Vaginal bacterial load in the second trimester is associated with early preterm birth recurrence: a nested case-control study.

OBJECTIVE: To assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM). DESIGN: Nested case-control study. SETTING: UK tertiary referral hospital. SAMPLE: High-risk women with previous sPTB/PPROM <34+0 weeks' gestation who had a recurrence (n = 22) or delivered at ≥37+0 weeks without PPROM (n = 87). METHODS: Vaginal swabs collected between 15 and 22 weeks' gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR. MAIN OUTCOME MEASURE: Recurrent early sPTB/PPROM. RESULTS: Of the 109 high-risk women, 28 had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (Lactobacillus iners 36/109, Lactobacillus crispatus 23/109, or other 22/109). VMB type and diversity were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 versus 7.89 log10 cells/mcl, adjusted odds ratio [aOR] 1.90, 95% CI 1.01-3.56, P = 0.047) and estimated Lactobacillus concentration (8.59 versus 7.48 log10 cells/mcl, aOR 2.35, (95% CI 1.20-4.61, P = 0.013). A higher recurrence risk was associated with higher median bacterial loads for each VMB type after stratification, although statistical significance was reached only for L. iners domination (aOR 3.44, 95% CI 1.06-11.15, P = 0.040). Women with anaerobic dysbiosis or L. iners domination had a higher median vaginal bacterial load than women with a VMB dominated by L. crispatus or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log10 cells/mcl, respectively). CONCLUSIONS: Vaginal bacterial load is associated with early sPTB/PPROM recurrence. Domination by lactobacilli other than L. iners may protect women from developing high bacterial loads. Future PTB studies should quantify vaginal bacteria and yeasts. TWEETABLE ABSTRACT: Increased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.

Lactobacilli-containing vaginal probiotics to cure or prevent bacterial or fungal vaginal dysbiosis: a systematic review and recommendations for future trial designs.

BACKGROUND: Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. OBJECTIVES: We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. SEARCH STRATEGY: We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. SELECTION CRITERIA: There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. DATA COLLECTION AND ANALYSIS: The authors independently extracted data. MAIN RESULTS: All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. CONCLUSIONS: Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development and to conduct future trials more rigorously. TWEETABLE ABSTRACT: Lactobacilli-containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis.

Family history of neurodegenerative and vascular diseases in ALS: a population-based study.

OBJECTIVE: To determine whether the frequency of Parkinson disease (PD), dementia, and vascular diseases in relatives of patients with amyotrophic lateral sclerosis (ALS) differs from the frequency of those diseases in relatives of controls, providing further information about the association between these diseases. METHODS: We studied the occurrence of neurodegenerative and vascular diseases in families of patients with ALS in a prospective, population-based, case-control study in the Netherlands between 2006 and 2009, using the recurrence risk λ. Family history data were obtained by asking participants to fill in questionnaires. RESULTS: A total of 635 patients and 1,616 controls were included. The frequency of dementia was mildly increased only among parents and siblings of patients with sporadic ALS (λ1.32; 95 confidence interval [CI] 1.10-1.59), not among grandparents, or aunts and uncles. The risk of PD was not elevated (any relative: λ 0.91; 95% CI 0.70-1.17). Among relatives of patients with familial ALS, no significantly increased risk of neurodegenerative diseases was found. A reduced risk of vascular diseases was found in relatives of patients with sporadic ALS (stroke: λ 0.90; 95% CI 0.80-1.01 and myocardial infarction: λ 0.86; 95% CI 0.79-0.94), and in relatives of patients with familial ALS (stroke: λ 0.88; 95% CI 0.61-1.27 and myocardial infarction: λ 0.61; 95% CI 0.43-0.86). CONCLUSIONS: This large, prospective, population-based study showed that familial aggregation of ALS, dementia, and PD is substantially lower than previously thought. The lowered risk of vascular diseases in relatives of patients with ALS supports the view that a beneficial vascular risk profile increases ALS susceptibility.