Development and validation of the Cannabis Exposure in Pregnancy Tool (CEPT): a mixed methods study.

BACKGROUND: Evidence of associations between prenatal cannabis use (PCU) and maternal and infant health outcomes remains conflicting amid broad legalization of cannabis across Canada and 40 American states. A critical limitation of existing evidence lies in the non-standardized and crude measurement of prenatal cannabis use (PCU), resulting in high risk of misclassification bias. We developed a standardized tool to comprehensively measure prenatal cannabis use in pregnant populations for research purposes. METHODS: We conducted a mixed-methods, patient-oriented tool development and validation study, using a bias-minimizing process. Following an environmental scan and critical appraisal of existing prenatal substance use tools, we recruited pregnant participants via targeted social media advertising and obstetric clinics in Alberta, Canada. We conducted individual in-depth interviews and cognitive interviewing in separate sub-samples, to develop and refine our tool. We assessed convergent and discriminant validity internal consistency and 3-month test-retest reliability, and validated the tool externally against urine-THC bioassays. RESULTS: Two hundred fifty four pregnant women participated. The 9-item Cannabis Exposure in Pregnancy Tool (CEPT) had excellent discriminant (Cohen's kappa = -0.27-0.15) and convergent (Cohen's kappa = 0.72-1.0) validity; as well as high internal consistency (Chronbach's alpha = 0.92), and very good test-retest reliability (weighted Kappa = 0.92, 95% C.I. [0.86-0.97]). The CEPT is valid against urine THC bioassay (sensitivity = 100%, specificity = 82%). CONCLUSION: The CEPT is a novel, valid and reliable measure of frequency, timing, dose, and mode of PCU, in a contemporary sample of pregnant women. Using CEPT (compared to non-standardized tools) can improve measurement accuracy, and thus the quality of research examining PCU and maternal and child health outcomes.

Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche.

Porphyromonas asaccharolytica and Porphyromonas uenonis are common inhabitants of the vaginal microbiome, but their presence has been linked to adverse health outcomes for women, including bacterial vaginosis and preterm birth. However, little is known about the pathogenesis mechanisms of these bacteria. The related oral opportunistic pathogen, Porphyromonas gingivalis, is comparatively well-studied and known to secrete numerous extracellular matrix-targeting proteases. Among these are the gingipain family of cysteine proteases that drive periodontal disease progression and hematogenic transmission to the placenta. In this study, we demonstrate that vaginal Porphyromonas species secrete broad-acting proteases capable of freely diffusing within the cervicovaginal niche. These proteases degrade collagens that are enriched within the cervix (type I) and chorioamniotic membranes (type IV), as well as fibrinogen, which inhibits clot formation. Bioinformatic queries confirmed the absence of gingipain orthologs and identified five serine, cysteine, and metalloprotease candidates in each species. Inhibition assays revealed that each species' proteolytic activity can be partially attributed to a secreted metalloprotease with broad substrate specificity that is distantly related to the P. gingivalis endopeptidase PepO. This characterization of virulence activities in vaginal Porphyromonas species highlights their potential to alter the homeostasis of reproductive tissues and harm human pregnancy through clotting disruption, fetal membrane weakening, and premature cervical remodeling.