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.

Background and Purpose Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported five-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. Methods The Vascular effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009–2014, and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of stroke etiologies, including arteriopathies. Other predictors were measured via parental interview or chart review. Results Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0–3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% CI 4.6–10%) at one month and 12% (8.5–15%) at one year. The sole predictor of recurrence was presence of an arteriopathy, which increased the risk of recurrence 5-fold compared to an idiopathic AIS (hazard ration 5.0, 95% CI 1.8–14). The one-year recurrence rate was 32% (95% CI 18–51%) for moyamoya, 25% (12–48%) for transient cerebral arteriopathy, and 19% (8.5–40%) for arterial dissection. Conclusions Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

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.

Background and Purpose Although arteriopathies are the most common cause of childhood arterial ischemic stroke (AIS), and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with AIS. Methods VIPS, an international prospective study, enrolled 355 cases of AIS (age 29d-18y) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results Cases were median 7.6 years of age (IQR 2.8, 14); 56% male. The majority (52%) were previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at Step 1, 90% at Step 2, and 94% at Step 3; specificity was high throughout (99%, 100%, 100%), as was agreement between reviewers (Kappa 0.77, 0.81, 0.78). Conclusions Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood AIS.

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 (β 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.

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.

Background and Purpose Among children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process, and that inflammatory biomarkers would predict recurrent AIS. Methods In an international study of childhood AIS, we selected cases classified into one of the three most common childhood AIS etiologies: definite arteriopathic (N=103), cardioembolic (N=55), or idiopathic (N=78). We measured serum concentrations of high sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), myeloperoxidase (MPO), and tumor necrosis factor alpha (TNF-α). We used linear regression to compare analyte concentrations across the subtypes, and Cox proportional hazards models to determine predictors of recurrent AIS. Results Median age at index stroke was 8.2 years (IQR 3.6, 14.3); serum samples were collected at median 5.5 days post-stroke (IQR 3, 10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of hsCRP and MPO, while both cardioembolic and arteriopathic groups had higher SAA. In the arteriopathic (but not cardioembolic) group, higher hsCRP and SAA predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend towards higher hsCRP and SAA, compared to children with stable or improved arteriopathies. Conclusion Among children with AIS, specific inflammatory biomarkers correlate with etiology and—in the arteriopathy group—risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

BACKGROUND AND PURPOSE In adult stroke, the advent of thrombolytic therapy led to the development of Primary Stroke Centers able 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 Prior to 2004 <25% of TIPS sites had continuous twenty-four hour availability of acute stroke teams, MRI capability, or stroke order sets, despite significant pediatric stroke expertise. Following 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 1–10 Likert scale on which 10 represented complete readiness, median center readiness increased from 6.2 prior to site preparation to 8.7 at the time of site activation (P=<0.001). CONCLUSIONS Prior to 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 tPA.