Reducing stillbirths: interventions during labour. Anaerobic coverage for intra-amnionic infection: maternal and perinatal impact. The efficacy of psychological, educational, and behavioral treatment. Confirmation from meta-analysis. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Tailoring systematic reviews to meet critical priorities in maternal health in the intrapartum period. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? Antibiotic optimization. An evaluation of patient safety and economic outcomes. Meconium-stained amniotic fluid-associated infectious morbidity: a randomized, double-blind trial of ampicillin-sulbactam prophylaxis. Chlorhexidine vs. Sterile vaginal wash during labor to prevent neonatal infection. A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team. Reducing infections among women undergoing cesarean section in Colombia by means of continuous quality improvement methods.
Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined.
                We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies.
                We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed.
                Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs. Although intrapartum antibiotics are beneficial to both the mother and newborn, there is no consensus as to the most efficacious antibiotic regimen in the treatment of intra-amnionic infection, especially with regard to anaerobic coverage. We randomized pregnant women with intra-amnionic infection to receive either dual agent therapy (ampicillin and gentamicin) or triple agent therapy (ampicillin, gentamicin, and clindamycin). The frequency of vaginal and cesarean delivery was similar in both groups. There was no significant difference in the incidence of endometritis between the two groups (10 of 69 versus 5 of 64; p = NS). There were no significant differences in either neonatal morbidity or mortality. The addition of clindamycin to provide anaerobic coverage for intra-amnionic infection does not significantly alter the incidence of endometritis in women delivered by cesarean section, although it may have an impact on women delivering vaginally. Conventional reviews of research on the efficacy of psychological, educational, and behavioral treatments often find considerable variation in outcome among studies and, as a consequence, fail to reach firm conclusions about the overall effectiveness of the interventions in question. In contrast meta-analytic reviews show a strong, dramatic pattern of positive overall effects that cannot readily be explained as artifacts of meta-analytic technique or generalized placebo effects. Moreover, the effects are not so small that they can be dismissed as lacking practical or clinical significance. Although meta-analysis has limitations, there are good reasons to believe that its results are more credible than those of conventional reviews and to conclude that well-developed psychological, educational, and behavioral treatment is generally efficacious. A randomized trial of intrapartum versus postpartum antibiotic treatment of women with intra-amniotic infection was conducted. Intra-amniotic infection was treated with ampicillin and gentamicin during labor (at the time of diagnosis) in 26 women and immediately after umbilical cord clamping in 19 women. Intrapartum treatment led to a lower incidence of neonatal sepsis (0 versus 21%; P = .03) and a shorter neonatal hospital stay (3.8 versus 5.7 days; P = .02) when compared with postpartum treatment. There were no significant differences in the microbiologic results, the gestational age, or the birth weight between the groups. Intrapartum-treated mothers had a shorter mean postpartum stay, a lower mean number of febrile days, and a lower mean peak postpartum temperature than did postpartum-treated mothers; these differences were all statistically significant (P = .05). The treatment of clinical intra-amniotic infection during labor results in improved outcome. Health care practitioners and researchers commonly call for greater reliance on evidence as a means to achieve improvement in quality of care. Systematic reviews provide a means to accelerate the use of evidence-based clinical interventions and public health practices. The extent to which these time- and resource-intensive systematic reviews currently address critical maternal health priorities in the intrapartum period is unclear. This analysis summarises key maternal health and research priorities, maps these priorities to existing reviews, identifies gaps in the literature that can be addressed with systematic reviews, and highlights key methodological concerns in conducting systematic reviews. The analysis draws on published data on maternal morbidities and an overview of 108 systematic reviews in Medline in the past 5 years using the MeSH terms 'Delivery, Obstetric,' to draw the links between health priorities, research priorities, existing evidence and missing evidence. Key causes of morbidity during labour and delivery in the United States include haemorrhage, pre-eclampsia and eclampsia, obstetric trauma and infection. Analyses of maternal morbidity and mortality suggest that key concerns include racial and ethnic disparities in health outcomes and the prevention of adverse events. Systematic reviews, however, generally tend to focus on the reduction of harms associated with interventions, are frequently limited to randomised designs, and do not address issues of health disparities. The results suggest that advances in evidence-based care in maternal health require that systematic reviews address issues of prevention of adverse events, include a larger variety of study designs when necessary and pay closer attention to health disparities. Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.
                To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.
                Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).
                Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.
                The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.
                Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data. Although numerous reports have described interventions designed to influence antibiotic utilization, to our knowledge none have been evaluated in a randomized study.
                Adult inpatients receiving 1 or more of 10 designated parenteral antibiotics for 3 or more days during a 3-month period were randomized to an intervention (n = 141) and a control (n = 111) group using an unblocked, computer-generated random number table. Obstetric patients and those seen in infectious disease consultation were excluded. The intervention group received antibiotic-related suggestions from a team consisting of an infectious disease fellow and a clinical pharmacist. Both groups were evaluated for clinical and microbiological outcomes as well as antibiotic utilization via prospective chart reviews and analysis of the hospital's administrative database.
                Sixty-two (49%) of the intervention group patients received a total of 74 suggestions. Sixty-three (84%) of these suggestions were implemented; the majority involved changes in antibiotic choice, dosing regimen, or route of administration. Per patient antibiotic charges were nearly $400 less in the intervention group vs controls (P = .05). Almost all the savings were related to lower intravenous antibiotic charges. Clinical and microbiological response, antibiotic-associated toxic effects, in-hospital mortality, and readmission rates were similar for both groups. Multiple linear regression analysis identified randomization to the intervention group and female sex as the sole predictors of lower antibiotic charges. There was a trend toward a shorter length of stay for the intervention group (20 vs 24.7 days, P = .11).
                This is the first randomized study to evaluate whether antibiotic choices can be influenced in a cost-effective fashion without sacrificing patient safety. We demonstrate that 50% of patients initially treated with expensive parenteral antibiotics can have their regimens refined after 3 days of therapy and that these modifications result in good clinical outcomes with a substantial reduction in antibiotic expense. To evaluate the efficacy of intrapartum prophylactic administration of ampicillin-sulbactam in reducing intraamniotic infection and postpartum endometritis in patients with meconium-stained amniotic fluid (AF).
                Patients with intrapartum meconium-stained AF were randomized to receive either ampicillin-sulbactam or normal saline (placebo) intravenously at the time of diagnosis of meconium and every 6 hours until delivery. The outcomes of the two groups were compared with respect to intra-amniotic infection and postpartum endometritis.
                During the study period, 332 patients with meconium-stained AF were approached for participation, and 120 patients met inclusion criteria and were enrolled. Patient demographics, labor, and delivery characteristics were similar. Ampicillin-sulbactam reduced the incidence of intra-amniotic infection from 23.3 to 6.7%, (P = .02; relative risk [RR] 0.48, 95% confidence interval [CI] 0.22-0.98). The incidence of postpartum endometritis was also reduced, but the difference was statistically nonsignificant (8.3 versus 16.7%, P = .16; RR 0.64, 95% CI 0.30-1.33).
                Prophylactic intravenous ampicillin-sulbactam significantly reduces intra-amniotic infection in patients with meconium-stained AF. Objective: The purpose of this study was to determine if a dilute solution of chlorhexidine used as a one-time vaginal wash intrapartum can reduce the use of postnatal antibiotics and neonatal infection.Methods: Term pregnant women in labor were prospectively randomized to receive either 20 cc of 0.4% chlorhexidine (n = 481) or 20 cc of sterile water (n = 466) placebo. Exclusion criteria included fetal distress, clinical infection, cervical dilatation >6 cm, and known allergy to chlorhexidine. Outcome variables included the incidence of neonatal pneumonia, culture proven neonatal sepsis, and use of the antibiotics in the neonate. Continuous variables were compared using the Mann-Whitney U-test and discrete variables were compared with the chi-square test.Results: The length of ruptured membranes (mean +/- S.D.) between the chlorhexidine group (408 +/- 589 min) and control group (352 +/- 318 min) was not significantly different (P = 0.85, 95% confidence interval 354-462). Fifteen neonates (3.2%) in the chlorhexidine group and 9 (1.9%) in the control group received antibiotics in the postnatal period (P = 0.32, 95% confidence interval 0.72-3.72). There was one case of pneumonia in the control group and no cases of sepsis in either group.Conclusions: A one-time chlorhexidine vaginal wash does not decrease the use of antibiotics or incidence of neonatal infection in our population. Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists, a clinical microbiologist, and an infectious disease specialist. Of 252 consecutive inpatients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist, 127 were prospectively randomized to intervention and 125 to a control group. The groups were similar with regard to severity of illness, infection type, and time from admission to randomization. Physicians received timely, detailed reviews of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices, dosages, and rationales. Median length of stay after randomization for control and intervention groups was 9.0 days and 5.7 days, respectively (3.3-day difference, p=0.0001). Fifteen (12.0%) and eight patients (6.3%), respectively, died, although the time-specific mortality risk was not significantly different when length of postrandomization follow-up and time to death were taken into account. Physician acceptance of suggestions was 89%. Median patient charges for radiology, laboratory, pharmacy, and room were reduced by $4404/intervention, and median hospital costs were reduced by $2642/intervention. A multidisciplinary antimicrobial therapy team can be a useful information source for physicians, improve outcomes in hospitalized patients receiving intravenous antimicrobials, and result in substantial cost savings. Improving obstetric care in resource-limited countries is a major international health priority.
                To reduce infection rates after cesarean section by optimizing systems of obstetric care for low-income women in Colombia by means of quality improvement methods.
                Multidisciplinary teams in 2 hospitals used simple methods to improve their systems for prescribing and administering perioperative antibiotic prophylaxis. Process indicators were the percentage of women in whom prophylaxis was administered and the percentage of these women in whom it was administered in a timely fashion. The outcome indicator was the surgical site infection rate.
                Before improvement, prophylaxis was administered to 71% of women in hospital A; 24% received prophylaxis in a timely fashion. Corresponding figures in hospital B were 36% and 50%. Systems improvements included implementing protocols to administer prophylaxis to all women and increasing the availability of the antibiotic in the operating room. These improvements were associated with increases in overall and timely administration of prophylaxis (P<.001) in both hospitals by time series analysis, with adjustment for volume and case mix. After improvement, overall and timely administration of prophylaxis was 95% and 96% in hospital A and 89% and 96% in hospital B. In hospital A, the surgical site infection rate decreased immediately after the improvements (P<.001). In hospital B, the infection rate began a downward trend before the improvements that continued after their implementation (P =.04).
                Simple quality improvement methods can be used to optimize obstetric services and improve outcomes of care in resource-limited settings.
The conclusions that can be drawn from this meta-analysis are limited due to the small number of studies. For none of the outcomes was a statistically significant difference seen between the different interventions. Current consensus is for the intrapartum administration of antibiotics when the diagnosis of intraamniotic infection is made; however, the results of this review neither support nor refute this although there was a trend towards improved neonatal outcomes when antibiotics were administered intrapartum. No recommendations can be made on the most appropriate antimicrobial regimen to choose to treat intraamniotic infection.
[Note: The six citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]