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Med Hypotheses. 2014 Jun;82(6):713-8. doi: 10.1016/j.mehy.2014.03.011. Epub 2014 Mar 13.

Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders?

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Department of Biomedicine and Prevention, University of Rome ''Tor Vergata", Rome, Italy; Centre for Communication and Neurorehabilitation Research - CNAPP, Rome, Italy. Electronic address:
Department of Neuroscience, Pediatric Neurology Unit, Tor Vergata University of Rome, Italy.
Centre for Communication and Neurorehabilitation Research - CNAPP, Rome, Italy.


The etiology of Autism Spectrum Disorders (ASDs) continues to be elusive. While ASDs have been shown to be heritable, several environmental co-factors, such as, e.g. pre- or perinatal adverse events, could play a role in the pathogenesis of the disorder as well. Prevalence of ASDs appears to have increased in the last three decades, but the causes of this surge are not fully understood. As perinatal adverse events have increased as well, they have been regarded as logical contributors to the risen prevalence of ASDs. Over the last three decades there has been also a considerable increase in the rates of induced labor and caesarean sections (CS). However, even if a causal association between CS and ASDs increase has been suggested, it has not yet been proven. Nevertheless, we hypothesize here that such an association is actual and that it might help to explain a part of the increase in ASD diagnoses. Our assumption is based on the wider epidemiological picture of ASDs and CS, as well as on the possible biological plausibility of this correlation, by postulating potential epigenetic and neurobiological mechanisms underpinning this relationship. Today, several observations point toward the existence of epigenetic dysregulation in ASDs and this raises the issue of the role of environmental factors in bringing about epigenetic modifications. Epigenetic dysregulations in some brain neuropeptide systems could play a role in the behavioral dysfunctions of ASDs. Particularly, some evidence suggests a dysregulation of the oxytocinergic system in autistic brains. Perinatal alterations of oxytocin (OT) can also have life-long lasting effects on the development of social behaviors. Within the perinatal period, various processes, like pitocin infusion or CS, can alter the OT balance in the newborn; OT dysregulation could then interact with genetic factors, leading ultimately to the development of ASDs. Large long-term prospective studies are needed to identify causal pathways for ASDs and examine whether and how (epi-)genetic susceptibility interacts with obstetric risk factors in the development of ASDs. A better understanding of such a potential interplay could become paradigmatic for a wide range of genetic-environmental interactions in ASDs.

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