Defining a Strategy for Laboratory Evaluation with Expectant Management of Preeclampsia.

OBJECTIVE: The objective of this study was to compare the frequency and timing of laboratory abnormalities and evaluate optimal laboratory testing strategies in women with preeclampsia (PE) undergoing expectant management. STUDY DESIGN: Retrospective cohort study of women with inpatient expectant management of PE at ≥23 weeks at a tertiary center from 2015 to 2018 was conducted. Women ineligible for expectant management or with less than two laboratory sets (platelets, aspartate aminotransferase, and serum creatinine) before the decision to deliver were excluded. Women were categorized as per the American College of Obstetricians and Gynecologists' definitions by initial diagnosis: PE without severe features, superimposed preeclampsia (SiPE) without severe features, and their forms with severe features. The frequency and timing of laboratory abnormalities were compared across the four PE categories. Kaplan-Meier curves modeled time to a laboratory abnormality (event) with censoring for delivery and were compared using log-rank tests. Logistic regression analysis modeled the development of a laboratory abnormality as a function of testing time intervals (days) for each PE type. Receiver operating characteristic curves and areas under the curve (AUC) were calculated; optimal cut points were determined using the Liu method. RESULTS: Among 636 women who met inclusion criteria, laboratory abnormalities were uncommon (6.3%). The median time to a laboratory abnormality among all women was ≤10 days, time being shortest in women with PE with severe features. Time to laboratory abnormality development did not differ significantly between the four PE groups (p = 0.36). Laboratory assessment intervals were most predictive for PE and SiPE with severe features (AUC = 0.87, AUC = 0.72). Optimal cutoffs were every 4 days for PE without severe features, 2 days for PE with severe features, 8 days for SiPE without severe features, and 3 days for SiPE with severe features. CONCLUSION: Most laboratory abnormalities in PE occur earlier and more frequently in those with severe features. Individual phenotypes should undergo serial evaluation based on this risk stratification. KEY POINTS: · Most laboratory abnormalities occur within 10 days of diagnosis.. · Laboratory abnormalities occur more often with severe features.. · Laboratory testing should occur according to disease severity..

Contemporary Trends in Cesarean Delivery Rates and Indications.

OBJECTIVE: This study aimed to describe cesarean delivery rates and indications at a single center in order to assess the impact of the guidelines published by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine on trends in labor management. STUDY DESIGN: This is a retrospective cohort study of patients ≥23 weeks' gestation delivering at a single tertiary care referral center from 2013 to 2018. Demographic characteristics, mode of delivery, and main indication for cesarean delivery were ascertained by individual chart review. Cesarean delivery indications (mutually exclusive) were the following: repeat cesarean delivery, nonreassuring fetal status, malpresentation, maternal indications (e.g., placenta previa or genital herpes simplex virus), failed labor (any stage labor arrest), or other (i.e., fetal anomaly and elective). Polynomial (cubic) regression models were used to model rates of cesarean delivery and indications over time. Subgroup analyses further examined trends in nulliparous women. RESULTS: Of the 24,637 patients delivered during the study period, 24,050 were included in the analysis; 7,835 (32.6%) had a cesarean delivery. The rates of overall cesarean delivery were significantly different over time (p < 0.001), declining to a minimum of 30.9% in 2014 and peaking at 34.6% in 2018. With regard to the overall cesarean delivery indications, there were no significant differences over time. When limited to nulliparous patients, the rates of cesarean delivery were also noted to be significantly different over time (p = 0.02) nadiring at 30% in 2015 from 35.4% in 2013 and then rising up to 33.9% in 2018. As for nulliparous patients, there was no significant difference in primary cesarean delivery indications over time except for nonreassuring fetal status (p = 0.049). CONCLUSION: Despite changes in labor management definitions and guidelines encouraging vaginal birth, the rates of overall cesarean delivery did not decrease over time. The indications for delivery, particularly failed labor, repeat cesarean delivery, and malpresentation have not significantly changed over time. KEY POINTS: · The rates of overall cesarean deliveries did not decrease despite the 2014 published recommendations for the reduction in cesarean deliveries.. · There were no significant differences in the indications of cesarean deliveries among nulliparous or multiparous women.. · Despite the adoption of strategies to reduce the overall and primary cesarean delivery rates, these trends remain unchanged.. · Indications for delivery, particularly failed labor, repeat cesarean delivery, and malpresentation have also not significantly changed over time.. · Additional strategies to encourage and increase vaginal delivery rates must be adopted..

Contemporary Test Performance of the Random Urine Protein-to-creatinine Ratio.

OBJECTIVE: The random urine protein-to-creatinine ratio (UPCR) is a screening test used for predicting clinically significant proteinuria (urine protein ≥ 300 mg) during pregnancy. No consensus exists on the optimal random UPCR cutoff for performing follow-up 24 hour urine (24H) total protein collection. We aim to evaluate the test performance of random UPCR in predicting proteinuria in a contemporary cohort. STUDY DESIGN: This was a retrospective cohort study of pregnant patients at our institution from 2014 to 2018 with a random UPCR and follow-up 24H protein collection. The primary analysis estimated the test characteristics (sensitivity, specificity, positive and negative predictive values) of using random UPCR for the detection of proteinuria defined as urine protein ≥300 mg on 24H protein collection. UPCR cutoffs from 0.10 to 0.30 mg/dL were evaluated, receiver operator characteristic (ROC) curve was constructed, and area under the curve (AUC) was determined. A secondary analysis examined the correlation between UPCR and 24H protein using least squares regression and Pearson correlation. RESULTS: Paired UPCR and 24H collection results were available for 1,120 patients. Mean gestational age at time of UPCR was 31.1 ± 5.1 weeks and 687 (61.3%) of patients had a 24H ≥300 mg. UPCR <0.10 mg/dL effectively excluded proteinuria ≥300 mg on 24H collection, while UPCR ≥0.18 mg/dL correctly classifies proteinuria with 91% sensitivity, 57% specificity, 77% positive predictive value, and 79% negative predictive value. UPCR ≥1.07 mg/dL had 100% specificity for 24 hour proteinuria. The area under ROC curve was 0.86. UPCR and 24H collection were highly correlated with a Pearson correlation coefficient of 0.85. After our institution lowered the threshold to obtain a 24H from UPCR ≥0.20 mg/dL to ≥0.10 mg/dL in May 2017, the percentage of patients meeting criteria for 24H collection increased from 57.8 to 84.4%. CONCLUSION: The AUC and Pearson correlation suggest random UPCR is a high performance test for the prediction of proteinuria on 24H. Optimal test performance is dependent upon clinical consideration and upon the implications of the disease or condition. A random UPCR screen positive threshold of 0.18 mg/dL maximizes sensitivity to identify clinically significant proteinuria. KEY POINTS: · Random urine protein to creatinine ratio is a high performance test for proteinuria.. · A random UPCR threshold of 0.18 mg/dL maximizes sensitivity to identify proteinuria.. · Optimal test performance is dependent on the disease or clinical condition..

Adjunctive Azithromycin Prophylaxis for Prelabor Cesarean Birth.

OBJECTIVE: To evaluate maternal postoperative infections before and after addition of adjunctive azithromycin to standard antibiotic prophylaxis for prelabor cesarean births. METHODS: We conducted a retrospective cohort study of patients with singleton gestations at more than 23 weeks of gestation who underwent prelabor cesarean birth at a single tertiary care center. Deliveries were categorized as those before implementation of 500 mg intravenous azithromycin in addition to standard preoperative cephalosporin antibiotic prophylaxis (pre-AZI group; January 2013-September 2015) and those after implementation of adjunctive azithromycin (post-AZI group; January 2016-December 2018). Cesarean births from October to December 2015 were excluded as a washout period. The primary outcome was a composite of postcesarean infections (endometritis, superficial or deep wound infections, intra-abdominal abscess, urinary tract infections). Secondary outcomes included composite components, other wound or postoperative complications, and select neonatal morbidities. Outcomes were compared between groups, and adjusted odds ratios (aORs) and 95% CIs were calculated using multivariable analysis. Propensity score matching was performed to assess the robustness our analysis. RESULTS: Of 2,867 delivering patients included for analysis, 1,391 (48.5%) were in the pre-AZI group and 1,476 (51.5%) were in the post-AZI group. Patients in the post-AZI group were older and were more likely to have private insurance, use aspirin, and receive predelivery antibiotics within 2 weeks. There were significantly lower odds of composite infection after azithromycin implementation (3.3% vs 4.8%, aOR 0.60, 95% CI 0.40-0.89), driven by a reduction in wound infection odds (2.4% vs 3.5%, aOR 0.61, 95% CI 0.39-0.98). There were lower odds of other postpartum complications, including wound seroma (0.5% vs 0.9%, aOR 0.34, 95% CI 0.13-0.90) and dehiscence (0.5% vs 1.2%, aOR 0.32, 95% CI 0.13-0.79). There were no differences in select neonatal morbidities between groups. Of 1,138 matching sets in the propensity analysis, the primary outcome remained significantly lower in the post-AZI group (aOR 0.64, 95% CI 0.41-0.99). CONCLUSION: Adopting adjunctive azithromycin for prelabor cesarean deliveries was associated with lower odds of postpartum infection.

Operative vaginal delivery as an independent risk factor for maternal postpartum infectious morbidity.

BACKGROUND: A recent study from the United Kingdom suggested that a single dosage of adjunctive amoxicillin/clavulanic acid with operative vaginal delivery reduces maternal infectious morbidity by 40% (from 19% to 11%). However, 89% of their study population received an episiotomy. OBJECTIVE: This study aimed to evaluate whether operative vaginal delivery is an independent risk factor for composite maternal postpartum infectious morbidity in a population with a low episiotomy rate. STUDY DESIGN: This was a retrospective cohort study of patients with viable singleton vaginal deliveries after ≥34 weeks gestation at a single perinatal center (2013-2018). The patients were categorized by the mode of delivery: spontaneous vaginal delivery or operative vaginal delivery (forceps or vacuum-assisted). The primary outcome was a composite of maternal infectious morbidity up to 6 weeks after delivery, defined as (1) endometritis, (2) perineal wound morbidity (infection, breakdown, or dehiscence), or (3) culture-proven urinary tract infection. The patient characteristics and outcomes were compared between the groups using appropriate tests. Multivariable models were used to estimate the association between operative vaginal delivery and study outcomes compared with spontaneous vaginal delivery, with adjustment for selected confounders. RESULTS: Of 14,647 deliveries meeting the inclusion criteria, 732 (5.0%) were operative vaginal deliveries: 354 (48%) forceps and 378 (52%) vacuums. Overall, 210 (1.4%) patients developed the morbidity composite. Patients having an operative vaginal delivery were more likely to be nulliparous, have labor inductions, develop intrapartum chorioamnionitis, receive an episiotomy, and sustain a third- or fourth-degree laceration. After adjusting for confounding factors, no significant association was observed between operative vaginal delivery and composite morbidity (adjusted odds ratio, 1.4 [0.8-2.4]) or any of its individual components. Administration of postpartum antibiotics and documented fever were also similar between groups. There was also no significant association between instrument (forceps vs vacuum) and the maternal infection composite. CONCLUSION: In this single-center US cohort, operative vaginal delivery was not an independent risk factor for maternal composite postpartum infectious morbidity.

Venous thromboembolism and adverse outcomes in highest thromboembolism risk patients compared with those at lower risk.

BACKGROUND: A risk-based institutional protocol for inpatient heparin-based venous thromboembolism prophylaxis in a general obstetrical population previously demonstrated a greater than 2-fold increase in wound hematomas with no change in the frequency of thromboembolism. OBJECTIVE: We sought to compare the rates of thromboembolism and bleeding outcomes in patients at the highest risk for thromboembolism (eg, those with a history of thromboembolism or thrombophilia who require anticoagulation prophylaxis or therapy throughout pregnancy) than low-risk patients. STUDY DESIGN: We performed a retrospective cohort study of all deliveries >20 weeks at a single center from 2013-2018. Patients were categorized as high-risk (received outpatient heparin-based prophylaxis or treatment) or low-risk (no outpatient anticoagulation). The primary outcome was newly diagnosed postpartum thromboembolism; the main secondary outcome was wound/perineal hematoma. The outcomes were compared between the high- and low-risk cohorts. Adjusted odds ratios (with 95% confidence intervals) were calculated with the low-risk group as reference. RESULTS: Of 24,303 total deliveries, 395 (1.7%) were high-risk and 23,905 (98.3%) were low-risk. Among the low-risk patients, 8.6% received anticoagulation prophylaxis in accordance with our risk-based inpatient thromboembolism prophylaxis protocol. High-risk patients were more likely to be older and have a higher body mass index, earlier delivery gestational age, medical comorbidities, and pregnancy complications, eg, preeclampsia. Despite outpatient antepartum anticoagulation, high-risk patients had an 11-fold increased risk of thromboembolism (adjusted odds ratio, 11.1 [4.7-26.2]) than low-risk patients. High-risk patients also had significantly more wound/perineal hematomas (adjusted odds ratio, 4.8 [2.7-8.4]), overall wound complications (adjusted odds ratio, 3.0 [2.0-4.4]), blood transfusions, intensive care unit admissions, maternal deaths, and longer maternal lengths of stay. CONCLUSION: Patients at the highest risk of obstetrical thromboembolism had an 11-fold increased risk of thromboembolism with a more moderate increase (∼5-fold) in postpartum wound and bleeding complications than low-risk patients. This more favorable risk or benefit profile supports current anticoagulation recommendations in high-risk patients.

Evaluation of a Risk-Stratified, Heparin-Based, Obstetric Thromboprophylaxis Protocol.

OBJECTIVE: To evaluate outcomes before and after implementation of a risk-stratified heparin-based obstetric thromboprophylaxis protocol. METHODS: We performed a retrospective cohort study of all patients who delivered at our tertiary care center from 2013 to 2018. Deliveries were categorized as preprotocol (2013-2015; no standardized heparin-based thromboprophylaxis) and postprotocol (2016-2018). Patients receiving outpatient anticoagulation for active venous thromboembolism (VTE) or high VTE risk were excluded. Coprimary effectiveness and safety outcomes were postpartum VTEs and wound hematomas, respectively, newly diagnosed after delivery and up to 6 weeks postpartum. Secondary outcomes were other wound or bleeding complications, including unplanned surgical procedures (eg, hysterectomies, wound explorations) and blood transfusions. Outcomes were compared between groups, and adjusted odds ratios (aORs) and 95% CIs were calculated using the preprotocol group as reference. RESULTS: Of 24,229 deliveries, 11,799 (49%) occurred preprotocol. Although patients were more likely to receive heparin-based prophylaxis postprotocol (15.6% vs 1.2%, P<.001), there was no difference in VTE frequency between groups (0.1% vs 0.1%, odds ratio 1.0, 95% CI 0.5-2.1). However, patients postprotocol experienced significantly more wound hematomas (0.7% vs 0.4%, aOR 2.34, 95% CI 1.54-3.57), unplanned surgical procedures (aOR 1.29, 95% CI 1.06-1.57), and blood transfusions (aOR 1.34, 95% CI 1.16-1.55). CONCLUSION: Risk-stratified heparin-based thromboprophylaxis in a general obstetric population was associated with increased wound and bleeding complications without a complementary decrease in postpartum VTE. Guidelines recommending this strategy should be reconsidered.

Effectiveness of female and male condoms in preventing exposure to semen during vaginal intercourse: a randomized trial.

OBJECTIVES: Comparison of male condom (MC) vs. female condom (FC) with respect to self-reported mechanical and acceptability problems and semen exposure using prostate-specific antigen (PSA) as an objective biological marker and evaluation of the effect of an educational intervention on self-reported problems and semen exposure, by condom type. DESIGN: Randomized crossover trial. METHODS: Four hundred women attending a family planning clinic in Brazil were randomized and either received in-clinic instruction or were encouraged to read the condom package insert; all used two FCs and two MCs. We measured the rates of self-reported user problems with MC and FC use and the rates of semen exposure during use (assessed by testing vaginal fluid for PSA). RESULTS: The educational intervention group reported fewer problems with either condom as compared with the control group (p = .0004, stratified by condom type). In both groups, self-reported problems were more frequent with FC use than with MC use (p < .0001, stratified by intervention). The educational intervention did not significantly reduce semen exposure. Overall, semen exposure occurred more frequently with FC use (postcoital PSA, > 1 ng/mL; 22%) than with MC use (15%); the difference, however, was small and nonsignificant for high PSA levels (> or = 150 ng/mL; 5.1% for FC vs. 3.6% for MC). CONCLUSIONS: In this study, the FC was less effective than the MC in preventing semen exposure during use and led more frequently to self-reported user problems. Both devices were highly protective against "high-level" semen exposure, as measured by postcoital PSA levels in vaginal fluid. In-clinic education may reduce user problems and increase acceptability and use of both devices.

The acceptability of the female and male condom: a randomized crossover trial.

CONTEXT: Although studies have assessed the acceptability of male and female condoms, comparative trial data are lacking. METHODS: A sample of 108 women in stable relationships recruited from an urban, reproductive health clinic were randomly assigned to use 10 male or female condoms, followed by use of 10 of the other type. A nurse provided instruction in correct method use. Demographic information was collected in a baseline questionnaire; acceptability data were collected in follow-up and exit questionnaires and coital logs. Nonparametric and chi-square statistics were used to analyze measures of the methods' relative acceptability. Bowker's test of symmetry was adapted to test the null hypothesis of no difference in acceptability between condom types. RESULTS: Participants used 678 female and 700 male condoms. Although neither method scored high on user satisfaction measures, the 63 women completing the study protocol preferred the male condom to the female condom for ease of application or insertion, ease of removal, general fit, feel of the condom during intercourse and ease of penetration. Participants reported that their partner also favored the male condom, although women generally appeared to like this method more than their partner did. In a direct comparison between the methods at the end of the study, women generally judged male condoms superior on specified preference criteria. CONCLUSIONS: Across a range of criteria, the female condom was less acceptable than the male condom to most women and their partners. Although both types had low acceptability, they are needed and valid methods of pregnancy and disease prevention. That neither rated high on user satisfaction measures underscores the need for more barrier methods that women and men can use.

Modified Kigali combined staging predicts risk of mortality in HIV-infected adults in Lusaka, Zambia.

We assessed the utility of the modified Kigali combined (MKC) staging system for predicting survival in HIV-infected Zambian adults in a prospective, longitudinal, open cohort. From 1995 to 2004, HIV-discordant couples (one HIV-infected partner and one HIV-negative partner) were recruited from couples' voluntary counseling and testing centers in Lusaka, Zambia and followed at 3-month intervals. MKC stage, which incorporates clinical stage with erythrocyte sedimentation rate (ESR), hematocrit, and body mass index (BMI), was determined at enrollment. Kaplan-Meier survival and Cox proportional hazard methods were used to calculate median survival and relative hazards. We enrolled 1479 HIV-discordant couples with a combined 7305 person-years of follow-up. Among HIV-infected participants over the 9-year study period, there were 333 confirmed deaths. The time to 50% mortality was 8.5 years with MKC stage 1 and 2 disease compared to 3.7 years with MKC stage 4 disease at enrollment. Survival rates at 3 years were 85% with MKC stage 1 and 2 disease, 74% with MKC stage 3 disease, and 51% with MKC stage 4 disease. A total of 275 HIV-negative partners seroconverted during follow-up. In comparison, survival rates at 3 years were 94% for HIV-negative participants and 92% for participants who seroconverted during follow-up. In multivariate analysis, MKC stage 4 disease (HR = 3.7, 95% CI = 2.7-5.0) remained a strong predictor of mortality. Incorporating ESR, hematocrit, and BMI with clinical staging is a powerful, low-cost tool to identify HIV-infected adults at high risk for mortality.

Efficacy of the male latex condom and of the female polyurethane condom as barriers to semen during intercourse: a randomized clinical trial.

In this 2000-2001 study, the authors compared the effectiveness of the male latex condom and the female polyurethane condom by assessing frequency and types of mechanical failure and by evaluating semen exposure during use. Eligible women from Birmingham, Alabama, were randomly assigned to begin the study with 10 male condoms and then switch to 10 female condoms (n = 55), or vice versa (n = 53), and were trained to use both types. Data collection included questionnaires for each condom use and measurement of prostate-specific antigen in specimens of vaginal fluid taken before and after intercourse. Participants returned 700 male condoms and 678 female condoms, and they reported mechanical problems for 9% and 34%, respectively. Moderate-high postcoital prostate-specific antigen levels (> or = 22 ng/ml) were detected in 3.5% of male condom uses and 4.5% of female condom uses (difference = 1%, 95% confidence interval: -1.6, 3.7). Moderate-high prostate-specific antigen values (> or = 22 ng/ml) were more frequent with mechanical problems (male condom, 9.6%; female condom, 9.4%) but less frequent with other problems (3.0% and 0.9%) or correct use with no problems (2.7% and 2.5%). This study indicates that although mechanical problems are more common with the female condom than with the male condom, these devices may involve a similar risk of semen exposure. Objectively assessed semen exposure is associated with self-reported mechanical problems.

HIV-infected Rwandan women have a high frequency of long-term survival.

OBJECTIVES: To evaluate rates of long-term survival in a prospective, longitudinal, closed HIV cohort in Africa between 1986 and 2006. METHODS: A total of 548 HIV-infected Rwandan women were recruited from prenatal clinics in Kigali and followed at 3-6 month intervals to February 2006. Overall, 401 women (73%) were HIV positive at initial cross-sectional testing in 1986 (seroprevalent cohort) and 147 women (27%) were initially HIV negative but seroconverted during follow-up from 1986 to 1993 (seroincident cohort). Kaplan-Meier survival methods were used to calculate survival times censored in mid-2003. RESULTS: In February 2006, 109 women (20%) remained alive in the cohort. Time to 50% non-genocide mortality was 11.9 years among seroincident women and 8.9 years among seroprevalent women. Smoothed mortality rates increased with duration of follow-up to a peak of 0.12 deaths per person-year at 9.5 years of follow-up but subsequently declined. After 15 years of follow-up (pre-HAART introduction), the survival probability was 36% for seroincident women and 26% for seroprevalent women. Most survivors had virological and immunological evidence of disease progression. The median CD4 cell count of survivors declined from 447 cells/mul in 1998 to 268 cells/mul in 2003. Among survivors, 57 women (52%) met treatment criteria and initiated antiretroviral treatment by 2006. CONCLUSION: Although median survival times in this cohort were similar to those observed in high-income countries, the rates of long-term survival after 15 years of follow-up were higher than expected. A levelling off of mortality rates during the late stages of follow-up may explain this high rate of long-term survival.