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1.
Dan Med J ; 68(9)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477096

RESUMO

INTRODUCTION: Although women rarely die during pregnancy and childbirth in Denmark, keeping track of the maternal mortality rate and causes of death is vital in identifying learning points for future management of critical illness among obstetric patients and in pinpointing risk factors. METHODS: We identified maternal deaths between 2002 and 2017 by linking four Danish national health registers, using death certificates and reports from hospitals. An audit group then categorised each case by cause of death before identifying any suboptimal care and learning points, which may serve as a foundation for national guidelines and educational strategies. RESULTS: Seventy women died during pregnancy or within six weeks of a pregnancy in the study period. The most frequent causes of death were cardiovascular disease (n = 14), hypertensive disorder (n = 10), suicide (n = 10) and thromboembolism (n = 7). Suboptimal care was identified in 30 of the 70 cases. CONCLUSIONS: Mortality from some of the most important causes of death decreased during the study period. No deaths from preeclampsia or thrombosis, two of the leading causes of death, were identified after 2011. In 2015-2017, suicide was the main cause of maternal death, which indicates that a stronger focus on vulnerability in pregnancy and childbirth is essential. Among the 70 deaths, 34% were potentially avoidable, indicating that it is essential continuously to focus on how to reduce severe maternal morbidity and mortality. FUNDING: none TRIAL REGISTRATION. not relevant.


Assuntos
Doenças Cardiovasculares , Morte Materna , Complicações na Gravidez , Suicídio , Causas de Morte , Estado Terminal , Feminino , Humanos , Morte Materna/etiologia , Mortalidade Materna , Gravidez
2.
Dan Med J ; 68(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34477097

RESUMO

INTRODUCTION: Women very rarely die during pregnancy and childbirth in Denmark. Although maternal deaths are registered worldwide, various studies indicate that underreporting does occur. This paper presents validated Danish register data for two periods between 1985 and 2017. METHODS: Maternal deaths were identified from 1985 to 1994 and from 2002 to 2017 by linking four national health registers, death certificates and notifications from maternity wards. A group of obstetricians categorised and assessed all medical records, classifying each case by cause of death. RESULTS: Linkage of four registers yielded valid data, leading to the identification of 143 maternal deaths in the abovementioned periods. From 1985-1994 there were 73 deaths and 618,021 live births, resulting in a maternal mortality rate of 11.8 per 100,000 live births with a non-significant 2% annual increase (95% confidence interval (CI): -6.0-11.0%). From 2002 to 2017 there were 70 maternal deaths and 999,206 live births, resulting in a maternal mortality rate of 7.0 per 100,000 live births (95% CI: 5.5-8.9) with a significant 9% annual decrease (95% CI: 4.0-14.0%). CONCLUSIONS: Overall maternal mortality decreased in the course of the two periods (n = 33 years), with a significant decrease during the last period. This is suggested to be a result of multiple clinical and organisational improvements as discussed in the paper. FUNDING: none. TRIAL REGISTRATION: not relevant.


Assuntos
Mortalidade Materna , Complicações na Gravidez , Causas de Morte , Dinamarca/epidemiologia , Feminino , Humanos , Registros Médicos , Gravidez
3.
Ugeskr Laeger ; 183(32)2021 Aug 09.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34378527

RESUMO

Impacted foetal head is common in emergency caesarean sections with consequences for mother and foetus, rarely but devastatingly resulting in cranial injuries and foetal death. In prevention, the Fetal Pillow is a simple inflatable device used to push the foetal head upwards, which can reduce complications. Evidence supports applying the reverse breech technique over other manoeuvres. In this review, we emphasise limiting uterine extensions and the push-method. An algorithm which can be integrated in obstetric training, is proposed for prophylaxis and treatment of an impacted foetal head.

4.
J Perinat Med ; 49(7): 923-931, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34280959

RESUMO

OBJECTIVES: To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS). METHODS: The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit's policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications. RESULTS: Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70). CONCLUSIONS: Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

5.
Immunity ; 54(6): 1338-1351.e9, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33862015

RESUMO

Despite advances in single-cell multi-omics, a single stem or progenitor cell can only be tested once. We developed clonal multi-omics, in which daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings in parallel "sister" assays are examined either for gene expression by RNA sequencing (RNA-seq) or for fate in culture. We identified, and then validated using CRISPR, genes that controlled fate bias for different dendritic cell (DC) subtypes. This included Bcor as a suppressor of plasmacytoid DC (pDC) and conventional DC type 2 (cDC2) numbers during Flt3 ligand-mediated emergency DC development. We then developed SIS-skew to examine development of wild-type and Bcor-deficient siblings of the same clone in parallel. We found Bcor restricted clonal expansion, especially for cDC2s, and suppressed clonal fate potential, especially for pDCs. Therefore, SIS-seq and SIS-skew can reveal the molecular and cellular mechanisms governing clonal fate.


Assuntos
Células Dendríticas/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Linhagem da Célula/genética , Feminino , Expressão Gênica/genética , Células HEK293 , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Células-Tronco/metabolismo
6.
Nat Cell Biol ; 23(3): 219-231, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33649477

RESUMO

Regulation of haematopoietic stem and progenitor cell (HSPC) fate is crucial during homeostasis and under stress conditions. Here we examine the aetiology of the Flt3 ligand (Flt3L)-mediated increase of type 1 conventional dendritic cells (cDC1s). Using cellular barcoding we demonstrate this occurs through selective clonal expansion of HSPCs that are primed to produce cDC1s and not through activation of cDC1 fate by other HSPCs. In particular, multi/oligo-potent clones selectively amplify their cDC1 output, without compromising the production of other lineages, via a process we term tuning. We then develop Divi-Seq to simultaneously profile the division history, surface phenotype and transcriptome of individual HSPCs. We discover that Flt3L-responsive HSPCs maintain a proliferative 'early progenitor'-like state, leading to the selective expansion of multiple transitional cDC1-primed progenitor stages that are marked by Irf8 expression. These findings define the mechanistic action of Flt3L through clonal tuning, which has important implications for other models of 'emergency' haematopoiesis.


Assuntos
Proliferação de Células/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Proteínas de Membrana/farmacologia , RNA-Seq , Análise de Célula Única , Transcriptoma/efeitos dos fármacos , Animais , Linhagem da Célula , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo
7.
Sci Rep ; 10(1): 9535, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533019

RESUMO

After preterm premature rupture of membranes (PPROM), antibiotics and antenatal steroids are effective evidence-based interventions, but the use of tocolysis is controversial. We investigated whether a unit policy of tocolysis use after PPROM is associated with prolonged gestation and improved outcomes for very preterm infants in units that systematically use these other evidence-based treatments. From the prospective, observational, population-based EPICE cohort study (all very preterm births in 19 regions from 11 European countries, 2011-2012), we included 607 women with a singleton pregnancy and PPROM at 24-29 weeks' gestation, of whom 101, 195 and 311 were respectively managed in 17, 32 and 45 units with no-use, restricted and liberal tocolysis policies for PPROM. The association between unit policies and outcomes (early-onset sepsis, survival at discharge, survival at discharge without severe morbidity and survival at two years without gross motor impairment) was investigated using three-level random-intercept logistic regression models, showing no differences in neonatal or two-year outcomes by unit policy. Moreover, there was no association between unit policies and prolongation of gestation in a multilevel survival analysis. Compared to a unit policy of no-use of tocolysis after PPROM, a liberal or restricted policy is not associated with improved obstetric, neonatal or two-year outcomes.


Assuntos
Ruptura Prematura de Membranas Fetais/tratamento farmacológico , Tocolíticos/uso terapêutico , Adulto , Estudos de Coortes , Europa (Continente) , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Doenças do Prematuro/prevenção & controle , Gravidez , Nascimento Prematuro/prevenção & controle , Estudos Prospectivos , Tocólise/métodos
9.
J Am Geriatr Soc ; 67(11): 2338-2345, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31433870

RESUMO

BACKGROUND/OBJECTIVES: Little is known about elder abuse and neglect in the lesbian, gay, bisexual, and transgender (LGBT) community; however, this population faces a greater risk of abuse and likely experiences abuse differently and needs different resources. We conducted focus groups to investigate LGBT older adults' perspectives on and experience with elder mistreatment. METHODS: We conducted three focus groups with 26 participants recruited from senior centers dedicated to LGBT older adults. A semistructured questionnaire was developed, and focus groups were audio recorded, professionally transcribed, and analyzed using grounded theory. RESULTS: Key themes that emerged included: definitions and etiologies of abuse, intersectionality of discrimination from multiple minority identities, reluctance to report, and suggestions for improving outreach. Participants defined elder abuse in multiple ways, including abuse from systems and by law enforcement and medical providers. Commonly reported etiologies included: social isolation due to discrimination, internalization of stigma, intersection of discrimination from multiple minority identities, and an abuser's desire for power and control. Participants were somewhat hesitant to report to police; however, most felt strongly that they would not report abuse to their medical provider. Most reported that they would feel compelled to report if they knew someone was being abused; however, they did not know who to report to. Strategies participants suggested to improve outreach included: increasing awareness about available resources and researchers engaging with the LGBT community directly. CONCLUSION: LGBT older adults conceptualize elder abuse differently and have different experiences with police and medical providers. Improved outreach to this potentially vulnerable population is critical to ensuring their safety. J Am Geriatr Soc 67:2338-2345, 2019.


Assuntos
Bissexualidade , Abuso de Idosos/estatística & dados numéricos , Homossexualidade Feminina/psicologia , Homossexualidade Masculina/psicologia , Comportamento Sexual , Estigma Social , Pessoas Transgênero/psicologia , Idoso , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Isolamento Social/psicologia , Apoio Social
10.
Int J Gynaecol Obstet ; 147(3): 397-403, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31402446

RESUMO

OBJECTIVE: To describe obstetrical care and in-hospital outcomes in very preterm triplet pregnancies in a European multiregional cohort. METHODS: Data from a prospective population-based study of very preterm births between 22 + 0 and 31 + 6 weeks of gestation in 19 regions from 11 European countries participating in the EPICE project in 2011/2012 were used to describe triplet pregnancies and compare them with twins and singletons. RESULTS: Triplets constituted 1.1% of very preterm pregnancies (97/8851) and 3.3% of very preterm live births (258/7900); these percentages varied from 0% to 2.6% and 0% to 6% respectively across the regions. In-hospital mortality after live birth was 12.4% and did not differ significantly from singletons or twins or by birth order. However, 28.9% of mothers with a triplet pregnancy experienced at least one neonatal death. Ninety percent of live-born triplets were delivered by cesarean. Vaginal delivery was associated with an Apgar score of less than 7, but not with in-hospital mortality. CONCLUSIONS: The prevalence of very preterm triplets varies across European regions. Most triplets were born by cesarean and those born vaginally had lower Apgar scores. Overall, in-hospital mortality after live birth was similar to singletons and twins.


Assuntos
Gravidez de Trigêmeos/estatística & dados numéricos , Nascimento Prematuro/epidemiologia , Trigêmeos/estatística & dados numéricos , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Cesárea/estatística & dados numéricos , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Nascido Vivo/epidemiologia , Gravidez , Estudos Prospectivos , Natimorto/epidemiologia
11.
J Math Biol ; 79(2): 673-704, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31069504

RESUMO

Motivated by a recently proposed design for a DNA coded randomised algorithm that enables inference of the average generation of a collection of cells descendent from a common progenitor, here we establish strong convergence properties for the average generation of a super-critical Bellman-Harris process. We further extend those results to a two-type Bellman-Harris process where one type can give rise to the other, but not vice versa. These results further affirm the estimation method's potential utility by establishing its long run accuracy on individual sample-paths, and significantly expanding its remit to encompass cellular development that gives rise to differentiated offspring with distinct population dynamics.


Assuntos
Diferenciação Celular/genética , Replicação do DNA , Modelos Genéticos , Algoritmos , Técnicas de Cultura de Células , Morte Celular/genética , Proliferação de Células/genética , Simulação por Computador , Microscopia Intravital , Homeostase do Telômero/genética , Imagem com Lapso de Tempo
12.
Nat Methods ; 16(6): 479-487, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31133762

RESUMO

Single cell RNA-sequencing (scRNA-seq) technology has undergone rapid development in recent years, leading to an explosion in the number of tailored data analysis methods. However, the current lack of gold-standard benchmark datasets makes it difficult for researchers to systematically compare the performance of the many methods available. Here, we generated a realistic benchmark experiment that included single cells and admixtures of cells or RNA to create 'pseudo cells' from up to five distinct cancer cell lines. In total, 14 datasets were generated using both droplet and plate-based scRNA-seq protocols. We compared 3,913 combinations of data analysis methods for tasks ranging from normalization and imputation to clustering, trajectory analysis and data integration. Evaluation revealed pipelines suited to different types of data for different tasks. Our data and analysis provide a comprehensive framework for benchmarking most common scRNA-seq analysis steps.


Assuntos
Adenocarcinoma/genética , Benchmarking , Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Humanos , Software , Células Tumorais Cultivadas
13.
Eur J Obstet Gynecol Reprod Biol ; 234: 96-102, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30682601

RESUMO

OBJECTIVE: Caesarean section (CS) may reduce mortality and morbidity for very preterm breech infants, but evidence is inconclusive. We evaluated neonatal outcomes for singleton breech infants by mode of delivery in a European cohort. STUDY DESIGN: Data come from the EPICE population-based cohort of very preterm births in 19 regions in 11 European countries (7770 live births). The study population was singleton spontaneous-onset breech births at 24-31 weeks gestational age (GA) without antenatal medical complications requiring caesarean delivery (N = 572). Mixed-effects regression models adjusting for maternal and pregnancy covariates and propensity score matching was used to examine the effect of (1) CS and (2) a unit policy of systematic CS for breech presentation by GA. The primary outcome was a composite of in-hospital mortality, intraventricular haemorrhage grades III & IV or cystic periventricular leukomalacia. Secondary outcomes were each component separately, five minute Apgar score below seven and mortality within six hours of delivery. RESULTS: 64.4% of infants were delivered by CS with a range across regions from 41% to 100%; these infants had higher GA and were more likely to be small for gestational age, receive antenatal steroids, and have mothers who were hospitalised for more than one day before delivery compared to those delivered vaginally. CS was associated with lower risks of all outcomes in mixed-effects adjusted models (odds ratio (OR) for the composite outcome: 0.50, 95% confidence interval (CI): 0.30-0.81), but not in propensity score matched models (OR: 0.72, 95% CI: 0.41; 1.29). A systematic CS policy was associated with lower mortality and morbidity in unadjusted, but not adjusted models (OR for composite outcome: 0.76, 95% CI: 0.44; 1.28). 35% of births 24-25 weeks were delivered by CS and protective effects were consistently stronger, but not statistically significant. CONCLUSIONS: Point estimates indicated protective effects of caesarean delivery for very preterm breech infants in conventional statistical models. However, analyses using propensity scores and based on unit policies did not confirm statistically significant associations. Prospective large-scale studies are needed to establish best practice and could be implemented in European regions where vaginal delivery remains an option.


Assuntos
Apresentação Pélvica/mortalidade , Cesárea/mortalidade , Mortalidade Perinatal , Adulto , Estudos de Coortes , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Gravidez
14.
Front Psychol ; 9: 2063, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555364

RESUMO

Different reference frames are used in daily life in order to structure the environment. The two-choice Simon task setting has been used to investigate how task-irrelevant spatial information influences human cognitive control. In recent studies, a Go/NoGo Simon task setting was used in order to divide the Simon task between a pair of participants. Yet, not only a human co-actor, but also even an attention-grabbing object can provide sufficient reference in order to reintroduce a Simon effect (SE) indicating cognitive conflict in Go/NoGo task settings. Interestingly, the SE could only occur when a reference point outside of the stimulus setup was available. The current studies exploited the dependency between different spatial reference frames (egocentric and allocentric) offered by the stimulus setup itself and the task setup (individual vs. joint Go/NoGot task setting). Two studies (Experiments 1 and 2) were carried out along with a human co-actor. Experiment 3 used an attention-grabbing object instead. The egocentric and allocentric SEs triggered by different features of the stimulus setup (global vs. local) were modulated by the task setup. When interacting with a human co-actor, an egocentric SE was found for global features of the stimulus setup (i.e., stimulus position on the screen). In contrast, an allocentric SE was yielded in the individual task setup illustrating the relevance of more local features of the stimulus setup (i.e., the manikin's ball position). Results point toward salience shifts between different spatial reference frames depending on the nature of the task setup.

15.
Front Immunol ; 9: 1313, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29951060

RESUMO

Adaptation of antibody-mediated immunity occurs in germinal centers (GC). It is where affinity maturation, class switching, memory and plasma cell differentiation synergize to generate specific high-affinity antibodies that aid both to clear and protect against reinfection of invading pathogens. Within GCs, light and dark zone are two compartments instrumental in regulating this process, by segregating T cell-dependent selection and differentiation from generation of GC B cells bearing hypermutated antigen receptors. Spatial segregation of GC B cells into the two zones relies on the chemokine receptor CXCR4, with textbooks attributing high and low expression to a dark and light zone phenotype. Interestingly, this bipolarity is not reflected in the CXCR4 expression profile of GC B cells, which is highly variable and unimodal, indicating a continuum of intermediate CXCR4 levels rather than a binary dark or light zone phenotype. Here, analysis of published BrdU pulse-chase data reveals that throughout cell cycle, average CXCR4 expression in GC B cells steadily increases close to twofold, scaling with cell surface area. CXCR4 expression in recently divided GC B cells in G0/G1 or early S phase shows intermediate levels compared to cells in G2M phase, consistent with their smaller size. The lowest number of CXCR4 receptors are displayed by relatively aged GC B cells in G0/G1 or early S phase. The latter, upon progressing through S phase, however, ramp up relative CXCR4 expression twice as much as recently divided cells. Twelve hours after the BrdU pulse, labeled GC B cells, while initially in S phase, are desynchronized in terms of cell cycle and match the CXCR4 profile of unlabeled cells. A model is discussed in which CXCR4 expression in GC B cell increases with cell cycle and cell surface area, with highest levels in G2 and M phase, coinciding with GC B cell receptor signaling in G2 and immediately preceding activation-induced cytidine deaminase (AID) activity in early G1. In the model, GC B cells compete for CXCL12 expression on the basis of their CXCR4 expression, gaining a relative advantage as they progress in cell cycle, but loosing the advantage at the moment they divide.

16.
Cell Stem Cell ; 22(1): 64-77.e6, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29276143

RESUMO

Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression leads to differential remodeling of vasculature in central and endosteal bone marrow regions. Endosteal AML cells produce pro-inflammatory and anti-angiogenic cytokines and gradually degrade endosteal endothelium, stromal cells, and osteoblastic cells, whereas central marrow remains vascularized and splenic vascular niches expand. Remodeled endosteal regions have reduced capacity to support non-leukemic HSCs, correlating with loss of normal hematopoiesis. Preserving endosteal endothelium with the small molecule deferoxamine or a genetic approach rescues HSCs loss, promotes chemotherapeutic efficacy, and enhances survival. These findings suggest that preventing degradation of the endosteal vasculature may improve current paradigms for treating AML.


Assuntos
Células-Tronco Hematopoéticas/patologia , Leucemia Mieloide Aguda/patologia , Nicho de Células-Tronco , Animais , Medula Óssea/irrigação sanguínea , Medula Óssea/patologia , Contagem de Células , Hematopoese , Humanos , Microscopia Intravital , Camundongos Endogâmicos C57BL , Baço/patologia , Células Estromais/patologia , Fatores de Tempo , Microambiente Tumoral
17.
JAMA Pediatr ; 171(7): 678-686, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28505223

RESUMO

Importance: Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective: To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure: Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results: Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance: Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.


Assuntos
Intervalo entre Nascimentos/estatística & dados numéricos , Glucocorticoides/administração & dosagem , Mortalidade Hospitalar , Mortalidade Infantil , Cuidado Pré-Natal/métodos , Estudos de Coortes , Europa (Continente) , Feminino , Idade Gestacional , Glucocorticoides/efeitos adversos , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Masculino , Gravidez , Estudos Prospectivos
18.
Dan Med J ; 63(11)2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27808034

RESUMO

INTRODUCTION: Iodine is essential for the production of thyroid hormones. In pregnancy, physiological changes occur that can lead to iodine deficiency and impairment of fetal neurological development. We aimed to assess the iodine intake in pregnant women in Eastern Denmark, compare iodine levels in Eastern and Western Denmark and to identify potentially vulnerable groups. METHODS: This was a cross-sectional cohort study of pregnant Danish women (n = 240). Questionnaires and urine samples were collected at the Ultrasound Clinic, Hvidovre Hospital, Denmark, and urinary iodine concentrations (UIC) (µg/l) were measured. Predictors of iodine supplement use were examined by multivariate logistic regression models. RESULTS: The pregnant women from Eastern Denmark had a median age of 30 years and the median gestational week at which they were included in the study was week 19. The majority took iodine-containing supplements (86%). The median UIC was 118 (interquartile range (IQR): 79-196) µg/l in iodine supplement users and 82 (IQR: 41-122) µg/l in non-users (p < 0.001). Predictors of not using iodine supplement in Eastern and Western Denmark were short maternal education, non-Danish origin and pre-pregnancy obesity. CONCLUSIONS: The iodine status in Danish pregnant women was below WHO recommendations. Iodine supplement non-users are at a particular risk of iodine deficiency. Low maternal education, non-Danish origin and pre-pregnancy obesity are predictors of non-iodine supplement use. An increase in iodine fortification may be recommended to improve the iodine status in pregnant Danish women. FUNDING: none. TRIAL REGISTRATION: not relevant.


Assuntos
Suplementos Nutricionais , Iodo/deficiência , Iodo/uso terapêutico , Complicações na Gravidez/epidemiologia , Adulto , Estudos de Coortes , Estudos Transversais , Dinamarca/epidemiologia , Escolaridade , Feminino , Humanos , Obesidade/epidemiologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/etnologia , Prevalência , Fatores de Risco , Adulto Jovem
20.
BMJ ; 354: i2976, 2016 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-27381936

RESUMO

OBJECTIVES:  To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity. DESIGN:  Prospective multinational population based observational study. SETTING:  19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project. PARTICIPANTS:  7336 infants born between 24+0 and 31+6 weeks' gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission. MAIN OUTCOME MEASURES:  Combined use of four evidence based practices for infants born before 28 weeks' gestation using an "all or none" approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital. RESULTS:  Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants. CONCLUSIONS:  More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity.


Assuntos
Prática Clínica Baseada em Evidências , Lactente Extremamente Prematuro , Doenças do Prematuro/mortalidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Taxa de Sobrevida
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