[Newborn blood spot screening (NBS) in Germany : Status quo and presentation of a concept for further development]. / Neugeborenen-Screening aus Trockenblut (NBS) in Deutschland : Status quo und Vorstellung eines Konzeptes zur Weiterentwicklung.

Newborn screening from dried blood spots (NBS) is a highly effective secondary prevention measure that has been established for many years. Against the background of the inclusion of "new diseases" that meet the screening criteria, a concept for the further advancement of NBS was developed on behalf of the GKV-Spitzenverband. This was based on a systematic literature review and a survey of the status quo of NBS in Germany using quantitative and qualitative methods.It is essential for the success of NBS that all newborns affected by a target disease are diagnosed and treated at an early stage and that the harm to be expected with each screening (e.g., due to false positive findings) is kept as low as possible. This requires the organisation of screening in the sense of an integrated programme through central coordination with standardised structures, continuous quality management and digitalisation in line with data protection requirements.Although in general NBS is being implemented successfully in Germany, the research project presented here also reveals weaknesses and a need for action. Proposals and recommendations were compiled in a concept paper, which shows approaches for further development of NBS in line with the current state of research in consideration of changing demands on the infrastructure and processes in the health system. This review article summarises the challenges, current status and possible solutions for the central topics of the concept paper.

[Newborn hearing screening in Germany-results of the 2011/2012 and 2017/2018 evaluations]. / Neugeborenen-Hörscreening in Deutschland ­ Ergebnisse der Evaluationen 2011/2012 und 2017/2018.

BACKGROUND: Newborn hearing screening (NHS) was introduced nationwide by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G­BA) in 2009. In this process, quality targets were also set in the pediatrics directive. In order to review the quality NHS in Germany, the G­BA commissioned a consortium to conduct an initial evaluation for the years 2011 and 2012 and a follow-up evaluation for 2017 and 2018. METHODS: The evaluations were based on NHS screening parameters (Sammelstatistiken) that must be documented by all obstetrics and neonatology departments as NHS providers and can also be compiled through cooperation with hearing screening centers (HSCs). Additional data were collected through questionnaires and interviews and routine data were used to evaluate the screening process. RESULTS: In 13 federal states, a total of 15 HSCs are involved in the screening process. Across Germany, an NHS screening rate of 86.1% was documented in 2018 (82.4% in 2012), but this differed significantly between the federal states. The specified quality targets could not yet be implemented everywhere. For example, only less than half of the obstetric departments achieved the specified screening rate of over 95%. A comparison of data from the follow-up evaluation and the first evaluation showed that the structural quality of NHS had improved, while the process quality remained the same or had deteriorated. The refer rate (children who were discharged without passing the screening) increased from 5.3% to 6.0%. DISCUSSION: To improve the quality of NHS, HSCs should be established nationwide and a second screening should be carried out more consistently before discharge in the case of a refer result in the initial screening.

[Comparison of diagnostic data after introduction of cystic fibrosis screening in newborns in Germany]. / Vergleich von Diagnosedaten nach der Einführung des Mukoviszidosescreenings bei Neugeborenen in Deutschland.

BACKGROUND: In Germany, newborn screening (NGS) for cystic fibrosis (CF) was introduced on 1 September 2016. There is no legally required follow-up of abnormal screening findings, so the exact number of final diagnoses is not known. Two data sources can support the evaluation of the cystic fibrosis screening: the German Society for Newborn Screening (DGNS) collects the results of NGS and confirmatory testing for quality assurance and the German Cystic Fibrosis Registry (DMR) collects diagnostic frequencies. The aim of this manuscript is to compare the data from the DGNS and the DMR and to present limitations and strengths of each data source. METHODS: Data from the DGNS (data as of 14 April 2023) and the DMR (data as of 12 April 2023) for children born between 2017 and 2021 were analyzed with regard to the frequencies of CF, number of patients with CF diagnosed after false-negative screening results, and ratio of CF to cases with positive cystic fibrosis screening and inconclusive diagnosis (CFSPID). RESULTS: The DGNS has 767 datasets of newborns with CF/CFSPID and the DMR has 910 confirmed cases of CF/CFSPID. A false-negative screening was reported by the DGNS for 37/767 (4.8%) and by the DMR for 49/910 (5.4%). The ratio of CF to CFSPID is 17.4:1 (DGNS, 2017-2020) and 28.1:1 (DMR), respectively. DISCUSSION: The DGNS and the DMR, each with different strengths in the documentation of screening (DGNS) and diagnostic data (DMR), provide important clues for the number of newly diagnosed cystic fibrosis patients after the introduction of NGS. Legal requirements for tracking those screened, recording all children with CF, and exchanging data between the DGNS and DMR could improve evaluation in the future.

Is Our Newborn Screening Working Well? A Literature Review of Quality Requirements for Newborn Blood Spot Screening (NBS) Infrastructure and Procedures.

Newborn screening using dried blood spots (NBS) is widely acknowledged as a highly successful procedure in secondary prevention. For a number of congenital disorders, severe disability or death are impressively prevented by early detection and early treatment through NBS. However, as with any other screening, NBS can also cause harm, and the principle that "the overall benefits of screening should outweigh the harms" must be considered when introducing and implementing NBS programmes. This publication compiles the results of a systematic literature research on requirements for NBS infrastructure and procedures which was conducted as part of a research project on the quality and shortcomings of the NBS pathway in Germany. The compilation contains the requirements and recommendations for realising the principle of "maximise benefits and minimise harms" in relevant NBS pathway components such as parental education and information, coverage, timeliness, laboratory quality assurance, follow-up of abnormal results, confirmatory diagnostics, documentation, and evaluation. The results reflect the complexity of NBS infrastructure, and thus, they illustrate the importance of considering and implementing NBS as a well-coordinated public health programme with continuous quality management. Special attention should be paid to the perspectives of parents and families. Some NBS issues can substantially benefit from digital instruments or international cooperation. The literature review presented here has contributed to a concept of proposals for the advancement of NBS in Germany, and despite different settings, it may as well be of interest for other countries to achieve the best possible course and outcome of NBS for each child.

Prospective Newborn Screening for SCID in Germany: A First Analysis by the Pediatric Immunology Working Group (API).

BACKGR OUND: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019. METHODS: Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5 years. RESULTS: Among 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn syndrome (OS)/idiopathic T-cell lymphocytopenia, and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4 months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in utero onset OS and died after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result. CONCLUSION: The German TREC-NBS represents the largest European SCID screening at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54,000, very similar to previous observations from North American and European regions and countries where TREC-NBS was implemented. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe.

German newborn screening for Cystic fibrosis: Parental perspectives and suggestions for improvements.

PURPOSE: Cystic fibrosis (CF) was added to the German newborn bloodspot screening (NBS) panel in 2016. This study assesses parental perceptions of CF-NBS and confirmatory testing. METHODS: Prospective questionnaire-based survey administered to parents of children with positive CF-NBS over 40 months after initiation of CF-NBS in Southwest Germany. Parental perceptions were compared to results from Bavaria and Switzerland. RESULTS: Questionnaires with 29 standardized questions were sent to 343 families with children born between October 2016 and January 2020. A total of 178 (51.9%) replied. Although required by law, only a minority were informed about CF-NBS by a physician. The information provided about NBS was sufficient for 78% of parents. Regarding the information about positive CF-NBS, 52.9% were satisfied but the majority expressed negative emotions (89.5%). While most of these were resolved after confirmatory diagnostics, 17% of parents of children with false-positive CF-NBS and 66.7% of children confirmed with CF remained anxious. Waiting time for sweat testing was >3 days in 56.1%, considerably longer than in more centralized screening systems. Parents who waited for a maximum of 3 days were significantly more satisfied. 70.7% of parents were satisfied with the information given during confirmatory diagnostics and 91.4% were satisfied with participating in CF-NBS. CONCLUSIONS: CF-NBS stands in high regard with parents. Smooth organization, timely initiation of confirmatory testing, and professional communication are most important to limit parental anxiety. A more centralized system of confirmatory diagnostics appears advantageous in several regards as it reduces time from positive NBS to final diagnosis and increases parental satisfaction.

Newbornscreening SMA - From Pilot Project to Nationwide Screening in Germany.

Now that targeted therapies for spinal muscular atrophy are available, attempts are being made worldwide to include screening for spinal muscular atrophy in general newborn screening. In Germany, after pilot projects from 2018-2021, it was included in the general newborn screening from October 2021. To ensure a smooth transition, criteria for follow-up were developed together with key stakeholders. At the beginning of the transition to nationwide screening, false positive findings were reported in 3 patients. After optimization of the screening method in the laboratories concerned, all findings have been subsequently confirmed. On average, the first presentation to a neuromuscular center occurred on day 12 of life, and in patients with 2 or 3 SMN2 copies, therapy started on day 26 of life. Compared with the pilot project, there was no significant delay in timing.

[Evaluation of a Screening Program: Challenges of Data Collection Using the Example of the Newborn Hearing Screening]. / Evaluation eines Screening-Programms: Herausforderungen der Datenerhebung am Beispiel des Neugeborenen-Hörscreenings.

BACKGROUND: The aim of the newborn hearing screening (NHS) is to identify and treat children with bilateral hearing disorders early. The NHS is regulated in Germany by the Pediatric Directive, which recommends an evaluation after 5 years. This evaluation was performed for the first time nationwide for children born between 2011 and 2012 regarding structural, process and result quality. OBJECTIVES: Challenges in the collection of appropriate data as basis for evaluation are described and possible improvements are suggested. METHODS: All maternity and neonatology wards performing the NHS were identified and their documentations of the NHS analysed. In addition, all pediatric audiologists were identified to gather data on children with bilateral permanent congenital hearing disorder. RESULTS: The identification of relevant maternity and neonatology wards was very burdensome. More than half of them were not aware that NHS had to be documented. There was no documentation on more than 15% of the children that were to be screened. Furthermore, data concerning bilateral congenital hearing disorders was only accessible for 60% of the expected number of affected children. CONCLUSIONS: Data required for the evaluation of the NHS regarding structural, process and result quality were incomplete and missing. The database for evaluations should be defined precisely and structures needed to obtain meaningful results have to be established in advance. Nevertheless, the evaluation of the NHS provides meaningful results concerning the screening process in Germany.

Neonatal Screening for Congenital Metabolic and Endocrine Disorders­Results From Germany for the Years 2006­2018.

BACKGROUND: The purpose of neonatal screening is the early detection of congenital metabolic and endocrine disorders that, if untreated, could lead to fatal crises or other long-term adverse sequelae. In Germany, neonatal screening is legally regulated. Quality-assurance reports ("DGNS reports") are created and published annually by the German Society for Neonatal Screening (Deutsche Gesellschaft für Neugeborenen-Screening). Data from the DGNS reports for the years 2006-2018 serve as the basis of the present publication. METHODS: For the years 2006-2018, prevalences were calculated and data on process quality were evaluated. RESULTS: Among 9 218 538 births, 6917 neonates were identified who had one of the target diseases. The overall prevalence was 75 per 100 000 neonates; the disorders most commonly found were congenital hypothyroidism (30 per 100 000) followed by phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase deficiency (MCAD) (10 per 100 000 each). Of the 272 205 follow-up screenings requested, 80% were received. The rate of positive screening findings (recall rate) declined over the observation period, from 0.90% in 2006 to 0.37% in 2018. For every five positive screening findings, one case of a target disorder was confirmed. 79% of the children for whom treatment was indicated began to receive treatment within two weeks. CONCLUSION: The low recall rate and the early initiation of treatment in 79% of the affected children indicate that neonatal screening for metabolic and endocrine disorders in Germany is effective. The incorporation of tracking structures and the introduction of a registry could further improve the quality of the program.

Implementing a tracking system for confirmatory diagnostic results after positive newborn screening for cystic fibrosis-implications for process quality and patient care.

Newborn screening for cystic fibrosis (CF-NBS) was introduced in Germany in 2016. Currently, systematic follow-up of positive CF-NBS results is not implemented or reimbursed in the NBS program. We investigated results of confirmatory testing over 24 months after implementation of CF-NBS for a large German NBS center before and after introduction of an active tracking system and performed a cost calculation for tracking. Results are compared with the federal state of Bavaria, where a centralized tracking system has been in place for many years. At the NBS center, 244 of 281,907 children had a positive CF-NBS result requiring diagnostic confirmation. Before implementation of a telephone tracking system, only 43% of confirmatory results were returned despite repeated written requests. The consecutive strategy including telephone tracking led to an increase of resolved cases to 84%. However, the centralized tracking system in Bavaria, assigning children with positive CF-NBS directly to a responsible CF-center, resolved 99% of cases. The calculated additional cost for a tracking system in Germany including telephone tracking is 1.20€ per newborn screened.Conclusion: The implementation of a tracking system achieves a distinct improvement in CF-NBS with justifiable costs. The effect can be limited by absence of centralized organization of confirmatory testing. What is Known: • Newborn screening for cystic fibrosis (CF-NBS) has been performed for many years in several countries worldwide • While many studies have focused on different CF-NBS strategies, the organization of confirmatory testing and process quality concerning returned information to the NBS center has so far received less attention. What is New: • The implementation of an active tracking system achieves a distinct improvement of clarified cases after positive CF-NBS with justifiable costs. • The effect of a tracking system can be limited by the absence of a centralized organization of confirmatory testing.

Parents' experience with positive newborn screening results for cystic fibrosis.

In Germany, screening for cystic fibrosis (CF) is part of the newborn screening since September 2016. The risk of psychological harm due to false-positive screening results is a longstanding concern. We investigated the parents' perception of the CF screening process in Bavaria and the communication after positive screening results with a questionnaire. Until August 2018, 192 children went through a final diagnostic testing after a positive CF screening result, and 105 (54.7%) families completed the questionnaire. Of these, only 30 parents obtained information about the newborn screening by a physician, despite this being mandatory in Germany. Parents being informed by a CF specialist (28.6%) about the positive screening result were more satisfied with the given information (80.0 versus 50% informed by the maternity ward), and the delay until the final diagnostic testing was shorter. More than 3 days between the information about the screening result and the diagnostic testing was too long for 77.7% of the families.Conclusion: Performing final diagnostic testing with only short delays and receiving satisfactory information is important. Therefore, parents should be informed directly by a CF center about positive screening results and only when sweat testing is possible within the next days. What is Known: • The risk of psychological harm due to false-positive screening results is a longstanding concern. • Satisfactory information about the positive CF screening result seem to reduce the parental stress. What is New: • Parents being informed directly by a CF specialist were more satisfied with the given information and the delay until the final diagnostic testing was shorter. • Our data support the concept that parents should better be informed directly by a CF specialist about positive screening results and only when sweat testing is possible within the next days to reduce parental stress.

Newborn Hearing Screening in Bavaria-Is It Possible to Reach the Quality Parameters?

Since the 1 January, 2009, newborn hearing screening (NHS) has been obligatory for every child in Germany. NHS is part of the Pediatrics Directive of the Federal Joint Committee. In this directive, details of the procedures and screening quality to be achieved are given. We evaluate if these quality criteria were met in Bavaria in 2016. The NHS data of children born in 2016 in Bavaria were evaluated for quality criteria, such as screening coverage in screening facilities, screening methods, referral rate (rate of failed tests at discharge) and a child's age at the diagnosis of a hearing disorder. NHS was documented for 116,776 children born in Bavaria in 2016. In the first step, 78,904 newborns were screened with transient evoked otoacoustic emissions and 37,865 with automated auditory brainstem response. Of these, 9182 (7.8%) failed the first test in one or both ears. A second screening before discharge was performed on 53.3% of the newborns with a refer result in the first test, out of which 58.7% received a pass result. After the screening process, 4.6% of the newborns were discharged with a refer result. Only 18% of the first controls after discharge were performed by a pediatric audiologist. In 37.9% of the newborns, the screening center intervened to assure the control of any failed screening test. The median age of diagnosis for bilateral hearing loss was 5.3 months. In Bavaria, NHS was implemented successfully. A tracking system for all children who failed the hearing screening test is pivotal for early diagnosis and therapy of children with hearing deficiency.

Respiratory diseases are associated with molar-incisor hypomineralizations.

The objective of our study was to evaluate the association of molar-incisor hypomineralizations (MIHs) with prospectively collected potential causative factors from the first 4 years of life, e.g. respiratory diseases, breastfeeding, maternal smoking and parental education. A total of 692 children (10 years old) from the GINI birth cohort study participated. The dental examination included the registration of enamel hypomineralizations (EHs) according to the EAPD criteria. Children with EH were sub-categorized into those with at least one EH (MIH/1), those with a minimum of one EH on at least one first permanent molar (MIH/2) and those with EH on at least one first permanent molar and a permanent incisor (MIH/3). All relationships between causative factors and caries or MIH were evaluated using simple and multiple logistic regression analyses. EHs were observed in 37.9% (MIH/1), 14.7% (MIH/2) and 9.2% (MIH/3) of all subjects. After adjustment for confounding factors, 10-year-old children with at least one episode of respiratory disease had a significantly higher risk (2.48 times, adjusted OR) for the development of MIH/3. In case of breastfeeding, a non-significant association was observed. None of the tested factors was associated with either MIH/1 or MIH/2. Early respiratory diseases seem to be directly or indirectly related to MIH/3 only. The role of (systemic) medications used for treatment of these diseases needs to be investigated in future studies.

Proportion and extent of manifestation of molar-incisor-hypomineralizations according to different phenotypes.

OBJECTIVE: This epidemiological study aimed to assess the proportion and extent of manifestation of enamel hypomineralization, including molar-incisor-hypomineralization (MIH), in the permanent and primary dentition. METHODS: A total of 693 children enrolled in an ongoing birth cohort study (GINIplus-10) were examined at their 10-year follow-up. Enamel hypomineralization was scored in the primary and permanent dentition on a tooth- and surface-related level based on the criteria of the European Academy of Paediatric Dentistry (EAPD). Children were grouped according to their distribution pattern of enamel hypomineralization: children with a minimum of one hypomineralized tooth in the primary dentition (ht ≥ 1) and permanent dentition (HT ≥ 1); with a minimum of one hypomineralization on at least one first permanent molar (MIH); and with hypomineralization on at least one first permanent molar and permanent incisor (M + IH). For each group, the mean values of hypomineralized primary teeth (ht), permanent teeth (HT), and permanent surfaces (HS) were calculated. RESULTS: The proportion of affected children was 36.5 percent (HT ≥ 1), 14.7 percent (MIH), and 9.4 percent (M + IH); 6.9 percent of the subjects had a minimum of one affected primary tooth (ht ≥ 1). The mean number of hypomineralized permanent teeth and surfaces were 2.3HT/2.9HS (HT ≥ 1), 3.4HT/4.8HS (MIH), and 4.2HT/5.9HS (M + IH). The mean number of hypomineralized primary teeth amounted to 0.1ht in the entire study population. CONCLUSIONS: Enamel hypomineralization can be detected frequently in this study sample. Children with M + IH showed the highest number of affected teeth and surfaces followed by those with MIH.

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.

Burden of otitis media and pneumonia in children up to 6 years of age: results of the LISA birth cohort.

Infections play an important role in childhood. For Germany, few data are available on the epidemiology of infectious diseases such as otitis media and pneumonia in children. We therefore described the prevalence, first episode proportions and recurrence of these childhood infection diseases in selected regions of Germany in children up to 6 years of age. The analysis was based on data from the LISA Study, a prospective population-based birth cohort study including 3,097 full-term infants. Information was collected by parent questionnaire. The first episode proportions for the first 6 years of life were high for otitis media (66.7%; 95%CI 0.65-0.69) and pneumonia (13.5%; 95%CI 0.12-0.15). The annual first episode proportions for otitis media ranged from 7.3% to 25.6% and for pneumonia from 1.4% to 3.4%; both peaked during the second year. The average number of otitis media episodes was 2.2 (SD 2.0) episodes per child within the first 2 years. During the first 2 years of life, hospitalisations due to otitis and pneumonia occurred in up to 7.8 per thousand and 3.0 per thousand of the children, respectively. On average, 50.6% of the children with otitis media were treated with antibiotics during the first year of life. In conclusion, this analysis shows that infectious diseases, especially otitis media, are very frequent childhood diseases in Germany. Thus, parents and physicians should not per se worry about a high frequency of otitis media during early childhood.

Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).

BACKGROUND: The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated. OBJECTIVE: We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow's milk formula (CMF) in a randomized, double-blind trial. METHODS: Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient. The cohort was followed from birth until 6 years of age with yearly questionnaires. Outcomes were physician-diagnosed allergic diseases (atopic dermatitis, food allergy, allergic urticaria, asthma, and hay fever/allergic rhinitis). Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis. RESULTS: In the intent-to-treat analysis the relative risk of a physician's diagnosis of allergic manifestation (AM) compared with CMF was 0.82 (95% CI, 0.70-0.96) for partially hydrolyzed whey formula, 0.90 (95% CI, 0.78-1.04) for extensively hydrolyzed whey formula, and 0.80 (95% CI, 0.69-0.93) for extensively hydrolyzed casein formula. The corresponding figures for atopic eczema were 0.79 (95% CI, 0.64-0.97), 0.92 (95% CI, 0.76-1.11), and 0.71 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis all effects were stronger and significant. No significant effect on other AMs was found. CONCLUSION: The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.

Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children.

RATIONALE: In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are inconsistent. OBJECTIVES: To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life. METHODS: We studied 2,860 children at the age of 4 years and 3,061 at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to particulate matter (PM(2.5)), PM(2.5) absorbance, and long-term exposure to nitrogen dioxide (NO(2)) was assessed at residential addresses using geographic information systems based regression models and air pollution measurements. The distance to the nearest main road was used as a surrogate for traffic-related air pollutants. MEASUREMENTS AND MAIN RESULTS: Strong positive associations were found between the distance to the nearest main road and asthmatic bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified, with the highest odds ratios (ORs) for children living less than 50 m from busy streets. For PM(2.5) absorbance, statistically significant effects were found for asthmatic bronchitis (OR, 1.56; 95% confidence interval [CI], 1.03-2.37), hay fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR, 1.40; 95% CI, 1.20-1.64). NO(2) exposure was associated with eczema, whereas no association was found for allergic sensitization. CONCLUSIONS: This study provides strong evidence for increased risk of atopic diseases and allergic sensitization when children are exposed to ambient particulate matter.

Timing of solid food introduction in relation to eczema, asthma, allergic rhinitis, and food and inhalant sensitization at the age of 6 years: results from the prospective birth cohort study LISA.

OBJECTIVE: Current prophylactic feeding guidelines recommend a delayed introduction of solids for the prevention of atopic diseases. This study investigates whether a delayed introduction of solids (past 4 or 6 months) is protective against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. METHODS: Data from 2073 children in the ongoing LISA birth cohort study were analyzed at 6 years of age. Multivariate logistic regression analyses were performed for all children and for children without skin or allergic symptoms within the first 6 months of life to take into account reverse causality. RESULTS: A delayed introduction of solids (past 4 or 6 months) was not associated with decreased odds for asthma, allergic rhinitis, or sensitization against food or inhalant allergens at 6 years of age. On the contrary, food sensitization was more frequent in children who were introduced to solids later. The relationship between the timing of solid food introduction and eczema was not clear. There was no protective effect of a late introduction of solids or a less diverse diet within the first 4 months of life. However, in children without early skin or allergic symptoms were considered, eczema was significantly more frequent in children who received a more diverse diet within the first 4 months. CONCLUSIONS: This study found no evidence supporting a delayed introduction of solids beyond 4 or 6 months for the prevention of asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. For eczema, the results were conflicting, and a protective effect of a delayed introduction of solids cannot be excluded. Positive associations between late introduction of solids and food sensitization have to be interpreted with caution. A true protective effect of a delayed introduction of solids on food sensitization seems unlikely.