Periconception endogenous and exogenous maternal sex steroid hormones and risk of asthma and allergy in offspring : protocol for a systematic review and meta-analysis

Introduction Pregnancy is associated with several hormonal changes which influence the developing fetus. Variations in maternal endogenous hormones and prepregnancy use of hormonal preparations have been linked to asthma and allergy in the offspring, but findings are inconsistent. We plan to undertake a systematic review to synthesise the evidence on the association between endogenous and exogenous maternal sex hormones and the risk of asthma and allergy in the offspring. Methods and analysis We will search Medline, Embase, Cochrane Library, Institute of Scientific Information Web of Science, Cumulative Index of Nursing and Allied Health, Scopus, Google Scholar, Allied and Complementary Medicine Database, Global Health, Psychological Information (PsycINFO), Centre for Agriculture and Bioscience (CAB) International and WHO Global Health Library from inception until 2016 to identify relevant studies on the topic. Additional studies will be identified by searching databases of proceedings of international conferences, contacting international experts in the field and searching the references cited in identified studies. We will include analytical epidemiological studies. Two researchers will independently screen identified studies, undertake data extraction and assess risk of bias in eligible studies, while a third reviewer will arbitrate any disagreement. We will use the Effective Public Health Practice Project tool to assess the risk of bias in the studies. We will perform a random-effects meta-analysis to synthesise the evidence. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate the strength and quality of the overall evidence with respect to each outcome. Ethics and dissemination Ethical approval is not required since the study is a systematic review of published literature. Our findings will be reported in a peer-reviewed scientific journal.Peer reviewe

A Prospective Evaluation of Infant Cerebellar-Cerebral Functional Connectivity in Relation to Behavioral Development in Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection. Methods: Data from the Infant Brain Imaging Study (n = 94, 68 male) were used to examine 6-month cerebellar functional connectivity magnetic resonance imaging in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning–based predictive tests examined cerebellar–frontoparietal network (FPN; subserves error signaling in support of EBL) and cerebellar–default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging enrichment examined brain-wide behavioral associations, with post hoc tests of cerebellar connections. Results: Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. Functional connectivity magnetic resonance imaging enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post hoc tests did not suggest a role for cerebellar connections. Conclusions: We failed to identify cerebellar functional connectivity–based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities

Common or distinct pathways to psychosis? A systematic review of evidence from prospective studies for developmental risk factors and antecedents of the schizophrenia spectrum disorders and affective psychoses

Background: Identifying the unique and shared premorbid indicators of risk for the schizophrenia spectrum disorders (SSD) and affective psychoses (AP) may refine aetiological hypotheses and inform the delivery of universal versus targeted preventive interventions. This systematic review synthesises the available evidence concerning developmental risk factors and antecedents of SSD and AP to identify those with the most robust support, and to highlight remaining evidence gaps.Methods: A systematic search of prospective birth, population, high-risk, and case-control cohorts was conducted in Medline and supplemented by hand searching, incorporating published studies in English with full text available. Inclusion/exclusion decisions and data extraction were completed in duplicate. Exposures included three categories of risk factors and four categories of antecedents, with case and comparison groups defined by adult psychiatric diagnosis. Effect sizes and prevalence rates were extracted, where available, and the strength of evidencesynthesised and evaluated qualitatively across the study designs.Results: Of 1775 studies identified by the search, 127 provided data to the review. Individuals who develop SSD experience a diversity of subtle premorbid developmental deficits and risk exposures, spanning the prenatal period through early adolescence. Those of greatest magnitude (or observed most consistently) included obstetric complications, maternal illness during pregnancy (especially infections), other maternal physical factors, negative family emotional environment, psychopathology and psychotic symptoms, and cognitive and motor dysfunctions. Relatively less evidence has accumulated to implicate this diversity of exposures in AP, and many yet remain unexamined, with the most consistent or strongest evidence to date being for obstetric complications, psychopathology, cognitive indicators and motor dysfunction. Among the few investigations affording direct comparison between SSD and AP, larger effect sizes and a greater number of significant associations are commonly reported for SSD relative to AP.Conclusions: Shared risk factors for SSD and AP may include obstetric complications, childhood psychopathology, cognitive markers and motor dysfunction, but the capacity to distinguish common versus distinct risk factors/antecedents for SSD and AP is limited by the scant availability of prospective data for AP, and inconsistency in replication. Further studies considering both diagnoses concurrently are needed. Nonetheless, the prevalence of the risk factors/antecedents observed in cases and controls helps demarcate potential targets for preventative interventions for these disorders