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OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.
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Anti-Hipertensivos , Hipertensão , Labetalol , Nifedipino , Resultado da Gravidez , Humanos , Gravidez , Feminino , Labetalol/administração & dosagem , Labetalol/efeitos adversos , Labetalol/uso terapêutico , Nifedipino/administração & dosagem , Nifedipino/efeitos adversos , Nifedipino/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Adulto , Hipertensão/tratamento farmacológico , Recém-Nascido , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Administração Oral , Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia/tratamento farmacológico , Doença CrônicaRESUMO
OBJECTIVE: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes. METHODS: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported. RESULTS: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38). CONCLUSION: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.
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Idade Gestacional , Hipertensão , Humanos , Feminino , Gravidez , Adulto , Recém-Nascido , Parto Obstétrico , Complicações Cardiovasculares na Gravidez/terapia , Resultado da Gravidez , Fatores de Tempo , Cesárea/estatística & dados numéricos , Doença Crônica , Adulto JovemRESUMO
OBJECTIVE: It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of prematurity. The objective of this study was to compare whether neonatal outcomes differ in term and preterm infants exposed to adjunctive azithromycin prophylaxis before non-elective cesarean delivery. STUDY DESIGN: A planned secondary analysis of a multi-center randomized controlled trial that enrolled women with singleton pregnancies ≥24 weeks gestation undergoing non-elective cesarean delivery (during labor or ≥4 h after membrane rupture). Women received standard antibiotic prophylaxis and were randomized to either adjunctive azithromycin (500 mg) or placebo. The primary composite outcome was neonatal death, suspected or confirmed neonatal sepsis, and serious neonatal morbidities (NEC, PVL, IVH, BPD). Secondary outcomes included NICU admission, neonatal readmission, culture positive infections and prevalence of resistant organisms. Odds ratios (OR) for the effect of azithromycin versus placebo were compared between gestational age strata (preterm [less than 37 weeks] versus term [37 weeks or greater]). Tests of interaction examined homogeneity of treatment effect with gestational age. RESULTS: The analysis includes 2,013 infants, 226 preterm (11.2%) and 1,787 term. Mean gestational ages were 34 and 39.5 weeks, respectively. Within term and preterm strata, maternal and delivery characteristics were similar between the azithromycin and placebo groups. There was no difference in the odds of composite neonatal outcome between those exposed to azithromycin versus placebo in preterm neonates (OR 0.82, 95% CI 0.48-1.41) and in term neonates (OR 1.06, 95% CI 0.77-1.46), with no difference between gestational age strata (p = 0.42). Analysis of secondary outcomes also revealed no differences in treatment effects within or between gestational age strata. CONCLUSION: Exposure to adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery does not increase neonatal morbidity or mortality in term or preterm infants. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT01235546.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Azitromicina , Cesárea , Recém-Nascido Prematuro , Humanos , Azitromicina/uso terapêutico , Azitromicina/administração & dosagem , Feminino , Antibioticoprofilaxia/métodos , Recém-Nascido , Gravidez , Cesárea/estatística & dados numéricos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Adulto , Idade Gestacional , Nascimento a Termo , Doenças do Recém-Nascido/prevenção & controle , Doenças do Recém-Nascido/epidemiologiaRESUMO
OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.
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Anti-Hipertensivos , Hipertensão , Complicações Cardiovasculares na Gravidez , Humanos , Feminino , Gravidez , Recém-Nascido , Adulto , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Resultado da Gravidez , Pressão Arterial , Hipertensão Induzida pela Gravidez/tratamento farmacológicoRESUMO
OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.
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Hipertensão , Pré-Eclâmpsia , Nascimento Prematuro , Gravidez , Humanos , Recém-Nascido , Feminino , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/etiologia , Nascimento Prematuro/epidemiologia , Placenta , Resultado da Gravidez , Retardo do Crescimento Fetal , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/complicaçõesRESUMO
BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). STUDY DESIGN: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. RESULTS: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. CONCLUSION: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.
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Aleitamento Materno , Hipertensão , Gravidez , Feminino , Humanos , Anti-Hipertensivos/efeitos adversos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pressão Sanguínea , Período Pós-PartoRESUMO
BACKGROUND: COVID-19 is caused by the SARS-CoV-2 virus and is associated with critical illness requiring hospitalization, maternal mortality, stillbirth, and preterm birth. SARS-CoV-2 has been shown to induce placental pathology. However, substantial gaps exist in our understanding of the pathophysiology of COVID-19 disease in pregnancy and the long-term impact of SARS-CoV-2 on the placenta and fetus. To what extent a SARS-CoV-2 infection of the placenta alters the placental antiviral innate immune response is not well understood. A dysregulated innate immune response in the setting of maternal COVID-19 disease may increase the risk of inflammatory tissue injury or placental compromise and may contribute to deleterious pregnancy outcomes. OBJECTIVE: We sought to determine the impact of a maternal SARS-CoV-2 infection on placental immune response by evaluating gene expression of a panel of 6 antiviral innate immune mediators that act as biomarkers of the antiviral and interferon cytokine response. Our hypothesis was that a SARS-CoV-2 infection during pregnancy would result in an up-regulated placental antiviral innate immune response. STUDY DESIGN: We performed a case-control study on placental tissues (chorionic villous tissues and chorioamniotic membrane) collected from pregnant patients with (N=140) and without (N=24) COVID-19 disease. We performed real-time quantitative polymerase chain reaction and immunohistochemistry, and the placental histopathology was evaluated. Clinical data were abstracted. Fisher exact test, Pearson correlations, and linear regression models were used to examine proportions and continuous data between patients with active (<10 days since diagnosis) vs recovered COVID-19 (>10 days since diagnosis) at the time of delivery. Secondary regression models adjusted for labor status as a covariate and evaluated potential correlation between placental innate immune gene expression and other variables. RESULTS: SARS-CoV-2 viral RNA was detected in placental tissues from 5 women with COVID-19 and from no controls (0/24, 0%). Only 1 of 5 cases with detectable SARS-CoV-2 viral RNA in placental tissues was confirmed to express SARS-CoV-2 nucleocapsid and spike proteins in syncytiotrophoblast cells. We detected a considerably lower gene expression of 5 critical innate immune mediators (IFNB, IFIT1, MXA, IL6, IL1B) in the chorionic villi and chorioamniotic membranes from women with active or recovered COVID-19 than controls, which remained significant after adjustment for labor status. There were minimal correlations between placental gene expression and other studied variables including gestational age at diagnosis, time interval between COVID-19 diagnosis and delivery, prepregnancy body mass index, COVID-19 disease severity, or placental pathology. CONCLUSION: A maternal SARS-CoV-2 infection was associated with an impaired placental innate immune response in chorionic villous tissues and chorioamniotic membranes that was not correlated with gestational age at COVID-19 diagnosis, time interval from COVID-19 diagnosis to delivery, maternal obesity, disease severity, or placental pathology.
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COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Feminino , Gravidez , Humanos , Recém-Nascido , COVID-19/patologia , Placenta/metabolismo , SARS-CoV-2 , Antivirais/metabolismo , Teste para COVID-19 , Estudos de Casos e Controles , Complicações Infecciosas na Gravidez/diagnóstico , Nascimento Prematuro/metabolismo , Imunidade Inata , RNA Viral/metabolismo , Expressão Gênica , Transmissão Vertical de Doenças InfecciosasRESUMO
OBJECTIVE: To estimate the association between timing of administration of adjunctive azithromycin for prophylaxis at unscheduled cesarean delivery and maternal infection and neonatal morbidity. METHODS: We conducted a secondary analysis of a randomized trial of adjunctive azithromycin prophylaxis in patients with singleton gestations who were undergoing unscheduled cesarean delivery. The primary exposure was the timing of initiation of the study drug (after skin incision or 0-30 minutes, more than 30-60 minutes, or more than 60 minutes before skin incision). The primary outcome was a composite of endometritis, wound infection, and other maternal infections occurring up to 6 weeks after cesarean delivery. Secondary outcomes included composite neonatal morbidity, neonatal intensive care unit admission for longer than 72 hours, and neonatal sepsis. The association of azithromycin with outcomes was compared within each antibiotic timing group and presented as risk ratios (RRs) with 95% CIs. A Breslow-Day homogeneity test was applied to assess differences in association by antibiotic timing. RESULTS: Of 2,013 participants, antibiotics were initiated after skin incision (median 3 minutes, range 0-229 minutes) in 269 (13.4%), 0-30 minutes before skin incision in 1,378 (68.5%), more than 30-60 minutes before skin incision in 270 (13.4%), and more than 60 minutes before skin incision (median 85 minutes, range 61-218 minutes) in 96 (4.8%). The RRs (95% CIs) of the infectious composite outcome for azithromycin compared with placebo were significantly lower for groups that initiated azithromycin after skin incision or within 1 hour before skin incision (after skin incision: RR 0.31, 95% CI 0.13-0.76; 0-30 minutes before: RR 0.62, 95% CI 0.44-0.89; more than 30-60 minutes before: 0.31, 95% CI 0.13-0.66). Risks were not significantly different in patients who received azithromycin more than 60 minutes before skin incision (RR 0.59, 95% CI 0.10-3.36). Results were similar when endometritis and wound infections were analyzed separately. Neonatal outcomes were not significantly different for azithromycin compared with placebo across all timing groups. CONCLUSION: Adjunctive azithromycin administration up to 60 minutes before or at a median of 3 minutes after skin incision was associated with reduced risks of maternal composite postoperative infection in unscheduled cesarean deliveries. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01235546.
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Azitromicina , Endometrite , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Azitromicina/uso terapêutico , Endometrite/prevenção & controle , Feminino , Humanos , Recém-Nascido , Gravidez , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).
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Anti-Hipertensivos/uso terapêutico , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Hipertensão , Resultado da Gravidez , Descolamento Prematuro da Placenta/epidemiologia , Descolamento Prematuro da Placenta/prevenção & controle , Peso ao Nascer , Doença Crônica , Feminino , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/prevenção & controle , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Recém-Nascido , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/prevenção & controle , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controleRESUMO
The single biggest factor driving health outcomes is patient behavior. The CHR Model (County Health Rankings Model) weights socioeconomic factors, lifestyle behaviors, and physical environment factors collectively at 80% in driving impact on health outcomes, to the 20% weight for access to and quality of clinical care. Commercial determinants of health affect everyone today and unhealthy choices worsen pre-existing economic, social, and racial inequities. Yet there is a disproportionate focus on therapeutic intervention to the exclusion of shaping patient behaviors to improve healthcare. If the recent pandemic taught us a critically important lesson, it is the imperative to look beyond clinical care. According to the Centers for Disease Control and Prevention (CDC), long-standing systemic health and social inequities put various groups of people at higher risk of getting sick and dying from COVID-19, including many racial and ethnic minority groups. The virus was simply more efficient in detecting such vulnerabilities than the guardians of these physiologies. These insights from the pandemic come at the heel of a confluence of three major accelerants that may radically reshape our approaches to hot-spotting vulnerabilities and managing them before they manifest in a derangement or disease. They are the recent strides in behavioral economics and behavior science; advances in remote monitoring and personal health technologies; and developments in artificial intelligence and data sciences. These accelerants allow us to imagine a previously impossible vision-we can now build and maintain a unified health algorithm for every individual that can dynamically track the two interdependent streams of risk, clinical and behavioral.
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OBJECTIVE: This study was aimed to evaluate the relationship between cesarean skin incision length and wound complications. STUDY DESIGN: Planned secondary analysis of a multicenter double-blind randomized trial of adjunctive azithromycin versus placebo (in addition to standard cefazolin) in women ≥24 weeks undergoing cesarean delivery during labor or ≥4 hours after membrane rupture. Skin incision length (cm) was measured just prior to skin closure. The primary outcome was a composite of wound complications (wound infection, separation, seroma, hematoma, or dehiscence) up to 6 weeks of postpartum. Individual components of the composite were examined as secondary outcomes. Outcomes were compared between groups defined by the lowest (≤25th), middle (25-75th) and highest (>75th) incision length quartiles. Logistic regression was used to adjust for potential confounding variables. RESULTS: Of the 2,013 women enrolled in the primary trial, 1,916 had recorded incision lengths and were included in this secondary analysis. The overall rate of composite wound complications was 7.8%. Median incision length was 15.0 cm (interquartile range: 14.0-16.5) with the lowest quartile defined as ≤14, middle as >14 to ≤16.5, and highest as >16.5 cm. Mean BMI, parity, use of staples, and duration of surgery differed significantly between the three incision length groups. In unadjusted analysis, the longest incision lengths were associated with an increased risk of the wound composite and wound infections (odds ratio [OR] = 2.27, 95% confidence interval [CI]: 1.43-3.60 and OR = 2.30, 95% CI: 1.27-4.15, respectively) compared with the shortest incision lengths. However, after multivariable adjustments, these associations were nullified. Additional analyses considering incision length as a continuous variable and using 10th/90th percentile cut-offs still did not suggest any associations with outcomes. CONCLUSION: Increasing skin incision length is not independently associated with an increased risk of postoperative wound complications. KEY POINTS: · After multivariable adjustments, skin incision length was not independently associated with an increased risk of postoperative wound complications.. · A reasonable incision length needed to safely perform the procedure should be used..
Assuntos
Complicações Pós-Operatórias , Infecção da Ferida Cirúrgica , Cesárea/efeitos adversos , Cesárea/métodos , Feminino , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gravidez , Seroma/epidemiologia , Seroma/etiologia , Deiscência da Ferida Operatória/epidemiologia , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Suturas/efeitos adversosRESUMO
OBJECTIVE: To compare the frequency of postoperative surgical site infection (SSI) by type of skin preparation used for unscheduled cesarean in the setting of adjunctive azithromycin prophylaxis. METHODS: Secondary analysis of a multi-center randomized controlled trial of adjunctive azithromycin (500 mg intravenous) versus placebo in women who were ≥24 weeks gestation and undergoing unscheduled cesarean (i.e. during labor or ≥4 h after membrane rupture). Type of skin preparation used was identified based on the protocol at the hospital at the time of delivery: iodine-alcohol, chlorhexidine, chlorhexidine-alcohol, or the combination of chlorhexidine-alcohol and iodine. The primary outcome of this analysis was incidence of post-operative SSI, as defined by CDC criteria. Multivariable logistic regression was applied for adjustments. RESULTS: All 2013 women in the primary trial were included in this analysis. Women were grouped according to type of skin preparation received: iodine-alcohol (n = 193), chlorhexidine (n = 733), chlorhexidine-alcohol (n = 656), and chlorhexidine-alcohol and iodine combined sequentially (n = 431). The unadjusted rates of wound infection ranged from 2.9% to 5.7%. Using iodine-alcohol as the referent, the adjusted odds ratios for wound SSI were 0.71 (95% CI 0.30-1.66) for chlorhexidine, 0.97 (95% CI 0.41-2.28) for chlorhexidine-alcohol, and 0.88 (95% CI 0.36-2.20) for chlorhexidine-alcohol with iodine combination. CONCLUSION: In women undergoing unscheduled cesarean delivery in a trial of adjunctive azithromycin, the type of skin preparation used did not appear to be associated with the frequency of wound SSI.
Assuntos
Anti-Infecciosos Locais , Iodo , Anti-Infecciosos Locais/uso terapêutico , Azitromicina/uso terapêutico , Clorexidina , Feminino , Humanos , Povidona-Iodo , Gravidez , Cuidados Pré-Operatórios/métodos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
BACKGROUND: As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types. This limits the ability of healthcare practitioners to thoroughly counsel patients who are considering pregnancy in the setting of congenital heart disease. OBJECTIVE: We aimed to evaluate the association between pregnancy and the subsequent long-term cardiovascular health of individuals with congenital heart disease. STUDY DESIGN: This was a retrospective longitudinal cohort study of individuals identifying as female who were receiving care in two adult congenital heart disease centers from 2014 to 2019. Patient data were abstracted longitudinally from a patient age of 15 years (or from the time of entry into the healthcare system) to the conclusion of the study, death, or exit from the healthcare system. The primary endpoint, a composite adverse cardiac outcome (death, stroke, heart failure, unanticipated cardiac surgery, or a requirement for a catheterized procedure), was compared between parous (at least one pregnancy >20 weeks' gestation) and nulliparous individuals. By accounting for differences in the follow-up, the effect of pregnancy was estimated based on the time to the composite adverse outcome in a proportional hazards regression model adjusted for the World Health Organization class, baseline cardiac medications, and number of previous sternotomies. Participants were also categorized according to their lesion type, including septal defects (ventricular septal defects, atrial septal defects, atrioventricular septal defects, or atrioventricular canal defects), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies, to evaluate if there is a differential effect of pregnancy on the primary outcome when adjusting for lesion type in a sensitivity analysis. RESULTS: Overall, 711 individuals were eligible for inclusion; 209 were parous and 502 nulliparous. People were classified according to the World Health Organization classification system with 86 (12.3%) being classified as class I, 76 (10.9%) being classified as class II, 272 (38.9%) being classified as class II to III, 155 (22.1%) being classified as class III, and 26 (3.7%) being classified as class IV. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common in nulliparous individuals. In multivariable modeling, pregnancy was associated with the composite adverse cardiac outcome (36.4%% vs 26.1%%; hazard ratio, 1.83; 95% confidence interval, 1.25-2.66). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons. The association between pregnancy and the primary outcome was similar in a sensitivity analysis that adjusted for cardiac lesion type (hazard ratio, 1.61; 95% confidence interval, 1.10-2.36). CONCLUSION: Among individuals with congenital heart disease, pregnancy was associated with an increase in subsequent long-term adverse cardiac outcomes. These data may inform counseling of individuals with congenital heart disease who are considering pregnancy.
Assuntos
Cardiopatias Congênitas , Comunicação Interventricular/epidemiologia , Complicações Cardiovasculares na Gravidez/epidemiologia , Adulto , Estudos de Coortes , Feminino , Comunicação Interventricular/mortalidade , Humanos , Estudos Longitudinais , Gravidez , Complicações Cardiovasculares na Gravidez/mortalidade , Estudos Retrospectivos , Fatores de Risco , Utah/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Determine incidence and risk factors for readmissions in early infancy. STUDY DESIGN: Secondary analysis of data from the Cesarean Section Optimal Antibiotic Prophylaxis trial. All unplanned revisits (unplanned clinic, ER visits, and hospital readmissions) and hospital readmissions (initial discharge to 3-month follow-up) were analyzed. RESULTS: 295 (15.9%) of 1850 infants had revisits with risk factors being ethnicity (adjusted odds ratio (aOR): 0.6 for Hispanic), maternal postpartum antibiotics (1.89), azithromycin treatment (1.22), small for gestational age (1.68), apnea (3.82), and hospital stay after birth >90th percentile (0.49). 71 (3.8%) of 1850 infants were readmitted with risk factors being antenatal steroids (aOR 2.49), elective repeat C/section (0.72), postpartum maternal antibiotics (2.22), O2 requirement after delivery room (2.82), and suspected/proven neonatal sepsis (0.55). CONCLUSION(S): Multiple risk factors were identified, suggesting potential impact on the neonatal microbiome (maternal postpartum antibiotics) or issues related to access/cost of care (Hispanic ethnicity associated with fewer revisits).
Assuntos
Cesárea , Readmissão do Paciente , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Recesariana , Feminino , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
OBJECTIVE: Hospital readmissions are increasingly tracked and assessed for value-based compensation. Our objective was to determine the incidence and risk factors associated with post-cesarean delivery (CD) readmissions or unexpected visits, defined as unexpected office or emergency room visits. STUDY DESIGN: This is a secondary analysis of a multicenter randomized controlled trial of adjunctive azithromycin prophylaxis for CD performed in laboring patients with viable pregnancies. Patients were followed up to 6 weeks postpartum. Our primary outcome was a composite of hospital readmission or unexpected visit, defined as unscheduled clinic or emergency department visits. Data of hospital readmissions, unexpected visits, and their reasons were collected. Demographics, antepartum, intrapartum, and postpartum risk factors were evaluated in bivariate analyses and multivariable logistic regression modeling. RESULTS: A total of 1,019 women were randomized to azithromycin and 994 to placebo. The prevalence of readmission or unexpected visit was 10.2% (95% confidence interval [CI]: 8.9-11.6), with rates of 3.8% (95% CI: 3.0-4.7%) hospital readmissions, 6.9% (95% CI: 5.8-8.0%) emergency room visits, and 4.2% (95% CI: 3.4-5.2%) unexpected clinic visits. The most common causes were infectious disease and hypertensive disorder. Women with readmissions or unexpected visits were more likely to be obese and diabetic, as well as experience longer length of ruptured membranes, intrauterine pressure catheter placement, and postpartum fevers. On multivariable analysis, diabetes (adjusted odds ratio [aOR]: 1.6, 95% CI: 1.1-2.4), prolonged ruptured membranes (aOR: 1.9, 95% CI: 1.3-2.8), and postpartum fevers (aOR: 4.6, 95% CI: 3.0-7.0) were significantly positively associated with readmission or unscheduled visit, while azithromycin was a protective (aOR: 0.6, 95% CI: 0.5-0.9). CONCLUSION: Women who had postpartum fever were at especially high risk for readmission or unexpected visits. Diabetes, prolonged ruptured membranes, and postpartum fevers were significantly associated with the adverse outcome, and azithromycin was associated with lower rates of readmission and unexpected visits.
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Cesárea , Readmissão do Paciente/estatística & dados numéricos , Adulto , Antibioticoprofilaxia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Febre/epidemiologia , Febre/prevenção & controle , Humanos , Incidência , Gravidez , Infecção Puerperal/epidemiologia , Infecção Puerperal/prevenção & controle , Fatores de RiscoRESUMO
OBJECTIVE: Adding azithromycin to standard antibiotic prophylaxis for unscheduled cesarean delivery has been shown to reduce postcesarean infections. Because wound infection with ureaplasmas may not be overtly purulent, we assessed the hypothesis that azithromycin-based extended-spectrum antibiotic prophylaxis also reduces wound complications that are identified as noninfectious. STUDY DESIGN: This is a secondary analysis of the C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) randomized controlled trial, which enrolled women with singleton pregnancies ≥24 weeks who were undergoing nonelective cesarean. Women were randomized to adjunctive azithromycin or identical placebo up to 1 hour preincision. All wound complications occurring within 6 weeks were adjudicated into infection and noninfectious wound complications (seroma, hematoma, local cellulitis, and other noninfectious wound breakdown). The primary outcome for this analysis is the composite of noninfectious wound complications. RESULTS: At a total of 14 sites, 2,013 women were randomized to adjunctive azithromycin (n = 1,019) or placebo (n = 994). Groups were similar at baseline. Although there was a lower rate of noninfectious wound complications in the azithromycin group compared with placebo (2.9 vs. 3.8%), this was not statistically significant (p = 0.22). CONCLUSION: While adding azithromycin to usual antibiotic prophylaxis for nonelective cesarean delivery does reduce the risk of postcesarean infections, it did not significantly reduce the risk of postcesarean noninfectious wound complications.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Azitromicina/uso terapêutico , Cesárea/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/prevenção & controle , Feminino , Hematoma/etiologia , Hematoma/prevenção & controle , Humanos , Gravidez , Risco , Seroma/etiologia , Seroma/prevenção & controleRESUMO
OBJECTIVE: To evaluate the association of institutional protocols for vaginal preparation with antiseptic solution and the surgical site infection rate in women undergoing cesarean delivery during labor. METHODS: This is a secondary analysis of a multicenter randomized controlled trial of adjunctive azithromycin prophylaxis for cesarean delivery performed in laboring patients with viable pregnancies. The primary outcome for this analysis was the rate of superficial or deep surgical site infection within 6 weeks postpartum, as per Centers for Disease Control and Prevention criteria. Maternal secondary outcomes included a composite of endometritis, wound infection or other infections, postoperative maternal fever, length of hospital stay, and the rates of hospital readmission, unexpected office visits, and emergency department visits. RESULTS: A total of 523 women delivered in institutions with vaginal antisepsis policies before cesarean delivery and 1,490 delivered in institutions without such policies. There was no difference in superficial and deep surgical site infection rates between women with and without vaginal preparation (5.5% vs 4.1%; odds ratio [OR] 1.38, 95% CI 0.87-2.17), even after adjusting for possible confounders (adjusted OR 0.86, 95% CI 0.43-1.73). The lack of significant benefit was noted in all other maternal secondary outcomes. CONCLUSION: Institutional policies for vaginal preparation before cesarean delivery were not associated with lower rates of surgical site infection in women undergoing cesarean delivery during labor.
Assuntos
Anti-Infecciosos Locais/administração & dosagem , Cesárea/métodos , Trabalho de Parto , Cuidados Pré-Operatórios/métodos , Infecção da Ferida Cirúrgica/epidemiologia , Vagina/microbiologia , Antibioticoprofilaxia , Clorexidina/administração & dosagem , Endometrite/epidemiologia , Feminino , Humanos , Recém-Nascido , Sepse Neonatal/epidemiologia , Razão de Chances , Povidona-Iodo/administração & dosagem , Gravidez , Streptococcus agalactiae/isolamento & purificaçãoRESUMO
OBJECTIVE: The objective of this study is to examine perinatal outcomes associated with cholestasis of pregnancy according to bile acid level and antenatal testing practice. STUDY DESIGN: Retrospective cohort study of women with symptoms and bile acid testing from 2005 to 2014. Women were stratified by bile acid level: no cholestasis (<10 µmol/L), mild (10-39 µmol/L), moderate (40-99 µmol/L), and severe (≥100 µmol/L). The primary outcome was composite neonatal morbidity (hypoxic ischemic encephalopathy, severe intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or death). RESULTS: 785 women were included; 487 had cholestasis (347 mild, 108 moderate, 32 severe) and 298 did not. After controlling for gestational age (GA), severe cholestasis was associated with the composite neonatal outcome (aRR 5.6, 95% CI 1.3-23.5) and meconium-stained fluid (aRR 4.82, 95%CI 1.6-14.2). Bile acid levels were not correlated with the frequency of testing (p = .50). Women who underwent twice weekly testing were delivered earlier (p = .016) than women tested less frequently, but the difference in GA was ≤4 d. Abnormal testing prompting delivery was uncommon. Among women with cholestasis, there were three stillbirths. One of these women was undergoing antenatal testing, which was normal 1 d prior to the fetal demise. CONCLUSION: Severe cholestasis is associated with neonatal morbidity which antenatal testing may not predict.
Assuntos
Ácidos e Sais Biliares/sangue , Colestase Intra-Hepática/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Colestase Intra-Hepática/sangue , Feminino , Humanos , Gravidez , Complicações na Gravidez/sangue , Diagnóstico Pré-Natal , Estudos Retrospectivos , Utah/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. METHODS: Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. RESULTS: The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions. CONCLUSIONS: The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.
RESUMO
BACKGROUND: Hypomethylated cell-free DNA from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor. OBJECTIVE: To determine the changes in cell-free DNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term vs women without labor. STUDY DESIGN: In this prospective cohort study, eligible participants carried a nonanomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded. Maternal blood samples were collected at 28 weeks, 36 weeks, and at admission for delivery. Total cell-free DNA concentration, methylation ratio, and interleukin-6 were analyzed. The primary outcome was the difference in methylation ratio in women with labor vs without labor. Secondary outcomes included the longitudinal changes in these biomarkers corresponding to labor status. RESULTS: A total of 55 women were included; 20 presented in labor on admission and 35 presented without labor. Women in labor had significantly greater methylation ratio (P = .001) and interleukin-6 (P < .001) on admission for delivery than women without labor. After we controlled for body mass index and maternal age, methylation ratio (adjusted relative risk, 1.38; 95% confidence interval, 1.13 to 1.68) and interleukin-6 (adjusted relative risk, 1.12, 95% confidence interval, 1.07 to 1.17) remained greater in women presenting in labor. Total cell-free DNA was not significantly different in women with labor compared with women without. Longitudinally, total cell-free DNA (P < .001 in labor, P = .002 without labor) and interleukin-6 (P < .001 in labor, P = .01 without labor) increased significantly across gestation in both groups. The methylation ratio increased significantly in women with labor from 36 weeks to delivery (P = .02). CONCLUSION: Spontaneous labor at term is associated with a greater cell-free DNA methylation ratio and interleukin-6 compared with nonlabored controls. As gestation advances, total cell-free DNA concentrations and interleukin-6 levels increase. A greater methylation ratio reflects a greater maternal contribution (vs placental) in women with labor, likely resulting from greater levels of neutrophils, lymphocytes, and uterine activation proteins at the time of labor. Although not significant, women in labor had a greater total cell-free DNA concentration and thus could theoretically have more hypomethylated DNA available for interaction with the inflammatory cascade. Larger studies are needed to investigate this theory.