Maternal stress, child behavior and the promotive role of older siblings

Abstract Background: In the first years of their lives, children develop the cognitive, social and emotional skills that will provide the foundations for their lifelong health and achievements. To increase their life prospects and reduce the long-term effects of early aversive conditions, it is therefore crucial to understand the risk factors that negatively affect child development and the factors that are instead beneficial. In this study, we tested (i) the effects of different social and environmental stressors on maternal stress levels, (ii) the dynamic relationship between maternal stress and child behavior problems during development, and (iii) the potential promotive (i.e. main) or protective (i.e. buffering) effect of siblings on child behavior problems during development.Methods: We used longitudinal data from 373 mother–child pairs (188 daughters, 185 sons) from pregnancy until 10 years of age. We assessed maternal stress and child behavior problems (internalizing and externalizing) with vali-dated questionnaires, and then used linear mixed models, generalized linear mixed models and longitudinal cross-lagged models to analyze the data.Results: Our results showed that higher maternal stress levels were predicted by socio-environmental stressors (i.e. the lack of sufficient social areas in the neighborhood). Moreover, prenatal maternal stress reliably predicted the occurrence of behavior problems during childhood. Finally, the presence of older siblings had a promotive function, by reducing the likelihood that children developed externalizing problems.Conclusions: Overall, our results confirm the negative effects that maternal stress during pregnancy may have on the offspring, and suggest an important main effect of older siblings in promoting a positive child development

Metabolomics reveals effects of maternal smoking on endogenous metabolites from lipid metabolism in cord blood of newborns

Introduction: A general detrimental effect of smoking during pregnancy on the health of newborn children is well-documented, but the detailed mechanisms remain elusive. Objectives: Beside the specific influence of environmental tobacco smoke derived toxicants on developmental regulation the impact on the metabolism of newborn children is of particular interest, first as a general marker of foetal development and second due to its potential predictive value for the later occurrence of metabolic diseases. Methods: Tobacco smoke exposure information from a questionnaire was confirmed by measuring the smoking related metabolites S-Phenyl mercapturic acid, S-Benzyl mercapturic acid and cotinine in maternal urine by LC–MS/MS. The impact of smoking on maternal endogenous serum metabolome and children’s cord blood metabolome was assessed in a targeted analysis of 163 metabolites by an LC–MS/MS based assay. The anti-oxidative status of maternal serum samples was analysed by chemoluminiscence based method. Results: Here we present for the first time results of a metabolomic assessment of the cordblood of 40 children and their mothers. Several analytes from the group of phosphatidylcholines, namely PCaaC28:1, PCaaC32:3, PCaeC30:1, PCaeC32:2, PCaeC40:1, and sphingomyelin SM C26:0, differed significantly in mothers and children’s sera depending on smoking status. In serum of smoking mothers the antioxidative capacity of water soluble compounds was not significantly changed while there was a significant decrease in the lipid fraction. Conclusion: Our data give evidence that smoking during pregnancy alters both the maternal and children’s metabolome. Whether the different pattern found in adults compared to newborn children could be related to different disease outcomes should be in the focus of future studies

Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies

A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0.022/patient-year, P /= 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0.101 event/infusion. The incidence of local related AEs was 0.069 event/infusion (0.036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0.032 event/infusion. Most related AEs were mild, none were severe. For 64.6% of patients and in 94.8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0.95 (range = 0.3-4.1) h using mainly one to two administration sites [median = 2 sites (range = 1-5)]. Almost all infusions (99.8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment

Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease

Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality‐of‐life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion‐centre administration, and the use of self‐ or health‐professional‐administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self‐infusion regimens, however, require independence and self‐reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self‐administer or a lack of self‐reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health‐related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed

Pro-inflammatory Diet Pictured in Children With Atopic Dermatitis or Food Allergy: Nutritional Data of the LiNA Cohort

Background: Lifestyle and environmental factors are known to contribute to allergic disease development, especially very early in life. However, the link between diet composition and allergic outcomes remains unclear. Methods: In the present population-based cohort study we evaluated the dietary intake of 10-year-old children and analyses were performed with particular focus on atopic dermatitis or food allergy, allergic diseases known to be affected by dietary allergens. Dietary intake was assessed via semi-quantitative food frequency questionnaires. Based on these data, individual nutrient intake as well as children’s Dietary Inflammatory Index (C-DIITM) scores were calculated. Information about atopic manifestations during the first 10 years of life and confounding factors were obtained from standardized questionnaires during pregnancy and annually thereafter. Results: Analyses from confounder-adjusted logistic regression models (n = 211) revealed that having atopic outcomes was associated with having a pro-inflammatory pattern at the age of 10 years: OR = 2.22 (95% CI: 1.14–4.31) for children with atopic dermatitis and OR = 3.82 (95% CI: 1.47–9.93) for children with food allergy in the first 10 years of life Conclusion: A pro-inflammatory dietary pattern might worsen the atopic outcome and reduce the buffering capacity of the individual against harmful environmental exposures or triggers. For pediatricians it is recommended to test for the individual tolerance of allergenic foods and to increase the nutrient density of tolerable food items to avoid undesirable effects of eating a pro-inflammatory diet

Pro-inflammatory Diet Pictured in Children With Atopic Dermatitis or Food Allergy:Nutritional Data of the LiNA Cohort

Background: Lifestyle and environmental factors are known to contribute to allergic disease development, especially very early in life. However, the link between diet composition and allergic outcomes remains unclear. Methods: In the present population-based cohort study we evaluated the dietary intake of 10-year-old children and analyses were performed with particular focus on atopic dermatitis or food allergy, allergic diseases known to be affected by dietary allergens. Dietary intake was assessed via semi-quantitative food frequency questionnaires. Based on these data, individual nutrient intake as well as children’s Dietary Inflammatory Index (C-DII™) scores were calculated. Information about atopic manifestations during the first 10 years of life and confounding factors were obtained from standardized questionnaires during pregnancy and annually thereafter. Results: Analyses from confounder-adjusted logistic regression models (n = 211) revealed that having atopic outcomes was associated with having a pro-inflammatory pattern at the age of 10 years: OR = 2.22 (95% CI: 1.14–4.31) for children with atopic dermatitis and OR = 3.82 (95% CI: 1.47–9.93) for children with food allergy in the first 10 years of life. Conclusion: A pro-inflammatory dietary pattern might worsen the atopic outcome and reduce the buffering capacity of the individual against harmful environmental exposures or triggers. For pediatricians it is recommended to test for the individual tolerance of allergenic foods and to increase the nutrient density of tolerable food items to avoid undesirable effects of eating a pro-inflammatory diet.</p

Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults

Higher Doses of Subcutaneous IgG Reduce Resource Utilization in Patients with Primary Immunodeficiency

The recommended dose of IgG in primary immunodeficiency (PID) has been increasing since its first use. This study aimed to determine if higher subcutaneous IgG doses resulted in improved patient outcomes by comparing results from two parallel clinical studies with similar design. One patient cohort received subcutaneous IgG doses that were 1.5 times higher than their previous intravenous doses (mean 213 mg/kg/week), whereas the other cohort received doses identical to previous subcutaneous or intravenous doses (mean 120 mg/kg/week). While neither cohort had any serious infections, the cohort maintained on higher mean IgG dose had significantly lower rates of non-serious infections (2.76 vs. 5.18 episodes/year, P < 0.0001), hospitalization (0.20 vs. 3.48 days/year, P < 0.0001), antibiotic use (48.50 vs. 72.75 days/year, P < 0.001), and missed work/school activity (2.10 vs. 8.00 days/year, P < 0.001). The higher-dose cohort had lower health care utilization and improved indices of well being compared to the cohort treated with traditional IgG doses