[Results of PCR Pool Testing In Primary and Special Needs Schools In Bavaria For The School Year 2021/2022: Sentinel Surveillance In Face-To-Face Teaching During The Sars-CoV-2 Pandemic]. / Ergebnisse von PCR-Pooltestungen an bayerischen Grund- und Förderschulen im Schuljahr 2021/2022 zur Surveillance im Präsenzunterricht während der SARS-CoV-2-Pandemie.

In the school years 2019/20 and 2020/21, children were physically, psychologically, and socially stressed by school closures caused by the SARS-CoV-2 pandemic. To ensure attendance with optimal infection protection, PCR pool testing was conducted during the 2021/22 school year at Bavarian elementary schools and schools for pupils with special needs for timely detection of SARS-CoV-2 infection. This study analyzes the results of PCR pool testing over time stratified by region, school type, and age of children. The data were obtained from classes in elementary and special needs schools, involving pupils aged 6 to 11 years, who participated in the Bavaria-wide PCR pool testing from 09/20/21 to 04/08/22. Samples were collected twice weekly, consisting of PCR pool samples and individual PCR samples, which were only evaluated in case of a positive pool test. A class was considered positive if at least one individual sample from that class was positive within a calendar week (CW). A school (class) was considered to be infection-prone if three or more classes in that school (students in that class) were positive within a CW. The data included 2,430 elementary schools (339 special needs schools) with 23,021 (2,711) classes and 456,478 (29,200) children. A total of 1,157,617 pools (of which 3.37% were positive) and 724,438 individual samples (6.76% positive) were analyzed. Larger schools exhibited higher PR compared to smaller schools. From January 2022, the Omicron variant led to a massive increase in PR across Bavaria. The incidence rates per 100,000 person-weeks within the individual school samples were significantly lower than the concurrently reported age-specific and general infection incidences in the overall Bavarian population. PCR pool testing revealed relatively few positive pools, with an average of four children per one hundred pools testing positive. Schools and classes were rarely considered infection-prone, even during periods of high incidences outside of schools. The combination of PCR pool testing and hygiene measures allowed for a largely safe in-person education for pupils in primary and special needs schools in the school year 2021/22.

Caring for a Child with Congenital Adrenal Hyperplasia Diagnosed by Newborn Screening: Parental Health-Related Quality of Life, Coping Patterns, and Needs.

Diagnosing a child by newborn screening with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) causes multiple challenges for the affected parents and the whole family. We aimed to examine the health-related Quality of Life (HrQoL), coping, and needs of parents caring for a child with CAH to develop demand-responsive interventions for improving the psychosocial situation of affected families. In a retrospective cross-sectional design, we assessed HrQoL, coping patterns, and the needs of parents caring for a CAH-diagnosed child using specific questionnaires. Data of 59 families with at least one child diagnosed with CAH were analyzed. The results show that mothers and fathers in this study reached significantly higher HrQoL scores compared to reference cohorts. Decisive for the above-average parental HrQoL were effective coping behaviors and the parental needs being met. These findings verify the importance of helpful coping patterns and rapid fulfillment of parental needs for maintaining a good and stable HrQoL of parents with a child diagnosed with CAH. It is crucial to strengthen the parental HrQoL to build a reasonable basis for a healthy upbringing and improve the medical care of CAH-diagnosed children.

The Impact of Migration Background on the Health Outcomes of Preschool Children: Linking a Cross-Sectional Survey to the School Entrance Health Examination Database in Bavaria, Germany.

AIM OF THE STUDY: This study investigated the impact of migration background on the health outcomes of preschool children from families of various social status levels. METHODS: During the school entrance health examination (Schuleingangsuntersuchung (SEU)) from October 2012 to August 2013, the parents of 5052 preschool children (62% response rate) participated in a cross-sectional health survey within the framework of health-monitoring units (Gesundheits-Monitoring-Einheiten (GME)) in Bavaria, Germany. They were handed a self-administered questionnaire with questions relating to the language spoken at home and other socio-demographic characteristics. By applying the record linkage method, 3747 participants were correctly linked to the corresponding data of the SEU. Based on the merged dataset, 4 definitions of migration background were explored regarding demographic indicators, the parents' mother tongue, and the language spoken at home. The association between migration background and health outcomes of preschool children was analyzed using multivariable logistic regression models separately. The risk estimates were presented for the study population and stratified into high, medium, and low social status. The models were repeated for each of the 4 migration background variables. RESULTS: The results show significant associations between migration background and health outcomes of preschool children (except in pronunciation). A migration background had the strongest impact on the development of word/sentence formation disorder. Compared to non-migrant preschool children, migrant children had twice the chances for full vaccination coverage (OR [95% CI]: 2.4 [1.9-3.1]) but only half the chance to participate in all health examinations from U1 to U9 (0.5 [0.4-0.6]). These children were also at two-fold increased risk to be overweight/obese (2.2 [1.7-2.8]). Moreover, preschool children with double-sided migration from medium social status families faced the highest risk for word/sentence formation disorder (9.5 [5.6-16.1] with SEU definition and 23.3 [10.3-52.6] with GME definition of a migration background). CONCLUSIONS: Future prevention programs at the preschool level should focus on children with double-sided migration from medium social status families. With respect to social and cultural integration, the definition of migration background based on the language spoken at home should be appropriate for future SEUs.

[Epidemiological studies with environmental relevance in Germany]. / Epidemiologische Studien mit Umweltbezug in Deutschland.

Our environment is a major factor in determining health and well-being throughout life, from conception into old age. This overview illustrates the most important epidemiological studies and health monitoring systems in Germany, which investigate environmental influences in various population subgroups and estimate related health effects. Environmental factors examined in each study are described. The mentioned studies in children and adults build the basis for predictions and preventive measures. The number of the assessed environmental factors, the depth of the examinations as well as the (phenotypical) characterization of the study participants differ. Still, the obtained data build a base for important future research. However, for this, a permanent and Germany-wide assessment of environmental factors is necessary.The proportion of the European population living in urban areas is projected to increase in the future. Therefore, environmental factors such as air pollution, air temperature, and noise, but also social inequality, are likely to have a negative effect on health and quality of life of the population. The challenge of the aging population as well as potential adaptation processes to the diverse environmental stimuli requires multidisciplinary approaches. From an environmental epidemiology view, the collected data from the described studies are of immense value because only with this data can associations between environment and health be investigated and public health-relevant preventive measures be identified.The NAKO health study will be the largest resource of health data and should therefore be included in future activities related to the investigation of environmental health effects in Germany.

Asthmatic/wheezing phenotypes in preschool children: Influential factors, health care and urban-rural differences.

BACKGROUND: Different wheezing and asthmatic phenotypes turned out to indicate differences in etiology, risk factors and health care. We examined influential factors and urban-rural differences for different phenotypes. METHODS: Parents of 4732 children filled out a questionnaire concerning children's health and environmental factors administered within the Health Monitoring Units (GME) in a cross-sectional study in Bavaria, Germany (2014/2015). To classify respiratory symptoms, five phenotype groups were built: episodic, unremitting and frequent wheeze, ISAAC (International Study of Asthma and Allergies in Children) - asthma and physician-diagnosed asthma (neither of the groups are mutually exclusive). For each phenotype, health care variables were presented and stratified for residence. Urban-rural differences were tested by Pearson's chi-squared tests. Multivariable logistic regression was performed to analyze associations between influential factors and belonging to a phenotype group, and to compare groups with regard to health care variables as outcome. RESULTS: Risk factors for wheezing phenotypes were male gender (OR = 2.02, 95%-CI = [1.65-2.48]), having older siblings (OR = 1.24, 95%-CI = [1.02-1.51]), and preterm delivery (OR = 1.61, 95%-CI = [1.13-2.29]) (ORs for unremitting wheeze). 57% of children with ISAAC asthma and 74% with physician-diagnosed asthma had performed allergy tests. Medication intake among all groups was more frequent in rural areas, and physician's asthma diagnoses were more frequent in urban areas. CONCLUSIONS: In accordance with previous research this study confirms that male gender, older siblings and preterm delivery are associated with several wheezing phenotypes. Overall, low numbers of allergy tests among children with physician's diagnoses highlight a discrepancy between common practice and current knowledge and guidelines. Residential differences in health care might encourage further research and interventions strategies.

[Predictors of Health-related Quality of Life in Bavarian Preschool Children]. / Prädiktoren gesundheitsbezogener Lebensqualität bei bayerischen Einschulungskindern.

BACKGROUND: Little data are available on health-related quality of life (HRQOL) of children in Germany at the age of school enrollment. OBJECTIVE: Aim of this study was to investigate the HRQOL of children during school enrollment and to determine its predictors with special focus on environmental factors. METHODS: Data from the fifth survey of the Health-Monitoring-Units (GME) conducted in Bavaria (2010/2011) were analyzed. Parent-reported data on HRQOL using the KINDL-R(evised), the Strength and Difficulties Questionnaire (SDQ), socio-demographic characteristics and characteristics of the living environment were assessed. RESULTS: The sample included a total of 3,744 children (45.9% female; mean age: 6.0; SD=0.4). Girls had significantly higher values than boys in total HRQOL (83.7 vs. 82.4, p ≤0.0001) and in all KINDL-R subscales except "psychological well-being" and "physical well-being". For the latter, boys had significantly higher values than girls (84.1 vs. 82.9, p=0.0103). Multiple linear regression analysis showed that parental annoyance with air or noise pollution, possibility for children to safely play outside and the time a child is outside on weekdays in the summertime were significant predictors of total HRQOL measured by the KINDL-R. Obesity was not linked to HRQOL. Children with migration background had significantly higher values in the subscales "family" and "friends". CONCLUSIONS: Environmental factors are associated with HRQOL in children at the age of school enrollment but only partially of relevant use. Although they show significant associations, their explanatory power of the variability observed is rather limited.

Exploring the associations between parent-reported biological indoor environment and airway-related symptoms and allergic diseases in children.

OBJECTIVES: Asthma and allergic rhinitis are diseases which require special attention in childhood. Risk factors for these diseases are manifold and include environmental factors. Previous studies have shown associations between indoor mould and respiratory diseases in children. Besides indoor mould, organic waste storage, potted plants, pets and crowding could influence the microbial indoor environment at home and the respiratory health of children. Our aim was therefore to explore the associations of these factors with airway-related symptoms and respiratory diseases in preschoolers. METHODS: In this cross-sectional study we evaluated data based on parent-questionnaires regarding the health of their children from the 2014/2015 Health Monitoring Units (GME) in Bavaria. Bivariate and multivariate odds ratios (OR) with 95% confidence intervals (95%-CI) were calculated with logistic regression to explore associations between exposures (visible mould, organic waste storage, potted plants, pets and crowding) and outcome variables (doctor diagnosed allergic rhinitis with symptoms in the last 12 months, doctor diagnosed asthma with symptoms in the last 12 months, 12 month prevalence of symptoms such as dry cough at night without a cold, wheeze, wheeze attacks and allergic rhinitis symptoms). RESULTS: We analysed data from 4732 children (response rate 56.7%) with a mean age of 5.3 years. Visible mould was present in 4.7% of all households and associated with doctor diagnosed asthma with symptoms in the last 12 months [aOR 2.16 (95%-CI 1.01-4.63)], wheeze in the last 12 months [aOR 1.60 (95%-CI 1.0-2.50)] and allergic rhinitis symptoms in the last 12 months [aOR 1.75 (95%-CI 1.07-2.87)]. Crowding was associated with dry cough at night without a cold in the last 12 months [aOR 1.71 (95%-CI 1.42-2.05). The other indoor factors showed no association with respiratory health of the children. CONCLUSION: Our results, in line with previous studies, showed positive associations between visible mould at home and airway-related symptoms and allergic diseases in children irrespective of the effect of the other considered indoor exposures. Despite the low prevalence of mould exposure in our study population, our results suggest intervention should be taken for those who do have visible mould exposure at home.

[Respiratory and allergic diseases of children : Temporal trends, urban-rural differences, and in association with environmental tobacco smoke exposure]. / Atemwegs- und Allergieerkrankungen bei Kindern : Zeitliche Trends, Stadt-Land-Unterschiede und Assoziationen mit einer Tabakrauchexposition.

BACKGROUND/OBJECTIVES: Ten years after the establishment of health monitoring units (GME) in Bavaria, temporal trends and urban-rural differences in parent-reported respiratory and allergic diseases as well as environmental tobacco smoke (ETS) exposure in preschoolers were analyzed in an explorative manner. Furthermore, associations between diseases and ETS exposure were studied. METHODS: Parent questionnaires were used as part of the school entrance examination in two cross sectional studies (S1:2004/2005, n 1 = 6350; S2:2012/2013, n 2 = 5052). Temporal trends and urban-rural-differences were tested by X2 tests. Associations between diseases and exposures were studied using multiple logistic regression analysis. RESULTS: The lifetime prevalence of atopic dermatitis declined from S1-S2 from 12.4 to 11.1 %, whereas those for hay fever, asthma, bronchitis and pseudocroup remained stable. In S1 and S2, bronchitis was less often reported in cities. The other diseases showed no urban-rural differences. The prevalence of children's ETS exposure at home declined from S1-S2 from 14.3 to 7.2 % and was generally higher in cities than in rural regions. There was no positive association between diseases and children's ETS exposure at home. In S2 an association was found between asthma and current parental smoking (OR = 1.60; 95 % CI = (1.10-2.32)). CONCLUSION: The GME provide important data for regional distribution of respiratory and allergic diseases and ETS exposure of preschoolers in Bavaria. The results of the study are important for further development of questionnaires, which will be used in future GME.

Children's exposure to second-hand smoke before and after the smoking ban in Bavaria-a multiple cross-sectional study.

BACKGROUND: The federal state of Bavaria, Germany enforced a comprehensive smoking ban across all enclosed public areas in 2008 to protect non-smokers from second-hand smoke (SHS). Evidence against displacement of smoking to homes is abundant, however long-term assessments are few. We aim to report prevalence of children's SHS exposure before and after the ban, parental smoking behaviour and exposure risk factors. METHODS: Cross-sectional data of children aged 5-6 years old in Bavaria (n = 22 944) were collected in 2004/5 and 2005/6 (S1 and S2) before the ban and after in 2008/9 and 2012/13 (S4 and S6). Parents reported their child's home SHS exposure, in enclosed public areas and private cars. Adjusted multivariable logistic regression assessed changes across time and predicted risk factors. RESULTS: Children's home SHS exposure before the ban was 14.3% (S1), 14.1% (S2) and 12.8% (S4) directly after the ban to 7.2% (S6) (P<0.0001). The proportion of homes where at least one parent smoked significantly reduced from 12.78% (S1) to 4.94% (S6) (P<0.0001) and homes with voluntary smoke-free rules increased. Exposure in cafes, restaurants and private cars also decreased. No significant changes in the proportion of parents that ceased smoking due to the ban were found. Among others, low parental education, crowding and unemployment were risk factors for higher SHS exposure. CONCLUSION: Since the smoking ban, no long-term displacement of SHS to homes was observed. Social smoking norms appear to have shifted in favour of the ban. Social inequalities still exist and should be addressed to further minimise SHS exposure.

Association of sociodemographic and environmental factors with the mental health status among preschool children-Results from a cross-sectional study in Bavaria, Germany.

AIM: It has been reported that a great proportion of mental health disorders have an origin in early childhood. In order to evaluate factors possibly associated with children's health, the health monitoring units have been established since 2004 in six study regions in Bavaria, Germany. The second health monitoring survey, implemented in 2005-06, focuses on the mental health status of preschool children. The goal of this study is (1) to examine the association of sociodemographic and environmental factors with mental health and (2) to analyze the applicability of the results of the health monitoring units to all preschool children in Bavaria by calculating weighting factors. METHODS: Data on 6206 preschool children are available. Logistic regression analysis is applied to analyze possible associations with mental health. A weighting method is applied to correct for deviances compared to the whole population of preschool children in Bavaria (N=132,783). RESULTS: 11% of preschool children show mental health problems. Regarding different indicators of sociodemographic status, low household income [unadjusted OR 3.34, 95% CI: 2.23-4.98] shows the strongest association of mental health problems. Non-accessibility of green space [unadjusted OR 2.74, 95% CI: 1.87-4.00] is also strongly associated with mental health. The results of the unweighted and weighted analysis are similar. CONCLUSION: Our findings suggest that sociodemographic status and factors in the living environment show associations with mental health of children. Based on the results of the unweighted and weighted analyses, the second health monitoring analysis shows little deviances compared to data of all Bavarian preschool children. Therefore, the results can be compared to all Bavarian preschool children.

Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study.

INTRODUCTION: Type 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care. METHODS AND ANALYSIS: Children aged 2-5 years in Bavaria, Germany, will be tested for the presence of multiple islet autoantibodies. Between February 2015 and December 2016, 100 000 children will be screened by primary care paediatricians. Islet autoantibodies are measured in capillary blood samples using a multiplex three-screen ELISA. Samples with ELISA results >97.5th centile are retested using reference radiobinding assays. A venous blood sample is also obtained to confirm the autoantibody status of children with at least two autoantibodies. Children with confirmed multiple islet autoantibodies are diagnosed with pre-type 1 diabetes. These children and their parents are invited to participate in an education and counselling programme at a local diabetes centre. Depression and anxiety, and burden of early diagnosis are also assessed. RESULTS: Of the 1027 Bavarian paediatricians, 39.3% are participating in the study. Overall, 26 760 children have been screened between February 2015 and November 2015. Capillary blood collection was sufficient in volume for islet autoantibody detection in 99.46% of the children. The remaining 0.54% had insufficient blood volume collected. Of the 26 760 capillary samples tested, 0.39% were positive for at least two islet autoantibodies. DISCUSSION: Staging for early type 1 diabetes within a public health setting appears to be feasible. The study may set new standards for the early diagnosis of type 1 diabetes and education. ETHICS DISSEMINATION: The study was approved by the ethics committee of Technische Universität München (Nr. 70/14).

No further increase in the parent reported prevalence of allergies in Bavarian preschool children: Results from three cross-sectional studies.

BACKGROUND: After three decades of an increase in the prevalence of asthma and allergies, new findings show a plateau in the prevalence of industrialized nations. The objective of this study was to determine whether there was a change in the parent reported prevalence of asthma and allergies among Bavarian preschool children since 2004. METHODS: A parent questionnaire was administered as part of the Bavarian school entrance examination in three cross-sectional studies from 2004/2005, 2006/2007 and 2012/2013. The questionnaire included items on allergy testing history, identified allergens, symptoms (e.g. wheezing, itchy eyes, rash), medically diagnosed asthma, hay fever and atopic dermatitis. Logistic regression was performed to observe time patterns and adjust for risk factors. RESULTS: Data were available for 6350 (2004/2005), 6483 (2006/2007) and 5052 (2012/2013) individuals. Symptoms and diseases were more frequent in boys, except for allergies which affect the skin. From 2004 to 2012 the parent reported prevalence of asthma (2.6% to 2.8%), hay fever (4.7% to 4.0%) and atopic dermatitis (12.4% to 11.1%) either remained quite stable or decreased not significantly. CONCLUSIONS: Results from these three cross-sectional surveys of parent reports suggest that the parent reported prevalences of asthma and allergies are quite stable with small fluctuations since 2004 for Bavarian preschool children. Future research is needed to determine if this trend will continue.

Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life.

OBJECTIVE: To evaluate adrenal crises after the start of treatment up to the age of 6 years in children with classic congenital adrenal hyperplasia (CAH). DESIGN: Analysis of data extracted from a population-based prospective long-term follow-up study of children detected in neonatal screening. METHODS: Data of 102 Bavarian children with classic CAH due to 21-hydroxylase deficiency were analyzed, using parental questionnaires and medical reports. Parent-reported hospital admissions of children diagnosed with acute health impairment were included in the analysis if salt loss (hyponatremia) or hypoglycemia was documented in the discharge summary. RESULTS: A total of 74 children (72.5%) had no report of hospital admissions with salt loss or hypoglycemia during the observational period. However, in 27.5% of the children, 22 salt-wasting crises (seven of these also with low blood glucose) and 16 hypoglycemic episodes without salt loss were reported. Furthermore, the cumulative incidence for seizures was elevated; 13 children experienced seizures during hyponatremia or hypoglycemia. Most adrenal crises were triggered by infections, often with inappropriate emergency management, but in 11 cases hypoglycemia occurred unexpectedly, without evidence of severe illness and without any management errors. Frequency of adrenal crises was 6.5 per 100 patient years (95% CI: 4.6-8.8). CONCLUSIONS: Crisis prevention remains a permanent challenge for families and physicians caring for children with classic CAH. Expert care and compliance with emergency recommendations are crucial. Further research on the interactions among glucocorticoid deficiency, adrenomedullary dysfunction, and glucose metabolism is necessary for the prevention of hypoglycemia, especially in young CAH patients.

The cost-effectiveness of tracking newborns with bilateral hearing impairment in Bavaria: a decision-analytic model.

BACKGROUND: Although several countries, including Germany, have established newborn hearing screening programmes for early detection and treatment of newborns with hearing impairments, nationwide tracking systems for follow-up of newborns with positive test results until diagnosis of hearing impairment have often not been implemented. However, a recent study on universal newborn hearing screening in Bavaria showed that, in a high proportion of newborns, early diagnosis was only possible with the use of a tracking system. The aim of this study was, therefore, to assess the cost-effectiveness of tracking newborns with bilateral hearing impairment in Bavaria. METHODS: Data from a Bavarian pilot project on newborn hearing screening and Bavarian newborn hearing screening facilities were used to assess the cost-effectiveness of the inclusion of a tracking system within a newborn hearing screening programme. A model-based cost-effectiveness analysis was conducted. The time horizon of the model was limited to the newborn hearing screening programme. Costs of the initial hearing screening test and subsequent tests were included, as well as costs of diagnosis and costs of tracking. The outcome measure of the economic analysis was the cost per case of bilateral hearing impairment detected. In order to reflect uncertainty, deterministic and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio of tracking vs. no tracking was €1,697 per additional case of bilateral hearing impairment detected. CONCLUSIONS: Compared with no tracking, tracking resulted in more cases of bilateral hearing impairment detected as well as higher costs. If society is willing to pay at least €1,697 per additional case of bilateral hearing impairment detected, tracking can be recommended.

Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population-based study.

AIM: To evaluate intellectual outcome, motor skills and anthropometric data of children with congenital hypothyroidism (CH). METHODS: Children with permanent CH who were born in 1999 in Bavaria were eligible for this prospective, population-based study. Cognitive performance was evaluated by the Kaufman Assessment Battery for Children and motor skills were assessed by the motor test, Motoriktest für vier-bis sechsjahrige Kinder (MOT) 4-6. RESULTS: Eighteen of 21 eligible children participated (86%). Median age of the children was 5.5 years (range 4.9-5.8). Treatment with levothyroxine was started after a median of 7.2 days (range 4-15) with a median dose of 12.0 microg/kg (range 7.2-17.0). Mean intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD] 10.1): no children had IQ values below the normal range. Reactivity and speed of movement were significantly reduced in children with CH. Children with an initial thyroid-stimulating hormone (TSH) value of >200 mU/L performed significantly worse than children with TSH value of

[Evidence and evaluation in health promotion and prevention: the example of the health promotion initiative "healthy living in Bavaria"]. / Evidenzbasierung und Evaluation in der Gesundheitsförderung und Prävention am Beispiel, Gesund. Leben. Bayern."

BACKGROUND: The use of evidence and evaluation is rapidly gaining importance in the field of health promotion and prevention. The evidence base, evaluation methods as well as the capacity and required competencies among practitioners are still being developed. AIMS: Beyond its specific health-related targets, the health promotion initiative "Healthy Living in Bavaria" aims to integrate the use of evidence and evaluation as key components into project funding as part of a total quality management concept. Another objective is the creation of new evidence for the field of health promotion and prevention. APPROACH: A core element of the quality management concept is the initiative's multistage evidence and evaluation model which embraces the initiative as a whole as well as the individual projects. The model is operationalized through a set of matching instruments for application, reporting, evaluation, and appraisal. CONCLUSION: Nationally as well as internationally, evidence and evaluation stand out as central aspects of quality improvement instruments in health promotion and prevention. Characteristic of Bavaria's quality improvement approach is the seamless process from the application to the evaluation under consideration of scientific as well as pragmatic aspects.

Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A>G identified by neonatal screening.

The incidence of severe metabolic crises in medium chain acyl-CoA dehydrogenase deficiency (MCADD) patients homozygous for the common c.985A>G mutation, who had been identified by neonatal screening, was assessed prospectively and compared to retrospective cohort data in unscreened patients with identical genotypes. Logrank test showed a significant reduction of severe metabolic crises in the screened cohort (p<0.01). Neonatal screening appears to reduce the rate of severe metabolic crisis or death in the most prevalent subset of MCADD.

Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent inherited defect of fatty acid oxidation, with a significant morbidity and mortality in undiagnosed patients. Adverse outcomes can effectively be prevented by avoiding metabolic stress and following simple dietary measures. Therefore, prospective newborn screening (NBS) is being proposed for this condition. However, technical validation of MCADD population screening and assessment of its overall benefit require broadening of the as-yet-scarce knowledge of the MCADD genetic heterogeneity unraveled by NBS and its phenotypic consequences. Here, we describe the entire spectrum of sequence variations occurring in newborns with MCADD in the population of Bavaria, Germany, in relation to the biochemical phenotype. Among 524,287 newborns, we identified 62 cases of MCADD, indicating a birth incidence of 1 in 8,456. In all of the 57 newborns available for analysis, two alterations within the MCADD gene (ACADM) were identified. The most prevalent alteration c.985A>G (Lys329Glu) occurred in 27 (47%) newborns in the homozygous and in 18 (32%) in the heterozygous state (63% of defective alleles). The mild folding variant c.199T>C (Tyr67His) was identified in nine individuals, six of them being compound heterozygous with c.985A>G (Lys329Glu). Neither of the prevalent alterations were found in the remaining nine newborns. A total of 18 sequence variations were identified; 13 of them were novel: eight missense mutations, one nonsense mutation, two splice variants, and two small deletions. The remaining five were previously reported in MCADD patients. The ACADM heterogeneity uncovered was larger as anticipated from previous c.985A>G (Lys329Glu) carrier screening data. In addition, we show that MCADD appears to occur as frequently in Turkish newborns as in the native German population. Our data validate that biochemical NBS for MCADD is a highly specific procedure for disease detection, with the identification of a significant share of milder biochemical phenotypes, such as c.199T>C (Tyr67His). These show statistically lower acylcarnitine markers, allowing us to distinguish subgroups within the spectrum of ACADM sequence variations that correlate to biochemical MCADD disease expression. Our data might provide technical and medical guidance for decision making in the worldwide efforts to introduce MCADD population screening.

Data required for the evaluation of newborn screening programmes.

Tandem mass spectrometry offers the chance to improve newborn screening (NBS) for phenylketonuria and to expand screening programmes at minimal additional costs. So far, however, there are only limited data available on the incidence of a broader range of disorders presently being considered, their natural course, the benefits achievable and potential harm associated with screening. Based on a literature search and experience from the Bavarian extended screening trial, these questions are addressed using medium-chain acyl-CoA dehydrogenase deficiency (MCADD) as an example. The data retrieved are sufficient for estimation of the incidence of MCADD cases identifiable by NBS and for diagnosis following clinical symptoms. Clinically detected cases ascertained by active surveillance in populations with highly developed and freely accessible health care systems consistently amount to only 33% of those identified by NBS. This difference cannot be explained by the difference in the proportion of the homozygous 985A-->G mutation, which accounts for about 50% of cases identified in NBS. Further research is needed to assess the contribution of MCADD to unexplained deaths in infancy. Retrospective cohort studies enrolling at least 500,000 children would allow for a more precise estimate of the natural course of disease in particular with regard to less severe adverse outcomes. The most relevant gap in knowledge concerns the long-term outcome of children identified following symptoms and by newborn screening. Since randomised controlled trials are unlikely to be feasible on this issue, a standardised documentation protocol should be implemented in follow-up studies for cases identified either by high risk screening or newborn screening. A proposal for the content of such observational studies is made.

Very high compliance in an expanded MS-MS-based newborn screening program despite written parental consent.

OBJECTIVES: In Bavaria, Germany, an expanded MS-MS-based newborn screening program was implemented in 1999. The coverage of new additional conditions and novelty of technology required introduction of written parental consent. Here we evaluated the influence of the consent procedure on compliance by systematic demographic tracking. METHODS: Comprehensive information was provided for parents, professionals, and the public. Screening notifications were matched with all birth notifications on name and date of birth. Parents of children without screening notification were contacted and counseled. RESULTS: Between August 1, 1999, and July 31, 2000, 123,284 children eligible for screening were born. Of these, 116,652 were matched successfully. Among 6,632 parents contacted, 2,516 (2%) did not respond. Three thousand thirty-four children were screened but the parents initially refused to participate in tracking. Five hundred ninety-four were screened outside the program. Four hundred eighty-eight untested newborns were identified. Three hundred twenty-five screening failures due to logistic problems were tested subsequently. Screening was definitely refused by the parents of 163 children (0.1% of target population). CONCLUSIONS: With appropriate information provided and surveillance by tracking, high compliance with newborn screening can be achieved despite a written consent requirement.