Imbalanced Folate and Vitamin B12 in the Third Trimester of Pregnancy and its Association with Birthweight and Child Growth up to 2 Years

Scope: Folic acid supplementation during pregnancy may lead to an imbalance when vitamin B12 intake is low (folate trap) and may affect child’s growth. Methods: The authors study the association between third trimester maternal intakes of folate and B12 and birthweight and postnatal growth of 2632 infants from the KOALA Birth Cohort Study. Plasma vitamin biomarkers are measured in 1219 women. Results: Imbalanced total intakes (folate > 430 µg day−1 combined with B12 < 5.5 µg day−1) are not associated with birthweight [ adj (95% CI) = –14.87 (–68.87, 39.13)] compared with high intakes of both. Imbalanced intake is associated with a lower z score of weight at 1–2 years [ adj = –0.14 (–0.25, –0.03)]. Having red blood cell folate > 745 nmol L−1 and plasma B12 < 172 pmol L−1 is not associated with birthweight [ adj = –7.10 (–97.90, 83.71) g]. Maternal dietary B12 intake [ adj = –9.5 (–15.6, –3.3)] and plasma methylmalonic acid [ adj = 234 (43, 426)] are associated with birthweight. Conclusion: Low maternal dietary B12 intake and elevated methylmalonic acid rather than imbalanced vitamins are associated with higher birthweight, suggesting that low maternal B12 can predispose the infants for later obesity

Early Life Antibiotic Exposure and Weight Development in Children

OBJECTIVE: To examine the timing, frequency, and type of antibiotic exposure during the first 10 years of life in association with (over)weight across this period in a cohort of 979 children. STUDY DESIGN: Within the Child, Parents and Health: Lifestyle and Genetic Constitution Birth Cohort Study, antibiotic exposure record was obtained from general practitioners. Anthropometric outcomes (age- and sex-standardized body mass index, weight and height z-scores, and overweight) were measured repeatedly at 7 time points during the first 10 years of life. Generalized estimating equations method was used for statistical analysis. RESULTS: After adjusting for confounding factors, children exposed to one course of antibiotics compared with none in the first 6 months of life had increased weight- (adjusted generalized estimating equations estimates [adjβ] 0.24; 95% CI 0.03-0.44) and height (adjβ 0.23; 95% CI 0.0002-0.46) z-scores; exposure to ≥2 courses during the second year of life was associated with both increased weight (adjβ 0.34; 95% CI 0.07-0.60), and height z-scores (adjβ 0.29; 95% CI -0.003 to 0.59). Exposure later in life was not associated with anthropometric outcomes. Associations with weight z-scores were mainly driven by exposure to broad- (≥2 courses: adjβ 0.11; 95% CI 0.003-0.22) and narrow-spectrum β-lactams (1 course: adjβ 0.18; 95% CI 0.005-0.35) during the follow-up period. Specific antibiotic used was not associated with body mass index z-scores and overweight. CONCLUSIONS: Repeated exposure to antibiotics early in life, especially β-lactam agents, is associated with increased weight and height. If causality of obesity can be established in future studies, this further highlights the need for restrictive antibiotic use and avoidance of prescriptions when there is minimal clinical benefit

Genetic Variation in FADS Genes and Plasma Cholesterol Levels in 2-Year-Old Infants

Single nucleotide polymorphisms (SNPs) in genes involved in fatty acid metabolism (FADS1 FADS2 gene cluster) are associated with plasma lipid levels. We aimed to investigate whether these associations are already present early in life and compare the relative contribution of FADS SNPs vs traditional (non-genetic) factors as determinants of plasma lipid levels. Information on infants' plasma total cholesterol levels, genotypes of five FADS SNPs (rs174545, rs174546, rs174556, rs174561, and rs3834458), anthropometric data, maternal characteristics, and breastfeeding history was available for 521 2-year-old children from the KOALA Birth Cohort Study. For 295 of these 521 children, plasma HDLc and non-HDLc levels were also known. Multivariable linear regression analysis was used to study the associations of genetic and non-genetic determinants with cholesterol levels. All FADS SNPs were significantly associated with total cholesterol levels. Heterozygous and homozygous for the minor allele children had about 4% and 8% lower total cholesterol levels than major allele homozygotes. In addition, homozygous for the minor allele children had about 7% lower HDLc levels. This difference reached significance for the SNPs rs174546 and rs3834458. The associations went in the same direction for non-HDLc, but statistical significance was not reached. The percentage of total variance of total cholesterol levels explained by FADS SNPs was relatively low (lower than 3%) but of the same order as that explained by gender and the non-genetic determinants together. FADS SNPs are associated with plasma total cholesterol and HDLc levels in preschool children. This brings a new piece of evidence to explain how blood lipid levels may track from childhood to adulthood. Moreover, the finding that these SNPs explain a similar amount of variance in total cholesterol levels as the non-genetic determinants studied reveals the potential importance of investigating the effects of genetic variations in early life

Edge and modular significance assessment in individual-specific networks.

peer reviewedIndividual-specific networks, defined as networks of nodes and connecting edges that are specific to an individual, are promising tools for precision medicine. When such networks are biological, interpretation of functional modules at an individual level becomes possible. An under-investigated problem is relevance or "significance" assessment of each individual-specific network. This paper proposes novel edge and module significance assessment procedures for weighted and unweighted individual-specific networks. Specifically, we propose a modular Cook's distance using a method that involves iterative modeling of one edge versus all the others within a module. Two procedures assessing changes between using all individuals and using all individuals but leaving one individual out (LOO) are proposed as well (LOO-ISN, MultiLOO-ISN), relying on empirically derived edges. We compare our proposals to competitors, including adaptions of OPTICS, kNN, and Spoutlier methods, by an extensive simulation study, templated on real-life scenarios for gene co-expression and microbial interaction networks. Results show the advantages of performing modular versus edge-wise significance assessments for individual-specific networks. Furthermore, modular Cook's distance is among the top performers across all considered simulation settings. Finally, the identification of outlying individuals regarding their individual-specific networks, is meaningful for precision medicine purposes, as confirmed by network analysis of microbiome abundance profiles

Preterm Birth and Childhood Wheezing Disorders:A Systematic Review and Meta-Analysis

Background: Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth. Methods and Findings: Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%. Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding. Conclusions: There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions. Review Registration PROSPERO CRD42013004965 Please see later in the article for the Editors' Summar

Decay resistance variability of European wood species thermally modified by industrial process

Thermal modification is now considered as a new ecofriendly industrial wood modification process improving mainly the material decay resistance and its dimensional stability. Most industrial thermal treatment processes use convection heat transfer which induces sometimes heterogeneous treatment temperature propagation within the oven and lead to the heterogeneity in treatment efficiency. Thus, it is common that treatment is not completely effective on several stack boards, in a same batch. The aim of this paper was to study the decay resistance variability of various European wood species thermally modified. Thermal modifications were performed around 240°C during 4h, on about 10 m3 of 27 x 152 x 2000 mm3 wood planks placed in an industrial oven having a volume of 20 m3, on the following wood species: spruce, ash, beech and poplar. All of the tests concerning the decay resistance were carried out in the laboratory using untreated beech and pine woods as reference materials. An agar block test was used to determine the resistance of thermally modified woods, leached beforehand according to EN 84 standard or not, to brown-rot and white-rot fungi, according to XP CEN/TS 15083-1. A large selection of treated wood samples was tested in order to estimate the variability of treatment efficiency. Thermal treatment increased the biological durability of all leached and un-leached modified wood samples, compared with native wood species. The treatment temperature of 240°C used in this study is sufficient to reach durability classes ''durable'' or ''very durable'' for the four wood species. However, the dispersion of weight loss values, due to the fungal attacks was very important and showed a large variability of the durability of wood which has been treated in a single batch. These results showed that there is a substantial need to develop process control and² indicator in order to insure that the quality of treated timber is properly evaluated with a view to putting this modified timber on the market under a chain of custody. (Résumé d'auteur

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

Background It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in c

An ADAM33 Polymorphism Associates with Progression of Preschool Wheeze into Childhood Asthma:A Prospective Case-Control Study with Replication in a Birth Cohort Study

The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined.To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma.In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis).In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze.Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma

Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 1990-2010: A Systematic Review of Epidemiological Studies

The prevalence of atopic eczema has been found to have increased greatly in some parts of the world. Building on a systematic review of global disease trends in asthma, our objective was to study trends in incidence and prevalence of atopic eczema. Disease trends are important for health service planning and for generating hypotheses regarding the aetiology of chronic disorders. We conducted a systematic search for high quality reports of cohort, repeated cross-sectional and routine healthcare database-based studies in seven electronic databases. Studies were required to report on at least two measures of the incidence and/or prevalence of atopic eczema between 1990 and 2010 and needed to use comparable methods at all assessment points. We retrieved 2,464 citations, from which we included 69 reports. Assessing global trends was complicated by the use of a range of outcome measures across studies and possible changes in diagnostic criteria over time. Notwithstanding these difficulties, there was evidence suggesting that the prevalence of atopic eczema was increasing in Africa, eastern Asia, western Europe and parts of northern Europe (i.e. the UK). No clear trends were identified in other regions. There was inadequate study coverage worldwide, particularly for repeated measures of atopic eczema incidence. Further epidemiological work is needed to investigate trends in what is now one of the most common long-term disorders globally. A range of relevant measures of incidence and prevalence, careful use of definitions and description of diagnostic criteria, improved study design, more comprehensive reporting and appropriate interpretation of these data are all essential to ensure that this important field of epidemiological enquiry progresses in a scientifically robust manner