The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis.

BACKGROUND: Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer. OBJECTIVE: To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta-analysis (registered in PROSPERO: CRD42018112862). SEARCH STRATEGY: PubMed, Web of science, Embase and Cochrane database. SELECTION CRITERIA: All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer. DATA COLLECTION AND ANALYSIS: For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals. MAIN RESULTS: Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus. CONCLUSIONS: These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease. TWEETABLE ABSTRACT: This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.

Expanding the reach of probiotics through social enterprises.

The rapid rise in microbiome and probiotic science has led to estimates of product creation and sales exceeding $50 billion within five years. However, many people do not have access to affordable products, and regulatory agencies have stifled progress. The objective of a discussion group at the 2017 meeting of the International Scientific Association for Probiotics and Prebiotics was to identify mechanisms to confer the benefits of probiotics to a larger portion of the world's population. Three initiatives, built around fermented food, were discussed with different methods of targeting populations that face enormous challenges of malnutrition, infectious disease, poverty and violent conflict. As new candidate probiotic strains emerge, and the market diversifies towards more personalised interventions, manufacturing processes will need to evolve. Information dissemination through scientific channels and social media is projected to provide consumers and healthcare providers with rapid access to clinical results, and to identify the nearest location of sites making new and affordable probiotic food and supplements. This rapid translation of science to individual well-being will not only expand the beneficiaries of probiotics, but also fuel new social enterprises and economic business models.

The Belgian Obstetric Surveillance System to monitor severe maternal morbidity.

BACKGROUND: In 2011 the Belgian Obstetric Surveillance System (B.OSS) was set up to monitor severe maternal morbidity in Belgium. AIM: The aim of B.OSS is to get an accurate picture of the obstetric complications under investigation and secondly, to improve the quality and safety of obstetric care in Belgium by practical recommendations based on the results. METHODOLOGY: Data are obtained through prospective active collection of cases by a monthly call according to the principle of nothing-to-report, along with data collection forms that confirm the diagnosis and gather detailed information. Data-collection occurs web-based since August 2013 through www.b-oss.be. RESULTS: B.OSS achieves excellent participation rates and response rates. The results of the first registration round are gradually brought out by means of scientific publications and presentations, biennial reports, newsletters and the website. The international comparison of results within the International Network of Obstetric Survey Systems (INOSS) gives important added value. No alternative mandatory data sources are appropriate to check for underreporting. CONCLUSIONS: B.OSS is successful in monitoring severe maternal morbidity thanks to the willingness of the Belgian OB-GYNs. The results of the first studies suggest the need to develop nationally adopted guidelines. Furthermore, the results invite to critically evaluate the current organisation of obstetric health care in Belgium. B.OSS aims to monitor the impact on patient safety in future surveys, when guidelines and recommendations are put into practice.

Nationwide population-based cohort study of uterine rupture in Belgium: results from the Belgian Obstetric Surveillance System.

OBJECTIVES: We aimed to assess the prevalence of uterine rupture in Belgium and to evaluate risk factors, management and outcomes for mother and child. DESIGN: Nationwide population-based prospective cohort study. SETTING: Emergency obstetric care. Participation of 97% of maternity units covering 98.6% of the deliveries in Belgium. PARTICIPANTS: All women with uterine rupture in Belgium between January 2012 and December 2013. 8 women were excluded because data collection forms were not returned. RESULTS: Data on 90 cases of confirmed uterine rupture were obtained, of which 73 had a previous Caesarean section (CS), representing an estimated prevalence of 3.6 (95% CI 2.9 to 4.4) per 10 000 deliveries overall and of 27 (95% CI 21 to 33) and 0.7 (95% CI 0.4 to 1.2) per 10 000 deliveries in women with and without previous CS, respectively. Rupture occurred during trial of labour after caesarean section (TOLAC) in 57 women (81.4%, 95% CI 68% to 88%), with a high rate of augmented (38.5%) and induced (29.8%) labour. All patients who underwent induction of labour had an unfavourable cervix at start of induction (Bishop Score ≤7 in 100%). Other uterine surgery was reported in the history of 22 cases (24%, 95% CI 17% to 34%), including 1 case of myomectomy, 3 cases of salpingectomy and 2 cases of hysteroscopic resection of a uterine septum. 14 cases ruptured in the absence of labour (15.6%, 95% CI 9.5% to 24.7%). No mothers died; 8 required hysterectomy (8.9%, 95% CI 4.6% to 16.6%). There were 10 perinatal deaths (perinatal mortality rate 117/1000 births, 95% CI 60 to 203) and perinatal asphyxia was observed in 29 infants (34.5%, 95% CI 25.2% to 45.1%). CONCLUSIONS: The prevalence of uterine rupture in Belgium is similar to that in other Western countries. There is scope for improvement through the implementation of nationally adopted guidelines on TOLAC, to prevent use of unsafe procedures, and thereby reduce avoidable morbidity and mortality.

Maternal Intensive Care': a systematic literature review.

OBJECTIVE: The objective of this systematic literature review is to review current scientific knowledge on the definition of and the indications for maternal/obstetric intensive care (MIC). METHODS: We conducted a extensive search in OVID MEDLINE, EMBASE, COCHRANE, CINHAL and CEBAM using the keywords: maternal/obstetric intensive care, subacute care, intermediate care, postacute care, critical care, sub intensive care, progressive patient care, postnatal care, perinatal care, obstetrical nursing, neonatology, pregnancy, maternal mortality/morbidity and pregnancy complication. A total of 180 articles and one guideline were identified and supplemented by a hand search. After title, abstract and full text evaluation, the articles and guideline were subjected to critical appraisal. RESULTS: Out of 180 potentially relevant articles, we identified 44 eligible articles of which 14 relevant MIC-articles of relatively good quality were selected. The concept 'maternal intensive care' was not found elsewhere, "high-dependency care" and "obstetrical intermediate care" appeared to be best comparable to what is understood as a MIC-service in Belgium. This thorough literature search resulted in a limited amount of scientific literature, with most studies retrospective observational tertiary centre based. No clear definition and admission criteria for maternal intensive care were found. CONCLUSION: This systematic literature review revealed that 1) there is no standard definition of maternal intensive care and 2) that admission criteria to a MIC unit differ widely. Further research is needed to create an evidence-based triage system to help clinicians attribute women to the appropriate level of care and thus stimulate an efficient utilization of maternal/obstetric intensive care services.

Gynaecological aspects of the treatment and follow-up of transsexual men and women.

The role of the gynaecologist in the treatment of female-to-male transsexual patients is largely confined to hysterectomy and vaginectomy. We showed that laparoscopic hysterectomy is feasible and safe in this group. When surgery is not performed completely, follow-up of the remaining organs is necessary. The major part of this thesis deals with the necessity and acceptability of gynaecological follow-up in male-to-female (MTF) transsexual patients. These patients function well on a physical, emotional, psychological and social level. Sexual function was less satisfactory, especially concerning arousal, lubrication and pain. Typical gynaecological exams proved to be feasible and well accepted. Transvaginal palpation of the prostate is of poor clinical value, in contrast to transvaginal ultrasound. Mammography was judged almost painless and 98% of transsexual women intend to return for screening. Since there is uncertainty about breast cancer risk in transsexual women, we conclude that breast screening in this population should not differ from that in biological women. Microflora and cytology of the penile skin-lined neovagina of transsexual women were described for the first time. Vaginal lactobacilli were largely lacking. A mixed microflora of aerobe and anaerobe species, usually found on skin, in bowel or in bacterial vaginosis microflora, was encountered. No high-grade cervical lesions were found, however, one patient displayed a low-grade lesion (positive for HR-HPV with koilocytes). Finally, low bone mass was highly prevalent in our study group. This finding appeared to be largely determined, in comparison to healthy males, by smaller bone size and a strikingly lower muscle mass.

Cytology of the 'penile' neovagina in transsexual women.

OBJECTIVE: The primary objective was to describe the neovaginal cytology in transsexual patients (n = 50) treated with the inverted penile skin technique. Secondary objectives were to compare our cytological findings with patient characteristics including use of oestrogens, sexual orientation and penetrative intercourse. METHODS: The medical and surgical history, sexual orientation and whether there was a current relationship were ascertained. A speculum examination was followed by microscopy of a Pap smear of the neovaginal vault. RESULTS: Well-preserved nucleated squamous cells were found in 72%. The correlation between their presence and sexual orientation was highly significant (P = 0.016), with those not sexually interested and homosexually oriented all having nucleated cells on the Pap smear. However, the correlation between these cells and penetrative intercourse failed to reach significance. Four samples showed atypical squamous cells of undetermined significance, all were negative for high-risk human papillomavirus (HR-HPV) types. One patient showed a low-grade squamous intraepithelial lesion that was HR-HPV positive. There was a significant correlation between the presence of cytological lesions and sexual orientation (P = 0.006). Four percentage of the specimens showed Döderlein bacilli. Inflammation was found in 30.6% of samples with squamous cells. CONCLUSIONS: The penile skin-lined neovagina of transsexual women can reflect the cytological findings present in biological women. However 'normal' cervical cytology, with superficial, intermediate and parabasal cells as well as Döderlein bacilli, was found in only 4% of transsexual women. Although one patient's Pap test showed koilocytes and was HR-HPV positive, no high-grade squamous intraepithelial lesions were identified.

Mammography and breast sonography in transsexual women.

Data on the necessity of performing screening mammographies in transsexual women are lacking. The main objective of this study was to assess the possibility to perform mammography and breast sonography in transsexual women. Fifty Dutch-speaking transsexual women were interviewed about the following: attitude towards mammography and breast sonography, importance attributed to and satisfaction with breast appearance, opinion about the necessity of breast check-up, expectations regarding discomfort during the exams and knowledge about the breast surgery. A fasting blood sample, clinical breast exam, mammography and breast sonography were performed. At mammography the following parameters were noted: density, technical quality, location of the prostheses, presence of any abnormalities and painfulness. At sonography the following parameters were recorded: density, presence of cysts, visualisation of retro-areolar ducts or any abnormalities. Twenty-three percent of patients are not aware of the type of breast implants and 79% do not know their position to the pectoral muscles. Patient satisfaction with the appearance of their breasts was rather high (7.94 on a scale of 0-10). Mean expected and experienced pain from mammography was low (4.37 and 2.00 respectively). There was no statistically significant difference in expected pain between those who already had mammography and those who did not. There was a significant positive correlation between the expected and the experienced pain. Mammography and breast sonography were technically feasible and no gross anomalies were detected. Since both exams were judged as nearly painless, 98% of transsexual women intended to come back if they would be invited. Since breast cancer risk in transsexual women is largely unknown and breast exams are very well accepted, breast screening habits in this population should not differ from those of biological women.

Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring.

Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.7-7.1 microg/ml. Mean dapivirine concentrations in vaginal and cervical tissues on day 7 were 0.3-0.7 microg/g in IPM001 and 1.5-3.5 microg/g in IPM008. Mean plasma concentrations of dapivirine were <50 pg/ml. Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations >1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.

Intimate Partner Violence. The gynaecologist's perspective.

Intimate partner violence (IPV) is an important public health problem, which has been extensively studied all over the world, yet Belgian data are limited. IPV remains a taboo resulting in denial and underreporting. For an obstetrician-gynaecologist (OB/GYN), IPV, committed by a male partner to a woman, is of particular interest, because of its negative impact on women's and children's health. In Belgium there are few data on IPV and guidelines for OB/GYN are -missing. In a multi-centered survey surveillance study which was carried out among pregnant women attending 5 large hospitals in the province of East Flanders, the lifetime prevalence of IPV was estimated to be 10.1% and the period prevalence during pregnancy and/or in the year preceding pregnancy 3.4%. In our highly medicalised society, only 19.2% and 6.6% of the victims of physical and sexual abuse respectively sought medical care. Routine screening for IPV by a general practitioner or OB/GYN was found to be largely acceptable. In a questionnaire-based Knowledge, Attitude, and Practice survey among OB/GYN in Flanders, OB/GYN prove -unfamiliar with IPV and largely underestimate the extent of the problem. Merely 6.8% of the respondents ever received any education on IPV. They refute the incentive of universal screening, even during pregnancy and one of the major barriers is fear of offending patients. Physician education was found to be the strongest predictor of a positive attitude towards screening and of current screening practices. Hence, there is a definite need to improve women's awareness regarding abuse and to endorse physician training on IPV.

Cutting edge: the vaginal microflora and bacterial vaginosis.

Under physiological conditions, the vaginal primarily harbours lactobacilli which ideally confer in mutualism with the vaginal epithelium colonisation resistance to other micro-organisms, thereby preventing ascending or systemic infection. Albeit only a few Lactobacillus species constitute the vaginal microflora, huge species- and strain-specific differences occur however, and these differences account for a wide variability in the intrinsic capability of the Lactobacillus microflora to maintain the vaginal ecosystem. Hence, among a substantial proportion of women, the picture of lactobacilli-driven mutualism is actually less ideal than one may assume. As the vagina is incessantly subjected to cyclic changes as well as behavioural exposures that may challenge the perpetuation of the Lactobacillus microflora, the intrinsic stability of the resident microflora is paramount to women's health. Considering the close concordance between the rectal and vaginal lactobacilli, future research may benefit from the study of food, oral, and intestinal microbiology in relation to the vaginal Lactobacillus microbiota. Loss of the hydrogen peroxide producing lactobacilli accompanied by massive anaerobic overgrowth is observed with bacterial vaginosis. Molecular studies of the bacterial vaginosis microflora have recently revealed a tremendous species variability further documenting the complex polymicrobial nature of this condition. Emerging issues include the predominance of G. vaginalis, a normal microflora constituent possibly eliciting a host of virulence mechanisms at increasing concentrations through quorum sensing, the associated abundance of A. vaginae as a rather specific marker of therapy failure and disease persistence or recurrence, and the discovery of an adherent, metronidazole-resistant biofilm consisting of the latter two species.

Sexual behaviour and contraceptive use among youth in the Balkans.

OBJECTIVES: To assess sexual and health seeking behaviour related to contraception among high school students in Bosnia (Sarajevo), the FYR of Macedonia (Skopje), and Serbia and Montenegro (Belgrade and Podgorica). METHODS: A standardized questionnaire was self-administered by 2150 urban high school students. Multiple logistic regression analyses accounting for within-class correlation were applied to identify determinants of sexual behaviour, and the use of contraception and sexual and reproductive health (SRH) care. RESULTS: In this group of youth with a mean age of 16.7 years, 41.3% of the boys and 20.8% of the girls had already experienced sexual intercourse. Mean age at sexual debut differed between sexually active boys (15.5) and girls (16.3). A condom was used at first sex by 73.7% of the boys and by 69.0% of the girls. Condoms were consistently used during sexual intercourse with the current or last partner by 64.3% of the boys and 48.5% of the girls. Oral contraception was resorted to by 0.0% (Macedonia) to 10.6% (Bosnia) of sexually active girls. One third of sexually active girls and 18.0% of sexually active boys had ever refrained from seeking medical advice on SRH despite feeling the need for it, mainly because of feelings of shame, fear and insecurity. TV or radio and friends were mostly mentioned as useful sources of information on contraceptives. CONCLUSIONS: Age at sexual debut and the proportion of sexually active youth in these Balkan states do not differ from those in other parts of Europe. However, declining condom use after sexual initiation is not compensated by having recourse to other contraceptive methods, as seen in some West-European countries. The role of mass media in dissemination of information and tackling barriers to SRH care should be explored.

Delayed childbearing and maternal mortality.

OBJECTIVES: To assess the maternal age trend in pregnant women in Flanders, Belgium, and examine the impact of maternal age on maternal mortality. STUDY DESIGN: Retrospective analysis of a population based regional perinatal database during one decade. RESULTS: Between 1991 and 2000 a significant increase in maternal age was found, in primiparous as well as in multiparous women. The maternal mortality ratio was 5.8, and strongly related to maternal age, with a relative risk of 7.0 (95% CI: 3.0-16.2) from the age of 35 on, and of 30.0 (95% CI: 11.4-80.6) in women aged 40 years or beyond. CONCLUSIONS: These data call for further research and action to facilitate career and reproduction, and for special care for older pregnant women.

Trends in caesarean section rates at a maternity hospital in Mumbai, India.

The steady rise in caesarean section rates is an emerging area of concern in mother-child healthcare and a matter of international attention, since the trend is no longer confined to western industrialized countries. Crude and caesarean section-related perinatal mortality and case-fatality rates may well serve as public-health indicators. Monitoring time-trends in caesarean section rates has been considered a useful approach in the recognition of this rapidly-changing health policy and in estimating the magnitude of this problem. The study examined the observed time-trends in caesarean section rates in relation to perinatal mortality rates and maternal case-fatality rates in a hospital setting in Mumbai, India, using 1957-1998 data on retrospective cohort. Both overall rates and those specific to type of delivery were assessed. During 1957-1998, the caesarean section rates in the Nowrosjee Wadia Maternity Hospital (NWMH) increased from 1.9% to 16%, with the most significant rise over the past decade. The perinatal mortality rate showed a significant reduction from 69 per 1,000 in 1957 to 36 per 1,000 in 1992 and remained steady in the 1990s despite the higher caesarean section rates. The caesarean section rate in the NWMH rose by almost 10-fold during 1957-1998. No improvement in perinatal outcome was observed beyond a caesarean section rate of 10%, but the perinatal mortality rate in caesarean births increased significantly due to a more liberal use of caesarean sections in preterm deliveries and those that yielded low-birth-weight babies.