OBJECTIVES: Few studies have investigated the association between the full range of birth weight and the risk of childhood obesity in high-, middle-and low-income countries. The aim of the present study is to assess the association between different levels of birth weight and the risk of obesity among children aged 9-11 years in 12 countries. METHODS: A multinational, cross-sectional study of 5141 children aged 9-11 years was conducted in 12 countries. Height and weight were obtained using standardized methods. Time spent in moderate-to-vigorous physical activity (MVPA), sedentary and sleeping were objectively measured using 24-h, waist-worn accelerometer (Actigraph GT3X+) monitored for 7 days. Birth weight and other factors (regions, parental education, maternal history of gestational diabetes, children age, gender, breast feeding, gestational age, unhealthy diet scores and healthy diet scores) were collected by parental and children's questionnaires. Multilevel modeling was used to account for the nested nature of the data. RESULTS: The overall prevalence of obesity (BMI z-score4+2 s.d.) was 15.4% for boys and 10.0% for girls. There was a positive association between birth weight and BMI z-scores. The multivariable-adjusted odds ratios (ORs) of childhood obesity were significantly higher among children whose birth weights were 3500-3999 g (OR 1.45; 95% confidence interval (CI): 1.10-1.92), and 44000 g (OR 2.08; 95% CI: 1.47-2.93), compared with the reference group (2500-2999 g). The positive association between birth weight and the odds of childhood obesity was seen in girls, whereas a U-shaped association appeared in boys. CONCLUSIONS: High levels of birth weight, defined as birth weight ⩾ 3500 g, were associated with increased odds of obesity among 9-11-year-old children in 12 countries. However, sex differences in the association between birth weight and the risk of obesity need to be considered when planning interventions to reduce childhood obesity.

Early establishment of the infant gut microbiome has been attributed to various environmental factors that may influence long-term health. The aim of this study was to determine the single and combined impacts of the delivery mode, feeding pattern and postnatal antibiotic exposure on the initial establishment of infant gut microbiome at 6 weeks postpartum. A cross-sectional study was conducted at a single center in China. Fecal samples were collected from 120 infants at 6 weeks postpartum. The V3-V4 regions of 16S rRNA gene were analyzed by Illumina sequencing, and clinical information was obtained from medical records and questionnaire survey. Compared with vaginally delivered infants, the gut microbial community structure of cesarean delivered infants were significantly different ( P = 0.044), in parallel with the decreased relative abundance of Bifidobacterium ( P = 0.028), which contrasts with the normal gut microbial establishment. Using the vaginally delivered and exclusively breastfed (VB) infants as a reference, the comparative analysis of cesarean delivered and exclusively breastfed (CB) infants with cesarean delivered and mixed-fed (CM) infants showed that both within- and between-group UniFrac distance were significantly smaller in CB infants ( P < 0.001, P < 0.001). LEfSe analysis showed that the relative abundances of Enterococcus, Veillonella , and Faecalibacterium were significantly different between CB and CM infants, whereas the relative abundances of those genera in VB infants were close to those of CB infants, and distinct from those of CM infants. Additionally, no significant difference of microbial composition, alpha diversity, or community structure was observed between postnatal antibiotics exposed infants and unexposed infants. In summary, delivery mode had a significant impact on the infant gut microbial community structure and composition, and the gut microbiota was disturbed in infants delivered by cesarean section. However, our study showed that this disturbance of gut microbiota in cesarean delivered infants was partially restored by exclusive breastfeeding in comparison with mixed feeding. No distinct impact of postnatal antibiotic exposure on infant gut microbiome was found at 6 weeks of age.

Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05), and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01). The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.