RESUMEN
BACKGROUND: Reproductive and menstrual factors have been evaluated as surrogates for long-term hormonal exposures in several prospective studies of colorectal cancer, yet findings have been conflicting. METHODS: The relation of reproductive and menstrual factors (self-reported via a reproductive history questionnaire) with incident colorectal cancer was investigated among women enrolled in the Women's Health Initiative Observational Study (WHI-OS), a longitudinal cohort of 93 676 postmenopausal women (aged 50-79 years at enrolment) in which 1149 incident cases of colorectal cancer occurred over a median follow-up of 11.9 years. Multivariable Cox proportional hazards models that included established colorectal cancer risk factors were constructed to examine the association of colorectal cancer incidence with reproductive and menstrual factors. RESULTS: Having had two children (vs nulliparous: hazard ratio (HR)=0.80, 95% confidence interval (CI): 0.64-0.99) was inversely associated with colorectal cancer risk. Compared with never users, ever use of oral contraceptives was associated with lower colorectal cancer risk (HR=0.74, 95% CI: 0.63-0.86); however, no relationship was observed for duration of oral contraceptives use (4 years vs 1 year: HR=0.94, 95% CI: 0.67-1.32). None of the remaining reproductive and menstrual factors was associated with colorectal cancer incidence. CONCLUSIONS: Parity and prior use of oral contraceptives were associated with lower colorectal cancer risk in this cohort of postmenopausal women.
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Neoplasias Colorrectales/epidemiología , Ciclo Menstrual/fisiología , Reproducción/fisiología , Factores de Edad , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Paridad , Embarazo , Historia Reproductiva , Factores de Riesgo , Salud de la MujerRESUMEN
OBJECTIVE: The aim of the study is to determine if umbilical cord serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and myeloperoxidase (MPO), in pregnancies at risk for preterm birth (PTB), are associated with neonatal morbidities and/or altered neurodevelopmental outcomes in the children. STUDY DESIGN: Umbilical cord serum samples were collected at birth from 400 newborns delivered within a multicenter randomized controlled trial of repeated versus single course of antenatal corticosteroids (ACs), in women at increased risk for PTB. Newborns were followed through discharge and were evaluated between 36 and 42 months corrected age with neurological examination and Bayley Scales of Infant Development. Umbilical cord serum concentrations of IL-6, CRP, and MPO were determined using enzyme-linked immunoassays. Multivariate logistic regression analyses explored the relationship between umbilical cord serum IL-6, CRP, and MPO levels, adverse newborn outcomes, and PTB < 32 weeks of gestational age (GA). RESULTS: Univariate analysis revealed that umbilical cord IL-6 above the 75th percentile was associated with increased respiratory distress syndrome (RDS) and chronic lung disease (CLD), but not with necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), or neonatal sepsis; however, this association was not significant after adjusting for GA at delivery and treatment group. No significant associations between CRP or MPO and RDS, CLD, NEC, sepsis, or IVH were evident. Regression analysis revealed that CRP above the 75th percentile was associated with a decreased risk of CLD (odds ratio, 0.10; 95% confidence interval, 0.02-0.41). No associations between umbilical cord IL-6, CRP, or MPO and MDI < 70 or PDI < 70 were evident. Umbilical cord serum concentrations of IL-6, CRP, and MPO, above the 75th percentile, were associated with more frequent PTB < 32 weeks of GA. CONCLUSION: Elevated umbilical cord serum concentration of CRP is associated with reduced risk for CLD even after adjusting for GA at delivery. Occurrence of levels > 75th percentile of IL-6, CRP, and MPO in umbilical cord serum was associated with PTB < 32 weeks of GA. Elevated umbilical cord serum concentrations of IL-6, CRP, and MPO at birth were not associated with poor neurodevelopmental outcomes.
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Proteína C-Reactiva/metabolismo , Desarrollo Infantil , Sangre Fetal/metabolismo , Enfermedades del Prematuro/sangre , Interleucina-6/sangre , Peroxidasa/sangre , Nacimiento Prematuro/sangre , Enterocolitis Necrotizante/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Edad Gestacional , Humanos , Recién Nacido , Enfermedades del Recién Nacido/sangre , Recien Nacido Prematuro , Hemorragias Intracraneales/sangre , Modelos Logísticos , Enfermedades Pulmonares/sangre , Análisis Multivariante , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido/sangre , Sepsis/sangreRESUMEN
Genome-wide association studies (GWAS) of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G × E) interactions in post-menopausal African-American and Hispanic women from the Women's Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumference ratio (WHR) adjusted for multidimensional-scaling-derived axes of ancestry and age was run in race-stratified data with 871,512 SNPs available from African-Americans (N = 8,203) and 786,776 SNPs from Hispanics (N = 3,484). Tests of G × E interaction at all SNPs for recreational physical activity (m h/week), dietary energy intake (kcal/day), alcohol intake (categorical), cigarette smoking years, and cigarette smoking (ever vs. never) were run in African-Americans and Hispanics adjusted for ancestry and age at interview, followed by meta-analysis of G × E interaction terms. The strongest evidence for concordant G × E interactions in African-Americans and Hispanics was for smoking and marker rs10133840 (Q statistic P = 0.70, beta = -0.01, P = 3.81 × 10(-7)) with BMI as the outcome. The strongest evidence for G × E interaction within a cohort was in African-Americans with WHR as outcome for dietary energy intake and rs9557704 (SNP × kcal = -0.04, P = 2.17 × 10(-7)). No results exceeded the Bonferroni-corrected statistical significance threshold.
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Negro o Afroamericano/genética , Índice de Masa Corporal , Interacción Gen-Ambiente , Hispánicos o Latinos/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple , Posmenopausia , Relación Cintura-Cadera , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Ingestión de Energía , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Modelos Logísticos , Persona de Mediana Edad , Actividad Motora , Estudios Prospectivos , Factores de Riesgo , Fumar/epidemiología , Estados Unidos/epidemiología , Salud de la MujerRESUMEN
IMPORTANCE: Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention. OBJECTIVE: To report a comprehensive, integrated overview of findings from the 2 Women's Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. INTERVENTIONS: Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506) or placebo (n = 8102). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 5310) or placebo (n = 5429). The intervention lasted a median of 5.6 years in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of cumulative follow-up until September 30, 2010. MAIN OUTCOMES AND MEASURES: Primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death. RESULTS: During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10,000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years. Quality-of-life outcomes had mixed results in both trials. CONCLUSIONS AND RELEVANCE: Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.
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Neoplasias de la Mama/prevención & control , Enfermedad Coronaria/prevención & control , Estrógenos Conjugados (USP)/administración & dosificación , Estrógenos/administración & dosificación , Terapia de Reemplazo de Hormonas/efectos adversos , Acetato de Medroxiprogesterona/administración & dosificación , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias Colorrectales/epidemiología , Enfermedad Coronaria/epidemiología , Quimioterapia Combinada , Neoplasias Endometriales/epidemiología , Estrógenos/efectos adversos , Estrógenos Conjugados (USP)/efectos adversos , Femenino , Estudios de Seguimiento , Fracturas de Cadera/epidemiología , Humanos , Acetato de Medroxiprogesterona/efectos adversos , Persona de Mediana Edad , Posmenopausia , Embolia Pulmonar/epidemiología , Calidad de Vida , Riesgo , Accidente Cerebrovascular/epidemiología , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Increased fluid intake, and decreased dietary sodium and animal protein intake are thought to reduce the risk of kidney stones but the role of calcium intake is controversial. We evaluated the relationship between dietary factors and incident kidney stone formation. MATERIALS AND METHODS: Secondary analysis was done of 78,293 women from the prospective WHI OS (Women's Health Initiative Observational Study) with no history of nephrolithiasis who completed the validated food frequency questionnaire. Multivariate logistic regression was used to determine demographic and dietary factors, and supplement use independently associated with incident kidney stones. RESULTS: Overall 1,952 women (2.5%) reported an incident kidney stone in 573,575 person-years of followup. The risk of incident kidney stones was decreased by 5% to 28% (p = 0.01) with higher dietary calcium intake and by 13% to 31% (p = 0.002) with higher water intake after adjusting for nephrolithiasis risk factors. Conversely higher dietary sodium intake increased the risk of nephrolithiasis by 11% to 61% (p <0.001) after adjustment with the most pronounced effect in women with the highest intake. Higher body mass index independently increased the risk of incident nephrolithiasis (adjusted OR 1.19-2.01, p <0.001). Animal protein intake was not associated with nephrolithiasis on multivariate analysis. CONCLUSIONS: This study adds to the growing evidence underscoring the importance of maintaining adequate fluid and dietary calcium intake. Greater dietary calcium intake significantly decreased the risk of incident kidney stones. In contrast, excess sodium intake increased the risk of incident nephrolithiasis, especially in women with the highest intake. Animal protein intake was not independently associated with nephrolithiasis.
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Calcio de la Dieta/administración & dosificación , Cálculos Renales/epidemiología , Sodio en la Dieta/administración & dosificación , Anciano , Índice de Masa Corporal , Agua Potable/administración & dosificación , Femenino , Humanos , Cálculos Renales/prevención & control , Modelos Logísticos , Persona de Mediana Edad , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Worship attendance has been associated with longer survival in prospective cohort studies. A possible explanation is that religious involvement may promote healthier lifestyle choices. Therefore, we examined whether attendance is associated with healthy behaviors, i.e. use of preventive medicine services, non-smoking, moderate drinking, exercising regularly, and with healthy dietary habits. The population included 71,689 post-menopausal women enrolled in the Women's Health Initiative observational study free of chronic diseases at baseline. Attendance and lifestyle behaviors information was collected at baseline using self-administered questionnaires. Healthy behaviors were modeled as a function of attendance using logistic regression. After adjustment for confounders, worship attendance (less than weekly, weekly, and more than weekly vs. never) was positively associated with use of preventive services [OR for mammograms: 1.34 (1.19, 1.51), 1.41 (1.26, 1.57), 1.33 (1.17, 1.52); breast self exams: 1.14 (1.02, 1.27), 1.33 (1.21, 1.48), 1.25 (1.1, 1.43); PAP smears: 1.22 (1.01, 1.47-weekly vs. none)]; non-smoking: [1.41 (1.35, 1.48), 1.76 (1.69, 1.84), 2.27 (2.15, 2.39)]; moderate drinking [1.35 (1.27, 1.45), 1.60 (1.52, 1.7), 2.19 (2.0, 2.4)]; and fiber intake [1.08 (1.03, 1.14), 1.16 (1.11, 1.22), 1.31 (1.23, 1.39), respectively], but not with regular exercise or with lower saturated fat and caloric intake. These findings suggest that worship attendance is associated with certain, but not all, healthy behaviors. Further research is needed to get a deeper understanding of the relationship between religious involvement and healthy lifestyle behaviors and of the inconsistent patterns in this association.
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Actitud Frente a la Salud , Conductas Relacionadas con la Salud , Posmenopausia , Religión y Medicina , Estudios de Cohortes , Femenino , Humanos , Estilo de Vida , Persona de Mediana Edad , Oportunidad Relativa , Religión y Psicología , Salud de la MujerRESUMEN
The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend routine rapid HIV testing in labor and delivery (L&D) for women with undocumented HIV status using an opt-out approach. Identifying factors associated with declining a rapid HIV test in L&D will be helpful in developing strategies to improve rapid HIV testing uptake. Data from the Mother-Infant Rapid Intervention at Delivery study were analyzed. Women ≥24 weeks gestation, in labor, with undocumented HIV status were offered rapid HIV testing using informed consent. Women who declined rapid HIV testing (decliners) but agreed to be interviewed were compared to women who accepted testing (acceptors). 102 decliners and 478 acceptors met inclusion criteria for analysis. Decliners of rapid HIV testing were more likely to have had prenatal care (PNC), after adjusting for age, Hispanic ethnicity, high-school education and city of enrollment (adjusted OR 2.4, 95% CI 1.06-5.58). Having had PNC was collinear with prior HIV education and previous offer of an HIV test during the current pregnancy, so these factors were not part of the model. During PNC, standard informed consent may involve discussions that negatively affect later uptake of testing in L&D. Therefore an opt-out approach to testing may improve testing rates. Furthermore, decliners may have felt that testing in L&D was redundant because of previous testing during PNC; however, if previous testing occurred, this was undocumented at L&D. Documentation and timely communication of HIV status is critical to provide appropriate HIV prophylaxis.
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Serodiagnóstico del SIDA/métodos , Anticuerpos Antivirales/sangre , Infecciones por VIH/diagnóstico , VIH-1/inmunología , Aceptación de la Atención de Salud/psicología , Complicaciones Infecciosas del Embarazo/diagnóstico , Adolescente , Adulto , Parto Obstétrico , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Consentimiento Informado , Entrevistas como Asunto , Trabajo de Parto , Valor Predictivo de las Pruebas , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Atención Prenatal , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period. METHODS: The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611. FINDINGS: After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups. INTERPRETATION: Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer. FUNDING: National Heart, Lung and Blood Institute, National Institutes of Health.
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Terapia de Reemplazo de Estrógeno/efectos adversos , Neoplasias Pulmonares , Posmenopausia , Anciano , Carcinoma de Pulmón de Células no Pequeñas/inducido químicamente , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Causas de Muerte , Método Doble Ciego , Terapia de Reemplazo de Estrógeno/métodos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología , Persona de Mediana Edad , Posmenopausia/efectos de los fármacos , Modelos de Riesgos Proporcionales , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Estados Unidos/epidemiología , Salud de la MujerRESUMEN
OBJECTIVE: To determine whether asthma-specific quality of life during pregnancy is related to asthma exacerbations and to perinatal outcomes. METHODS: This was a secondary analysis of data from a randomized controlled trial of inhaled beclomethasone versus theophylline in the treatment of moderate asthma during pregnancy. The Juniper Asthma Quality of Life Questionnaire (AQLQ) was administered to patients at enrollment. Exacerbations were defined as asthma symptoms requiring a hospitalization, unscheduled medical visit, or oral corticosteroid course. RESULTS: Quality of life assessments were provided by 310 of the 385 participants who completed the study. There was more than a 25% decrease in the odds of a subsequent asthma exacerbation for every 1-point increase in AQLQ score for the overall score (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.55-0.96), emotion domain (OR 0.72, 95% CI 0.59-0.88), and symptoms domain (OR 0.73, 95% CI 0.57-0.94). These relationships were not significantly influenced by initial symptom frequency or forced expiratory volume in 1 s (FEV(1)). No significant relationships were demonstrated between enrollment AQLQ scores and preeclampsia, preterm birth, low birth weight, or small for gestational age. CONCLUSION: Asthma-specific quality of life in early pregnancy is related to subsequent asthma morbidity during pregnancy but not to perinatal outcomes.
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Asma/epidemiología , Asma/psicología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Resultado del Embarazo/epidemiología , Resultado del Embarazo/psicología , Calidad de Vida/psicología , Adolescente , Adulto , Asma/tratamiento farmacológico , Asma/fisiopatología , Femenino , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/psicología , Volumen Espiratorio Forzado/fisiología , Humanos , Recién Nacido de Bajo Peso/psicología , Recién Nacido , Morbilidad , Oportunidad Relativa , Preeclampsia/epidemiología , Preeclampsia/psicología , Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To determine if maternal asthma or asthma severity affects newborn morphometry. STUDY DESIGN: A secondary analysis was performed on data collected in a multicenter prospective observational cohort study of asthma in pregnancy. Patients enrolled included women with asthma stratified by severity of disease and controls. Asthma severity was defined according to the classification proposed by the National Asthma Education Program (NAEP) Report of the Working Group on Asthma and Pregnancy, modified to include medication requirements. Newborn morphometry measurements included birth weight (BW) and multiples of the median birth weight (BW-MOM), head circumference (HC), length (L), HC:BW ratio, and ponderal index (PI). RESULTS: Of 2480 patients there were 828 nonasthmatic controls, 828 with mild, 775 with moderate, and 49 with severe disease. Comparing all groups, there were statistically significant differences in maternal age (p < .001), race (p = .005), parity (p = .006), prepregnancy weight (p = .028), and medical care source (p = .001), with the severe asthma group having the highest mean maternal age (25.7 years), and proportion of African Americans (71.4%), proportion of multiparous patients (63.3%), and proportion of patients receiving government assistance (85.7%). When the control group was excluded from the comparisons, differences in prepregnancy weight and medical care source were no longer significant. BW-MOM and L did not differ between groups. The HC:BW ratio increased with asthma severity (p = .029) and was increased compared to controls (p = .010). This remained significant after controlling for confounding variables (both p <.001). HC was statistically significantly different between all groups (p = .032), as well as among women with varying degrees of asthma severity (p = .013), which was not clinically significant. After covariates adjustment, HC was not significantly different among all groups (p = .228), nor the asthma groups (p = .144). CONCLUSION: Asthma severity is associated with an increased HC:BW ratio. Severity was not found to impact HC, BW-MOM, L, or PI independently. However, the magnitudes of the effects were too small to suggest a clinically significant effect of asthma on neonatal morphometry in this large prospectively studied sample.
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Asma/diagnóstico , Pesos y Medidas Corporales , Desarrollo Fetal , Recién Nacido , Complicaciones del Embarazo , Adolescente , Adulto , Peso al Nacer , Estatura , Peso Corporal , Femenino , Cabeza/anatomía & histología , Humanos , Seguro de Salud/estadística & datos numéricos , Edad Materna , Paridad , Embarazo , Estudios Prospectivos , Grupos Raciales/estadística & datos numéricos , Fumar/epidemiología , Estados Unidos , Adulto JovenRESUMEN
Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB <32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery.
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Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Enfermedades del Recién Nacido/etiología , Interleucina-6/sangre , Intercambio Materno-Fetal , Metaloproteinasa 9 de la Matriz/sangre , Segundo Trimestre del Embarazo/sangre , Tercer Trimestre del Embarazo/sangre , Nacimiento Prematuro/sangre , Enterocolitis Necrotizante/congénito , Enterocolitis Necrotizante/diagnóstico , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/fisiopatología , Enterocolitis Necrotizante/terapia , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/metabolismo , Enfermedades del Recién Nacido/terapia , Hemorragias Intracraneales/congénito , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/metabolismo , Hemorragias Intracraneales/fisiopatología , Hemorragias Intracraneales/terapia , Enfermedades Pulmonares/congénito , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/fisiopatología , Enfermedades Pulmonares/terapia , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/mortalidad , Nacimiento Prematuro/fisiopatología , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/metabolismo , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatología , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Factores de Riesgo , Sepsis/congénito , Sepsis/diagnóstico , Sepsis/metabolismo , Sepsis/fisiopatología , Sepsis/terapiaRESUMEN
BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).
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Carbonato de Calcio/uso terapéutico , Fracturas Óseas/prevención & control , Vitamina D/uso terapéutico , Anciano , Densidad Ósea/efectos de los fármacos , Calcio/uso terapéutico , Carbonato de Calcio/efectos adversos , Carbonato de Calcio/farmacología , Método Doble Ciego , Combinación de Medicamentos , Interacciones Farmacológicas , Terapia de Reemplazo de Estrógeno , Femenino , Estudios de Seguimiento , Fracturas Óseas/epidemiología , Fracturas de Cadera/prevención & control , Humanos , Cálculos Renales/inducido químicamente , Persona de Mediana Edad , Cooperación del Paciente , Posmenopausia , Modelos de Riesgos Proporcionales , Riesgo , Fracturas de la Columna Vertebral/prevención & control , Vitamina D/efectos adversos , Vitamina D/sangre , Vitamina D/farmacologíaRESUMEN
BACKGROUND: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study. RESULTS: The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).
Asunto(s)
Adenocarcinoma/prevención & control , Carbonato de Calcio/uso terapéutico , Neoplasias Colorrectales/prevención & control , Vitamina D/uso terapéutico , Adenocarcinoma/epidemiología , Anciano , Calcio/uso terapéutico , Carbonato de Calcio/efectos adversos , Carbonato de Calcio/farmacología , Pólipos del Colon/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Método Doble Ciego , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Posmenopausia , Modelos de Riesgos Proporcionales , Vitamina D/efectos adversos , Vitamina D/sangre , Vitamina D/farmacologíaRESUMEN
OBJECTIVE: To estimate the effect of single and recurrent doses of antenatal corticosteroids on fetal bone metabolism. METHODS: This was a secondary analysis of a cohort of pregnant women from a previously reported randomized, placebo-controlled, multicenter trial of women at risk for preterm delivery who received weekly courses of betamethasone (active) or placebo after an initial course of corticosteroids. Umbilical cord serum levels of carboxy-terminal carboxy-terminal propeptide of type I procollagen and cross-linked carboxy-terminal telopeptide of type I procollagen were measured to assess the rate of fetal bone formation and resorption, respectively. Analysis was stratified according to number of repeat antenatal study courses of betamethasone or placebo (one to three compared with at least four courses, not including the initial course). RESULTS: Of the 251 umbilical cord serum samples, the median serum carboxy-terminal telopeptide of type I procollagen levels, but not carboxy-terminal propeptide of type I procollagen levels, was significantly lower with repeat betamethasone exposure (55.0 compared with 57.9 micrograms/L, P=.01). In the fetuses exposed to at least four repeat study courses, there was a significant decrease in median carboxy-terminal telopeptide of type-I procollagen levels between repeat betamethasone exposure and placebo (53.4 compared with 58.6 micrograms/L, respectively, P=.04), but there was no difference between groups in the fetuses exposed to 1-3 repeat study courses (57.4 compared with 56.7 micrograms/L, respectively, P=.29). CONCLUSION: Levels of umbilical cord serum markers of bone resorption but not formation are reduced in fetuses exposed to repeat courses of antenatal betamethasone. Up to four courses of antenatal betamethasone do not seem to affect fetal bone metabolism. LEVEL OF EVIDENCE: II.
Asunto(s)
Corticoesteroides/administración & dosificación , Huesos/metabolismo , Feto/metabolismo , Betametasona/administración & dosificación , Femenino , Sangre Fetal/química , Feto/efectos de los fármacos , Glucocorticoides/administración & dosificación , Humanos , Trabajo de Parto Prematuro/prevención & control , Embarazo , Procolágeno/sangreRESUMEN
OBJECTIVE: To compare the rates of gestational diabetes among women who received serial doses of 17-alpha hydroxyprogesterone caproate vs placebo. STUDY DESIGN: Secondary analysis of 2 double-blind randomized placebo-controlled trials of 17-alpha hydroxyprogesterone caproate given to women at risk for preterm delivery. The incidence of gestational diabetes was compared between women who received 17-alpha hydroxyprogesterone caproate or placebo. RESULTS: We included 1094 women; 441 had singleton and 653 had twin gestations. Combining the 2 studies, 616 received 17-alpha hydroxyprogesterone caproate and 478 received placebo. Among singleton and twin pregnancies, rates of gestational diabetes were similar in women receiving 17-alpha hydroxyprogesterone caproate vs placebo (5.8% vs 4.7%; P = .64 and 7.4% vs 7.6%; P = .94, respectively). In the multivariable model, progesterone was not associated with gestational diabetes (adjusted odds ratio, 1.04; 95% confidence interval, 0.62-1.73). CONCLUSION: Weekly administration of 17-alpha hydroxyprogesterone caproate is not associated with higher rates of gestational diabetes in either singleton or twin pregnancies.
Asunto(s)
Diabetes Gestacional/epidemiología , Hidroxiprogesteronas/uso terapéutico , Progestinas/uso terapéutico , Caproato de 17 alfa-Hidroxiprogesterona , Método Doble Ciego , Femenino , Humanos , Análisis Multivariante , Embarazo , Embarazo Múltiple , Factores de RiesgoRESUMEN
Women with HIV infection report elevated and persisting psychosocial distress, sleep difficulty, and fatigue. The objective of this study was to examine psychosocial distress, sleep difficulty, and fatigue in a group of lower socioeconomic status women co-infected with HIV and HPV (N = 60). After controlling for relevant health behavioral and medical variables, multiple regression analyses indicated that greater psychosocial distress was associated with greater fatigue (p < .01), as well as greater sleep difficulty (p < .01). Sleep difficulty partially mediated the relationship between distress and fatigue (Sobel test, z = 2.39, p = .02). Stress management and sleep-based cognitive behavioral intervention approaches may be useful for treating fatigue in these women, possibly through reductions in psychosocial distress and improvements in sleep quality.
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Fatiga/complicaciones , Infecciones por VIH/complicaciones , Infecciones por Papillomavirus/complicaciones , Trastornos del Sueño-Vigilia/complicaciones , Estrés Psicológico/complicaciones , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: Prior work has related elevated life stress to greater risk of cervical neoplasia in women with human immunodeficiency virus (HIV) and human papillomavirus (HPV). PURPOSE: This study investigated associations between depressive symptoms and cervical neoplasia in HIV+ HPV+ women. Participants were 58 HIV+ HPV+ women. METHOD: Participants underwent colposcopy, including HPV screening, Papanicolaou smear, and cervical biopsy to determine study eligibility. Eligible participants completed the Beck Depression Inventory (BDI) and the Center for Epidemiologic Studies-Depression (CES-D) scale. RESULTS: Presence and severity of clinically significant depressive symptomatology were associated with cervical neoplasia. Hierarchical logistic regression analysis revealed that women with greater depressive symptoms had marginally greater odds of presenting with cervical neoplasia (BDI: OR = 1.16, p = 0.092; CES-D: OR = 1.15, p = 0.067. Women with greater somatic depressive symptoms, specifically, had significantly greater odds of presenting with cervical neoplasia (BDI: OR = 1.86, p = 0.027; CES-D: OR = 1.56, p = 0.017). CONCLUSION: These findings suggest that screening HIV+ women for somatic depression may help identify those at risk for cervical neoplasia. Future depression research with medical populations should discern somatic depressive symptoms from disease symptoms, as they may have important value in independently predicting health outcomes.
Asunto(s)
Trastorno Depresivo/epidemiología , Trastorno Depresivo/virología , Infecciones por VIH/psicología , Infecciones por Papillomavirus/psicología , Neoplasias del Cuello Uterino/psicología , Centros Médicos Académicos , Adolescente , Adulto , Alphapapillomavirus , Trastorno Depresivo/psicología , Etnicidad/psicología , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Entrevista Psicológica , Modelos Logísticos , Persona de Mediana Edad , Pobreza , Factores de Riesgo , Sudeste de Estados Unidos/epidemiología , Adulto JovenRESUMEN
The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.
Asunto(s)
Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/epidemiología , Terapia de Reemplazo de Estrógeno/efectos adversos , Estrógenos Conjugados (USP)/efectos adversos , Estrógenos/efectos adversos , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Estados Unidos/epidemiología , Salud de la MujerRESUMEN
OBJECTIVE: This study was undertaken to evaluate the effect of change of shift for physicians and nurses on complications associated with cesarean delivery. STUDY DESIGN: 17,996 term women undergoing an unscheduled cesarean delivery in 13 centers from 1999-2000 were included. Maternal and neonatal morbidities were evaluated by time of infant delivery vis-à-vis nursing change of shift (6 AM-8 AM, 2 PM-4 PM, 10 PM-12 AM vs all other hours). The sample was then limited to weekdays only and physician shift changes were evaluated (physician shift change 6 AM-8 AM, 5 PM-7 PM vs all others). A composite of 30 maternal morbidities was also evaluated by logistic regression, controlling for potentially confounding factors. RESULTS: Physician change of shift had no measurable effect on maternal and neonatal outcomes. Neonatal facial nerve palsies were increased at nursing change of shift (5 vs 0) as were hysterectomies (33 [0.24%] vs 23 [0.53%]; P < .007). Nursing change of shift had no impact on composite maternal morbidity after controlling for age, race, insurance, medical problems, prior incision type, weekend day, and prenatal care (odds ratio = 0.98; 95% confidence interval = 0.89-1.08). CONCLUSION: Physician change of shift does not appear to be associated with an increase in morbidities. However, cesarean delivery during nursing change of shift is associated with increased risk of neonatal facial nerve palsy and hysterectomy. Further investigation is needed to understand the cause of this association.
Asunto(s)
Cesárea/efectos adversos , Complicaciones del Trabajo de Parto/epidemiología , Sistema de Registros , Tolerancia al Trabajo Programado , Adulto , Cesárea/estadística & datos numéricos , Traumatismos del Nervio Facial , Femenino , Humanos , Histerectomía , Enfermeras y Enfermeros , Complicaciones del Trabajo de Parto/etiología , Complicaciones del Trabajo de Parto/mortalidad , Complicaciones del Trabajo de Parto/prevención & control , Médicos , Embarazo , Estudios Prospectivos , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Risk for developing cervical neoplastic disease is greatly increased in women infected with oncogenic sexually transmitted human papillomaviruses (HPVs) and who have lowered cellular immunity due to coinfection with human immunodeficiency virus (HIV) infection. The majority of these individuals are low-income minority women. Factors associated with promotion of HPV to cervical neoplasia in HIV-infected populations include degree of immunosuppression as well as behavioral factors such as tobacco smoking and psychological stress. This study examined the effects of a cognitive behavioral stress management (CBSM) intervention on life stress and cervical neoplasia in HIV+ minority women. METHODS: Participants were 39 HIV+ African-American, Caribbean, and Hispanic women with a recent history of an abnormal Papanicolaou smear. Participants underwent colposcopic examination, psychosocial interview, and peripheral venous blood draw at study entry and 9 months after being randomly assigned to either a 10-week CBSM group intervention (n=21) or a 1-day CBSM workshop (n=18). RESULTS: Women assigned to the 10-week group-based CBSM intervention reported decreased perceived life stress and had significantly lower odds of cervical neoplasia over a 9-month follow-up. CBSM effects on life stress and neoplasia appeared independent of presence of neoplasia at study entry, HPV type, CD4+CD3+ cell count, HIV viral load, and substance use. Furthermore, CBSM intervention effects on cervical neoplasia were especially pronounced among women with residual life stress at follow-up. CONCLUSION: These findings suggest that stress management decreases perceived life stress and may decrease the odds of cervical neoplasia in women with HIV and a history of abnormal Papanicolaou smears. Although preliminary, these findings suggest the utility of stress management as a cancer prevention strategy in this high-risk population.