Faculty Bibliography

Since its emergence in Wuhan as a novel coronavirus disease, it has taken only a few months since January 2020 for it to be recognized as a widespread COVID-19 pandemic which has contributed to global health devastation. As pointed out by health experts, it is a once in a century pandemic of our times. Clinical observations so far indicate that the older population and immune compromised individuals, particularly in African American and Hispanic/Latino communities, are at much higher risk for infection with this novel coronavirus. In this regard, pregnancy offers an altered immunity scenario which may allow severe COVID-19 disease. The literature is so far highly conflicting on this issue. This review will offer a conceptual basis for severe or controlled disease and address trepidations for pregnant women associated with COVID-19 pandemic, particularly in the comparative context of clinical consequences of other coronaviruses such as SARS and MERS. We will highlight the possible consequences of COVID-19 on the general health of pregnant women as well as its possible effects at the maternal-fetal interface. For the placenta-related pathology, we will focus our discussion on the temporal expression of ACE2 throughout gestation for possible propagation of SARS-CoV-2 in the placenta in infected women and ensuing consequences.

OBJECTIVE:To assess the impact of separation of SARS-CoV-2 PCR-positive mother-newborn dyads on breastfeeding outcomes. STUDY DESIGN/METHODS:This is an observational longitudinal cohort study of SARS-CoV-2 PCR-positive mothers and their infants at three NYU Langone Health hospitals from March 25, 2020 through May 30, 2020. Mothers were surveyed by telephone regarding pre-delivery feeding plans, in-hospital feeding, and home feeding of their neonates. Any change prompted an additional question to determine whether this change was due to COVID-19. RESULTS:Of the 160 mother-newborn dyads, 103 mothers were reached by telephone, and 85 consented to participate. No significant difference was observed in pre-delivery feeding plan between the separated and unseparated dyads (P = .268). Higher rates of breastfeeding were observed in the unseparated dyads compared with the separated dyads in the hospital (p<0.001), and at home (p=0.012). Only two mothers in each group reported expressed breast milk as the hospital feeding source (5.6% of unseparated vs 4.1% of separated). COVID-19 was more commonly cited as the reason for change among the separated compared with the unseparated group (49.0% vs 16.7%, p<0.001). When dyads were further stratified by symptom status into four groups (asymptomatic separated, asymptomatic unseparated, symptomatic separated, and symptomatic unseparated), results remained unchanged. CONCLUSION/CONCLUSIONS:In the setting of COVID-19, separation of mother-newborn dyads impacts breastfeeding outcomes, with lower rates of breastfeeding both during hospitalization and at home following discharge compared with unseparated mothers and infants. No evidence of vertical transmission was observed; one case of postnatal transmission occurred from an unmasked symptomatic mother who held her infant at birth.

OBJECTIVE:The primary objective was to evaluate hydrocortisone's efficacy for decreasing respiratory support in premature infants with developing bronchopulmonary dysplasia (BPD). Secondary objectives included assessment of the impact of intrauterine growth restriction (IUGR), maternal history of chorioamnionitis, side effects and route of administration associated with hydrocortisone's efficacy. Dexamethasone as second-line treatment to decrease respiratory support was reviewed. METHODS:Retrospective chart review of preterm infants requiring respiratory support receiving hydrocortisone. RESULTS:A total of 48 patients were included. Successful extubation was achieved in 50% of intubated patients after hydrocortisone treatment with no major complications. In our small study, history of maternal chorioamnionitis, IUGR or route of administration did not affect the response. Rescue dexamethasone after hydrocortisone therapy was ineffective in the ten patients who failed extubation following hydrocortisone. CONCLUSION/CONCLUSIONS:Hydrocortisone is effective in decreasing respiratory support in patients with developing BPD without major complications. Randomized studies are warranted to confirm our findings.

The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

OBJECTIVE:To determine whether delaying oral feeding until coming off NCPAP will alter feeding and respiratory-related morbidities in preterm infants. DESIGN/METHODS:In this retrospective pre-post analysis, outcomes were compared in two preterm infant groups (≤32 weeks gestation). Infants in Group 1 were orally fed while on NCPAP, while infants in Group 2 were only allowed oral feedings after ceasing NCPAP. RESULTS:Although infants in Group 2 started feeds at a later postmenstrual age (PMA), they reached full oral feeding at a similar PMA compared with Group 1. Interestingly, there was a positive correlation between the duration of oral feeding while on NCPAP and the time spent on respiratory support in Group 1. CONCLUSIONS:Delayed oral feeding until ceasing NCPAP did not contribute to feeding-related morbidities. We recommend caution when initiating oral feedings in preterm infants on NCPAP without evaluating the safety of the infants and their readiness for oral feedings.

Gestational age-dependent immune intolerance at the maternal-fetal interface might be a contributing factor to placental pathology and adverse pregnancy outcomes. Although the intrauterine setting is highly choreographed and considered to be a protective environment for the fetus, unscheduled inflammation might overwhelm the intrauterine milieu to cause a cascade of events leading to adverse pregnancy outcomes. The old paradigm of a sterile intrauterine microenvironment has been challenged, and altered microflora has been detected in gestational tissues and amniotic fluid in the absence of induction of significant inflammation. Is there a role for endotoxin tolerance at the maternal-fetal interface? Endotoxin tolerance is a phenomenon in which tissues or cells exposed to the bacterial product, particularly lipopolysaccharide, become less responsive to subsequent exposures accompanied by decreased expression of pro-inflammatory mediators. This could also be related to trained or experienced immunity that leads to the successful outcome of subsequent pregnancies. Adaptation to endotoxin tolerance or trained immunity might be critical in preventing rejection of the fetus by the maternal immune system and protecting the fetus from excessive maternal inflammatory responses to infectious agents; however, to date, the exact mechanisms contributing to the establishment and maintenance of tolerance at the maternal-fetal interface remain incompletely understood. There is now extensive evidence suggesting that microRNAs (miRNAs) play important roles in the maintenance of a healthy pregnancy. miRNAs not only circulate freely in extracellular fluids but are also packaged within extracellular vesicles (EVs) produced by various cells and tissues. The placenta is a known, abundant, and transient source of EVs; therefore, our proposed model suggests that repeated exposure to infectious agents induces a tolerant phenotype at the maternal-fetal interface mediated by specific miRNAs mostly contained within placental EVs. We hypothesize that impaired endotoxin tolerance or failed trained immunity at the maternal-fetal interface will result in a pathological inflammatory response contributing to early or late pregnancy maladies.

Introduction/UNASSIGNED:Premature babies are at increased risk of hypothermia, core body temperature <97°F. Delivery room environment may contribute and lead to complications. The objective was to reduce hypothermia in babies <32 weeks of gestation in the delivery room to <40% using a checklist and sustain it for 6 months. Methods/UNASSIGNED:We created a delivery room checklist in 2012. Chart review established a baseline rate of hypothermia (<97°F). The team analyzed the checklist's effect on hypothermia from 2012 to 2018 and utilized numerous interventions to maintain compliance. Chi-square test and Fisher's exact test analyzed hypothermia and hyperthermia as a balancing measure. All calculations performed in SAS 9.3. Results/UNASSIGNED:The checklist reduced hypothermia from a baseline of 50% in 2011 (n = 104) to 33% in 2012 (n = 106). In 2013, the proportion of hypothermia slightly increased to 36% (n = 81). The year 2014 brought larger drift, and proportion of hypothermia increased to 44% (n = 117). In 2015, we reinforced the use of the checklist and proportion of hypothermia improved to 36% (n = 99). Further interventions through 2018 decreased hypothermia further to 14% to achieve statistical significance. Conclusions/UNASSIGNED:A checklist is a simple tool that may yield beneficial changes in practice and helped to decrease the proportion of neonatal hypothermia.

PROBLEM/OBJECTIVE:Placental infection induces increased levels of pro-inflammatory cytokines, which have been implicated in the pathogenesis of preterm labor. Endotoxin tolerance is a phenomenon in which exposure to a dose of endotoxin makes tissue less responsive to subsequent exposures. The objective of our study is to determine if repeated exposure to endotoxin will induce a tolerant phenotype in normal human second trimester placental tissue. METHODS OF STUDY/METHODS:Human second trimester placental explants from elective termination of pregnancy were cultured and exposed to endotoxin (LPS). After 24 hours, the media was collected for analysis, and the explants were re-exposed to LPS after adding fresh media for another 24 hours. This process was repeated for a total of 4 LPS doses. The media was collected from each day and analyzed for cytokine levels. RESULTS:The first LPS treatment stimulated the secretion of the pro-inflammatory cytokines IL-1β, TNF-α. However, their production was significantly diminished with repeated LPS doses. Production of anti-inflammatory cytokines, IL-1ra and IL-10, was also stimulated by the first LPS treatment, but secretion was more gradually and moderately decreased with repeated LPS doses compared to the pro-inflammatory cytokines. The ratios of the anti-inflammatory/pro-inflammatory mediators (IL-1ra/IL-1β and IL-10/ TNF-α) indicate a progressively more anti-inflammatory milieu with repeated LPS doses. CONCLUSIONS:Repeated LPS exposure of human second trimester placental tissues induced endotoxin tolerance. We speculate that endotoxin tolerance at the maternal-fetal interface will protect the fetus from exaggerated inflammatory responses after repeated infectious exposure.