The Relationship between Zinc Levels and Autism: A Systematic Review and Meta-analysis

How to Cite This Article: Babaknejad N, Sayehmiri F, Sayehmiri K, Mohamadkhani A, Bahrami S. The Relationship between Zinc Levelsand Autism: Systematic Review and Meta-analysis. Iran J Child Neurol. Autumn 2016; 10(4):1-9. AbstractObjectiveAutism is a complex behaviorally defined disorder. There is a relationship between zinc (Zn) levels in autistic patients and development of pathogenesis, but the conclusion is not permanent. Materials & MethodsThe present study conducted to estimate this probability using meta-analysis method. In this study, Fixed Effect Model, twelve articles published from 1978 to 2012 were selected by searching Google scholar, PubMed, ISI Web of Science, and Scopus and information were analyzed. I² statistics were calculated to examine heterogeneity. The information was analyzed using R and STATA Ver. 12.2. ResultsThere was no significant statistical difference between hair, nail, and teeth Zn levels between controls and autistic patients: -0.471 [95% confidence interval (95% CI): -1.172 to 0.231]. There was significant statistical difference between plasma Zn concentration and autistic patients besides healthy controls: -0.253 (95% CI: 0.498 to -0.007). Using a Random Effect Model, the overall Integration of data from the two groups was -0.414 (95% CI: -0.878 to -0.051).ConclusionBased on sensitivity analysis, zinc supplements can be used for the nutritional therapy for autistic patients. References1. Arnold LE, Farmer C, Kraemeret HC, et al. Moderators, mediators, and other predictors of Risperidoneresponse in children with Autistic Disorder and Irritability. J Child Adolesc Psychopharmacol 2012; 20(2): 83-92.2. Karimzadeh P. Recent finding about etiology of autism. Rehabilitation 2000; 1(2):58-63.3. Dufault R, Schnoll R, Lukiw WJ, et al. Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children. Behav Brain Funct 2009; 5(44): 1-15.4. Morris CR, Agin CM. Syndrome of allergy, apraxia, and malabsorption: characterization of a neurodevelopmental phenotype that responds to omega 3 and vitamin E supplementation. Altern Ther Health Med 2009; 15(4): 34-43.5. An centers for Disease Control and Prevention (2012). Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network, Prevalence of Autism Spectrum Disorders (ASDs) Among Multiple Areas of the United States in 2008, United States, Morbidity and Mortal Weekly Report (MMWR); Vol. 61(3).6. Dufault R, Lukiw WJ, Crider R, et al. A macro epigenetic approach to identify factors responsible for the autism epidemic in the United States. Clin Epigenetics 2012; 4(6): 2-12.7. Faber S, Zinn GM, Kern GC, et al. The plasma zinc/ serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers 2009; 14(3): 171–180.8. Cornish E. Gluten and casein free diets in autism: a study of the effects on food choice and nutrition. J Hum Nutr Dietet 2012; 15: 261-268.9. De Palma G, Catalani S, Franco A, et al. Lack of correlation between metallic elements analyzed in hair by ICP-MS and Autism. J Autism Dev Disord 2012; 42(3):342–353.10. Adams JB, Romdalvik J, Ramanujam VM, Legator MS, et al. Mercury, Lead, and Zinc in Baby teeth of children with Autism versus controls. J Toxicol Environ Health A 2007;7(12): 1046-1051.11. Blaurock-Busch E, Amin OR, Rabah T. Heavy metals and Trace elements in hair and urine of a sample of Arab children with Autistic Spectrum Disorder. Maedica (Buchar) 2011;6(4): 247-252.12. Russo AJ, Devito R. Analysis of Copper and Zinc Plasma Concentration and the efficacy of Zinc therapy in individuals with Asperger’s syndrome, pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) and Autism. Biomarker Insights 2011; 6:127–133.13. Shearer TR, Larson K, Neuschwander J, Gedney B. Minerals in the hair and nutrient intake of Autistic children. J Autism Dev Disord 1982; 12(1): 25-30.14. Liberati A, Tetzlaff J, Mulrow C, et al. The PRISMA statement for reporting systematic reviews and metaanalyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 21: 339- b2700.15. Hartung J, Knapp G, Sinha BK. Statistical Meta- analysis with application. John Willey and Sons 2008, INC, USA.16. Babaknejad N, Sayehmiri F, Sayehmiri K, et al. The relationship between selenium levels and breast cancer: a systematic review and meta-analysis. Biol Trace Elem Res 2014;159(1-3):1-7.17. Al-Ayadehi LY. Heavy metals and trace elements in hair samples of autistic children in central Saudi Arabia. Neurosciences (Riyadh) 2005; 10(3):213-8.18. Blaurock-Busch E, Amin OR, Dessoki HH, Rabah T. Toxic metals and essential elements in hair and severity of symptoms among children with Autism. Mædica J Clin Med 2012;7(1): 38-47.19. Elsheshtawy E, Tobar S, Sherra K, et al, Study of some biomarkers in hair of children with autism. MECPsych 2011;18 18:6–10.20. Russo AJ. Increased Copper in individuals with Autism normalizes post Zinc therapy more efficiently in Individuals with in current GI Disease. Nutr Metab Insights 2011;4: 49–54.21. Jackson MJ, Garrod PJ. Plasma Zinc, Copper, and Amino Acid levelsin the blood of Autistic Children. J Autism Child Schizophr 1978; 8(2): 203-206.22. Priya MDL, Geetha A. Level of trace elements (Copper, Zinc, Magnesium and Selenium) and toxic elements(Lead and Mercury)in the Hair and Nail of Children with Autism. Biol Trace Elem Res 2011; 142(2): 148–158.23. Wecker L, Miller SB, Cochran SR, Dugger DL, Johnson WD. Trace element concentrations in hair from autistic children. J Ment Defic Res 1985; 29(1): 15-22.24. Adams JB, Audhya T, McDonough-Means S, et al. Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond) 2011; 8(34): 1-30.25. Adams JB, Holloway CE, George F, Quig D. Analyses of toxic metals and essential minerals in the hair of Arizona Children with Autism and associated conditions, and their mothers. Biol Trace Elem Res 2006; 110: 194-207.26. Al-Farsi YM, Waly MI, Al-Sharbati MM, et al. Levels of heavy metals and essential minerals in hair samples of children with Autism in Oman: a Case–Control Study. Biol Trace Elem Res 2013;151(2): 181-6.27. Russo AJ. Decreased serum Cu/Zn SOD in children with Autism. Nutr Metab Insights 2009; 2: 27-35.28. Xia W, Zhou Y, Sun C, Wang J, Wu L. A preliminary study on nutritional status and intake in Chinese children with autism. Eur J Pediatr 2010; 169(10):1201-1205.29. Russo AJ, Bazin AP, Bigega R, et al. Plasma Copper and Zinc Concentration in Individuals with Autism Correlate with Selected Symptom Severity. Nutr Metab Insights 2012;5: 41–47.30. Bjørklund G. The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp 2013; 73: 225–236.31. Yasuda H, Yoshida K, Yasuda Y, Tsutsui T. Infantile zinc deficiency: Association with autism spectrum disorders. Sci Rep 2011; 1(129): 1-4.32. Frye RE, Rossignol D2, Casanova MF, et al. A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel. Front Public Health 2013; 1(31): 1-17.33. Yasuda H, Tsutsui T. Assessment of Infantile Mineral Imbalances in Autism Spectrum Disorders (ASDs). Int J Environ Res Public Health 2013;10(11): 6027–6043

Surveying the relationship between Gly1057Asp polymorphism of IRS-2 gene and susceptibility to type 2 diabetes; a systematic review and meta-analysis study

Type 2 diabetes mellitus (T2DM) is a multi-factorial disease in which influenced by several genetic and environmental factors. Insulin receptor substrate 2 (IRS 2) is the main mediator of insulin in the liver which controls insulin sensitivity. Gly1057Asp polymorphism is one of the candidates to increase risk of T2DM. The present study is an attempt to study the relationship of Gly1057Asp polymorphism of IRS-2 and T2DM by a meta-analysis. A systemic search was conducted in English and Persian databases such as Scopus, PubMed, Google Scholar, SID, and other academic databases for studies that have investigated the relationship of Gly1057Asp polymorphism of IRS-2 and T2DM. This association was determined using odds ratios (ORs) with a confidence interval of 95% (CIs). Heterogeneity of the studies was examined by I2 index. Funnel plots and Egger tests were used to determine bias or publication bias. The collected data was analyzed in STATA through meta-analysis. Nine articles were selected as eligible for further analysis, which represented 3,196 patients with T2DM and 3409 controls subjects without T2DM. The present meta-analysis showed a significant relationship between GA genotype of Gly1057Asp polymorphism and T2DM (OR=0.88; 95% confidence interval, 0.79-0.98), whereas no significant relationship between GG and AA genotype with T2DM was seen; OR for GG and AA genotypes were 1.10 (95% CI, 0.99 -1.22) and 1.13 (95% CI, 0.95- 1.33), respectively. The results of our study show that genotype GA of Gly1057Asp polymorphism of IRS-2 gene plays a protective role and may decrease the risk of T2DM, whereas GG and AA genotypes are considered as a risk factor and related to development of T2DM to some extents. Keywords: Type 2 diabetes mellitus, Gly1057Asp polymorphism, Meta-analysi

Effects of vitamin B6 on premenstrual syndrome: A systematic review and meta-Analysis

Background and Objective: Premenstrual syndrome (PMS) refers to a range of physical and psychological symptoms which regularly occur during the luteal phase of a menstrual cycle and disappear short after menstruation starts. Considering the negative effects of PMS on women's daily life, various treatments have been developed to alleviate its symptoms. Vitamin B6 is one of the complementary therapies used to treat PMS. The present meta-Analysis aimed to investigate the effects of vitamin B6 on PMS. Methodology: Different databases including PubMed, ISI, Scopus, SID, Magiran, Science Direct, and Medlib were searched to identify studies addressing the effects of vitamin B6 on PMS. The relevant data obtained from these papers were analyzed by a random-effects model. Data were analyzed using R Ver. 3.2.3 Software and STATA. Results: There were significant reductions in the mean scores of PMS after treatment with vitamin B6 compare to control groups. Moreover, the mean PMS scores of the two groups were also significantly different after the treatment. The mean difference between the two groups was -1.19 [95% CI: -1.94,-0.44; P = 0.002]. Significant reductions were also observed in physical symptoms (P = 0.006) and psychological symptoms (P < 0.001) of PMS after the intervention. Conclusion: The results of our meta-Analysis confirmed vitamin B6 as a beneficial, inexpensive, and effective treatment for PMS symptoms. Therefore, the administration of this treatment option will enable midwives to achieve the important goal of reducing PMS symptoms

Prevalence of Anaerobic Bacteria (P.gingivalis) as Major Microbial Agent in the Incidence Periodontal Diseases by Meta-analysis

Statement of the Problem: Periodontal diseases are complex oral diseases characterized by bacterial-induced inflammatory destruction of tooth-supporting tissues. Porphyromonas gingivalis (P. gingivalis) is a common gram-negative anaerobic oral bacteria strongly associated with periodontal disease. Purpose: The present study was conducted to estimate prevalence of P. gingivalis in patients with periodontal diseases by using meta-analysis method. Martials and Method: Different databases including PubMed, EmBase, Scopus, the Institute for Scientific Information (ISI) Web of Science, and the Cochrane Library were searched to identify original English-language studies addressing prevalence of P. gingivalis in periodontal diseases up to December 2014. The random effects model was applied in the meta-analysis and the heterogeneity between studies was assessed using a Cochran test and the I2 index. Funnel plots and Egger test were used to examine publication bias. Statistical analyses were performed using STATA version 12. Results: Forty-two eligible studies published during 1993- 2016 were selected for meta-analysis. Considering all the included studies, the total sample size was 5,884 individuals containing 2,576 healthy people with a mean age of 37.21±7.45 years and 3,308 periodontal patients with a mean age of 44.16±8.35 years. Overall, the prevalence of P. gingivalis was 78% [95% CI: 74-81] in periodontal diseases group and 34% [95% CI: 26-41] in healthy individuals. There was a significantly higher prevalence of P.gingivalis in individuals with periodontal diseases compared to healthy subjects [78% versus 34%, respectively]. Conclusion: This study indicates that P. gingivalis is highly present in subjects with periodontal diseases and it also appears in periodontally healthy people, although to a lesser extent. Thus, the presence of P. gingivalis increases the chance of periodontal disease and it can be considered as a main potential risk factor

Possible cognition changes in women with polycystic ovary syndrome: a narrative review

Nowadays, polycystic ovary syndrome (PCOS) and cognitive dysfunction are major health problems among female. This narrative review aimed to investigate cognitive dysfunction in female with PCOS. English and Persian articles published in PubMed, Scopus, Web of Science, Google Scholar, PsycINFO, Scientific Information Database, and Cochrane Database of Systematic Reviews until May 2022 were searched. Sixteen studies involving 850 female with PCOS and 974 controls were assessed. In these studies, the association between biochemical factors and symptoms of PCOS and memory, attention, executive functioning, information processing speed, and visuospatial skills was evaluated. The literature review revealed the possible cognitive changes in female with PCOS. This study summarized the different aspects of cognitive function in female with PCOS due to medication, psychological problems (mood disorders caused by disease symptoms and complications), and biochemical markers, such as metabolic and sex hormone abnormalities. Considering the existing scientific gap regarding the possibility of cognitive complications in female with PCOS, further biological studies should be conducted to evaluate the potential mechanisms involved

Prevalence of cagA and vacA among Helicobacter pylori-infected patients in Iran: a systematic review and meta-analysis

The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and host-related factors. This study aimed to investigate the prevalence of cagA and vacA genes among H. pylori-infected patients in Iran and analyze their relevance to the disease status between two clinical groups via a meta-analysis method. Different databases including PubMed, ISI, Scopus, SID, Magiran, Science Direct, and Medlib were investigated, and 23 relevant articles from the period between 2001 and 2012 were finally analyzed. The relevant data obtained from these papers were analyzed by a random-effects model. Data were analyzed using R software and STATA. The prevalence of cagA and vacA genes among H. pylori-infected patients was 70% (95% CI, 64–75) and 41% (95% CI, 24.3–57.7), respectively. The prevalence of duodenal ulcers, peptic ulcers, and gastritis among cagA+ individuals was 53% (95% CI, 20–86), 65% (95% CI, 34–97), and 71% (95% CI, 59–84), respectively. Odds ratio (OR) between cagA-positive compared with cagA-negative patients showed a 1.89 (95% CI, 1.38–2.57) risk of ulcers. In conclusion, the frequency of cagA gene among H. pylori strains is elevated in Iran and it seems to be more frequently associated with gastritis. Therefore, any information about cagA and vacA prevalence among different H. pylori-infected clinical groups in the country can help public health authorities to plan preventive policies to reduce the prevalence of diseases associated with H. pylori infection

One Decade “Narcotic Addicted Patients with Deep Vein Thrombosis” in St. Alzahra Hospital of Isfahan, Iran

Abstract Background: Behavior and substance addiction is one of the risk factors for deep vein thrombosis (DVT). The aim of this study investigating the relationship between the different clinical manifestations pattern of DVT with the way, the amount and duration of narcotic drugs in patients admitted to St. Alzahra Hospital in Isfahan, Iran, during 10 years. Methods: In a cross-sectional study we studied all of the patients with DVT in St. Alzahra Hospital since 2003-2013 were studied. Findings: A total of 238 (59.1%) of the patients were male and 165 (40.9%) female. The mean age of men and women were 18.80 ± 48 and 19.60 ± 3.48 years old. The mean length of staying in the hospital was 5.40 ± 7.20 days. Addiction among patients with DVT was 19.1%. 28.2% of men suffered from DVT and 6% of the women were drug addicts (P < 0.001). Among the 77 patients taking the drug, 53.2% were heroin, 35.1%opium, and 11.7% used other injectable drugs. The results showed that 19 patients (28.6%) were taking the drug once daily, 27.3% twice a day, 6.5% three times a day, 15.6% once a week, and 26% taking the drug twice a week. From 403 patients, 2.2% had a problem in the upper limb, 44.4% in the left hand, and 55.6 in the right hand. The results showed that none of the 77 studied patients had involvement of upper limbs, but all of them in the lower limb. About 11.2% of studied patients were addicted to injective drugs. Also, 6% were addicted to non-injectable drugs and 2% to both injectable and non-injectable drugs. Conclusion: DVT has many risk factors and addiction and intravenously (IV)‎ drug abuse one of the most important for this illness and this problem mast be noticed by health worker and physicians. Keywords: Deep vein thrombosis, Prevalence, IV drug abuser, Addictio

Evaluating the effect of magnesium supplementation and cardiac arrhythmias after acute coronary syndrome: a systematic review and meta-analysis

Abstract Background Atrial and ventricular cardiac arrhythmias are one of the most common early complications after cardiac surgery and these serve as a major cause of mortality and morbidity after cardiac revascularization. We want to evaluate the effect of magnesium sulfate administration on the incidence of cardiac arrhythmias after cardiac revascularization by doing this systematic review and meta-analysis. Methods The search performed in several databases (SID, Magiran, IranDoc, IranMedex, MedLib, PubMed, EmBase, Web of Science, Scopus, the Cochrane Library and Google Scholar) for published Randomized controlled trials before December 2017 that have reported the association between Magnesium consumption and the incidence of cardiac arrhythmias. This relationship measured using odds ratios (ORs) with a confidence interval of 95% (CIs). Funnel plots and Egger test used to examine publication bias. STATA (version 11.1) used for all analyses. Results Twenty-two studies selected as eligible for this research and included in the final analysis. The total rate of ventricular arrhythmia was lower in the group receiving magnesium sulfate than placebo (11.88% versus 24.24%). The same trend obtained for the total incidence of supraventricular arrhythmia (10.36% in the magnesium versus 23.91% in the placebo group). In general the present meta-analysis showed that magnesium could decrease ventricular and supraventricular arrhythmias compared with placebo (OR = 0.32, 95% CI 0.16–0.49; p < 0.001 and OR = 0.42, 95% CI 0.22–0.65; p < 0.001, respectively). Subgroup analysis showed that the effect of magnesium on the incidence of cardiac arrhythmias was not affected by clinical settings and dosage of magnesium. Meta-regression analysis also showed that there was no significant association between the reduction of ventricular arrhythmias and sample size. Conclusion The results of this meta-analysis study suggest that magnesium sulfate can be used safely and effectively and is a cost-effective way in the prevention of many of ventricular and supraventricular arrhythmias

Association of Chlamydia trachomatis infections with preterm delivery; a systematic review and meta-analysis

Abstract Background Premature birth is a primary cause of infant mortality and its etiology varies in different countries. Chlamydia trachomatis (CT) is a common infectious agent transmitted through sexual contact. The purpose of this study is to investigate the connection between CT infections and preterm birth by meta-analysis. Methods All articles published in literature databases including Google Scholar, PubMed, ISI (Web of Science), Biological Abs, IranMedex, SID, and Scopus were investigated. Twenty-four relevant articles, authored betweenm 1998–2014 were analyzed through a random effects model. Heterogeneity of the studies was evaluated by I2 index. The relationship between years of data collection, sample size, and CT infections with preterm delivery prevalence was examined by meta-regression. Data were analyzed with R and STATA [Ver. 12]. Results The overall prevalence of CT infections leading to preterm deliveries was estimated to be 0.13% (CI 95%: 0.11–0.16). The prevalence of CT infections leading to preterm deliveries were calculated based on the study method including PCR [0.06 (CI 95%: 0.04–0.09)], serology [0.23 (CI 95%: 0.10–0.35)] and culture [0.17 (CI 95%: 0.10–0.24)]. Analysis indicates that women with chlamydia infections were 2.28 more likely to deliver pre-term in comparison with those who were not infected. It can be concluded that chlamydia infections increase the risks of preterm delivery, OR = 2.28 (95% CI:1.64–3.16). Conclusions In regard to the results in numerous studies performed on different continents, this meta- analysis showed a clear association between preterm delivery and prior CT colonization

Changed mitochondrial enzymes activity in alzheimer’s diseas: a systematic review and meta-analysis

Thus far, a substantial body of research has demonstrated significant abnormalities in mitochondria within the brain of individuals diagnosed with Alzheimer's disease.(8) In line with the finding that compromised energy metabolism consistently occurs before the clinical manifestation of Alzheimer's disease (AD), it has been firmly shown that mitochondrial dysfunction is an early and conspicuous characteristic of the disease. This indicates that mitochondrial dysfunction likely plays a crucial role in the development of AD. In the present study, we investigated correlations of the activity of several enzymes such as Choline acetyltransferase (ChAT), an example of a transmitter-related enzyme and the distribution of KGDHC, a mitochondrial factor that is very deficient in AD, and also other aforementioned enzymes such GDH, PDHC, and Citrate synthase in the brain of our specimen from temporal lobe and parietal lobe in AD and control Subjects.(8) To our knowledge, this study is the first of its kind to conduct a meta-analysis on the changed enzymatic activity of mitochondria in relation to Alzheimer’s disease and to report the corresponding changes