Introduction: Preterm birth is the leading cause of perinatal mortality worldwide, with prevalence rates showing little reduction. Although mortality rates have decreased, morbidity rates remain concerningly high. In recent years, there has been a surge in studies examining the etiology, risk factors, and management of preterm birth. The use of vaginal probiotics in pregnant women at risk of preterm birth has garnered attention as a potential approach for improving perinatal outcomes and modulating the vaginal microbiota. However, the efficacy of this intervention remains unclear. Therefore, this study explored the impact of vaginal probiotics on perinatal outcomes and vaginal microbiota composition in pregnant women at risk of preterm birth. Materials and Methods: This was a randomized, prospective, longitudinal, double-blind, placebo-controlled, multicentric trial conducted across seven maternities in Spain from October 2017 to August 2022 in pregnant women at risk of preterm birth. Participants were randomly assigned to receive vaginal probiotics containing four lactobacilli strains or a placebo. The primary outcome was to explore a potential correlation between probiotic use among pregnant women at risk of preterm birth and the actual rate of preterm birth before 37 gestational weeks. Secondary outcomes included an evaluation of preterm birth rates, neonatal morbidity, the vaginal microbiota, and changes in the vaginal microbiota after receiving probiotics. Other secondary outcomes were identifying vaginal microbiota patterns associated with preterm birth and exploring potential therapeutic mechanisms involving probiotics. Trial registration: Clinicaltrials.gov, identifier: NCT03689166. Results: A total of 200 participants were included. Of those, birth data were obtained for 181 women. Demographics were similar between both groups. An analysis of perinatal outcomes found no significant differences in preterm birth rates, prematurity rates, gestational weeks at delivery, neonatal complications, time to birth, or latency time to delivery. Microbiota analysis showed no significant differences in vaginal microbiota changes between groups. No serious or unexpected adverse reactions were reported. Conclusions: There were no statistically significant differences for spontaneous preterm birth between pregnant women receiving probiotics and pregnant women receiving the placebo.

Background and Aims: Emerging evidence suggests adverse pregnancy outcomes (APOs) may increase future cardiovascular risk. This study aimed to assess in a Spanish cohort the long-term risk of cardiovascular disease in women with APOs compared to those without such complications. Methods: A retrospective longitudinal cohort study was conducted at Hospital Vall d’Hebron (Barcelona, Spain), including pregnant women delivering between January 2010 and December 2015. Women with pre-existing medical conditions were excluded. APOs included preeclampsia, gestational diabetes, preterm birth, late miscarriage, and stillbirth. Cardiovascular events were defined as acute myocardial infarction or stroke. Both APO and non-APO groups were compared for their risk of cardiovascular events in the years following delivery, using unadjusted and adjusted models. Results: Out of 12,071 pregnant women delivered at Hospital Vall d’Hebron during the study period. 10,734 met the inclusion criteria (8234 in the non-APO group and 2500 in the APO group). The adjusted model revealed a significant association between APOs and cardiovascular events post-delivery (HR 2.5; 95% CI 1.4–4.4). Furthermore, an increased number of APOs (≥2) correlated with a higher risk of post-delivery cardiovascular events (HR 8.6; 95% CI 2.8–26.8). Conclusions: Women with adverse pregnancy outcomes (APOs), particularly those experiencing preeclampsia, preterm birth, and late miscarriage, exhibit an elevated long-term risk of cardiovascular events. Our findings highlight that these associations persist even after adjusting for traditional cardiovascular risk factors, indicating that APOs may independently influence long-term cardiovascular health. This underscores the importance of recognizing pregnancy as a critical window for early cardiovascular health interventions and counseling. Addressing these risks proactively could improve long-term health outcomes for women with a history of APOs.