Impact of perinatal COVID on fetal and neonatal brain and neurodevelopmental outcomes

After three years of the COVID-19 pandemic, we have learned many aspects of the disease and the virus: its molecular structure, how it infects human cells, the clinical picture at different ages, potential therapies, and the effectiveness of prophylaxis. Research is currently focused on the short- and long-term consequences of COVID-19. We review the available information on the neurodevelopmental outcome of infants born during the pandemic from infected and non-infected mothers, as well as the neurological impact of neonatal SARS-CoV-2 infection. We also discuss the mechanisms that could potentially affect the fetal or neonatal brain including direct impact after vertical transmission, maternal immune activation with a proinflammatory cytokine storm, and finally the consequences of complications of pregnancy secondary to maternal infection that could affect the fetus. Several follow-up studies have noted a variety of neurodevelopmental sequelae among infants born during the pandemic. There is controversy as to the exact etiopathogenesis of these neurodevelopmental effects: from the infection itself or as a result of parental emotional stress during that period. We summarize case reports of acute neonatal SARS-CoV-2 infections associated with neurological signs and neuroimaging changes. Many infants born during previous pandemics caused by other respiratory viruses demonstrated serious neurodevelopmental and psychological sequelae that were only recognized after several years of follow-up. It is essential to warn health authorities about the need for very long-term continuous follow up of infants born during the SARS-CoV-2 pandemic for early detection and treatment that could help mitigate the neurodevelopmental consequences of perinatal COVID-19.

Impact of perinatal COVID on fetal and neonatal brain and neurodevelopmental outcomes.

After three years of the COVID-19 pandemic, we have learned many aspects of the disease and the virus: its molecular structure, how it infects human cells, the clinical picture at different ages, potential therapies, and the effectiveness of prophylaxis. Research is currently focused on the short- and long-term consequences of COVID-19. We review the available information on the neurodevelopmental outcome of infants born during the pandemic from infected and non-infected mothers, as well as the neurological impact of neonatal SARS-CoV-2 infection. We also discuss the mechanisms that could potentially affect the fetal or neonatal brain including direct impact after vertical transmission, maternal immune activation with a proinflammatory cytokine storm, and finally the consequences of complications of pregnancy secondary to maternal infection that could affect the fetus. Several follow-up studies have noted a variety of neurodevelopmental sequelae among infants born during the pandemic. There is controversy as to the exact etiopathogenesis of these neurodevelopmental effects: from the infection itself or as a result of parental emotional stress during that period. We summarize case reports of acute neonatal SARS-CoV-2 infections associated with neurological signs and neuroimaging changes. Many infants born during previous pandemics caused by other respiratory viruses demonstrated serious neurodevelopmental and psychological sequelae that were only recognized after several years of follow-up. It is essential to warn health authorities about the need for very long-term continuous follow up of infants born during the SARS-CoV-2 pandemic for early detection and treatment that could help mitigate the neurodevelopmental consequences of perinatal COVID-19.

Maternal-Fetal Immunologic Response to SARS-CoV-2 Infection in a Symptomatic Vulnerable Population: A Prospective Cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disproportionally affects pregnant women and their newborn; however, little is known about variables that modulate maternal-fetal immune response to infection. METHODS: We prospectively studied socioeconomic, biologic, and clinical factors affecting humoral immunity in 87 unvaccinated pregnant women hospitalized in Buenos Aires for symptoms consistent with COVID-19. RESULTS: The number of days between symptom onset and childbirth predicted maternal and newborn virus spike protein receptor binding domain (RBD)-specific immunoglobulin G (IgG). These findings suggest newborns may benefit less when mothers deliver soon after COVID-19 infection. Similarly, a longer time between symptom onset and birth predicted higher in utero transfer of maternal IgG and its concentration in cord blood. Older gestational age at birth was associated with lower maternal to cord blood IgG ratio. Of women with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 87% developed RBD-specific IgA responses in breast milk within 96 hours of childbirth. IgA was not significantly associated with time from infection but correlated with maternal serum IgG and placental transfer. CONCLUSIONS: These results demonstrate the combined role of biologic, clinical, and socioeconomic variables associated with maternal RBD-specific antibodies and supports early vaccination strategies for COVID-19 in socioeconomically vulnerable pregnant women. CLINICAL TRIALS REGISTRATION: NCT04362956.

Ischemic Lesions in the Brain of a Neonate With SARS-CoV-2 Infection.

AIM: To describe a term newborn with acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and multisystem involvement including seizures associated to ischemic lesions in the brain. BACKGROUND: Coronavirus disease 2019 (COVID-19) is predominantly a respiratory infection, but it may affect many other systems. Most pediatric COVID-19 cases range from asymptomatic to mild-moderate disease. There are no specific clinical signs described for neonatal COVID-19 infections. In children, severe central nervous system compromise has been rarely reported. CASE DESCRIPTION: We describe a 17-day-old newborn who acquired a SARS-CoV-2 infection in a family meeting that was admitted for fever, seizures and lethargy and in whom consumption coagulopathy, ischemic lesions in the brain and cardiac involvement were documented. CONCLUSIONS: SARS-CoV-2 neonatal infection can be associated with multi-organic involvement. In our patient, significant central nervous system compromise associated to ischemic lesions and laboratory findings of consumption coagulopathy were found. CLINICAL SIGNIFICANCE: Although neonatal SARS-CoV-2 infections are infrequent, they can be associated with multi-organic involvement. Neonatologists and pediatricians should be aware of this unusual way of presentation of COVID-19 in newborn infants.

COVID-19 preparedness-a survey among neonatal care providers in low- and middle-income countries.

OBJECTIVE: To evaluate COVID-19 pandemic preparedness, available resources, and guidelines for neonatal care delivery among neonatal health care providers in low- and middle-income countries (LMICs) across all continents. STUDY DESIGN: Cross-sectional, web-based survey administered between May and June, 2020. RESULTS: Of 189 invited participants in 69 LMICs, we received 145 (77%) responses from 58 (84%) countries. The pandemic provides significant challenges to neonatal care, particularly in low-income countries. Respondents noted exacerbations of preexisting shortages in staffing, equipment, and isolation capabilities. In Sub-Saharan Africa, 9/35 (26%) respondents noted increased mortality in non-COVID-19-infected infants. Clinical practices on cord clamping, isolation, and breastfeeding varied widely, often not in line with World Health Organization guidelines. Most respondents noted family access restrictions, and limited shared decision-making. CONCLUSIONS: Many LMICs face an exacerbation of preexisting resource challenges for neonatal care during the pandemic. Variable approaches to care delivery and deviations from guidelines provide opportunities for international collaborative improvement.

Preparedness strategies in neonatology units during the COVID-19 pandemic: A survey conducted at maternity centers in Argentina. / Estrategias de preparación en unidades de neonatología durante la pandemia de COVID-19: Encuesta en maternidades de la Argentina.

INTRODUCTION: The objective of this study was to analyze available resources, guidelines in use, and preparedness to care for newborn infants at maternity centers in Argentina during the COVID-19 pandemic. METHOD: Cross-sectional study based on a survey administered to medical and nursing staff. In May 2020, Argentine facilities with more than 500 annual births were contacted; 58 % of these were from the public sector. RESULTS: In total, 104/147 facilities answered (71 %). All had guidelines for care during the pandemic, and 93 % indicated they had been trained on how to use them. A companion was not allowed during childbirth in 26 % of private facilities and in 60 % of public ones (p < 0.01). Deferred cord clamping was recommended in 87 %; rooming-in with asymptomatic newborns was promoted in 62 %; breastfeeding using protective measures was recommended in 70 %; and breast milk using a bottle, in 23 %. In 94 %, family visiting in the Neonatology Unit was restricted. Difficulties included the unavailability of individual rooms for symptomatic newborn infants and a potential shortage of health care staff and personal protective equipment. CONCLUSIONS: All facilities are aware of the national guidelines to fight the pandemic. Most have the resources to comply with the recommended protective measures. There is uncertainty as to whether personal protective equipment, staff, and physical space available at the different facilities would be enough if cases increased significantly.

Introducción. El objetivo de este estudio fue analizar recursos disponibles, guías utilizadas y preparación para la atención de neonatos en maternidades de Argentina durante la pandemia de COVID-19. Método. Estudio transversal mediante una encuesta enviada a equipos médicos y de enfermería. En mayo de 2020, se contactaron instituciones de más de 500 nacimientos anuales en la Argentina, el 58 % del sector público. Resultados. Respondieron 104/147 instituciones (el 71 %). Todas contaban con guías para la atención durante la pandemia, y un 93 % refirió haber recibido capacitación para su uso. No autorizaban la presencia de acompañante en el parto el 26 % de instituciones privadas y el 60 % de las públicas (p < 0,01). El 87 % recomendaba ligadura oportuna del cordón, el 62 % promovía internación conjunta en neonatos asintomáticos, un 70 % recomendaba la puesta al pecho con medidas de protección, y el 23 %, leche materna mediante biberón. El 94 % restringía el ingreso de familiares a Neonatología. Las dificultades incluyeron imposibilidad de contar con habitaciones individuales para neonatos sintomáticos y potencial limitación del personal de salud y equipos de protección personal. Conclusiones. Todas las instituciones conocen las guías nacionales para enfrentar la pandemia. La mayoría cuenta con recursos para respetar las medidas de protección recomendadas. Existe incertidumbre sobre si, ante un aumento significativo en el número de casos, serán suficientes los elementos de protección personal, el personal y el espacio físico disponible en los distintos centros.