Biodistribution of mRNA COVID-19 vaccines in human breast milk.

BACKGROUND: COVID-19 mRNA vaccines play a vital role in the fight against SARS-CoV-2 infection. However, lactating women have been largely excluded from most vaccine clinical trials. As a result, limited research has been conducted on the systemic distribution of vaccine mRNA during lactation and whether it is excreted in human breast milk (BM). Here, we evaluated if COVID-19 vaccine mRNA is detectable in BM after maternal vaccination and determined its potential translational activity. METHODS: We collected BM samples from 13 lactating, healthy, post-partum women before and after COVID-19 mRNA vaccination. Vaccine mRNA in whole BM and BM extracellular vesicles (EVs) was assayed using quantitative Droplet Digital PCR, and its integrity and translational activity were evaluated. FINDINGS: Of 13 lactating women receiving the vaccine (20 exposures), trace mRNA amounts were detected in 10 exposures up to 45 h post-vaccination. The mRNA was concentrated in the BM EVs; however, these EVs neither expressed SARS-COV-2 spike protein nor induced its expression in the HT-29 cell line. Linkage analysis suggests vaccine mRNA integrity was reduced to 12-25% in BM. INTERPRETATION: Our findings demonstrate that the COVID-19 vaccine mRNA is not confined to the injection site but spreads systemically and is packaged into BM EVs. However, as only trace quantities are present and a clear translational activity is absent, we believe breastfeeding post-vaccination is safe, especially 48 h after vaccination. Nevertheless, since the minimum mRNA vaccine dose to elicit an immune reaction in infants <6 months is unknown, a dialogue between a breastfeeding mother and her healthcare provider should address the benefit/risk considerations of breastfeeding in the first two days after maternal vaccination. FUNDING: This study was supported by the Department of Pediatrics, NYU-Grossman Long Island School of Medicine.

Is Lactoferrin Supplementation Beneficial for All Preterm Infants?

OBJECTIVE: Human milk (HM) has antibacterial properties due to the presence of immune-modulators, including lactoferrin (LF). This study will determine effect(s) of HM maturation, fortification, and storage conditions on LF levels and its antibacterial properties. STUDY DESIGN: HM samples (n = 30) were obtained from preterm and term mothers. The LF levels were analyzed by ELISA, and the antibacterial activity was measured after inoculation with Escherichia coli. RESULTS: The highest level of LF in preterm HM was observed in the first week of lactation. However, storage of preterm HM at 4°C decreased LF levels significantly. Both LF levels and antibacterial activity in preterm HM was lower compared with term HM, but significantly higher than donor HM even after HM-based fortification. LF supplementation of donor HM improved its antibacterial activity. CONCLUSION: Preterm infants fed donor HM, formula, or stored HM at 4°C may benefits from LF supplementation to improve HM antibacterial properties. KEY POINTS: · Milk LF levels vary with storage and maturity.. · Donor milk is deficient in LF even after adding HM-based fortification.. · Donor HM and formula fed infants may benefit from LF..

Detection of Messenger RNA COVID-19 Vaccines in Human Breast Milk.

This cohort study investigates the presence of COVID-19 vaccine mRNA in the expressed breast milk of lactating individuals who received the vaccination within 6 months after delivery.

A quality improvement initiative to reduce hypothermia in a Baby-Friendly nursery - our story of algorithms, K-cards, and Key cards.

BACKGROUND: Baby-Friendly hospitals encourage rooming-in newborns with mothers. In our institution, we noticed increased incidence of hypothermia following Baby-Friendly designation. We aimed to reduce the incidence of hypothermia in the mother-baby-unit to <15% and to decrease the rate of isolated hypothermia admissions to the neonatal intensive care unit (NICU) by 20% over two years. METHODS: After a retrospective review of newborns ≥35 weeks gestation in the mother-baby-unit with hypothermia, we implemented multiple interventions such as nursing education, hypothermia algorithm, Kamishibai cards, and Key cards. RESULTS: Hypothermia incidence in the mother-baby-unit decreased from 20.9 to 14.5% (p < 0.001) and infants requiring NICU admission decreased by 71% (p < 0.001) following all interventions. Apart from nursing education, all interventions led to significant reductions in both outcomes from baseline. CONCLUSION: Instituting a hypothermia algorithm and utilizing K-cards and Key cards reduces the incidence of hypothermia in the mother-baby-unit and NICU admissions for isolated hypothermia.

Pneumothorax in Neonates Born to COVID-19-Positive Mothers: Fact or Fortuity?

Neonates born to mothers with coronavirus disease 2019 (COVID-19) have been largely asymptomatic based on initial reports. All neonates born to mothers with COVID-19 have tested negative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in our institution (published data as of April 12, 2020). As novel presentations of COVID-19, such as multisystem inflammatory syndrome in children are being increasingly reported, we raise the possibility of increased incidence of pneumothorax in neonates born to SARS-CoV-2-positive mothers. Two recently described neonates with COVID-19 infection were noted to have pneumothoraces. We describe two SARS-CoV-2-negative neonates born to COVID-19-positive mothers at 38 and 33 weeks, respectively, admitted to our neonatal intensive care unit for respiratory distress and subsequently developed pneumothoraces. As diverse clinical presentations in various age groups are being described, it becomes difficult to differentiate the increased incidence of complications related to an underlying illness, from COVID-19-related illness. It remains to be seen if neonates with in utero exposure to SARS-CoV-2 have an elevated inflammatory response with pneumonitis and exaggerated lung disease, similar to adult COVID-19 patients, due to in utero exposure.

A Quality Improvement Initiative to Improve Perioperative Hypothermia Rates in the NICU Utilizing Checklists.

Premature infants are at high risk for heat loss. Infants undergoing surgical procedures outside of the neonatal intensive care unit have an increased risk of hypothermia. Hypothermia can lead to delayed recovery, hypoglycemia, metabolic acidosis, sepsis, and emotional stress for the parents. We aimed to reduce the incidence of hypothermia for infants undergoing surgical procedures from a baseline of 44.4% to less than 25% over 3 years (2016-2018) with the utilization of a checklist and education. METHODS: We conducted a retrospective chart review for all infants undergoing surgical procedures from 2014 to 2015 and prospective data for 2016-2018. Next, we created a multidisciplinary team, educated staff members, and instituted a checklist comprising 9 tasks. We conducted Plan-Do-Study-Act cycles quarterly and audited checklist compliance monthly. RESULTS: From 2014 to 2015, the total incidence of perioperative hypothermia was 44.4% (n = 54). After the initiation of the checklist, the overall incidence of hypothermia decreased to 23.4% (n = 124, P = 0.007). Hypothermia occurred most frequently while the patient was in the operating room. Furthermore, we noticed that hypothermia was significantly associated with neonates requiring emergency procedures. There was an inverse correlation between overall compliance with checklist usage and the incidence of hypothermia. CONCLUSION: A checklist is a useful and simple tool for maintaining an optimal temperature for postsurgical neonates. Frequent re-education and enforcement of the protocol is necessary. Overall, implementation of the checklist, along with regular education, decreased the total incidence of perioperative hypothermia in the neonatal intensive care unit.

Methicillin-Resistant Staphylococcus aureus Endovascular Infection in a Neonate: Prolonged, Safe, and Effective Use of Daptomycin and Enoxaparin.

We report on a former 28-week gestation neonate with persistent methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, with a heterozygous Factor V Leiden mutation. The neonate became clinically ill after 1 week of life, with positive blood cultures for MRSA. Echocardiography revealed large thrombi in the inferior vena cava and right atrium. Bacteremia persisted despite removal of umbilical arterial and venous catheters and empiric administration of therapeutic doses of vancomycin (minimum inhibitory concentration [MIC] 2 mg/L) and ceftazidime. To narrow therapy, ceftazidime was discontinued, while gentamicin and rifampin were added. Cultures remained positive and, therefore, linezolid was added, and subsequent blood cultures became negative. Since prolonged linezolid use of 2 weeks or longer carries potential adverse effects, antibiotics were changed to daptomycin, which is bactericidal and recommended for treatment of invasive MRSA infections when vancomycin MICs are ≥2 mg/L to minimize vancomycin treatment failure. Enoxaparin was initiated, with anti-Xa assay monitoring. A workup for thrombophilia revealed heterozygous Factor V Leiden mutation. Serial echocardiograms demonstrated decreasing size of the thrombi, which were no longer visualized at 2 months of age. Creatinine kinase remained normal. The infant had no seizures on daptomycin. The management of persistent MRSA bacteremia in neonates associated with a large thrombus poses a unique challenge due to the long duration of treatment. To our knowledge, this is the first case of prolonged and safe daptomycin and enoxaparin use in a preterm neonate. Daptomycin may be considered in cases of clinical failure with vancomycin when a lengthy treatment course is contemplated.

Impact of time-of-day on diffusivity measures of brain tissue derived from diffusion tensor imaging.

Diurnal fluctuations in MRI measures of structural and functional properties of the brain have been reported recently. These fluctuations may have a physiological origin, since they have been detected using different MRI modalities, and cannot be explained by factors that are typically known to confound MRI measures. While preliminary evidence suggests that measures of structural properties of the brain based on diffusion tensor imaging (DTI) fluctuate as a function of time-of-day (TOD), the underlying mechanism has not been investigated. Here, we used a longitudinal within-subjects design to investigate the impact of time-of-day on DTI measures. In addition to using the conventional monoexponential tensor model to assess TOD-related fluctuations, we used a dual compartment tensor model that allowed us to directly assess if any change in DTI measures is due to an increase in CSF/free-water volume fraction or due to an increase in water diffusivity within the parenchyma. Our results show that Trace or mean diffusivity, as measured using the conventional monoexponential tensor model tends to increase systematically from morning to afternoon scans at the interface of grey matter/CSF, most prominently in the major fissures and the sulci of the brain. Interestingly, in a recent study of the glymphatic system, these same regions were found to show late enhancement after intrathecal injection of a CSF contrast agent. The increase in Trace also impacts DTI measures of diffusivity such as radial and axial diffusivity, but does not affect fractional anisotropy. The dual compartment analysis revealed that the increase in diffusivity measures from PM to AM was driven by an increase in the volume fraction of CSF-like free-water. Taken together, our findings provide important insight into the likely physiological origins of diurnal fluctuations in MRI measurements of structural properties of the brain.

A Quality Improvement Intervention to Decrease Hypothermia in the Delivery Room Using a Checklist.

INTRODUCTION: 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: 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: 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: A checklist is a simple tool that may yield beneficial changes in practice and helped to decrease the proportion of neonatal hypothermia.

Trifluoroacetic acid-promoted Michael addition-cyclization reactions of vinylogous carbamates.

A simple and efficient methodology has been developed for the synthesis of pyrrolobenzoxazine and 3-arylamino coumarin derivatives promoted by trifluoroacetic acid. The initial step in the current protocol involves a Michael addition of the 1,4-benzoxazinone derivatives, a novel class of vinylogous carbamates to the Michael acceptors and subsequent cyclization.