Faculty Bibliography

BACKGROUND:Haemophilus influenzae (Hi) is an emerging cause of early onset neonatal sepsis, but mechanisms of transmission are not well understood. We aimed to determine the prevalence of vaginal carriage of Hi in reproductive age women and to examine behavioral and demographic characteristics associated with its carriage. METHODS:) value < 35 were defined as positive. Sanger sequencing confirmed the presence of hpd. Behavioral and demographic characteristics associated with vaginal carriage of Hi were examined. RESULTS:415 samples were available. 315 (75.9%) had sufficient bacterial DNA and were included. 14 (4.4%) were positive for hpd. There were no demographic or behavioral differences between the women with Hi vaginal carriage and those without. There was no difference in history of bacterial vaginosis, vaginal microbiome community state type, or presence of Group B Streptococcus in women with and without vaginal carriage of Hi. CONCLUSION:Hi was present in vaginal lavage specimens of 4.4% of this cohort. Hi presence was unrelated to clinical or demographic characteristics, though the relatively small number of positive samples may have limited power to detect such differences.

Group B Streptococcus (GBS) is a pathobiont that can ascend to the placenta and cause adverse pregnancy outcomes, in part through production of the toxin β-hemolysin/cytolysin (β-h/c). Innate immune cells have been implicated in the response to GBS infection, but the impact of β-h/c on their response is poorly defined. We show that GBS modulates innate immune cell states by subversion of host inflammation through β-h/c, allowing worse outcomes. We used an ascending mouse model of GBS infection to measure placental cell state changes over time following infection with a β-h/c-deficient and isogenic wild type GBS strain. Transcriptomic analysis suggests that β-h/c-producing GBS elicit a worse phenotype through suppression of host inflammatory signaling in placental macrophages and neutrophils, and comparison of human placental macrophages infected with the same strains recapitulates these results. Our findings have implications for identification of new targets in GBS disease to support host defense against pathogenic challenge.

OBJECTIVE: The study aimed to evaluate the effects of inhaled iloprost on oxygenation indices in neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN/METHODS:) were recorded. RESULTS: < 0.05), with no significant change in required mean airway pressure over that same period. There was no change in vasopressor use or clinically significant worsening of platelets count, liver, and kidney functions after initiating iloprost. CONCLUSION/CONCLUSIONS: Inhaled iloprost is well tolerated and seems to have beneficial effects in improving oxygenation indices in neonates with PPHN who do not respond to iNO. There is a need of well-designed prospective trials to further ascertain the benefits of using inhaled iloprost as an adjunct treatment in neonates with PPHN who do not respond to iNO alone. KEY POINTS/CONCLUSIONS:· Inhaled iloprost seems to have beneficial effects in improving oxygenation indices in PPHN.. · Inhaled iloprost is generally well tolerated in newborns with PPHN.. · There is a need for prospective RCTs to further ascertain the benefits of using inhaled iloprost..

OBJECTIVE:Inequity between genders with regards to leadership achievement, compensation, scholarly productivity, and grant funding exist among physicians. This study explores whether similar inequities exist among board certified neonatologists within the USA. STUDY DESIGN/METHODS:A voluntary anonymous survey was distributed to 3575 members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine with 560 respondents (15.7% response rate). The survey contained questions assessing clinician characteristics, work environment, compensation, professional productivity, and social factors. Statistical analysis was done using JMP Pro 15.0.0 by SAS. RESULTS:Female neonatologists, compared to male peers, were less likely to hold leadership positions (OR 0.36, p = 0.005), received lower compensation by an average of $34,916 or 12.47% (p < 0.001), and had 6.71 fewer primary authored publications (p = 0.025) after adjusting for several confounding factors. CONCLUSION/CONCLUSIONS:Gender remains a significant independent factor influencing leadership attainment, compensation, and academic productivity in this cohort of neonatologists.

BACKGROUND:(GBS) is an important precursor to late-onset (LO) disease in infants. The host-pathogen interactions that mediate progression to invasive disease remain unknown due, in part, to a paucity of robust model systems. Passively acquired maternal GBS-specific antibodies protect newborns from early-onset disease, yet their impact on GI colonization and LO disease is unexplored. METHODS:Using murine models of both perinatal and postnatal GBS acquisition, we assessed the kinetics of GBS GI colonization, progression to invasive disease and the role of GBS-specific IgG production in exposed offspring and juvenile mice at age 12-14 days, respectively. We defined LO disease as >7 days of life in the perinatal model. We studied the impact of maternal immunization using a whole-cell GBS vaccine on the duration of intestinal colonization and progression to invasive disease after postnatal GBS exposure in offspring. RESULTS:Animals exhibit sustained GI colonization following both perinatal and postnatal exposure to GBS, with 21% and 27% developing invasive disease respectively. Intestinal colonization with GBS induces an endogenous IgG response within 20 days of exposure. Maternal vaccination with whole-cell GBS induces production of GBS-specific IgG in dams that is vertically transmitted to their offspring but does not decrease the duration of GBS intestinal colonization or reduce LO mortality following postnatal GBS exposure. CONCLUSION(S)/CONCLUSIONS:Both perinatal and postnatal murine models of GBS acquisition closely recapitulate the human disease state, in which GBS colonizes the intestine and causes LO disease. We demonstrate both endogenous production of anti-GBS IgG in juvenile mice and vertical transfer of antibodies to offspring following maternal vaccination. These models serve as a platform to study critical host-pathogen interactions that mediate LO GBS disease.

Background Group B Streptococcus (GBS) is a common cause of neonatal sepsis. GBS colonization of the newborn gastrointestinal tract (GIT) may be a critical precursor for late-onset infection. Assessment of the rate of neonatal GBS intestinal colonization has generally relied upon culture-based methods. We used polymerase chain reaction (PCR) and culture to determine the rate of GBS transmission to neonates. We hypothesized that PCR may enhance the detection of neonatal GBS colonization of the GIT, and that the rate will be higher when evaluated with PCR as compared to culture. Methods This was a cross-sectional study, in which mothers who were positive for GBS on routine screening and their healthy infants were eligible for recruitment. Newborn stool was collected after 24 h of life and before hospital discharge, and stored at -80°C for culture and PCR targeting the GBS-specific surface immunogenic protein (sip) gene. Results A total of 94 mother-infant pairs were enrolled; of these pairs, stool was collected from 83 infants. Based on PCR, the overall GBS transmission rate was 3.6% (3/83). The transmission rate was 2.4% (1/41) among vaginal deliveries and 4.8% (2/42) among cesarean deliveries. The results of culture-based transmission detection were identical. Conclusion These results indicate that the rate of GBS transmission is low and that detection may not be enhanced by PCR methods.