Vaginal microbiota and spontaneous preterm birth in pregnant women at high risk of recurrence.

We describe vaginal microbiota, including Gardnerella species and sexually transmitted infections (STIs), during pregnancy and their associations with recurrent spontaneous preterm birth (sPTB). We performed a prospective cohort study in a tertiary referral centre in the Netherlands, among pregnant women with previous sPTB <34 weeks' gestation. Participants collected three vaginal swabs in the first and second trimester. Vaginal microbiota was profiled with 16S rDNA sequencing. Gardnerella species and STI's were tested with qPCR. Standard care was provided according to local protocol, including screening and treatment for bacterial vaginosis (BV), routine progesterone administration and screening for cervical length shortening. Of 154 participants, 26 (16.9 %) experienced recurrent sPTB <37 weeks' gestation. Microbiota composition was not associated with sPTB. During pregnancy, the share of Lactobacillus iners-dominated microbiota increased at the expense of diverse microbiota between the first and second trimester. This change coincided with treatment for BV, demonstrating a similar change in microbiota composition after treatment. In this cohort of high-risk women, we did not find an association between vaginal microbiota composition and recurrent sPTB. This should be interpreted with care, as these women were offered additional preventive therapies to reduce sPTB according to national guidelines including progesterone and BV treatment. The increase observed in L. iners dominated microbiota and the decrease in diverse microbiota mid-gestation was most likely mediated by BV treatment. Our findings suggest that in recurrent sPTB occurring despite several preventive therapies, the microbe-related etiologic contribution might be limited.

Changes in the Prevalence of Infection in Pregnant Women during the COVID-19 Lockdown.

BACKGROUND: During the outbreak of SARS-CoV-2, strict mitigation measures and national lockdowns were implemented. Our objective was to investigate to what extent the prevalence of some infections in pregnancy was altered during different periods of the COVID-19 pandemic. METHODS: This was a single centre retrospective cohort study conducted in the Netherlands on data collected from electronic patient files of pregnant women from January 2017 to February 2021. We identified three time periods with different strictness of mitigation measures: the first and second lockdown were relatively strict; the inter-lockdown period was less strict. The prevalence of the different infections (Group B Streptococcus (GBS)-carriage, urinary tract infections and Cytomegalovirus infection) during the lockdown was compared to the same time periods in previous years (2017-2019). RESULTS: In the first lockdown, there was a significant decrease in GBS-carriage (19.5% in 2017-2019 vs. 9.1% in 2020; p = 0.02). In the period following the first lockdown and during the second, no differences in prevalence were found. There was a trend towards an increase in positive Cytomegalovirus IgM during the inter-lockdown period (4.9% in 2017-2019 vs. 12.8% in 2020; p = 0.09), but this did not reach statistical significance. The number of positive urine cultures did not significantly change during the study period. CONCLUSIONS: During the first lockdown there was a reduction in GBS-carriage; further studies are warranted to look into the reason why.

Working conditions in low risk nulliparous women in The Netherlands: are legislation and guidelines a guarantee for a healthy working environment? A cohort study.

OBJECTIVE: Hazardous working conditions increase the risk of adverse pregnancy outcomes. In this study, we examine adherence to legislation and guidelines aimed at improving working conditions in pregnancy. METHODS: Between 2014 and 2016, we recruited a prospective cohort of low-risk nulliparous pregnant women in paid employment or self-employed in 16 community midwifery practices in The Netherlands. Participants completed two questionnaires concerning demographics, education, general health and working conditions between 10-16 and 20-24 weeks of pregnancy. We calculated the proportion of participants with work-related risk factors not in accordance with legislation and/or guidelines. RESULTS: Of 269 participants included, 214 (80%) completed both questionnaires. At 10-16 weeks 110 (41%) participants and at 20-24 weeks 129 (63%) participants continued to work under circumstances that did not meet recommendations. Employers provided mandated information on work adjustment to 37 (15%) participants and 96 (38%) participants received no information about the potential hazards while working with biological and chemical hazards. Participants with lower educational attainment (aOR 2.2 95%CI 1.3-3.9), or employment in healthcare (aOR 4.5, 95%CI 2.2-9.0), education/childcare and social service (aOR 2.6, 95%CI 1.1-6.0 2),, catering (aOR 3.6, 95%CI 1.1-12) and industry, construction and cleaning (aOR 3.3, 95%CI 1.1-10.3) more often continued work which did not meet recommendations. CONCLUSION: There is poor adherence to national legislation and guidelines for safe working in pregnancy in The Netherlands: 50% of the pregnant women worked under hazardous conditions. Given the impact on adverse pregnancy outcomes as well as on the public purse, action to improve compliance must be taken by all stakeholders.

Risk factors for spontaneous preterm birth among healthy nulliparous pregnant women in the Netherlands, a prospective cohort study.

Introduction: Spontaneous preterm birth (sPTB) is a major contributor to neonatal morbidity and mortality worldwide. The pathophysiology of sPTB is poorly understood, in particular among nulliparous women without apparent medical or obstetric risk factors. Therefore, we aimed to identify risk factors for sPTB in healthy nulliparous women. Material and Methods: We performed a prospective cohort study. Recruitment took place from February 2014 to December 2016 in 16 community midwifery centers in the Netherlands. Eligibility criteria were: ≥18 years, no previous pregnancy >16 weeks of gestation, healthy singleton pregnancy, and antenatal booking <24 weeks of gestation. At study inclusion, participants completed a questionnaire, including details on lifestyle, work, and medical history. Cervical length was measured by vaginal ultrasound at the second-trimester anomaly scan. Detailed information concerning pregnancy and birth was collected via antenatal charts. We calculated the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for various risk factors with correction for socioeconomic status (SES) using logistic regression and Firth's correction. Results: We included 363 women of whom pregnancy outcomes were available in 349 (96.1%) participants. The cervical length measurement was available for 225 (62.0%) participants. sPTB occurred in 26 women (7.5%). SES was associated with sPTB (OR: 3.7, 95%  CI: 1.6-8.5) in univariate analysis. First or second trimester vaginal bleeding (aOR: 3.6, 95% CI: 1.4-9.0) and urinary tract infection during pregnancy (aOR: 4.9, 95% CI: 1.7-13.9) were associated with sPTB in multivariate analysis. Conclusions: This prospective cohort confirms established risk factors for sPTB in nulliparous women deemed at low risk of sPTB.

Enhanced IgA coating of bacteria in women with Lactobacillus crispatus-dominated vaginal microbiota.

BACKGROUND: Immunoglobulin A (IgA) plays an important role in maintaining a healthy intestinal microbiome, but little is known about the interaction between local immunoglobulins and the vaginal microbiome. We assessed immunoglobulins (unbound and bound to bacteria), their association with vaginal microbiota composition and the changes over time in 25 healthy women of reproductive age. RESULTS: In both Lactobacillus crispatus-dominated and non-L. crispatus-dominated microbiota, IgA and IgG (unbound and bound to bacteria) were higher during menses (T = 1) compared to day 7­11 (T = 2) and day 17­25 (T = 3) after menses onset. The majority of vaginal bacteria are coated with IgA and/or IgG. Women with L. crispatus-dominated microbiota have increased IgA coating of vaginal bacteria compared to women with other microbiota compositions, but contained less IgA per bacterium. Presence of a dominantly IgA-coated population at T = 2 and/or T = 3 was also strongly associated with L. crispatus-dominated microbiota. In women with non-L. crispatus-dominated microbiota, more bacteria were uncoated. Unbound IgA, unbound IgG, and bound IgG levels were not associated with microbiota composition. CONCLUSIONS: In conclusion, L. crispatus-dominated vaginal microbiota have higher levels of bacterial IgA coating compared to non-L. crispatus-dominated vaginal microbiota. Similar to its regulating function in the intestinal tract, we hypothesize that IgA is involved in maintaining L. crispatus-dominated microbiota in the female genital tract. This may play a role in L. crispatus-associated health benefits. Video abstract.

Asymptomatic vaginal Candida colonization and adverse pregnancy outcomes including preterm birth: a systematic review and meta-analysis.

OBJECTIVE: During pregnancy, vaginal colonization by Candida spp is common. Some studies suggest an association between asymptomatic vaginal Candida colonization and adverse pregnancy outcomes, but the evidence is inconsistent. This review aimed to systematically review the association between asymptomatic vaginal colonization by Candida spp and adverse pregnancy outcomes, including preterm birth. DATA SOURCES: We searched Ovid MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials from inception to May 6, 2020 for published studies on vaginal Candida/yeast and pregnancy outcomes. STUDY ELIGIBILITY CRITERIA: Cohort studies, case-control studies, and randomized controlled trials that included pregnant women who were tested for asymptomatic vaginal Candida colonization and reported on adverse pregnancy outcomes were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently selected and extracted the data. Critical appraisal was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies and the revised Cochrane risk-of-bias tool for randomized controlled trials. RESULTS: We found no significant difference in preterm birth rate between Candida-positive and Candida-negative women (odds ratio, 1.10; 95% confidence interval, 0.99-1.22; I2, 0%) in 15 studies among 33,321 women for either spontaneous preterm birth only (odds ratio, 1.13, 95% confidence interval, 0.97-1.31; I2, 0%) or all preterm birth (odds ratio, 1.04; 95% confidence interval, 0.79-1.35; I2, 21%). Subgroup analyses for a treatment strategy including only studies reporting on spontaneous preterm birth did not reveal any statistically significant associations either, although the odds ratio was increased for the untreated Candida-positive women (odds ratio, 1.28; 95% confidence interval, 0.90-1.81; I2, 13%) in 3 studies among 5175 women. Asymptomatic vaginal Candida colonization was not associated with small for gestational age, perinatal mortality, or any other adverse pregnancy outcome. CONCLUSION: Asymptomatic vaginal Candida colonization is not associated with preterm birth and other adverse pregnancy outcomes. Previous studies reported that treatment of this microorganism reduces preterm birth rate. Our results suggest that this effect is unlikely to rely on treatment of vaginal Candida.