Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

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.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

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.

Neonatal outcomes in term and preterm infants following adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery.

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.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

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.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

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.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial.

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.

Outcomes of shared institutional review board compared with multiple individual site institutional review board models in a multisite clinical trial.

BACKGROUND: Institutional review boards play a crucial role in initiating clinical trials. Although many multicenter clinical trials use an individual institutional review board model, where each institution uses their local institutional review board, it is unknown if a shared (single institutional review board) model would reduce the time required to approve a standard institutional review board protocol. OBJECTIVE: This study aimed to compare processing times and other processing characteristics between sites using a single institutional review board model and those using their individual site institutional review board model in a multicenter clinical trial. STUDY DESIGN: This was a retrospective study of sites in an open-label, multicenter randomized control trial from 2014 to 2021. Participating sites in the multicenter Chronic Hypertension and Pregnancy trial were asked to complete a survey collecting data describing their institutional review board approval process. RESULTS: A total of 45 sites participated in the survey (7 used a shared institutional review board model and 38 used their individual institutional review board model). Most sites (86%) using the shared institutional review board model did not require a full-board institutional review board meeting before protocol approval, compared with 1 site (3%) using the individual institutional review board model (P<.001). Median total approval times (41 vs 56 days; P=.42), numbers of submission rounds (1 vs 2; P=.09), and numbers of institutional review board stipulations (1 vs 4; P=.12) were lower for the group using the shared institutional review board model than those using the individual site institutional review board model; however, these differences were not statistically significant. CONCLUSION: The findings supported the hypothesis that the shared institutional review board model for multicenter studies may be more efficient in terms of cumulative time and effort required to obtain approval of an institutional review board protocol than the individual institutional review board model. Given that these data have important implications for multicenter clinical trials, future research should evaluate these findings using larger or multiple multicenter trials.

Timing of Adjunctive Azithromycin for Unscheduled Cesarean Delivery and Postdelivery Infection.

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.

Planned delivery or expectant management in preeclampsia: an individual participant data meta-analysis.

OBJECTIVE: Pregnancy hypertension is a leading cause of maternal and perinatal mortality and morbidity. Between 34+0 and 36+6 weeks gestation, it is uncertain whether planned delivery could reduce maternal complications without serious neonatal consequences. In this individual participant data meta-analysis, we aimed to compare planned delivery to expectant management, focusing specifically on women with preeclampsia. DATA SOURCES: We performed an electronic database search using a prespecified search strategy, including trials published between January 1, 2000 and December 18, 2021. We sought individual participant-level data from all eligible trials. STUDY ELIGIBILITY CRITERIA: We included women with singleton or multifetal pregnancies with preeclampsia from 34 weeks gestation onward. METHODS: The primary maternal outcome was a composite of maternal mortality or morbidity. The primary perinatal outcome was a composite of perinatal mortality or morbidity. We analyzed all the available data for each prespecified outcome on an intention-to-treat basis. For primary individual patient data analyses, we used a 1-stage fixed effects model. RESULTS: We included 1790 participants from 6 trials in our analysis. Planned delivery from 34 weeks gestation onward significantly reduced the risk of maternal morbidity (2.6% vs 4.4%; adjusted risk ratio, 0.59; 95% confidence interval, 0.36-0.98) compared with expectant management. The primary composite perinatal outcome was increased by planned delivery (20.9% vs 17.1%; adjusted risk ratio, 1.22; 95% confidence interval, 1.01-1.47), driven by short-term neonatal respiratory morbidity. However, infants in the expectant management group were more likely to be born small for gestational age (7.8% vs 10.6%; risk ratio, 0.74; 95% confidence interval, 0.55-0.99). CONCLUSION: Planned early delivery in women with late preterm preeclampsia provides clear maternal benefits and may reduce the risk of the infant being born small for gestational age, with a possible increase in short-term neonatal respiratory morbidity. The potential benefits and risks of prolonging a pregnancy complicated by preeclampsia should be discussed with women as part of a shared decision-making process.

Treatment for Mild Chronic Hypertension during Pregnancy.

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.).

Timing of Maternal Discharge after Cesarean Delivery and Risk of Maternal Readmission.

OBJECTIVE: Despite legislation and hospital policies (present in some institutions) mandating a minimum length of stay in an effort to decrease the frequency of hospital readmissions, the effectiveness of this approach remains uncertain.We hypothesized that following cesarean delivery (CD), the rates of maternal readmission or unscheduled health care visits are lower in patients discharged on postoperative day (POD) 3 or ≥4 as compared with those discharged earlier on POD 2. METHODS: This is a secondary analysis of a multicenter randomized trial comparing adjunctive azithromycin for unscheduled CD to prevent infection. Groups were compared based on the duration of hospitalization measured in days from delivery (POD 0) to day of discharge and categorized as POD 2, 3, and ≥4. The primary outcome was the composite of any maternal postpartum readmission, unscheduled clinic, or emergency room (ER) visit, within 6 weeks of delivery. Secondary outcomes included components of the primary outcome and neonatal readmissions. We excluded women with hypertensive disorders of pregnancy and infections diagnosed prior to POD 2. RESULTS: A total of 1,391 patients were included. The rate of the primary outcome of any readmission increased with POD at discharge: 5.9% for POD 2, 9.4% for POD 3, and 10.9% for POD ≥4 group (trend for p = 0.03). The primary outcome increased with later discharge (POD ≥4 when compared with POD 2). Among components of the composite, ER and unscheduled clinic visits, but not maternal readmissions, increased with the timing of discharge for patients discharged on POD ≥4 when compared with POD 2. Using logistic regression, discharge on POD 3 and on POD ≥4 was significantly associated with the composite (adjusted odds ratios [aOR] 2.6, 95% confidence interval [CI] [1.3-5.3]; aOR 2.9, 95% CI [1.3-6.4], respectively) compared with POD 2. CONCLUSION: The risk of maternal readmission composite following uncomplicated but unscheduled CD was not lower in patients discharged home on POD 3 or ≥4 compared with patients discharged earlier (POD 2). KEY POINTS: · Risk of maternal readmission is higher in patients discharged on POD 3 or 4 compared with POD 2.. · No significant differences by the timing of discharge were observed for any neonatal readmissions.. · Timing of discharge should include an individualized approach with the option of discharge by POD 2..

The Association of Cesarean Skin Incision Length and Postoperative Wound Complications.

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..

Skin preparation type and post-cesarean infection with use of adjunctive azithromycin prophylaxis.

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.

Epidemiology of readmissions in early infancy following nonelective cesarean delivery.

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).

The Use of Ketamine for Air Medical Rapid Sequence Intubation Was Not Associated With a Decrease in Hypotension or Cardiopulmonary Arrest.

OBJECTIVE: Rapid sequence intubation (RSI) is associated with a number of complications that can increase morbidity and mortality. Among RSI agents used to blunt awareness of the procedure and produce amnesia, ketamine is unique in its classification as a dissociative agent rather than a central nervous system depressant. Thus, ketamine should have a lower risk of peri-RSI hypotension because of the minimal sympatholysis compared with other agents. Recent recommendations include the use of ketamine for RSI in hemodynamically unstable patients. The main goal of this analysis was to explore the incidence of hypotension and/or cardiopulmonary arrest in patients receiving ketamine, etomidate, midazolam, and fentanyl during air medical RSI. We hypothesized that ketamine would be associated with a lower risk of hemodynamic complications, particularly after adjusting for covariables reflecting patient acuity. In addition, we anticipated that an increased prevalence of ketamine use would be associated with a decreased incidence of peri-RSI hypotension and/or arrest. METHODS: This was a retrospective, observational study using a large air medical airway database. A waiver of informed consent was granted by our institutional review board. Descriptive statistics were used to present demographic and clinical data. The incidence rates of hypotension and cardiopulmonary arrest were calculated for each sedative/dissociative agent. Multivariable logistic regression was used to calculate the odds ratios of both hypotension and arrest for each of the sedative/dissociative agents. The prevalence of use for each agent and the incidence of hemodynamic complications (hypotension and arrest) were determined over time. RESULTS: A total of 7,466 RSI patients were included in this analysis. The use of ketamine increased over the duration of the study. Ketamine was associated with a higher incidence of both hypotension and arrest compared with other agents, even after adjustment for multiple covariables. The overall incidence of hypotension, desaturation, and cardiopulmonary arrest did not change over the study period. CONCLUSIONS: Although the incidence of hemodynamic complications was higher in patients receiving ketamine, this may reflect a selection bias toward more hemodynamically unstable patients in the ketamine cohort. The incidence of hypotension and arrest did not change over time despite an increase in the prevalence of ketamine use for air medical RSI. These data do not support a safer hemodynamic profile for ketamine.

Modeling the Effects of Stress, Anxiety, and Depression on Rumination, Sleep, and Fatigue in a Nonclinical Sample.

Stress and affective distress have previously been shown to predict sleep quality, and all the factors have been shown to predict fatigue severity. However, few prior studies have examined the likely indirect mediational relationships between stress, affective distress, and sleep quality in predicting fatigue severity, and the potential role played by ruminative thinking. A short questionnaire asked 229 participants about their recent experiences of stress, affective distress, rumination, sleep, and fatigue in a community sample. High stress, anxiety, and depression were related to more ruminative thinking, which in turn was related to poor sleep quality (composed of subjective sleep quality, daytime dysfunction, sleep latency, and sleep disturbance) and poor sleep quality predicted worse fatigue. The results suggest that rumination parsimoniously explains the tendency of stress and affective distress to contribute to poor sleep quality, and together with poor sleep, it may also contribute to worse fatigue in some individuals.

Incidence and Risk Factors for Hospital Readmission or Unexpected Visits in Women Undergoing Unscheduled Cesarean Delivery.

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.

Models of Outpatient Palliative Care Clinics for Patients With Cancer.

PURPOSE: Early integration of outpatient palliative care (OPC) benefits patients with advanced cancer and also the health care systems in which these patients are seen. Successful development and implementation of models of OPC require attention to the needs and values of both the patients being served and the institution providing service. SUMMARY: In the 2016 clinical guideline, ASCO recommended integrating palliative care early in the disease trajectory alongside cancer-directed treatment. Despite strong endorsement and robust evidence of benefit, many patients with cancer lack access to OPC. Here we define different models of care delivery in four successful palliative care clinics in four distinct health care settings: an academic medical center, a safety net hospital, a community health system, and a hospice-staffed clinic embedded in a community cancer center. The description of each clinic includes details on setting, staffing, volume, policies, and processes. CONCLUSION: The development of robust and capable OPC clinics is necessary to meet the growing demand for these services among patients with advanced cancer. This summary of key aspects of functional OPC clinics will enable health care institutions to evaluate their specific needs and develop programs that will be successful within the environment of an individual institution.

Impact of Azithromycin-Based Extended-Spectrum Antibiotic Prophylaxis on Noninfectious Cesarean Wound Complications.

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.