Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California

Windham, Gayle C.; Lyall, Kristen; Anderson, Meredith; Kharrazi, Martin

doi:10.1007/s10803-015-2587-2

Cited by 30 publications

(24 citation statements)

References 56 publications

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“…This finding appears to contradict an earlier report by Windham et al [32] that showed that lower levels of oestriol in second trimester were modestly associated with a later diagnosis of autism in the offspring. However, our samples correspond to a slightly earlier time point in pregnancy compared to Windham et al (mean gestational week = 14.9 vs. 17.2 respectively) (see Table 1) [32], which could potentially better capture the steroid surge during the PMW [14]. Furthermore, our samples are of different origin, as Windham et al assayed maternal serum, rather than foetal amniotic fluid.…”

Section: Discussioncontrasting

confidence: 94%

“…With regard to clinical studies in humans, low oestriol in maternal serum during the second trimester of pregnancy significantly increases the likelihood of autism in the foetus, as demonstrated in a large study of n = 2586 autistic pregnancies [32]. This study may have been confounded by a variety of pregnancy complications, such as pre-eclampsia [33] and being small for gestational age [34], since these are also more frequent in autism [35][36][37].…”

Section: Introductionmentioning

confidence: 99%

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Foetal oestrogens and autism

et al. 2019

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Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.

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Section: Discussioncontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Foetal oestrogens and autism

et al. 2019

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“…Higher levels of several steroid hormones present in amniotic fluid during pregnancy, including cortisol, progesterone and testosterone, predict higher rates of autism diagnosis 92 . Low maternal levels of the oestrogen oestriol and both low and high levels of the placental hormone human chorionic gonadotropin during pregnancy have been associated with a higher risk of autism in male, but not female, offspring 93 . Thus, too much exposure to hormones involved in sexual differentiation may lead to ASD and possibly contribute to the male bias in autism risk.…”

Section: Gender Biased Human Neuropathologymentioning

confidence: 99%

Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain

2017

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The study of sex differences in the brain is a topic of neuroscientific study that has broad reaching implications for culture, society and biomedical science. Recent research in rodent models has led to dramatic shifts in our views of the mechanisms underlying the sexual differentiation of the brain. These include the surprising discoveries of a role for immune cells and inflammatory mediators in brain masculinization and a role for epigenetic suppression in brain feminization. How and to what degree these findings will translate to human brain development will be questions of central importance in future research in this field.

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“…Polycystic ovary syndrome (PCOS) is a disorder that induces increased testosterone levels in women, and women with PCOS are more likely to have a child with autism (Kosidou et al, ). Higher maternal levels of the hormone‐sequestering protein α‐fetoprotein as well as lower levels of the estrogen estriol have also been associated with increased autism risk in offspring (Windham et al, ). Overall these data suggest that changes in the steroid hormone environment of developing fetuses may alter brain development to produce autism.…”

Section: Implications: Sex Differences In Neurodevelopmental Disordersmentioning

confidence: 99%

The immune system as a novel regulator of sex differences in brain and behavioral development

Nelson

Lenz

2016

J of Neuroscience Research

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Sexual differentiation of the brain occurs early in life as a result of sex-typical hormone action and sex chromosome effects. Immunocompetent cells are being recognized as underappreciated regulators of sex differences in brain and behavioral development, including microglia, astrocytes, and possibly other less well studied cell types, including T cells and mast cells. Immunocompetent cells in the brain are responsive to steroid hormones, but their role in sex-specific brain development is an emerging field of interest. This Review presents a summary of what is currently known about sex differences in the number, morphology, and signaling profile of immune cells in the developing brain and their role in the early-life programming of sex differences in brain and behavior. We review what is currently known about sex differences in the response to early-life perturbations, including stress, inflammation, diet, and environmental pollutants. We also discuss how and why understanding sex differences in the developing neuroimmune environment may provide insight into understanding the etiology of several neurodevelopmental disorders. This Review also highlights what remains to be discovered in this emerging field of developmental neuroimmunology and underscores the importance of filling in these knowledge gaps. © 2016 Wiley Periodicals, Inc.

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Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California

Cited by 30 publications

References 56 publications

Foetal oestrogens and autism

Foetal oestrogens and autism

Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain

The immune system as a novel regulator of sex differences in brain and behavioral development

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