Tingting Zhu

Peripheral brain-derived neurotrophic factor in autism spectrum disorder: a systematic review and meta-analysis

Brain-derived neurotrophic factor (BDNF) regulates neuronal survival and growth and promotes synaptic plasticity. Recently, researchers have begun to explore the relationship between peripheral BDNF levels and autism spectrum disorder (ASD), but the findings are inconsistent. We undertook the first systematic review and meta-analysis of studies examining peripheral BDNF levels in ASD compared with healthy controls. The PubMed, Embase, and Cochrane Library databases were searched for studies published before February 2016. Fourteen studies involving 2,707 participants and 1,131 incident cases were included. The meta-analysis provided evidence of higher peripheral BDNF levels in ASD compared with controls [standardized mean difference (SMD) = 0.63, 95% confidence interval (95% CI) = 0.18–1.08; P = 0.006]. Subgroup analyses revealed higher BDNF levels in ASD compared with controls for both serum [SMD = 0.58, 95% CI = 0.11–1.04; P = 0.02] and plasma [SMD = 1.27, 95% CI = 0.92–1.61; P < 0.001]. Studies of childhood yielded similar cumulative effect size [SMD = 0.78, 95% CI = 0.31–1.26; P = 0.001], while this was not true for the studies of adulthood [SMD = 0.04, 95% CI = −1.72–1.80; P = 0.97]. This meta-analysis suggests that peripheral BDNF levels are a potential biomarker of ASD.

Prenatal, Perinatal and Neonatal Risk Factors for Intellectual Disability: A Systemic Review and Meta-Analysis

Background The etiology of non-genetic intellectual disability (ID) is not fully known, and we aimed to identify the prenatal, perinatal and neonatal risk factors for ID. Method PubMed and Embase databases were searched for studies that examined the association between pre-, peri- and neonatal factors and ID risk (keywords “intellectual disability” or “mental retardation” or “ID” or “MR” in combination with “prenatal” or “pregnancy” or “obstetric” or “perinatal” or “neonatal”. The last search was updated on September 15, 2015. Summary effect estimates (pooled odds ratios) were calculated for each risk factor using random effects models, with tests for heterogeneity and publication bias. Results Seventeen studies with 55,344 patients and 5,723,749 control individuals were eligible for inclusion in our analysis, and 16 potential risk factors were analyzed. Ten prenatal factors (advanced maternal age, maternal black race, low maternal education, third or more parity, maternal alcohol use, maternal tobacco use, maternal diabetes, maternal hypertension, maternal epilepsy and maternal asthma), one perinatal factor (preterm birth) and two neonatal factors (male sex and low birth weight) were significantly associated with increased risk of ID. Conclusion This systemic review and meta-analysis provides a comprehensive evidence-based assessment of the risk factors for ID. Future studies are encouraged to focus on perinatal and neonatal risk factors and the combined effects of multiple factors.

Association Between Perinatal Hypoxic-Ischemic Conditions and Attention-Deficit/Hyperactivity Disorder A Meta-Analysis

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder worldwide, but its etiology is still not fully understood. Previous studies have reported that perinatal hypoxic-ischemic conditions may be a potential cause of ADHD. Methods: An online search of potential English studies published before September 2015 was conducted using the PsycINFO, EMBASE, Web of Science, and PubMed databases. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects models. Results: Ten studies were included, with 45 821 cases and 9 207 363 controls. The metaresults found that the following were associated with ADHD: preeclampsia (OR 1.31; 95% CI 1.26-1.37), an Apgar score <7 at 5 minutes (OR 1.31; 95% CI 1.12-1.54), breech/transverse presentations (OR 1.14; 95% CI 1.06-1.23), and a prolapsed/nuchal cord (OR 1.10; 95% CI 1.06-1.15). Conclusion: Our results support that perinatal hypoxia-ischemia may contribute to ADHD. However, more clinical studies are warranted.

Blood Glutamate Levels in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Objective Glutamate plays an important role in brain development, neuronal migration, differentiation, survival and synaptogenesis. Recent studies have explored the relationship between blood glutamate levels and autism spectrum disorder (ASD). However, the findings are inconsistent. We undertook the first systematic review with a meta-analysis of studies examining blood glutamate levels in ASD compared with controls. Methods A literature search was conducted using PubMed, Embase, and the Cochrane Library for studies published before March 2016. A random-effects model was used to calculate the pooled standardized mean difference (SMD) of the outcomes. Subgroup analyses were used to explore the potential sources of heterogeneity, and the publication bias was estimated using Egger’s tests. Results Twelve studies involving 880 participants and 446 incident cases were included in this meta-analysis. The meta-analysis provided evidence for higher blood glutamate levels in ASD [SMD = 0.99, 95% confidence interval (95% CI) = 0.58–1.40; P < 0.001] with high heterogeneity (I2 = 86%, P < 0.001) across studies. The subgroup analyses revealed higher glutamate levels in ASD compared with controls in plasma [SMD = 1.04, 95% CI = 0.58–1.50; P < 0.001] but not true in serum [SMD = 0.79, 95% CI = -0.41–1.99; P = 0.20]. Studies employing high performance liquid chromatography (HPLC) or liquid chromatography-tandem mass spectrometry (LC-MS) assays also revealed higher blood glutamate levels in ASD. A sensitivity analysis found that the results were stable, and there was no evidence of publication bias. Conclusions Blood glutamate levels might be a potential biomarker of ASD.

Association between maternal obesity and offspring Apgar score or cord pH: a systematic review and meta-analysis.

Previous results are inconsistent regarding the association between maternal obesity and Apgar score or cord pH in humans. The aim of this study was to investigate the association between maternal pre-pregnancy and pregnancy body mass index (BMI) and infant Apgar score or cord pH. We conducted a systematic review of studies published in English before 20 August 2015 using PubMed, EMBASE, and Cochrane Library. Eleven cohort studies with a total of 2,586,265 participants finally met our inclusion criteria. Pooled results revealed the following factors associated with Apgar score <7 at 5 minutes: overweight (odds ratio [OR] 1.13; 95% confidence interval [CI], 1.08–1.20), obese (OR 1.40; 95% CI, 1.27–1.54), and very obese (OR 1.71; 95% CI, 1.55–1.89). The pooled analysis also revealed that maternal overweight or obesity increased the risk for Apgar score <7 at 1 minute. There was no association between maternal BMI and neonatal cord pH. Thus, this study suggests that maternal overweight and obesity affect baby’s condition immediately after birth in general. More studies are needed to confirm these results and detect the influence of variables across studies.

Association between Asthma and Autism Spectrum Disorder: A Meta-Analysis

Objective We conducted a meta-analysis to summarize the evidence from epidemiological studies of the association between asthma and autism spectrum disorder (ASD). Methods A literature search was conducted using PubMed, Embase, and Cochrane library for studies published before February 2nd, 2016. Observational studies investigating the association between asthma and ASD were included. A random effects model was used to calculate the pooled risk estimates for the outcome. Subgroup analysis was used to explore potential sources of heterogeneity and publication bias was estimated using Beggs and Eggers tests. Results Ten studies encompassing 175,406 participants and 8,809 cases of ASD were included in this meta-analysis. In the cross-sectional studies, the prevalence of asthma in ASD was 20.4%, while the prevalence of asthma in controls was 15.4% (P < 0.001). The pooled odds ratio (OR) for the prevalence of asthma in ASD in the cross-sectional studies was 1.26 (95% confidence interval (CI): 0.98–1.61) (P = 0.07), with moderate heterogeneity (I2 = 65.0%, P = 0.02) across studies. In the case-control studies, the pooled OR for the prevalence of asthma in ASD was 0.98 (95% CI: 0.68–1.43) (P = 0.94), and there was no evidence of an association between asthma and ASD. No evidence of significant publication bias on the association between asthma and ASD was found. Conclusions In conclusion, the results of this meta-analysis do not suggest an association between asthma and ASD. Further prospective studies ascertaining the association between asthma and ASD are warranted.

Meta-analysis of antenatal infection and risk of asthma and eczema.

Background:The influence of maternal infection during pregnancy on allergic disorders in offspring is not well understood. We performed a systematic review and meta-analysis to evaluate current evidence on the association between maternal infection during pregnancy and asthma or eczema in offspring. Methods:We searched databases (PubMed, EMBASE, Medline, and Web of Science) for all relevant studies published before March 2016. Any cohort studies, case–control studies, or cross-sectional studies published in English and focused on the association between maternal infection during pregnancy and the risk of asthma or eczema in offspring were included. Random-effects models were used for combined analyses. Results:A total of 10 studies with 299,830 participants were included. Maternal infection was associated with an increased risk for asthma (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.24–1.92; P < 0.01) and eczema (OR: 1.36; 95% CI: 1.13–1.64; P < 0.01). Further analyses showed associations between asthma and several specific maternal infections: fever episode (OR: 1.73; 95% CI: 1.35–2.23), chorioamnionitis (OR: 1.42; 95% CI: 0.96–2.11), respiratory infection (OR: 1.49; 95% CI: 0.94–2.36), and urogenital infection (OR: 1.39; 95% CI: 1.18–1.64). Conclusion:The results from this meta-analysis and systematic review provide evidence that maternal infection during pregnancy might be related to subsequent asthma and eczema in offspring. However, there was variation of included studies with regard to type of maternal infection, age of children, and methods of exposure ascertainment. Additional studies are needed to further confirm these associations.

Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury

High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining. Cortical levels of HMGB1, its receptor for advanced glycation end-products (RAGE), and downstream effecter, nuclear factor kappa-B (NF-κB) subunit p65, were detected via western blot.HMGB1was increased in the cytoplasm via translocation from the nucleus predominantly in neurons. Moreover, RAGE and NF-κB p65 were upregulated after septic brain injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of RAGE and NF-κB p65via inhibiting HMGB1 expression in the cytoplasm. Collectively, our findings suggest that HMGB1 and its signaling transduction have critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might be a potential new therapeutic target for septic brain injury.

Association of maternal hypertensive disorders with retinopathy of prematurity: A systematic review and meta-analysis

Backgroud The role of maternal hypertensive disorders in pregnancy (HDP) in the development of retinopathy of prematurity (ROP) is unclear. Methods Studies were retrieved through literature searches in PubMed, EMBASE, Web of Science and the Cochrane Library up to May 5, 2016 without language restrictions. Cohort or case–control studies that reported the association of maternal hypertensive disorders and retinopathy of prematurity were eligible. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Results Thirteen cohort studies involving a total of 45082 individuals were included in the review. The pooled odds ratios of maternal hypertensive disorders in pregnancy for any stage and severe stages of ROP was 1.12 (95%CI: 0.90–1.40) and 0.80 (95%CI: 0.47–1.35), respectively. Sensitivity analyses confirmed that no single study qualitatively influenced the pooled OR. However, substantial heterogeneity and publication bias were observed in the meta-analysis. Conclusions Additional larger, prospective and well-adjusted studies are needed to determine the association between HDP and ROP, especially regarding the effects of different types of maternal hypertensive disorders in pregnancy on retinopathy of prematurity.

Maternal Smoking and Attention-Deficit/Hyperactivity Disorder in Offspring: A Meta-analysis

Causes of ADHD are complex, and our meta-analysis revealed that prenatal nicotine exposure may be implicated in the development of ADHD. CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood. Exploring the risk factors for ADHD is helpful in preventing ADHD. OBJECTIVE: To explore the association between maternal smoking during pregnancy and the occurrence of ADHD in offspring. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched from inception to May 2017 for studies. STUDY SELECTION: Cohort or case-control studies in which the association between maternal smoking and ADHD in offspring were investigated were eligible if they included odds ratios (ORs), hazard ratios, or risk ratios and 95% confidence intervals (CIs). DATA EXTRACTION: Two investigators independently extracted data on definition of exposure and outcome, number of cases and total sample population, and potential confounders adjusted. Any dose-relationship data for smoking and ADHD risk were also extracted. RESULTS: Fifteen cohort studies and 5 case-control studies with 50 044 cases and 2 998 059 participants were included. Smoking during pregnancy increased the risk of offspring ADHD (OR: 1.60; 95% CI: 1.45–1.76). The risk of ADHD was greater for children whose mothers were heavy smokers (OR: 1.75; 95% CI: 1.51–2.02) than for those mothers were light smokers (OR: 1.54; 95% CI: 1.40–1.70). LIMITATIONS: The limitations of our study included different assessment tools of ADHD and a lack of objective biological measures for maternal smoking. CONCLUSIONS: With our meta-analysis, we provide evidence for an association between maternal smoking and offspring ADHD but do not solve the causality issues concerning potential confounding by other risk factors. More high-quality studies are needed to establish whether the association with smoking is causal.