Zhangbin Yu

Pre-Pregnancy Body Mass Index in Relation to Infant Birth Weight and Offspring Overweight/Obesity: A Systematic Review and Meta-Analysis

Background Overweight/obesity in women of childbearing age is a serious public-health problem. In China, the incidence of maternal overweight/obesity has been increasing. However, there is not a meta-analysis to determine if pre-pregnancy body mass index (BMI) is related to infant birth weight (BW) and offspring overweight/obesity. Methods Three electronic bibliographic databases (MEDLINE, EMBASE and CINAHL) were searched systematically from January 1970 to November 2012. The dichotomous data on pre-pregnancy overweight/obesity and BW or offspring overweight/obesity were extracted. Summary statistics (odds ratios, ORs) were used by Review Manager, version 5.1.7. Results After screening 665 citations from three electronic databases, we included 45 studies (most of high or medium quality). Compared with normal-weight mothers, pre-pregnancy underweight increased the risk of small for gestational age (SGA) (odds ratios [OR], 1.81; 95% confidence interval [CI], 1.76–1.87); low BW (OR, 1.47; 95% CI, 1.27–1.71). Pre-pregnancy overweight/obesity increased the risk of being large for gestational age (LGA) (OR, 1.53; 95% CI, 1.44–1.63; and OR, 2.08; 95% CI; 1.95–2.23), high BW (OR, 1.53; 95% CI, 1.44–1.63; and OR, 2.00; 95% CI; 1.84–2.18), macrosomia (OR, 1.67; 95% CI, 1.42–1.97; and OR, 3.23; 95% CI, 2.39–4.37), and subsequent offspring overweight/obesity (OR, 1.95; 95% CI, 1.77–2.13; and OR, 3.06; 95% CI, 2.68–3.49), respectively. Sensitivity analyses revealed that sample size, study method, quality grade of study, source of pre-pregnancy BMI or BW had a strong impact on the association between pre-pregnancy obesity and LGA. No significant evidence of publication bias was observed. Conclusions Pre-pregnancy underweight increases the risk of SGA and LBW; pre-pregnancy overweight/obesity increases the risk of LGA, HBW, macrosomia, and subsequent offspring overweight/obesity. A potential effect modification by maternal age, ethnicity, gestational weight gain, as well as the role of gestational diseases should be addressed in future studies.

Trends in Overweight and Obesity among Children and Adolescents in China from 1981 to 2010: A Meta-Analysis

Background Overweight/obesity is a serious public health problem that affects a large part of the world population across all age and racial/ethnic groups. However, there has not been a meta-analysis of the prevalence of childhood and adolescent overweight/obesity in China during the past 30 years. Methods The China National Knowledge Infrastructure and Wanfang DATA, MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature were searched for relevant studies published between January 1970 and June 2012. The prevalence of overweight/obesity over time was pooled using Stata/SE, version 9. Summary statistics (odds ratios, ORs) were used to compare sex-specific and urban-rural preponderance of overweight/obesity using Review Manager. Results After screening 1326 papers, we included 35 papers (41 studies), most of medium quality. The prevalence of overweight/obesity increased from 1.8% (95% confidence interval [CI], 0.4%–3.1%) and 0.4% (95% CI, −0.1% to −0.8%) respectively in 1981–1985 to 13.1% (95% CI, 11.2%–15.0%) and 7.5% (95% CI, 6.6%–8.4%) respectively in 2006–2010. The average annual increase was 8.3% and 12.4% respectively. Boys were more likely to be overweight/obese than girls (OR, 1.36; 95% CI, 1.24–1.49 and OR, 1.68; 95% CI, 1.52–1.86 respectively). The prevalence of overweight/obesity was higher in urban areas than in rural areas (OR, 1.66; 95% CI, 1.54–1.79 and OR, 1.97; 95% CI, 1.68–2.30 respectively). For age-specific subgroup analyses, both overweight and obesity increased more rapidly in the toddler stage than in other developmental stages. Sensitivity analyses showed that sample-size differences, study quality, overweight/obesity criteria and geographical distribution affected overweight/obesity prevalence. Conclusions Toddlers and urban boys were at particularly high risk; the prevalence in these groups increased more rapidly than in their counterparts. Public health prevention strategies are urgently needed to modify health behaviors of children and adolescents and control overweight/obesity in China.

Genetic Polymorphisms in Adipokine Genes and the Risk of Obesity: A Systematic Review and Meta‐Analysis

Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin‐1β (IL‐1β), IL‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian‐designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty‐one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39–1.81), IL‐1β C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18–2.20), and TNF‐α G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02–1.39) polymorphisms were associated with an increased risk of obesity. The IL‐6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37–2.77), 1.44 (1.15–1.80), and 1.36 (1.16–1.59), respectively. No significant evidence of publication bias was present. However, these “null” results were underpowered due to a small pooled sample size, and analysis of additional case‐control studies with larger sample sizes should provide further clarifications.

Intelligence in relation to obesity: a systematic review and meta‐analysis

We performed a systematic review describing obesity/intelligent quotient (IQ) association, particularly childhood IQ in relation to adulthood obesity. After screening 883 citations from five electronic databases, we included 26 studies, most of medium quality. The weighted mean difference (WMD) of the full IQ (FIQ)/obesity association in the pre‐school children was −15.1 (P > 0.05). Compared with controls, the WMD of FIQ and performance IQ of obese children were −2.8 and −10.0, respectively (P < 0.05), and the WMD of verbal IQ was −7.01 (P > 0.05). With increasing obesity, the FIQ in pre‐school children declined, with a significant difference for severely obese children and FIQ. In pubertal children, a slightly different effect of FIQ and obesity emerged. Two studies reported an inverse FIQ/obesity association in adults, but it was non‐significant after adjusting for educational attainment. Four papers found that childhood FIQ was inversely associated with adult body mass index, but after adjusting for education, became null. Overall there was an inverse FIQ/obesity association, except in pre‐school children. However, after adjusting for educational attainment, FIQ/obesity association was not significantly different. A lower FIQ in childhood was associated with obesity in later adulthood perhaps with educational level mediating the persistence of obesity in later life.

The accuracy of the procalcitonin test for the diagnosis of neonatal sepsis: A meta-analysis

Abstract A meta-analysis was performed to assess the accuracy of the procalcitonin (PCT) test for diagnosing neonatal sepsis. The major databases, MEDLINE, EMBASE and the Cochrane Library were searched for studies published between January 1996 and May 2009 that evaluated PCT as a diagnostic marker for neonatal sepsis and provided sufficient data to calculate sensitivity and specificity. Twenty-two studies were included in the analysis. Trials that evaluated the PCT test for the diagnosis of early-onset neonatal sepsis at different time points (birth, 0–12 h, 12–24 h, and 24–48 h) and late-onset neonatal sepsis (LONS) all showed moderate accuracy (Q* = 0.79, 0.86, 0.81, 0.82, and 0.77, respectively). The PCT test was more accurate than the C-reactive protein (CRP) test for the diagnosis of LONS. A sensitivity analysis found that differences in PCT assay producer, gestational age and severity of sepsis in the study population may partially explain the between-studies heterogeneity. The PCT test showed moderate accuracy in diagnosing neonatal sepsis, regardless of differences in diagnostic criteria and time points for testing. For the diagnosis of LONS, the PCT test showed better accuracy than the CRP test. PCT is a valuable additional tool for the diagnosis of neonatal sepsis.

Identification of maternal serum microRNAs as novel non-invasive biomarkers for prenatal detection of fetal congenital heart defects.

BACKGROUND Congenital heart defects (CHD) are the most common form of malformation during embryonic development. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of maternal serum miRNAs and their correlation with fetal CHD. METHODOLOGY/PRINCIPLE FINDINGS We systematically performed SOLiD sequencing followed by individual quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays to identify and validate the expression of maternal serum miRNAs at 18-22 weeks of gestation. Four miRNAs (miR-19b, miR-22, miR-29c and miR-375) were found to be significantly up-regulated in pregnant women with fetal CHD, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.79, 0.671, 0.767 and 0.693, respectively. Furthermore, the combination of the four miRNAs using multiple logistic regression analysis showed a larger AUC (0.813) that was more efficient for the early detection of fetal CHD. CONCLUSIONS/SIGNIFICANCE We identified and validated a class of four maternal serum miRNAs which could act as novel non-invasive biomarkers for the prenatal detection of fetal CHD.

Effects of miR - 19b Overexpression on Proliferation, Differentiation, Apoptosis and Wnt/β-Catenin Signaling Pathway in P19 Cell Model of Cardiac Differentiation In Vitro

MicroRNA (miR)-19b is part of the miR-17–92 cluster associated with cardiac development. Here, we investigated the effects of overexpressing miR-19b on proliferation, differentiation, apoptosis, and regulation of the Wnt/β-catenin signaling pathway in the multipotent murine P19 cell line that can be induced to undergo cardiogenesis. P19 cells were transfected with the miR-19b plasmid or empty vector, and miR-19b overexpression was verified by Quantitative Real-Time PCR (qPCR). The miR-19b or vector control stable cell lines were selected using Blasticidin S HCl, and their proliferation, cell cycle, and apoptosis levels were analyzed using the Cell Counting Kit-8 and flow cytometry. P19 cell differentiation markers, apoptosis-related genes (bax, bcl-2), and Wnt/β-catenin signaling pathway-related genes were detected by qPCR, the corresponding proteins by Western blot. Expression of the Wnt pathway and differentiation marker proteins was also verified by immunofluorescence. Morphological changes associated with apoptosis were observed by electron microscopy and Hoechst staining. On the basis of these results, we demonstrated that miR-19b overexpression promoted proliferation and differentiation but inhibited apoptosis in P19 cells; Wnt and β-catenin expressions were decreased, while that of GSK3β was increased with miR-19b overexpression. Overexpression of miR-19b inhibited activation of the Wnt/β-catenin signaling pathway in P19 cells, which may regulate cardiomyocyte differentiation. Our findings may bring new insights into the mechanisms underlying cardiac diseases and suggest that miR-19b is a potential new therapeutic target for cardiovascular diseases.

microRNA expression profiling of the developing mouse heart

microRNAs (miRNAs) play an important role in regulating normal organ physiology and development. Many miRNAs show spatially and temporally restricted expression patterns during embryogenesis and organogenesis. This study aimed to characterize the miRNA profile of the fetal mouse heart at 4 key time-points [embryonic day (E)12.5, E14.5, E16.5 and E18.5] in its development, by performing a sequencing by oligonucleotide ligation and detection (SOLiD) miRNA screen. The 4 time-points were designated as groups M1 (E18.5), M2 (E16.5), M3 (E14.5) and M4 (E12.5). miRNAs found to have consistent fold-changes of >2.0) between the 4 time-points were selected for further analysis. Ten miRNAs (mmu-miR-23b, mmu-miR-24, mmu-miR-23a, mmu-miR-375, mmu-miR-29a, mmu-miR-93, mmu-miR-21, mmu-miR-25, mmu-let-7b and mmu-miR-27b) that were the most highly expressed in the 4 groups, including the percentage >1% of total read counts, were identified. No miRNA was consistently downregulated or upregulated. There were 16 differentially expressed miRNAs between the later development group (M1+M2) and the early development group (M3+M4), which were validated by quantitative real-time PCR. Several members of the let-7 miRNA cluster (mmu-let-7a/7d/7e/7f) were upregulated in the later development group compared with the early development group. A network analysis of the predicted targets of mmu-let-7a/7d/7e/7f identified 5 target genes (FOXP1, TBX5, HAND1, AKT2 and PPARGC1A), known to be involved in cardiac development. Therefore, this study identified several miRNAs that are abundantly expressed in the developing heart, several of which are differentially expressed in the 4 time-points studied. Findings of this analysis may thus clarify the mechanisms of normal heart development and provide a physiological basis for future studies on congenital heart disease.

Potential role of maternal serum microRNAs as a biomarker for fetal congenital heart defects

Congenital heart defects (CHD) are the most common form of major birth defect, affecting almost 1% of live births. These defects place a significant economic burden on the National Health Service and on the psychological wellbeing of affected families. The early screening and identification of neonates with CHD could reduce morbidity and mortality by allowing proactive medical treatment and parental counseling about options during pregnancy, including termination. Fetal echocardiography is the principal screening tool for the identification of CHD, but its accuracy mainly depends on the skill and experience of the operator. Various biomarkers of screening for fetal CHD are currently available, such as nuchal translucency (NT), β-hCG and PAPP-A; however, these are non-specific indexes with high incidences of false positive results. Certain specific microRNAs (miRNAs) of cardiogenesis have been identified, which correlate positively with placental miRNA expression. These miRNAs of placental origin can be detected in maternal peripheral blood. Therefore, we postulate that these maternal serum miRNAs may be a potential biomarker for fetal CHD.

Integrated Analysis of Dysregulated lncRNA Expression in Fetal Cardiac Tissues with Ventricular Septal Defect

Ventricular septal defects (VSD) are the most common form of congenital heart disease, which is the leading non-infectious cause of death in children; nevertheless, the exact cause of VSD is not yet fully understood. Long non-coding RNAs (lncRNAs) have been shown to play key roles in various biological processes, such as imprinting control, circuitry controlling pluripotency and differentiation, immune responses and chromosome dynamics. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with VSD has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNAs, focusing specifically on the identification and characterization of lncRNAs potentially involving in initiation of VSD. Comparison of the transcriptome profiles of cardiac tissues from VSD-affected and normal hearts was performed using a second-generation lncRNA microarray, which covers the vast majority of expressed RefSeq transcripts (29,241 lncRNAs and 30,215 coding transcripts). In total, 880 lncRNAs were upregulated and 628 were downregulated in VSD. Furthermore, our established filtering pipeline indicated an association of two lncRNAs, ENST00000513542 and RP11-473L15.2, with VSD. This dysregulation of the lncRNA profile provides a novel insight into the etiology of VSD and furthermore, illustrates the intricate relationship between coding and ncRNA transcripts in cardiac development. These data may offer a background/reference resource for future functional studies of lncRNAs related to VSD.