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BACKGROUND: Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS: We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS: A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, -0.04 kg; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS: Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.).
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Diabetes Gestacional , Femenino , Humanos , Recién Nacido , Embarazo , Australia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Hipertensión/etiología , Preeclampsia/epidemiología , Preeclampsia/etiología , Preeclampsia/prevención & control , Resultado del Embarazo , Mortinato , Primer Trimestre del EmbarazoRESUMEN
INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.
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Hipertensión Inducida en el Embarazo , Humanos , Embarazo , Femenino , Australia , Nueva Zelanda , Hipertensión Inducida en el Embarazo/diagnóstico , Hipertensión Inducida en el Embarazo/terapia , Hipertensión Inducida en el Embarazo/prevención & control , Preeclampsia/diagnóstico , Preeclampsia/prevención & control , Preeclampsia/terapia , Sociedades Médicas , Obstetricia/normas , Antihipertensivos/uso terapéutico , Guías de Práctica Clínica como AsuntoRESUMEN
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy liver disease, characterised by pruritus and increased total serum bile acids (TSBA), Australian incidence 0.6-0.7%. ICP is diagnosed by non-fasting TSBA ≥19 µmol/L in a pregnant woman with pruritus without rash without a known pre-existing liver disorder. Peak TSBA ≥40 and ≥100 µmol/L identify severe and very severe disease respectively, associated with spontaneous preterm birth when severe, and with stillbirth, when very severe. Benefit-vs-risk for iatrogenic preterm birth in ICP remains uncertain. Ursodeoxycholic acid remains the best pharmacotherapy preterm, improving perinatal outcome and reducing pruritus, although it has not been shown to reduce stillbirth.
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INTRODUCTION: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (F ENO)-based asthma management improves perinatal outcomes compared to usual care. METHODS: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6-12â weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat). RESULTS: Pregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05). CONCLUSION: F ENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.
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Asma , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Embarazo , Humanos , Óxido Nítrico , Espiración , Asma/tratamiento farmacológico , RespiraciónRESUMEN
BACKGROUND: Rheumatic heart disease (RHD) poses significant perinatal risks. We aimed to describe the spectrum, severity and outcomes of rheumatic mitral valve disease in pregnancy in Australia and New Zealand. METHODS: A prospective, population-based cohort study of pregnant women with RHD recruited 2013-14 through the hospital-based Australasian Maternity Outcomes Surveillance System. Outcome measures included maternal and perinatal morbidity and mortality. Univariable and multivariable logistic regression analyses were undertaken to test for predictors of adverse maternal and perinatal outcomes. RESULTS: Of 274 pregnant women identified with RHD, 124 (45.3%) had mitral stenosis (MS) and 150 (54.7%) had isolated mitral regurgitation (MR). One woman with mild MS/moderate MR died. There were six (2.2%) stillbirths and two (0.7%) neonatal deaths. Babies born to women with MS were twice as likely to be small-for-gestational-age (22.7% vs 11.4%, p=0.013). In women with MS, use of cardiac medication (AOR 7.42) and having severe stenosis (AOR 16.35) were independently associated with adverse cardiac outcomes, while New York Heart Association (NYHA) class >1 (AOR 3.94) was an independent predictor of adverse perinatal events. In women with isolated MR, use of cardiac medications (AOR 7.03) and use of anticoagulants (AOR 6.05) were independently associated with adverse cardiac outcomes. CONCLUSIONS: Careful monitoring and specialist care for women with RHD in pregnancy is required, particularly for women with severe MS, those on cardiac medication, and those on anticoagulation, as these are associated with increased risk of adverse maternal cardiac outcomes. In the context of pregnancy, contraception and preconception planning are important for young women diagnosed with RHD.
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Estenosis de la Válvula Mitral , Complicaciones Cardiovasculares del Embarazo , Cardiopatía Reumática , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Válvula Mitral , Estenosis de la Válvula Mitral/diagnóstico , Estenosis de la Válvula Mitral/epidemiología , Nueva Zelanda/epidemiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Mujeres Embarazadas , Estudios Prospectivos , Cardiopatía Reumática/complicaciones , Cardiopatía Reumática/diagnóstico , Cardiopatía Reumática/epidemiologíaRESUMEN
Miscarriage is the most common complication in early pregnancy. It was recently reported in mice that miscarriage can be prevented through the administration of niacin. We conducted a prospective, exploratory pilot study involving 24 women who were less than 14 weeks pregnant. Neither niacin intake (P = 0.24) nor urinary vitamin B3 measured as the 1-methyl-5-carboxylamide-2-pyridone/N-1-methylnicotinamide (2-pyr/MNA) ratio (P = 1.00) predicted miscarriage. However, the difference in mean 2-pyr/MNA ratios between women who miscarried and controls suggests there may be a threshold niacin level protective in miscarriage prevention warranting further investigation.
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Aborto Espontáneo , Niacina , Animales , Femenino , Humanos , Ratones , Niacinamida , Proyectos Piloto , Embarazo , Primer Trimestre del Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: Eclampsia is a serious consequence of pre-eclampsia. There are limited data from Australia and New Zealand (ANZ) on eclampsia. AIM: To determine the incidence, management and perinatal outcomes of women with eclampsia in ANZ. MATERIALS AND METHODS: A two-year population-based descriptive study, using the Australasian Maternity Outcomes Surveillance System (AMOSS), carried out in 263 sites in Australia, and all 24 New Zealand maternity units, during a staggered implementation over 2010-2011. Eclampsia was defined as one or more seizures during pregnancy or postpartum (up to 14 days) in any woman with clinical evidence of pre-eclampsia. RESULTS: Of 136 women with eclampsia, 111 (83%) were in Australia and 25 (17%) in New Zealand. The estimated incidence of eclampsia was 2.2 (95% confidence interval (CI) 1.9-2.7) per 10 000 women giving birth. Aboriginal and Torres Strait Islander women were over-represented in Australia (n = 9; 8.1%). Women with antepartum eclampsia (n = 58, 42.6%) were more likely to have a preterm birth (P = 0.04). Sixty-three (47.4%) women had pre-eclampsia diagnosed prior to their first eclamptic seizure of whom 19 (30.2%) received magnesium sulphate prior to the first seizure. Nearly all women (n = 128; 95.5%) received magnesium sulphate post-seizure. No woman received prophylactic aspirin during pregnancy. Five women had a cerebrovascular haemorrhage, and there were five known perinatal deaths. CONCLUSIONS: Eclampsia is an uncommon consequence of pre-eclampsia in ANZ. There is scope to reduce the incidence of this condition, associated with often catastrophic morbidity, through the use of low-dose aspirin and magnesium sulphate in women at higher risk.
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Eclampsia , Nacimiento Prematuro , Australia/epidemiología , Eclampsia/tratamiento farmacológico , Eclampsia/epidemiología , Femenino , Humanos , Recién Nacido , Sulfato de Magnesio , Nueva Zelanda/epidemiología , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time. METHODS: Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment. RESULTS: At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication; and was significantly reduced following education. CONCLUSIONS: There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.
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Corticoesteroides/administración & dosificación , Asma/tratamiento farmacológico , Periodo Posparto , Complicaciones del Embarazo/tratamiento farmacológico , Automanejo , Administración por Inhalación , Adulto , Femenino , Humanos , Embarazo , Estudios Prospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Rheumatic heart disease (RHD) is a preventable cardiac condition that escalates risk in pregnancy. Models of care informed by evidence-based clinical guidelines are essential to optimal health outcomes. There are no published reviews that systematically explore approaches to care provision for pregnant women with RHD and examine reported measures. The review objective was to improve understanding of how attributes of care for these women are reported and how they align with guidelines. METHODS: A search of 13 databases was supported by hand-searching. Papers that met inclusion criteria were appraised using CASP/JBI checklists. A content analysis of extracted data from the findings sections of included papers was undertaken, informed by attributes of quality care identified previously from existing guidelines. RESULTS: The 43 included studies were predominantly conducted in tertiary care centers of low-income and middle-income countries. Cardiac guidelines were referred to in 25 of 43 studies. Poorer outcomes were associated with higher risk scores (detailed in 36 of 41 quantitative studies). Indicators associated with increased risk include anticoagulation during pregnancy (28 of 41 reported) and late booking (gestation documented in 15 of 41 studies). Limited access to cardiac interventions was discussed (19 of 43) in the context of poorer outcomes. Conversely, early assessment and access to regular multidisciplinary care were emphasized in promoting optimal outcomes for women and their babies. CONCLUSIONS: Despite often complex care requirements in challenging environments, pregnancy provides an opportunity to strengthen health system responses and address whole-of-life health for women with RHD. A standard set of core indicators is proposed to more accurately benchmark care pathways, outcomes, and burden.
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Complicaciones Cardiovasculares del Embarazo/terapia , Garantía de la Calidad de Atención de Salud/normas , Cardiopatía Reumática/terapia , Anticoagulantes/uso terapéutico , Consejo , Diagnóstico Tardío , Parto Obstétrico , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Grupo de Atención al Paciente , Embarazo , Atención Prenatal , Cardiopatía Reumática/diagnóstico , Medición de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Maternal kidney disease (acute kidney injury (AKI), advanced chronic kidney disease (CKD), dependence on dialysis or a kidney transplant) has a substantial impact on pregnancy, with risks of significant perinatal morbidity. These pregnancies require integrated multidisciplinary care to manage a complex and often challenging clinical situation. The ability to deliver optimal care is currently hindered by a lack of understanding around prevalence, management and outcomes in Australia. This study aims to expand an evidence base to improve clinical care of women with serious kidney impairment in pregnancy. METHODS/DESIGN: The "Kidney Disease in Pregnancy Study" is a national prospective cohort study of women with stage 3b-5 CKD (including dialysis and transplant) and severe AKI in pregnancy, using the Australasian Maternity Outcomes Surveillance System (AMOSS). AMOSS incorporates Australian maternity units with > 50 births/year (n = 260), capturing approximately 96% of Australian births. We will identify women meeting the inclusion criteria who give birth in Australia between 1st August 2017 and 31st July 2018. Case identification will occur via monthly review of all births in Australian AMOSS sites and prospective notification to AMOSS via renal or obstetric clinics. AMOSS data collectors will capture key clinical data via a web-based data collection tool. The data collected will focus on the prevalence, medical and obstetric clinical care, and maternal and fetal outcomes of these high-risk pregnancies. DISCUSSION: This study will increase awareness of the issue of serious renal impairment in pregnancy through engagement of 260 maternity units and obstetric and renal healthcare providers across the country. The study results will provide an evidence base for pre-pregnancy counselling and development of models of optimal clinical care, clinical guideline and policy development in Australia. Understanding current practices, gaps in care and areas for intervention will improve the care of women with serious renal impairment, women with high-risk pregnancies, their babies and their families.
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Enfermedades Renales/diagnóstico , Enfermedades Renales/epidemiología , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Índice de Severidad de la Enfermedad , Adulto , Australia/epidemiología , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Enfermedades Renales/fisiopatología , Embarazo , Complicaciones del Embarazo/fisiopatología , Estudios ProspectivosRESUMEN
BACKGROUND: Early-term delivery is an important cause of short-term neonatal morbidity and associated high healthcare costs, with possible additional long-term developmental ramifications. As a form of 'iatrogenic' delivery, induction of labour (IOL) is a potentially modifiable contributor to this burden. AIMS: To determine patterns of, and primary indication for, early-term IOL, as well as temporal trends in this primary indication and differences from other modes of delivery with respect to maternal factors and maternal/neonatal outcomes. MATERIALS AND METHODS: The Canberra Hospital births database (2012-2016) was queried; patients who underwent IOL were included in the analysis. RESULTS: Total deliveries and the proportion of early-term IOL procedures rose markedly over the time period. Gestational diabetes mellitus (GDM) was the most frequent and an increasing main indication for IOL. GDM was associated with significantly higher body mass index, an increased proportion of obesity, and a greater incidence of labour complications related to macrosomia. Birthweight of neonates of diabetic mothers was significantly higher, which was associated with decreased rates of admission to the special care nursery/neonatal intensive care unit (SCN/NICU) compared to all other babies. GDM increased relative risk of early-term IOL in obese women by 1.8 times. CONCLUSIONS: The burden of GDM and early-term IOL have increased at The Canberra Hospital although adverse short-term neonatal outcomes have not, possibly suggesting appropriate management of these patients. Nonetheless, effort should be made to identify patients who can safely continue pregnancy to full term, given the higher proportion of SCN/NICU admissions among early-term neonates.
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Macrosomía Fetal/complicaciones , Trabajo de Parto Inducido/estadística & datos numéricos , Obesidad/complicaciones , Australia , Femenino , Edad Gestacional , Humanos , Selección de Paciente , Pautas de la Práctica en Medicina , Embarazo , Utilización de Procedimientos y Técnicas , Factores de RiesgoRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (< 20 weeks' gestation) at risk of ODIP will be recruited from 12 hospital antenatal booking clinics and referred for an oral glucose tolerance test (OGTT). 800 women with hyperglycaemia (ie, booking GDM) according to the 2014 Australasian Diabetes-in-Pregnancy Society criteria for pregnant women at 24-28 weeks' gestation will be randomised to immediate treatment for GDM (intervention) or to no treatment (control), pending the results of a second OGTT at 24-28 weeks' gestation. Antenatal and GDM care will otherwise follow local guidelines. Randomisation will be stratified by site and OGTT glycaemic risk strata. The primary pregnancy outcome is a composite of respiratory distress, phototherapy, birth trauma, birth before 37 weeks' gestation, stillbirth or death, shoulder dystocia, and birthweight ≥ 4.5 kg. The primary neonatal outcome is neonatal lean body mass. The primary maternal outcome is pre-eclampsia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000924459.
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Diabetes Gestacional/terapia , Edad Gestacional , Hiperglucemia/terapia , Complicaciones del Embarazo/terapia , Adulto , Australia , Diabetes Gestacional/diagnóstico , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hiperglucemia/diagnóstico , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones del Embarazo/diagnóstico , Resultado del Embarazo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes. METHODS/DESIGN: BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician-diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12-22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3-6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO <19 ppb, and no change when FENO is between 19 and 29 ppb). A long acting beta agonist (LABA) will be added when symptoms remain uncontrolled. Both the control and intervention groups will report on exacerbations at a postpartum phone interview. The primary outcome is adverse perinatal outcome (a composite measure including preterm birth, intrauterine growth restriction, neonatal hospitalisation at birth or perinatal mortality), assessed from hospital records. Secondary outcomes will be each component of the primary outcome, maternal exacerbations requiring medical intervention during pregnancy (both smokers and non-smokers), and hospitalisation and emergency department presentation for wheeze, bronchiolitis or croup in the first 12 months of infancy. Outcome assessment and statistical analysis of the primary outcome will be blinded. To detect a reduction in adverse perinatal outcomes from 35 % to 26 %, 600 pregnant women with asthma per group are required. DISCUSSION: This trial will provide evidence for the effectiveness of a FENO-based management strategy in improving perinatal outcomes in pregnant women with asthma. If successful, this would improve the management of pregnant women with asthma worldwide. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000202763 .
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Corticoesteroides/administración & dosificación , Asma/tratamiento farmacológico , Espiración/fisiología , Óxido Nítrico/metabolismo , Complicaciones del Embarazo/tratamiento farmacológico , Terapia Respiratoria/métodos , Administración por Inhalación , Adulto , Asma/fisiopatología , Pruebas Respiratorias , Protocolos Clínicos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Exposición Materna/efectos adversos , Óxido Nítrico/análisis , Embarazo , Complicaciones del Embarazo/fisiopatología , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Resultado del Tratamiento , Adulto JovenRESUMEN
Transplacental immune regulation refers to the concept that during pregnancy, significant cross-talk occurs between the maternal and fetal immune system with potential long-term effects for both the mother and child. In this study, we made the surprising observation that there is a strong correlation of peripheral blood regulatory T (Treg) cells between the mother and the fetus. In contrast, there is no significant Treg cell correlation between paternal fetal dyads (pairs), suggesting that the specific context of pregnancy, rather than the genetic parental similarity to the fetus, is responsible for this correlation. Gene microarray analysis of Treg cells identified a typical IL-10-dependent signature in maternal and fetal Treg cells. In addition, a direct correlation of serum IL-10 protein levels between maternal fetal dyads was observed. Furthermore, we show that maternal serum IL-10 levels correlate with serum estradiol and estriol, implicating hormonal involvement in this alignment. Interestingly, we show that Treg cells possess higher expression of IL-10 receptor α and that Treg cell IL-10 receptor α expression directly correlates with their Bcl-2 expression. Indeed, in vitro data in both humans and mice demonstrate that IL-10 upregulates Bcl-2 specifically in Treg cells but not non-Treg cells. Our results provide evidence for transplacental regulation of cellular immunity and suggest that IL-10 may influence Treg cell homeostasis through its effect on Treg cell Bcl-2 expression. These novel findings have important implications on immune tolerance in pregnancy and beyond in areas of autoimmunity, allergy, and transplantation.
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Interleucina-10/biosíntesis , Intercambio Materno-Fetal/inmunología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Regulación hacia Arriba/inmunología , Animales , Células Cultivadas , Femenino , Humanos , Interleucina-10/sangre , Interleucina-10/fisiología , Masculino , Intercambio Materno-Fetal/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Análisis de Secuencia por Matrices de Oligonucleótidos , Embarazo , Proteínas Proto-Oncogénicas c-bcl-2/sangre , Transducción de Señal/genética , Transducción de Señal/inmunología , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Amniotic fluid embolism (AFE) is a major cause of direct maternal mortality in Australia and New Zealand. There has been no national population study of AFE in either country. The aim of this study was to estimate the incidence of amniotic fluid embolism in Australia and New Zealand and to describe risk factors, management, and perinatal outcomes. METHODS: A population-based descriptive study using the Australasian Maternity Outcomes Surveillance System (AMOSS) carried out in 263 eligible sites (>50 births per year) covering an estimated 96% of women giving birth in Australia and all 24 New Zealand maternity units (100% of women giving birth in hospitals) between January 1 2010-December 31 2011. A case of AFE was defined either as a clinical diagnosis (acute hypotension or cardiac arrest, acute hypoxia and coagulopathy in the absence of any other potential explanation for the symptoms and signs observed) or as a post mortem diagnosis (presence of fetal squames/debris in the pulmonary circulation). RESULTS: Thirty-three cases of AFE were reported from an estimated cohort of 613,731women giving birth, with an estimated incidence of 5.4 cases per 100,000 women giving birth (95% CI 3.5 to 7.2 per 100,000). Two (6%) events occurred at home whilst 46% (n = 15) occurred in the birth suite and 46% (n = 15) in the operating theatre (location not reported in one case). Fourteen women (42%) underwent either an induction or augmentation of labour and 22 (67%) underwent a caesarean section. Eight women (24%) conceived using assisted reproduction technology. Thirteen (42%) women required cardiopulmonary resuscitation, 18% (n = 6) had a hysterectomy and 85% (n = 28) received a transfusion of blood or blood products. Twenty (61%) were admitted to an Intensive Care Unit (ICU), eight (24%) were admitted to a High Dependency Unit (HDU) and seven (21%) were transferred to another hospital for further management. Five woman died (case fatality rate 15%) giving an estimated maternal mortality rate due to AFE of 0.8 per 100,000 women giving birth (95% CI 0.1% to 1.5%). There were two deaths among 36 infants. CONCLUSIONS: A coordinated emergency response requiring resource intense multi-disciplinary input is required in the management of women with AFE. Although the case fatality rate is lower than in previously published studies, high rates of hysterectomy, resuscitation, and admission to higher care settings reflect the significant morbidity associated with AFE. Active, ongoing surveillance to document the risk factors and short and long-term outcomes of women and their babies following AFE may be helpful to guide best practice, management, counselling and service planning. A potential link between AFE and assisted reproductive technology warrants further investigation.
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Cesárea/efectos adversos , Embolia de Líquido Amniótico/diagnóstico , Embolia de Líquido Amniótico/epidemiología , Mortalidad Materna , Adolescente , Adulto , Australia/epidemiología , Femenino , Humanos , Incidencia , Trabajo de Parto , Nueva Zelanda/epidemiología , Vigilancia de la Población , Embarazo , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Super-obesity is associated with significantly elevated rates of obstetric complications, adverse perinatal outcomes and interventions. The purpose of this study was to determine the prevalence, risk factors, management and perinatal outcomes of super-obese women giving birth in Australia. METHODS: A national population-based cohort study. Super-obese pregnant women (body mass index (BMI) >50 kg/m(2) or weight >140 kg) who gave birth between January 1 and October 31, 2010 and a comparison cohort were identified using the Australasian Maternity Outcomes Surveillance System (AMOSS). Outcomes included maternal and perinatal morbidity and mortality. Prevalence estimates calculated with 95% confidence intervals (CIs). Adjusted odds ratios (ORs) were calculated using multivariable logistic regression. RESULTS: 370 super-obese women with a median BMI of 52.8 kg/m(2) (range 40.9-79.9 kg/m(2)) and prevalence of 2.1 per 1 000 women giving birth (95% CI: 1.96-2.40). Super-obese women were significantly more likely to be public patients (96.2%), smoke (23.8%) and be socio-economically disadvantaged (36.2%). Compared with other women, super-obese women had a significantly higher risk for obstetric (adjusted odds ratio (AOR) 2.42, 95% CI: 1.77-3.29) and medical (AOR: 2.89, 95% CI: 2.64-4.11) complications during pregnancy, birth by caesarean section (51.6%) and admission to special care (HDU/ICU) (6.2%). The 372 babies born to 365 super-obese women with outcomes known had significantly higher rates of birthweight ≥ 4500 g (AOR 19.94, 95 % CI: 6.81-58.36), hospital transfer (AOR 3.81, 95 % CI: 1.93-7.55) and admission to Neonatal Intensive Care Unit (NICU) (AOR 1.83, 95% CI: 1.27-2.65) compared to babies of the comparison group, but not prematurity (10.5% versus 9.2%) or perinatal mortality (11.0 (95% CI: 4.3-28.0) versus 6.6 (95% CI: 2.6- 16.8) per 1 000 singleton births). CONCLUSIONS: Super-obesity in pregnancy in Australia is associated with increased rates of pregnancy and birth complications, and with social disadvantage. There is an urgent need to further address risk factors leading to super-obesity among pregnant women and for maternity services to better address pre-pregnancy and pregnancy care to reduce associated inequalities in perinatal outcomes.
Asunto(s)
Índice de Masa Corporal , Obesidad Mórbida/epidemiología , Preeclampsia/epidemiología , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Puntaje de Apgar , Australia/epidemiología , Peso al Nacer , Peso Corporal , Cesárea/efectos adversos , Femenino , Humanos , Recién Nacido , Servicios de Salud Materna , Oportunidad Relativa , Mortalidad Perinatal , Embarazo , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To compare pregnancy outcomes among women with a normal oral glucose tolerance test (OGTT) before 20 weeks' gestation (early) and at 24-28 weeks' gestation (late) (no gestational diabetes mellitus, or No-GDM), those with early GDM randomized to observation with a subsequent normal OGTT (GDM-Regression), and those with GDM on both occasions (GDM-Maintained). RESEARCH DESIGN AND METHODS: Women at <20 weeks' gestation with GDM risk factors who were recruited for a randomized controlled early GDM treatment trial were included. Women with treated early GDM and late GDM (according to the World Health Organization's 2013 criteria) were excluded from this analysis. Logistic regression compared pregnancy outcomes. RESULTS: GDM-Regression (n = 121) group risk factor profiles and OGTT results generally fell between the No-GDM (n = 2,218) and GDM-Maintained (n = 254) groups, with adjusted incidences of pregnancy complications similar between the GDM-Regression and No-GDM groups. CONCLUSIONS: Women with early GDM but normal OGTT at 24-28 weeks' gestation had pregnancy outcomes that were similar to those of individuals without GDM. Identifying early GDM likely to regress would allow treatment to be avoided.
RESUMEN
OBJECTIVE: We evaluated associations between early-pregnancy oral glucose tolerance test (OGTT) glucose and complications in the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) cohort to inform prognostic OGTT thresholds. RESEARCH DESIGN AND METHODS: Individuals with risk factors for hyperglycemia were recruited for an international, multicenter, randomized controlled gestational diabetes mellitus (GDM) (World Health Organization 2013 criteria) treatment trial. A 2-h 75-g OGTT was performed at <20 weeks' gestation. Individuals with early treated hyperglycemia in pregnancy were excluded from the primary analysis. Early OGTT glucose concentrations were analyzed continuously and in glycemic categories (normal, low band, and high band). RESULTS: Overall, 3,645 individuals had an OGTT at (mean ± SD) 15.6 ± 2.5 weeks. For each 1-SD increase in fasting, 1-h, and 2-h glucose values, there were continuous positive associations with late GDM: adjusted odds ratio (aOR) 2.04 (95% CI 1.82-2.27), 3.05 (2.72-3.43), and 2.21 (1.99-2.45), respectively. There were continuous positive associations between 1-h and 2-h glucose and the perinatal composite (birth <37 + 0 weeks, birth trauma, birth weight ≥4,500 g, respiratory distress, phototherapy requirement, stillbirth/neonatal death, and shoulder dystocia), with aOR 1.15 (95% CI 1.04-1.26) and 1.14 (1.04-1.25), respectively, and with large-for-gestational-age offspring, with aOR 1.18 (1.06-1.31) and 1.26 (1.01-1.25), respectively. Significant associations were also observed between 1-h glucose and cesarean section and between fasting and 2-h glucose and neonatal hypoglycemia. In categorical analysis, only the high-band 1-h glucose (≥10.6 mmol/L [191 mg/dL]) predicted the perinatal composite. CONCLUSIONS: There is a continuous positive association between early-pregnancy OGTT glucose and complications. In individuals with hyperglycemia risk factors, only the high-glycemic-band 1-h glucose corresponded to increased risk of major perinatal complications.
RESUMEN
Background: A recently undertaken multicenter randomized controlled trial (RCT) "Treatment Of BOoking Gestational diabetes Mellitus" (TOBOGM: 2017-2022) found that the diagnosis and treatment of pregnant women with early gestational diabetes mellitus (GDM) improved pregnancy outcomes. Based on data from the trial, this study aimed to assess the cost-effectiveness of diagnosis and treatment of early GDM (from <20 weeks') among women with risk factors for hyperglycemia in pregnancy compared with usual care (no treatment until 24-28 weeks') from a healthcare perspective. Methods: Participants' healthcare resource utilization data were collected from their self-reported questionnaires and hospital records, and valued using the unit costs obtained from standard Australian national sources. Costs were reported in US dollars ($) using the purchasing power parity (PPP) estimates to facilitate comparison of costs across countries. Intention-to-treat (ITT) principle was followed. Missing cost data were replaced using multiple imputations. Bootstrapping method was used to estimate the uncertainty around mean cost difference and cost-effectiveness results. Bootstrapped cost-effect pairs were used to plot the cost-effectiveness (CE) plane and cost-effectiveness acceptability curve (CEAC). Findings: Diagnosis and treatment of early GDM was more effective and tended to be less costly, i.e., dominant (cost-saving) [-5.6% composite adverse pregnancy outcome (95% CI: -10.1%, -1.2%), -$1373 (95% CI: -$3,749, $642)] compared with usual care. Our findings were confirmed by both the CE plane (88% of the bootstrapped cost-effect pairs fall in the south-west quadrant), and CEAC (the probability of the intervention being cost-effective ranged from 84% at a willingness-to-pay (WTP) threshold value of $10,000-99% at a WTP threshold value of $100,000 per composite adverse pregnancy outcome prevented). Sub-group analyses demonstrated that diagnosis and treatment of early GDM among women in the higher glycemic range (fasting blood glucose 95-109 mg/dl [5.3-6.0 mmol/L], 1-h blood glucose ≥191 mg/dl [10.6 mmol/L] and/or 2-h blood glucose 162-199 mg/dl [9.0-11.0 mmol/L]) was more effective and less costly (dominant) [-7.8% composite adverse pregnancy outcome (95% CI: -14.6%, -0.9%), -$2795 (95% CI: -$6,638, -$533)]; the intervention was more effective and tended to be less costly [-8.9% composite adverse pregnancy outcome (95% CI: -15.1%, -2.6%), -$5548 (95% CI: -$16,740, $1547)] among women diagnosed before 14 weeks' gestation as well. Interpretation: Our findings highlight the potential health and economic benefits from the diagnosis and treatment of early GDM among women with risk factors for hyperglycemia in pregnancy and supports its implementation. Long-term follow-up studies are recommended as a key future area of research to assess the potential long-term health benefits and economic consequences of the intervention. Funding: National Health and Medical Research Council (grants 1104231 and 2009326), Region O¨rebro Research Committee (grants Dnr OLL-970566 and OLL-942177), Medical Scientific Fund of the Mayor of Vienna (project 15,205 and project 23,026), South Western Sydney Local Health District Academic Unit (grant 2016), and Western Sydney University Ainsworth Trust Grant (2019).