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1.
Eur J Obstet Gynecol Reprod Biol ; 247: 111-115, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32087421

RESUMO

OBJECTIVE: Preterm birth is the most important cause of perinatal morbidity and mortality. Over the past years several preventive measures have been studied and implemented. Preterm birth percentage in 2015 in the Netherlands was 6.9 %, according to data from the European Peristat project, reporting on perinatal health in Europe. Various preventive measures might have influenced the incidence and outcome of preterm birth. Our aim was to give an overview of the trends in preterm births for both singleton and multiple gestations in the Netherlands in order to guide future research. STUDY DESIGN: We studied a nationwide cohort including both singleton and multiple gestations without congenital anomalies between 2008 and 2015. Outcomes were total preterm birth (defined as birth before 37 weeks of gestation), spontaneous and iatrogenic preterm birth < 37 weeks, spontaneous and iatrogenic preterm birth percentages between 34-36 weeks, 32-34 weeks, 28-31 weeks and ≤ 27 weeks using a moving average technique. Trend analysis was performed using the Cochran Armitage test. Singleton and multiple gestations were analyzed separately. RESULTS: Our final study population comprised 1,303.786 women with a singleton and 44,951 women with a multiple pregnancy. Preterm birth < 37 weeks in singletons decreased from 5.6 % in 2008 to 5.3 % in 2015 (P < 0.0001), in both spontaneous and iatrogenic preterm birth. Preterm birth ≤ 27 weeks increased from 0.40 % to 0.45 % (P for trend <0.0001). The number of multiple gestations decreased over the years, as well as the percentage of multiples conceived through IVF/ICSI. There was an increase in total and iatrogenic preterm birth < 37 weeks from 36.7-38.2% (P < 0.0001) in multiples. The number of multiples <32 decreased, in both the spontaneous and iatrogenic group. CONCLUSION: In the Netherlands preterm birth risk in singletons decreased between 2008 and 2015 but an increase was noted in preterm birth ≤ 27 weeks. In multiples the total preterm birth risk increased, due to an increase in indicated preterm birth.

2.
BMJ Open ; 9(11): e029101, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772083

RESUMO

INTRODUCTION: Preterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed. METHODS AND ANALYSIS: We designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30-34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 1514 participants (757 per group) will detect a reduction in adverse neonatal outcome from 10% to 6% (alpha 0.05, beta 0.2). A cost-effectiveness analysis will be performed from a societal perspective. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC's in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results. TRIAL REGISTRATION NUMBER: Nederlands Trial Register (Trial NL6469).

3.
Pediatrics ; 143(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31160512

RESUMO

OBJECTIVES: To develop a nationwide, evidence-based framework to support prenatal counseling in extreme prematurity, focusing on organization, decision-making, content, and style aspects. METHODS: A nationwide multicenter RAND-modified Delphi method study was performed between November 2016 and December 2017 in the Netherlands. Firstly, recommendations were extracted from literature and previous studies. Secondly, an expert panel (n = 21) with experienced parents, obstetricians, and neonatologists rated the recommendations on importance for inclusion in the framework. Thirdly, ratings were discussed in a consensus meeting. The final set of recommendations was approved and transformed into a framework. RESULTS: A total of 101 recommendations on organization, decision-making, content, and style were included in the framework, including tools to support personalization. The most important recommendations regarding organization were to have both parents involved in the counseling with both the neonatologist and obstetrician. The shared decision-making model was recommended for deciding between active support and comfort care. Main recommendations regarding content of conversation were explanation of treatment options, information on survival, risk of permanent consequences, impossibility to predict an individual course, possibility for multiple future decision moments, and a discussion on parental values and standards. It was considered important to avoid jargon, check understanding, and provide a summary. The expert panel, patient organization, and national professional associations (gynecology and pediatrics) approved the framework. CONCLUSIONS: A nationwide, evidence-based framework for prenatal counseling in extreme prematurity was developed. It contains recommendations and tools for personalization in the domains of organization, decision-making, content, and style of prenatal counseling.


Assuntos
Aconselhamento/normas , Pessoal de Saúde/normas , Lactente Extremamente Prematuro , Doenças do Prematuro/diagnóstico , Cuidado Pré-Natal/normas , Desenvolvimento de Programas/normas , Atitude do Pessoal de Saúde , Tomada de Decisão Clínica/métodos , Aconselhamento/métodos , Técnica Delfos , Feminino , Humanos , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/terapia , Países Baixos/epidemiologia , Gravidez , Cuidado Pré-Natal/métodos , Desenvolvimento de Programas/métodos , Inquéritos e Questionários
5.
J Perinatol ; 39(8): 1050-1056, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30940928

RESUMO

OBJECTIVE: Our aim was to investigate the association between large-for-gestational-age and the risk of spontaneous preterm birth. STUDY DESIGN: We studied nulliparous women with a singleton gestation using data from the Dutch perinatal registry from 1999 to 2010. Neonates were categorized according to the Hadlock fetal weight standard, into 10th to 90th percentile, 90th to 97th percentile, or above 97th percentile. Outcomes were preterm birth <37+0 weeks and preterm birth between 25+0-27+6 weeks, 28+0-30+6 weeks, 31+0-33+6 weeks, and 34+0-36+6 weeks. RESULTS: We included 547,418 women. The number of spontaneous preterm births <37 weeks was significantly increased in the large-for-gestational-age group ( > p97) compared with fetuses with a normal growth (p10-p90) (11.3% vs. 7.3%, odds ratio (OR) 1.8; 95% CI 1.7-1.9). The same results were found when limiting analyses to women with certain pregnancy duration (after in vitro fertilization). CONCLUSION: Large-for-gestational-age increases the risk of spontaneous preterm delivery from 25 weeks of gestation onwards.

6.
BMC Pregnancy Childbirth ; 19(1): 65, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744577

RESUMO

BACKGROUND: Bioethicists argue that inclusion of pregnant women in clinical research should be more routine to increase the evidence-base for pregnant women and foetuses. Yet, it is unknown whether pregnant women and others directly involved are willing to be routinely included. Therefore, we first need to establish what these stakeholders think about research participation in regular pregnancy-related research. However, studies on their views are scarce. In our study, we piggy-backed on a relatively conventional RCT, the APOSTEL VI study, to identify the views of stakeholders on inclusion of pregnant women in this study. METHODS: We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed pregnant women (n = 14) recruited for the APOSTEL VI study, in addition to healthcare professionals (n = 14), Research Ethics Committee members (RECs) (n = 5) and regulators (n = 7) involved in clinical research in pregnant women. RESULTS: Three themes characterise stakeholders' views on inclusion of pregnant women in the APOSTEL VI study. Additionally, one theme characterises stakeholders' interest in inclusion of pregnant women in clinical research in general. First, pregnant women participate in the APOSTEL VI study for potential individual benefit and secondarily for altruistic motives, contrary to hypothetical studies. Second, a gatekeeping tendency hampers recruitment of pregnant women who might be eligible and willing, and questions about pregnant women's decisional capacities surface. Third, healthcare professionals sometimes use the counselling conversation to steer pregnant women in a direction. Fourth, all stakeholders are hesitant about inclusion of pregnant women in clinical research in general due to a protective sentiment. CONCLUSIONS: Pregnant women are willing to participate in the APOSTEL VI study for potential individual benefit and altruistic motives. However, an underlying protective sentiment, resulting in gatekeeping and directive counselling, sometimes hampers recruitment in the APOSTEL VI study as well as in clinical research in general. While bioethicists claim that inclusion of pregnant women should be customary, our study indicates that healthcare professionals, regulators, RECs and pregnant women themselves are not necessarily interested in inclusion. Advancing the situation and increasing the evidence-base for pregnant women and foetuses may require additional measures such as investing in the recruitment and feasibility of RCTs and stimulating pregnant women's decisional capacities.


Assuntos
Pesquisa Biomédica/ética , Estudos Clínicos como Assunto/psicologia , Gestantes/psicologia , Sujeitos da Pesquisa/psicologia , Adulto , Estudos Clínicos como Assunto/ética , Tomada de Decisões , Feminino , Grupos Focais , Humanos , Motivação , Gravidez , Estudos Prospectivos , Pesquisa Qualitativa
7.
Acta Obstet Gynecol Scand ; 98(7): 920-928, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30723900

RESUMO

INTRODUCTION: When women with a previous cesarean section and an unfavorable cervix have an indication for delivery, the choice is to induce labor or to perform a cesarean section. This study aims to assess the effectiveness and safety of a balloon catheter as a method of induction of labor in women with one previous cesarean section and an unfavorable cervix compared with an elective repeat cesarean section. MATERIAL AND METHODS: We performed a prospective cohort study in 51 hospitals in the Netherlands on term women with one previous cesarean section, a live singleton fetus in cephalic position, an unfavorable cervix and an indication for delivery. We recorded obstetric, maternal and neonatal characteristics. We compared the outcome of women who were induced with a balloon catheter with the outcome of women who delivered by elective repeat cesarean section. Main outcomes were maternal and neonatal morbidity. Mode of delivery was a secondary outcome for women who were induced. Adjusted odds ratios (aOR) were calculated using logistic regression, adjusted for potential confounders. RESULTS: Analysis was performed on 993 women who were induced and 321 women who had a repeat cesarean section (August 2011 until September 2012). Among the women who were induced, 560 (56.4%) delivered vaginally and 11 (1.1%) sustained a uterine rupture. Composite adverse maternal outcome (uterine rupture, severe postpartum hemorrhage or postpartum infection) occurred in 73 (7.4%) in the balloon and 14 (4.5%) women in the repeat cesarean section group (aOR 1.58, 95% confidence interval [CI] 0.85-2.96). Composite adverse neonatal outcome (Apgar score <7 at 5 minutes or umbilical pH <7.10) occurred in 57 (5.7%) and 10 (3.2%) neonates, respectively (aOR 1.40, 95% CI 0.87-3.48). Women who were induced had a shorter postpartum admission time (2.0 vs 3.0 days (P < 0.0001)). CONCLUSIONS: In women with a previous cesarean section and a need for delivery, induction of labor with a balloon catheter does not result in a significant increase in adverse maternal and neonatal outcomes as compared with planned cesarean section.

8.
BMJ ; 364: l344, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30786997

RESUMO

OBJECTIVE: To compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk women. DESIGN: Open label, randomised controlled non-inferiority trial. SETTING: 123 primary care midwifery practices and 45 hospitals (secondary care) in the Netherlands, 2012-16. PARTICIPANTS: 1801 low risk women with an uncomplicated singleton pregnancy: randomised to induction (n=900) or to expectant management until 42 weeks (n=901). INTERVENTIONS: Induction at 41 weeks or expectant management until 42 weeks with induction if necessary. PRIMARY OUTCOME MEASURES: Primary outcome was a composite of perinatal mortality and neonatal morbidity (Apgar score <7 at five minutes, arterial pH <7.05, meconium aspiration syndrome, plexus brachialis injury, intracranial haemorrhage, and admission to a neonatal intensive care unit (NICU). Secondary outcomes included maternal outcomes and mode of delivery. The null hypothesis that expectant management is inferior to induction was tested with a non-inferiority margin of 2%. RESULTS: Median gestational age at delivery was 41 weeks+0 days (interquartile range 41 weeks+0 days-41 weeks+1 day) for the induction group and 41 weeks+2 days (41 weeks+0 days-41 weeks+5 days) for the expectant management group. The primary outcome was analysed for both the intention-to-treat population and the per protocol population. In the induction group, 15/900 (1.7%) women had an adverse perinatal outcome versus 28/901 (3.1%) in the expectant management group (absolute risk difference -1.4%, 95% confidence interval -2.9% to 0.0%, P=0.22 for non-inferiority). 11 (1.2%) infants in the induction group and 23 (2.6%) in the expectant management group had an Apgar score <7 at five minutes (relative risk (RR) 0.48, 95% CI 0.23 to 0.98). No infants in the induction group and three (0.3%) in the expectant management group had an Apgar score <4 at five minutes. One fetal death (0.1%) occurred in the induction group and two (0.2%) in the expectant management group. No neonatal deaths occurred. 3 (0.3%) neonates in the induction group versus 8 (0.9%) in the expectant management group were admitted to an NICU (RR 0.38, 95% CI 0.10 to 1.41). No significant difference was found in composite adverse maternal outcomes (induction n=122 (13.6%) v expectant management n=102 (11.3%)) or in caesarean section rate (both groups n=97 (10.8%)). CONCLUSIONS: This study could not show non-inferiority of expectant management compared with induction of labour in women with uncomplicated pregnancies at 41 weeks; instead a significant difference of 1.4% was found for risk of adverse perinatal outcomes in favour of induction, although the chances of a good perinatal outcome were high with both strategies and the incidence of perinatal mortality, Apgar score <4 at five minutes, and NICU admission low. TRIAL REGISTRATION: Netherlands Trial Register NTR3431.


Assuntos
Plexo Braquial/lesões , Trabalho de Parto Induzido/efeitos adversos , Trabalho de Parto/fisiologia , Conduta Expectante/estatística & dados numéricos , Adolescente , Adulto , Cesárea/métodos , Feminino , Morte Fetal/etiologia , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil/tendências , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/epidemiologia , Trabalho de Parto Induzido/métodos , Síndrome de Aspiração de Mecônio/complicações , Síndrome de Aspiração de Mecônio/epidemiologia , Países Baixos/epidemiologia , Mortalidade Perinatal/tendências , Gravidez , Risco , Adulto Jovem
9.
Lancet ; 393(10174): 899-909, 2019 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-30773280

RESUMO

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. METHODS: We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. FINDINGS: We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 µmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 µmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 µmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). INTERPRETATION: The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 µmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. FUNDING: Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust.


Assuntos
Ácidos e Sais Biliares/sangue , Colestase Intra-Hepática/sangue , Complicações na Gravidez/sangue , Nascimento Prematuro/sangue , Natimorto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Colestase Intra-Hepática/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Morte Perinatal , Gravidez , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Curva ROC , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Natimorto/epidemiologia
10.
BMJ ; 362: k3478, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30209050

RESUMO

OBJECTIVE: To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. DESIGN: Randomised, phase III, double blinded international, multicentre clinical trial. SETTING: 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). PARTICIPANTS: 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. INTERVENTION: Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. MAIN OUTCOME MEASURE: The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). RESULTS: Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. CONCLUSION: Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.


Assuntos
Suplementos Nutricionais/efeitos adversos , Ácido Fólico/administração & dosagem , Hipertensão/prevenção & controle , Pré-Eclâmpsia/prevenção & controle , Adulto , Argentina/epidemiologia , Austrália/epidemiologia , Canadá/epidemiologia , Diabetes Gestacional/prevenção & controle , Método Duplo-Cego , Feminino , Ácido Fólico/provisão & distribução , Síndrome HELLP/etiologia , Humanos , Jamaica/epidemiologia , Gravidez , Proteinúria/etiologia , Fatores de Risco , Reino Unido/epidemiologia , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/provisão & distribução , Adulto Jovem
11.
Int J Cardiol ; 268: 106-112, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29848449

RESUMO

BACKGROUND: We evaluate pregnancy outcome and anticoagulation regimes in women with mechanical and biological prosthetic heart valves (PHV) for congenital heart disease. METHODS: Retrospective multicenter cohort studying pregnancy outcomes in an existing cohort of patients with PHV. RESULTS: 52 women had 102 pregnancies of which 78 pregnancies (46 women) ≥20 weeks duration (59 biological, 19 mechanical PHV). Miscarriages (n = 19, ≤20 weeks) occurred more frequently in women using anticoagulation (P < .05). During 42% of pregnancies of women with mechanical PHV a combined low molecular weight heparin (LMWH) vitamin-K-antagonist anticoagulation regime was used (n = 8). Overall, cardiovascular, obstetric and fetal/neonatal complications occurred in 17% (n = 13), 68% (n = 42) and 42% (n = 27) of the pregnancies. Women with mechanical PHV had significantly higher cardiovascular (12% vs 32%, P < .05), obstetric (59% vs 85%, P = .02) and fetal/neonatal (34% vs 61%, P < .05) complication rates than women with biological PHV. This was related to PHV thrombosis (n = 3, P < .02), post-partum hemorrhage (P < .02), cesarean section (P < .02), low birth weight and small for gestational age (both P < .05). PHV thrombosis occurred in 3 pregnancies, including 2/5 pregnancies with pulmonary mechanical PHV. PHV thrombosis was related to necessary cessation of anticoagulation therapy or insufficient monitoring of LMWH. Other cardiovascular complications occurred equally frequent in both groups. CONCLUSION: Complications occur more often in pregnancies of women with a mechanical PHV than in women with a biological PHV, mainly caused by PHV thrombosis and bleeding complications. Meticulous monitoring of anticoagulation in pregnant women is necessary. Women with a pulmonary mechanical PHV are at high risk of complications.


Assuntos
Bioprótese/efeitos adversos , Cardiopatias Congênitas/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Cardiovasculares na Gravidez/cirurgia , Adulto , Bioprótese/tendências , Estudos de Coortes , Feminino , Cardiopatias Congênitas/epidemiologia , Doenças das Valvas Cardíacas/epidemiologia , Próteses Valvulares Cardíacas/tendências , Humanos , Países Baixos/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Adulto Jovem
12.
Trials ; 19(1): 78, 2018 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-29378652

RESUMO

BACKGROUND: Since pregnant women are severely underrepresented in clinical research, many take the position that the exclusion of pregnant women from research must be justified unless there are compelling "scientific reasons" for their exclusion. However, it is questionable whether this approach renders research with pregnant women fair. This paper analyzes and evaluates when research with pregnant women can be considered as fair and what constitutes scientific reasons for exclusion. METHODS: Conceptual ethical and methodological analysis and evaluation of fair inclusion. RESULTS: Fair inclusion of pregnant women means (1) that pregnant women who are eligible are not excluded solely for being pregnant and (2) that the research interests of pregnant women are prioritized, meaning that they ought to receive substantially more attention. Fairness does not imply that pregnant women should be included in virtually every research project, as including only a few pregnant women in a population consisting only of women will not help to determine the effectiveness and safety of a treatment in pregnant women. Separate trials in pregnant women may be preferable once we assume, or know, that effects of interventions in pregnant women differ from the effects in other subpopulations, or when we assume, or know, that there are no differences. In the latter case, it may be preferable to conduct post-marketing studies or establish registries. If there is no conclusive evidence indicating either differences or equivalence of effects between pregnant and non-pregnant women, yet it seems unlikely that major differences or exact equivalence exist, the inclusion of pregnant women should be sufficient. Depending on the research question, this boils down to representativeness in terms of the proportion of pregnant and non-pregnant women, or to oversampling pregnant women. CONCLUSIONS: Fair inclusion of pregnant women in research implies that separate trials in pregnant women should be promoted. Inclusion of pregnant women has to be realized at the earliest phases of the research process. In addition to researchers and research ethics committees, scientific advisory councils, funders, drug regulatory agencies, pharmaceutical companies, journal editors and others have a joint responsibility to further develop the evidence base for drug use in pregnant women.


Assuntos
Ensaios Clínicos como Assunto/ética , Definição da Elegibilidade/ética , Consentimento Livre e Esclarecido/ética , Seleção de Pacientes/ética , Sujeitos da Pesquisa , Comitês de Ética em Pesquisa , Feminino , Humanos , Segurança do Paciente , Gravidez , Medição de Risco , Fatores de Risco
13.
Int J Gynaecol Obstet ; 141(2): 206-211, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29215704

RESUMO

OBJECTIVE: To determine whether women delivering preterm have unfavorable cardiovascular profiles as compared with women who deliver at term. METHODS: A prospective observational cohort study enrolled 165 women with spontaneous preterm delivery (sPTD) at 24+0 and 36+6 gestational weeks in three perinatal care centers in The Netherlands between August 2012 and August 2014. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein, glucose, and homocysteine were measured within 24 hours after delivery. Lipids and cardiovascular biochemical risk factors were compared between women with sPTD and an external comparison group of 30 women with term delivery via analysis of covariance. RESULTS: Mean gestational age at delivery was 30.7 ± 3.6 weeks in the sPTD group and 40.3 ± 1.3 weeks in the reference group. Data were adjusted for body mass index, age, and center. As compared with the reference group, total cholesterol and LDL-cholesterol levels were lower and glucose levels were higher among women with sPTD. CONCLUSION: An association between sPTD and unfavorable lipids and cardiovascular biochemical risk factors was not established. The higher levels of glucose in the sPTD group might be due to increased insulin resistance, which is associated with a higher risk of sPTD.


Assuntos
Doenças Cardiovasculares/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Índice de Massa Corporal , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Países Baixos , Gravidez , Estudos Prospectivos , Fatores de Risco , Nascimento a Termo , Triglicerídeos/sangue , Adulto Jovem
14.
Int J Cardiol ; 249: 145-150, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28966042

RESUMO

OBJECTIVE: Women with repaired coarctation of the aorta (rCoA) are at risk of hypertensive disorders and other complications during pregnancy. Hypertensive disorders in pregnant women are associated with inadequate uteroplacental flow, which is related to adverse offspring outcome. The aim of this study was to investigate the relationship of maternal cardiac function, placental function and pregnancy complications in women with rCoA. METHODS: We included 49 pregnant women with rCoA and 69 controls from the prospective ZAHARA-studies (Zwangerschap bij Aangeboren HARtAfwijkingen, pregnancy in congenital heart disease). Clinical evaluation, echocardiography and uteroplacental Doppler flow (UDF) measurements were performed at 20 and 32weeks gestation. Univariable regression analysis was performed. RESULTS: Comparison of rCoA and healthy women. In women with rCoA, tricuspid annular plane systolic excursion (TAPSE) decreased during pregnancy (25.7mm to 22.8mm, P=0.006). UDF indices and pregnancy complication rates were similar in both groups. Offspring of rCoA women had lower birth weight (3233g versus 3578g, P=0.001), which was associated with ß-blocker use during pregnancy (ß=-418.0, P=0.01). Association of cardiac function and UDF. Right ventricular (RV) function before pregnancy (TAPSE) and at 20weeks gestation (TAPSE and RV fractional area change) were associated with impaired UDF indices (umbilical artery pulsatility index at 20weeks ß=-0.02, P=0.01, resistance index at 20 and 32weeks ß=-0.01, P=0.02 and ß=-0.02, P=0.01 and uterine artery pulsatility and resistance index at 20weeks gestation ß=-0.02, P=0.05 and ß=-0.01, P=0.02). CONCLUSIONS: Women with rCoA tolerate pregnancy well. However, RV function is altered and is associated with impaired placentation.


Assuntos
Coartação Aórtica/fisiopatologia , Fluxometria por Laser-Doppler/tendências , Circulação Placentária/fisiologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Resultado da Gravidez , Adulto , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/cirurgia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
15.
BMC Pregnancy Childbirth ; 17(1): 284, 2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28870155

RESUMO

BACKGROUND: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. METHODS/DESIGN: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. DISCUSSION: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. TRIAL REGISTRATION: Trial registration number: NTR 4414 . Date of registration January 29th 2014.


Assuntos
Colo do Útero/patologia , Pessários , Nascimento Prematuro/prevenção & controle , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Doenças do Colo do Útero/complicações , Administração Intravaginal , Adolescente , Adulto , Medida do Comprimento Cervical , Protocolos Clínicos , Feminino , Humanos , Gravidez , Resultado da Gravidez , Nascimento Prematuro/etiologia , Resultado do Tratamento , Doenças do Colo do Útero/diagnóstico por imagem , Doenças do Colo do Útero/patologia , Adulto Jovem
16.
BMC Pregnancy Childbirth ; 17(1): 223, 2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28705190

RESUMO

BACKGROUND: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. METHODS/DESIGN: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. DISCUSSION: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. TRIAL REGISTRATION: Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.


Assuntos
Aspirina/administração & dosagem , Trabalho de Parto Prematuro/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Cuidado Pré-Natal/métodos , Prevenção Secundária/métodos , Adolescente , Adulto , Aspirina/economia , Análise Custo-Benefício , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Trabalho de Parto Prematuro/economia , Inibidores da Agregação de Plaquetas/economia , Gravidez , Resultado da Gravidez , Cuidado Pré-Natal/economia , Recidiva , Prevenção Secundária/economia , Resultado do Tratamento , Adulto Jovem
17.
J Med Ethics ; 43(10): 657-663, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28716977

RESUMO

BACKGROUND: Notwithstanding the need to produce evidence-based knowledge on medications for pregnant women, they remain underrepresented in clinical research. Sometimes they are excluded because of their supposed vulnerability, but there are no universally accepted criteria for considering pregnant women as vulnerable. Our aim was to explore whether and if so to what extent pregnant women are vulnerable as research subjects. METHOD: We performed a conceptual and empirical analysis of vulnerability applied to pregnant women. ANALYSIS: A conceptual analysis supports Hurst's definition of vulnerability. Consequently, we argue that pregnant women are vulnerable if they encounter an identifiably increased likelihood of incurring additional or greater wrong. According to the literature, this increased likelihood could exist of four alleged features for pregnant women's vulnerability: (i) informed consent, (ii) susceptibility to coercion, (iii) higher exposure to risk due to lack of knowledge, (iv) vulnerability of the fetus. DISCUSSION: Testing the features against Hurst's definition demonstrates that they all concern the same issue: pregnant women are only vulnerable because a higher exposure to risk due to lack of scientific knowledge comprises an increased wrong. Research Ethics Committees have a responsibility to protect the vulnerable, but a higher exposure to risk due to lack of scientific knowledge is a much broader issue and also needs to be addressed by other stakeholders. CONCLUSIONS: The only reason why pregnant women are potentially vulnerable is to the extent that they are increasingly exposed to higher risks due to a lack of scientific knowledge. Accordingly, the discussion can advance to the development of practical strategies to promote fair inclusion of pregnant women in clinical research.


Assuntos
Pesquisa Biomédica/ética , Comitês de Ética em Pesquisa , Gestantes , Sujeitos da Pesquisa , Comitês de Ética em Pesquisa/ética , Feminino , Humanos , Consentimento Livre e Esclarecido/ética , Gravidez , Populações Vulneráveis
19.
BMC Med Ethics ; 18(1): 35, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28506267

RESUMO

BACKGROUND: There is ambiguity with regard to what counts as an acceptable level of risk in clinical research in pregnant women and there is no input from stakeholders relative to such research risks. The aim of our paper was to explore what stakeholders who are actively involved in the conduct of clinical research in pregnant women deem an acceptable level of risk for pregnant women in clinical research. Accordingly, we used the APOSTEL VI study, a low-risk obstetrical randomised controlled trial, as a case-study. METHODS: We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed healthcare professionals, Research Ethics Committee members (RECs) and regulators who are actively involved in the conduct of clinical research in pregnant women, in addition to pregnant women recruited for the APOSTEL VI case-study in the Netherlands. RESULTS: Three themes characterise the way stakeholders view risks in clinical research in pregnant women in general. Additionally, one theme characterises the way healthcare professionals and pregnant women view risks with respect to the case-study specifically. First, ideas on what constitutes an acceptable level of risk in general ranged from a preference for zero risk for the foetus up to minimal risk. Second, the desirability of clinical research in pregnant women in general was questioned altogether. Third, stakeholders proposed to establish an upper limit of risk in potentially beneficial clinical research in pregnant women in order to protect the foetus and the pregnant woman from harm. Fourth and finally, the case-study illustrates that healthcare professionals' individual perception of risk may influence recruitment. CONCLUSIONS: Healthcare professionals, RECs, regulators and pregnant women are all risk adverse in practice, possibly explaining the continuing underrepresentation of pregnant women in clinical research. Determining the acceptable levels of risk on a universal level alone is insufficient, because the individual perception of risk also influences behaviour towards pregnant women in clinical research. Therefore, bioethicists and researchers might be interested in changing the perception of risk, which could be achieved by education and awareness about the actual benefits and harms of inclusion and exclusion of pregnant women.


Assuntos
Pesquisa Biomédica/ética , Gestantes , Adulto , Feminino , Grupos Focais , Pessoal de Saúde/psicologia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Pesquisa Qualitativa , Medição de Risco , Adulto Jovem
20.
Obstet Gynecol ; 129(2): 327-336, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28079785

RESUMO

OBJECTIVE: Spontaneous preterm birth is an important cause of neonatal mortality and morbidity. An increasing body of evidence suggests that uteroplacental ischemia plays an important role in the etiology of spontaneous preterm birth. We aimed to study whether antiplatelet agents reduce the risk of spontaneous preterm birth. DATA SOURCES: We included data from an individual participant data meta-analysis of studies that had evaluated the effect of antiplatelet agents to reduce preeclampsia (Perinatal Antiplatelet Review of International Studies Individual Participant Data). METHODS OF STUDY SELECTION: The meta-analysis included 31 studies that randomized women to low-dose aspirin-dipyridamole or placebo-no treatment as a primary preventive strategy for preeclampsia. For the current study we analyzed data from 17 trials (28,797 women) that supplied data on type of delivery (spontaneous compared with indicated birth). TABULATION, INTEGRATION, AND RESULTS: Primary endpoints were spontaneous preterm birth at less than 37 weeks, less than 34 weeks, and less than 28 weeks of gestation. We analyzed outcomes for each trial separately using χ statistics and combined in an individual participant data meta-analysis using a binary logistic regression model. Women assigned to antiplatelet treatment compared with placebo or no treatment had a lower risk of spontaneous preterm birth at less than 37 weeks (relative risk [RR] 0.93, 95% confidence interval [CI] 0.86-0.996) and less than 34 weeks of gestation (RR 0.86, 95% CI 0.76-0.99). The RR of having a spontaneous preterm birth at less than 37 weeks of gestation was 0.83 (95% CI 0.73-0.95) for women who have had a previous pregnancy and 0.98 (95% CI 0.89-1.09) for women in their first pregnancy. The treatment effect was stable in all other prespecified subgroups. CONCLUSION: Antiplatelet agents reduce spontaneous preterm birth in pregnant women at risk for preeclampsia.


Assuntos
Aspirina/administração & dosagem , Dipiridamol/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Pré-Eclâmpsia/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Adulto , Feminino , Idade Gestacional , Humanos , Modelos Logísticos , Gravidez , Resultado da Gravidez , Nascimento Prematuro/etiologia , Fatores de Risco , Resultado do Tratamento
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