The association between placental histopathology and autism spectrum disorder

Straughen, Jennifer K.; Misra, Dawn P.; Divine, George; Shah, Ruchit; Perez, G De La Mata; VanHorn, Samantha; Onbreyt, Victoria; Dygulska, Beata; Schmitt, Rebecca; Lederman, Sanford; Narula, Pramod; Salafia, Carolyn M.

doi:10.1016/j.placenta.2017.07.006

Cited by 60 publications

(50 citation statements)

References 45 publications

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“…Several lines of evidence suggest a contributory role for the placenta in the aetiology of autism. First, there is increased placental inflammation in autism [44]. Second, there is atypical placental morphology [45] and increased placental size [46] in cases of autism and at high familial risk respectively.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

Foetal oestrogens and autism

et al. 2019

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“…Therefore, maternal inflammation, a recognised risk factor for poor neurodevelopmental outcome, could act as a mediator between preeclampsia and development of ASD, and the proinflammatory cytokine interleukin (IL)-6 may be a leading candidate in this regard (Jiang et al, 2018). Straughen et al (2017) demonstrated that placental inflammation of any type is associated with an increased likelihood of ASD, while circulating levels of maternal IL-6 have been shown to be inversely associated with brain connectivity and offspring cognition at 12 months of age, as well as short and long-term influences in offspring behaviour in separate studies (Rasmussen et al, 2018;Spann, Monk, Scheinost, & Peterson, 2018). This may also partially explain the increased HR when results were Table 3 Association between preeclampsia and autism spectrum disorder with and without intellectual disability among singleton live births in Sweden by decade Children born 1982-1989Children born 1990Children born 2000-2010 ASD (n = 24,237) ASD (n = 18,896)…”

Section: Discussionmentioning

confidence: 99%

“…Thus, while uncomplicated pregnancies have a normal systemic inflammatory response (Redman, Sacks, & Sargent, 1999), preeclampsia results in a state of exaggerated maternal inflammation (Maher, McCarthy et al, 2018;Redman et al, 1999). Straughen et al (2017) demonstrated that placental inflammation of any type is associated with an increased likelihood of ASD, while circulating levels of maternal IL-6 have been shown to be inversely associated with brain connectivity and offspring cognition at 12 months of age, as well as short and long-term influences in offspring behaviour in separate studies (Rasmussen et al, 2018;Spann, Monk, Scheinost, & Peterson, 2018). Straughen et al (2017) demonstrated that placental inflammation of any type is associated with an increased likelihood of ASD, while circulating levels of maternal IL-6 have been shown to be inversely associated with brain connectivity and offspring cognition at 12 months of age, as well as short and long-term influences in offspring behaviour in separate studies (Rasmussen et al, 2018;Spann, Monk, Scheinost, & Peterson, 2018).…”

Section: 592 Multiple Births Excludedmentioning

confidence: 99%

Association between preeclampsia and autism spectrum disorder: a population‐based study

Maher

O’Keeffe

Dalman

et al. 2019

Child Psychology Psychiatry

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Background The environmental contribution of autism spectrum disorder (ASD) is approximately 17%–50%, highlighting the importance of investigating factors potentially contributing to the likelihood of its development, and of gaining a greater understanding of the pathogenesis surrounding ASD. The objective of this study was to examine the association between preeclampsia and ASD using a population‐based cohort study. Methods All singleton live births in Sweden from 1982 to 2010 were included, using data from Swedish National Registers. Exposures of interest included: (a) preeclampsia (classified according to ICD‐8, ICD‐9 and ICD‐10) and (b) preeclampsia and small for gestational age (SGA) combined, used as a proxy for preeclampsia with placental dysfunction. ASD status was based on ICD‐9 and ICD‐10. The cohort consisted of 2,842,230 children, with 54,071 cases of ASD. Follow‐up began from the child's first birthday, and data were censored at first diagnosis of ASD, death, migration or end of study period (31st December 2016). We conducted multivariate Cox proportional hazards regression analysis, adjusting for several perinatal and sociodemographic factors, selected a priori. We further controlled for shared genetic and familial confounding using sibling‐matched analysis. Results In the adjusted Cox proportional hazards regression analysis, preeclampsia was associated with a 25% increase in the likelihood of ASD (Hazard Ratio (HR): 1.25, 95% CI:1.19, 1.30) compared with those unexposed to preeclampsia, while in the sibling‐matched analysis the HR was 1.17 (95% CI: 1.06, 1.28). The HR for preeclampsia and SGA combined was 1.66 (95% CI: 1.49, 1.85) in the adjusted Cox model and 1.95 (95% CI: 1.53, 2.48) in the sibling‐matched analysis. Conclusions Exposure to preeclampsia or preeclampsia/SGA (i.e. SGA baby exposed to preeclampsia) was associated with ASD. The stronger association with preeclampsia/SGA than preeclampsia alone suggests that placental pathology may be a mechanism for the increased likelihood of ASD.

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“…Two previous studies regarding connections between maternal CRP at mid-pregnancy (weeks [15][16][17][18][19] and risk of ASD in children [127,128] showed opposite results.…”

Section: Discussionmentioning

confidence: 83%

“…Among them are variations in maternal metabolism at pregnancy [13,14]. Beside maternal metabolism, adverse health conditions during early pregnancy such as viral infections, inflammation, and immune activation are considered as risk factors for psychiatric disorders in the offspring [15][16][17][18][19]. Environmental factors may act via epigenetic mechanisms that are potentially modifiable and preventable [20]; therefore, the understanding of such risk factors may indicate a path to reduce incidence of ASD onset.…”

Section: Introductionmentioning

confidence: 99%

Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers

et al. 2020

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Background: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. Methods: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B 9 ) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. Results: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D 3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. Conclusions: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

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The association between placental histopathology and autism spectrum disorder

Cited by 60 publications

References 45 publications

Foetal oestrogens and autism

Foetal oestrogens and autism

Association between preeclampsia and autism spectrum disorder: a population‐based study

Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers

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