Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

Background Filaggrin-derived natural moisturizing factors (NMF) play an important role in skin barrier function and in atopic dermatitis (AD). Its deficiency is associated with dry skin and increased surface pH. Studies on childhood environmental exposures and associations with NMF levels are scarce.Objectives To investigate previous exposures and genetic factors and their associations with NMF levels in young children.Methods In a case-control study nested in a prospective birth cohort (Odense Child Cohort), 169 healthy controls (HC) and 99 children with AD were included consecutively at the age of 7 years based on previous responses from questionnaires administered at 18 months, 3 years and 5 years, pertaining to past medical history, including allergy-specific questions. NMF levels were measured via a stratum corneum tape-stripping technique, genotyping for filaggrin (FLG) gene variants was performed and data on external exposures, including usage of moisturizer and topical steroids, antibiotics and early pet exposures, were obtained from questionnaires.Results Natural moisturizing factors levels were significantly lower in AD participants compared to HC (P < 0.001). This significance persisted after stratifying for AD subgroups of present AD, current AD during the last year and previous AD (P < 0.001, P = 0.039, P = 0.009 respectively). There was a significant association between NMF and FLG genotype (P = 0.016, P = 0.002 for HC, AD respectively). NMF levels were negatively correlated with early age moisturizer use (<18 months, P = 0.001) in HC but not significant in AD. ConclusionsWe found decreased levels of NMF with early moisturizer use and a genetic influence of the FLG variant on these levels. NMF was decreased in the AD subgroup with previous AD compared with HC, which could suggest the persistence of a Th 2 cytokine milieu suppressing these levels.

Background: Diverse pathways stemming from a history of atopic dermatitis (AD) might modulate different biomarkers associated with the development of asthma.Biomarkers associated with AD and asthma separately have been investigated, but none have characterized a combined AD+asthma phenotype. We investigated the clinical and molecular characteristics associated with an AD+asthma phenotype compared with AD, asthma and controls.Methods: From a prospective birth cohort and the outpatient allergy clinic, we included four groups of 6-12-year-old children: (1) healthy controls (2) previous, current, or present AD without asthma, (3) previous, current, or present AD and current asthma and (4) current asthma without AD. We performed clinical examinations and interviews and measured serum IgE, natural moisturizing factors (NMF), and plasma cytokine levels. Results:We found an increased number of IgE sensitizations in AD+asthma, prominent after stratifying for food allergens (p < .05). Pro-Th 2 cytokines CCL18, TSLP, and Eotaxin-3 were elevated in AD+asthma, though not significantly higher than asthma, and elevated in asthma compared with controls. NMF levels were decreased in AD compared with asthma and control groups (p = .019, p < .001, respectively). NMF levels correlated negatively to sensitization (p = .026), though nonsignificant with only the patient groups. Conclusion:Our results indicate that Th 2 cytokines and increased number of sensitizations are associated with AD + asthma phenotypes compared with AD alone andThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.