Recent advances in the diagnosis and management of sepsis in pregnancy.

Background: Maternal sepsis accounts for 11% of all maternal deaths worldwide. It is the third most common direct cause of maternal death and is a major contributor to other common causes of maternal death, such as haemorrhage and thromboembolism. Methods: This review addresses important topics, including the epidemiology, risk factors, prevention, diagnosis, care bundles and management of maternal sepsis, including antibiotic treatment, and critical care interventions such as extracorporeal membrane oxygenation. Preventative measures that have had an impact on maternal sepsis as well as future research directions are also covered in this review. Case studies of maternal sepsis which highlight key learning points relevant to all clinicians involved in the management of obstetric patients will also be presented. Results: Although, historically, maternal death from sepsis was considered to be a problem for low-income countries, severe obstetric morbidity and maternal death from sepsis are increasing in high-income countries. The global burden of maternal sepsis and the obstetric-related and patient-related risk factors and the likely sources are presented. Recent changes in definition and nomenclature are outlined, and challenges in diagnosis and identification are discussed. Conclusions: Following maternal sepsis, early diagnosis and early intervention are critical to save lives and prevent long-term adverse sequelae. Dogma surrounding critical care interventions in pregnancy is being challenged, and future research is warranted to maximise therapeutic options available for maternal septic shock.

The quality of nifedipine studies used to assess tocolytic efficacy: a systematic review.

OBJECTIVE: To assess the quality of studies of nifedipine used to treat spontaneous preterm labor. DESIGN: A systematic review of study quality using a novel validity assessment tool, examining method-specific and topic-specific items in the domains of selection, performance and measurement biases. DATA SOURCES: Medline (1996-2003), EMBASE (1996-2003), BIOSIS (1993-2003), Current Contents (1995-2003), DERWENT DRUGFILE (1983-2003), Cochrane Database of Systematic Reviews. Bibliographies of existing meta-analyses and systematic reviews of nifedipine as a tocolytic. METHODS OF STUDY SELECTION: Forty-five studies evaluating the effectiveness of nifedipine were identified. DATA EXTRACTION: Each study was assessed for 40 method-specific and topic-specific items of quality in duplicate using piloted data extraction forms. Disagreements between assessors were settled by consensus/arbitration. DATA SYNTHESIS: Very few of the studies complied with adequacy criteria of quality for either method-specific or topic-specific items. There was no improvement in quality over time. The quality of method-specific items was significantly poorer when compared with topic-specific items of quality overall (P<0.0001) and in the domains of selection bias (P<0.0001) and performance bias (P<0.0001). CONCLUSION: Studies of the effectiveness of nifedipine as a tocolytic are of poorer quality with respect to method-specific items than topic-specific items. These deficiencies should be highlighted in meta-analyses or systematic reviews which measure efficacy and should influence the generation of guideline statements or recommendations for the use of nifedipine as a tocolytic. A large randomized trial fulfilling the quality items is necessary to assess the real efficacy of nifedipine in preterm labor.

Can antibiotics prevent preterm birth--the pro and con debate.

Studies using different diagnostic methods and outcome parameters have used different antibiotics and dose/administration regimes to women of differing risk of preterm birth with, not surprisingly, different results. Studies which have shown benefit have been criticised for having either poor methodology, low sample size or having only showed benefit after a non-prespecified subgroup analysis. Studies which have failed to show any benefit have been criticised for unacceptable methods of diagnosing abnormal genital tract flora or having excluded a large percentage of patients eligible for the study, for having permitted a long period to elapse from diagnosis of abnormal genital tract flora to administration of treatment and for having employed treatment too late in pregnancy. A Cochrane Systematic Review of these studies failed to provide a definitive answer because this was published one month before two randomised double-blind placebo-controlled trials were published, in which clindamycin used either systemically or intravaginally in low risk, unselected women resulted in a 60% reduction in the incidence of preterm birth. This would have influenced the inconclusive results of the Cochrane review, with respect to general population studies. Very early spontaneous preterm labour and preterm birth is more likely to be of infectious aetiology than preterm birth just before term. The earlier in pregnancy at which abnormal genital tract flora is detected, the greater is the risk of an adverse outcome. Women with abnormal flora in early pregnancy, who subsequently revert to normal, continue to have a high risk of adverse outcome of pregnancy, at a degree similar to women with abnormal genital tract flora in early pregnancy who were treated with placebo. This suggests that whatever damage abnormal flora induces, this is at an early gestation, even if the flora subsequently reverts to normal. It follows therefore that if antibiotics are to be of help in preventing spontaneous preterm labour and preterm birth of infectious aetiology, these must be administered early in pregnancy. Antibiotics used prophylactically for the prevention of preterm birth are more likely to be successful if: they are used in women with abnormal genital tract flora (rather than other risk factors for preterm birth, e.g. low BMI, twins, generic previous preterm birth); they are used early in pregnancy prior to infection (tissue penetration/inflammation and tissue damage); they are used in women with the greatest degree of abnormal genital tract flora; and if they are used in women with a predisposition to mount a damaging inflammatory response to infection.

Recent evidence associated with the condition of preterm prelabour rupture of the membranes.

PURPOSE OF REVIEW: The published literature on preterm prelabour rupture of the membranes is voluminous yet despite advances in obstetric and neonatal care, the problem remains a major cause of perinatal mortality and morbidity. The purpose of this review is to present recent evidence pertaining to the role of inflammatory mediators such as cytokines and the tissue damage and long-term handicap they cause, the molecular biology and physiology of membrane structure, the role of host susceptibility and the genetics of preterm birth and therapeutic options for the management of preterm prelabour rupture, including antibiotics, amnioinfusion and special situations. RECENT FINDINGS: Neonatal morbidity from preterm prelabour rupture of the membranes is mainly related to oligohydramnios and pulmonary hypoplasia. Occupational factors have a significant effect on the occurrence and outcome following rupture. Matrix metalloproteinases control growth and remodelling of the pregnant uterus, placenta and membranes and are linked to a genetic predisposition to preterm birth through gene expression and variation. Transvaginal ultrasound scan, oncofetal fibronectin and the presence of abnormal genital tract flora (bacterial vaginosis) in pregnancy may help in the prediction of preterm birth. SUMMARY: Preterm prelabour membrane rupture remains a management problem, particularly at very early gestations, yet obstetric and neonatal care can make a difference to outcome. While at early gestations the prognosis is poor, it is not hopeless. Careful selection of the recent literature on the subject might interest and inform those faced regularly with the problem, prevent therapeutic nihilism, promote confidence in our ability to make a difference and realise that we are not alone when faced with the therapeutic dilemma that is this condition.