AUTOP 2: Screen-and-treat Strategy for Vaginal Flora Abnormalities by Molecular Biology in Pregnant Women at High Risk of Preterm Birth

Overview

Preterm birth is a major cause of mortality and long-term disability. Bacterial vaginosis (BV) is a frequent form of dysbiosis that is often asymptomatic and increases the risk of preterm birth. BV is usually diagnosed using conventional tools such as the Nugent score. Molecular diagnosis of BV has now been shown to be more reproducible and to provide a more accurate characterization of dysbiosis. The main objective of this study is to evaluate the effectiveness of a self screen and treat strategy for vaginal flora dysbiosis, based on molecular point of care (POC) multiplex technology before 18 weeks' gestation, in reducing the rate of preterm birth among pregnant women at high risk, compared with usual care. The hypothesis is that a Screen-and-Treat strategy using molecular biology among women with previous preterm or/and an history of late abortion could be effective in reducing preterm births by 40%.

Preterm birth is an important cause of death and disabilities. Bacterial vaginosis (BV) is a common vaginal dysbiosis or abnormal microbiota, with a predominance of anaerobic bacteria with a lack of Lactobacillus with various diagnosis methods. Often asymptomatic, BV increases the risk of preterm birth according to the gestational age at diagnosis. BV is usually diagnosed by conventional diagnosis such as Nugent score. Molecular diagnosis of BV has now been demonstrated to be more reproducible, accurate and to better define dysbiosis. AUTOP was a large randomized multicentre trial to evaluate a "Screen and Treat" strategy for bacterial vaginosis using molecular diagnosis of self-collected vaginal samples in low-risk pregnant women during early pregnancy, with an evaluation of treatment success, and including vaginal swab controls. Among 6,671 randomized women, the Intent to treat analysis of the primary clinical outcome showed no evidence of a reduction in the rate of preterm birth with the screen and treat strategy compared with usual care. The rate of preterm birth was 3.9% (events=127) among 3,333 women in the screen and treat strategy group and 4.6% (events=153) among 3,338 in the control group (aOR, 0.82 \[95%CI, 0.65 to 1.05\]; P=.12). In the subgroup of nulliparous women (n=3,438), Screening and treating strategy was significantly more effective than usual care (aOR 0.61, 95% CI 0.44 to 0.82; Pinteraction=0.001). AUTOP I has been submit to JAMA at the beginning of 2023. AUTOP was the first randomized study that evaluates the impact of Screen and Treat strategies using molecular biology during pregnancy, except one ongoing study. The main objective of AUTOP 2 is to evaluate the effectiveness of a self screen and treat strategy for vaginal flora dysbiosis, based on molecular point of care (POC) multiplex technology before 18 weeks' gestation, in reducing the rate of preterm birth among pregnant women at high risk, compared with usual care. AUTOP 2 is a multicenter, prospective, randomized and parallel, open-label comparative, phase 3 study comparing 2 groups of pregnancy management in a population of pregnant women at high risk of preterm birth: * The experimental group (group A) with self vaginal screening with molecular multiplex biology. * The usual care group (group B) with no screening with multiplex molecular biology. Women will be screened for BV with conventional tools (pH, Amsel or Nugent score) as recommended by ANAES. Women under 25 years of age who are sexually active and/or at risk for sexually transmitted infections will be screened for Chlamydia trachomatis, as recommended by HAS. The recruitment goal is of 1794 women (897 per group).The period of inclusion has been scheduled to be 24 months s. Each woman will be followed until her newborn is discharged from the hospital, for a maximum of 4 months after delivery. Therefore, the maximum participation period is 12 months. A reduction in prematurity and/or late abortions in the group screening and treatment of vaginal flora abnormalities is expected. This strategy could be implemented routinely if the results were significant.