Multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) associated with COVID-19: optimizing definition and management.

During the SARS-CoV-2-associated infection (COVID-19), pandemic initial reports suggested relative sparing of children inversely related to their age. Children and neonates have a decreased incidence of SARS-CoV-2 infection, and if infected they manifested a less severe phenotype, in part due to enhanced innate immune response. However, a multisystem inflammatory syndrome in children (MIS-C) or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 emerged involving coronary artery aneurysms, cardiac dysfunction, and multiorgan inflammatory manifestations. MIS-C has many similarities to Kawasaki disease and other inflammatory conditions and may fit within a spectrum of inflammatory conditions based on immunological results. More recently neonates born to mothers with SARS-CoV-2 infection during pregnancy demonstrated evidence of a multisystem inflammatory syndrome with raised inflammatory markers and multiorgan, especially cardiac dysfunction that has been described as multisystem inflammatory syndrome in neonates (MIS-N). However, there is a variation in definitions and management algorithms for MIS-C and MIS-N. Further understanding of baseline immunological responses to allow stratification of patient groups and accurate diagnosis will aid prognostication, and inform optimal immunomodulatory therapies. IMPACT: Multisystem inflammatory system in children and neonates (MIS-C and MIS-N) post COVID require an internationally recognized consensus definition and international datasets to improve management and plan future clinical trials. This review incorporates the latest review of pathophysiology, clinical information, and management of MIS-C and MIS-N. Further understanding of the pathophysiology of MIS-C and MIS-N will allow future targeted therapies to prevent and limit clinical sequelae.

Exposure to umbilical cord management approaches and death or neurodevelopmental impairment at 22-26 months' corrected age after extremely preterm birth.

OBJECTIVE: To compare death or severe neurodevelopmental impairment (NDI) at 22-26 months' corrected age (CA) among extremely preterm infants following exposure to different forms of umbilical cord management. DESIGN: Retrospective study. SETTING: Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network registry. PATIENTS: Infants born <27 weeks' gestation in 2016-2018 without severe congenital anomalies who received active treatment after birth and underwent neurodevelopmental assessments between 22 and 26 months' CA. EXPOSURES: Immediate cord clamping (ICC), delayed cord clamping (DCC) or umbilical cord milking (UCM). MAIN OUTCOMES AND MEASURE: Primary composite outcome of death or severe NDI at 22-26 months' CA, defined as severe cerebral palsy, Bayley-III cognitive/motor composite score <70, bilateral deafness or blindness; individual components were examined as secondary outcomes. Multivariable regression examined associations, adjusting for risk factors identified a priori and potential confounders. Mediation analysis explored the effect of severe intraventricular haemorrhage (IVH) on the exposure-outcome relationship. RESULTS: Among 1900 infants, 64.1% were exposed to ICC, 27.8% to DCC and 8.1% to UCM. Compared with ICC-exposed infants, DCC-exposed infants had lower odds of death or severe NDI (adjusted OR 0.64, 95% CI 0.50 to 0.83). No statistically significant differences were observed when comparing UCM with either ICC or DCC, or between secondary outcomes across groups. Association between cord management and the primary outcome was not mediated by severe IVH. CONCLUSION: Compared with ICC, DCC exposure was associated with lower death or severe NDI at 22-26 months' CA among extremely preterm infants, which was not mediated by severe IVH.

Pregnancy and Severe ARDS with COVID-19: Epidemiology, Diagnosis, Outcomes and Treatment

Pregnancy-related acute respiratory distress syndrome (ARDS) is fast becoming a growing and clinically relevant subgroup of ARDS amidst global outbreaks of various viral respiratory pathogens that include H1N1-influenza, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and the most recent COVID-19 pandemic. Pregnancy is a risk factor for severe viral-induced ARDS and commonly associated with poor maternal and fetal outcomes including fetal growth-restriction, preterm birth, and spontaneous abortion. Physiologic changes of pregnancy further compounded by mechanical and immunologic alterations are theorized to impact the development of ARDS from viral pneumonia. The COVID-19 sub-phenotype of ARDS share overlapping molecular features of maternal pathogenicity of pregnancy with respect to immune-dysregulation and endothelial/microvascular injury (i.e.. preeclampsia) that may in part explain a trend toward poor maternal and fetal outcomes seen with severe COVID-19 maternal infections. To date, current ARDS diagnostic criteria and treatment management fail to include and consider physiologic adaptations that are unique to maternal physiology of pregnancy and consideration of maternal-fetal interactions. Treatment focused on lung-protective ventilation strategies have been shown to improve clinical outcomes in adults with ARDS but may have adverse maternal-fetal interactions when applied in pregnancy-related ARDS. No specific pharmacotherapy has been identified to improve outcomes in pregnancy with ARDS. Adjunctive therapies aimed at immune-modulation and anti-viral treatment with COVID-19 infection during pregnancy has been reported but data in regard to its efficacy and safety is currently lacking.

Pregnancy and Severe ARDS with COVID-19: Epidemiology, Diagnosis, Outcomes and Treatment.

Pregnancy-related acute respiratory distress syndrome (ARDS) is fast becoming a growing and clinically relevant subgroup of ARDS amidst global outbreaks of various viral respiratory pathogens that include H1N1-influenza, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and the most recent COVID-19 pandemic. Pregnancy is a risk factor for severe viral-induced ARDS and commonly associated with poor maternal and fetal outcomes including fetal growth-restriction, preterm birth, and spontaneous abortion. Physiologic changes of pregnancy further compounded by mechanical and immunologic alterations are theorized to impact the development of ARDS from viral pneumonia. The COVID-19 sub-phenotype of ARDS share overlapping molecular features of maternal pathogenicity of pregnancy with respect to immune-dysregulation and endothelial/microvascular injury (i.e., preeclampsia) that may in part explain a trend toward poor maternal and fetal outcomes seen with severe COVID-19 maternal infections. To date, current ARDS diagnostic criteria and treatment management fail to include and consider physiologic adaptations that are unique to maternal physiology of pregnancy and consideration of maternal-fetal interactions. Treatment focused on lung-protective ventilation strategies have been shown to improve clinical outcomes in adults with ARDS but may have adverse maternal-fetal interactions when applied in pregnancy-related ARDS. No specific pharmacotherapy has been identified to improve outcomes in pregnancy with ARDS. Adjunctive therapies aimed at immune-modulation and anti-viral treatment with COVID-19 infection during pregnancy have been reported but data in regard to its efficacy and safety is currently lacking.

Protecting Breastfeeding during the COVID-19 Pandemic.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has impacted all patient populations including pregnant mothers. There is an incomplete understanding of SARS-CoV-2 pathogenesis and transmission potential at this time and the resultant anxiety has led to variable breastfeeding recommendations for suspected or confirmed mothers with novel coronavirus disease 2019 (COVID-19). Due to the potential concern for transmission of infection from maternal respiratory secretions to the newborn, temporary separation of the maternal-baby dyad, allowing for expressed breast milk to be fed to the infant, was initially recommended but later revised to include breastfeeding by the American Academy of Pediatrics in contrast to international societies, which recommend direct breastfeeding. This separation can have negative health and emotional implications for both mother and baby. Only two publications have reported SARS-CoV-2 in human breast milk but the role of breast milk as a vehicle of transmission of COVID-19 to the newborns still remains unclear and may indeed be providing protective antibodies against SARS-CoV-2 infection even in infected neonates. Other modes of transmission of infection to neonates from infected mothers or any care providers cannot be overemphasized. Symptomatic mothers on hydroxychloroquine can safely breastfeed and no adverse effects were reported in a baby treated with remdesivir in another drug trial. The excretion of sarilumab in human breast milk is unknown at this time. Hence, given the overall safety of breast milk and both short-term and long- term nutritional, immunological, and developmental advantages of breast milk to newborn, breast milk should not be withheld from baby. The setting of maternal care, severity of maternal infection and availability of resources can impact the decision of breastfeeding, the role of shared decision making on breastfeeding between mother and physician needs to be emphasized. We strongly recommend direct breastfeeding with appropriate hygiene precautions unless the maternal or neonatal health condition warrants separation of this dyad. KEY POINTS: · Breastmilk does not appear to play a significant role in transmission of SARS-CoV-2.. · Mother-baby separation has negative health and emotional consequences.. · Mothers with suspected or confirmed COVID-19 can directly breastfeed with appropriate precautions..

Management of Placental Transfusion to Neonates After Delivery.

This review summarizes high-quality evidence supporting delayed umbilical cord clamping to promote placental transfusion to preterm and term neonates. In preterm neonates, delayed cord clamping may decrease mortality and the need for blood transfusions. Although robust data are lacking to guide cord management strategies in many clinical scenarios, emerging literature is reviewed on numerous topics including delivery mode, twin gestations, maternal comorbidities (eg, gestational diabetes, red blood cell alloimmunization, human immunodeficiency virus [HIV] infection, and severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and neonatal complications (eg, fetal growth restriction, congenital heart disease, and the depressed neonate). Umbilical cord milking is an alternate method of rapid placental transfusion, but has been associated with severe intraventricular hemorrhage in extremely preterm neonates. Data on long-term outcomes are discussed, as well as potential contraindications to delayed cord clamping. Overall, delayed cord clamping offers potential benefits to the estimated 140 million neonates born globally every year, emphasizing the importance of this simple and no-cost strategy.

Neonatal Multisystem Inflammatory Syndrome (MIS-N) Associated with Prenatal Maternal SARS-CoV-2: A Case Series.

Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious immune-mediated condition, seen 3-5 weeks after COVID-19. Maternal SARS-CoV-2 may potentially cause a similar hyperinflammatory syndrome in neonates due to transplacental transfer of antibodies. We reviewed the perinatal history, clinical features, and outcomes of 20 neonates with features consistent with MIS-C related to maternal SARS-CoV-2 in Kolhapur, India, from 1 September 2020 to 30 April 2021. Anti-SARS-CoV-2 IgG and IgM antibodies were tested in all neonates. Fifteen singletons and five twins born to eighteen mothers with a history of COVID-19 disease or exposure during pregnancy presented with features consistent with MIS-C during the first 5 days after birth. Nineteen were positive for anti-SARS-CoV-2 IgG and all were negative for IgM antibodies. All mothers were asymptomatic and therefore not tested by RTPCR-SARS-CoV-2 at delivery. Eighteen neonates (90%) had cardiac involvement with prolonged QTc, 2:1 AV block, cardiogenic shock, or coronary dilatation. Other findings included respiratory failure (40%), fever (10%), feeding intolerance (30%), melena (10%), and renal failure (5%). All infants had elevated inflammatory biomarkers and received steroids and IVIG. Two infants died. We speculate that maternal SARS-CoV-2 and transplacental antibodies cause multisystem inflammatory syndrome in neonates (MIS-N). Immunomodulation may be beneficial in some cases, but further studies are needed.

Perinatal SARS-CoV-2 Infection and Neonatal COVID-19: A 2021 Update.

The coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept across the world like an indiscriminating wildfire. Pregnant women and neonates are particularly vulnerable to this infection compared with older children and healthy young adults, with unique challenges in their management. Unfamiliarity with the consequences of this novel virus and lack of high-quality data led to considerable heterogeneity in obstetrical and neonatal management early in the pandemic. The aim of the this review is to summarize the impact of SARS-CoV-2 infection on pregnancy and childbirth and to examine care and possible outcomes for neonates with Covid-19-positive mothers. A brief review of vaccines currently approved by the United States Food and Drug Administration for emergency use and their potential effects on pregnant and lactating women in included.

Evaluation of Seasonal Respiratory Virus Activity Before and After the Statewide COVID-19 Shelter-in-Place Order in Northern California.

Importance: Public health initiatives that include shelter-in-place orders are expensive and unpopular. Demonstrating the success of these initiatives is essential to justify their systemic or individual cost. Objective: To examine the association of a shelter-in-place order with lower rates of seasonal respiratory viral activity. Design, Setting, and Participants: This cohort study with interrupted time series analysis obtained monthly counts of respiratory virus testing results at UC Davis Health from August 1, 2014, to July 31, 2020. Patients of all ages underwent testing conducted by the laboratory at UC Davis Health, a referral center for a 65 000-square-mile area that includes 33 counties and more than 6 million Northern California residents. Exposures: A statewide shelter-in-place order was instituted on March 19, 2020, restricting residents to their homes except for traveling for essential activities. Large social gatherings were prohibited, schools were closed, and nonessential personnel worked remotely. Those who had to leave their homes were mandated to wear face masks, engage in frequent handwashing, and maintain physical distancing. Main Outcomes and Measures: Positivity rates of common respiratory viruses within the community served by UC Davis Health. Results: A total of 46 128 tests for viral respiratory pathogens over a 6-year period were included in the analysis. For the postexposure period (March 25-July 31), approximately 168 positive test results occurred for the studied organisms in the 2020 virus year, a positivity rate of 9.88 positive results per 100 tests that was much lower than the positivity rate of 29.90 positive results per 100 tests observed for this date range in the previous 5 virus years. In contrast, the positivity rates were similar for the preexposure time frame (August 1-March 24) in the 2020 virus year and for the same time periods in the 5 previous years (30.40 vs 33.68 positive results per 100 tests). In the regression analyses, statistically significant decreases in viral activity were observed in the postexposure period for influenza (93% decrease; incidence rate ratio [IRR], 0.07; 95% CI, 0.02-0.33) and for rhinovirus or enterovirus (81% decrease; IRR, 0.19; 95% CI, 0.09-0.39) infections. Lower rates of postexposure viral activity were seen for respiratory syncytial virus, parainfluenzavirus, coronaviruses, and adenoviruses; however, these associations were not statistically significant. Conclusions and Relevance: Using interrupted time series analysis of testing for viral respiratory pathogens, this study found that statistically significant lower rates of common community respiratory viruses appeared to be associated with a shelter-in-place order during the coronavirus disease 2019 pandemic.

Perinatal aspects on the covid-19 pandemic: a practical resource for perinatal-neonatal specialists.

BACKGROUND: Little is known about the perinatal aspects of COVID-19. OBJECTIVE: To summarize available evidence and provide perinatologists/neonatologists with tools for managing their patients. METHODS: Analysis of available literature on COVID-19 using Medline and Google scholar. RESULTS: From scant data: vertical transmission from maternal infection during the third trimester probably does not occur or likely it occurs very rarely. Consequences of COVID-19 infection among women during early pregnancy remain unknown. We cannot conclude if pregnancy is a risk factor for more severe disease in women with COVID-19. Little is known about disease severity in neonates, and from very few samples, the presence of SARS-CoV-2 has not been documented in human milk. Links to websites of organizations with updated COVID-19 information are provided. Infographics summarize an approach to the pregnant woman or neonate with suspected or confirmed COVID-19. CONCLUSIONS: As the pandemic continues, more data will be available that could lead to changes in current knowledge and recommendations.

Interprofessional/interdisciplinary teamwork during the early COVID-19 pandemic: experience from a children's hospital within an academic health center.

The COVID-19 pandemic has created multiple, complex and intense demands on hospitals, including the need for surge planning in the many locations outside epicenters such as northern Italy or New York City. We here describe such surge planning in an Academic Health Center that encompasses a children's hospital. Interprofessional teams from every aspect of inpatient care and hospital operations worked to prepare for a COVID-19 surge. In so doing, they successfully innovated ways to integrate pediatric and adult care and maximize bed capacity. The success of this intense collaborative effort offers an opportunity for ongoing teamwork to enhance efficient, effective, and high-quality patient care.

Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). The clinical presentation of MIS-C includes fever, severe illness, and the involvement of two or more organ systems, in combination with laboratory evidence of inflammation and laboratory or epidemiologic evidence of SARS-CoV-2 infection. Some features of MIS-C resemble Kawasaki Disease, toxic shock syndrome, and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. Patients with MIS-C should ideally be managed in a pediatric intensive care environment since rapid clinical deterioration may occur. Specific immunomodulatory therapy depends on the clinical presentation. The relationship between the immune response to SARS-CoV-2 vaccines in development and MIS-C requires further study.

Management of mothers and neonates in low resources setting during covid-19 pandemia.

The coronavirus disease (COVID-19) epidemic started in the Hubei province of China, but is rapidly spreading all over the world. Much of the information and literature have been centered on the adult population while a few reports pertaining to COVID-19 and neonates have been published so far. Actual guidelines are based on expert opinion and show significant differences among the official neonatal societies around the world. Recommendations for the care of neonates born to suspected or confirmed COVD-19 positive mothers in low-resource settings are very limited. This perspective aims to provide practical support for the planning of delivery, resuscitating, stabilizing, and providing postnatal care to an infant born to a mother with suspected or confirmed COVID-19 in low-resource settings where resources for managing emergency situations are limited.