Outcomes of Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection at a Large Medical Center in New York City.

Importance: Limited data on vertical and perinatal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and health outcomes of neonates born to mothers with symptomatic or asymptomatic coronavirus disease 2019 (COVID-19) are available. Studies are needed to inform evidence-based infection prevention and control (IP&C) policies. Objective: To describe the outcomes of neonates born to mothers with perinatal SARS-CoV-2 infection and the IP&C practices associated with these outcomes. Design, Setting, and Participants: This retrospective cohort analysis reviewed the medical records for maternal and newborn data for all 101 neonates born to 100 mothers positive for or with suspected SARS-CoV-2 infection from March 13 to April 24, 2020. Testing for SARS-CoV-2 was performed using Cobas (Roche Diagnostics) or Xpert Xpress (Cepheid) assays. Newborns were admitted to well-baby nurseries (WBNs) (82 infants) and neonatal intensive care units (NICUs) (19 infants) in 2 affiliate hospitals at a large academic medical center in New York, New York. Newborns from the WBNs roomed-in with their mothers, who were required to wear masks. Direct breastfeeding after appropriate hygiene was encouraged. Exposures: Perinatal exposure to maternal asymptomatic/mild vs severe/critical COVID-19. Main Outcomes and Measures: The primary outcome was newborn SARS-CoV-2 testing results. Maternal COVID-19 status was classified as asymptomatic/mildly symptomatic vs severe/critical. Newborn characteristics and clinical courses were compared across maternal COVID-19 severity. Results: In total, 141 tests were obtained from 101 newborns (54 girls [53.5%]) on 0 to 25 days of life (DOL-0 to DOL-25) (median, DOL-1; interquartile range [IQR], DOL-1 to DOL-3). Two newborns had indeterminate test results, indicative of low viral load (2.0%; 95% CI, 0.2%-7.0%); 1 newborn never underwent retesting but remained well on follow-up, and the other had negative results on retesting. Maternal severe/critical COVID-19 was associated with newborns born approximately 1 week earlier (median gestational age, 37.9 [IQR, 37.1-38.4] vs 39.1 [IQR, 38.3-40.2] weeks; P = .02) and at increased risk of requiring phototherapy (3 of 10 [30.0%] vs 6 of 91 [7.0%]; P = .04) compared with newborns of mothers with asymptomatic/mild COVID-19. Fifty-five newborns were followed up in a new COVID-19 Newborn Follow-up Clinic at DOL-3 to DOL-10 and remained well. Twenty of these newborns plus 3 newborns followed up elsewhere had 32 nonroutine encounters documented at DOL-3 to DOL-25, and none had evidence of SARS-CoV-2 infection, including 6 with negative retesting results. Conclusions and Relevance: No clinical evidence of vertical transmission was identified in 101 newborns of mothers positive for or with suspected SARS-CoV-2 infection, despite most newborns rooming-in and direct breastfeeding practices.

A review of newborn outcomes during the COVID-19 pandemic.

As the COVID-19 pandemic continues to spread worldwide, it is crucial that we determine populations that are at-risk and develop appropriate clinical care policies to protect them. While several respiratory illnesses are known to seriously impact pregnant women and newborns, preliminary data on the novel SARS-CoV-2 Coronavirus suggest that these groups are no more at-risk than the general population. Here, we review the available literature on newborns born to infected mothers and show that newborns of mothers with positive/suspected SARS-CoV-2 infection rarely acquire the disease or show adverse clinical outcomes. With this evidence in mind, it appears that strict postnatal care policies, including separating mothers and newborns, discouraging breastfeeding, and performing early bathing, may be more likely to adversely impact newborns than they are to reduce the low risk of maternal transmission of SARS-CoV-2 or the even lower risk of severe COVID-19 disease in otherwise healthy newborns.

Dyslipidemia in Children With Arterial Ischemic Stroke: Prevalence and Risk Factors.

BACKGROUND: Risk factors for pediatric stroke are poorly understood and require study to improve prevention. Total cholesterol and triglyceride values peak to near-adult levels before puberty, a period of increased stroke incidence. The role of lipids in childhood arterial ischemic stroke has been minimally investigated. METHODS: We performed a cross-sectional analysis of lipid and Lp(a) concentrations in children with arterial ischemic stroke in the International Pediatric Stroke Study to compare the prevalence of dyslipidemia and high- or low-ranking lipid values in our dataset with reported population values. We analyzed sex, body mass index, race, ethnicity, family history, and stroke risk factors for associations with dyslipidemia, high non-high-density lipoprotein cholesterol, and hypertriglyceridemia. RESULTS: Compared with the National Health and Nutrition Examination Survey, a higher proportion of children ≥5 years with arterial ischemic stroke had dyslipidemia (38.4% versus 21%), high total cholesterol (10.6% versus 7.4%), high non-high-density lipoprotein cholesterol (23.1% versus 8.4%), and low high-density lipoprotein cholesterol (39.8% versus 13.4%). The lipid values that corresponded to one standard deviation above the mean (84th percentile) in multiple published national studies generally corresponded to a lower ranking percentile in children aged five years or older with arterial ischemic stroke. Dyslipidemia was more likely associated with an underweight, overweight, or obese body mass index compared with a healthy weight. Ethnic background and an acute systemic illness were also associated with abnormal lipids. CONCLUSIONS: Dyslipidemia and hypertriglyceridemia may be more prevalent in children with arterial ischemic stroke compared with stroke-free children.

Aligning Animal Models of Clinical Germinal Matrix Hemorrhage, From Basic Correlation to Therapeutic Approach.

BACKGROUND: Germinal matrix hemorrhage is a leading cause of mortality and morbidity from prematurity. This brain region is vulnerable to bleeding and re-bleeding within the first 72 hours of preterm life. Cerebroventricular expansion of blood products contributes to the mechanisms of brain injury. Consequences include lifelong hydrocephalus, cerebral palsy, and intellectual disability. Unfortunately little is known about the therapeutic needs of this patient population. OBJECTIVES: This review discusses the mechanisms of germinal matrix hemorrhage, the animal models utilized, and the potential therapeutic targets. CONCLUSION: Potential therapeutic approaches identified in pre-clinical investigations include corticosteroid therapy, iron chelator administration, and transforming growth factor-ß pathway modulation, which all warrant further investigation. Thus, effective preclinical modeling is essential for elucidating and evaluating novel therapeutic approaches, ahead of clinical consideration.

Orbital Hemangioma with Intracranial Vascular Anomalies and Hemangiomas: A New Presentation of PHACE Syndrome?

We present two cases of infants with a similar constellation of clinical findings: retro-orbital infantile hemangioma (IH), internal carotid artery (ICA) arteriopathy, and intracranial IH. In both cases, intracranial vascular anomalies and hemangiomas were found incidentally during evaluation of unilateral proptosis. Neither infant had evidence of cutaneous segmental IH of the face or neck, which might have provided a clue to the diagnosis of PHACE syndrome or of intracranial hemangiomas. In one case, intracranial involvement was particularly extensive and function threatening, with mass effect on the brain parenchyma. These cases serve to highlight the fact that clinical findings of proptosis, globe deviation, and strabismus should prompt immediate imaging to confirm the presence of orbital IHs and to exclude other diagnoses. Moreover, based on our cases and the embryologic origin of the orbit as a unique developmental unit, patients with confirmed retro-orbital IHs should undergo evaluation for anomalies associated with PHACE syndrome. Patients with orbital IHs and an additional major criterion for PHACE syndrome should be considered to have definite, and not just possible, PHACE syndrome.

Predictive validity of severity grading for cerebral steno-occlusive arteriopathy in recurrent childhood ischemic stroke.

BACKGROUND: Cerebral arteriopathy is a risk factor for incident and recurrent childhood AIS. There are no standardized criteria to quantify arteriopathy severity. AIMS: To evaluate a method of scoring severity of steno-occlusive arteriopathy in childhood arterial ischemic stroke (AIS) and its association with recurrence. METHODS: In a single-center prospectively enrolled cohort of 49 children with first AIS and arteriopathy, a composite cerebrovascular stenosis score (CVSS) was measured by two independent raters as the sum of stenosis scores in each of 18 intracranial large and medium arteries, where 0 = none; 1 = low-grade, 1-50%; 2 = high-grade, >50-99%; 3 = occlusion, 100%. Cox proportional-hazards models were used to determine the association of CVSS with recurrence. The analysis was stratified by presence or absence of moyamoya arteriopathy (syndrome or disease). RESULTS: At a median follow-up period of 2.5 years (range: 0.8-9), 18/49 children (37%) experienced a recurrence. Median time to recurrence was 0.2 (range: 0.02-2.8) years. Interrater agreement was good, with an intraclass correlation coefficient of 0.77 [95% confidence interval (CI) 0.63-0.87, P < 0.001). Higher CVSS was associated with higher recurrence rate [hazard ratio (HR) per point 1.09, 95% CI 1.04-1.16, P = 0.001]. Among those with moyamoya arteriopathy, CVSS was associated with recurrence (HR per point of CVSS 1.11, 95% CI 1.03-1.19, P = 0.004), but there was no association in those without moyamoya arteriopathy (HR per point of CVSS 0.91, 95% CI 0.75-1.09, P = 0.32). CONCLUSIONS: The CVSS is a reliable measure of severity of steno-occlusive arteriopathy in childhood stroke. This preliminary study suggests that higher CVSS is associated with stroke recurrence in children with moyamoya arteriopathy.

Clinical spectrum of capillary malformation-arteriovenous malformation syndrome presenting to a pediatric dermatology practice: a retrospective study.

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is an autosomal dominant disorder caused by RASA1 mutations. The prevalence and phenotypic spectrum are unknown. Evaluation of patients with multiple CMs is challenging because associated AVMs can be life threatening. The objective of this study was to describe the clinical characteristics of children presenting with features of CM-AVM to an academic pediatric dermatology practice. After institutional review board approval was received, a retrospective chart review was performed of patients presenting between 2009 and 2012 with features of CM-AVM. We report nine cases. Presenting symptoms ranged from extensive vascular stains and cardiac failure to CMs noted incidentally during routine skin examination. All demonstrated multiple CMs, two had Parkes Weber syndrome, and two had multiple infantile hemangiomas. Seven patients had family histories of multiple CMs; three had family histories of large, atypical CMs. Six had personal or family histories of AVMs. Genetic evaluation was recommended for all and was pursued by six families; four RASA1 mutations were identified, including one de novo. Consultations with neurology, cardiology, and orthopedics were recommended. Most patients (89%) have not required treatment to date. CM-AVM is an underrecognized condition with a wide clinical spectrum that often presents in childhood. Further evaluation may be indicated in patients with multiple CMs. This study is limited by its small and retrospective nature.

Predictors of cholesterol and lipoprotein(a) testing in children with arterial ischemic stroke.

BACKGROUND: Professional societies recommend screening lipids in healthy children. Dyslipidemia and elevated lipoprotein(a) are risk factors for adult cardiovascular disease and stroke. Their role in childhood arterial ischemic stroke is unexplored. Inconsistencies in testing limit analysis of existing lipid data. The objective of this study is to identify predictors and modifiable barriers to lipid testing in pediatric stroke. METHODS: In this cross-sectional analysis, children (28 days-18 years) with arterial ischemic stroke were identified from the International Pediatric Stroke Study registry (January 2003-April 2012). Analyzed predictors of recorded lipid or lipoprotein a (Lp(a)) testing were age, sex, race, ethnicity, body mass index (BMI) category, other stroke risk factors, country, US region, and recurrent thrombosis. RESULTS: Among 1652 participants (median, 6 years [interquartile range, 1.7-12.7]; 59.0% male; 40.8% white; 7.0% black), at least 1 lipid parameter or Lp (a) was available for 461 (27.9%). Compared with infants, testing was incrementally higher for older age categories. Compared with whites, testing was lower in blacks (adjusted odds ratio [OR], .5; 95% confidence interval [CI], .4-.5; P < .0001). Hispanic ethnicity only predicted testing within the United States (OR, 2.2; 95% CI, 1.4-3.4; P = .001]. Testing was lower in the United States and Australia and higher in Chile. Any thrombotic recurrence and recurrent symptomatic arterial ischemic stroke were associated with testing, unlike male sex, BMI, other stroke risk factors, and region in the United States. CONCLUSIONS: Only a quarter of children with stroke had recorded lipid testing. Older age, white race, and recurrence predicted testing. In future study adjusting for these predictors may be necessary. Standardized lipid testing in children with arterial ischemic stroke may further our understanding of this potential risk factor.

Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial.

BACKGROUND AND PURPOSE: In adult stroke, the advent of thrombolytic therapy led to the development of primary stroke centers capable to diagnose and treat patients with acute stroke rapidly. We describe the development of primary pediatric stroke centers through preparation of participating centers in the Thrombolysis in Pediatric Stroke (TIPS) trial. METHODS: We collected data from the 17 enrolling TIPS centers regarding the process of becoming an acute pediatric stroke center with capability to diagnose, evaluate, and treat pediatric stroke rapidly, including use of thrombolytic therapy. RESULTS: Before 2004, <25% of TIPS sites had continuous 24-hour availability of acute stroke teams, MRI capability, or stroke order sets, despite significant pediatric stroke expertise. After TIPS preparation, >80% of sites now have these systems in place, and all sites reported increased readiness to treat a child with acute stroke. Use of a 1- to 10-Likert scale on which 10 represented complete readiness, median center readiness increased from 6.2 before site preparation to 8.7 at the time of site activation (P≤0.001). CONCLUSIONS: Before preparing for TIPS, centers interested in pediatric stroke had not developed systematic strategies to diagnose and treat acute pediatric stroke. TIPS trial preparation has resulted in establishment of pediatric acute stroke centers with clinical and system preparedness for evaluation and care of children with acute stroke, including use of a standardized protocol for evaluation and treatment of acute arterial stroke in children that includes use of intravenous tissue-type plasminogen activator. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01591096.

Review of lipid and lipoprotein(a) abnormalities in childhood arterial ischemic stroke.

National organizations recommend cholesterol screening in children to prevent vascular disease in adulthood. There are currently no recommendations for cholesterol and lipoprotein (a) testing in children who experience an arterial ischemic stroke. While dyslipidemia and elevated lipoprotein (a) are associated with ischemic stroke in adults, the role of atherosclerotic risk factors in childhood arterial ischemic stroke is not known. A review of the literature was performed from 1966 to April 2012 to evaluate the association between childhood arterial ischemic stroke and dyslipidemia or elevated lipoprotein (a). Of 239 citations, there were 16 original observational studies in children (with or without neonates) with imaging-confirmed arterial ischemic stroke and data on cholesterol or lipoprotein (a) values. Three pairs of studies reported overlapping subjects, and two were eliminated. Among 14 studies, there were data on cholesterol in 7 and lipoprotein (a) in 10. After stroke, testing was performed at >three-months in nine studies, at ≤three-months in four studies, and not specified in one study. There were five case-control studies: four compared elevated lipoprotein (a) and one compared abnormal cholesterol in children with arterial ischemic stroke to controls. A consistent positive association between elevated lipoprotein (a) and stroke was found [Mantel-Haenszel OR 4·24 (2·94-6·11)]. There was no association in one study on total cholesterol, and a positive association in one study on triglycerides. The literature suggests that elevated lipoprotein (a) may be more likely in children with arterial ischemic stroke than in control children. The absence of confirmatory study on dyslipidemia should be addressed with future research.

Circle of Willis configuration as a determinant of intracranial dolichoectasia.

BACKGROUND: Circle of Willis (COW) variants might influence arterial caliber in the brain. We hypothesized that these variants would be associated with the prevalence of intracranial dolichoectasia (DE). METHODS: We examined COW variants and DE in a sample of stroke-free participants (n = 436) undergoing magnetic resonance angiography (MRA) as part of a population-based study. Large intracranial arterial diameters were obtained when available; if not, the artery was defined as hypoplastic or absent according to its visibility on MRA. Subscores for the anterior and the posterior circulations were created. DE was defined as arterial diameters ≥2 SD above the population mean for that artery, adjusting for intracranial volume. Generalized linear models with a Poisson distribution were used to evaluate predictors of both absent and hypoplastic vessels, and logistic regression was used to assess the odds ratio (OR) and 95% confidence interval (95% CI) of DE depending on COW variants. RESULTS: Only 44% of the sample had all 14 arteries present, 32% lacked 1 artery, 18% lacked 2 and 6% lacked 3 or more. DE of at least 1 artery was not associated with the total number of hypoplastic or absent arteries, but DE in a posterior circulation artery was weakly associated with the number of absent arteries in the posterior circulation (ß coefficient = 0.36, p = 0.06). DE of at least 1 artery was more frequent in those with 1 or more absent arteries (OR 1.27, 95% CI 1.03-1.57). Posterior circulation DE was more frequent in participants with at least 1 or more absent arteries at any location (OR 1.35, 95% CI 1.02-1.78). Participants with an incomplete posterior COW were more likely to have DE in the anterior circulation (OR 1.52, 95% CI 1.01-2.33). Having an absent left anterior cerebral artery (ACA) A1 segment was associated with right ACA DE (OR 34.1, 95% CI 3.16-368.2); an absent right ACA was associated with left ACA DE (OR 14.1, 95% CI 1.69-118.28). Absence of 1 (OR 1.9, 95% CI 1.1-3.4) or 2 (OR 3.0, 95% CI 1.4-6.6) of the 2 arteries connecting the anterior to the posterior circulation was associated with basilar artery DE. CONCLUSION: The COW is a pleomorphic structure that allows collateral flow to compensate for an insufficient or absent arterial component at the base of the skull. By presumed flow diversion, arteries might undergo outward remodeling. Whether this compensatory arterial dilatation is beneficial or not remains unknown.

The growing problem of stroke among young adults.

Although overall stroke incidence has been declining in developed countries, there is evidence that stroke in the young is increasing. Increasing incidence may be particularly pronounced among minorities in whom historically a higher burden of stroke has been reported. Compared with older adults, time spent with disability is longer for those affected at younger ages, and new data suggests that among 30-day young adult stroke survivors, increased mortality persists for as long as 20 years. Stroke in young adults is often missed by less experienced clinicians due to its unexpectedness, leading to lost opportunities for intervention. The causes and risk factors for stroke in the young are often rare or undetermined, but young adults with stroke also have a high burden of traditional cardiovascular risk factors, including hypertension, diabetes, obesity, and substance abuse. Disseminating awareness and promoting research on young adult stroke are steps towards reducing the burden of stroke.