Faculty Bibliography

Congenital heart defects are the most common birth anomaly affecting approximately 1% of births. With improved survival in this population, there is enhanced ability to assess long-term morbidities including neurodevelopment. There is a wide range of congenital heart defects, from those with minimal physiologic consequence that do not require medical or surgical intervention, to complex structural anomalies requiring highly specialized medical management and intricate surgical repair or palliation. The impact of congenital heart disease on neurodevelopment is multifactorial. Susceptibility for adverse neurodevelopment increases with advancing severity of the defect with initial risk factors originating during gestation. Complex structural heart anomalies may pre-dispose the fetus to abnormal circulatory patterns in utero that ultimately impact delivery of oxygen rich blood to the fetal brain. Thus, the brain of a neonate born with complex congenital heart disease may be particularly vulnerable from the outset. That vulnerability is compounded during the newborn period and through childhood, as this population endures a myriad of medical and surgical interventions. For each individual patient, these factors are likely cumulative and synergistic with progression from fetal life through childhood. This review discusses the spectrum of risk factors that may impact neurodevelopment in children with congenital heart disease, describes current recommendations and practices for neurodevelopmental follow-up of children with congenital heart disease and reviews important neurodevelopmental trends in this high risk population.

Vaginolysin (VLY), a cytotoxic protein produced by Gardnerella vaginalis, may contribute to bacterial vaginosis (BV). Women with G. vaginalis, low levels of lactobacilli, history of vaginal douching, higher Nugent scores, and higher vaginal pH had increased VLY. Inflammatory markers were not highly expressed with increasing VLY. VLY's role in BV warrants further evaluation.

Background: Streptococcus agalactiae (group B Streptococcus [GBS]) is an important neonatal pathogen and emerging cause of disease in adults. The major risk factor for neonatal disease is maternal vaginal colonization. However, little is known about the relationship between GBS and vaginal microbiota. Methods: Vaginal lavage samples from nonpregnant women were tested for GBS, and amplicon-based sequencing targeting the 16S ribosomal RNA V3-V4 region was performed. Results: Four hundred twenty-eight of 432 samples met the high-quality read threshold. There was no relationship between GBS carriage and demographic characteristics, alpha-diversity, or overall vaginal microbiota community state type (CST). Within the non-Lactobacillus-dominant CST IV, GBS positive status was significantly more prevalent in CST IV-A than CST IV-B. Significant clustering by GBS status was noted on principal coordinates analysis, and 18 individual taxa were found to be significantly associated with GBS carriage by linear discriminant analysis. After adjusting for race/ethnicity, 4 taxa were positively associated with GBS, and 6 were negatively associated. Conclusions: Vaginal microbiota CST and alpha-diversity are not related to GBS status. However, specific microbial taxa are associated with colonization of this important human pathogen, highlighting a potential role for the microbiota in promotion or inhibition of GBS colonization.

Gardnerella vaginalis, the bacterial species most frequently isolated from women with bacterial vaginosis (BV), produces a cholesterol-dependent cytolysin (CDC), vaginolysin (VLY). At sublytic concentrations, CDCs may initiate complex signaling cascades crucial to target cell survival. Using live-cell imaging, we observed the rapid formation of large membrane blebs in human vaginal and cervical epithelial cells (VK2 and HeLa cells) exposed to recombinant VLY toxin and to cell-free supernatants from growing liquid cultures of G. vaginalis. Binding of VLY to its human-specific receptor (hCD59) is required for bleb formation, as antibody inhibition of either toxin or hCD59 abrogates this response, and transfection of nonhuman cells (CHO-K1) with hCD59 renders them susceptible to toxin-induced membrane blebbing. Disruption of the pore formation process (by exposure to pore-deficient toxoids or pretreatment of cells with methyl-beta-cyclodextrin) or osmotic protection of target cells inhibits VLY-induced membrane blebbing. These results indicate that the formation of functional pores drives the observed ultrastructural rearrangements. Rapid bleb formation may represent a conserved response of epithelial cells to sublytic quantities of pore-forming toxins, and VLY-induced epithelial cell membrane blebbing in the vaginal mucosa may play a role in the pathogenesis of BV.