RESUMEN
BACKGROUND: Childhood cancer survivors (CCS) are at increased risk of cardiomyopathy during pregnancy if they have prior cardiotoxic exposure. Currently, there is no consensus on the necessity, timing and modality of cardiac monitoring during and after pregnancy. Therefore, we examined cardiac function using contemporary echocardiographic parameters during pregnancy in CCS with cardiotoxic treatment exposure, and we observed obstetric outcomes in CCS, including in women without previous cardiotoxic treatment exposure. METHOD: A single-center retrospective cohort study was conducted among 39 women enrolled in our institution's cancer survivorship outpatient clinic. Information on potential cardiotoxic exposure in childhood, cancer diagnosis and outcomes of all pregnancies were collected through interviews and review of health records. Echocardiographic exams before and during pregnancy were retrospectively analyzed for left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) if available. The primary outcomes were (i) left ventricular dysfunction (LVD) during pregnancy, defined as LVEF < 50% or a decline of ≥ 10% in LVEF below normal (< 54%), and (ii) symptomatic heart failure (HF). Rate of obstetric and fetal complications was compared to the general population through the national perinatal registry (PERINED). RESULTS: All pregnancies (91) of 39 women were included in this study. The most common malignancy was leukemia (N = 17, 43.6%). In 22 patients, echocardiograms were retrospectively analyzed. LVEFbaseline was 55.4 ± 1.2% and pre-existing subnormal LVEF was common (7/22, 31.8/%). The minimum value of LVEF during pregnancy was 3.8% lower than baseline (p = 0.002). LVD occurred in 9/22 (40.9%) patients and HF was not observed. When GLS was normal at baseline (< -18.0%; N = 12), none of the women developed LVD. Nine of out ten women with abnormal GLS at baseline developed LVD later in pregnancy. In our cohort, the obstetric outcomes seemed comparable with the general population unless patients underwent abdominal irradiation (N = 5), where high rates of preterm birth (only 5/18 born at term) and miscarriage (6/18 pregnancies) were observed. CONCLUSION: Our study suggests that women with prior cardiotoxic treatment have a low risk of LVD during pregnancy if GLS at baseline was normal. Pregnancy outcomes are similar to the healthy population except when patients underwent abdominal irradiation.
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Nacimiento Prematuro , Disfunción Ventricular Izquierda , Recién Nacido , Embarazo , Humanos , Femenino , Función Ventricular Izquierda , Volumen Sistólico , Estudios Retrospectivos , Cardiotoxicidad/epidemiología , Cardiotoxicidad/etiología , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/epidemiologíaRESUMEN
OBJECTIVE: To compare guidelines from eight high-income countries on prevention and management of postpartum haemorrhage (PPH), with a particular focus on severe PPH. DESIGN: Comparative study. SETTING: High-resource countries. POPULATION: Women with PPH. METHODS: Systematic comparison of guidance on PPH from eight high-income countries. MAIN OUTCOME MEASURES: Definition of PPH, prophylactic management, measurement of blood loss, initial PPH-management, second-line uterotonics, non-pharmacological management, resuscitation/transfusion management, organisation of care, quality/methodological rigour. CONCLUSIONS: Our study highlights areas where strong evidence is lacking. There is need for a universal definition of (severe) PPH. Consensus is required on how and when to quantify blood loss to identify PPH promptly. Future research may focus on timing and sequence of second-line uterotonics and non-pharmacological interventions and how these impact maternal outcome. Until more data are available, different transfusion strategies will be applied. The use of clear transfusion-protocols are nonetheless recommended to reduce delays in initiation. There is a need for a collaborative effort to develop standardised, evidence-based PPH guidelines. RESULTS: Definitions of (severe) PPH varied as to the applied cut-off of blood loss and incorporation of clinical parameters. Dose and mode of administration of prophylactic uterotonics and methods of blood loss measurement were heterogeneous. Recommendations on second-line uterotonics differed as to type and dose. Obstetric management diverged particularly regarding procedures for uterine atony. Recommendations on transfusion approaches varied with different thresholds for blood transfusion and supplementation of haemostatic agents. Quality of guidelines varied considerably.
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Oxitócicos , Hemorragia Posparto , Embarazo , Femenino , Humanos , Hemorragia Posparto/prevención & control , Hemorragia Posparto/tratamiento farmacológico , Oxitócicos/uso terapéutico , Oxitocina/uso terapéutico , Parto Obstétrico/métodos , Quimioterapia CombinadaRESUMEN
BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. METHODS AND FINDINGS: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. CONCLUSIONS: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. TRIAL REGISTRATION: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.
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Aspirina/administración & dosificación , Trabajo de Parto Prematuro/prevención & control , Adulto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Países Bajos , Embarazo , Nacimiento Prematuro/prevención & controlRESUMEN
Patients with SLE are often young females of childbearing age and a pregnancy wish in this patient group is common. However, SLE patients are at high risk for adverse pregnancy outcomes that require adequate guidance. It is widely acknowledged that pre-pregnancy counselling is the pivotal first step in the management of SLE patients with a wish to become pregnant. Next, management of these patients is usually multidisciplinary and often requires specific expertise from the different physicians involved. Very recently a EULAR recommendation was published emphasizing the need for adequate preconception counselling and risk stratification. Therefore the present review specifically addresses the issue of pre-pregnancy counselling for SLE patients with an evidence-based approach. The review summarizes data retrieved from recently published, high-quality cohort studies that have contributed to a better understanding and estimation of pregnancy-related risks for SLE patients. The present review categorizes risks from a patient-oriented point of view, that is, the influence of pregnancy on SLE, of SLE on pregnancy, of SLE on the foetus/neonate and of SLE-related medication. Lastly, pre-pregnancy counselling of SLE patients with additional secondary APS is reviewed. Collectively these data can guide clinicians to formulate appropriate preventive strategies and patient-tailored monitoring plans during pre-pregnancy counselling of SLE patients.
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Consejo/métodos , Servicios de Planificación Familiar/métodos , Lupus Eritematoso Sistémico/psicología , Atención Preconceptiva/métodos , Complicaciones del Embarazo/psicología , Adulto , Femenino , Humanos , Recién Nacido , Lupus Eritematoso Sistémico/complicaciones , Embarazo , Complicaciones del Embarazo/etiología , Resultado del Embarazo , Adulto JovenRESUMEN
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.
Asunto(s)
Aspirina/administración & dosificación , Trabajo de Parto Prematuro/prevención & control , Inhibidores de Agregación Plaquetaria/administración & dosificación , Atención Prenatal/métodos , Prevención Secundaria/métodos , Adolescente , Adulto , Aspirina/economía , Análisis Costo-Beneficio , Método Doble Ciego , Femenino , Edad Gestacional , Humanos , Trabajo de Parto Prematuro/economía , Inhibidores de Agregación Plaquetaria/economía , Embarazo , Resultado del Embarazo , Atención Prenatal/economía , Recurrencia , Prevención Secundaria/economía , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
Asunto(s)
Cuello del Útero/patología , Pesarios , Nacimiento Prematuro/prevención & control , Progesterona/administración & dosificación , Progestinas/administración & dosificación , Enfermedades del Cuello del Útero/complicaciones , Administración Intravaginal , Adolescente , Adulto , Medición de Longitud Cervical , Protocolos Clínicos , Femenino , Humanos , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/etiología , Resultado del Tratamiento , Enfermedades del Cuello del Útero/diagnóstico por imagen , Enfermedades del Cuello del Útero/patología , Adulto JovenRESUMEN
BACKGROUND: Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor. METHODS/DESIGN: This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and ß 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat. DISCUSSION: The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth. TRIAL REGISTRATION: Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.
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Cuello del Útero/anatomía & histología , Trabajo de Parto Prematuro , Pesarios , Nacimiento Prematuro/prevención & control , Medición de Longitud Cervical , Cuello del Útero/diagnóstico por imagen , Femenino , Fibronectinas/sangre , Humanos , Tamaño de los Órganos , Embarazo , Proyectos de Investigación , Factores de TiempoRESUMEN
AIM: The aim of this study was to examine the incidence, placental characteristics and outcome in acute peripartum twin-twin transfusion syndrome (TTTS). MATERIAL AND METHODS: All consecutive cases of monochorionic (MC) twins admitted to our center were included in the study. We excluded cases with chronic TTTS or twin anemia polycythemia sequence. Acute peripartum TTTS was defined when the inter-twin hemoglobin difference at birth was >8 g/dL. RESULTS: A total of 241 MC twin pregnancies were included in the study. Acute peripartum TTTS was detected in six cases (2.5%, 6/241). Vaginal delivery occurred more often in the acute peripartum TTTS group compared to the control group of uncomplicated MC pregnancies, 100% (6/6) versus 57% (135/235) (P = 0.002), respectively. Acute anemia was detected only in firstborn twins. Placental angioarchitecture in acute peripartum TTTS was similar to the placentas in the control group. CONCLUSIONS: The incidence of acute peripartum TTTS is low (2.5%). Birth order and mode of delivery appear to be associated with increased risk of acute peripartum TTTS.
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Transfusión Feto-Fetal/fisiopatología , Placenta/patología , Enfermedad Aguda , Adulto , Femenino , Transfusión Feto-Fetal/epidemiología , Transfusión Feto-Fetal/patología , Humanos , Incidencia , Mortalidad Infantil , Recién Nacido , Masculino , Países Bajos/epidemiología , Periodo Periparto , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. METHODS: In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. FINDINGS: Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10â355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47-0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55-2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35-4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74-3·58]; I2=0%), preterm birth (2·65 [1·87-3·77]; I2=0%), and pre-eclampsia (5·86 [3·41-10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96-4·33]; I2=21%) and pre-eclampsia (2·32 [1·40-3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27-0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44-5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29-2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. INTERPRETATION: We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. FUNDING: None.
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Cerclaje Cervical/métodos , Medición de Longitud Cervical , Pesarios , Nacimiento Prematuro/prevención & control , Incompetencia del Cuello del Útero/terapia , Adulto , Cuello del Útero/patología , Protocolos Clínicos , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: SLE and/or antiphospholipid syndrome (SLE/APS) are complex and rare systemic autoimmune diseases that predominantly affect women of childbearing age. Women with SLE/APS are at high risk of developing complications during pregnancy. Therefore, clinical practice guidelines recommend that patients with SLE/APS should receive multidisciplinary counselling before getting pregnant. We investigated the clinical effectiveness of implementing a multidisciplinary clinical pathway including prepregnancy counselling of patients with SLE/APS. METHODS: A clinical pathway with specific evaluation and prepregnancy counselling for patients with SLE/APS was developed and implemented in a tertiary, academic hospital setting. Patients were prospectively managed within the clinical pathway from 2014 onwards and compared with a retrospective cohort of patients that was not managed in a clinical pathway. Primary outcome was a combined outcome of disease flares for SLE and thromboembolic events for APS. Secondary outcomes were maternal and fetal pregnancy complications. RESULTS: Seventy-eight patients with 112 pregnancies were included in this study. The primary combined outcome was significantly lower in the pathway cohort (adjusted OR (aOR) 0.20 (95% CI 0.06 to 0.75)) which was predominantly determined by a fivefold risk reduction of SLE flares (aOR 0.22 (95% CI 0.04 to 1.09)). Maternal and fetal pregnancy complications were not different between the cohorts (respectively, aOR 0.91 (95% CI 0.38 to 2.17) and aOR 1.26 (95% CI 0.55 to 2.88)). CONCLUSIONS: The outcomes of this study suggest that patients with SLE/APS with a pregnancy wish benefit from a multidisciplinary clinical pathway including prepregnancy counselling.
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Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Síndrome Antifosfolípido/complicaciones , Vías Clínicas , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Embarazo , Complicaciones del Embarazo/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: While epidural analgesia (EA) is associated with maternal fever during labor, the impact on the risk for maternal and/or neonatal sepsis is unknown. OBJECTIVES: The aim of this systematic review was to investigate the effect of epidural-related intrapartum fever on maternal and neonatal outcomes. METHODS: OVID MEDLINE, OVID Embase, the Cochrane Library, Cochrane Controlled Register of Trials, and clinical trial registries were searched for randomized controlled trials (RCT) and observational cohort studies from inception to November 2018. A total of 761 studies were identified with 100 eligible for full-text review. Only articles investigating the relationship between EA and maternal fever during labor were eligible for inclusion. Study quality was assessed using the Cochrane's Risk of Bias tool and National Institute of Health Quality Assessment Tool. Two meta-analyses - one each for the RCT and observational cohort groups - were performed using the random-effects model of Mantel-Haenszel to produce summary risk ratios (RR) with 95% CI. RESULTS: Twelve RCTs and 16 observational cohort studies involving 579,157 parturients were included. RRs for maternal fever for the RCT and cohort analyses were 3.54 (95% CI 2.61-4.81) and 5.60 (95% CI 4.50-6.97), respectively. Meta-analyses of RR for maternal infection in both groups were infeasible given few occurrences. Meta-analysis of data from observational studies showed an increased risk for maternal antibiotic treatment in the epidural group (RR 2.60; 95% CI 1.31-5.17). For both analyses, neonates born to women with an epidural were not evaluated more often for suspected sepsis. Neither analysis reported an increased rate of neonatal bacteremia or neonatal antibiotic treatment after EA, although data precluded conclusiveness. CONCLUSION: EA increases the risk of intrapartum fever and maternal antibiotic treatment. However, a definite conclusion on whether EA increases the risk for a proven maternal and/or neonatal bacteremia cannot be drawn due to the low quality of data. Further research on whether epidural-related intrapartum fever is of infectious origin or not is therefore needed.
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Analgesia Epidural , Analgesia Epidural/efectos adversos , Antibacterianos/uso terapéutico , Femenino , Fiebre/tratamiento farmacológico , Fiebre/epidemiología , Fiebre/etiología , Humanos , Recién Nacido , Morbilidad , Parto , EmbarazoRESUMEN
OBJECTIVE: Maternal heart disease (HD) complicates 1-4 % of pregnancies and is associated with adverse maternal and fetal outcomes. Although vaginal birth is generally recommended in the guidelines, cesarean section (CS) rates in women with HD are often high. Aim of the present study was to evaluate mode of birth and pregnancy outcomes in women with HD in a tertiary care hospital in the Netherlands. STUDY DESIGN: The study population consisted of 128 consecutive pregnancies in 99 women with HD, managed by a pregnancy heart team between 2012-2017 and ending in births after 24 weeks' gestation. Pregnancy risk was assessed per modified World Health Organization class. Mode of birth (planned and performed) and maternal and fetal complications (cardiovascular events, postpartum hemorrhage, prematurity, small for gestational age and death) were assessed for each pregnancy. RESULTS: Pregnancy risk was classified as modified World Health Organization class I in 23 %, class II in 50 %, class III in 21 % and class IV in 6% of pregnancies. Planned mode of birth was vaginal in 114 pregnancies (89 %) and CS in 14 (11 %; nine for obstetric and five for cardiac indication). An unplanned CS was performed in 18 pregnancies (16 %; 16 for obstetric and two for cardiac indications). Overall mode of birth was vaginal in 75 % and CS in 25 %. Twelve cardiovascular events occurred in eight pregnancies (6 %), postpartum hemorrhage in nine (7 %) and small for gestational age in 14 (11 %). No maternal or fetal deaths occurred. CONCLUSIONS: Findings of this study indicate that - given that pregnancies are managed and mode of birth is meticulously planned by a multidisciplinary pregnancy heart team - vaginal birth is a suitable option for women with HD.
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Parto Obstétrico/estadística & datos numéricos , Cardiopatías/epidemiología , Complicaciones Cardiovasculares del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Parto Obstétrico/clasificación , Femenino , Cardiopatías/clasificación , Humanos , Países Bajos/epidemiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/clasificación , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria/estadística & datos numéricosRESUMEN
Importance: Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes. Objective: To determine whether sildenafil reduces perinatal mortality or major morbidity. Design, Setting, and Participants: This placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants. Interventions: Participants were randomized to sildenafil, 25 mg, 3 times a day vs placebo. Main Outcomes and Measures: The primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge. Results: Out of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weight, 464 [186] g). In July 2018, the trial was halted owing to concerns that sildenafil may cause neonatal pulmonary hypertension, whereas benefit on the primary outcome was unlikely. The primary outcome, perinatal mortality or major neonatal morbidity, occurred in the offspring of 65 participants (60.2%) allocated to sildenafil vs 58 participants (54.2%) allocated to placebo (relative risk, 1.11; 95% CI, 0.88-1.40; P = .38). Pulmonary hypertension, a predefined outcome important for monitoring safety, occurred in 16 neonates (18.8%) in the sildenafil group vs 4 neonates (5.1%) in the placebo group (relative risk, 3.67; 95% CI, 1.28-10.51; P = .008). Conclusions and Relevance: These findings suggest that antenatal maternal sildenafil administration for severe early onset fetal growth restriction did not reduce the risk of perinatal mortality or major neonatal morbidity. The results suggest that sildenafil may increase the risk of neonatal pulmonary hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT02277132.
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Peso al Nacer , Terminación Anticipada de los Ensayos Clínicos , Retardo del Crecimiento Fetal/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Enfermedades Placentarias/tratamiento farmacológico , Citrato de Sildenafil/uso terapéutico , Adulto , Método Doble Ciego , Femenino , Retardo del Crecimiento Fetal/etiología , Edad Gestacional , Humanos , Hipertensión Pulmonar/inducido químicamente , Recién Nacido , Enfermedades del Recién Nacido/inducido químicamente , Enfermedades del Recién Nacido/prevención & control , Análisis de Intención de Tratar , Masculino , Arteria Cerebral Media/fisiología , Mortalidad Perinatal , Inhibidores de Fosfodiesterasa 5/efectos adversos , Enfermedades Placentarias/fisiopatología , Preeclampsia/etiología , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Flujo Pulsátil , Citrato de Sildenafil/efectos adversos , Arterias Umbilicales/fisiologíaRESUMEN
INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6134; Pre-results.
Asunto(s)
Diabetes Gestacional/tratamiento farmacológico , Gliburida/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Administración Oral , Glucemia/efectos de los fármacos , Análisis Costo-Beneficio , Diabetes Gestacional/sangre , Quimioterapia Combinada , Estudios de Equivalencia como Asunto , Femenino , Edad Gestacional , Humanos , Insulina/uso terapéutico , Estudios Multicéntricos como Asunto , Embarazo , Resultado del EmbarazoRESUMEN
AIM: Perinatal mortality and morbidity in monochorionic (MC) twins appears to be increasing compared to dichorionic (DC) twins. The aim of our study was to determine the difference in perinatal mortality and morbidity in MC and DC twins born after 37 weeks' gestation. DESIGN: A retrospective, cross-sectional study of medical records. Setting. Large tertiary care centre in the Netherlands. POPULATION: All twins delivered > or =37 gestational weeks at the Leiden University Medical Centre between 1988 and 2004 were included in the study. METHODS: Perinatal outcome was assessed in all term twins. Differentiation between a MC study group and a DC control group was made based on gender, intertwin membrane histology, or first trimester ultrasound. MAIN OUTCOME MEASURES: Perinatal mortality and morbidity was assessed. Morbidity was defined as admission to the neonatal nursery. RESULTS: We included 383 DC and 74 MC twin pregnancies. Three fetuses died in utero in two MC pregnancies at 38 gestational weeks. One surviving MC co-twin had a right-sided hemiparesis due to a large parenchymal defect in the left cerebral hemisphere. Perinatal mortality was 2% (3/148) in MC and 0% (0/766) in DC twins (p=0.004). The admission rate to the neonatal nursery was 27% in MC and 19% in DC twins (p=0.031). CONCLUSIONS: At term, MC twins have a higher risk for perinatal mortality and a higher admission rate to the neonatal nursery compared to DC twins. Given the increased mortality, a prospective study is needed to determine the effects of elective delivery in uncomplicated MC twin pregnancies at around 37 weeks' gestation.
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Mortalidad Infantil , Gemelos Dicigóticos , Gemelos Monocigóticos , Estudios Transversales , Femenino , Humanos , Recién Nacido , Cuidado Intensivo Neonatal , Masculino , Morbilidad , Embarazo , Embarazo Múltiple , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess the effectiveness of cervical pessary in reducing the rate of preterm birth in women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor. METHODS: In a multicenter open-label randomized controlled trial, a cervical pessary was compared with no intervention (control group) (one-to-one ratio). Women between 24 and 34 weeks of gestation at high risk for preterm birth based on a short cervical length (less than 15 mm) or an intermediate cervical length (between 15 and 30 mm) with a positive fetal fibronectin test who did not deliver after an episode of threatened preterm labor were eligible. The primary outcome was birth before 37 weeks of gestation. Secondary outcomes were a composite adverse neonatal outcome, preterm birth before 34 and 32 weeks of gestation, and side effects. A total sample size of 200 women carrying singletons was planned so as to have adequate statistical power to detect a reduction in the rate of preterm birth from 40% to 20%. Women with twin gestations were also enrolled but were considered only in secondary analyses. After a planned interim analysis, the trial was stopped for futility. RESULTS: From November 2013 through September 2016, 130 women with a singleton pregnancy (65 pessary, 65 no treatment) were recruited. The groups had comparable baseline characteristics. In the cervical pessary group, 31 (48%) women delivered before 37 weeks of gestation compared with 25 (39%) in the no-treatment group (relative risk 1.2, 95% CI 0.83-1.8). Nine (15%) children in the cervical pessary group had the composite adverse perinatal outcome compared with eight (13%) in the control group (relative risk 1.2, 95% CI 0.49-2.9). CONCLUSION: In women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor, treatment with a cervical pessary is not effective. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, NTR4210.
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Trabajo de Parto Prematuro/prevención & control , Pesarios/estadística & datos numéricos , Adulto , Femenino , Humanos , Embarazo , Prevención Secundaria , Adulto JovenRESUMEN
OBJECTIVE: The objective of this study was to determine the incidence of velamentous cord insertion and placental territory discordancy in monochorionic twins with and without twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: All consecutive placentas of monochorionic twins delivered at our center between June 2002 and April 2006 were studied with vascular injection of the umbilical vessels with colored dyes. Velamentous cord insertions were recorded and individual placental territories were calculated by computer analysis. RESULTS: A total of 76 monochorionic placentas with TTTS and 63 monochorionic placentas without TTTS were studied. The incidence of velamentous cord insertion (per fetus) in the TTTS group and the non-TTTS group was 13% (20 of 152) and 14% (18 of 126), respectively (P = .79). Placental territory discordancy in the TTTS group and the non-TTTS group was 20% and 20% (P = 0.83). In the TTTS group, donor twins had a velamentous cord insertion more often than recipient twins (24% and 3%, respectively, P < .001) and a smaller placental territory (44% and 56%, respectively, P < .001). CONCLUSION: Our findings suggest that velamentous cord insertion and unequal placental territory are not critical factors for the development of TTTS.
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Transfusión Feto-Fetal/etiología , Enfermedades Placentarias/epidemiología , Cordón Umbilical/anomalías , Femenino , Humanos , Incidencia , Placenta/anomalías , Embarazo , Gemelos MonocigóticosRESUMEN
OBJECTIVE: This study was undertaken to determine the long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome treated with laser. STUDY DESIGN: All twin-to-twin transfusion syndrome cases treated at our center with laser between August 2000 and December 2003 were included in the study. Neurologic, mental, and psychomotor development at 2 years of age corrected for prematurity was assessed in all twin-to-twin transfusion syndrome survivors. Neurodevelopmental impairment was defined as any of the following: cerebral palsy, deafness, blindness, mental, or psychomotor development index of the Bayley Scales of Infant Development II less than 2 SD. RESULTS: A total of 82 twin-to-twin transfusion syndrome pregnancies were treated with fetoscopic laser surgery during the study period. Perinatal survival was 70% (115/164). The incidence of neurodevelopmental impairment was 17% (19/115) and was due to cerebral palsy (n = 8), mental developmental delay (n = 9), psychomotor developmental delay (n = 12), and deafness (n = 1). CONCLUSION: The incidence of neurodevelopmental impairment in twin-to-twin transfusion syndrome survivors treated with laser is high and warrants long-term follow-up.
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Discapacidades del Desarrollo/etiología , Transfusión Feto-Fetal/cirugía , Fetoscopía/efectos adversos , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Enfermedades del Sistema Nervioso/etiología , Trastornos Psicomotores/etiología , Preescolar , Discapacidades del Desarrollo/epidemiología , Femenino , Humanos , Masculino , Enfermedades del Sistema Nervioso/epidemiología , Embarazo , Trastornos Psicomotores/epidemiología , Factores de TiempoRESUMEN
OBJECTIVE: Laser coagulation of anastomotic vessels on the placental surface is the treatment of choice in severe second trimester twin-to-twin transfusion syndrome (TTTS). This procedure is associated with technical difficulties when the placenta is located on the anterior side of the uterus. We describe a novel technique for fetoscopy in TTTS with completely anterior placenta where laparoscopy is used to guide safe percutaneous insertion of the fetoscope through the lateral abdominal wall and the dorsal side of the uterus. METHODS: Prospective controlled series of 16 TTTS pregnancies with completely anterior placenta (study group) treated with this novel technique. Studied outcomes were technical result of the procedure and perinatal survival. Outcome in the study group was compared with outcome of 49 TTTS pregnancies treated with conventional percutaneous fetoscopic laser without laparoscopy, 9 of these with partially anterior placenta (control group A) and 40 with lateral or posterior placenta (control group B). RESULTS: In the study group, the procedure-related complication rate was 25% (4/16). In 1 case, uterine entry of the fetoscope from the lateral abdominal wall was not possible due to complex bowel adhesions. In 3 patients, intra-amniotic haemorrhage occurred after fetoscopic entry, preventing complete laser coagulation of anastomoses. One of these patients required 2 units of blood transfusion. The procedure-related complication rate in control groups A and B was 22% (2/9) and 5% (2/40), respectively (intra-amniotic haemorrhage n = 3, severe leakage of amniotic fluid into the peritoneal cavity, n = 1). Perinatal survival in the study group, control group A and control group B was 63% (20/32), 78% (14/18) and 70% (56/80), respectively. CONCLUSION: Combined laparoscopy and fetoscopy is a novel technique that enables safe uterine entry and creates optimal visualisation for laser coagulation of inter-twin anastomoses in TTTS pregnancies with completely anterior placenta. The procedure-related complication rate and perinatal survival rate were similar compared to the conventional percutaneous technique. Procedure-related complications occur more often with partially or completely anterior placenta.