Increased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells, inflammatory metabolites, epithelial barrier disruption, and the depletion of L. crispatus.

BACKGROUND: Cervicovaginal inflammation has been linked to negative reproductive health outcomes including the acquisition of HIV, other sexually transmitted infections, and cervical carcinogenesis. While changes to the vaginal microbiome have been linked to genital inflammation, the molecular relationships between the functional components of the microbiome with cervical immunology in the reproductive tract are understudied, limiting our understanding of mucosal biology that may be important for reproductive health. RESULTS: In this study, we used a multi'-omics approach to profile cervicovaginal samples collected from 43 Canadian women to characterize host, immune, functional microbiome, and metabolome features of cervicovaginal inflammation. We demonstrate that inflammation is associated with lower amounts of L. crispatus and higher levels of cervical antigen-presenting cells (APCs). Proteomic analysis showed an upregulation of pathways related to neutrophil degranulation, complement, and leukocyte migration, with lower levels of cornified envelope and cell-cell adherens junctions. Functional microbiome analysis showed reductions in carbohydrate metabolism and lactic acid, with increases in xanthine and other metabolites. Bayesian network analysis linked L. crispatus with glycolytic and nucleotide metabolism, succinate and xanthine, and epithelial proteins SCEL and IVL as major molecular features associated with pro-inflammatory cytokines and increased APCs. CONCLUSIONS: This study identified key molecular and immunological relationships with cervicovaginal inflammation, including higher APCs, bacterial metabolism, and proteome alterations that underlie inflammation. As APCs are involved in HIV transmission, parturition, and cervical cancer progression, further studies are needed to explore the interactions between these cells, bacterial metabolism, mucosal immunity, and their relationship to reproductive health. Video Abstract.

Early Neurodevelopmental Outcomes after Previable Preterm Prelabour Rupture of Membranes (pPPROM).

Objective: To describe the early neurodevelopmental outcomes following fetal exposure to previable preterm prelabour rupture of membranes (pPPROM). Methods: This was a secondary analysis of a subgroup of neonates born following pPPROM from a retrospective cohort study (2009-2015). Surviving infants who underwent standardized neurodevelopmental evaluation at 18-24 months corrected age (CA) between 2017 and 2019 were eligible for inclusion. Data abstracted from hospital charts were linked to prospectively collected developmental outcomes stored in an electronic database from a regional neonatal follow-up clinic. The primary outcome was Bayley-III composite scores (compared to the population mean 100, standard deviation (SD) 15). Secondary outcomes included presence of cerebral palsy, vision loss, hearing impairment, and requirement of rehabilitation therapy. Descriptive statistics were used to present results. Results: 25.7% (19/74) of neonates born after pPPROM survived to hospital discharge, but only 21.6% (16/74) survived to 18-24 months CA. Of these, 9 infants were eligible for follow-up at the regional clinic and 7 had developmental outcomes stored in the electronic database. Infants exposed to pPPROM exhibited Bayley-III scores more than 1 SD below the population mean across all three domains: cognitive 84.9 (SD 12.2); motor 82.3 (SD 11.5); and language 66.4 (SD 18.9). There were particular deficiencies in language development with 71% (5/7) scoring more than 2 SDs below the population mean. There were no cases of cerebral palsy. Conclusions: Only 1 in 5 infants born following expectantly managed pPPROM survived to 18-24 months CA. These infants born after pPPROM had significantly lower Bayley-III scores and particular deficiencies in language development. Better understanding of early neurodevelopmental challenges following pPPROM will help refine counselling of families contemplating expectant management and provide insights into the postnatal educational resources required to improve long-term developmental outcomes for these children.

Maternal hypothermia from environmental exposure in the third trimester.

A primigravida at 32 weeks gestation developed hypothermia after prolonged exposure to the elements at -30.0°C. Her core temperature dropped to 29.8°C with associated foetal bradycardia. Passive rewarming was undertaken with forced warm air blankets and warmed IV fluids. The foetal heart rate normalised once normothermia was achieved. Serial foetal assessments showed appropriate growth and normal Doppler studies. She went to on deliver a healthy term infant. This case highlights conservative management and prioritising of maternal well-being with a good maternal and foetal outcome.