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Snijders BEP, Stelma FF, Reijmerink NE, Thijs C, van der Steege G, Damoiseaux JGMC, van den Brandt PA, van Ree R, Postma DS, Koppelman GH. CD14 polymorphisms in mother and infant, soluble CD14 in breast milk and atopy development in the infant (KOALA Study). Pediatr Allergy Immunol 2010: 21: 541–549. © 2009 John Wiley & Sons A/S Different CD14 polymorphisms have been associated with atopic phenotypes in infants. In addition, CD14 genotypes of breastfeeding mothers have been associated with soluble CD14 (sCD14) levels in breast milk. The role of CD14 genotypes of infant and mother and their interaction with sCD14 levels in breast milk in atopy development remain to be established. We aimed to study the associations of CD14 single nucleotide polymorphisms (SNPs), and their interaction with breast milk sCD14, with atopy development until age two. In addition, we assessed whether levels of sCD14 in breast milk associated with SNPs in CD14. Four SNPs in CD14 gene were investigated in 698 infants and 188 mothers. Associations between these SNPs, sCD14 and atopy development were analyzed in multiple logistic or linear regression models. The CD14/-1619 SNP was associated with eczema. CC homozygotes showed a lower risk of eczema vs. TT homozygotes (adjusted odds ratio = 0.56, 95% confidence interval 0.33–0.96) in a co-dominant model. Breast milk sCD14 levels did not significantly modify the effect of the child’s CD14 genotype on atopy development (p interaction ≥0.10). Maternal CD14 SNPs were not significantly associated with sCD14 levels in breast milk (anova, p ≥ 0.48). We found only an association between CC homozygozity of SNP CD14/-1619 and eczema. Our data did not support a modifying role of breast milk sCD14 levels on the relationship between CD14 genotype and atopy development until age 2 yr. [ABSTRACT FROM AUTHOR]

Background: Disability Adjusted Life Years (DALYs) quantify the loss of healthy years of life due to dying prematurely and due to living with diseases and injuries. Current methods of attributing DALYs to underlying risk factors fall short on two main points. First, risk factor attribution methods often unjustly apply incidence-based population attributable fractions (PAFs) to prevalence-based data. Second, it mixes two conceptually distinct approaches targeting different goals, namely an attribution method aiming to attribute uniquely to a single cause, and an elimination method aiming to describe a counterfactual situation without exposure. In this paper we describe dynamic modeling as an alternative, completely counterfactual approach and compare this to the approach used in the Global Burden of Disease 2010 study (GBD2010).Methods: Using data on smoking in the Netherlands in 2011, we demonstrate how an alternative method of risk factor attribution using a pure counterfactual approach results in different estimates for DALYs. This alternative method is carried out using the dynamic multistate disease table model DYNAMO-HIA. We investigate the differences between our alternative method and the method used by the GBD2010 by doing additional analyses using data from a synthetic population in steady state.Results: We observed important differences between the outcomes of the two methods: in an artificial situation where dynamics play a limited role, DALYs are a third lower as compared to those calculated with the GBD2010 method (398,000 versus 607,000 DALYs). The most important factor is newly occurring morbidity in life years gained that is ignored in the GBD2010 approach. Age-dependent relative risks and exposures lead to additional differences between methods as they distort the results of prevalence-based DALY calculations, but the direction and magnitude of the distortions depend on the particular situation.Conclusions: We argue that the GBD2010 approach is a hybrid of an attributional and counterfactual approach, making the end result hard to understand, while dynamic modelling uses a purely counterfactual approach and thus yields better interpretable results. [ABSTRACT FROM AUTHOR]

The aim of the KOALA Birth Cohort Study in the Netherlands is to identify factors that influence the clinical expression of atopic disease with a main focus on lifestyle (e.g., anthroposophy, vaccinations, antibiotics, dietary habits, breastfeeding and breast milk composition, intestinal microflora composition, infections during the first year of life, and gene–environment interaction). The recruitment of pregnant women started in October 2000. First, participants with ‘conventional lifestyles’ (n = 2343) were retrieved from an ongoing prospective cohort study (n = 7020) on pregnancy-related pelvic girdle pain. In addition, pregnant women (n = 491) with ‘alternative lifestyles’ with regard to child rearing practices, dietary habits (organic, vegetarian), vaccination schemes and/or use of antibiotics, were recruited through organic food shops, anthroposophic doctors and midwives, Steiner schools, and dedicated magazines. All participants were enrolled between 14 and 18 wk of gestation and completed an intake questionnaire on family history of atopy and infant care intentions. Documentation of other relevant variables started in the pregnant mother and covered the first and third trimester as well as early childhood by repeated questionnaires at 14–18, 30, and 34 wk of gestation and 3, 7, 12, and 24 months post-partum. A subgroup of participants, including both conventional and alternative lifestyles, was asked to consent to maternal blood sampling, breast milk and a faecal sample of the infant at 1 month post-partum, capillary blood at age 1 yr, venous blood and observation of manifestation of atopic dermatitis during home visits at the age of 2 yr (using the UK working party criteria and the severity scoring of atopic dermatitis index), and buccal swabs for DNA isolation from child–parent trios. From the start, ethical approval and informed consent procedures included gene–environment interaction studies. Follow-up at 3 and 7 months post-partum was completed with high response rates (respectively 90% and 88% in the conventional group, and 97% and 97% in the alternative group). The home visits at 2 yr of age will be completed in 2005. Preliminary results show that we have succeeded in recruiting a large population with various lifestyle choices with a fairly large contrast with regard to dietary habits (including organic foods, vegetarian diet), vaccination schemes and/or use of antibiotics. We have also been able to collect a large number of faecal samples (n = 1176) and capillary blood samples at age 1 yr (n = 956). Furthermore, a large proportion of the participants have consented with genetic studies. Mid 2006 we expect to report our first results on the relationship between the various exposures in early life and childhood atopy. An outline of the focus and design of the KOALA Birth Cohort Study is presented. [ABSTRACT FROM AUTHOR]