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1.  Antibiotics for treating bacterial vaginosis in pregnancy 
Bacterial vaginosis is an imbalance of the normal vaginal flora with an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary flora. Bacterial vaginosis during pregnancy has been associated with poor perinatal outcome and, in particular, preterm birth (PTB). Identification and treatment may reduce the risk of PTB and its consequences.
To assess the effects of antibiotic treatment of bacterial vaginosis in pregnancy.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (May 2006). We updated this search on 18 November 2010 and added the results to the awaiting classification section.
Selection criteria
Randomized trials comparing antibiotic treatment with placebo or no treatment, or comparing two or more antibiotic regimens in pregnant women with bacterial vaginosis or intermediate vaginal flora.
Data collection and analysis
Two review authors assessed trials and extracted data independently. We contacted study authors for additional information.
Main results
We included fifteen trials of good quality, involving 5888 women. Antibiotic therapy was effective at eradicating bacterial vaginosis during pregnancy (Peto odds ratio (OR) 0.17, 95% confidence interval (CI) 0.15 to 0.20; 10 trials, 4357 women). Treatment did not reduce the risk of PTB before 37 weeks (Peto OR 0.91, 95% CI 0.78 to 1.06; 15 trials, 5888 women), or the risk of preterm prelabour rupture of membranes (PPROM) (Peto OR 0.88, 95% CI 0.61 to 1.28; four trials, 2579 women). However, treatment before 20 weeks’ gestation may reduce the risk of preterm birth less than 37 weeks (Peto OR 0.72, 95% CI 0.55 to 0.95; five trials, 2387 women). In women with a previous PTB, treatment did not affect the risk of subsequent PTB (Peto OR 0.83, 95% CI 0.59 to 1.17, five trials of 622); however, it may decrease the risk of PPROM (Peto OR 0.14, 95% CI 0.05 to 0.38) and low birthweight (Peto OR 0.31, 95% CI 0.13 to 0.75)(two trials, 114 women). In women with abnormal vaginal flora (intermediate flora or bacterial vaginosis) treatment may reduce the risk of PTB before 37 weeks (Peto OR 0.51, 95% CI 0.32 to 0.81; two trials, 894 women). Clindamycin did not reduce the risk of PTB before 37 weeks (Peto OR 0.80, 95% CI 0.60 to 1.05; six trials, 2406 women).
Authors’ conclusions
Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. This review provides little evidence that screening and treating all pregnant women with asymptomatic bacterial vaginosis will prevent PTB and its consequences. However, there is some suggestion that treatment before 20 weeks’ gestation may reduce the risk of PTB. This needs to be further verified by future trials.
[Note: The eleven citations in the awaiting assessment section of the review may alter the conclusions of the review once assessed.]
PMCID: PMC4164464  PMID: 17253447
Anti-Bacterial Agents [*therapeutic use]; Pregnancy Complications, Infectious [*drug therapy]; Premature Birth [*prevention & control]; Randomized Controlled Trials as Topic; Vaginosis, Bacterial [*drug therapy]; Female; Humans; Pregnancy
2.  A cross-sectional study of maternal perception of fetal movements and antenatal advice in a general pregnant population, using a qualitative framework 
Maternal perception of fetal movements has been used as a measure of fetal well-being. Yet a Cochrane review does not recommend formal fetal movement counting compared to discretional fetal movement counting. There is some evidence that suggests that the quality of fetal movements can precede quantitative changes however there has been almost no assessment of how women describe movements and whether these descriptions may be useful in a clinical setting. Therefore we aimed to examine maternal perception of fetal movements using a qualitative framework.
Using a cross-sectional design we identified women during routine antenatal care at a tertiary referral hospital, in Sydney, Australia. Eligible women were pregnant ≥ 28 weeks, carrying a single child, > 18 years old, and with sufficient English literacy to self-complete a questionnaire. Post-natally the medical records were reviewed and demographic, pregnancy and fetal outcome data were extracted. Text responses to questions regarding maternal descriptions of fetal movements throughout pregnancy, were analysed using thematic analysis in an explicit process.
156 women participated. There was a general pattern to fetal movement descriptions with increasing gestation, beginning with words such as “gentle”, to descriptions of “strong” and “limb” movements, and finally to “whole body” movements. Women perceived and described qualitative changes to fetal movements that changed throughout gestation. The majority (83%) reported that they were asked to assess fetal movements in an implicit qualitative method during their antenatal care. In contrast, only 16% regularly counted fetal movements and many described counting as confusing and reported that the advice they had received on counting differed.
This is the first study to use qualitative analysis to identify that pregnant women perceive fetal movements and can describe them in a relatively homogenous way throughout pregnancy that follow a general pattern of fetal growth and development. These findings suggest that women’s perception of fetal wellbeing based on their own assessment of fetal movement is used in an ad hoc method in antenatal care by clinicians.
PMCID: PMC3572429  PMID: 23383737
Pregnancy; Fetal movement; Qualitative analysis; Cross-sectional study
3.  Risk factors for antepartum stillbirth and the influence of maternal age in New South Wales Australia: A population based study 
Maternal age is a known risk factor for stillbirth and delayed childbearing is a societal norm in developed country settings. The timing and reasons for age being a risk factor are less clear. This study aimed to document the gestational specific risk of maternal age throughout pregnancy and whether the underlying causes of stillbirth differ for older women.
Using linkage of state maternity and perinatal death data collections the authors assessed risk factors for antepartum stillbirth in New South Wales Australia for births between 2002 – 2006 (n = 327,690) using a Cox proportional hazards model. Gestational age specific risk was calculated for different maternal age groups. Deaths were classified according to the Perinatal Mortality Classifications of the Perinatal Society of Australia and New Zealand.
Maternal age was a significant independent risk factor for antepartum stillbirth (35 – 39 years HR 1.4 95% CI 1.12 – 1.75; ≥ 40 years HR 2.41 95% CI 1.8 – 3.23). Other significant risk factors were smoking HR 1.82 (95% CI 1.56 –2.12) nulliparity HR 1.23 (95% CI 1.08 – 1.40), pre-existing hypertension HR 2.77 (95% CI 1.94 – 3.97) and pre-existing diabetes HR 2.65 (95% CI 1.63 – 4.32). For women aged 40 or over the risk of antepartum stillbirth beyond 40 weeks was 1 in 455 ongoing pregnancies compared with 1 in 1177 ongoing pregnancies for those under 40. This risk was increased in nulliparous women to 1 in 247 ongoing pregnancies. Unexplained stillbirths were the most common classification for all women, stillbirths classified as perinatal infection were more common in the women aged 40 or above.
Women aged 35 or older in a first pregnancy should be counselled regarding stillbirth risk at the end of pregnancy to assist with informed decision making regarding delivery. For women aged 40 or older in their first pregnancy it would be reasonable to offer induction of labour by 40 weeks gestation.
PMCID: PMC3552834  PMID: 23324309
Stillbirth; Maternal age; Risk factors; Population-based; Data linkage
4.  A method for developing standardised interactive education for complex clinical guidelines 
BMC Medical Education  2012;12:108.
Although systematic use of the Perinatal Society of Australia and New Zealand internationally endorsed Clinical Practice Guideline for Perinatal Mortality (PSANZ-CPG) improves health outcomes, implementation is inadequate. Its complexity is a feature known to be associated with non-compliance. Interactive education is effective as a guideline implementation strategy, but lacks an agreed definition. SCORPIO is an educational framework containing interactive and didactic teaching, but has not previously been used to implement guidelines. Our aim was to transform the PSANZ-CPG into an education workshop to develop quality standardised interactive education acceptable to participants for learning skills in collaborative interprofessional care.
The workshop was developed using the construct of an educational framework (SCORPIO), the PSANZ-CPG, a transformation process and tutor training. After a pilot workshop with key target and stakeholder groups, modifications were made to this and subsequent workshops based on multisource written observations from interprofessional participants, tutors and an independent educator. This participatory action research process was used to monitor acceptability and educational standards. Standardised interactive education was defined as the attainment of content and teaching standards. Quantitative analysis of positive expressed as a percentage of total feedback was used to derive a total quality score.
Eight workshops were held with 181 participants and 15 different tutors. Five versions resulted from the action research methodology. Thematic analysis of multisource observations identified eight recurring education themes or quality domains used for standardisation. The two content domains were curriculum and alignment with the guideline and the six teaching domains; overload, timing, didacticism, relevance, reproducibility and participant engagement. Engagement was the most challenging theme to resolve. Tutors identified all themes for revision whilst participants identified a number of teaching but no content themes. From version 1 to 5, a significant increasing trend in total quality score was obtained; participants: 55%, p=0.0001; educator: 42%, p=0.0004; tutor peers: 57%, p=0.0001.
Complex clinical guidelines can be developed into a workshop acceptable to interprofessional participants. Eight quality domains provide a framework to standardise interactive teaching for complex clinical guidelines. Tutor peer review is important for content validity. This methodology may be useful for other guideline implementation.
PMCID: PMC3533506  PMID: 23131137
Practice guidelines as a topic; Implementation; Information dissemination; Education medical continuing; Interprofessional education; Action research; Perinatal mortality; Stillbirth; Fetal death
5.  Histological Chorioamnionitis Is Increased at Extremes of Gestation in Stillbirth: A Population-Based Study 
Objective. To determine the incidence of histological chorioamnionitis and a fetal response in stillbirths in New South Wales (NSW), and to examine any relationship of fetal response to spontaneous onset of labour and to unexplained antepartum death. Study Design. Population-based cohort study. Setting. New South Wales Australia. Population. All births between 2002 and 2004 with stillbirths reviewed and classified by the state perinatal mortality review committee. Methods. Record linkage of the Midwives Data Collection and the Perinatal Death Database including placental histopathology and standardised cause of death classification. Results. 952 stillbirths were included. The incidence of histopathological chorioamnionitis was 22.6%, with a bimodal distribution. A fetal inflammatory response was present in 10.1% and significantly correlated with spontaneous onset of labour. The absence of a fetal inflammatory response was strongly associated with unexplained antepartum death. Conclusions. The increased incidence of histological chorioamnionitis at extremes of gestation is confirmed in the largest dataset to date using population data. This has important implications for late gestation stillbirth as the percentage of unexplained stillbirths increases near term.
PMCID: PMC3140189  PMID: 21785555
6.  An evaluation of classification systems for stillbirth 
Audit and classification of stillbirths is an essential part of clinical practice and a crucial step towards stillbirth prevention. Due to the limitations of the ICD system and lack of an international approach to an acceptable solution, numerous disparate classification systems have emerged. We assessed the performance of six contemporary systems to inform the development of an internationally accepted approach.
We evaluated the following systems: Amended Aberdeen, Extended Wigglesworth; PSANZ-PDC, ReCoDe, Tulip and CODAC. Nine teams from 7 countries applied the classification systems to cohorts of stillbirths from their regions using 857 stillbirth cases. The main outcome measures were: the ability to retain the important information about the death using the InfoKeep rating; the ease of use according to the Ease rating (both measures used a five-point scale with a score <2 considered unsatisfactory); inter-observer agreement and the proportion of unexplained stillbirths. A randomly selected subset of 100 stillbirths was used to assess inter-observer agreement.
InfoKeep scores were significantly different across the classifications (p ≤ 0.01) due to low scores for Wigglesworth and Aberdeen. CODAC received the highest mean (SD) score of 3.40 (0.73) followed by PSANZ-PDC, ReCoDe and Tulip [2.77 (1.00), 2.36 (1.21), 1.92 (1.24) respectively]. Wigglesworth and Aberdeen resulted in a high proportion of unexplained stillbirths and CODAC and Tulip the lowest. While Ease scores were different (p ≤ 0.01), all systems received satisfactory scores; CODAC received the highest score. Aberdeen and Wigglesworth showed poor agreement with kappas of 0.35 and 0.25 respectively. Tulip performed best with a kappa of 0.74. The remainder had good to fair agreement.
The Extended Wigglesworth and Amended Aberdeen systems cannot be recommended for classification of stillbirths. Overall, CODAC performed best with PSANZ-PDC and ReCoDe performing well. Tulip was shown to have the best agreement and a low proportion of unexplained stillbirths. The virtues of these systems need to be considered in the development of an international solution to classification of stillbirths. Further studies are required on the performance of classification systems in the context of developing countries. Suboptimal agreement highlights the importance of instituting measures to ensure consistency for any classification system.
PMCID: PMC2706223  PMID: 19538759
7.  Causes of death and associated conditions (Codac) – a utilitarian approach to the classification of perinatal deaths 
A carefully classified dataset of perinatal mortality will retain the most significant information on the causes of death. Such information is needed for health care policy development, surveillance and international comparisons, clinical services and research. For comparability purposes, we propose a classification system that could serve all these needs, and be applicable in both developing and developed countries. It is developed to adhere to basic concepts of underlying cause in the International Classification of Diseases (ICD), although gaps in ICD prevent classification of perinatal deaths solely on existing ICD codes.
We tested the Causes of Death and Associated Conditions (Codac) classification for perinatal deaths in seven populations, including two developing country settings. We identified areas of potential improvements in the ability to retain existing information, ease of use and inter-rater agreement. After revisions to address these issues we propose Version II of Codac with detailed coding instructions.
The ten main categories of Codac consist of three key contributors to global perinatal mortality (intrapartum events, infections and congenital anomalies), two crucial aspects of perinatal mortality (unknown causes of death and termination of pregnancy), a clear distinction of conditions relevant only to the neonatal period and the remaining conditions are arranged in the four anatomical compartments (fetal, cord, placental and maternal).
For more detail there are 94 subcategories, further specified in 577 categories in the full version. Codac is designed to accommodate both the main cause of death as well as two associated conditions. We suggest reporting not only the main cause of death, but also the associated relevant conditions so that scenarios of combined conditions and events are captured.
The appropriately applied Codac system promises to better manage information on causes of perinatal deaths, the conditions associated with them, and the most common clinical scenarios for future study and comparisons.
PMCID: PMC2706222  PMID: 19515228
8.  Dopamine and Ethanol Cause Translocation of εPKC Associated with εRACK: Cross-talk Between PKA and PKC Signaling Pathways 
Molecular pharmacology  2008;73(4):1105-1112.
Previously we found that neural responses to ethanol and the dopamine D2 receptor (D2) agonist NPA involve both epsilon protein kinase C (εPKC) and cAMP-dependent protein kinase A (PKA). However, little is known about the mechanism underlying ethanol- and D2-mediated activation of εPKC and the relationship to PKA activation. In the present study, we used a new εPKC antibody, 14E6, that selectively recognizes active εPKC when not bound to its anchoring protein εRACK (receptor for activated C-kinase), and PKC isozyme-selective inhibitors and activators, to measure PKC translocation and catalytic activity. We show here that ethanol and NPA activated εPKC and also induced translocation of both εPKC and its anchoring protein, εRACK to a new cytosolic site. The selective εPKC agonist, pseudo-εRACK, activated εPKC but did not cause translocation of the εPKC/εRACK complex to the cytosol. These data suggest a step-wise activation and translocation of εPKC following NPA or ethanol treatment where εPKC first translocates and binds to its RACK and subsequently the εPKC/εRACK complex translocates to a new subcellular site. Direct activation of PKA by Sp-cAMPS, PGE1 or the adenosine A2A receptor is sufficient to cause εPKC translocation to the cytosolic compartment in a process that is dependent on PLC activation and requires PKA activity. These data demonstrate a novel cross-talk mechanism between εPKC and PKA signaling systems. PKA and PKC signaling have been implicated in alcohol rewarding properties in the mesolimbic dopamine system. Cross-talk between PKA and PKC may underlie some of the behaviors associated with alcoholism.
PMCID: PMC2692587  PMID: 18202306

Results 1-8 (8)