Prenatal, perinatal, and postnatal factors associated with autism: A meta-analysis.
TL;DR: A meta-analysis confirmed the relation between some prenatal, perinatal, and postnatal factors with autism, but it was still unclear that whether these factors are causal or play a secondary role in the development of autism.
About: This article is published in Medicine.The article was published on 2017-05-01 and is currently open access. It has received 214 citations till now. The article focuses on the topics: Autism.
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TL;DR: It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification to enhance the understanding of role of environmental factors in the etiology of ASD.
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition of heterogeneous etiology. While it is widely recognized that genetic and environmental factors and their interactions contribute to autism phenotypes, their precise causal mechanisms remain poorly understood. This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabetes, enhanced steroidogenic activity, immune activation, and possibly altered zinc–copper cycles and treatment with selective serotonin reuptake inhibitors. Epidemiological studies demonstrate no evidence for vaccination posing an autism risk. It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification. Our understanding of autism etiology could be advanced by research aimed at disentangling the causal and non-causal environmental effects, both founding and moderating, and gene–environment interplay using twin studies, longitudinal and experimental designs. The specificity of many environmental risks for ASD remains unknown and control of multiple confounders has been limited. Further understanding of the critical windows of neurodevelopmental vulnerability and investigating the fit of multiple hit and cumulative risk models are likely promising approaches in enhancing the understanding of role of environmental factors in the etiology of ASD.
259 citations
TL;DR: Evidence that ASD is a neurobiological disorder influenced by both genetic and environmental factors affecting the developing brain is reviewed, and factors that correlate with ASD risk are enumerated.
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. There have been recent concerns about increased prevalence, and this article seeks to elaborate on factors that may influence prevalence rates, including recent changes to the diagnostic criteria. The authors review evidence that ASD is a neurobiological disorder influenced by both genetic and environmental factors affecting the developing brain, and enumerate factors that correlate with ASD risk. Finally, the article describes how clinical evaluation begins with developmental screening, followed by referral for a definitive diagnosis, and provides guidance on screening for comorbid conditions.
243 citations
TL;DR: The prevalence of ASD is significantly high in the preterm population and adequate resources are needed to improve the outcomes of these children.
Abstract: CONTEXT: Evidence is emerging that preterm infants are at risk for autism spectrum disorder (ASD). OBJECTIVES: To conduct a systematic review and meta-analysis to estimate the prevalence of ASD in preterm infants. DATA SOURCES: Medline (via PubMed and Ovid), Embase, PsycINFO, and relevant conference proceedings were searched in May 2017. STUDY SELECTION: Original studies in which researchers report on the prevalence of ASD using diagnostic tests in children born preterm were included. Studies in which researchers used only ASD screening tools were excluded. DATA EXTRACTION: Relevant data were extracted independently by 3 authors. RESULTS: Researchers in a total of 18 studies (3366 preterm infants) used ASD diagnostic tools. The median gestation, birth weight, and age at assessment were 28.0 weeks (range: 25.1–31.3 weeks), 1055 g (range: 719–1565 g), and 5.7 years (range: 1.5–21 years), respectively. Meta-analysis revealed that the overall prevalence rate for ASD was 7% (95% confidence interval: 4% to 9%). The funnel plot and Egger’s test revealed that there was probably no evidence of publication bias. LIMITATIONS: The limitations were significant heterogeneity and a lack of studies from middle- and low-income countries. CONCLUSIONS: The prevalence of ASD is significantly high in the preterm population. Adequate resources are needed to improve the outcomes of these children.
196 citations
Cites methods from "Prenatal, perinatal, and postnatal ..."
...Risk of bias was assessed by using the quality assessment tool for prevalence studies from the Joanna Briggs Institute19 by using the following criteria: (1) Was the sample frame appropriate to address the target population? (2) Was the study population sampled in an appropriate way? (3) Was the sample size adequate? (4) Were the study subjects and settings described in detail? (5) Was the data analysis conducted with sufficient coverage of the identified sample? (6) Were valid methods used for identification of the condition? (7) Was the condition measured in a standard, reliable way for all the participants? (8) Was there appropriate statistical analysis? (9) Was the response rate adequate, and if not, was the low response rate managed appropriately? The criteria were rated as either yes, no, not clear, or not applicable....
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Yonsei University1, Washington University in St. Louis2, Luton and Dunstable University Hospital NHS Foundation Trust3, French Institute of Health and Medical Research4, Centre for Addiction and Mental Health5, University of Barcelona6, Carlos III Health Institute7, University of Toronto8, South London and Maudsley NHS Foundation Trust9, King's College London10, University of Padua11, University of Toledo Medical Center12, Boston Children's Hospital13
TL;DR: Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome, are associated with risk of autism spectrum disorder.
150 citations
TL;DR: A systematic review on human studies examining associations between maternal inflammatory states and offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS) was performed in this article.
Abstract: Inflammation is increasingly recognized as a cause or consequence of common problems of humanity including obesity, stress, depression, pollution and disease states such as autoimmunity, asthma, and infection. Maternal immune activation (MIA), triggered by both acute and systemic chronic inflammation, is hypothesized to be one of the mechanisms implicated in the pathogenesis of neurodevelopmental disorders (NDD). Although there is substantial preclinical evidence to support the MIA hypothesis, the human evidence is disparate. We performed a systematic review on human studies examining associations between maternal inflammatory states and offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS). 32 meta-analyses and 26 additional individual studies were identified. Maternal states associated with ASD include obesity, gestational diabetes mellitus, pre-eclampsia, pollution, stress, depression, autoimmune diseases, and infection. Maternal states associated with ADHD include obesity, pre-eclampsia, smoking, low socioeconomic status (SES), stress, autoimmune disease, and asthma. Maternal states associated with TS include low SES, depression, and autoimmune diseases. Diverse maternal inflammatory states in pregnancy are associated with common offspring NDDs. Given the increased prevalence of NDDs, there is urgent need to explore relative and cumulative maternal risk factors and disease mechanisms. Defining preventable risk factors in high-risk pregnancies could mitigate the expression and severity of NDDs.
110 citations
References
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TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
62,157 citations
TL;DR: A new quantity is developed, I 2, which the authors believe gives a better measure of the consistency between trials in a meta-analysis, which is susceptible to the number of trials included in the meta- analysis.
Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
45,105 citations
"Prenatal, perinatal, and postnatal ..." refers methods in this paper
...1 or I(2) >50% was considered to have significant heterogeneity.([21]) The DerSimonian–Laird method with random-effects model([22]) was used to calculate the pooled RRs with 95% CIs when the heterogeneity was identified; otherwise, a fixed-effects model (Mantel–Haenszel method) was used to pool the estimates....
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TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
"Prenatal, perinatal, and postnatal ..." refers methods in this paper
...The results showed that no significant publication bias was observed between all the risk factors and autism with the Begg test; whereas using Egger test, significant publication bias was identified for gestational age 36 weeks, gestational diabetes, and gestational hypertension....
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...Publications bias was evaluated by the Begg[24] and Egger[25] test....
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...Publications bias was evaluated by the Begg([24]) and Egger([25]) test....
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TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
33,234 citations
"Prenatal, perinatal, and postnatal ..." refers methods in this paper
...The DerSimonian–Laird method with random-effects model([22]) was used to calculate the pooled RRs with 95% CIs when the heterogeneity was identified; otherwise, a fixed-effects model (Mantel–Haenszel method) was used to pool the estimates....
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TL;DR: A structured summary is provided including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings.
31,379 citations
"Prenatal, perinatal, and postnatal ..." refers methods in this paper
...This study was conducted and reported in adherence to Preferred Reporting Items for Systematic Reviews and Meta-analysis.([19])...
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...This study was conducted and reported in adherence to Preferred Reporting Items for Systematic Reviews and Meta-analysis....
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