Metabolomic data presents challenges for epidemiological meta-analysis: a case study of childhood body mass index from the ECHO consortium.

INTRODUCTION: Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility. OBJECTIVE: The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework. METHODS: We used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure. RESULTS: Only 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P < 0.05) with offspring BMI z-scores at age 2 years in a meta-analytic framework including at least two studies: arabinose (Coefmeta = 0.40 [95% CI 0.10,0.70], Pmeta = 9.7 × 10-3), guanidinoacetate (Coefmeta = - 0.28 [- 0.54, - 0.02], Pmeta = 0.033), 3-ureidopropionate (Coefmeta = 0.22 [0.017,0.41], Pmeta = 0.033), 1-methylhistidine (Coefmeta = - 0.18 [- 0.33, - 0.04], Pmeta = 0.011), serine (Coefmeta = - 0.18 [- 0.36, - 0.01], Pmeta = 0.034), and lysine (Coefmeta = - 0.16 [- 0.32, - 0.01], Pmeta = 0.044). No associations were robust to multiple testing correction. CONCLUSIONS: Despite including three cohorts with large sample sizes (N > 100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.

Association of Maternal Prenatal Vitamin Use With Risk for Autism Spectrum Disorder Recurrence in Young Siblings.

Importance: Maternal use of folic acid supplements has been inconsistently associated with reduced risk for autism spectrum disorder (ASD) in the child. No study to date has examined this association in the context of ASD recurrence in high-risk families. Objective: To examine the association between maternal prenatal vitamin use and ASD recurrence risk in younger siblings of children with ASD. Design, Setting, and Participants: This prospective cohort study analyzed data from a sample of children (n = 332) and their mothers (n = 305) enrolled in the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) study. Participants in the MARBLES study were recruited at the MIND Institute of the University of California, Davis and were primarily from families receiving services for children with ASD in the California Department of Developmental Services. In this sample, the younger siblings at high risk for ASD were born between December 1, 2006, and June 30, 2015, and completed a final clinical assessment within 6 months of their third birthday. Prenatal vitamin use during pregnancy was reported by mothers during telephone interviews. Data analysis for this study was conducted from January 1, 2017, to December 3, 2018. Main Outcomes and Measures: Autism spectrum disorder, other nontypical development (non-TD), and typical development (TD) were algorithmically defined according to Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning subscale scores. Results: After exclusions, the final sample comprised 241 younger siblings, of which 140 (58.1%) were male and 101 (41.9%) were female, with a mean (SD) age of 36.5 (1.6) months. Most mothers (231 [95.9%]) reported taking prenatal vitamins during pregnancy, but only 87 mothers (36.1%) met the recommendations to take prenatal vitamins in the 6 months before pregnancy. The prevalence of ASD was 14.1% (18) in children whose mothers took prenatal vitamins in the first month of pregnancy compared with 32.7% (37) in children whose mothers did not take prenatal vitamins during that time. Children whose mothers reported taking prenatal vitamins during the first month of pregnancy were less likely to receive an ASD diagnosis (adjusted relative risk [RR], 0.50; 95% CI, 0.30-0.81) but not a non-TD 36-month outcome (adjusted RR, 1.14; 95% CI, 0.75-1.75) compared with children whose mothers reported not taking prenatal vitamins. Children in the former maternal prenatal vitamin group also had statistically significantly lower autism symptom severity (adjusted estimated difference, -0.60; 95% CI, -0.97 to -0.23) and higher cognitive scores (adjusted estimated difference, 7.1; 95% CI, 1.2-13.1). Conclusions and Relevance: Maternal prenatal vitamin intake during the first month of pregnancy may reduce ASD recurrence in siblings of children with ASD in high-risk families. Additional research is needed to confirm these results; to investigate dose thresholds, contributing nutrients, and biologic mechanisms of prenatal vitamins; and to inform public health recommendations for ASD prevention in affected families.

The Nurses Self-Concept Instrument (NSCI): assessment of psychometric properties for Australian domestic and international student nurses.

BACKGROUND: Professional self-concept is a critical driver of job satisfaction. In Australia, as international nursing enrolments rise, nursing is increasingly characterised by a professional body of international nurses who may differ from domestic Australian nurses in their nursing self-concept. At present, no psychometrically sound instrument for assessing nursing self-concept for Australian domestic and international nursing students is available. PURPOSE: The purpose of this study was to: (1) develop an instrument (the Nurses' Self-Concept Instrument (NSCI)) to measure the professional self-concept of domestic and international nursing students in Australia, and (2) test the psychometric properties of this newly developed instrument. METHOD: A literature review was conducted to generate the initial dimension and item pools to measure nurses' professional self-concept (NSCI). Two stakeholders examined the content and face validity of dimensions and items. Analysis was performed on data collected from 253 undergraduate nursing students in a large public university in Sydney, Australia, and consisted of domestic (n=218) and international (n=35) nursing students. Internal reliability was assessed using Cronbach's Alpha. Confirmatory factor analysis (CFA) was used to assess the construct validity of the NSCI. RESULTS: The resulting NSCI consisted of 14 items across four self-concept domains: care, leadership, staff relations, and knowledge. The CFA supported the hypothesised factor structure of the self-concept model. All reliabilities were acceptable for both domestic and international students (ranging from r=.78 to .93). CONCLUSIONS: The NSCI was shown to be a valid and reliable tool for assessing Australian domestic and international student nurses' professional self-concept. This instrument may also enable those responsible for recruitment of students into nursing courses to assess students' professional self-concept and implement appropriate strategies to foster the growth of lifelong career development.

The nurses' self-concept instrument (NSCI): a comparison of domestic and international student nurses' professional self-concepts from a large Australian University.

Professional self-concept is a critical driver of job satisfaction. In Australia, as international nursing enrolments rise, nursing is increasingly characterised by a professional body of international nurses who may differ from domestic Australian nurses in their nursing self-concept. At present, little is known about the extent to which domestic and international students nurses' self-concepts may differ. The present study aimed to elucidate and contrast domestic and international nursing students' self-concepts from one large Australian university. A total of 253 domestic (n=218) and international (n=35) undergraduate nursing students from a large public university in Sydney, Australia completed the Nurses' Self-Concept Instrument (NSCI). Multiple-Indicator-Multiple-Indicator-Cause (MIMIC) modelling was used to assess the effects of student group (domestic and international) on the latent self-concept factors of the NSCI. Domestic and international students' professional self-concepts were similarly high. MIMIC modelling demonstrated that domestic students had a higher patient care self-concept in comparison to international students. Results imply that it may be useful for Australian universities to foster strategies that enhance specific domains of self-concepts (e.g., care) which may be underdeveloped for at least some cultural groups within the international nursing student population compared with domestic nursing students.