RESUMO
OBJECTIVE: To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension. DESIGN: Secondary analysis of CHIPS Trial cohort. SETTING: International randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation. METHODS: Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors. MAIN OUTCOME MEASURES: CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks. RESULTS: Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32-0.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), pre-eclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85). CONCLUSION: These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes. TWEETABLE ABSTRACT: There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Induzida pela Gravidez/prevenção & controle , Labetalol/uso terapêutico , Metildopa/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Hipertensão Induzida pela Gravidez/fisiopatologia , Recém-Nascido de Baixo Peso , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/prevenção & controle , Resultado da GravidezRESUMO
OBJECTIVE: To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS. DESIGN: Secondary analysis of CHIPS Trial data. SETTING: International multicentre randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: A total of 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation. MAIN OUTCOME MEASURES: Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight < 10th centile, severe maternal hypertension, pre-eclampsia, and delivery at < 34 or < 37 weeks. RESULTS: Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy. CONCLUSION: Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalol. TWEETABLE ABSTRACT: In the CHIPS Trial, maternal and infant outcomes were not dependent on use of labetalol or methyldopa.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Labetalol/uso terapêutico , Metildopa/uso terapêutico , Adulto , Tomada de Decisão Clínica , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Recém-Nascido de Baixo Peso , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/fisiopatologia , Nascimento Prematuro/etiologia , Cuidado Pré-Natal/métodos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Placenta-mediated diseases (PMDs) including preeclampsia and fetal growth restriction are often characterized by shallow trophoblast invasion and incomplete spiral artery remodeling leading to impaired placental perfusion. In this context, umbilical artery (UA) Doppler can be used to detect high resistance to flow characteristic of very late-stage placental disease. We propose that evaluation of intraplacental villous artery (IPVA) resistance can provide earlier detection of increased resistance in placental flow. STUDY DESIGN: Seventy-five patients were recruited from the Ottawa Hospital. All had scans at 18 to 20, 28 and 34 weeks of gestation. IPVAs arising perpendicular to the chorionic plate in three regions (placental tips 4 cm away from cord insertion and within 1 cm from cord insertion) were sampled at each gestational age for resistance index (RI) and pulsatility index (PI). UA Doppler was also obtained from a free loop of cord. Pregnancy outcomes were collected from a chart review. Data were analyzed using SAS version 9.4 and standard statistic tests (mean±s.d., Student's t-test, mixed-effects modeling). RESULT: A total of 53 patients completed the study. Of these, 38 had normal pregnancy outcomes (controls) and 15 (cases) developed PMD (preeclampsia, n=8 and low birth weight/intrauterine growth restriction, n=7). Mean birth weight in the study group was 2482.1±518.85 g. At 18 to 20, 28 and 34 weeks gestation, the mean IPVA resistance indices in the control group were 0.86±0.16, 0.81±0.12 and 0.71±0.12 for PI and 0.57±0.07, 0.55±0.06 and 0.49±0.06 for RI, respectively. However, in the cases developing PMDs, the PIs were 1.09±0.17, 0.95±0.21 and 0.78±0.07 and RIs 0.66±0.07, 0.60±0.07 and 0.54±0.04, respectively (P<0.05). UA PI and RI Doppler did not differ between the groups as early as 18 to 20 weeks gestation. CONCLUSION: Doppler measures of IPVA appear superior to UA in detecting early changes related to PMD. IPVA PI and RI Doppler may be useful in the early identification of patients at risk of PMD.
Assuntos
Retardo do Crescimento Fetal/diagnóstico por imagem , Doenças Placentárias/diagnóstico , Placenta/irrigação sanguínea , Pré-Eclâmpsia/diagnóstico por imagem , Artérias Umbilicais/diagnóstico por imagem , Adulto , Peso ao Nascer , Velocidade do Fluxo Sanguíneo , Córion/diagnóstico por imagem , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of 'omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution.
Assuntos
Biologia Computacional/métodos , Placenta/patologia , Placentação , Pré-Eclâmpsia/etiologia , Animais , Evolução Biológica , Feminino , Perfilação da Expressão Gênica , Humanos , GravidezRESUMO
Maternal obesity is associated with increased risks of pregnancy complications. Excessive fat mass, common to obese women, has the potential to influence production and secretion of adipose tissue derived proteins called adipokines. The adipokine leptin is involved in the regulation of multiple aspects of maternal metabolic homeostasis. In addition, leptin has been shown to be important for placentation and maternal-fetal exchanges processes regulating growth and development. In later stages of a healthy pregnancy, central leptin resistance occurs to allow increased nutrient availability for the fetus. Disruption of the signaling capacity of leptin associated with obesity is emerging as a potential risk factor leading to pregnancy complications as a result of aberrant fuel partitioning in utero. In this review we discuss the influence of obesity on the roles of leptin and leptin resistance at the central and placental level.
Assuntos
Leptina/metabolismo , Obesidade/metabolismo , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Tecido Adiposo/metabolismo , Adulto , Resistência a Medicamentos/fisiologia , Feminino , Humanos , Troca Materno-Fetal/fisiologia , Gravidez , Transdução de SinaisRESUMO
PC4 or PCSK4 belongs to the 9-member superfamily of mammalian subtilases collectively called Proprotein Convertases or Proprotein Convertase Subtilisin/Kexins that convert inactive precursor proteins into their active mature forms by endoproteolytic cleavage. PC4-activity plays a crucial role in mammalian fertilization via activation of sperm surface proteins. PC4 knockout mice exhibit severely impaired male fertility due to premature sperm acrosome reaction. Regulation of sperm-PC4 activity during its storage and transport through epididymis is an important determinant for ultimate egg-binding and fertilizing capacities of sperms. Herein we show that epididymal serpin CRES (cystatin related epididymal spermatogenic) recombinant protein inhibits PC4 activity in vitro in a differential manner when measured against the fluorogenic substrate Boc- RVRR-MCA depending on its oligomeric state. Thus while CRES-dimer exhibits K(i) â¼8 µM, the corresponding monomer showed K(i) > 100 µM. Both forms also blocked PC4-mediated processing of human proIGF-2 in human placenta tropoblast cell line with dimer being more efficient. Using specific inhibitors and substrates, we also demonstrated the presence of PC4-like activity and CRES protein in varying levels in the fluids of various epididymal compartments. Our observations suggest a potential function of CRES as a regulator of PC4 in sperm-egg interaction and fertilization.
Assuntos
Cistatinas/química , Epididimo/enzimologia , Serina Endopeptidases/química , Inibidores de Serina Proteinase/química , Sequência de Aminoácidos , Animais , Ligação Competitiva , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Cistatinas/biossíntese , Cistatinas/isolamento & purificação , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Pró-Proteína Convertases , Ligação Proteica , Multimerização Proteica , Estrutura Quaternária de Proteína , Proteólise , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Serina Endopeptidases/biossíntese , Serina Endopeptidases/isolamento & purificação , Inibidores de Serina Proteinase/biossíntese , Inibidores de Serina Proteinase/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , SubtilisinasRESUMO
STUDY QUESTION: Does maternal obesity affect insulin-like growth factor (IGF) axis protein expression patterns in maternal and cord blood? SUMMARY ANSWER: Maternal obesity attenuates cord blood expression of IGF-binding protein (IGFBP)-4. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The IGF axis plays a critical role in fetal growth and development. Maternal obesity compromises IGF axis protein expression in fetal circulation, which is consistent with the findings of epidemiological studies suggesting that maternal obesity has an independent effect on fetal growth signals during in utero development. STUDY DESIGN: This cross-sectional case-control study involved 12 lean [body mass index (BMI) 18.5-24.9 kg/m2] and 12 obese (BMI≥30 kg/m2) women and their neonates at term. At the completion of the study, IGF axis protein expression and hormone concentrations in both maternal and cord blood were examined. PARTICIPANTS AND SETTING: We obtained fasting serum samples from cases and controls matched for age, gestation, mode of delivery, parity and glucose tolerance prior to and immediately following elective caesarean section. The corresponding umbilical cord blood was also collected at birth. MAIN RESULTS AND THE ROLE OF CHANCE: Between-group comparisons revealed elevated maternal insulin (P=0.03) and leptin (P<0.01) concentrations in obese gravidas. After adjustment, the maternal homeostasis model of assessment-insulin resistance (HOMA-IR) score was positively correlated with both maternal BMI and leptin levels (P<0.01). Umbilical cord blood levels of IGFBP-3 showed an inverse trend to maternal HOMA-IR (P=0.03) but were directly related to the fetal-placental weight ratio (P<0.01). In cord serum from obese mothers, IGFBP-4 expression was attenuated compared with the controls (P<0.05). LIMITATIONS: The limitations of our study include the cross-sectional design and relatively small sample size. WIDER IMPLICATIONS: Our results provide preliminary evidence for the applicability of our findings to other ethnic groups when pregnancy is complicated by obesity. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the University of Ottawa, Faculty of Health Sciences/Children's Hospital of Eastern Ontario Research Partnership Grant awarded to K.B.A. and Z.M.F. The authors have no conflicts of interest to declare.
Assuntos
Sangue Fetal/metabolismo , Perfilação da Expressão Gênica , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Obesidade/metabolismo , Somatomedinas/metabolismo , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Feminino , Glucose/metabolismo , Humanos , Recém-Nascido , Insulina/metabolismo , Resistência à Insulina , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Leptina/metabolismo , Gravidez , Complicações na GravidezRESUMO
OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.
Assuntos
Pré-Eclâmpsia/urina , Resultado da Gravidez , Proteinúria/diagnóstico , Adulto , Estudos de Coortes , Creatinina/urina , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez , Estudos Prospectivos , Curva ROC , Fitas Reagentes , Fatores de Risco , Coleta de Urina/métodosRESUMO
NUMB is a multifunctional protein involved in asymmetric cell differentiation, proliferation and maintenance. Four mammalian NUMB isoforms have been identified, which utilize the phosphotyrosine binding (PTB) domain and the proline rich region (PRR) domain to regulate cell growth and differentiation in the developing nervous system. The observation that a decrease in spongiotrophoblast number and thickness of placentae of null (Numb(-/-)) mouse embryos, which died at E10.5, suggests NUMB may play a role in placental development. In this study, we demonstrated for the first time, that NUMB isoforms 1, 2, 3, and 4 are present in the human placenta and the human extravillous trophoblast (EVT) cell line HTR8/SVneo. We report three novel isoforms, NUMB 7, 8, and 9, identified by cloning of RT-PCR products and sequencing. Corresponding sequences of novel isoforms were submitted to genebank (accession numbers for each new isoform: NUMB 7- EU265736, NUMB 8- EU265737 and NUMB 9-EU265738). Western blot analysis confirmed the presence of all NUMB isofoms in human placental samples in all trimesters and in EVT cells. NUMB immunosignals were extensively localized in human extravillous trophoblasts and decidual cells at the maternal-fetal interface. NUMB 8 appeared to be the predominant isoform in placental villi. Furthermore, cell migration studies revealed NUMB isoform 1 to be involved in EVT cell migration and NUMB isoforms 2 and 4 to induce EVT apoptosis.
Assuntos
Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Trofoblastos/metabolismo , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Gravidez , Isoformas de Proteínas , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies.
Assuntos
Retardo do Crescimento Fetal/tratamento farmacológico , Piperazinas/uso terapêutico , Sulfonas/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/mortalidade , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Recém-Nascido , Mortalidade Perinatal , Placenta/irrigação sanguínea , Gravidez , Resultado da Gravidez , Purinas/uso terapêutico , Citrato de Sildenafila , Útero/irrigação sanguíneaRESUMO
BACKGROUND: Satisfaction with maternity care is strongly related to the patient-caregiver relationship and involvement in the decision-making process. We sought to compare women's views about their care in a randomized trial of 'less tight' vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension in pregnancy. METHODS: In the CHIPS Pilot Trial, women completed a postpartum questionnaire to assess their likes and dislikes about their blood pressure (BP) management and trial participation. Comparisons were descriptive. RESULTS: Baseline information was similar for the 'less tight' and 'tight' control groups. Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire, usually within days of delivery. At least 90% of women in both groups were satisfied with their care, and would be willing to participate again or recommend participation to a friend. Women in both the 'less tight' and 'tight' groups were satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of maternal and fetal well being. Half of women in both groups perceived that their BP was too high and that caregivers thought that their BP was too high. More women in the 'less tight' (vs. the 'tight') control group took less medication than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight') group took more medication than they expected (60.0% vs. 22.2%). At least 60% of all women used home BP monitoring. CONCLUSION: In the CHIPS Pilot Trial, while women stated that they were satisfied with their BP management and care, a surprising 50% in both groups thought that their BP was too high. The majority of women used home BP monitoring, the role of which must be further defined in hypertensive pregnancies.
Assuntos
Hipertensão Induzida pela Gravidez/prevenção & controle , Satisfação do Paciente , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Atitude Frente a Saúde , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão Induzida pela Gravidez/psicologia , Prontuários Médicos , Cooperação do Paciente , Participação do Paciente , Relações Médico-Paciente , Projetos Piloto , Cuidado Pré-Natal , Projetos de Pesquisa , Autocuidado , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the association between adverse maternal/perinatal outcomes and Canadian and U.S. preeclampsia severity criteria. METHODS: Using PIERS data (Preeclampsia Integrated Estimate of RiSk), an international continuous quality improvement project for women hospitalized with preeclampsia, we examined the association between preeclampsia severity criteria and adverse maternal and perinatal outcomes (univariable analysis, Fisher's exact test). Not evaluated were variables performed in <80% of pregnancies (e.g., 24-hour proteinuria). RESULTS: Few of the evaluated variables were associated with adverse maternal (chest pain/dyspnea, thrombocytopenia, 'elevated liver enzymes', HELLP syndrome, and creatinine >110 microM) or perinatal outcomes (dBP >110 mm Hg and suspected abruption) (at p < 0.01). CONCLUSIONS: In the PIERS cohort, most factors used in the Canadian or American classifications of severe preeclampsia do not predict adverse maternal and/or perinatal outcomes. Future classification systems should take this into account.
Assuntos
Pré-Eclâmpsia/classificação , Resultado da Gravidez , Descolamento Prematuro da Placenta/classificação , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Canadá , Dor no Peito/classificação , Estudos de Coortes , Creatinina/sangue , Dispneia/classificação , Feminino , Doenças Fetais/classificação , Previsões , Síndrome HELLP/classificação , Humanos , Recém-Nascido , L-Lactato Desidrogenase/sangue , Fígado/enzimologia , Gravidez , Medição de Risco , Índice de Gravidade de Doença , Trombocitopenia/classificação , Estados UnidosRESUMO
OBJECTIVE: To determine whether 'less tight' (versus 'tight') control of nonsevere hypertension results in a difference in diastolic blood pressure (dBP) between groups. DESIGN: Randomised controlled trial (ISRCTN#57277508). SETTING: Seventeen obstetric centres in Canada, Australia, New Zealand, and UK. POPULATION: Inclusion: pregnant women, dBP 90-109 mmHg, pre-existing/gestational hypertension; live fetus(es); and 20-33(+6) weeks. Exclusion: systolic blood pressure > or = 170 mmHg and proteinuria, contraindication, or major fetal anomaly. METHODS: Randomisation to less tight (target dBP, 100 mmHg) or tight (target dBP, 85 mmHg) blood pressure control. MAIN OUTCOME MEASURES: Primary: mean dBP at 28, 32 and 36 weeks. Secondary: clinician compliance and women's satisfaction. Other: serious perinatal and maternal complications. RESULTS: A total of 132 women were randomised to less tight (n = 66; seven had no study visit) or tight control (n= 66; one was lost to follow up; seven had no study visit). Mean dBP was significantly lower with tight control: -3.5 mmHg, 95% credible interval (-6.4, -0.6). Clinician compliance was 79% in both groups. Women were satisfied with their care. With less tight (versus tight) control, the rates of other treatments and outcomes were the following: post-randomisation antenatal antihypertensive medication use: 46 (69.7%) versus 58 (89.2%), severe hypertension: 38 (57.6%) versus 26 (40.0%), proteinuria: 16 (24.2%) versus 20 (30.8%), serious maternal complications: 3 (4.6%) versus 2 (3.1%), preterm birth: 24 (36.4%) versus 26 (40.0%), birthweight: 2675 +/- 858 versus 2501 +/- 855 g, neonatal intensive care unit (NICU) admission: 15 (22.7%) versus 22 (34.4%), and serious perinatal complications: 9 (13.6%) versus 14 (21.5%). CONCLUSION: The CHIPS pilot trial confirms the feasibility and importance of a large definitive trial to determine the effects of less tight control on serious perinatal and maternal complications.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/prevenção & controle , Labetalol/uso terapêutico , Complicações Cardiovasculares na Gravidez/prevenção & controle , Adulto , Feminino , Humanos , Satisfação do Paciente , Projetos Piloto , Gravidez , Resultado da Gravidez , Resultado do TratamentoRESUMO
BACKGROUND: How Canadian practitioners are diagnosing and managing the hypertensive disorders of pregnancy (HDP), particularly in relation to the 1997 recommendations published by the Canadian Hypertension Society (CHS), is not known. METHODS: A survey, with French and English versions (and covering diagnosis, evaluation, and management of pregnancy hypertension), was mailed to all members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) (N = 1757, including obstetricians, family doctors practicing obstetrics, and midwives). Additionally, internists [i.e., all nephrologists (N = 191) and a random sample of 25% of general internists (N = 450)] registered with the Royal College of Physicians and Surgeons of Canada were sampled. The survey was distributed in two mailings and one reminder card. Data were entered into Microsoft Access, and Graph Pad Prism used to summarize responses [N (%)]. Differences in practice between specialties were examined, with a Bonferonni correction used to calculate a significant p value based on the number of comparisons and alpha of 0.05. RESULTS: Respondents numbered 1187 (49.5%), with 466 not informative for the purpose of the study (due to retirement, or practices that do not include pregnant women with hypertension). The final analysis included 721 completed surveys. Most (609, 84.5% of) respondents take blood pressure (BP) with women in the sitting position, and use a mercury sphygmomanometer (79%) and the 5th Korotkoff (61%) sound to designate diastolic BP (dBP). To monitor pregnancies complicated by preeclampsia, most clinicians use the proposed laboratory tests of maternal well-being (usually at least once/week), fetal well-being [nonstress test (NST, at least once/week), and ultrasonographic studies (once weekly to every two weeks)]. There is general agreement that women with preeclampsia should be delivered for uncontrolled hypertension, end-organ dysfunction, or fetal compromise (nonreassuring NST, severe oligohydramnios, biophysical profile < 4, estimated fetal weight < 5th centile, and reversed end-diastolic flow by umbilical artery Doppler velocimetry). Less consensus was seen for delivery for preeclampsia at > 34 weeks, mild asymptomatic HELLP syndrome, hyperreflexia, and absent end-diastolic flow by umbilical artery Doppler velocimetry. INTERPRETATION: This survey has clarified the current state of practice with respect to the diagnosis and evaluation of women with all types of HDP. In particular, we have identified areas of potential variability in BP measurement, and provided data on the feasibility of enrolling women with sub types of preeclampsia into intervention studies aimed at prolonging pregnancy.
Assuntos
Inquéritos Epidemiológicos , Hipertensão/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Canadá/epidemiologia , Feminino , Monitorização Fetal , Idade Gestacional , Humanos , Hipertensão/fisiopatologia , Bem-Estar Materno , Tocologia , Obstetrícia , Médicos de Família , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações Cardiovasculares na Gravidez/fisiopatologia , Resultado da Gravidez , Encaminhamento e Consulta/estatística & dados numéricosRESUMO
Epidermal growth factor (EGF) is present in the maternal-fetal environment and has an important role in placental development. Matrix metalloproteinase-9 (MMP-9) expression/activation is a pre-requisite in extravillous trophoblast invasion. Whereas EGF up-regulates MMP-9 activity in a variety of cell types, there is no direct evidence for the stimulation of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion by EGF in extravillous trophoblasts. In addition, the signalling pathways involved in this regulation are not clear. In the present study, we have examined the possible involvement of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in the regulation of the MMP-9/TIMP-1 system by EGF in vitro. We used a well-established invasive extravillous trophoblast cell line (HTR8/Svneo) and measured gene and protein expression by semi-quantitative RT-PCR and western analysis respectively. MMP activity was determined by zymography. We showed for the first time that EGF activated both PI3K/Akt and MAPK/extracellular-signal regulated kinase (ERK) signalling in HTR8/SVneo, and increased both MMP-9 and TIMP-1 mRNAs and protein concentrations. Interfering with either signalling pathway via PI3K inhibitor LY294002 or MEK inhibitor U0126 in EGF-stimulated HTR8/SVneo cells blocked the induction of MMP-9 and TIMP-1. LY294002 inhibited Akt phosphorylation, but had no effect on ERK phosphorylation; U0126 suppressed ERK phosphorylation without interfering with the phosphorylation of Akt. In addition, expression of constitutively active Akt (Myr-Akt1, Myr-Akt2, Myr-Akt3) was not sufficient to induce proMMP-9 and TIMP-1 secretion. Our results suggest that the activation of both PI3K and MAPK pathways in extravillous trophoblasts is necessary for the up-regulation of MMP-9 and TIMP-1 expression by EGF.
Assuntos
Fator de Crescimento Epidérmico/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Trofoblastos/metabolismo , Western Blotting/métodos , Butadienos/farmacologia , Linhagem Celular , Cromonas/farmacologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Morfolinas/farmacologia , Nitrilas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Gravidez , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/genéticaRESUMO
BACKGROUND: How Canadian practitioners are managing the hypertensive disorders of pregnancy (HDP) is not known, particularly in relation to the 1997 guidelines published by the Canadian Hypertension Society (CHS). METHODS: A survey, with French and English versions (and covering diagnosis, evaluation, and management of pregnancy hypertension), was mailed to all members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) (N = 1757, including obstetricians, family doctors practicing obstetrics, and midwives). Additionally, internists [i.e., all nephrologists (N = 191) and a random sample of 25% of general internists (N = 450)] registered with the Royal College of Physicians and Surgeons of Canada were sampled. The survey was distributed in two mailings and one reminder card. Data were entered into Microsoft Access, and Graph Pad Prism used to summarize responses [N (%)]. Differences in practice between specialties were examined, with a Bonferroni correction used to calculate a significant p value based on the number of comparisons and alpha of 0.05. RESULTS: Respondents numbered 1187 (49.5%), with 466 not informative for the purpose of the study (due to retirement, or practices that do not include pregnant women with hypertension). The final analysis included 721 completed surveys. For all types of HDP, most internists, family doctors, and midwives initiate nonpharmacological therapy (most common advice to quit work) at dBP 80-89 mmHg (i.e., primary prevention). Only for preeclampsia do obstetricians most frequently use this threshold; otherwise, dBP 90-99 mmHg is usually chosen. For nonsevere hypertension, antihypertensive drug therapy (most commonly methyldopa or labetalol) is started by most practitioners at dBP 90-99 mmHg, although obstetricians are more likely to choose a higher threshold (p < 0.0001). There is little agreement about dBP treatment goal; most internists and family doctors normalize dBP, whereas obstetricians appear to be divided on dBP goals of 80-89 (46-51%) vs. 90-99 mmHg (41-44%) for all HDP (p = 0.66). Severe hypertension is commonly treated with parenteral hydralazine, labetalol, or magnesium sulphate. Short-acting or sustained release nifedipine is used rarely/never by most practitioners. Approximately one-third of obstetricians and family doctors use diazepam to treat eclampsia. The vast majority use MgSO4 prophylactically in women with preeclampsia. INTERPRETATION: This survey has clarified current stated management of women with HDP, and identified the need for both research into the dBP treatment goal that optimizes pregnancy outcomes among women with HDP, and translation of definitive studies into clinical practice.
Assuntos
Hipertensão/terapia , Médicos de Família , Complicações Cardiovasculares na Gravidez/terapia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canadá/epidemiologia , Coleta de Dados , Diástole/fisiologia , Gerenciamento Clínico , Feminino , Humanos , Hipertensão/fisiopatologia , Sulfato de Magnésio/uso terapêutico , Bem-Estar Materno , Tocologia , Obstetrícia , Guias de Prática Clínica como Assunto , GravidezRESUMO
Maternal smoking is associated with severe perinatal complications and significant placental pathologies with underlying ultrastructural changes. In this study, we examined the influence of maternal smoking on trophoblast apoptosis throughout development and correlated those findings with changes in expression of X-linked inhibitor of apoptosis protein (Xiap) as well as Fas and Fas ligand (FasL). Trophoblast apoptosis was determined by DNA fragmentation and TUNEL. Protein expression was assessed by Western blotting and immunohistochemistry. Maternal smoking was associated with increased trophoblast apoptosis in the first trimester but decreased trophoblast apoptosis near term. Placental Xiap levels decreased significantly throughout development in nonsmokers (P < 0.05) but remained elevated in smokers. Fas and FasL levels did not vary significantly throughout development nor between groups. However, procaspase-3 levels were significantly increased in smokers at term. Our results suggest that maternal smoking has different effects at different stages of trophoblast differentiation and that this is regulated in part through modulations in placental Xiap expression.
Assuntos
Apoptose , Idade Gestacional , Fumar/efeitos adversos , Trofoblastos/citologia , Caspase 3 , Caspases/metabolismo , Fragmentação do DNA , Precursores Enzimáticos/metabolismo , Proteína Ligante Fas , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Glicoproteínas de Membrana/análise , Gravidez , Antígeno Nuclear de Célula em Proliferação/análise , Proteínas/análise , Trofoblastos/química , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X , Receptor fas/análiseRESUMO
Substance use disorders (SUDs) in pregnancy are becoming increasingly prevalent. Our study aimed to measure the effect of a teaching module on alcohol, tobacco, and drug use on the attitude of second year medical students toward pregnant women with SUDs. A questionnaire was administered to 84 medical students before a 5-week systems block on human reproduction, which included specific learning events related to SUDs. The questionnaire was readministered at the completion of the block. Pre- and postintervention scores were compared. Students showed significant improvement (p < .05, reliability coefficient 0.90) in their level of comfort in dealing with womenwith SUD in pregnancy. Other positive trends relating to attitudes toward drug- and alcohol-dependent women during pregnancy were also identified. SUD teaching interventions among medical students can improve their comfort level and attitude toward pregnant women with SUDs. This supports the current initiative of Project CREATE (Curriculum Renewal and Evaluation of Addiction Training and Education) to implement a comprehensive undergraduate SUD teaching program in Canadian medical schools.
Assuntos
Atitude do Pessoal de Saúde , Estudantes de Medicina/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Canadá , Currículo , Educação Médica , Feminino , Humanos , Gravidez , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Numerous studies have assessed the significance of meconium-stained amniotic fluid (MSAF) at term. However, to date, there has been very little documentation on the incidence and significance of meconium in the preterm population. Our objective was to define the incidence of MSAF in patients delivering prematurely (<37 weeks) and examine its association with underlying fetal acidosis, Apgars and admission to the neonatal intensive care unit (NICU). METHOD: All patients delivering at a single tertiary care center between June 1994 and September 1997 were reviewed for the presence of meconium and gestational age <37 weeks at delivery. Maternal demographics and birth outcomes including cord gases, Apgar scores and admission to the NICU were collected. Exclusion criteria included multiple gestations, breech presentations, fetal anomalies and patients not in labor. RESULTS: Out of a total of 9570 patients there were 506 (5.3%) preterm births meeting the inclusion criteria, of whom 24 (4.8%) had MSAF noted either during labor or at delivery. Comparing the preterm group with and without meconium, there were no differences in maternal age, gravidity, rate of Cesarean section, or gestational age at delivery. Cord pH (7.27 meconium vs. 7.29 no meconium) and base excess (-5.1 meconium vs. -4.0 no meconium) were similar in both groups. There were no clinically significant differences in mean Apgar scores at 1 and 5 minutes. However, an increased number of NICU admissions were noted in the group with meconium (75% vs. 53%, p=0.04). CONCLUSION: The incidence of meconium staining of the amniotic fluid in labor in the preterm population is less than 5% and by itself is not a significant marker of fetal acidosis.