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OBJECTIVES: Postpartum stratification of cardiovascular risk for women with pregnancies complicated by pre-eclampsia is challenging. Our aim was to identify potential clinical and biomarker predictors of future cardiovascular risk at six weeks postpartum in women with hypertensive pregnancies. STUDY DESIGN: Prospective longitudinal cohort. MAIN OUTCOME MEASURES: Ten year-Framingham cardiovascular risk scores were calculated for 477 women (94 with gestational hypertension, 288 with pre-eclampsia, 30 with superimposed pre-eclampsia, 51 with chronic hypertension, 14 women with uncomplicated pregnancies). B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and placental growth factor (PlGF) were quantified at six weeks postpartum. RESULTS: Framingham cardiovascular risk scores were not higher in women with pregnancies complicated by pre-eclampsia than healthy controls, nor were scores higher in women with pre-existing chronic hypertension complicated with superimposed pre-eclampsia compared with those without superimposed pre-eclampsia. Women with gestational hypertension had higher risk scores than women with pre-eclampsia and healthy controls. Established risk factors of cardiovascular disease including diastolic blood pressure and previously diagnosed chronic hypertension were associated with higher scores, and African ethnicity, parity and estimated glomerular filtration rate also were independently associated with higher Framingham risk scores at six weeks postpartum. PlGF, BNP and NGAL concentrations were not associated with Framingham cardiovascular risk scores after adjustment for independent variables. CONCLUSIONS: A history of pre-eclampsia or superimposed pre-eclampsia in most recent pregnancy was not associated with elevated Framingham risk score at six weeks postpartum. Established clinical predictors may enable risk stratification at six weeks postpartum, which are not enhanced by the biomarkers included in this study.
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Presión Sanguínea , Enfermedades Cardiovasculares/diagnóstico , Hipertensión Inducida en el Embarazo/diagnóstico , Periodo Posparto , Preeclampsia/diagnóstico , Adulto , Biomarcadores/sangre , Población Negra , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etnología , Enfermedades Cardiovasculares/fisiopatología , Inglaterra/epidemiología , Femenino , Tasa de Filtración Glomerular , Humanos , Hipertensión Inducida en el Embarazo/sangre , Hipertensión Inducida en el Embarazo/etnología , Hipertensión Inducida en el Embarazo/fisiopatología , Riñón/fisiopatología , Lipocalina 2/sangre , Estudios Longitudinales , Péptido Natriurético Encefálico/sangre , Paridad , Factor de Crecimiento Placentario/sangre , Periodo Posparto/sangre , Preeclampsia/sangre , Preeclampsia/etnología , Preeclampsia/fisiopatología , Valor Predictivo de las Pruebas , Embarazo , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Previous researchers have studied circadian changes in the fetal heart rate (FHR) on small sample sizes and in a strictly controlled environment. This study was undertaken to investigate these changes during the late second and third trimesters, using a portable fetal electrocardiogram recording device (Monica AN24) in pregnant women in home and hospital environments with unrestricted mobility. METHODS: This was a prospective cohort study of 54 pregnant women with uncomplicated singleton pregnancies between 25 and 40 weeks gestation. FHR recordings were made up to 16 h at home or in the hospital setting in the United Kingdom. FHR data over 90 min periods were averaged and the day (7:00 am-11:00 pm) and night (11:00 pm-7:00 am) data from the same individual were compared. Data were examined for evidence of sex-related differences. RESULTS: During the night, there was a significant reduction in basal heart rate (bFHR) and a significant increase in short term variation (STV) and long term variation (LTV) (P < 0.05). Basal FHR decreased (P < 0.002), whereas LTV increased (P = 0.014) with advancing gestation. Male fetuses showed greater day: night variation than females regardless of gestation (P = 0.014). There was a higher bFHR in fetuses monitored during the day in hospital (P = 0.04). CONCLUSION: This study demonstrates that there are sex-, environment and time-related differences in the FHR parameters measured. These differences may need to be considered taken when interpreting FHR data.
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OBJECTIVES: To investigate effects of maternal smoking on the fetal heart rate (FHR) in ambulatory patients using a portable fetal electrocardiogram recording device. METHODS: A prospective cohort study of 43 pregnant smokers and 43 non-smoking gestation-matched controls with uncomplicated singleton pregnancies. Smokers were divided into light (1-10) and moderate (11-20 cigarettes/d). The FHR was recorded for 16 h with smokers smoking at will, using an event button to record when they lit a cigarette. Fifty recordings were made in the patients' homes with 36 in ambulatory inpatients. Three consecutive 30-min epochs (before, during and after smoking) were compared with the controls. RESULTS: Basal FHR was significantly lower before smoking in the foetuses of smokers compared with non-smokers (p = 0.048). During smoking, there was a significant dose-dependent fall in short-, long-term and true beat-to-beat variabilities (p = 0.004, p < 0.0001 and p = 0.024, respectively). CONCLUSION: Maternal smoking leads to reversible changes in FHR variability that mimic those associated with an increased incidence of adverse cardiovascular events in adults. As heart rate and variability reflect the autonomic control of the heart, our findings suggest that maternal smoking interferes with the autonomic control of the FHR.
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Frecuencia Cardíaca Fetal/fisiología , Conducta Materna , Embarazo , Fumar/efectos adversos , Adulto , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Electrocardiografía , Femenino , Monitoreo Fetal , Humanos , Efectos Tardíos de la Exposición Prenatal/etiología , Estudios ProspectivosRESUMEN
Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk.
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INTRODUCTION: There is increasing evidence that hypertensive pregnancy is a risk factor for renal disease [1]. OBJECTIVES: To examine the correlation between maternal and offspring characteristics and impaired glomerular filtration rate following a hypertensive pregnancy. METHOD: We calculated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula corrected for body surface area in a cohort of 422 women at 6 weeks following a pregnancy complicated by all types of hypertension (pre-eclampsia, gestational hypertension, essential hypertension with and without superimposed pre-eclampsia). We performed statistical analysis using Spearmans rho to examine for correlations with maternal and fetal characteristics. RESULTS: 2.1% women had poor renal function at 6 weeks after delivery with a GFR <60ml/min/1.73m(2). Older mothers were more likely to have a lower GFR (p=0.001). Women with poor renal function at 6 weeks were more likely to have had a low birth weight baby (p=0.002). The median birth weight for women with GFR<60ml/min/1.73m(2) was 2.85kg as opposed to 3.23kg for women with a GFR >60ml/min/1.73m(2). CONCLUSIONS: Clinically significant renal impairment following a hypertensive pregnancy is a rare. Advancing maternal age represents an important risk factor for on-going renal disease in this population. Small babies are more likely in a hypertensive pregnancy [2] and may also represent a marker for poorer maternal health after birth in this population.
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INTRODUCTION: There is increasing evidence to suggest that both preeclampsia and microalbuminuria are linked to long term cardiovascular and renal disease [1,2]. OBJECTIVES: To identify the proportion and characteristics of women with persistent significant proteinuria at 6 weeks following delivery. METHOD: We examined the blood pressure, serum electrolytes and urine protein creatinine ratio (PCR) in a cohort of 219 women who were seen following a pre-eclamptic pregnancy in a postnatal clinic at a minimum of 6 weeks following delivery. RESULTS: A PCR>50mg/mmol (considered to be clinically significant) was seen in 4.1% women at 6 weeks after delivery. Women with a higher antenatal PCR were more likely to have a PCR>50mg/mmol at 6 weeks postnatal (p=0.003). Antenatal or postnatal blood pressure was not correlated with persistent significant proteinuria. Neither estimated nor calculated glomerular filtration rate (eGFR) at 6 weeks correlated with those having persistent proteinuria, however there was a trend towards lower eGFR and higher serum creatinine antenatally in this group (p=0.138 and p=0.088). CONCLUSION: There are a small but worrying number of women who still have clinically significant proteinuria at 6 weeks after a pre-eclamptic pregnancy. This represents a group of women who may have a higher risk of cardiovascular and renal disease.
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This study investigates the contractile response to 5 hydroxytryptamine (5HT) of chorionic artery and vein segments from normotensive (NT) and pre-eclamptic (PE) placentae. It also looked at the effectiveness of ketanserin (KET), a 5HT(2A) receptor antagonist, in reducing 5HT-mediated vasoconstriction. 5HT induced vasoconstriction in all of the vessels was studied. Compared to NT vessels, Emax (%KCl) was significantly reduced in PE arteries (p<0.05) and veins (p<0.0005). The mean Emax for NT arteries was 104.1 (±10.71) whilst PE arteries showed a mean Emax of 57.02 (±12.13). KET produced a statistically significant reduction of Emax in both vessels in NT and the arteries in PE. However the antagonistic effect of KET was not pronounced in PE veins. The EC50 values for NT and PE arteries and veins did not change significantly. There were no noticeable changes in the expression profiles of 5HT(2A) receptor mRNA and protein expressions. The data from this study suggest that in PE, the vascular reactivity of chorionic vessels to 5HT is reduced and it was not due to the altered expression of 5HT(2A) receptors.
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Corion/irrigación sanguínea , Placenta/irrigación sanguínea , Circulación Placentaria , Preeclampsia/fisiopatología , Receptor de Serotonina 5-HT2A/metabolismo , Serotonina/metabolismo , Vasoconstricción , Adolescente , Adulto , Arterias/efectos de los fármacos , Arterias/metabolismo , Arterias/fisiopatología , Corion/efectos de los fármacos , Corion/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Técnicas In Vitro , Ketanserina/farmacología , Placenta/efectos de los fármacos , Placenta/metabolismo , Circulación Placentaria/efectos de los fármacos , Preeclampsia/metabolismo , Embarazo , Tercer Trimestre del Embarazo , ARN Mensajero/metabolismo , Receptor de Serotonina 5-HT2A/química , Receptor de Serotonina 5-HT2A/genética , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Vasoconstricción/efectos de los fármacos , Venas/efectos de los fármacos , Venas/metabolismo , Venas/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS: We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS: 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION: The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING: Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.
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Preeclampsia/mortalidad , Adulto , Femenino , Humanos , Recién Nacido , Mortalidad Materna , Modelos Estadísticos , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Curva ROC , Medición de RiesgoRESUMEN
OBJECTIVES: The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. DESIGN: A multicentre randomised controlled trial (RCT). SETTING: Fetal medicine units. POPULATION: Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). METHODS: Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. MAIN OUTCOME MEASURES: The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. FUNDING: Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].
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Enfermedades Fetales/cirugía , Atención Prenatal/métodos , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Femenino , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Enfermedades Renales/etiología , Masculino , Embarazo , Resultado del Tratamiento , Obstrucción del Cuello de la Vejiga Urinaria/embriologíaRESUMEN
Progressive stenosis of the semilunar valves in utero can be life threatening. We treated two fetuses with complete or almost complete pulmonary atresia and imminent hydrops (increased cardiothoracic ratio, pericardial effusion, holosystolic tricuspid regurgitation extending into diastole, and abnormal venous Dopplers). We dilated the pulmonary valve of two fetuses in utero at 28 and 30 weeks' gestation, through the mothers' abdomens. After the procedure, the fetuses had decreased signs of circulatory failure and gestation continued until near term. In the neonatal period, we did a repeat valvuloplasty with systemic-to-pulmonary arterial shunt. Both children (now aged 18 months and 12 months) now have biventricular circulation. Surgery on selected fetuses with semilunar valve stenosis or atresia, or both, can extend pregnancy and favourably change the postnatal surgical options.