RESUMO
Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin-angiotensin-aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.
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Hipertensão Induzida pela Gravidez , Hormônios Peptídicos , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Sistema Renina-Angiotensina , Aldosterona , Cromatografia Líquida , Renina , Espectrometria de Massas em Tandem , Angiotensina IIRESUMO
Marine classification schemes based on abiotic surrogates often inform regional marine conservation planning in lieu of detailed biological data. However, these schemes may poorly represent ecologically relevant biological patterns required for effective design and management strategies. We used a community-level modeling approach to characterize and delineate representative mesoscale (tens to thousands of kilometers) assemblages of demersal fish and benthic invertebrates in the Northwest Atlantic. Hierarchical clustering of species occurrence data from four regional annual multispecies trawl surveys revealed three to six groupings (predominant assemblage types) in each survey region, broadly associated with geomorphic and oceanographic features. Indicator analyses identified 3-34 emblematic taxa of each assemblage type. Random forest classifications accurately predicted assemblage distributions from environmental covariates (AUC > 0.95) and identified thermal limits (annual minimum and maximum bottom temperatures) as important predictors of distribution in each region. Using forecasted oceanographic conditions for the year 2075 and a regional classification model, we projected assemblage distributions in the southernmost bioregion (Scotian Shelf-Bay of Fundy) under a high emissions climate scenario (RCP 8.5). Range expansions to the northeast are projected for assemblages associated with warmer and shallower waters of the Western Scotian Shelf over the 21st century as thermal habitat on the relatively cooler Eastern Scotian Shelf becomes more favorable. Community-level modeling provides a biotic-informed approach for identifying broadscale ecological structure required for the design and management of ecologically coherent, representative, well-connected networks of Marine Protected Areas. When combined with oceanographic forecasts, this modeling approach provides a spatial tool for assessing sensitivity and resilience to climate change, which can improve conservation planning, monitoring, and adaptive management.
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Peixes , Invertebrados , Animais , Mudança Climática , Ecossistema , TemperaturaRESUMO
NEW FINDINGS: What is the central question of this study? Is chemerin, an adipokine implicated in obesity, increased in neonates following in utero cigarette smoke exposure. What is the main finding and its importance? Chemerin mRNA expression was increased and chemerin DNA methylation was decreased in babies born to mothers who smoked during pregnancy. These data provide a potential mechanism that may be mediating the increased obesity risk in individuals that are born to mothers who smoked during pregnancy. ABSTRACT: It has been shown that in utero tobacco exposure increases offspring risk for obesity, but the mechanisms responsible for this increased risk are not well understood. Chemerin is an adipokine that regulates adipocyte differentiation. This chemokine is elevated in obese individuals and with smoke exposure, but its levels have not been measured in neonates exposed to cigarette smoke in utero. We examined chemerin gene expression [n = 31 non-smoker (NS) and 15 smoker (S)] and DNA methylation (n = 28 NS and n = 11 S) in skin collected from babies born to mothers who smoked during pregnancy as compared to non-smoking controls. Quality RNA and DNA were isolated from foreskin tissue following circumcision, and chemerin gene expression and DNA methylation were assessed. Further, in a second cohort, we utilized primary dermal foreskin fibroblasts as a functional measure of adipogenesis in living cells (n = 11 NS and n = 8 S). Cells were stimulated with an adipogenic cocktail, mRNA was isolated from cells after 14 days, and chemerin gene expression assessed via real-time PCR. Chemerin mRNA was elevated in both whole tissue (NS: 2409.20 ± 555.28 counts and S: 2966.72 ± 636.84 counts; P < 0.01) and primary fibroblasts (NS: 1.12 ± 0.55 2 Δ Δ C T and S: 2.13 ± 1.34 2 Δ Δ C T ; P = 0.04) collected from infants born to smoking mothers. Chemerin DNA methylation was reduced in whole tissue of offspring born to smokers (NS: 4.18 ± 1.28 and S: 3.07 ± 1.31%; P = 0.02), which may contribute to the increased gene expression. Neonates born to mothers who smoke during pregnancy exhibit distinct changes in chemerin gene expression in response to in utero tobacco smoke exposure which are regulated in part by epigenetic alterations.
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Quimiocinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fumar/efeitos adversos , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Adulto JovemRESUMO
BACKGROUND: The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study. OBJECTIVE: To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix. STUDY DESIGN: We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm. This was a systematic review and meta-analysis of individual patient data. The primary outcome was preterm birth <33 weeks of gestation. Secondary outcomes included adverse perinatal outcomes and neurodevelopmental and health outcomes at 2 years of age. Individual patient data were analyzed using a 2-stage approach. Pooled relative risks with 95% confidence intervals were calculated. Quality of evidence was assessed using the GRADE methodology. RESULTS: Data were available from 974 women (498 allocated to vaginal progesterone, 476 allocated to placebo) with a cervical length ≤25 mm participating in 5 high-quality trials. Vaginal progesterone was associated with a significant reduction in the risk of preterm birth <33 weeks of gestation (relative risk, 0.62; 95% confidence interval, 0.47-0.81; P = .0006; high-quality evidence). Moreover, vaginal progesterone significantly decreased the risk of preterm birth <36, <35, <34, <32, <30, and <28 weeks of gestation; spontaneous preterm birth <33 and <34 weeks of gestation; respiratory distress syndrome; composite neonatal morbidity and mortality; birthweight <1500 and <2500 g; and admission to the neonatal intensive care unit (relative risks from 0.47-0.82; high-quality evidence for all). There were 7 (1.4%) neonatal deaths in the vaginal progesterone group and 15 (3.2%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.18-1.07; P = .07; low-quality evidence). Maternal adverse events, congenital anomalies, and adverse neurodevelopmental and health outcomes at 2 years of age did not differ between groups. CONCLUSION: Vaginal progesterone decreases the risk of preterm birth and improves perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, without any demonstrable deleterious effects on childhood neurodevelopment.
Assuntos
Nascimento Prematuro/prevenção & controle , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Doenças do Colo do Útero/tratamento farmacológico , Administração Intravaginal , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Nascimento Prematuro/etiologia , Risco , Resultado do Tratamento , Doenças do Colo do Útero/complicaçõesRESUMO
BACKGROUND: An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic short cervix. The efficacy of vaginal progesterone has been challenged after publication of the OPPTIMUM study. However, this has been resolved by an individual patient-data meta-analysis (Am J Obstet Gynecol. 2018;218:161-180). OBJECTIVE: To compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. DATA SOURCES: MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm. STUDY APPRAISAL AND SYNTHESIS METHODS: Updated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth <35 weeks of gestation and perinatal mortality. Pooled relative risks (RRs) with 95% confidence intervals were calculated. RESULTS: Five trials comparing vaginal progesterone vs placebo (265 women) and 5 comparing cerclage vs no cerclage (504 women) were included. Vaginal progesterone, compared to placebo, significantly reduced the risk of preterm birth <35 and <32 weeks of gestation, composite perinatal morbidity/mortality, neonatal sepsis, composite neonatal morbidity, and admission to the neonatal intensive care unit (RRs from 0.29 to 0.68). Cerclage, compared to no cerclage, significantly decreased the risk of preterm birth <37, <35, <32, and <28 weeks of gestation, composite perinatal morbidity/mortality, and birthweight <1500 g (RRs from 0.64 to 0.70). Adjusted indirect comparison meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes. CONCLUSION: Vaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions and patient/physician's preferences.
Assuntos
Cerclagem Cervical , Nascimento Prematuro/prevenção & controle , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Administração Intravaginal , Medida do Comprimento Cervical , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Sepse Neonatal/epidemiologia , Mortalidade Perinatal , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Prevenção SecundáriaAssuntos
Medicaid , Medicare , Idoso , Humanos , Estados Unidos , Negociação , Economia Médica , InflaçãoRESUMO
Small invertebrate grazers can disproportionately reduce plant fitness by discriminately consuming valuable tissues, but the context and attendant consequences of this activity at higher levels of ecological organization rarely are considered. To assess the impact of a gastropod mesograzer Lacuna vincta on fecundity and potential reproductive output of the habitat-forming kelp Saccharina latissima, we measured the intensity and distribution of grazing damage on kelp blades at five sites of varying kelp density, during the annual reproductive peak (October-November) in Nova Scotia. We found most grazing damage on reproductive individuals consisted of superficial excavations, and was concentrated on the central sorus (region where sporangia develop) compared to the vegetative blade margins. Grazing intensity on sori (percent grazed) averaged 29.6% across sites and sampling periods. The distribution of grazing on non-reproductive individuals was opposite to that of reproductive ones, indicating that snails shift feeding from blade margins to the center as sori develop. Choice and no-choice feeding assays in the laboratory revealed that focused grazing on sori is likely due to an active feeding preference for sporogenous over vegetative tissue. This preference was correlated with the distribution of chemical defense between tissues (phlorotannin content was ~2.5 times higher in vegetative tissue than sori), but not nutritional quality (no difference in C/N ratio). We deduce, with support from histological observations, that consumption of sorus tissue by L. vincta reduces fecundity of S. latissima. Extrapolating our results to estimate potential reproductive output within kelp beds suggests that spore supply and recruitment limitation may be predominantly imposed by the scarcity of reproductive individuals in the most degraded kelp beds. However, loss of reproductive output to grazing could extend recruitment limitations that impede recovery of waning kelp populations in Nova Scotia.
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Preferências Alimentares , Kelp , Phaeophyceae , Caramujos/fisiologia , Animais , Ecossistema , Nova EscóciaRESUMO
Progestogens are the first drugs to demonstrate reproducibly a reduction in the rate of early preterm birth. The efficacy and safety of progestogens are related to individual pharmacologic properties of each drug within this class of medication and characteristics of the population that is treated. The synthetic 17-hydroxyprogesterone caproate and natural progesterone have been studied with the use of a prophylactic strategy in women with a history of preterm birth and in women with a multiple gestation. Evidence from a single large comparative efficacy trial suggests that vaginal natural progesterone is superior to 17-hydroxyprogesterone caproate as a prophylactic treatment in women with a history of mid-trimester preterm birth. Progestogen therapy is indicated for women with this highest risk profile based on evidence from 2 trials. A therapeutic approach based on the identification of a sonographic short cervix has been studied in several phase III trials. Independent phase III trials and an individual patient metaanalysis suggest that vaginal progesterone is efficacious and safe in women with a singleton and a short cervix. Two trials that tested 17-hydroxyprogesterone caproate in women with a short cervix showed no benefit. No consistent benefit for the prophylactic or therapeutic use of progestogens has been demonstrated in larger trials of women whose pregnancies were complicated by a multiple gestation (twins or triplets), preterm labor, or preterm rupture of membranes. Unfortunately, several large randomized trials in multiple gestations have identified harm related to 17-hydroxyprogesterone caproate exposure, and the synthetic drug is contraindicated in this population. The current body of evidence is evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines to derive the strength of recommendation in each of these populations. A large confirmatory trial that is testing 17-hydroxyprogesterone caproate exposure in women with a singleton pregnancy and a history of preterm birth is near completion. Additional study of the efficacy and safety of progestogens is suggested in well-selected populations based on the presence of biomarkers.
Assuntos
Hidroxiprogesteronas/uso terapêutico , Nascimento Prematuro/prevenção & controle , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Caproato de 17 alfa-Hidroxiprogesterona , Administração Intravaginal , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Feminino , Humanos , Hidroxiprogesteronas/efeitos adversos , Hidroxiprogesteronas/farmacocinética , Gravidez , Progesterona/efeitos adversos , Progesterona/farmacocinética , Progestinas/efeitos adversos , Progestinas/farmacocinéticaRESUMO
OBJECTIVE: We hypothesized that, as has been shown outside of pregnancy, endothelial dysfunction would be seen in a dose-dependent fashion among women who smoke in the midtrimester of pregnancy. STUDY DESIGN: Endothelial function in women with singleton pregnancies between 16 and 23 weeks was analyzed utilizing the Endo-PAT2000 device (Itamar Medical Ltd., Caesarea, Israel) and expressed as a reactive hyperemia ratio (RHI). Serum was drawn to check cotinine and high-sensitivity C-reactive protein (CRP) levels. SAS 9.2 (SAS Institute, Cary, NC) was used to perform statistical tests including Student t test, analysis of variance, Fisher exact test, and Pearson coefficient. RESULTS: Endothelial function was noninvasively examined in 29 smokers and 31 nonsmokers. Demographics including age, race, and parity were similar between groups. Mean RHI was not significantly different between smokers and nonsmokers (1.43 ± 0.32 versus 1.53 ± 0.39, p = 0.27). No correlation was noted when cotinine values were plotted against RHI or CRP values in smokers (rho = 0.24, p = 0.21 and rho = 0.26, p = 0.18, respectively). RHI did correlate with diastolic blood pressure (rho = -0.40, p = 0.002), systolic blood pressure (rho = -0.35, p = 0.006), and heart rate (rho = -0.37, p = 0.004). CONCLUSION: We did not find an association between smoking status and endothelial dysfunction in the midtrimester utilizing a noninvasive methodology.
Assuntos
Endotélio Vascular/fisiopatologia , Manometria , Segundo Trimestre da Gravidez/fisiologia , Fumar/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Gravidez , Adulto JovemRESUMO
OBJECTIVE: No randomized controlled trial has compared vaginal progesterone and cervical cerclage directly for the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. STUDY DESIGN: Adjusted indirect metaanalysis of randomized controlled trials. RESULTS: Four studies that evaluated vaginal progesterone vs placebo (158 patients) and 5 studies that evaluated cerclage vs no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth at <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect metaanalyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes. CONCLUSION: Based on state-of-the-art methods for indirect comparisons, either vaginal progesterone or cerclage are equally efficacious in the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous preterm birth. Selection of the optimal treatment needs to consider adverse events, cost and patient/clinician preferences.
Assuntos
Cerclagem Cervical , Colo do Útero/diagnóstico por imagem , Nascimento Prematuro/prevenção & controle , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Administração Intravaginal , Feminino , Humanos , Gravidez , Nascimento Prematuro/diagnóstico por imagem , Nascimento Prematuro/tratamento farmacológico , Progesterona/administração & dosagem , Progestinas/administração & dosagem , UltrassonografiaRESUMO
BACKGROUND: The likelihood of cesarean is in part related to maternal body mass index (BMI). Myometrial changes may be responsible. METHODS: Myometrial biopsies were collected from the upper edge of the hysterotomy from women undergoing scheduled cesarean with term, singleton gestations. Oxytocin receptor and connexin-43 mRNA protein expression was quantified with real-time polymerase chain reaction and Western blot. RESULTS: Twenty subjects were recruited: 13 repeat and 7 primary cesareans. Oxytocin receptor mRNA was associated with BMI among women undergoing primary (r = 0.75; p = 0.05) but not repeat cesarean (p > 0.05). Controlling for gestational age, this association strengthened (p = 0.004). Receptor protein expression showed a linear correlation with BMI in the primary cesarean group (p = 0.002). Connexin-43 mRNA expression was not related to BMI in women undergoing primary (r = -0.14, p = 0.76) or repeat (r = -0.01, p = 0.86) cesarean. CONCLUSIONS: Oxytocin receptor, but not connexin-43, expression is related to BMI, suggesting an alteration in oxytocin receptor expression or function related to obesity.
Assuntos
Cesárea , Receptores de Ocitocina/metabolismo , Regulação para Cima/fisiologia , Adulto , Western Blotting , Índice de Massa Corporal , Conexina 43/metabolismo , Feminino , Humanos , Subunidades beta de Inibinas/metabolismo , Miométrio/metabolismo , Gravidez , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Emerging evidence indicates a previously unrecognized, clinically relevant spectrum of abnormal aldosterone secretion associated with hypertension severity. It is not known whether excess aldosterone secretion contributes to hypertension during pregnancy. We quantified aldosterone concentrations and angiotensin peptides in serum (using liquid chromatography with tandem mass spectrometry) in a cohort of 128 pregnant women recruited from a high-risk obstetrics clinic and followed prospectively for the development of gestational hypertension, pre-eclampsia, superimposed pre-eclampsia, chronic hypertension, or remaining normotensive. The cohort was grouped by quartile of aldosterone concentration in serum measured in the first trimester, and blood pressure, angiotensin peptides, and hypertension outcomes compared across the four quartiles. Blood pressures and body mass index were greatest in the top and bottom quartiles, with the top quartile having the highest blood pressure throughout pregnancy. Further stratification of the top quartile based on increasing (13 patients) or decreasing (19 patients) renin activity over gestation revealed that the latter group was characterized by the highest prevalence of chronic hypertension, use of anti-hypertensive agents, pre-term birth, and intrauterine growth restriction. Serum aldosterone concentrations greater than 704 pmol/L, the 75th percentile defined within the cohort, were evident across all categories of hypertension in pregnancy, including normotensive. These findings suggest that aldosterone excess may underlie the development of hypertension in pregnancy in a significant subpopulation of individuals.
RESUMO
OBJECTIVE: To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (≤ 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN: Individual patient data metaanalysis of randomized controlled trials. RESULTS: Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80), <35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and <28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight <1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION: Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.
Assuntos
Nascimento Prematuro/prevenção & controle , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Administração Intravaginal , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Progesterona/administração & dosagem , Risco , Resultado do TratamentoRESUMO
The safety of supplemental progestin therapy during pregnancy reflects whether an agent exclusively promotes or potentially inhibits progestational cellular functions and whether treatment incites a metabolic derangement or other pathophysiology to initiate rare untoward events. No safety signal has been identified from intravaginal administration of natural progesterone from phase III clinical trials. The Food and Drug Administration has identified a legitimate safety signal regarding second-trimester miscarriage and stillbirth with exposure to 17-hydroxyprogesterone caproate (17-OHPC). Results from recent phase II and III trials in multiples also demonstrates concern with exposure to this synthetic for fetal loss and increased severe respiratory distress in neonates (one study each), as well as repeated significant associations for shorter duration of pregnancy and poorer fetal growth in others. The biological plausibility for 17-OHPC to be associated with adverse outcomes can be suggested from pharmacogenomic observations, ex vivo experimentation, and clinical observations. Further data are needed interrogating the potential for rare fetal or maternal adverse events/safety outcomes with exposure to progestins. Safety concerns should be incorporated into prescribing decisions.
Assuntos
Hidroxiprogesteronas/efeitos adversos , Nascimento Prematuro/prevenção & controle , Progesterona/efeitos adversos , Progestinas/efeitos adversos , Caproato de 17 alfa-Hidroxiprogesterona , Aborto Espontâneo , Animais , Glicemia/efeitos dos fármacos , Ensaios Clínicos como Assunto , Feminino , Morte Fetal , Desenvolvimento Fetal/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Humanos , Hidroxiprogesteronas/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Gravidez , Gravidez Múltipla , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Receptores de Progesterona/agonistas , Receptores de Progesterona/antagonistas & inibidores , Receptores de Progesterona/genética , Receptores de Progesterona/fisiologia , NatimortoRESUMO
PURPOSE: The goal of this study was to evaluate how rural/urban status and other risk factors alter women's odds of severe maternal morbidity (SMM) at delivery. METHODS: This study used 48,608 Kentucky resident delivery hospitalization records from 2017. We used multiple logistic regression with interaction terms to evaluate the moderating effect of rural/urban residence with other risk factors. We reported adjusted odds ratios (aORs) and 95% confidence intervals (CIs) as measures for association with the outcome of SMM at delivery. FINDINGS: The percentage of delivery hospitalizations with SMM was higher for women with rural (2.4%) versus metro (1.1%) or metro-adjacent (1.5%) residence (p < .001). Rural status moderated the effect of anemia on SMM. The aOR for SMM for women with anemia versus those without was 8.56 (CI: 4.89-14.97) in rural areas, two times higher than in metro areas (aOR 3.87; CI: 3.09-4.86). Kentucky Appalachian region (aOR 1.90; CI: 1.46-2.47), Black race (aOR 1.30; CI: 1.02-1.66), history of cesarean section (aOR 1.28; CI: 1.07-1.52), hypertension (aOR 10.55; CI: 5.67-19.62), and opioid use (aOR 1.72; CI: 1.19-2.47) were significantly associated with SMM. CONCLUSION: Rural women in Kentucky are at an increased risk for SMM. Quality and safety programming should specifically address the needs of isolated subpopulations. Women living in rural areas are more likely to experience SMM given an anemia diagnosis. The underlying cause and clinical management of anemia may differ between rural and urban areas.
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Cesárea , Internato e Residência , Feminino , Humanos , Razão de Chances , Gravidez , Fatores de Risco , População RuralRESUMO
We sought to reduce long-term complications after cesarean delivery by improving myometrial healing. Eight sheep (three with twins) underwent cesarean delivery. Hysterotomy sites were repaired in equal parts by suture alone or suture with a juxtaposed graft (Cook Medical, Bloomington, IN). At 90 days postsurgery, scar characteristics and tensile strength testing were assessed. The mean hysterotomy closure time was on average 1 minute, 14 seconds longer for those undergoing graft placement ( P=0.36). The mean scar thickness was 3.0 ± 0.4 mm for controls versus 3.8 ± 1.2 mm for the intervention group ( P=0.047). Tensile strength testing did not demonstrate a significant difference between groups. Histological examination of the myometrial scar showed no significant differences in inflammatory reaction or endometrial inclusions; however, neoangiogenesis was significantly enhanced. Myometrial repair incorporating a graft increased scar thickness and neoangiogenesis. This methodology did not incite adenomyosis or enhance inflammation within the scar.
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Cesárea , Histerotomia , Mucosa Intestinal/transplante , Miométrio/fisiologia , Cicatrização , Animais , Cicatriz/patologia , Feminino , Modelos Animais , Miométrio/cirurgia , Gravidez , Ovinos , Resistência à Tração , Aderências Teciduais , Transplante Autólogo , Cicatrização/fisiologiaRESUMO
We evaluated uterine contraction frequency in women receiving 17 alpha-hydroxyprogesterone caproate (17-OHP-C) for the prevention of preterm delivery. Women with singleton pregnancies and receiving weekly 17-OHP-C and outpatient tococardiography were identified from a database. The mean and maximum contraction frequencies per hour were compared from 3 days before to 3 days after 17-OHP-C dosing. McNemar chi(2), Mann-Whitney U, and Friedman test statistics were used for analysis. Data were obtained from 388 women. Median contraction frequency was greater for women with subsequent preterm birth versus those delivering at term (1.5 [range 0, 14.5] versus 1.2 [range 0, 21.0] contractions per hour, P < 0.001). No reduction in contraction frequency was observed after 17-OHP-C administration, and in fact, the converse was observed for the average contractions 3 days prior compared with 3 days posttreatment ( P < 0.001). In the subgroup of women with a subsequent spontaneous preterm, the proportion who had an average contraction frequency of more than five per hour 1 day preinjection versus 1 day postinjection was not significantly different (2.6% versus 3.0%, P = 1.0). Administration of 17-OHP-C was not associated with a reduction in contraction frequency. To be effective, this drug likely has effects by mechanisms other than tocolysis. Although a statistically significant increase in contractions was identified posttherapy versus pretherapy, the clinical importance of this observation is unknown.
Assuntos
Hidroxiprogesteronas/uso terapêutico , Nascimento Prematuro/prevenção & controle , Progestinas/uso terapêutico , Contração Uterina/efeitos dos fármacos , Caproato de 17 alfa-Hidroxiprogesterona , Adulto , Feminino , Humanos , Injeções , Gravidez , Estudos RetrospectivosRESUMO
Progesterone plays a central role in the mechanisms of parturition in many species. Despite remarkable advances in our understanding of this hormone's mechanism of action, its roles in human pregnancy maintenance and parturition are not fully appreciated. Proper scientific hypothesis testing of progestins to prevent preterm birth has been limited because of the issues that can plague interventional trials in obstetrics, including patient selection, choice of outcome and power. The largest studies enrolling patients with a history of prior preterm birth alone to prevent recurrence appear contradictory. In contrast, consistent evidence from one multinational trial and a secondary analysis of another suggests cervical length may serve to identify potential responders to this therapy. Finally, the safety of progestin administration is a legitimate concern and a meta-analysis justifies the need for further investigation of safety issues. This review presents recent findings regarding progestin therapy from both clinical and laboratory data and considers unresolved issues for use of these agents.
Assuntos
Nascimento Prematuro/prevenção & controle , Progestinas/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Caproato de Gestonorona/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Gravidez , Progesterona/fisiologia , Progesterona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This cross-sectional study describes and historically benchmarks Medicare Part D coverage in 2019 and 2023 for the first 10 drugs selected for negotiation.