Reducing stillbirths: interventions during labour. Anaerobic coverage for intra-amnionic infection: maternal and perinatal impact.
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.
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.]