Pregnancy-Related Deaths, Florida, 1999-2012: Opportunities to Improve Maternal Outcomes.

Objectives To examine pregnancy-related deaths (PRDs) in Florida, to identify quality improvement (QI) opportunities, and to recommend strategies aimed at reducing maternal mortality. Methods The Florida Pregnancy-Associated Mortality Review (PAMR) Committee reviewed PRDs occurring between 1999 and 2012. The PAMR Committee determined causes of PRDs, identified contributing factors, and generated recommendations for prevention and quality improvement. Information from the PAMR data registry, and live births from Florida vital statistic data were used to calculate pregnancy-related mortality ratios (PRMR) and PRD univariate risk ratios (RR) with 95% confidence intervals (CI). Results Between 1999 and 2012, the PRMR fluctuated between 14.7 and 26.2 PRDs per 100,000 live births. The five leading causes of PRD were hypertensive disorders (15.5%), hemorrhage (15.2%), infection (12.7%), cardiomyopathy (11.1%), and thrombotic embolism (10.2%), which accounted for 65% of PRDs. Principal contributing factors were morbid obesity (RR = 7.0, 95% CI 4.9-10.0) and late/no prenatal care (RR = 4.2, 95% CI 3.1-5.6). The PRMR for black women was three-fold higher (RR = 3.3, 95% CI 2.7-4.0) than white women. Among the five leading causes of PRDs, 42.5% had at least one clinical care or health care system QI opportunity. Two-third of these were associated with clinical quality of care, which included standards of care, coordination, collaboration, and communication. The QI opportunities varied by PRD cause, but not by race/ethnicity. Conclusion Gaps in clinical care or health care systems were assessed as the primary factors in over 40% of PRDs leading the PAMR Committee to generate QI recommendations for clinical care and health care systems.

Pregnancy-associated mortality review: the Florida experience.

At the beginning of the 20th century, maternal mortality was a leading cause of death for women of reproductive age in the United States. Obstetrical care was not standardized, and there was a lack of universal systems for monitoring maternal deaths. Public health efforts of surveillance, along with advances in medicine and sanitation, resulted in a significant decrease in maternal deaths by the early 1980s. Today, maternal death is considered to be a rare event; however, the rates of maternal mortality have not improved in almost 3 decades. There is growing evidence that many maternal deaths can still be prevented through enhanced surveillance that influences improvements in overall health and delivery of care. This paper describes the experience of establishing and maintaining a pregnancy-associated mortality surveillance system in Florida. Emphasis is placed on the process and importance of a statewide review and the value of engagement with the medical community.

Fetal fibronectin as a short-term predictor of preterm birth in symptomatic patients: a meta-analysis.

OBJECTIVE: To appraise critically the diagnostic accuracy of cervicovaginal fetal fibronectin as a short-term predictor of preterm birth in patients with signs and symptoms of preterm labor. DATA SOURCES: We searched MEDLINE, Current Contents, Index Medicus, EMBASE, the Cochrane Library, and syllabi from scientific meetings, and we performed manual searches of references from textbooks and of known primary and systematic review articles. We also contacted authors, experts on this subject, and the manufacturer. METHODS OF STUDY SELECTION: We targeted cohort studies reporting data on the diagnostic accuracy of fetal fibronectin for the prediction of preterm birth within 7 days in symptomatic patients before 37 weeks of gestation. Case-control studies were excluded. The total analysis included 32 trials with 5,355 overall participants. TABULATION, INTEGRATION, AND RESULTS: Two authors independently assessed methodological quality and constructed 2x2 tables for assessment of diagnostic measures. Pooled estimates of sensitivity, specificity, and likelihood ratios were obtained using a bivariate random effects model. Tests for publication bias and meta-regression were performed. Sensitivity analyses were performed for studies using different fetal fibronectin assays. The overall pooled estimates for sensitivity and specificity were 76.1% (95% confidence interval [CI] 69.1-81.9) and 81.9% (95% CI 78.9-84.5), respectively. Likelihood ratios for a positive and negative fetal fibronectin test were 4.20 (95% CI 3.53-4.99) and 0.29 (95% CI 0.22-0.38), respectively. Meta-regression analyses found that test accuracy was affected by prevalence, publication year, and blinding of studies. When subgroup analyses were performed for studies using the same assay, the results were similar. CONCLUSION: The cervicovaginal fetal fibronectin assay has limited accuracy in predicting preterm birth within 7 days of sampling in symptomatic pregnant women.

Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA.

BACKGROUND: Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European than in American cohort studies, possibly due to differences in population characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from the US and Western Europe enrolling in the same clinical trial provided the opportunity to identify and explore differences in their characteristics and in the use of non-study interventions to reduce MTCT. METHODS: In this secondary analysis, 1350 women were categorized according to enrollment in centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active antiretroviral therapy and with elective caesarean delivery were identified with logistic regression. RESULTS: In Europe, women enrolled were more likely to be white and those of black race were mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous pregnancies and miscarriages and a history of sexually transmitted infections. More than 90% of women did not report symptoms of their HIV infection; however, more women from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy. The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US (22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of transmission between Europe and the US despite the different approaches to treatment and delivery. CONCLUSION: These findings confirm that there are important historical differences between the HIV-infected pregnant populations in Western Europe and the USA, both in terms of the characteristics of the women and their obstetric and therapeutic management. Although highly active antiretroviral therapy predominates in pregnancy in both settings now, population differences are likely to remain. TRIAL REGISTRATION: NCT00000869.

Progestational agents to prevent preterm birth: a meta-analysis of randomized controlled trials.

OBJECTIVE: To perform an updated systematic review with meta-analysis to further elucidate the efficacy of progestational agents for the prevention of preterm births in patients at elevated risk. DATA SOURCES: Computerized databases, references in published studies, and textbook chapters in all languages were used to identify randomized controlled trials (RCTs) evaluating the use of progestational agents for the prevention of preterm births in women at elevated risk. METHODS OF STUDY SELECTION: We identified RCTs that compared progestational agents with placebo for patients at risk for preterm birth and evaluated at least one of the following: delivery before 37 weeks of gestation, birth weight less than 2,500 g, threatened preterm labor, respiratory distress syndrome, and perinatal mortality. The primary outcomes assessed were preterm delivery and perinatal mortality. TABULATION, INTEGRATION, AND RESULTS: Ten studies met inclusion criteria for this review. For each study with binary outcomes, an odds ratio (OR) with 95% confidence intervals (CIs) was calculated for selected outcomes. Homogeneity was tested across the studies. Compared with women allocated to receive placebo, those who received progestational agents had lower rates of preterm delivery (26.2% versus 35.9%; OR 0.45, 95% CI 0.25-0.80). Similar results were noted when comparing patients who were specifically treated with 17alpha-hydroxyprogesterone caproate (29.3% versus 40.9%; OR 0.45, 95% CI 0.22-0.93). Additionally, subjects allocated to receive 17alpha-hydroxyprogesterone caproate had lower rates of birth weights less than 2,500 g (OR 0.50, 95% CI 0.36-0.71). No differences in rates of hospital admissions for threatened preterm labor or perinatal mortality were noted for subjects receiving progestational agents in general or for those receiving only 17alpha-hydroxyprogesterone caproate specifically. CONCLUSION: The use of progestational agents and 17alpha-hydroxyprogesterone caproate reduced the incidence of preterm birth and low birth weight newborns.

Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group protocol 332.

This study evaluates the safety, tolerance, and pharmacokinetics of stavudine (d4T) in human immunodeficiency virus (HIV)-infected zidovudine (ZDV)-intolerant/refusing pregnant women and of single-dose d4T in their infants. Women received d4T and lamivudine (3TC) from enrollment until labor. During labor, women received oral 3TC and either intravenous or oral d4T. Infants received ZDV and 3TC for 6 weeks and a single dose of oral d4T at weeks 1 and 6. Mean maternal antenatal d4T pharmacokinetics (terminal plasma half-life [T1/2], 83.5+/-16.8 min; area under the plasma-concentration time curve [AUC0-infinity), 81.6+/-22.0 microg.min/mL; n=6) were not significantly different from those during labor (T(1/2), 87.3+/-24.7 min; AUC0-infinity, 88.1+/-16.6 microg.min/mL; n=6). Umbilical-cord and maternal plasma concentrations were not significantly different from one another. The oral clearance of d4T in infants was significantly greater at week 6 versus week 1 (6.8+/-1.0 vs. 5.6+/-1.2 mL/min/kg). There were no toxicities, in women or infants, that required discontinuation or modification of the study drug. No infants had positive HIV viral diagnostic tests. d4T with or without 3TC is a potential alternative to ZDV for HIV-infected pregnant women.

The impact of race/ethnicity on mother-to-child HIV transmission in the United States in Pediatric AIDS Clinical Trials Group Protocol 316.

The present analysis was designed to determine whether race/ethnicity was independently associated with mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intra-partum nevirapine in combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity, predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression models were fit to evaluate possible association of factors with HIV transmission and with viral load at delivery. Variables associated with the outcome at P < 0.05 level were retained in the final models. Of 1052 women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206 (23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic (11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant (0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women were more likely than white women to start therapy during their current pregnancy but did not initiate prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P < or = 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P = 0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have significant implications for the health of these women and their newborns. Race/ethnicity is significant in predicting viral suppression at the time of delivery.

Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316.

OBJECTIVE: The purpose of this study was to evaluate rates of maternal toxicity, pregnancy complications, and peripartum morbidity by type and duration of antiretroviral therapy (ART) during pregnancy. STUDY DESIGN: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 316 (PACTG 316) study evaluated the addition of intrapartum/neonatal nevirapine to background ART to reduce perinatal transmission of human immunodeficiency virus-1 (HIV-1). For this secondary analysis, women were categorized into one of six groups on the basis of ART during pregnancy (monotherapy [monoRx], combination without protease inhibitor [PI], combination with PI), and start time (early: before or during first trimester; late: second or third trimester). RESULTS: One thousand four hundred seven women were included: 288 monoRx late, 34 monoRx early, 327 combo, no PI late, 175 combo, no PI early, 320 combo, PI late, and 263 combo, PI early. Symptoms and laboratory abnormalities of moderate grade or more occurred in less than 5% of women. Only gestational diabetes (highest in combo PI early) varied significantly by therapy group. CONCLUSION: In HIV-infected women receiving prenatal care and ART, adverse events were uncommon.

Labor induction versus expectant management for postterm pregnancies: a systematic review with meta-analysis.

OBJECTIVE: To compare routine labor induction with expectant management for patients who reach or exceed 41 weeks' gestation. DATA SOURCES: Computerized databases, references in published studies, and textbook chapters in all languages were used to identify randomized controlled trials (RCTs) evaluating induction and expectant management of labor for postterm pregnancies. METHODS OF STUDY SELECTION: We identified RCTs that compared induction and expectant management for uncomplicated, singleton, live pregnancies of at least 41 weeks' gestation and evaluated at least one of the following: perinatal mortality, mode of delivery, meconium-stained fluid, meconium aspiration syndrome, meconium below the cords, fetal heart rate (FHR) abnormalities during labor, cesarean deliveries for FHR abnormalities, abnormal Apgar scores, and neonatal intensive care unit (NICU) admissions. The primary outcomes assessed were cesarean delivery rate and perinatal mortality. TABULATION, INTEGRATION, AND RESULTS: Sixteen studies met inclusion criteria for this review. For each study with binary outcomes, an odds ratio (OR) with 95% confidence intervals (CIs) was calculated for selected outcomes. Estimates of ORs for dichotomous outcomes were calculated using fixed and random-effects models. Homogeneity was tested across the studies. Compared with women allocated to expectant management, those who underwent labor induction had lower cesarean delivery rates (20.1% versus 22.0%) (OR 0.88; 95% CI 0.78, 0.99). Although subjects whose labor was induced experienced a lower perinatal mortality rate (0.09% versus 0.33%) (OR 0.41; 95% CI 0.14, 1.18), this difference was not statistically significant. Similarly, no significant differences were noted for NICU admission rates, meconium aspiration, meconium below the cords, or abnormal Apgar scores. CONCLUSION: A policy of labor induction at 41 weeks' gestation for otherwise uncomplicated singleton pregnancies reduces cesarean delivery rates without compromising perinatal outcomes.

Special considerations for the HIV-infected patient with preterm labor.

It is essential that women admitted for PTL have a confidential review of maternal history and prenatal record for HIV serostatus. Combination ARV therapy should be continued during tocolysis of PTL and, if tocolysis fails, through delivery. Counseling and rapid HIV testing should be performed in the intrapartum or postnatal periods if the woman's serostatus has not been determined. Women identified as being HIV infected who are in labor should be treated with (1) ZDV in labor and for 6 weeks to the neonate, (2) NVP single dose to the mother in labor and single dose to the neonate, (3) ZDV-3TC in labor and to the neonate for 1 week, or (4) NVP (as above) and the ZDV regimen (as above). Cesarean delivery should be recommended to all women when the most recent viral load is greater than or equal to 1000 copies/mL or is unknown. Those charged with the care of HIV-infected pregnant women should make frequent use of the Public Health Service Website (http://www.aidsinfo.nih.gov), which provides a regularly updated, practical, and thorough guide to management of patients who have HIV.

The effect of tablet moistening on labor induction with intravaginal misoprostol: a randomized trial.

OBJECTIVE: To estimate whether a dosage of 50 microg of misoprostol tablets moistened with 3% acetic acid and administered intravaginally is more efficacious for labor induction than a similar dosage regimen using dry tablets. METHODS: A total of 177 women who presented with an indication for cervical ripening and labor induction were randomly assigned to one of two treatment groups: 1) intravaginal misoprostol in dry tablet form, or 2) intravaginal misoprostol moistened with 1 mL of 3% acetic acid solution. The primary outcome assessed was the interval from start of induction to vaginal delivery. To detect at least a 3.5-hour difference in the primary outcome with 80% power, 87 subjects were required in each group. RESULTS: Among 162 patients evaluated, 80 were allocated to the misoprostol dry group and 82 to the misoprostol moistened group. No significant difference was noted for the mean +/- standard deviation interval to vaginal delivery: 1130 +/- 636 minutes for the group who received dry tablets and 1004 +/- 636 minutes for those who received moistened misoprostol tablets (P =.25). Additionally, no statistically significant differences were noted between the groups with respect to need for oxytocin, proportion of patients delivered after a single dose, intrapartum complications (including tachysystole and uterine hyperstimulation), mode of delivery, or perinatal outcomes. CONCLUSION: Tablet moistening with 3% acetic acid solution does not seem to improve the efficacy of intravaginally administered misoprostol for labor induction.

Labor induction with 25 microg versus 50 microg intravaginal misoprostol: a systematic review.

OBJECTIVE: To systematically review published randomized controlled trials (RCTs) to compare the safety and efficacy of 25 microg versus 50 microg of intravaginal misoprostol for cervical ripening and labor induction. DATA SOURCES: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify RCTs of misoprostol for cervical ripening and labor induction, which compared repeated doses of 25 microg and 50 microg. STUDY SELECTION: We evaluated, abstracted data, and assessed the quality of RCTs to compare the safety and efficacy of 25 microg versus 50 microg of intravaginal misoprostol for cervical ripening and labor induction. TABULATION, INTEGRATION, AND RESULTS: Five RCTs met inclusion criteria for meta-analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for each outcome (random- and fixed-effects models). In addition, we aggregated the results of two separate studies, permitting an indirect comparison of the two doses being analyzed. In the meta-analysis, tachysystole and hyperstimulation syndrome appear to occur less frequently among women who received 25 microg of misoprostol than with 50 microg. However, neonatal outcomes appear to be comparable with the two doses. Regarding efficacy, use of the 50-microg dose was associated with a shorter interval to vaginal delivery, greater proportion of deliveries within 24 hours, and less frequent need for oxytocin augmentation. The indirect comparison of two studies yielded similar results. CONCLUSION: Published data indicate that intravaginal misoprostol at doses of 50 microg for cervical ripening and labor induction is more efficacious but it is unclear whether it is as safe as the 25-microg dose.