Dual-comb optical parametric oscillator in the mid-infrared based on a single free-running cavity.

We demonstrate a free-running single-cavity dual-comb optical parametric oscillator (OPO) pumped by a single-cavity dual-comb solid-state laser. The OPO ring cavity contains a single periodically-poled MgO-doped LiNbO3 (PPLN) crystal. Each idler beam has more than 245-mW average power at 3550 nm and 3579 nm center wavelengths (bandwidth 130 nm). The signal beams are simultaneously outcoupled with more than 220 mW per beam at 1499 nm and 1496 nm center wavelength. The nominal repetition rate is 80 MHz, while the repetition rate difference is tunable and set to 34 Hz. To evaluate the feasibility of using this type of source for dual-comb applications, we characterize the noise and coherence properties of the OPO signal beams. We find ultra-low relative intensity noise (RIN) below -158 dBc/Hz at offset frequencies above 1 MHz. A heterodyne beat note measurement with a continuous wave (cw) laser is performed to determine the linewidth of a radio-frequency (RF) comb line. We find a full-width half-maximum (FWHM) linewidth of around 400 Hz. Moreover, the interferometric measurement between the two signal beams reveals a surprising property: the center of the corresponding RF spectrum is always near zero frequency, even when tuning the pump repetition rate difference or the OPO cavity length. We explain this effect theoretically and discuss its implications for generating stable low-noise idler combs suitable for high-sensitivity mid-infrared dual-comb spectroscopy (DCS).

51-W average power, 169-fs pulses from an ultrafast non-collinear optical parametric oscillator.

We present a high power optical parametric oscillator (OPO) synchronously pumped by the second-harmonic of a modelocked 1030-nm thin-disk laser (TDL) oscillator. The OPO delivers an average power of 51.1 W around degeneracy (1030 nm) with a 10.2-MHz repetition-rate. After extra-cavity dispersion compensation using dispersive mirrors, we obtain a pulse duration of 169 fs, which is 4.6× shorter than the TDL pulse duration of 770 fs. The TDL has 250 W average power, which is converted to 215 W at the second-harmonic. Hence, the OPO exhibits a high photon conversion efficiency of 47% (ratio of signal photons to 515-nm pump photons). Moreover, the OPO generates a peak power of 26.2 MW, which is very similar to the 28.0-MW peak power of the TDL. To facilitate continuous tuning around degeneracy and convenient extraction of the pump and idler beams, the OPO is operated in a noncollinear configuration. A linear cavity configuration was chosen since it offers easy alignment and straightforward cavity length tuning. To the best of our knowledge, this source has the highest average power generated by any ultrafast OPO, and the shortest pulse duration for any >5-W OPO. This result is an important step to adding wavelength tunability to high power Yb-based laser sources without the complexity of either laser or parametric amplifier systems.

Evolution of the IgE and IgG repertoire to a comprehensive array of allergen molecules in the first decade of life.

BACKGROUND: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood. OBJECTIVE: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10 years. METHODS: We examined the sera collected between birth and age 10 years from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cutoff ≥0.30 ISU) and IgG (cutoff ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™). RESULTS: IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule. CONCLUSIONS: The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens, while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects.

Early life travelling does not increase risk of atopic outcomes until 15 years: results from GINIplus and LISAplus.

BACKGROUND: Westernized lifestyle has been blamed for allergy epidemics. One of its characteristics is increased distances and frequency of travelling from early life onwards. Early life travelling to places which substantially differ from home environment in terms of climate, vegetation and food could increase the exposure to further unknown allergens and hence promote the development of allergies, but no epidemiological study has investigated this speculation. METHODS: Detailed data on travelling during the first 2 years of life as well as a range of atopic outcomes along with potential confounders up to age 15 years were collected prospectively within two large population-based multicentre German birth cohorts - GINIplus and LISAplus. Farthest travelling destination (within Germany; middle/northern/eastern Europe; southern Europe; outside Europe), total number of trips and their combination were considered as exposures. Six atopic outcomes were used: (1) doctor-diagnosed asthma, (2) doctor-diagnosed allergic rhinitis, (3) nose and eye symptoms, (4) sensitization to food allergens, (5) sensitization to indoor and (6) outdoor inhalant allergens. Longitudinal associations between each exposure and health outcome pair were analysed using generalized estimation equations (GEEs). RESULTS: The results of our longitudinal analyses of 5674 subjects do not support the research hypothesis that travelling abroad to different regions in Europe or beyond Europe and frequency of travelling increase prevalence of doctor-diagnosed asthma and allergic rhinitis, nose and eye symptoms and allergic sensitization up to 15 years of age. Furthermore, there was no indication of age-varying effects. CONCLUSIONS: Early life travelling does not seem to increase risk of atopic outcomes. Nevertheless, as we could not account for the type of visited environment or length of stay, these first findings should be interpreted with caution.

Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study.

BACKGROUND: Data on the long-term impact of hydrolyzed formulas on allergies are scarce. OBJECTIVE: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence. METHODS: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. RESULTS: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula. CONCLUSION: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

Parental allergic disease before and after child birth poses similar risk for childhood allergies.

Whether the strength of associations between parental and child allergic diseases differs by whether the first onset of the parental disease is before or after a child's birth has never been examined and is the aim of this study. Yearly childhood asthma, allergic rhinitis, and eczema diagnoses were longitudinally regressed against the effect of a parental disease (pre- vs post-child birth) of the same type separately for each parent using generalized estimation equations. Both a maternal and paternal history of asthma were associated with childhood asthma prevalence up to 15 years of age. Effect estimates were similar for parental asthma with first onset before and after the birth of the child. The results for allergic rhinitis and eczema were less consistent. Parental allergic diseases with first onsets before and after the birth of a child both pose risks to childhood allergic disease in the offspring, especially for asthma.

Peer problems are associated with elevated serum leptin levels in children.

BACKGROUND: Leptin is thought to act as an important mediator in stress reactions. To date, no study has examined the association between psychological stress and leptin levels in children. This study aimed to assess the association between emotional symptoms and peer problems and serum leptin levels in children aged 10 years of the two population-based GINI-plus and LISA-plus birth cohorts. METHOD: Cross-sectional data from 2827 children aged 10 years were assessed with regard to leptin concentrations in serum and behavioral problems using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Linear regression modeling was applied to determine the likelihood of elevated leptin levels in children with emotional symptoms and peer problems, controlling for socio-economic status (SES), body mass index (BMI), fasting serum leptin levels, pubertal development and sex hormones. RESULTS: We found that increases in emotional symptoms (exp ß adj = 1.03, s.e. = 0.02, p < 0.04) and peer problems (exp ß adj = 1.05, s.e. = 0.01, p = 0.0001) were significantly associated with higher serum leptin levels controlled for BMI and sociodemographic factors. Similar results were found when the fasting serum leptin sample was examined (exp ß adj = 1.08, s.e. = 0.04, p = 0.0294). Gender-stratified analyses showed a significant relationship between serum leptin and peer problems in girls (exp ß adj = 1.05, s.e. = 0.02, p = 0.03), and a borderline significant association in boys (exp ß adj = 1.04, s.e. = 0.02, p = 0.05). CONCLUSIONS: Children with peer problems have higher stress and eat more, acquire a higher body fat mass and thus, through increased leptin resistance, exhibit higher leptin levels.

Epidemiology of urticaria in infants and young children in Germany--results from the German LISAplus and GINIplus Birth Cohort Studies.

BACKGROUND: Although urticaria is considered one of the most frequent skin diseases, reliable epidemiologic data are scarce. OBJECTIVE: To evaluate the incidence and cumulative prevalence of urticaria in infants and children up to age of 10, to characterize the relationship of specific IgE levels (food and inhalative allergens) with urticaria, and to monitor the joint occurrence of urticaria with other diseases, such as eczema, asthma, and hay fever. METHODS: The study population consisted of two prospective birth cohort studies: the LISAplus and GINIplus studies. Information on physician-diagnosed urticaria, asthma, eczema, or hay fever was collected using self-administered questionnaires completed by the parents. Blood samples were drawn, and specific immunoglobulin E measured at 2 (only LISAplus), 6 and 10 yr of age. RESULTS: The incidence of urticaria was approximately 1% per year of age. The cumulative prevalence of urticaria in children up to the age of 10 yr was 14.5% for boys and 16.2% for girls. Cumulative prevalence of urticaria at the age of ten was significantly (p < 0.05) associated with allergic sensitization to peanut, soy, and wheat flour, but not with inhalant allergens. Both a parental history of atopy/urticaria and the children's diagnosis of asthma, eczema, and hay fever were strongly related (p < 0.0001) to the occurrence of urticaria. CONCLUSIONS: Urticaria is a frequent event during childhood, with highest incidence in infants and preschool children. Comorbidity with atopic disease is high.

Long-term exposure to traffic-related air pollution and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts.

AIMS/HYPOTHESIS: Epidemiological studies that have examined associations between long-term exposure to traffic-related air pollution and type 2 diabetes mellitus in adults are inconsistent, and studies on insulin resistance are scarce. We aimed to assess the association between traffic-related air pollution and insulin resistance in children. METHODS: Fasting blood samples were collected from 397 10-year-old children in two prospective German birth cohort studies. Individual-level exposures to traffic-related air pollutants at the birth address were estimated by land use regression models. The association between air pollution and HOMA of insulin resistance (HOMA-IR) was analysed using a linear model adjusted for several covariates including birthweight, pubertal status and BMI. Models were also further adjusted for second-hand smoke exposure at home. Sensitivity analyses that assessed the impact of relocating, study design and sex were performed. RESULTS: In all crude and adjusted models, levels of insulin resistance were greater in children with higher exposure to air pollution. Insulin resistance increased by 17.0% (95% CI 5.0, 30.3) and 18.7% (95% CI 2.9, 36.9) for every 2SDs increase in ambient NO2 and particulate matter ≤10 µm in diameter, respectively. Proximity to the nearest major road increased insulin resistance by 7.2% (95% CI 0.8, 14.0) per 500 m. CONCLUSIONS/INTERPRETATION: Traffic-related air pollution may increase the risk of insulin resistance. Given the ubiquitous nature of air pollution and the high incidence of insulin resistance in the general population, the associations examined here may have potentially important public health effects despite the small/moderate effect sizes observed.

German national consensus recommendations on nutrition and lifestyle in pregnancy by the 'Healthy Start - Young Family Network'.

Diet and physical activity before and during pregnancy affect short- and long-term health of mother and child. The energy needs at the end of pregnancy increase only by about 10% compared to nonpregnant women. An excessive energy intake is undesirable since maternal overweight and excessive weight gain can increase the risks for a high birth weight and later child overweight and diabetes. Maternal weight at the beginning of pregnancy is especially important for pregnancy outcome and child health. Women should strive to achieve normal weight already before pregnancy. Regular physical activity can contribute to a healthy weight and to the health of pregnant women. The need for certain nutrients increases more than energy requirements. Before and during pregnancy, foods with a high content of essential nutrients should be preferentially selected. Supplements should include folic acid and iodine, iron (in case of suboptimal iron stores), the ω-3 fatty acid docosahexaenoic acid (in case of infrequent consumption of ocean fish) and vitamin D (in case of decreased sun exposure and decreased endogenous vitamin D synthesis). Pregnant women should not smoke and not stay in rooms where others smoke or have smoked before (passive smoking). Alcohol consumption should be avoided, since alcohol can harm unborn children.

FADS gene cluster modulates the effect of breastfeeding on asthma. Results from the GINIplus and LISAplus studies.

BACKGROUND: The protective effect of breastfeeding (BF) on the development of asthma has been widely recognized, even if not all results have been consistent. Gene variants of the FADS gene cluster have a major impact on fatty acid composition in blood and in breast milk. Therefore, we evaluated the influence of the FADS1 FADS2 gene cluster polymorphisms on the association between BF and asthma. METHODS: The analysis was based on data (N=2245) from two German prospective birth cohort studies. Information on asthma and BF during the first 6 months was collected using questionnaires completed by the parents. Logistic regression modelling was used to analyse the association between exclusive BF and ever having asthma stratified by genotype. RESULTS: In the stratified analyses, BF for 3 or 4 months after birth had a protective effect for heterozygous and homozygous carriers of the minor allele (adjusted odds ratio between 0.37 (95% CI: 0.18-0.80) and 0.42 (95% CI: 0.20-0.88). Interaction terms of BF with genotype were significant and ranged from -1.17 (P-value: 0.015) to -1.33 (0.0066). Moreover, heterozygous and homozygous carriers of the minor allele who were exclusively breastfed for 5 or 6 months after birth had a reduced risk of asthma [0.32 (0.18-0.57) to 0.47 (0.27-0.81)] in the stratified analyses. For individuals carrying the homozygous major allele, BF showed no significant effect on the development of asthma. CONCLUSIONS: The association between exclusive BF and asthma is modified by the genetic variants of FADS genotypes in children.

Growth velocity during infancy and onset of asthma in school-aged children.

BACKGROUND: Growth velocities during infancy might affect the risk of asthma in childhood. This study examines the association between peak height and weight velocities during the first 2 years of life and onset of asthma and wheeze up to 10 years of age. METHODS: Data from 9086 children who participated in the GINIplus and LISAplus birth cohorts were analyzed. Information on asthma was requested annually from 1 to 10 years and information on wheeze at 1, 2, 4, 6, and 10 years. Peak height and weight velocities were calculated using height and weight measurements obtained between birth and 2 years of age. Cox proportional hazards models and generalized linear mixed models were calculated after adjustment for potential confounding factors including birth weight and body mass index at 10 years of age. RESULTS: Per interquartile range increase in peak weight velocity (PWV), the risk of asthma increased significantly (adjHR: 1.22; CI: 1.02-1.47). The relationship between peak height velocity (PHV) and onset of asthma was nonsignificant (adjHR: 1.08; CI: 0.88-1.31). Wheeze was not significantly associated with PHV or with PWV (adjOR: 1.07; CI: 0.64-1.77 and adjOR: 1.11; CI: 0.68-1.79, respectively). CONCLUSIONS: Weight gain during infancy is positively associated with physician-diagnosed asthma in school-aged children.

Association of gas cooking with children's respiratory health: results from GINIplus and LISAplus birth cohort studies.

UNLABELLED: Previous studies have found inconsistent results on the association between asthma in children and gas cooking emissions. We aimed to assess the effects of the long-term exposure to gas cooking on the onset of asthma and respiratory symptoms, focusing on wheezing, in children from two German birth cohorts: LISAplus and GINIplus. A total of 5078 children were followed until the age of 10 years. Asthma, wheezing, gas cooking, and exposure to other indoor factors were assessed through parental reported questionnaires administered periodically. Logistic and multinomial regressions adjusting for potential confounders were performed. The prevalence of asthma and persistent wheezing was higher among children exposed to gas cooking but the results were not statistically significant. Exposure to gas cooking was positively associated (P-value < 0.05) with exposure to other indoor factors (dampness, environmental tobacco smoke, and pets). Our results did not show a statistically significant association between the exposure to gas cooking and children's respiratory health. PRACTICAL IMPLICATIONS: These analyses are consistent with the assumption of no effect of the exposure to low doses of nitrogen dioxide. The strong positive associations found between gas cooking and other indoor factors highlight the importance of considering other indoor factors when assessing health effects of gas cooking. Low-dose exposure to indoor nitrogen dioxide through gas cooking might not contribute to increase the risk of asthma and respiratory symptoms in children.

[Two German Birth Cohorts: GINIplus and LISAplus]. / Die zwei deutschen Geburtskohorten GINIplus und LISAplus.

Numerous chronic diseases in childhood and adulthood have their origins in perinatal life and are potentially influenced by trans-generational epigenetic processes. Therefore, prospective birth cohorts can substantially contribute to our knowledge about the etiology of diseases including modifiable risk factors. The two population-based German birth cohorts GINIplus and LISAplus aim to describe the natural course of chronic diseases and intermediate phenotypes in childhood and its determinants, and to identify potential genetic effect modifications. In the mid-1990s, 5,991 (GINIplus) and 3,097 (LISAplus) healthy, term newborns were recruited for long-term follow-up in four regions of Germany. The follow-up rate for the first 10 years was about 55%. We analyzed the growth and development of overweight, infections and allergic diseases, mental and oral health, metabolic and inflammatory parameters and the role of potential risk factors including genetics. The results of these two birth cohorts substantially contribute to the current knowledge about the natural course of these health parameters. These data were included in many international projects and consortia for purposes of international comparisons of prevalence and consistency of findings, and to increase the power of the analyses.

Respiratory health in children, and indoor exposure to (1,3)-ß-D-glucan, EPS mould components and endotoxin.

For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-ß-D-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-ß-D-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case-control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-ß-D-glucan, EPS and endotoxin were measured in settled house dust sampled from children's mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children's mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39-0.92) and 0.55 (95% CI 0.31-0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31-0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.

FADS gene variants modulate the effect of dietary fatty acid intake on allergic diseases in children.

BACKGROUND: The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter-individual genetic differences in fatty acid metabolism. OBJECTIVE: The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10-year-old children. METHODS: The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype. RESULTS: No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n-3/total n-6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%-CI: 1.00-1.57) to 1.31 (95%-CI: 1.01-1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03-1.34) to 1.22 (1.06-1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing. CONCLUSIONS & CLINICAL RELEVANCE: The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children.

Association between attendance of day care centres and increased prevalence of eczema in the German birth cohort study LISAplus.

BACKGROUND: Day care centre attendance is much more common in East than in West Germany. Although there is evidence that early day care might be protective against atopic diseases, several studies have shown a higher prevalence of childhood eczema in East Germany compared to West Germany. OBJECTIVES: To compare prevalence and cumulative incidence of eczema in a birth cohort study in East and West Germany and to identify risk factors that are associated with eczema, which might explain regional differences. METHODS: We used data from the ongoing population-based birth cohort study Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany Plus the influence of traffic emissions and genetics. In 1997, 3097 children from study areas in East and West Germany were recruited. Cumulative incidence and 1-year prevalences of eczema up to the age of 6 years were determined from yearly questionnaires. Cox regression and generalized estimating equations/logistic regression were used to quantify regional differences and to identify risk factors that might explain them. RESULTS: Prevalence and incidence of eczema were higher in children living in East Germany than those living in West Germany. We identified 11 risk factors that showed significant regional differences. From these factors, only 'day care attendance during the first 2 years of life' was significantly associated with eczema (odds ratio 1.56, 95% confidence interval CI 1.31-1.86). The regional differences in eczema could be explained by differences in early day care utilization. CONCLUSION: Day care centre attendance is associated with an increased prevalence and incidence of eczema. Regional differences in eczema prevalence could be explained by regional differences in utilization of early day care.

[Indications and approaches in rehabilitation with children]. / Indikationen und Konzepte der Kinderrehabilitation.

Against the background of rising prevalence of chronic diseases in childhood and adolescence, the rehabilitation of children and adolescents plays a major role in medical treatment. Early diagnosis and multimodal intervention are necessary to prevent a chronic course of disease and disease consequences for those affected and their families. In recent years, significant content and structural improvement of child and youth rehabilitation has been observed; currently some trends that affect not only the access to rehabilitation but also the quality of outcomes are becoming apparent. These include salutogenetic approaches, the development of specific diagnostic and treatment guidelines, the establishment of networks, integrated care, modularization, and flexibility of rehabilitation measures.

Impact of early feeding on childhood eczema: development after nutritional intervention compared with the natural course - the GINIplus study up to the age of 6 years.

BACKGROUND: Nutritional intervention with hydrolysed infant formulas has been shown efficacious in preventing eczema in children predisposed to allergy. However, this preventive effect has never been related to the natural course of eczema in children with or without a family history of allergy. The aim of this study therefore was to compare the course of eczema in predisposed children after nutritional intervention to the natural course of eczema. METHOD: The prospective German birth cohort study GINIplus includes a total of 5991 children, subdivided into interventional and non-interventional groups. Children with a familial predisposition for allergy whose parents agreed to participate in the prospective, double-blind intervention trial (N=2252) were randomly assigned at birth to one of four formulas: partially or extensively hydrolysed whey, extensively hydrolysed casein (eHF-C) or standard cow's milk formula. Children with or without familial predisposition represented the non-interventional group (N=3739). Follow-up data were taken from yearly self-administered questionnaires from 1 up to 6 years. The outcome was physician-diagnosed eczema and its symptoms. The cumulative incidence of eczema in predisposed children with or without nutritional intervention was compared with that of non-predisposed children who did not receive intervention. Cox regression was used to adjust for confounding. RESULTS: Predisposed children without nutritional intervention had a 2.1 times higher risk for eczema [95% confidence interval (CI) 1.6-2.7] than children without a familial predisposition. The risk was smaller with nutritional intervention even levelling out to 1.3 (95% CI 0.9-1.9) in children fed eHF-C formula. CONCLUSION: Although direct comparability is somewhat restricted, the data demonstrate that early intervention with hydrolysed infant formulas can substantially compensate up until the age of 6 years for an enhanced risk of childhood eczema due to familial predisposition to allergy.