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Exposure to Hypertensive Disorders of Pregnancy Increases the Risk of Autism Spectrum Disorder in Affected Offspring

Abstract

There is growing awareness that prenatal adversity may increase the risk of autism spectrum disorder (ASD). Here, we examined the association between hypertensive disorders of pregnancy (HDP) and ASD risk at 7 years of age using the Millennium Cohort Study (MCS), a representative cohort of 13,192 children born in the UK from 2000 to 2001. We also sought to examine cytokine expression in the serum of women with pre-eclampsia, which is the most common HDP, and whether exposure of foetal neurons to this serum could change patterns of neuronal growth. HDP were reported by mothers 9 months post-delivery. ASD was parent reported at age seven, based on a doctor or health care professional’s diagnosis. Weighted logistic regression was used for data analysis, adjusting for several potential confounders including maternal alcohol consumption, education, depression, age, and poverty status. Sensitivity analyses were performed excluding pre-term births, small for gestational age (SGA), and pre-pregnancy hypertension and depression. There was a significant association between HDP and a twofold increased risk of ASD (AOR = 2.10 [95% CI 1.20–3.70]). Excluding preterm births, SGA births, and offspring of women who had pre-pregnancy hypertension or over the age of 40 did not change the results materially. At the cellular level, exposure of foetal cortical neurons to 3% serum isolated from women with an established HDP increased neuronal growth and branching in vitro. These findings indicate that HDP exposure may increase the risk of ASD in the offspring.

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Funding

This study was funded by a research centre’s grant (Grant#: INFANT-12/RC/2272) (L.K.) from Science Foundation Ireland. This study has also emanated from research supported in part by a research grant from SFI under the grant number 15/CDA/3498 (G.OK).

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Correspondence to Ali S. Khashan or Louise C. Kenny.

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The authors declare that they have no conflict of interest.

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Eileen A. Curran and Gerard W. O’Keeffe have joint contribution

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Curran, E.A., O’Keeffe, G.W., Looney, A.M. et al. Exposure to Hypertensive Disorders of Pregnancy Increases the Risk of Autism Spectrum Disorder in Affected Offspring. Mol Neurobiol 55, 5557–5564 (2018). https://doi.org/10.1007/s12035-017-0794-x

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Keywords

  • Autism spectrum disorder
  • ASD
  • Autism
  • Pre-eclampsia
  • Pregnancy
  • Hypertensive disorders