Faculty Bibliography

The increasing availability of novel therapies highlights the importance of screening newborns for rare genetic disorders so that they may benefit from early therapy, when it is most likely to be effective. Pilot newborn screening (NBS) studies are a way to gather objective evidence about the feasibility and utility of screening, the accuracy of screening assays, and the incidence of disease. They are also an optimal way to evaluate the complex ethical, legal and social implications (ELSI) that accompany NBS expansion for disorders. ScreenPlus is a consented pilot NBS program that aims to enroll over 100,000 infants across New York City. The initial ScreenPlus panel includes 14 disorders and uses an analyte-based, multi-tiered screening platform in an effort to enhance screening accuracy. Infants who receive an abnormal result are referred to a ScreenPlus provider for confirmatory testing, management, and therapy as needed, along with longitudinal capture of outcome data. Participation in ScreenPlus requires parental consent, which is obtained in active and passive manners. Patient-facing documents are translated into the ten most common languages spoken at our nine pilot hospitals, all of which serve diverse communities. At the time of consent, parents are invited to receive a series of online surveys to capture their opinions about specific ELSI-related topics, such as NBS policy, residual dried blood spot retention, and the types of disorders that should be on NBS panels. ScreenPlus has developed a stakeholder-based, collective funding model that includes federal support in addition to funding from 14 advocacy and industry sponsors, all of which have a particular interest in NBS for at least one of the ScreenPlus disorders. Taken together, ScreenPlus is a model, multi-sponsored pilot NBS program that will provide critical data about NBS for a broad panel of disorders, while gathering key stakeholder opinions to help guide ethically sensitive decision-making about NBS expansion.

Late-onset disease is the most common clinical presentation of Group B Streptococcus (GBS) infection during infancy, and gastrointestinal (GI) colonization is an important precursor. Previously, we described a murine model of postnatal GBS GI colonization that resulted in sustained colonization and progression to invasive disease. Capsular polysaccharide is an important GBS virulence factor. Vaccines based on a subset of capsular serotypes are in clinical trials. However, little is known regarding the role of specific GBS capsular serotypes in GI colonization. We examined the role of GBS capsule in GI colonization using capsule-producing and acapsular strains derived from GBS strain A909 (serotype Ia) in a murine model. Using isogenic GBS strains differing only in capsular serotypes, we explored the role of specific serotypes in GI colonization by determining competitive indices during cocolonization. We found that GBS A909 colonizes the murine GI tract without causing invasive disease. In monocolonization experiments, there was colonization persistence with the capsule-producing strain (100%) compared to the acapsular mutant strain (13%). In cocolonization experiments, the capsule-producing strain outcompeted its isogenic acapsular mutant, with a geometric mean competitive index of 8, 95% confidence interval (CI) [1.7, 38.9] in the colon at 7 days post-colonization. A909 expressing its native serotype Ia capsule outcompeted an isogenic mutant that expresses serotype III capsule, with a geometric mean competitive index of 2.5, 95% CI [1.2, 5.1] in the colon at 7 days post-colonization. Thus, polysaccharide capsule production enhances GBS GI colonization in vivo. In an A909 genetic background, the production of a serotype Ia capsule provides a competitive advantage over an isogenic strain producing type III capsule. The murine model is a valuable tool to understand the role of GBS capsule types in GI colonization. IMPORTANCE The establishment of GBS intestinal colonization is believed to be a critical precursor to late-onset disease in neonates, which has a significant impact on neurodevelopment outcomes in this population. Our prior work described a murine model of postnatal Group B Streptococcus (GBS) acquisition and invasive disease. Using this model, we explored the importance of GBS polysaccharide capsule production on gastrointestinal colonization. We found that the expression of capsule (compared to isogenic acapsular strains) provides an advantage in intestinal colonization and, importantly, that capsule type Ia has an advantage over capsule type III in a GBS A909 strain background. We speculate that specific serotypes may differ in colonization fitness, which may play a role in serotype distribution in neonatal disease.

OBJECTIVES/OBJECTIVE:We aimed to critically evaluate the effectiveness of a designated ECMO team in our ECMO selection process and patient outcomes in the first 3 years of our low-volume pediatric ECMO program. METHODS:We conducted a retrospective chart review of patients who received an ECMO consultation between the start of our program in March 2015 and May 2018. We gathered clinical and demographic information on patients who did and did not receive ECMO, and described our selection process. We reflected on the processes used to initiate our program and our outcomes in the first 3 years. RESULTS:, lactate, and pH between the patients who went on ECMO and who did not. We improved our outcomes from 0% survival to discharge in 2015, to 60% in 2018, with an average of 63% survival to discharge over the first 3 years of our program. CONCLUSIONS:In a low-volume pediatric ECMO center, having a designated team to assist in the patient selection process and management can help provide safe and efficient care to these patients, and improve patient outcomes. Having a strict management protocol and simulation sessions involving all members of the medical team yields comfort for the providers and optimal care for patients. This study describes our novel structure, processes, and outcomes, which we hope will be helpful to others seeking to develop a new pediatric ECMO program.

OBJECTIVES/OBJECTIVE:colonization rates before and after the visitor policy change, which coincided with the exponential rise of COVID-19 cases in New York City (NYC). METHODS:colonization. RESULTS:=0.02). CONCLUSIONS:colonization rate. Hospital unit leaders may need to focus on other strategies in order to reduce colonization.

OBJECTIVES/OBJECTIVE:Antenatal corticosteroids (ACS) administered to mothers at risk for preterm delivery before 34 weeks has been standard care to improve neonatal outcomes. After introducing a new obstetric policy based on updated recommendations advising the administration of ACS to pregnant women at risk for late preterm (LPT) delivery (34-36 6/7 weeks), we set out to determine the short-term clinical impact on those LPT neonates. METHODS:Retrospective chart review of LPT neonates delivered at NYU Langone Medical Center both one year before and after the policy went into place. We excluded subjects born to mothers with pre-gestational diabetes, multiple gestations, and those with congenital/genetic abnormalities. We also excluded subjects whose mothers already received ACS previously in pregnancy. Subjects were divided into pre-policy and post-policy groups. Neonatal and maternal data were compared for both groups. RESULTS:388 subjects; 180 in the pre-policy and 208 in the post-policy group. This policy change resulted in a significant increase in ACS administration to mothers who delivered LPT neonates (67.3 vs. 20.6%, p<0.001). In turn, there was a significant reduction in LPT neonatal intensive care unit (NICU) admissions (44.2 vs. 54.4%, p=0.04) and need for respiratory support (27.9 vs. 42.8%, p<0.01). However, we also found an increased incidence of hypoglycemia (49.5 vs. 28.3%, p<0.001). CONCLUSIONS:This LPT ACS policy appears effective in reducing the need for LPT NICU level care overall. However, clinicians must be attentive to monitor for adverse effects like hypoglycemia, and there remains a need for better understanding of potential long-term impacts.

OBJECTIVE:To screen for neurodevelopmental delays in a cohort of full-term infants born to mothers with SARS-CoV-2. STUDY DESIGN/METHODS:-3) at 16 to 18 months age. RESULTS:Of 51 subjects, twelve (24%) were below cutoff, and twenty-seven (53%) were either below or close to the cutoff in at least one developmental domain. Communication (29%), fine motor (31%), and problem-solving (24%) were the most affected domains. There were no differences in outcomes between infants born to asymptomatic and mildly symptomatic mothers. CONCLUSION/CONCLUSIONS:We observed increased risk of neurodevelopmental delays during screening of infants born at full-term to mothers with SARS-CoV-2 at 16 to 18 months age. These results highlight the urgent need for follow-up studies of infants born to mothers with SARS-CoV-2.

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:Objective structured clinical exams (OSCE) are used to train and assess resident foundational family-centered communication skills incorporating key stakeholders. In 2020 encounters were conducted virtually. We sought to compare standardized patient (SP) and family faculty (FF) assessment across OSCE and virtual OSCE (VOSCE) formats. METHODS:The intern classes of 2019 and 2020 completed a live OSCE and VOSCE respectively where they disclosed an error to an SP. The 10 minute encounter was observed by an FF and facilitator followed by a 20 minute debrief. The SP and FF completed a behavioral checklist to evaluate skill mastery. RESULTS:Eighteen (90%) of the 20 interns completed the encounter each year. Total mastery scores were significantly higher for SP assessment than for FF assessment in both OSCE [68% vs 46% (z=-3.005, p<.05)] and VOSCE formats [68% vs 53% (z=-2.105, p<0.05)]. Total mastery scores of SPs across OSCE and VOSCE formats did not significantly differ, nor did FF scores based on evaluation format. CONCLUSIONS:Our current experience suggests VOSCEs are a viable alternative to in person sessions given the comparable assessment across the two modalities. The ease of participating in virtual sessions may provide a way to more easily partner with key stakeholders.