Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort / Dina TERLOYEVA in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) Titre : Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort Type de document : Texte imprimé et/ou numérique Auteurs : Dina TERLOYEVA, Auteur ; Alexander J. FREY, Auteur ; Bo Y. PARK, Auteur ; Elizabeth M. KAUFFMAN, Auteur ; Leny MATHEW, Auteur ; Anna BOSTWICK, Auteur ; Erika L. VARNER, Auteur ; Brian K. LEE, Auteur ; Lisa A. CROEN, Auteur ; Margaret D. FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Nathaniel W. SNYDER, Auteur Langues : Anglais (eng) Mots-clés : Androgen  Autism-related traits  Meconium  Prenatal exposure  Sex difference  Sibling Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results. METHODS: To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS. RESULTS: Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P???0.01) were positively associated with AOSI scores, while u-T (P?=?0.004) and u-DHEA (P?=?0.007) were positively associated with SRS total score among females with female probands (n?=?10). Additionally, higher concentrations of u-T (P?=?0.01) and t-T (P?=?0.01) predicted higher SRS total score in males with male probands (n?=?63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium. CONCLUSIONS: This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies. En ligne : http://dx.doi.org/10.1186/s13229-020-00395-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 [article] Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort [Texte imprimé et/ou numérique] / Dina TERLOYEVA, Auteur ; Alexander J. FREY, Auteur ; Bo Y. PARK, Auteur ; Elizabeth M. KAUFFMAN, Auteur ; Leny MATHEW, Auteur ; Anna BOSTWICK, Auteur ; Erika L. VARNER, Auteur ; Brian K. LEE, Auteur ; Lisa A. CROEN, Auteur ; Margaret D. FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Nathaniel W. SNYDER, Auteur. Langues : Anglais (eng) in Molecular Autism > 11 (2020) Mots-clés : Androgen  Autism-related traits  Meconium  Prenatal exposure  Sex difference  Sibling Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results. METHODS: To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS. RESULTS: Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P???0.01) were positively associated with AOSI scores, while u-T (P?=?0.004) and u-DHEA (P?=?0.007) were positively associated with SRS total score among females with female probands (n?=?10). Additionally, higher concentrations of u-T (P?=?0.01) and t-T (P?=?0.01) predicted higher SRS total score in males with male probands (n?=?63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium. CONCLUSIONS: This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies. En ligne : http://dx.doi.org/10.1186/s13229-020-00395-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438

Polyunsaturated Fatty Acids in Newborn Bloodspots: Associations With Autism Spectrum Disorder and Correlation With Maternal Serum Levels / Anna BOSTWICK in Autism Research, 13-9 (September 2020)  

Public ISBD [article]  inAutism Research > 13-9 (September 2020) . - p.1601-1613 Titre : Polyunsaturated Fatty Acids in Newborn Bloodspots: Associations With Autism Spectrum Disorder and Correlation With Maternal Serum Levels Type de document : Texte imprimé et/ou numérique Auteurs : Anna BOSTWICK, Auteur ; Nathaniel W. SNYDER, Auteur ; Gayle C. WINDHAM, Auteur ; Casey WHITMAN, Auteur ; Michelle PEARL, Auteur ; Lucy ROBINSON, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur Article en page(s) : p.1601-1613 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : We conducted a population-based case–control study to examine newborn polyunsaturated fatty acid (PUFA) levels in association with autism spectrum disorder (ASD) and assess PUFA correlation across two time points. ASD cases (n = 200) were identified through the Department of Developmental Services and matched to live-birth population controls (n = 200) on birth month, year (2010–2011), and sex. Nonesterified PUFAs were measured by isotope dilution liquid chromatography-high resolution mass spectrometry from archived newborn dried blood spots and maternal mid-pregnancy serum samples. Crude and adjusted conditional logistic regression models were used to examine the association between neonatal PUFA levels, categorized in quartiles and according to distributional extremes, and ASD. Cubic splines were utilized to examine nonlinear relationships between continuous neonatal PUFAs and ASD. The correlation between neonatal and maternal levels was examined using Pearson correlation coefficients. In adjusted analyses of neonatal PUFA levels, no clear trends emerged, though there was an elevated odds ratio of ASD for the third quartile of linoleic acid, relative to the first (adjusted odds ratio = 2.49, 95% confidence interval: 1.31, 4.70). Cubic spline analysis suggested a nonlinear association between linoleic acid and ASD, though this was not robust to sensitivity analyses. While individual PUFAs were significantly correlated with one another within a given time point, aside from docohexaseanoic acid, PUFAs were not correlated across maternal and neonatal samples. Overall, our findings do not support an association between neonatal PUFA levels and ASD. Future work should confirm and expand these findings by examining associations with phenotypic subgroups and considering PUFAs in other time points. Lay Summary In this study, we examined whether levels of fats known as polyunsaturated fatty acids, measured in newborns, were related to later child diagnosis of autism spectrum disorder (ASD). Overall, we did not find strong evidence for hypothesized reduction in risk of ASD based on newborn levels of these fats. Future studies in larger samples and considering other time points may be useful to explain whether these fats are important in brain development related to ASD. Autism Res 2020, 13: 1601–1613. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2365 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431 [article] Polyunsaturated Fatty Acids in Newborn Bloodspots: Associations With Autism Spectrum Disorder and Correlation With Maternal Serum Levels [Texte imprimé et/ou numérique] / Anna BOSTWICK, Auteur ; Nathaniel W. SNYDER, Auteur ; Gayle C. WINDHAM, Auteur ; Casey WHITMAN, Auteur ; Michelle PEARL, Auteur ; Lucy ROBINSON, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur . - p.1601-1613. Langues : Anglais (eng) in Autism Research > 13-9 (September 2020) . - p.1601-1613 Index. décimale : PER Périodiques Résumé : We conducted a population-based case–control study to examine newborn polyunsaturated fatty acid (PUFA) levels in association with autism spectrum disorder (ASD) and assess PUFA correlation across two time points. ASD cases (n = 200) were identified through the Department of Developmental Services and matched to live-birth population controls (n = 200) on birth month, year (2010–2011), and sex. Nonesterified PUFAs were measured by isotope dilution liquid chromatography-high resolution mass spectrometry from archived newborn dried blood spots and maternal mid-pregnancy serum samples. Crude and adjusted conditional logistic regression models were used to examine the association between neonatal PUFA levels, categorized in quartiles and according to distributional extremes, and ASD. Cubic splines were utilized to examine nonlinear relationships between continuous neonatal PUFAs and ASD. The correlation between neonatal and maternal levels was examined using Pearson correlation coefficients. In adjusted analyses of neonatal PUFA levels, no clear trends emerged, though there was an elevated odds ratio of ASD for the third quartile of linoleic acid, relative to the first (adjusted odds ratio = 2.49, 95% confidence interval: 1.31, 4.70). Cubic spline analysis suggested a nonlinear association between linoleic acid and ASD, though this was not robust to sensitivity analyses. While individual PUFAs were significantly correlated with one another within a given time point, aside from docohexaseanoic acid, PUFAs were not correlated across maternal and neonatal samples. Overall, our findings do not support an association between neonatal PUFA levels and ASD. Future work should confirm and expand these findings by examining associations with phenotypic subgroups and considering PUFAs in other time points. Lay Summary In this study, we examined whether levels of fats known as polyunsaturated fatty acids, measured in newborns, were related to later child diagnosis of autism spectrum disorder (ASD). Overall, we did not find strong evidence for hypothesized reduction in risk of ASD based on newborn levels of these fats. Future studies in larger samples and considering other time points may be useful to explain whether these fats are important in brain development related to ASD. Autism Res 2020, 13: 1601–1613. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2365 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431

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