Background Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult. Objective To assess the effect of supplementation of an infant ...and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life. Methods Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Results A total of 414 infants were randomized to the prebiotic group and 416 infants to the control group. A total of 300 infants were followed in the breast-feeding group. Up to the first birthday, atopic dermatitis occurred in significantly fewer infants from the prebiotic group (5.7%) than from the control group (9.7%; P = .04). The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group (7.3%). In a Cox regression model, the rate of atopic dermatitis was significantly lower by 44% in the prebiotic group versus the control group ( P = .04). The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants. Conclusion Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.
...supplementation of OS has been limited to the first year of life in these trials.4,5,8,9,E5 Whether supraphysiologic duration of OS supplementation would have an allergy-preventive effect ...persisting beyond the first year is an interesting research question that has not been adequately studied yet. ...there are indications that supplementation of infant diet in the first year of life with the immunoactive prebiotics tested here may have preventive potential against early AD, but the effect is not sustained in low-atopy-risk strata.
Background IL-31 is a novel cytokine that, when overexpressed in transgenic mice, induces severe itching dermatitis resembling human eczema. Objective We aimed to evaluate the importance of ...polymorphisms in the human IL-31 gene ( IL31 ) in the genetic susceptibility to eczema. Methods We sequenced the entire IL-31 gene, including the promoter region, and determined the haplotype structure. Single nucleotide polymorphisms tagging the main haplotypes were genotyped in 3 independent European populations comprising 690 affected families. An association analysis of IL31 gene variants with atopic and nonatopic eczema was performed. Results We found significant association of a common IL31 haplotype with the nonatopic type of eczema in all 3 study populations (combined P = 4.5 × 10−5 ). Analysis of PBMCs in healthy individuals revealed a strong induction IL31 mRNA expression on stimulation with anti-CD3 and anti-CD28 that was 3.8-fold higher in individuals homozygous for the risk haplotype (AA) in contrast to non-A haplotype carriers, suggesting that altered regulation of IL-31 gene expression is the disease-causing factor. Conclusion Our results lend strong support to an important role of IL-31 in the pathogenesis of nonatopic eczema. Clinical implications This study presents the first genetic risk factor for the nonatopic type of eczema and indicates a primary role of IL-31–induced pruritus in the initiation of this disease, thus proposing a new target for the prevention and therapy of eczema.
Objective Prenatal imaging has identified alterations of brain growth in fetuses with congenital heart disease. However, little is known about the timing of altered brain development and its ...occurrence in specific congenital heart disease subgroups. This magnetic resonance imaging study aimed to identify early (median, 25 gestational weeks GW) changes in fetal total brain (TBV), gray matter (GMV), and subcortical brain (SBV) volumes in Tetralogy of Fallot (TOF) cases in utero. Study Design Fetal magnetic resonance imaging (1.5 Tesla) was performed in 24 fetuses who were diagnosed with TOF and 24 normal age-matched control fetuses (20-34 GW). TBV, GMV, SBV, intracranial cavity, cerebellar, ventricular, and external cerebrospinal fluid volumes were quantified by manual segmentation based on coronal T2-weighted sequences. Mixed model analyses of variance and t -tests were conducted to compare cases and control fetuses. Results TBV was significantly lower ( P < .001) in early (<25 GW) and late TOF cases. Both GMV ( P = .003) and SBV ( P = .001) were affected. The GMV-to-SBV ratio declined in fetuses with TOF ( P = .026). Compared with normal fetuses, ventricular volume was increased ( P = .0048). External cerebrospinal fluid was enlarged in relation to head size ( P < .001). Intracranial cavity volume ( P = .314) and cerebellar volume ( P = .074) were not significantly reduced in fetuses with TOF. Conclusion TOF is associated with smaller volumes of gray and white matter and enlarged cerebrospinal fluid spaces. These changes are present at ≤25 GW and indicate altered fetal brain growth in this pathophysiologic entity during early stages of human brain development.
Objective Behavioural studies have implicated working memory (WM) deficits in obsessive–compulsive disorder (OCD). However, findings are inconsistent, which could be explained by compensation ...strategies used by a subgroup of OCD patients. To test this hypothesis, we examined patients without a behavioural deficit in WM during performance of different WM tasks using functional magnetic resonance imaging (fMRI). Methods We scaned 11 patients and 11 matched control subjects while they performed 3 verbal and spatial item-recognition tasks. Results Patients and healthy subjects engaged the same set of brain regions. However, in direct comparison, the patients exhibited significantly greater task-related activation in several frontal and parietal brain areas known to underlie WM. Conclusion Patients without manifest WM deficits exhibit increased activation in frontal and parietal brain areas relative to healthy subjects during WM task performance. These hyperactivations may permit them to compensate for reduced efficiency of their WM systems and may thus serve as markers of latent WM dysfunctions.
