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Aim To identify maternal, obstetric, and neonatal risk factors related to perinatal arterial ischaemic stroke (PAIS) diagnosed within 28 days after birth and to understand the underlying pathophysiology. Method For case and control ascertainment, we used active surveillance in 345 paediatric hospitals and a population‐based perinatal database for quality assurance of hospital care. We analysed complete cases of PAIS using logistic regression. Multivariate analysis was guided by a directed acyclic graph. Results After exclusion of records with missing data, we analysed 134 individuals with PAIS and 576 comparison individuals. In univariate analysis, male sex, preterm birth (<37wks gestational age), small for gestational age (SGA), low umbilical artery pH (<7.1), low 5‐minute‐Apgar score (<7), multiple pregnancies, hypoxia, intubation/mask ventilation, nulliparity, Caesarean section, vaginal‐operative delivery, chorioamnionitis, and oligohydramnios were associated with an increased risk. Mutual adjustment yielded male sex (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.20–2.73), multiple birth (OR 3.22; 95% CI 1.21–8.58), chorioamnionitis (OR 9.89; 95% CI 2.88–33.94), preterm birth (OR 1.86; 95% CI 1.01–3.43), and SGA (OR 3.05; 95% CI 1.76–5.28) as independent risk factors. Interpretation We confirmed the increased risk in males and the role of chorioamnionitis and SGA for PAIS, pointing to the importance of inflammatory processes and fetal–placental insufficiency. Multiple birth and preterm birth were additional risk factors. What this paper adds Chorioamnionitis and small for gestational age (SGA) precede perinatal arterial ischaemic stroke (PAIS). Chorioamnionitis and SGA are independent risk factors for PAIS. Inflammatory processes and fetal–placental insufficiency are the likely underlying mechanisms. Multiple birth and preterm birth are additional risk factors.

BackgroundAlthough children and adolescents have a lower burden of SARS-CoV-2-associated disease as compared to adults, assessing absolute risk among children remains difficult due to a high rate of undetected cases. However, without more accurate case numbers, reliable risk analyses are impossible.MethodsWe combine data from three sources — a national seroprevalence study (the SARS-CoV-2 KIDS study), the German statutory notification system and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or Pediatric Inflammatory Multisystem Syndrome (PIMS-TS) — in order to provide reliable estimates on children’s hospitalization, intensive care admission and death due to COVID-19 and PIMS-TS.ResultsWhile the overall hospitalization rate associated with SARS-CoV-2 infection was 35.9 per 10,000 children, ICU admission rate was 1.7 per 10,000 and case fatality was 0.09 per 10,000. Children without comorbidities were found to be significantly less likely to suffer from a severe or fatal disease course. The lowest risk was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.2 per 10,000 and case fatality could not be calculated, due to an absence of cases. The overall PIMS-TS rate was 1 per 4,000 SARS-CoV-2 infections, the majority being children without comorbidities.ConclusionOverall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5-11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in overall disease burden among all pediatric age groups.

The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 12.9) in March 2021 with little change up to May 2021. Rates increased by migrant background (2.8%, 4.4% and 7.8% for no, one and two parents born outside Germany). Children under three were initially 3.6 (95% CI 2.3, 5.7) times more likely to be seropositive with levels equalising later. The ratio of seropositive cases per recalled infection decreased from 8.6 to 2.8. Since seropositivity exceeds the rate of recalled infections considerably, serologic testing may provide a more valid estimate of infections, which is required to assess both the spread and the risk for severe outcomes of SARS-CoV-2 infections.

Aim To describe the incidence of term and preterm neonatal cerebral sinovenous thrombosis (CSVT) and identify perinatal risk factors. Method This was a national capture‐recapture calculation‐corrected surveillance and nested case–control study. Infants born preterm and at term with magnetic resonance imaging‐confirmed neonatal CSVT were identified by surveillance in all paediatric hospitals in Germany (2015–2017). Incidence was corrected for underreporting using a capture‐recapture method in one federal state and then extrapolated nationwide. We reviewed PubMed for comparisons with previously reported incidence estimators. We used a population‐based perinatal database for quality assurance to select four controls per case and applied univariate and multivariable regression for risk factor analysis. Results Fifty‐one newborn infants (34 males, 17 females; 14 born preterm) with neonatal CSVT were reported in the 3‐year period. The incidence of term and preterm neonatal CSVT was 6.6 (95% confidence interval [CI] 4.4–8.7) per 100 000 live births. Median age at time of confirmation of the diagnosis was 9.95 days (range 0–39d). In the univariate analysis, male sex, preterm birth, hypoxia and related indicators (umbilical artery pH <7.1; 5‐minute Apgar score <7; intubation/mask ventilation; perinatal asphyxia), operative vaginal delivery, emergency Caesarean section, and pathological fetal Doppler sonography were associated (p<0.05) with neonatal CSVT. Multivariable regression yielded hypoxia (odds ratio=20.3; 95% CI 8.1–50.8) as the independent risk factor. Interpretation Incidence of neonatal CSVT was within the range of other population‐based studies. The results suggest that hypoxia is an important perinatal risk factor for the aetiology of neonatal CSVT.

ImportanceDuring the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures.ObjectiveTo assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents.Design, Setting, and ParticipantsThis substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years.ExposuresSeropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays.Main Outcomes and MeasuresKey symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue.ResultsAmong 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2–seropositive (40.0%) and 158 of 534 SARS-CoV-2–seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS–related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue.Conclusions and RelevanceThese findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.

Purpose To investigate the relationship between the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children and the predominance of different SARS-CoV-2 variants of concern (VOC) over time. Methods In relation to the Alpha, Delta, and Omicron VOC phases of the pandemic, the risk of developing PIMS-TS was calculated by analyzing data for rtPCR-confirmed SARS-CoV-2 infections reported to the German statutory notification system, along with data captured by a separate, national PIMS-TS registry. Both overall infection rates and age group-specific ratios of PIMS-TS during the different pandemic phases were calculated using the Alpha period as the baseline. Results The PIMS-TS rate changed significantly over time. When the Alpha VOC was dominant [calendar week (CW) 11 in March–CW 31 in August 2021], the PIMS-TS rate was 6.19 [95% confidence intervals (95% CI) 5.17, 7.20]. When Delta prevailed (CW 32 in August 2021–CW 4 in January 2022), the rate decreased to 1.68 (95% CI 1.49, 1.87). During the Omicron phase (CW 5 in January–CW 16 in April 2022), the rate fell further to 0.89 (95% CI 0.79, 1.00). These changes correspond to a decreased PIMS-TS rate of 73% (rate ratio 0.271, 95% CI 0.222; 0.332) and 86% (rate ratio 0.048, 95% CI 0.037; 0.062), respectively, in comparison to the Alpha period. Rate ratios were nearly identical for all age groups. Conclusion The data strongly suggest an association between the risk for PIMS-TS and the prevailing VOC, with highest risk related to Alpha and the lowest to Omicron. Given the uniformity of the decreased risk across age groups, vaccination against SARS-CoV-2 does not appear to have a significant impact on the risk of children developing PIMS-TS.

<b><i>Introduction:</i></b> Relative risk, risk factors, clinical presentation, onset of symptoms, and age at diagnosis differ between arterial ischaemic stroke (AIS) and cerebral sinovenous thrombosis (CSVT) in neonates. Distinguishing these 2 entities in time clinically can be of eminent importance. <b><i>Methods:</i></b> Active surveillance for AIS and CSVT was performed in 345 German paediatric hospitals. Only cases confirmed by cerebral MRI were included in our analysis. Patients with AIS were compared to CSVT cases with regard to age at diagnosis, pattern of clinical symptoms, and risk factors. <b><i>Results:</i></b> Data on 144 AIS and 51 CSVT neonatal cases were collected from 2015 to 2017. The relative risk of AIS was 2.8 (95% CI 2.1; 3.9) times higher than that of CSVT. CSVT patients were more likely to be born premature (CSVT 14/48, 29.2%; AIS 19/140, 13.2%; <i>p</i> = 0.02) and to have signs of perinatal acidosis (e.g., umbilical artery pH ≤ 7.1 30.2% CSVT vs. 13.5% AIS <i>p</i> = 0.01). Generalized seizures and lethargy were more likely to occur in infants with CSVT (<i>p</i> &#x3c; 0.0001). Age at onset of symptoms and at time of diagnoses was shifted to older ages in CSVT (<i>p</i> &#x3c; 0.0001). <b><i>Discussion/Conclusion:</i></b> The risk for AIS is about 3 times higher than that for CSVT in neonates. A higher proportion of critically ill infants in CSVT and a later onset of symptoms may indicate that perinatal and postnatal risk factors are more important for CSVT than for AIS. The data underline the need for an increased awareness of CSVT in critically ill infants.