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.

Escalating topotecan in combination with treosulfan has acceptable toxicity in advanced pediatric sarcomas.

Patients with advanced pediatric sarcomas have a poor prognosis and novel combination therapies are needed to improve the response rates. Hematological and organ related toxicities have been observed when administering topotecan in combination with, e.g., high dose thiotepa. This study evaluates the toxicity of escalating doses of topotecan alone or in combination with thiotepa or treosulfan. We compared the toxicity including death of complication (DOC) of topotecan alone or in combination with thiotepa or treosulfan in advanced pediatric sarcomas (n = 12). Ten of 12 patients (0.83) suffered from advanced tumors of the Ewing family (i.e., bone or marrow metastases or relapse <24 month after diagnosis, including one neuroepithelial tumor of the kidney) and two from alveolar rhabdomyosarcoma stage IV (0.17). Median age was 15 years (range 5-28). Ratio of female to male was 1:1. Two patients received topotecan alone (1.25 mg/m(2) q 5d and 1.5 mg/m(2) q 5d), three patients received four courses of topotecan (2 mg/m(2) q d 1-5) in combination with thiotepa (100 mg/m(2) q d 1-5), and seven patients received topotecan (2 mg/m(2) q d 1-5) in combination with treosulfan (10g/m(2) q d 3-5). Overall toxicity was not different between all three groups; mean scores were 1.6, 1.8, and 1.7 according to WHO grading (Scale 0-4). Organ related toxicity ranged between 0 and 4 and was not different as well. DOC was 0/2, 1/3, and 0/7 patients respectively. Escalating therapy with topotecan in combination with treosulfan has acceptable toxicity and warrants further investigation in advanced pediatric sarcomas.

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.

The German Infant Nutritional Intervention Study (GINI) for the preventive effect of hydrolyzed infant formulas in infants at high risk for allergic diseases. Design and selected results.

In the complex interaction between certain environmental factors and genetic disposition, the early allergen exposure plays a major role in the development of allergic diseases. In aiming to reduce the allergen burden for the infant at risk during early infancy, cow's milk protein hydrolysate infant formulas (hypoallergenic infant formulas) are appropriate alternatives to breastfeeding for primary allergy prevention. The German Infant Nutritional Intervention-Program (GINI) was supported for the first 3 years by the German Ministry for Education and Research (BMBF) (FKZ 01 EE 9401-4). It is a birth cohort which was primarily scheduled until the children were 3 years old. The aim of the prospective, randomized, double-blind intervention study was to investigate the impact of different cow's milk protein hydrolysate infant formulas in the first 4 - 6 months on the development of allergic diseases in children at risk due to at least one parent or biological sibling with a history of allergic disease. The allocation to one of the 4 intervention formulas (partial whey hydrolysate, extensive whey hydrolysate, extensive casein hydrolysate or standard cow's milk formula) was randomised and stratified by family history (single/biparental) and the respective obstetric clinic. Recruitment was carried out by the three clinical centers (Research Institute Marien-Hospital Wesel, Children's Department, Ludwigs-Maximilians-University Munich and Children's Department Technical University Munich) in 18 obstetric clinics between 01.09.1995 and 30.06.1998. Along with the intervention study a non-interventional, complementary observational cohort of children with or without allergy risk was recruited and followed by annual self-reporting parental questionnaires. The GINI intervention study (GINI-I, N = 2.252) and the non-interventional observation study (GINI-NI, N = 3.739) are combined in the population-based GINIplus study (see article J. Heinrich et al. in this journal). The results of the GINI intervention study confirm that, cow's milk protein hydrolysate infant formulas have a preventive effect on allergic manifestation compared with a standard cow's milk formula, until school age. However, the dimension of the effect is different between the formulas. This effect, which is mainly driven by the effect on atopic eczema, develops in the first months of life and persists without rebound. In the formula groups the cumulative incidence of atopic eczema until school age is reduced between 26% and 45% compared with standard cow's milk formula. A beneficial effect of the hydrolysate formulas on the respiratory manifestations asthma and rhinoconjunctivitis, however, could not be shown. By comparing the GINI intervention and non-intervention arm of the GINIplus study it was demonstrated, that a family history for allergy doubles the risk for eczema in the offspring. Early intervention with cow's milk protein hydrolysate infant formulas is able to substantially compensate this risk for eczema until the age of 6 years. In contrast, by randomization to standard cow's milk formula this risk showed a trend towards a higher incidence compared with children at risk from the non-intervention group. Thus, the results of the GINIplus study have contributed to answer some of the controversially discussed questions.

[External quality assurance in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Procedure and results]. / Externe Qualitätssicherung im Kinder- und Jugendgesundheitssurvey (KiGGS). Vorgehensweise und Ergebnisse.

The results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) of the Robert Koch Institute (RKI) will be of great importance for health policy and research. Therefore, in this study internal quality assurance was supplemented by an external quality assurance which was carried out by the institute of epidemiology at the GSF National Research Center for Environment and Health. The subjects were the interviewer training, sampling and response, field work and data management. External quality assurance was defined as 'an audit of internal quality assurance measures and systematic observation and spot checks to ensure quality requirements were fulfilled'. The requirements followed the manual of operation and the recognized epidemiologic standards and guidelines. For the different subjects, tests and detailed check-lists were developed and used. The quality requirements were fulfilled: The field work was performed with high quality and remarkable engagement over the whole time from May 2003 to May 2006, which resulted in high response and data quality. An extensive, efficient quality management system was in place for the data management.

Caesarean section and gastrointestinal symptoms, atopic dermatitis, and sensitisation during the first year of life.

AIMS: To investigate the effect of caesarean section on gastrointestinal symptoms, atopic dermatitis, and sensitisation to nutritional allergens in infants. METHODS: A total of 865 healthy full term neonates with parental history of allergy participating in the prospective German Infant Nutritional Intervention Program (GINI) were exclusively breast fed during the first four months of life and had a one year follow up. Data were obtained by follow up visits at age 1, 4, 8, and 12 months, weekly diaries for the first six months, and measurement of total and specific IgE at birth and 12 months. RESULTS: Infants born by caesarean section (147/865, 17%) had a greater risk of diarrhoea (OR(adj) 1.46, 95% CI 1.022 to 2.10) and sensitisation to food allergens, both in adjusted (OR(adj) 2.06, 95% CI 1.123 to 3.80) and stratified analyses (by cord blood IgE). Caesarean delivery was not associated with colicky pain and atopic dermatitis. CONCLUSION: Caesarean delivery might be a risk factor for diarrhoea and sensitisation in infants with family history of allergy. Further research in this area seems warranted as choosing caesarean section becomes increasingly popular.

[German Environmental Survey for Children (GerES IV). Environmental module of KiGGS. Part 2: The first year of field work]. / Kinder-Umwelt-Survey-das Umweltmodul im KiGGSTeil 2: Das erste Jahr Feldarbeit.

The field work of the German Environmental Survey for Children (GerES IV) was started nationwide in May 2003. The survey is a module of the National Health Interview and Examination Survey for Children and Adolescents (KiGGS). This environmental survey includes a representative subsample of 1800 children from the 18,000 participants of the KiGGS who are being examined regarding health-relevant environmental exposure. The investigational programme of the survey was tested successfully in a pilot study (pretest) the results of which contributed to the optimisation of the main study. The field work is essentially done by the environmental interviewer of the three teams of the KiGGS. Preparation, organization and accompaniment of the work is done by the coordination centre of the Robert Koch Institute on Federal Environmental Agency (UBA) instructions. Funding agencies are the Federal Ministry of Education and Research (BMBF) and the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU). Both the KiGGS and the environmental module are evaluated by internal and external quality assurance during the whole study period (May 2003-May 2006). Up to now the established teams have done their field work very well and the coordination of the overall project by the Robert Koch Institute works well, too. A total of 722 subjects had taken part in the GerES IV by July 2004.