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Introduction: Obstetric violence, or mistreatment of women in obstetric care, can have severe consequences such as fear of future childbirth, post-traumatic stress disorder, and depression., Material and Methods: The primary objective was to estimate the prevalence of obstetric violence in high-income countries. The secondary objective was to extract the main domains of obstetric violence perceived by women from qualitative studies. Following prospective registration (PROSPERO CRD42023468570), PubMed, Web of Science, Scopus, CINAHL, Embase, and Cochrane Library were searched with no restrictions. Included studies were cross-sectional, cohort, mixed methods, and qualitative studies based on populations from high-income countries. The review was conducted by two independent reviewers. Risk of bias was assessed. Rates of obstetric violence were pooled using random effects model, computing 95% confidence intervals (CI) and assessing heterogeneity using I 2 statistic. Funnel plots and Egger's test were used to detect potential reporting biases and small-study effects., Results: Of the 1821 records screened, 25 studies were included: 14 quantitative and 2 mixed methods studies, comprising 60 987 women, and 9 qualitative studies were included, comprising an additional 4356 women. 81.25% of quantitative studies, including the quantitative component of the mixed methods studies, were considered satisfactory or better regarding risk of bias. The prevalence of obstetric violence was overall 45.3% (95% CI 27.5-63.0; I 2  = 100.0%). The prevalence of specific forms of mistreatment was also estimated. Lack of access to analgesia was 17.3% (95% CI 6.9-27.7; I 2  = 99.7%). Ignored requests for help was 19.2% (95% CI 11.7-26.6; I 2  = 99.0%). Shouting and scolding 19.7% (95% CI 13.0-26.4; I 2  = 98.7%). The use of fundal pressure during the second stage of labor (Kristeller maneuver) was 30.3% (95% CI 22.1-38.5; I 2  = 97.6%). There was no funnel asymmetry. Lack of information and/or consent were the most frequent domains extracted from the qualitative articles and the qualitative component of the mixed methods studies., Conclusions: The results demonstrate that obstetric violence is a prevalent problem that women in high-income countries experience. Lack of information and/or consent were the domains most frequently described in the qualitative studies and the qualitative component of the mixed methods studies., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

The manuscript disputes the exclusive mono-infectious way of thinking, which presumes that for every infection only one pathogen is responsible and sufficient, when infectious vectors, close contact and reduced immunity meet. In situations involving heavily colonized anatomical sites such an approach often ends in insoluble contradictions. Upon critical reflection and evaluation of 20 years research on spatial organization of vaginal microbiota it is apparent, that in some situations, pathogens may act and operate in permanent, structurally organized consortia, whereas its individual components may be innocuous and innocent, failing to express any pathogenic effect. In these cases, consortia are the true pathogens responsible for many infectious conditions, which usually remain unrecognized as long as improperly diagnosed. The structure of such consortia can be unraveled using ribosomal fluorescence in situ hybridization (FISH). FISH methodology, that not only offers an ex vivo opportunity to recognize bacterial species, but provides unique physical insight into their specific role in the pathogenesis of polymicrobial infections. Ribosomal FISH technique applied to both, women with bacterial vaginosis (BV) and their male partners, has added significantly to our understanding of the pathogenesis of this condition and contributed to appreciating the mechanisms of polymicrobial, community-based infection, potentially leading to therapeutic advances., Competing Interests: Declaration of competing interest The authors have no conflict of interest (including financial commitments or ethical concerns). The data of this publication were not presented previously. The work has not been published previously and is not under consideration for publication elsewhere. No generative artificial intelligence was used. The publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out. If accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Phthalates freely cross the placenta and have the potential to influence pregnancy outcomes, with evidence of an increased incidence of preterm birth, low birth weight, pregnancy loss, and gestational diabetes. There is no regulation of phthalate concentrations in medications, which is often found in enteric coatings. Ingestion of phthalate containing medication during pregnancy may result in materno-fetal harm., Areas Covered: Phthalate subtypes, sources of phthalate exposure, mechanisms of phthalate toxicity, associations between phthalate exposure and incidence of preterm birth, low birth weight, fetal growth, gestational diabetes, and placental development., Expert Opinion: There is robust evidence to link exposure to phthalates in medical products including preterm birth, gestational diabetes, pregnancy-induced hypertension, and miscarriage. Nevertheless, future studies need to address standardization to avoid the heterogeneity of current studies. In future, the use of naturally occurring biopolymers may be safer, and the role of vitamin D as an immune modulator also has promise.

Background: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD., Objectives: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery., Data Sources: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis")., Study Selection and Data Extraction: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I 2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors., Results: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I 2  = 62%, and 0.59 (95% CI 0.42, 0.82), I 2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I 2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I 2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history., Conclusions: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Background: Listeria monocytogenes is a commonly found organism in processed and prepared food and the disease of listeriosis is associated with a high morbidity and mortality. Compared with the general population, the risk of being diagnosed with listeriosis increases during pregnancy. Listeriosis can lead to miscarriage, spontaneous preterm labour and preterm birth, stillbirth and congenital neonatal infections., Objectives: We conducted a universal review of listeriosis in pregnancy and in the newborn., Search Strategy: The EMBASE, PubMed, Cinahl and Web of Science databases were searched for systematic reviews indexed before 1 December 2020., Selection Criteria: Any systematic reviews evaluating the prevalence, treatment, diagnosis and effects of listeriosis during pregnancy and up to 4 weeks postnatally were included., Data Collection and Analysis: Eligibility assessment, data extraction and quality assessment by the Methodological Quality Assessment of Systematic Reviews (AMSTAR-2) were performed in duplicate., Main Results: We identified 397 citations of which nine systematic reviews comprising 330 studies and 487 patients' reviews were included. Most systematic reviews (seven of nine) were of moderate to high quality. Prevention in pregnant women was based on adherence to strict dietary recommendations, such as reheating leftovers until steamed and avoiding unpasteurised dairy products. Listeriosis infections were likely to occur in the third trimester (66%) rather than in the first trimester (3%) of pregnancy. Symptoms are mostly fever and other flu-like symptoms, such as fatigue. Diagnosis was primarily made by culture of the pathogen. Intravenous amoxicillin or ampicillin were first-line treatment., Conclusions: Listeriosis, a rare but serious infectious disease in pregnancy, can cause devastating consequences for the fetus and newborn. Appropriate preventative treatment should be initiated during early pregnancy to avoid complications., Tweetable Abstract: Listeria is commonly found in processed and prepared food. Prevention is the best way to avoid listeriosis during pregnancy., (© 2022 John Wiley & Sons Ltd.)

Bacteriophages are obligate intracellular viruses that parasitize bacteria, making use of the host biosynthetic machinery. Bacterial vaginosis (BV) causes serious adverse sequelae, such as sexually transmitted infections, seroconversion to HIV positivity, and preterm birth. The aetiology of BV is multifactorial, and the vaginal microbiota, the response to antibiotics, and the phenotypic outcomes differ between cases. The choice of antibiotics to treat BV depends on the clinician's personal experience, which contributes to the poor outcome of BV treatment and high recurrence rate. In this review, we classify BV into two subtypes based on whether or not the BV case is sexually associated (potentially phage-related). An appropriate antibiotic can be selected on the basis of this BV-typing to optimise the short- and long-term effects of treatment. Not all Lactobacillus spp. are helpful or protective and some may sequestrate metronidazole, which mitigates its therapeutic efficacy. Phages, used therapeutically, could contribute to eubiosis by sparing beneficial species of Lactobacilli . However, Lactobacilli have an important role in maintaining vaginal eubiosis, so conventional wisdom has been that treatment of BV may benefit from metronidazole that conserves lactobacilli rather than clindamycin, which destroys lactobacilli. Furthermore, if the quality and quantity of vaginal lactobacilli are compromised by phage colonisation, as in the sexually transmitted subtype, eradication of lactobacilli with clindamycin followed by replacement by probiotics may be better therapeutically than metronidazole and reduce recurrence rates. Accordingly, the subtype of BV may provide a more scientific approach to antibiotic selection, which is absent in current clinical guidelines. We provide support for the role of bacteriophages in the aetiology, recurrence or failure to cure BV following treatment, through parasitic colonisation of lactobacilli that may be sexually transmitted and may be enhanced by other risk factors like smoking, a factor associated with BV., Competing Interests: The authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2022 Lamont RF et al.)

Genital mycoplasmas (GM), such as Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum , and Ureaplasma urealyticum are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of membranes (PPROM). This study determined the association between GM and such adverse pregnancy outcomes. We searched for studies published 1980-2019 in MEDLINE, EMBASE, and Web of Science. Studies were eligible when GM was detected during pregnancy. We included 93 and 51 studies in determining the prevalence and the inflammatory biomarkers associated with GM, respectively, using the "metafor" package within R. The protocol was registered with PROSPERO (registration no. CRD42016047297). Women with the studied adverse pregnancy outcomes had significantly higher odds of presence with GM compared to women who delivered at term. For PTB, the odds ratios were: M. hominis (OR: 2.25; CI: 1.35-3.75; I 2 : 44%), M. genitalium (OR: 2.04; CIL 1.18-3.53; I 2 : 20%), U. parvum (OR: 1.75; CI: 1.47-2.07; I 2 : 0%), U. urealyticum (OR: 1.50; CI: 1.08-2.07; I 2 : 58%). SPTL had significantly higher odds with M. hominis (OR: 1.96; CI: 1.19-3.23; I 2 : 1%) or U. urealyticum (OR: 2.37; CI: 1.20-4.70; I 2 : 76%) compared to women without SPTL. Women with PPROM had significantly higher odds with M. hominis (OR: 2.09; CI: 1.42-3.08; I 2 : 0%) than women without PPROM. However, our subgroup analysis based on the diagnostic test and the sample used for detecting GM showed a higher prevalence of GM in maternal samples than in fetal samples. GM presence of the cervix and vagina was associated with lower odds of PTB and preterm labor (PTL). In contrast, GM presence in the AF, fetal membrane, and placenta was associated with increased odds of PTB and PTL. However, genital mycoplasmas may not elicit the massive inflammation required to trigger PTB. In conclusion, GM presence in the fetal tissues was associated with significantly increased odds of PTB and PTL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Noda-Nicolau, Tantengco, Polettini, Silva, Bento, Cursino, Marconi, Lamont, Taylor, Silva, Jupiter and Menon.)

Abnormal vaginal discharge may be caused by bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis and/or aerobic vaginitis. For the development of a diagnostic algorithm, tree-based classification analysis was performed on symptoms, signs and bedside test results of 56 patients, and laboratory tests (culture, Nugent score, qPCRs) were compared. Amplicon sequencing of the 16S rRNA gene was used as reference test for bacterial vaginosis and aerobic vaginitis, culture for vulvovaginal candidiasis and qPCR for trichomoniasis. For bacterial vaginosis, the best diagnostic algorithm was to screen at the bedside with a pH and odour test and if positive, to confirm by qPCR (sensitivity 94%; specificity 97%) rather than Nugent score (sensitivity of 59%; specificity 97%; P = 0.031). The analysis for the other infections was less conclusive due to the low number of patients with these infections. For bacterial vaginosis, the developed algorithm is sensitive, specific, and reduces the need for laboratory tests in 50% of the patients., Competing Interests: Declaration of competing interest WQ is a shareholder of DDL Diagnostic Laboratory. The other authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

"The bacterial vaginosis syndrome" has significant adverse effects for women and babies, including preterm birth and increased risk of acquisition of sexually transmitted infections and HIV. Currently, the gold standard for diagnosis is Gram stain microscopy of vaginal secretions, which is not readily available, is somewhat subjective, and does not differentiate between the likely different subtypes of vaginal dysbioses that may have different etiologies, microbiology, responses to antibiotics, and phenotypic outcomes. With new information from molecular-based, cultivation-independent studies, there is increasing interest in the use of molecular techniques for the diagnosis of bacterial vaginosis. We reviewed the current evidence on and the rationale behind the use of molecular techniques for the diagnosis of bacterial vaginosis. We found a number of commercially available molecular diagnostic tests, a few of which have US Food and Drug Administration (FDA) and/or Conformité Européenne in vitro diagnostic (CE-IVD) approval, and we have compared their performance with respect to sensitivities and specificities. Molecular-based tests have the advantage of objectivity, quantification, detection of fastidious organisms, and validity for self-obtained vaginal swabs. The performance of the molecular tests against standard microscopy is impressive, but further education of users on interpretation is needed. Bacterial vaginosis is the major cause of vaginal dysbiosis and should be recognized for the threat it is to women's genital tract health. Quantitative assessment of microbial abundance, the diversity of other organisms present, specific primers for gene sequence regions, and clades and biovars of target microbes should be recognized and incorporated into future molecular diagnostic tests to better differentiate between vaginal eubiosis and dysbiosis., Competing Interests: Ronald F. Lamont has advised Bayer, Becton, Dickinson and Company, Osmotech, and Symbiomix and has contributed to Scientific Meetings supported by Becton Dickinson and Hologic. Jan Stener Jorgensen has contributed to Scientific Meetings supported by Becton Dickinson and Hologic. Ellen H. A. van den Munckhof, Birgitte Møller Luef, and Christina Anne Vinter declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2020 Lamont RF et al.)

Introduction: Globally, preterm birth has replaced congenital malformation as the major cause of perinatal mortality and morbidity. The reduced rate of congenital malformation was not achieved through a single biophysical or biochemical marker at a specific gestational age, but rather through a combination of clinical, biophysical and biochemical markers at different gestational ages. Since the aetiology of spontaneous preterm birth is also multifactorial, it is unlikely that a single biomarker test, at a specific gestational age will emerge as the definitive predictive test., Methods: The Biomarkers Group of PREBIC, comprising clinicians, basic scientists and other experts in the field, with a particular interest in preterm birth have produced this commentary with short, medium and long-term aims: i) to alert clinicians to the advances that are being made in the prediction of spontaneous preterm birth; ii) to encourage clinicians and scientists to continue their efforts in this field, and not to be disheartened or nihilistic because of a perceived lack of progress and iii) to enable development of novel interventions that can reduce the mortality and morbidity associated with preterm birth., Results: Using language that we hope is clear to practising clinicians, we have identified 11 Sections in which there exists the potential, feasibility and capability of technologies for candidate biomarkers in the prediction of spontaneous preterm birth and how current limitations to this research might be circumvented., Discussion: The combination of biophysical, biochemical, immunological, microbiological, fetal cell, exosomal, or cell free RNA at different gestational ages, integrated as part of a multivariable predictor model may be necessary to advance our attempts to predict sPTL and PTB. This will require systems biological data using "omics" data and artificial intelligence/machine learning to manage the data appropriately. The ultimate goal is to reduce the mortality and morbidity associated with preterm birth., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Preterm birth remains the major cause of death and disability among children under the age of five. In developing countries antenatal preterm birth prevention clinics are set up to provide cervical length surveillance and/or treatment modalities such as cerclage or progesterone for those women with identified risk factors such as previous cervical treatment or preterm birth. However, 85% of women have no risk factors for PTB and currently there is no biomarker to screen women early in pregnancy. Women will present unexpectedly in threatened preterm labour and we have no choice but to adopt a re-active approach to their care by using predication and preparation strategies such as fetal fibronectin, tocolytic therapy and steroids. Despite these strategies approximately 15-20% of these women will give birth preterm before 34 weeks. There is a urgent need to re-design primary, secondary and tertiary prevention strategies for spontaneous preterm labour (sPTL) in singleton pregnancies aimed at identifying and addressing key gaps in clinical practice and research., (Copyright © 2020. Published by Elsevier Ltd.)

Background: There are concerns that the use of antibiotics before, during or immediately after pregnancy may have adverse effects on the neonatal gut microbiome and adversely affect the development of the infant immune system, leading to the development of childhood allergy, asthma, atopic disease and obesity. Methods: In this narrative review, we have explored a number of hypotheses, including the "Barker hypothesis", the "hygiene hypothesis", the link between inflammation and metabolic disease, and the influence of the neonatal gut microbiota on the development of the immune system in infants. Results: We found evidence to link the use of antibiotics before, during or immediately after pregnancy with an increased risk of childhood allergy, asthma, atopy and obesity. Conclusions : Although we found robust evidence to link antibiotic use in pregnancy with obesity and an "allergic triad" of asthma, eczema and hay fever, care must be taken when interpreting the findings because of the lack of adjustment for confounding variables in published studies. These may be (i) whether or not the mother had the same outcome variable (for example, asthma) as the infant, for which the mother may have received the antibiotics; (ii) the indication, timing or number of antibiotic courses given; (iii) the use of broad-spectrum or narrow-range antibiotics; (iv) the dose-dependent nature of the effector; and (v) the class of antibiotics used., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.Competing interests: David Eschenbach and Ronnie Lamont both hold Section Head positions on F1000Prime., (Copyright: © 2020 Lamont RF et al.)

Opioid use during pregnancy has serious consequences for mother and baby. The true extent of the problem is unknown and there is a need for better screening. Existing guidelines with respect to the management of pregnant women with opioid use are based on limited evidence. To improve recommendations for optimal identification, management, and treatment, publications on opioids in pregnancy were reviewed. Published literature from 2007 to 2017 was searched in PubMed, Cochrane and Embase databases. The review employed 60 publications from 210 studies identified, that were of varying quality and included randomized controlled trials, systematic reviews, meta-analyses, and Cochrane reviews. The prevalence of opioid use in pregnancy is underestimated. Screening by urine testing and self-reporting is acceptable to identify fetal exposure. To minimize risk, opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy. Future studies should elaborate on better objective screening methods to prevent the consequences of fetomaternal opioid exposure., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Over the past decades, there has been an increase in overweight and obesity in women of childbearing age, as well as the general population. Overweight and obesity are related to a later, increased risk of type 2 diabetes and cardiovascular diseases. Increasing weight between pregnancies has a negative impact on the development of the fetus in a subsequent pregnancy. It is also related to long-term obesity and overweight for the woman. Accordingly, weight control in women of the childbearing age is important for both women and their offspring. Information and communication technology (ICT) has become an integrated part of many peoples' lives, and it has the potential to prevent disease. In this systematic review, we summarize the evidence from randomized controlled trials to compare effects of different ICT-based interventions to support postpartum women to achieve weight loss., Methods: A systematic search was performed in PubMed, Embase, PsycInfo, CINAHL, Web of Science, Scopus, and Cochrane, searching on terms, such as postpartum, weight loss, telemedicine, and randomized controlled trials. Two independent researchers undertook study selection and data extraction. Results were reported narratively. The systematic review only included studies that were randomized controlled trials., Results: Eight studies were included in the systematic review. All of them were characterized by applying one or more ICT components to assist postpartum women in weight control, and had weight loss as an outcome measure. A significant difference was found in weight loss between control group and intervention group in the majority of the studies. However, five of the studies had a relatively short follow-up period (40 days to 16 weeks), six of the studies had a relatively small sample size (18 to 66 women), and half of the studies indicated challenges with adherence to the interventions over time., Conclusion: ICT-based interventions can support postpartum women to achieve a healthy lifestyle and weight control. Future studies should focus on larger sample sizes, longer follow-up periods, and adherence to the interventions., Systematic Review Registration: PROSPERO CRD42018080731.

Objective: To describe midwives' and obstetricians' experiences on the level of support from colleagues and managers in Danish labor wards following adverse events., Design, Setting and Participants: A 2012 National survey of Danish obstetricians and midwives was conducted to assess the level of support received in the workplace., Main Outcome Measures: Scales on social community at work, social support from colleagues and immediate superiors, and use of support mechanisms on labor wards after serious adverse events were assessed., Results: 2098 midwives and obstetricians were invited to complete the survey (response rate 59%), and the analyses were carried out on the 593 respondents who had been involved in at least one traumatic childbirth at their current place of work. Respondents experienced high levels of social support from colleagues and social community at work, midwives significantly higher than obstetricians, and 95% of respondents had talked to colleagues about an adverse event. Respondents generally experienced low levels of social support and feedback from immediate superiors, and only 49% had talked to their immediate superior about an adverse event. Fifty% believed that the hospital had a clear process through which they could report adverse events, and 44% knew how to access the necessary confidential emotional support at work., Conclusions: Midwives and obstetricians experienced high levels of social support and feedback from colleagues who are the most frequent individuals to consult after adverse events. We strongly suggest developing second victim support programmes with a focus on offering peer support from qualified and trained peers., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Phthalates are chemical compounds present in a wide range of consumer products and are thought to be endocrine disruptors. Though not commonly known, phthalates are present in some medication with previous studies finding up to 50-fold higher urinary metabolite concentrations among exposed compared to the general population. Previous studies on environmental phthalate exposure and pregnancy outcomes have been contradictory and inconclusive and all previous studies have assessed phthalate exposure using biomarkers despite a known rapid metabolism of phthalates., Objective: To determine whether phthalate exposure from pharmaceutical drugs have effects on preterm birth (PTB) and small for gestational age (SGA)., Study Design: We conducted a nested case-control study among women in Denmark with a recorded singleton birth and included women who conceived between January 1st, 2004 and December 31st, 2015. To mitigate drug effect and confounding by underlying disease we included pregnancies exposed to selected study drugs, and compared pregnancies exposed to phthalate containing drugs to pregnancies exposed to phthalate free generic drugs. Using Danish health registries, we identified 30,899 singleton pregnancies exposed to study drugs available in both phthalate-containing and phthalate free versions. Using conditional logistic regression, we estimated associations between phthalate exposure and the risk of PTB and SGA. Birth weight according to gestational age was defined by INTERGROWTH-21st (SGA-I) and by Marsal's equation (SGA-M) for expected birthweight., Results: We included 1965 PTBs, 1315 SGA-Is, and 891 SGA-M cases, matched to 19,537, 12,008, and 7573 controls, respectively. Orthophthalate exposure during the third trimester was positively associated with PTB with a crude OR of 1.36 (95% CI: 1.06-1.76). The association was mainly due to diethyl phthalate. Exposure to phthalate polymers in third trimester was associated with a risk of PTB with crude ORs of 2.08 (CI: 1.16-3.71. No associations were found between orthophthalate or phthalate polymer exposure and SGA., Conclusion: Exposure to some phthalate-containing pharmaceutical drugs during third trimester is associated with preterm birth., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Bacterial vaginosis (BV) is a common gynaecological condition. Diagnosis of BV is typically based on Amsel criteria, Nugent score and/or bacterial culture. In this study, these conventional methods and two CE-IVD marked quantitative real-time (q)PCR assays were compared with microbiota analysis for the diagnosis of BV. Eighty women were evaluated for BV during two sequential hospital visits by Amsel criteria, Nugent score, culture, the AmpliSens® Florocenosis/Bacterial vaginosis-FRT PCR kit (InterLabService, Moscow, Russia), and the BD MAX™ Vaginal Panel (BD Diagnostics, MD, USA). Microbiota analysis based on amplicon sequencing of the 16S ribosomal RNA gene was used as reference test. The microbiota profile of 36/115 (31%) included cases was associated with BV. Based on microbiota analysis, the sensitivity of detecting BV was 38.9% for culture, 61.15% for Amsel criteria, 63.9% for Nugent score and the BD MAX assay, and 80.6% for the AmpliSens assay, while the specificity of all methods was ≥ 92.4%. Microbiota profiles of the cases with discrepant results between microbiota analysis and the diagnostic methods were variable. All five diagnostic methods missed BV positive cases with a relatively high abundance of the genus Alloscardovia, Bifidobacterium, or Dialister, which were categorised as unspecified dysbiosis by the AmpliSens assay. Compared to Amsel criteria, Nugent score, culture, and the BD MAX assay, the AmpliSens assay was most in agreement with microbiota analysis, indicating that currently, the AmpliSens assay may be the best diagnostic method available to diagnose BV in a routine clinical setting.

Objective: To evaluate the cost-effectiveness of incisional negative pressure wound therapy (iNPWT) in preventing surgical site infection in obese women after caesarean section., Design: A cost-effectiveness analysis conducted alongside a clinical trial., Setting: Five obstetric departments in Denmark., Population: Women with a pregestational body mass index (BMI) ≥30 kg/m 2 ., Method: We used data from a randomised controlled trial of 876 obese women who underwent elective or emergency caesarean section and were subsequently treated with iNPWT (n = 432) or a standard dressing (n = 444). Costs were estimated using data from four Danish National Databases and analysed from a healthcare perspective with a time horizon of 3 months after birth., Main Outcome Measures: Cost-effectiveness based on incremental cost per surgical site infection avoided and per quality-adjusted life-year (QALY) gained., Results: The total healthcare costs per woman were €5793.60 for iNPWT and €5840.89 for standard dressings. Incisional NPWT was the dominant strategy because it was both less expensive and more effective; however, no statistically significant difference was found for costs or QALYs. At a willingness-to-pay threshold of €30,000, the probability of the intervention being cost-effective was 92.8%. A subgroup analysis stratifying by BMI shows that the cost saving of the intervention was mainly driven by the benefit to women with a pre-pregnancy BMI ≥35 kg/m 2 ., Conclusion: Incisional NPWT appears to be cost saving compared with standard dressings but this finding is not statistically significant. The cost savings were primarily found in women with a pre-pregnancy BMI ≥35 kg/m 2 ., Tweetable Abstract: Prophylactic incisional NPWT reduces the risk of SSI after caesarean section and is probably dominant compared with standard dressings #healtheconomics., (© 2018 Royal College of Obstetricians and Gynaecologists.)

Objective: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section., Design: Multicentre randomised controlled trial., Setting: Five hospitals in Denmark., Population: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m 2 ) undergoing elective or emergency caesarean section., Method: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention., Main Outcome Measures: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life., Results: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups., Conclusion: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section., Tweetable Abstract: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI., (© 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Objective: This systematic review aims to identify, critically appraise and summarize the results of studies examining the relationship between the vaginal microbiota and preterm birth (PTB)., Methods: We searched the electronic databases Medline, EMBASE and the Cochrane Controlled Register of Trials for studies in any language reporting on vaginal microbiota and PTB published from 1990 to November 29th, 2017. We included any study that performed lower genital tract microbiota assessment in asymptomatic pregnant women and reported on spontaneous preterm birth, with either intact or ruptured membranes., Results: The search strategy yielded 2171 unique citations, of which nine studies were eligible for inclusion in this review. In six studies an association was found between the composition of the vaginal microbiota and PTB, but findings differed between subgroups, ethnicities and degree of risk of PTB. In three studies no association was found. Two of these studies found a significant difference in richness and Shannon diversity between term and PTB., Conclusions: We have demonstrated that there is a paucity of molecular based, culture-independent studies that analyse the relationship between the vaginal microbiota and PTB as an outcome. The heterogeneity precluded a meta-analysis. Studies provide contradictory evidence and the quality of the clinical information in the studies is poor. To improve quality of future studies we have provided a database of essential and desirable items of quality that are method and topic specific., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: The objective was to provide an update of progress made over time (including personal reflection) of our attempts to reduce the mortality and morbidity associated with spontaneous preterm labour that leads to preterm birth., Methods: An experienced and evidence based approach was taken to provide an overview of progress made over a generation (∼40 years) in our understanding of spontaneous preterm labour., Results: It is evident that we have made significant progress in our understanding of the aetiology, the measurement of the burden, the basic science, systems biology and mechanical pathways of the preterm parturition syndrome. We have better ways of predicting, preventing and managing spontaneous preterm labour than existed a generation ago., Conclusions: The profile of spontaneous preterm labour that leads to preterm birth, thanks to organisations such as the March of Dimes, WHO and PREBIC is much more evident than before. However, while we have come a long way, we must not be complacent, and clinicians and basic scientists must continue to work in harmony, while recruiting and encouraging young investigators to join the effort to improve survival and handicap in what is one of the Great Obstetric Syndromes., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The use of antibiotics prenatally, during pregnancy, or neonatally may have adverse effects on the neonatal gut microbiome, and adversely affect the development of the infant immune system, leading to childhood atopy, asthma, allergy and obesity., Areas Covered: Vaginal eubiosis and dysbiosis from molecular-based, cultivation-independent techniques, and how this affects the neonatal gut microbiome and early development of the immune system, the association between maternal antibiotics and the beneficial role of vitamin D in the development of atopy, asthma, allergy and obesity, efforts to reduce the use of antibiotics in pregnancy and therapeutic interventions such as vaginal 'seeding', probiotics, breastfeeding and neonatal dietary supplementation., Expert Opinion: Currently available research gives insufficient attention to confounding variables. There remains uncertainty as to whether it is relevant that the mother suffered from the same condition as the purported infant outcome variable, for which she may have received antibiotics. In most studies, there is a lack of control for the number of antibiotic courses administered, the timing of use, the use of broad spectrum or narrow range antibiotics, the indication for antibiotics, the dose-dependent nature of the effect, the class of antibiotics used, or a varying degree of risk.

Background: Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous preterm labour., Objective: We have reviewed the evidence concerning the safety and efficacy of various classes of tocolytic agents., Results: The evidence to support the use of magnesium sulfate or nitric oxide donors as a tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and β2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of β2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses., Conclusion: The perfect tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

When a life is lost or severely impaired during childbirth, the midwife and obstetrician involved may experience feelings of guilt in the aftermath. Through three empirical cases, the paper examines the sense of guilt in the context of the current patient safety culture in healthcare where a blame-free approach is promoted in the aftermath of adverse events. The purpose is to illustrate how healthcare professionals may experience guilt without being at fault after adverse events, and Gamlund's theory on forgiveness without blame is used as the theoretical framework for this analysis. Philosophical insight has proven to be a useful resource in dealing with psychological issues of guilt and Gamlund's view on error and forgiveness elucidates an interesting dilemma in the field of traumatic events and medical harm in healthcare, where healthcare professionals experience that well-intended actions may cause injury, harm or even death to their patients. Failing to recognise and acknowledge guilt or guilty feelings may preclude self-forgiveness, which could have a negative impact on the recovery of midwives and obstetricians after adverse events. Developing and improving support systems for healthcare professionals is a multi-factorial task, and the authors suggest that the narrow focus on medico-legal and patient safety perspectives is complemented with moral philosophical perspectives to promote non-judgemental recognition and acknowledgement of guilt and of the fallible nature of medicine., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Infection/inflammation is responsible for a significant percentage of preterm birth, particularly at early gestations. A recent clinical recommendation by a guidelines group of the Danish Society of Obstetrics and Gynecology advised against the use of clindamycin for the treatment of bacterial vaginosis in pregnancy to reduce the risk of spontaneous preterm birth based on lack of evidence of efficacy. We believe that the evidence for the use of clindamycin for this indication is robust and that this recommendation was reached erroneously on the basis of flawed inclusion criteria: the inclusion of an unpublished study with poorly diagnosed bacterial vaginosis and the exclusion of an important pivotal study on the use of clindamycin in early pregnancy for the prevention of preterm birth. Had these errors been corrected, the conclusions would have been different., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Early onset neonatal Group B streptococcal disease is preventable. Intrapartum antibiotic prophylaxis has resulted in a significant reduction in neonatal mortality and morbidity. National guidelines for the selection of women eligible for intrapartum antibiotic prophylaxis, whether screening-based or risk-based, differ according to the local burden of disease. Despite the introduction of intrapartum antibiotic prophylaxis, there remains a significant burden of disease, which can be resolved by better adherence to guidelines, rapid identification of maternal colonization or in the future, vaccination. Areas covered: The introduction of a vaccine to women in the third trimester is likely to further reduce the burden of disease and provide benefits beyond the prevention of early neonatal disease, including meningitis and disability following late onset disease. Development of specific polyvalent vaccines continues, but testing has challenges and may require surrogate markers or molecular-based techniques to manipulate antigenicity and immunogenicity. Expert commentary: Group B streptococcal vaccination using conjugated polyvalent vaccines against the major disease causing serotypes of Group B streptococcus, either alone, or in combination with a policy of intrapartum antibiotic prophylaxis, may decrease the burden of Group B streptococcus beyond that achieved by current use of intrapartum antibiotic prophylaxis alone.

Objective: Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis., Materials and Methods: Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal biomarkers associated with PTB published from January 2005 to March 2014., Results: Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods., Conclusion: By this systematic review, we conclude that multiplex assays are a potential technological advancement for identifying biomarkers of PTB, although no single or combination of biomarkers could be identified to predict PTB risk.

Objective: this study investigates the self-reported psychosocial health and well-being of obstetricians and midwives in Denmark during the most recent four weeks as well as their recall of their health and well-being immediately following their exposure to a traumatic childbirth., Material and Methods: a 2012 national survey of all Danish obstetricians and midwives (n=2098). The response rate was 59% of which 85% (n=1027) stated that they had been involved in a traumatic childbirth. The psychosocial health and well-being of the participants was investigated using six scales from the Copenhagen Psychosocial Questionnaire (COPSOQII). Responses were assessed on six scales: burnout, sleep disorders, general stress, depressive symptoms, somatic stress and cognitive stress. Associations between COPSOQII scales and participant characteristics were analysed using linear regression., Results: midwives reported significantly higher scores than obstetricians, to a minor extent during the most recent four weeks and to a greater extent immediately following a traumatic childbirth scale, indicating higher levels of self-reported psychosocial health problems. Sub-group analyses showed that this difference might be gender related. Respondents who had left the labour ward partly or primarily because they felt that the responsibility was too great a burden to carry reported significantly higher scores on all scales in the aftermath of the traumatic birth than did the group who still worked on the labour ward. None of the scales were associated with age or seniority in the time after the traumatic birth indicating that both junior and senior staff may experience similar levels of psychosocial health and well-being in the aftermath. KEY CONCLUSIONS AND IMPLICATIONS: this study shows an association between profession (midwife or obstetrician) and self-reported psychosocial health and well-being both within the most recent four weeks and immediately following a traumatic childbirth. The association may partly be explained by gender. This knowledge may lead to better awareness of the possibility of differences related to profession and gender when conducting debriefings and offering support to HCPs in the aftermath of traumatic childbirth. As many as 85% of the respondents in this national study stated that they had been involved in at least one traumatic childbirth, suggesting that the handling of the aftermath of these events is important when caring for the psychosocial health and well-being of obstetric and midwifery staff., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%., Areas Covered: Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use., Expert Opinion: No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

Millions of doses of HPV vaccine have been administered globally. Inadvertent administration of HPV vaccine during pregnancy occurs given that the main recipients of the vaccine are fertile young women, who might be unaware of their pregnancy at the time of their vaccination. To investigate the subject of HPV vaccine and pregnancy , the databases of PubMed and Embase were searched to find the relevant literature published in English within the last 10 y. Most of the evidence pertaining to fetal adverse events following HPV vaccination relates to spontaneous miscarriage. None of the relevant studies found any significantly increased rate of spontaneous abortion in the overall analyses. There was no indication of other HPV vaccine-associated adverse events in pregnancy or immediately post-conception.

Introduction: When complications arise in the delivery room, midwives and obstetricians operate at the interface of life and death, and in rare cases the infant or the mother suffers severe and possibly fatal injuries related to the birth. This descriptive study investigated the numbers and proportions of obstetricians and midwives involved in such traumatic childbirth and explored their experiences with guilt, blame, shame and existential concerns., Material and Methods: A mixed methods study comprising a national survey of Danish obstetricians and midwives and a qualitative interview study with selected survey participants., Results: The response rate was 59% (1237/2098), of which 85% stated that they had been involved in a traumatic childbirth. We formed five categories during the comparative mixed methods analysis: the patient, clinical peers, official complaints, guilt, and existential considerations. Although blame from patients, peers or official authorities was feared (and sometimes experienced), the inner struggles with guilt and existential considerations were dominant. Feelings of guilt were reported by 36-49%, and 50% agreed that the traumatic childbirth had made them think more about the meaning of life. Sixty-five percent felt that they had become a better midwife or doctor due to the traumatic incident., Conclusions: The results of this large, exploratory study suggest that obstetricians and midwives struggle with issues of blame, guilt and existential concerns in the aftermath of a traumatic childbirth., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Postoperative wound complications are common following surgical procedures. Negative-pressure wound therapy (NPWT) is well recognized for the management of open wounds and has been applied recently to closed surgical incisions. The evidence base to support this intervention is limited. The aim of this study was to assess whether NPWT reduces postoperative wound complications when applied to closed surgical incisions., Methods: This was a systematic review and meta-analysis of randomized clinical trials of NPWT compared with standard postoperative dressings on closed surgical incisions., Results: Ten studies met the inclusion criteria, reporting on 1311 incisions in 1089 patients. NPWT was associated with a significant reduction in wound infection (relative risk (RR) 0·54, 95 per cent c.i. 0·33 to 0·89) and seroma formation (RR 0·48, 0·27 to 0·84) compared with standard care. The reduction in wound dehiscence was not significant. The numbers needed to treat were three (seroma), 17 (dehiscence) and 25 (infection). Methodological heterogeneity across studies led to downgrading of the quality of evidence to moderate for infection and seroma, and low for dehiscence., Conclusion: Compared with standard postoperative dressings, NPWT significantly reduced the rate of wound infection and seroma when applied to closed surgical wounds. Heterogeneity between the included studies means that no general recommendations can be made yet., (© 2016 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Introduction: The aim of this study was to evaluate the effect of an eHealth intervention (interactive website) on pregnant women's ability to make an informed choice about Down syndrome screening., Material and Methods: The study was designed as a randomized controlled trial with allocation to an intervention group and a control group in a ratio of 1:1. Subsequent subgroup analysis was conducted. Participants were recruited from 5 August 2013 to 25 April 2014 at Odense University Hospital, Denmark. Inclusion criteria were: pregnant women aged ≥18 years who were invited to participate in Down syndrome screening. Exclusion criteria were: high risk of abortion, psycho-socially vulnerable women, late referral, inability to speak Danish and women declining to participate. The primary outcome was informed choice about Down syndrome screening. The Multidimensional Measure of Informed Choice was used to assess whether the choice was informed or uninformed., Results: A total of 1150 participants were included in the study, of which 910 (79%) completed the questionnaire. Only a minority (30% of the women in the intervention group) actually used the website. There was no significant difference in the groups with respect to making an informed choice. The mean knowledge scores were significantly higher for those in the intervention group who used the intervention., Conclusions: An interactive website with information about Down syndrome screening had no direct effect on making an informed choice. However, the majority of the pregnant women who used the website were satisfied with the website and would recommend it to others., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Infection-related preterm birth (PTB) is more common at early gestational ages and is associated with major neonatal mortality and morbidity. Abnormal genital tract microflora in early pregnancy predicts late miscarriage and early PTB. Accordingly, it is logical to consider antibiotics as an intervention. Unfortunately, the conclusions of systematic reviews and meta-analyses (SR&MAs) carried out in an attempt to explain the confusion over the heterogeneity of individual studies are flawed by the fact that undue reliance was placed on studies which: (a) had a suboptimal choice of antibiotic (mainly metronidazole) or used antibiotics not recommended for the treatment of bacterial vaginosis (BV) or BV-related organisms; (b) used antibiotics too late in pregnancy to influence outcome (23-27 weeks); and (c) included women whose risk of PTB was not due to abnormal genital tract colonization and hence unlikely to respond to antibiotics. These risks included: (a) previous PTB of indeterminate etiology; (b) low weight/body mass index; or (c) detection of fetal fibronectin, ureaplasmas, Group B streptococcus or Trichomonas vaginalis). While individual studies have found benefit of antibiotic intervention for the prevention of PTB, in meta-analyses these effects have been negated by large methodologically flawed studies with negative results. As a result, many clinicians think that any antibiotic given at any time in pregnancy to any woman at risk of PTB will cause more harm than good. Recently, a more focused SR&MA has demonstrated that antibiotics active against BV-related organisms, used in women whose risk of PTB is due to abnormal microflora, and used early in pregnancy before irreversible inflammatory damage has occurred, can reduce the rate of PTB. This review presents those data, the background and attempts to explain the confusion using new information from culture-independent molecular-based techniques. It also gives guidance on the structure of putative future antibiotic intervention studies.