short-term effect. METHODS: Puerperal women in a Danish maternity ward were cluster randomized to treatment with the HEMOCIN® patch (intervention) or no systematic treatment (control group). On inclusion and after 2 weeks, they completed a questionnaire regarding history and hemorrhoid symptoms scored from 0 to 10. Women in the intervention group also reported on the usability of the patch and any side effects. RESULTS: We included 31 women in the intervention group and 33 in the control group. Twenty-eight (90.3%) women in the intervention group and 27 (81.8%) women in the control group responded to follow-up. Except from a difference in the severity of swelling at inclusion, there were no differences between the two groups for any symptoms, neither at inclusion, nor at follow-up, or in the change of symptoms during the two weeks (p > 0.05). Twenty-three women (85.2%) in the control group used medical treatment vs. one woman in the intervention group. The patch was used on an average of 9.3 days, 15.5 h/day and for 7.1 h before changing the patch. No severe side effects were reported. CONCLUSION: This pilot study finds that the HEMOCIN® patch is a safe and feasible treatment option for hemorrhoids. However, we did not detect any significant effect on hemorrhoid symptoms. The patch could be an option for people who seek non-pharmacological treatment for symptomatic hemorrhoids or need long-term treatment without steroid side effects.
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Hemorroidas , Feminino , Hemorroidas/tratamento farmacológico , Humanos , Projetos Piloto , Gravidez , Silicones , Inquéritos e QuestionáriosRESUMO
Background: Offspring of mothers with gestational diabetes mellitus (GDM) have increased risk of developing metabolic disorders as they grow up. Microbial colonization of the newborn gut and environmental exposures affecting the configuration of the gut microbiota during infancy have been linked to increased risk of developing disease during childhood and adulthood. In a convenience sample, we examined whether the intestinal tract of children born to mothers with GDM is differentially colonized in early life compared to offspring of mothers with normal gestational glucose regulation. Secondly, we examined whether any such difference persists during infancy, thus potentially conferring increased risk of developing metabolic disease later in life. Methods: Fecal samples were collected from children of mothers with (n = 43) and without GDM (n = 82) during the first week of life and again at an average age of 9 months. The gut microbiota was characterized by 16S rRNA gene amplicon sequencing (V1-V2). Differences in diversity and composition according to maternal GDM status were assessed, addressing potential confounding by mode of delivery, perinatal antibiotics treatment, feeding and infant sex. Results: Children of mothers with GDM were featured by a differential composition of the gut microbiota, both during the first week of life and at 9 months, at higher taxonomic and OTU levels. Sixteen and 15 OTUs were differentially abundant after correction for multiple testing during the first week of life and at 9 months, respectively. Two OTUs remained differentially abundant after adjustment for potential confounders both during the first week of life and at 9 months. Richness (OTU) was decreased in neonates born to mothers with GDM; however, at 9 months no difference in richness was observed. There was no difference in Shannon's diversity or Pielou's evenness at any timepoint. Longitudinally, we detected differential changes in the gut microbiota composition from birth to infancy according to GDM status. Conclusion: Differences in glycaemic regulation in late pregnancy is linked with relatively modest variation in the gut microbiota composition of the offspring during the first week of life and 9 months after birth.
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Diabetes Gestacional , Microbioma Gastrointestinal , Adulto , Glicemia , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Mães , Gravidez , RNA Ribossômico 16S/genéticaRESUMO
Untreated hypoglycaemia in newborns may result in permanent cognitive damage, why early diagnosis and treatment is important. This case report describes a newborn girl, who developed hypoglycaemia, when she was two hours old despite early feeding. The father of the child had maturity-onset diabetes of the young Type 1, which is caused by an autosomal dominant inherited mutation in the HNF4A gene. Due to this, early blood glucose measurements were performed. The child was treated with extra feeding and recovered without any consequences. A later gene test showed, that the child was carrier of the mutation.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Glicemia , Criança , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Feminino , Fator 4 Nuclear de Hepatócito/genética , Humanos , Hipoglicemia/etiologia , Hipoglicemia/genética , Recém-Nascido , Mutação , Período Pós-PartoRESUMO
INTRODUCTION: In pregnancy after Roux-en-Y gastric bypass (RYGB), there is increased risk of low birthweight in the offspring. The present study examined how offspring body composition was affected by RYGB. MATERIAL AND METHODS: Mother-newborn dyads, where the mothers had undergone RYGB were included. Main outcome measure was neonatal body composition. Neonatal body composition was assessed by dual-energy X-ray absorptiometry scanning (DXA) within 48 hours after birth. In a statistical model offspring born after RYGB were compared with a reference material of offspring and analyses were made to estimate the effect of maternal pre-pregnancy body mass index (BMI), gestational weight gain, parity, gestational age at birth and newborn sex on newborn body composition. Analyses were made to estimate the impact of maternal weight loss before pregnancy and of other effects of bariatric surgery respectively. The study was performed at a university hospital between October 2012 and December 2013. RESULTS: We included 25 mother-newborn dyads where the mothers had undergone RYGB and compared them to a reference material of 311 mother-newborn dyads with comparable pre-pregnancy BMI. Offspring born by mothers after RYGB had lower birthweight (335g, p<0.001), fat-free mass (268g, p<0.001) and fat% (2.8%, p<0.001) compared with reference material. Only 2% of the average reduction in newborn fat free mass could be attributed to maternal pre-pregnancy weight loss whereas other effects of RYGB accounted for 98%. Regarding reduction in fat mass 52% was attributed to weight loss and 47% to other effects of surgery. CONCLUSION: Offspring born after maternal bariatric surgery, had lower birthweight, fat-free mass and fat percentage when compared with a reference material. RYGB itself and not the pre-pregnancy weight loss seems to have had the greatest impact on fetal growth.
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Cirurgia Bariátrica/efeitos adversos , Peso ao Nascer , Composição Corporal , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações na Gravidez/etiologia , Adulto , Índice de Massa Corporal , Feminino , Desenvolvimento Fetal , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
BACKGROUND: An aberrant composition of the salivary microbiota has been found in individuals with type 2 diabetes, and in pregnant women salivary microbiota composition has been associated with preeclampsia and pre-term birth. Pregnant women, who develop gestational diabetes (GDM), have a high risk of developing type 2 diabetes after pregnancy. In the present study we assessed whether GDM is linked to variation in the oral microbial community by examining the diversity and composition of the salivary microbiota. METHOD: In this observational study the salivary microbiota of pregnant women with GDM (n = 50) and normal glucose regulation (n = 160) in third trimester and 9 months postpartum was assessed by 16S rRNA gene amplicon sequencing of the V1-V3 region. GDM was diagnosed in accordance with the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Cross-sectional difference in alpha diversity was assessed using Student's t-test and longitudinal changes were assessed by mixed linear regression. Cross-sectional and longitudinal difference in beta diversity was assessed by permutational multivariate analyses of variance. Differentially abundant genera and OTUs were identified by negative binomial regression. RESULTS: In the third trimester, two species-level operational taxonomic units (OTUs), while eight OTUs postpartum were differentially abundant in women with GDM compared with normoglycaemic women. OTU richness, Shannon diversity and Pielou evenness decreased from late pregnancy to 9 months after delivery regardless of glycaemic status. CONCLUSION: GDM is associated with a minor aberration of the salivary microbiota during late pregnancy and postpartum. For unknown reasons richness of the salivary microbiota decreased from late pregnancy to postpartum, which might be explained by the physiological changes of the immune system during human pregnancy.
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Diabetes Gestacional/microbiologia , Microbiota , Período Pós-Parto/sangue , Terceiro Trimestre da Gravidez/sangue , Saliva/microbiologia , Adulto , Glicemia , Índice de Massa Corporal , Feminino , Teste de Tolerância a Glucose , Humanos , Estudos Longitudinais , Gravidez , RNA Ribossômico 16SRESUMO
INTRODUCTION: Vaginal birth increases the risk of urinary retention and overdistention of the bladder. To avoid unnecessary discomfort by catheterization, it is preferable to use ultrasound for diagnosis of these conditions. The aim of this study was to determine the validity of transabdominal ultrasound and a portable ultrasound system, Biocon-700, to measure bladder volume in women postpartum. METHODS: Fifty women were included in this method comparison study. Within 48 h of giving birth, their bladder volume was measured in randomized order with both transabdominal ultrasound and Biocon-700. After urination, participants were scanned with Biocon-700 to measure residual bladder volume, and finally the bladder was emptied by catheterization. The total bladder volume was calculated as the voided volume plus the catheterized volume. RESULTS: Biocon-700 measured 43.4 ml ± 117.4 ml (mean ± SD) lower than the total bladder volume, while volumes measured by transabdominal ultrasound were 117.8 ml ± 110.0 ml (mean ± SD) lower. Linear regression showed significant proportional bias in both methods. The Biocon-700 could detect a residual bladder volume > 150 ml with a positive predictive value of 66.7% and a negative predictive value of 100%. CONCLUSIONS: Neither transabdominal ultrasound nor the portable ultrasound system, Biocon-700, can be used to measure bladder volume precisely after vaginal delivery. However, both ultrasound methods can be used as screening tools to prevent overdistention of the bladder, and Biocon-700 can furthermore be used to screen women for a residual bladder volume > 150 ml.
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Bexiga Urinária , Cateterismo Urinário , Feminino , Humanos , Período Pós-Parto , Gravidez , Estudos Prospectivos , Ultrassonografia , Bexiga Urinária/diagnóstico por imagemRESUMO
Underweight, defined as BMI ≤ 18.5 kg/m2, is found in 4.2% of pregnancies in Denmark. Pre-pregnancy underweight is more often seen in relation to psychiatric disorders, e.g. anorexia nervosa, and diet restrictions and associates with adverse pregnancy outcomes, such as antepartum haemorrhage requiring blood transfusion, preterm birth, small for gestational age infants, and impaired ability to breastfeed. In this review, we recommend identification of possible underlying medical or psychiatric disorders, focus on sufficient gestational weight gain, and relevant vitamin and mineral substitution.
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Complicações na Gravidez , Magreza , Índice de Massa Corporal , Dinamarca , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de RiscoAssuntos
Incontinência Fecal , Complicações do Trabalho de Parto , Canal Anal , Feminino , Humanos , Incidência , GravidezRESUMO
INTRODUCTION: Obstetric anal sphincter injuries (OASIS) are serious complications to vaginal delivery causing anal incontinence in 50% of the women in the long term. In Norway, the incidence of OASIS has been significantly reduced from 4%-5% to 1%-2% after implementation of prevention programs focusing on perineal protection. The aim of our study was to evaluate whether implementation of formal prevention programs was associated with a reduced incidence of OASIS over time. MATERIAL AND METHODS: We performed a historical cohort study, evaluating incidence, change of incidence and risk factors of OASIS during the years 2011-2015 at the four delivery departments in the Capital Region of Denmark. Two of the four departments implemented formal prevention programs in 2012-2013. We performed trend tests and uni- and multivariable analyses, adjusting for important risk factors and calculating interactions between risk factors. RESULTS: There were 75 173 vaginal deliveries during the study period; of those, 2670 (3.6%) were complicated by OASIS. The incidence of OASIS decreased during the study period from 4.3% (n = 636) in 2011 to 2.6% (n = 399) in 2015. There was a significant decrease in the incidence of OASIS at both the departments with formal prevention programs and those without. After adjustment for other important risk factors of OASIS, we found no significant difference in the risk reduction between departments with and without formal prevention programs. CONCLUSIONS: We found that the general focus on prevention of OASIS in Denmark was associated with a significant decrease in the incidence of OASIS, but implementation of formal prevention programs did not lead to a further reduction. It is possible that more rigorous interventions at the hospitals with formal prevention programs could have resulted in a significant difference in incidence of OASIS.
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Canal Anal/lesões , Parto Obstétrico/efeitos adversos , Lacerações/epidemiologia , Complicações do Trabalho de Parto/epidemiologia , Adulto , Estudos de Casos e Controles , Intervalos de Confiança , Parto Obstétrico/métodos , Dinamarca , Feminino , Idade Gestacional , Humanos , Incidência , Lacerações/etiologia , Noruega , Complicações do Trabalho de Parto/diagnóstico , Razão de Chances , Gravidez , Prognóstico , Estudos Retrospectivos , Medição de RiscoRESUMO
PURPOSE: To describe the association between quantity of blood loss, duration of the third stage of labour, retained placenta and other risk factors, and to describe the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage. METHODS: Cohort study of all vaginal deliveries at two Danish maternity units between 1 January 2009 and 31 December 2013 (n = 43,357), univariate and multivariate linear regression statistical analyses. RESULTS: A retained placenta was shown to be a strong predictor of quantity of blood loss and duration of the third stage of labour a weak predictor of quantity of blood loss. The predictive power of the third stage of labour was further reduced in the multivariate analysis when including retained placenta in the model. There was an increase in the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage, increasing from 12% in cases of blood loss ≥ 500 ml to 53% in cases of blood loss ≥ 2000 ml CONCLUSION: The predictive power of duration of the third stage of labour in regard to postpartum blood loss was diminished by the influence of a retained placenta. A retained placenta was, furthermore, present in the majority of most severe cases.
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Terceira Fase do Trabalho de Parto/fisiologia , Placenta Retida/fisiopatologia , Hemorragia Pós-Parto/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum. METHODS: Gut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy. RESULTS: Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy. CONCLUSION: GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits.
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Diabetes Gestacional/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Trato Gastrointestinal/microbiologia , Período Pós-Parto/sangue , Terceiro Trimestre da Gravidez/sangue , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Adulto , Glicemia , Índice de Massa Corporal , Clostridium/genética , Clostridium/isolamento & purificação , Desulfovibrio/genética , Desulfovibrio/isolamento & purificação , Faecalibacterium/genética , Faecalibacterium/isolamento & purificação , Feminino , Glucose/metabolismo , Humanos , Gravidez , RNA Ribossômico 16S/genética , Inquéritos e QuestionáriosRESUMO
CONTEXT: Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with first recognition during pregnancy, is a heterogeneous form of diabetes characterized by various degrees of ß-cell dysfunction. OBJECTIVES: We aimed to estimate the prevalence of possibly pathogenic variants in the maturity-onset diabetes of the young genes GCK, HNF1A, HNF4A, HNF1B, and INS among women with GDM. Furthermore, we examined the glucose tolerance status in variant carriers vs noncarriers at follow-up. DESIGN SETTING AND PATIENTS: We sequenced the coding regions and intron/exon boundaries of GCK, HNF1A, HNF4A, HNF1B, and INS using targeted region capture and next-generation sequencing in 354 Danish women with diet-treated GDM. Glucose tolerance was examined at follow-up 10 years after the index pregnancy. MAIN OUTCOME MEASURES: The prevalence of possibly pathogenic variants in GCK, HNF1A, HNF4A, HNF1B, and INS was estimated, and differences in anthropometric traits, high-sensitivity C-Reactive Protein (CRP), and glucose metabolism were measured. RESULTS: At baseline, 17 possibly disease-causing variants were found in 21 women, revealing a combined GCK, HNF1A, HNF4A, HNF1B, and INS variant prevalence of 5.9% (95% confidence interval: 3.5% to 8.4%). At follow-up, 15 out of 135 women with diabetes (11%) were carriers of variants in GCK, HNF1A, HNF4A, HNF1B, or INS. CONCLUSIONS: Almost 6% of Danish women with diet-treated GDM have possibly pathogenic variants in GCK, HNF1A, HNF4A, HNF1B, or INS. These women are at high risk of developing diabetes after pregnancy. Thus screening for variants in GCK, HNF1A, HNF4A, HNF1B, and INS should be considered among women with GDM.