Trends of mortality rate in patients with congenital heart defects in Germany-analysis of nationwide data of the Federal Statistical Office of Germany.

BACKGROUND: Congenital heart defects (CHD) are still associated with an increased morbidity and mortality. The aim of this study was to analyze trends of mortality rates in patients with CHD between 1998 and 2018 in Germany. METHODS: Data of registered deaths with an underlying diagnosis of CHD were used to evaluate annual mortality between 1998 and 2018. Polynomial regressions were performed to assess annual changes in CHD-associated mortality rates by age groups. RESULTS: During the 21-year study period, a total of 11,314 deaths were attributed to CHD with 50.9% of deaths in infants (age < 1 year) and 28.2% in neonates (age ≤ 28 days). The most frequent underlying CHDs associated with death were hypoplastic left heart syndrome (n = 1498, 13.2%), left ventricular outflow tract obstruction (n = 1009, 8.9%), atrial septal defects (n = 771, 6.8%), ventricular septal defects (n = 697, 6.2%), and tetralogy of Fallot (n = 673, 5.9%), and others (n = 6666, 58.9%). Among all patients, annual CHD-related mortality rates declined significantly between 1998 and 2010 (p < 0.0001), followed by a significant annual increase until 2018 (p < 0.0001). However, mortality rates in 2018 in all ages were significantly lower than in 1998. CONCLUSION: Mortality in CHD patients decreased significantly between 1998 and 2010, but a substantial number of deaths still occurred and even significantly increased in the last 3 years of the observation period particularly in neonates and infants. This renewed slight increase in mortality rate during the last years was influenced mainly by high-risk neonates and infants. Assessment of factors influencing the mortality rate trends in association with CHD in Germany is urgently needed. Obligatory nationwide registration of death cases in relation to surgical and catheter interventions in CHD patients is necessary to provide additional valuable data on the outcome of CHD.

SARS-CoV-2 sero-immunity and quality of life in children and adolescents in relation to infections and vaccinations: the IMMUNEBRIDGE KIDS cross-sectional study, 2022.

PURPOSE: The study evaluates the effects on sero-immunity, health status and quality of life of children and adolescents after the upsurge of the Omicron variant in Germany. METHODS: This multicenter cross-sectional study (IMMUNEBRIDGE Kids) was conducted within the German Network University Medicine (NUM) from July to October 2022. SARS-CoV-2- antibodies were measured and data on SARS-CoV-2 infections, vaccinations, health and socioeconomic factors as well as caregiver-reported evaluation on their children's health and psychological status were assessed. RESULTS: 497 children aged 2-17 years were included. Three groups were analyzed: 183 pre-schoolchildren aged 2-4 years, 176 schoolchildren aged 5-11 years and 138 adolescents aged 12-18 years. Positive antibodies against the S- or N-antigen of SARS-CoV-2 were detected in 86.5% of all participants (70.0% [128/183] of pre-schoolchildren, 94.3% of schoolchildren [166/176] and 98.6% of adolescents [136/138]). Among all children, 40.4% (201/497) were vaccinated against COVID-19 (pre-schoolchildren 4.4% [8/183], schoolchildren 44.3% [78/176] and adolescents 83.3% [115/138]). SARS-CoV-2 seroprevalence was lowest in pre-school. Health status and quality of life reported by the parents were very positive at the time of the survey (Summer 2022). CONCLUSION: Age-related differences on SARS-CoV-2 sero-immunity could mainly be explained by differences in vaccination rates based on the official German vaccination recommendations as well as differences in SARS-CoV-2 infection rates in the different age groups. Health status and quality of life of almost all children were very good independent of SARS-CoV-2 infection and/or vaccination. TRIAL REGISTRATION: German Registry for Clinical Trials Identifier Würzburg: DRKS00025546 (registration: 11.09.2021), Bochum: DRKS00022434 (registration:07.08.2020), Dresden: DRKS 00022455 (registration: 23.07.2020).

Growth patterns in children and adolescents with cerebral palsy from Argentina and Germany.

To analyze growth patterns of children with CP between countries; to examine differences in growth; and to assess the fit of growth charts. Cross-sectional study in children with CP from 2 to 19 years old, 399 from Argentina and 400 from Germany. Growth measures were converted into z-scores and compared to WHO reference and US CP growth charts. Generalized Linear Model was used to analyze the growth expressed as mean z-scores. 799 children. Mean age 9 years (± 4). Compared to the WHO reference, the decrease in Height z-scores (HAZ) with age in Argentina (- 0.144/year) was double that in Germany (- 0.073/year). For children in GMFCS IV-V, BMI z-scores (BMIZ) decreased with age (- 0.102/year). Using the US CP charts, both countries showed decreasing HAZ with age, in Argentina (- 0.066/year) and in Germany (- 0.032/year). BMIZ increased more among children with feeding tubes (0.062/year), similar in both countries. Argentinian children with oral feeding decrease their Weight z-score (WAZ) by - 0.553 compared to their peers. With WHO charts BMIZ presented an excellent fit for GMFCS I-III. HAZ presents a poor fit to growth references. BMIZ and WAZ presented a good fit to US CP Charts. Growth differences due to ethnicity also act in children with CP, and are related to motor impairment, age and feeding modality, possibly reflecting differences in environment or health care.

[COVID-19 vaccination in children and adolescents]. / COVID-19-Impfung bei Kindern und Jugendlichen: Hatten wir alles im Blick?

Background: The COVID-19 pandemic posed special challenges for the existing structures for vaccination prevention in Germany with respect to 1) understanding the role and aims of those involved and the interests of the children and 2) the definition of adequate criteria and assessment of the risk of severe diseases in children. Objectives: Do the priorities of different groups of interest differ in the recommendations for COVID-19 vaccination? Which data on the pathogenicity of different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) are necessary and how did they change during the pandemic? Methods: The tasks, objectives and perception of politics and the German national vaccination advisory committee regarding vaccination of children are discussed in the face of summarized recent data on clinical manifestations of pediatric SARS-CoV­2 infections among children and adolescents in Germany, which could be estimated by combining different German data sources. Results: The perspectives of politics and children differ but are legitimate when they are clearly stated. The decisive risk for a severe course or the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV­2 (PIMS-TS) per 10,000 SARS-CoV­2 infections for the decision on vaccination from the perspective of children, decreased during the course of the pandemic with dominance of the omicron variant. Severe courses of COVID-19 still predominantly affect children with underlying diseases. The age-stratified analysis of vaccinated and nonvaccinated children showed that the alterations in the pathogenicity of the virus in the course of the pandemic is particularly reflected in the reduction in the risk of PIMS-TS. The general reduction of severe courses of COVID-19 again can be explained by the characteristics of variants of concern (VOC) as well as increasing vaccination rates and immunity following a SARS-CoV­2 infection. Conclusion: The primary goal of COVID-19 vaccination in children and adolescents is the prevention of severe courses of the disease. In pediatric risk groups the best possible immunity or immune protection by vaccination should be strived for. It is currently unclear whether catch-up vaccination in already infected or vaccinated children or whether forthcoming healthy children will need vaccination, aiming for hybrid immunity.

Comparing SARS-CoV-2 variants among children and adolescents in Germany: relative risk of COVID-19-related hospitalization, ICU admission and mortality.

PURPOSE: SARS-CoV-2 infections cause COVID-19 and have a wide spectrum of morbidity. Severe disease courses among children are rare. To date, data on the variability of morbidity in relation to variant of concern (VOC) in children has been sparse and inconclusive. We compare the clinical severity of SARS-CoV-2 infection among children and adolescents in Germany during the Wildtype and Alpha combined, Delta and Omicron phases of the COVID-19 pandemic. METHODS: Comparing risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death due to COVID-19 in children and adolescents, we used: (1) a multi-center seroprevalence study (SARS-CoV-2-KIDS study); (2) a nationwide registry of pediatric patients hospitalized with SARS-CoV-2 infections; and (3) compulsory national reporting for RT-PCR-confirmed SARS-CoV-2 infections in Germany. RESULTS: During the Delta predominant phase, risk of COVID-19-related hospitalization among all SARS-CoV-2 seropositive children was 3.35, ICU admission 1.19 and fatality 0.09 per 10,000; hence about halved for hospitalization and ICU admission and unchanged for deaths as compared to the Wildtype- and Alpha-dominant period. The relative risk for COVID-19-related hospitalization and ICU admission compared to the alpha period decreased during Delta [0.60 (95% CI 0.54; 0.67) and 0.51 (95% CI 0.42; 0.61)] and Omicron [0.27 (95% CI 0.24; 0.30) and 0.06 (95% CI 0.05; 0.08)] period except for the < 5-year-olds. The rate of case fatalities decreased slightly during Delta, and substantially during Omicron phase. CONCLUSION: Morbidity caused by SARS-CoV-2 infections among children and adolescents in Germany decreased over the course of the COVID-19 pandemic, as different VOCs) emerged.

Burden of Pediatric SARS-CoV-2 Hospitalizations during the Omicron Wave in Germany.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents were not yet available. Given Omicron's high transmissibility, the ability to assess its impact on admission and hospitalization rates in children's hospitals is critical for the purpose of understanding the scope of its burden on the German healthcare system. (2) Methods: From 24 January 2022 to 31 July 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and the need for respiratory support, were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4-3) per reporting pediatric hospital per day was hospitalized in general wards, whereas a median of 0.1 cases (range 0-0.4 cases) was admitted to intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with the need for intensive care treatment and respiratory support due to symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children's hospitals.

Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany.

Importance: During 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. Objective: To 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 Participants: This 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. Exposures: Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays. Main Outcomes and Measures: Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue. Results: Among 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 Relevance: These 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.

Risk for severe outcomes of COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany.

Although children and adolescents have a lower burden of SARS-CoV-2-associated disease compared to adults, assessing the risk for severe outcomes among SARS-CoV-2-infected children remains difficult due to a high rate of undetected cases. We combine data from three data sources - a national seroprevalence study (the SARS-CoV-2 KIDS study), the nationwide, state-based reporting system for PCR-confirmed SARS-CoV-2 infections in Germany, and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or pediatric inflammatory multisystem syndrome (PIMS-TS, also known as MIS-C) - in order to provide estimates on the risk of hospitalization for COVID-19-related treatment, intensive care admission, and death due to COVID-19 and PIMS-TS in children. The rate of hospitalization for COVID-19-related treatment among all SARS-CoV-2 seropositive children was 7.13 per 10,000, ICU admission 2.21 per 10,000, and case fatality was 0.09 per 10,000. In children without comorbidities, the corresponding rates for severe or fatal disease courses were substantially lower. The lowest risk for the need of COVID-19-specific treatment was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.37 per 10,000, and case fatality could not be calculated due to the absence of cases. The overall PIMS-TS rate was 2.47 per 10,000 SARS-CoV-2 infections, the majority being children without comorbidities. CONCLUSION: Overall, 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 the overall disease burden among all pediatric age groups. WHAT IS KNOWN: • SARS-CoV-2-associated burden of disease in children is considered to be low, but accurate risk estimates accounting for clinically undiagnosed infections are lacking. • Asymptomatic SARS-CoV-2 infections are common in children. WHAT IS NEW: • We provide risk estimates for hospitalization for COVID-19-related treatment, ICU admission, death from COVID-19, and PIMS-TS for children with SARS-CoV-2 infections by pooling different data sources. • The risk for PIMS-TS exceeds the risk for severe COVID-19 in all age groups; the risk for severe COVID-19 is the lowest in 5-11 years old.

Cognitive disorders in childhood epilepsy: a comparative longitudinal study using administrative healthcare data.

OBJECTIVE: The study aimed to assess the risk of cognitive impairment in patients with epilepsy, the impact of age of epilepsy onset on cognition and the temporal relationship of epilepsy onset and intellectual impairment. METHODS: This longitudinal study analyzed birth cohorts and followed-up children born 2005-2007 up to the age of ten using administrative healthcare data of about 8.9 million members insured by the statutory health insurance "BARMER" in Germany. We compared prevalence of cognitive impairment (ICD-code F7*) in children with epilepsy (ICD-code G40) to controls, and calculated relative risks by age groups at onset of epilepsy and assessed differences in relation to the temporal sequence of the diagnoses. RESULTS: Of the 142,563 pre-pubertal children included in the analysis, 2728 (1.9%) had an epilepsy diagnosis within the first 10 years of life. 17.4% (475/2728) of children with epilepsy had a diagnosis of cognitive impairment compared to 1.7% (2309/139835) in controls. The relative risk for cognitive impairment compared to age-matched controls was 10.5 (95% CI 9.6, 11.6) and was highest in epilepsy cases with seizure manifestation within the first 2 years of life compared to older children. The prevalence of cognitive impairment before epilepsy diagnosis was slightly increased compared to controls, while it was increased by a factor of nine in children diagnosed with cognitive impairment in the year of onset of epilepsy or afterwards. CONCLUSIONS: Pre-pubertal children with epilepsy have a ten-fold higher risk for intellectual impairment compared to age-matched controls. This risk inversely correlates with the age of epilepsy manifestation. Cognitive impairment was diagnosed after epilepsy manifestation in the majority of patients.

Test-Retest Reliability and Construct Validity of the German Translation of the Gait Outcome Assessment List (GOAL) Questionnaire for Children with Ambulatory Cerebral Palsy.

The Gait Outcome Assessment List (GOAL) is a patient or caregiver-reported assessment of gait-related function across different domains of the International Classification of Functioning, Disability, and Health (ICF) developed for ambulant children with cerebral palsy (CP). So far, the questionnaire is only available in English. The aim of this study was to translate the GOAL into German and to evaluate its reliability and validity by studying the association between GOAL scores and gross motor function as categorized by the gross motor function classification system (GMFCS) in children with cerebral palsy (CP). The GOAL was administered to primary caregivers of n = 91 children and adolescents with CP (n = 32, GMFCS levels I; n = 27, GMFCS level II; and n = 32, GMFCS level III) and n = 15 patients were capable of independently completing the whole questionnaire (GMFCS level I). For assessing test-retest reliability, the questionnaire was completed for a second time 2 weeks after the first by the caregivers of n = 36 patients. Mean total GOAL scores decreased significantly with increasing GMFCS levels with scores of 71 (95% confidence interval [CI]: 66.90-74.77) for GMFCS level I, 56 (95% CI: 50.98-61.86) for GMFCS level II, and 45 (95% CI: 40.58-48.48) for GMFCS level III, respectively. In three out of seven domains, caregivers rated their children significantly lower than children rated themselves. The test-retest reliability was excellent as was internal consistency given the GOAL total score. The German GOAL may serve as a much needed patient-reported outcome measure of gait-related function in ambulant children and adolescents with CP.

Impact of School Closures on the Proportion of Children in the COVID-19 Pandemic: An Example from the Winter Lockdown in Germany.

BACKGROUND: In addition to widely used basic hygiene measures in school, school closures are applied to contain SARS-CoV-2 spread, although the effect on the pandemic is unclear. We proposed a simple approach to disentangle the effect of school closures from other lockdown measures on the pandemic course based on publicly available data in Germany. METHODS: We used data on the number of SARS-CoV-2 cases from the onset of the pandemic to 14th April 2021. We compared the proportion of children (5-14 years old) in all cases prior to the lockdown measures, including school closure, to that during a ten-week lockdown in Germany. The total number of paediatric cases occurring during lockdown was compared to the number expected in absence of school closures. The latter was calculated based on the actual weekly number of all cases and the pre-lockdown proportion of paediatric cases. RESULTS: The proportion of children in all cases was 2.3 percentage points lower at the nadir than the proportion before the lockdown. The estimated total number of paediatric cases prevented by school closures was estimated at 13,246 amounting to 24% of the expected cases in absence of school closures. CONCLUSION: School closure during the winter lockdown reduced the number of expected SARS-CoV-2 cases in children in absence of school closures. The contribution of these prevented cases to the total population incidence is small. These data might provide the basis to model the effect of school closures in addition to basic hygiene measures on the course of the COVID-19 pandemic.

Total health insurance costs in children with a migraine diagnosis compared to a control group.

BACKGROUND: Health care costs of migraine constitute a major issue in health economics. Several publications analyzed health care costs for adult migraine patients, based on questionnaires or secondary (health insurance) data. Although migraine often starts already in primary school age, data on migraine related costs in children is scarce. In this paper we aimed to assess the migraine-related health care costs in 6 to 11 year old children in Germany. METHODS: Using claims data of a large German health insurer (BARMER), overall annual health care costs of 6 to 11 year old children with a diagnosis of migraine in 2017 (n = 2597) were compared to a control group of 6 to 11 year old children without a headache diagnosis between 2013 and 2017 (n = 306,926). The association of migraine and costs was modeled by generalized linear regression (Gamma regression) with adjustment for sex, age and comorbidities. RESULTS: Children with migraine caused considerably higher annual per capita health care costs than children without a headache diagnosis (migraine group: € 1018, control group: € 618). Excess costs directly related to migraine amounted to € 115. The remaining excess costs were related to comorbidities, which were more frequent in the migraine group. Mental and behavioural disorders constituted the most expensive comorbidity, accounting for € 105 of the € 400 annual excess costs in the migraine group. CONCLUSION: 6 to 11 year old children with a migraine diagnosis cause significant direct and comorbidity related excess costs in the German health care system.

Is the BNT162b2 COVID-19 vaccine effective in elderly populations? Results from population data from Bavaria, Germany.

BACKGROUND: The efficacy of the BioNTech-Pfizer BNT162b2 vaccination in the elderly (≥80 years) could not be fully assessed in the BioNTech-Pfizer trial due to low numbers in this age group. We aimed to evaluate the effectiveness of the BioNTech-Pfizer (BNT162b2) vaccine to prevent SARS-CoV-2 infection and severe outcomes in octo- and novo-generians in a German state setting. METHODS AND FINDINGS: A prospective observational study of 708,187 persons aged ≥80 years living in Bavaria, Germany, was conducted between Jan 9 to Apr 11, 2021. We assessed the vaccine effectiveness (VE) for two doses of the BNT162b2 vaccine with respect to SARS-CoV-2 infection and related hospitalisations and mortality. Additionally, differences in VE by age groups ≥80 to ≤89 years and ≥90 years were studied. Analyses were adjusted by sex. By the end of follow-up, 63.8% of the Bavarian population ≥80 years had received one dose, and 52.7% two doses, of the BNT162b2 vaccine. Two doses of the BNT162b2 vaccine lowered the proportion of SARS-CoV-2 infections and related outcomes, resulting in VE estimates of 68.3% (95% confidence interval (CI) 65.5%, 70.9%) for infection, 73.2% (95% CI 65.3%, 79.3%) for hospitalisation, and 85.1% (95% CI 80.0%, 89.0%) for mortality. Sex differences in the risk of COVID-19 outcomes observed among unvaccinated persons disappeared after two BNT162b2 vaccine doses. Overall, the BNT162b2 vaccine was equally effective in octo- and novo-genarians. CONCLUSIONS: Two doses of BioNTech-Pfizer's BNT162b2 vaccine is highly effective against COVID-19 outcomes in elderly persons.

Migraine and the development of additional psychiatric and pain disorders in the transition from adolescence to adulthood.

INTRODUCTION: The transition from childhood to adolescence and from adolescence to adulthood are vulnerable phases in life. In these phases, late or insufficient treatment of diseases may lead to chronification and favor development of additional disorders. In adolescents, migraine often has a highly negative impact on school performance and everyday life. The hypothesis of the present study was that adolescents with migraine have a higher risk for developing additional disorders such as psychiatric disorders or other pain syndromes in the course of the disease. MATERIALS AND METHODS: In this study, we analyzed health insurance data of 56,597 German adolescents at the age of 15 years in the year 2006. By using the International Classification of Diseases (ICD 10), we determined a group with migraine diagnosis in the year 2006 and a control group without any headache diagnosis in 2006. We then compared both groups regarding the development of additional disorders (based on the ICD 10) during the following 10 years (2007 to 2016). RESULTS: Adolescents with migraine had a 2.1 fold higher risk than persons without migraine diagnosis to develop an additional affective or mood disorder, a 1.8 fold higher risk to obtain neurotic, stress-related and somatoform disorders, a 1.8 fold higher risk to subsequently suffer from behavioral syndromes, a 1.6 higher risk to get back pain and a 1.5 fold higher risk for irritable bowel syndrome during the next 10 years. CONCLUSION: Adolescents with migraine are at risk for developing additional disorders later. Considering and addressing the patient's risks and potential medical and psychosocial problems might improve the long-term outcome significantly.

Incidence trends of parapneumonic pleural effusions/empyema in children 2009 to 2018 from health insurance data: Only temporal reduction after the introduction of PCV13.

BACKGROUND: Recently, emergence of a higher proportion of serotype 3 in children with parapneumonic pleural effusion/empyema (PPE/PE) were observed in Germany despite general immunization with 13-valent pneumococcal conjugate vaccine (PCV13) since 2009. The impact of PCV13 on the overall incidence of PPE/PE in children is unclear. METHODS: Annual incidence of PPE/PE in children were determined using secondary health care data for 2009-2018, provided by the Barmer statutory health insurer, serving about 11% of the German population. Temporal trends of the annual incidence were modelled applying generalized additive models. RESULTS: Overall incidence of PPE/PE in children ( ≤18 years) in the ten-year observation period was 18.17 per 100,000. The 0-1 year olds showed the highest incidence (43.09 per 100 000). PPE/PE incidence decreased from 2009 until 2013 (nadir 2013 was 15.36; 95% CI: 13.41-17.31). Since 2013, the data show an annual increase. The nadir of incidence for the 2-5 year olds (15.85; 95% CI: 11.27-20.43) and the 6-18 year olds (12.29; 95% CI: 10.23-14.36) was also in 2013, whereas for the 0-1 year olds it was found in 2014 (32.66; 95% CI: 23.79-41.54). The GAM across all age groups showed a nearly U-shaped curve between time and incidence of PPE/PE by calendar year (p-non-linear = 0.0017). The model confirms the nadir in the year 2013. DISCUSSION: We found a nonlinear temporal trend of PPE/PE incidence in children with a decrease from 2009 to 2013 and a subsequent increase until 2018. The former might be explained by a quasi elimination of serotype 1, the latter by an increase in the proportion of serotype 3 as demonstrated in German surveillance data of pediatric PPE/PE cases generated during the same observation period.

Incidence Estimates of Perinatal Arterial Ischemic Stroke in Preterm- and Term-Born Infants: A National Capture-Recapture Calculation Corrected Surveillance Study.

INTRODUCTION: Data on valid incidence estimates of perinatal arterial ischemic stroke (PAIS) are scarce. This analysis aims to determine incidence of PAIS in term- and preterm-born infants and to investigate clinical differences related to prematurity. METHODS: This surveillance study (2015-2017) in all German paediatric hospital estimated incidences for MRI-confirmed PAIS in term and preterm infants. To correct for under-reporting, we performed capture-recapture-calculations (CRC) in the most populous federal state and extrapolated nationwide. Differences in clinical presentation in term- and preterm-born infants were assessed. RESULTS: 126 term- and 19 preterm-born infants with PAIS were reported. CRC corrected incidence of PAIS was 22 (95% confidence interval [CI] 17, 27) per 100,000 live births. Stratified by prematurity, the incidence was 32 (95% CI 15, 49) per 100,000 in preterm-born infants and 21 (95% CI 16, 26) per 100,000 term-born infants (significant difference p = 0.001). In symptomatic cases only (n = 120 term born, n = 12 preterm born), incidences did not differ. Risk factor patterns were similar, but number of risk factors in preterm babies was elevated (mean 3.8 vs. 2.9; p = 0.01) and median age at diagnosis was increased (5 vs. 3 days; p = 0.04). Clinical seizures were observed in 88% (106/120) of symptomatic term infants compared to 33% (4/12) in preterm-born infants (p < 0.0001). CONCLUSION: PAIS incidence rates in Germany, extrapolated from estimates for completeness of reporting in the largest federal state, were within the range of other population-based studies. As a novel finding, we detected symptomatic PAIS in preterm-born infants to be as common as in term-born infants although their symptoms were often unspecific.

Clinical Diversity of Cerebral Sinovenous Thrombosis and Arterial Ischaemic Stroke in the Neonate: A Surveillance Study.

INTRODUCTION: Incidence, risk factors, clinical presentation, onset of symptoms, and age at diagnosis differ between neonatal arterial ischaemic stroke (AIS) and cerebral sinovenous thrombosis (CSVT). A more accurate and earlier discrimination of these two entities can be of eminent importance. METHODS: Active surveillance for AIS and CSVT was performed in 345 German paediatric hospitals. Only MRI confirmed cases were included in our analysis. Patients with AIS were compared to CSVT cases with regard to age at diagnosis, pattern of clinical symptoms, and case characteristics. RESULTS: Data on 144 AIS and 51 CSVT neonatal cases were collected from 2015 to 2017. The frequency of reported AIS cases was 2.8 [95% CI 2.1; 3.9] times higher compared to reported CSVT cases. CSVT patients were more likely to be born premature (CSVT 14/48, 29.2%; AIS 19/140, 13.2%; p = 0.02) and to have signs of perinatal acidosis (30.2% CSVT vs. 13.5% AIS; p = 0.01). Generalized seizures and lethargy were more likely to occur in infants with CSVT (p < 0.0001). Age at onset of symptoms and at time of diagnosis were shifted to older ages in CSVT (p < 0.0001). DISCUSSION/CONCLUSION: In the neonatal period, AIS is about three times more common than CSVT. A higher proportion of critically ill infants in CSVT and a later onset of symptoms may indicate that perinatal and postnatal complications are more important for CSVT than for AIS.

Incidence and risk factors of cerebral sinovenous thrombosis in infants.

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.

[Decrease in Group B Streptococcal Infections in Neonates: Analysis of Health Insurance Data 2005 to 2017]. / Rückgang von Infektionen durch Streptokokken der Gruppe B bei Neugeborenen: Analyse von Krankenversicherungsdaten 2005 bis 2017.

BACKGROUND: In the German guidelines for prophylaxis of group B streptococcal (GBS) early onset sepsis in neonates (EOS), GBS screening of all pregnant women has been recommended, but is not yet included in the Maternity Directives. Aim of the study was to identify temporal trends in incidence of EOS and their association to GBS Screening. METHODS: The analysis based on health insurance data of the statutory health insurance provider Barmer from 2005 to 2017 of 313,385 mother-child pairs. Annual frequency of GBS infections in newborns was determined by ICD-10 P36.0. The frequency of maternal GBS colonization was indicated by ICD-10 B95.1, which was used as surrogate for GBS screening. Temporal trends of the risk of EOS in neonates were assessed in logistic regression models. Pearson's correlation coefficient of EOS incidence and the surrogate marker for maternal GBS colonization was calculated. RESULTS: The risk of EOS in neonates caused by GBS has decreased annually by 9.3%, resulting in an overall decrease in the observation period of 72.0%. There was no statistical significant change in the risk for LOS (Late Onset Sepsis). The decrease of EOS could not be explained by temporal changes in Caesarian section, risk factors or preterm delivery. The 3.5 fold increase in the proportion of mothers with documented positive GBS colonization in the same period correlated inversely with the incidence of EOS (r=- 0.75; p=0.002). CONCLUSION: The decrease of EOS in neonates caused by GBS in Germany and the unchanged risk of LOS in neonates may be explained by the increasing application of the GBS Screening in pregnant women.