Controlling the maternal inflammation may be key to autism prevention
Several lines of evidences suggest that both genetic and environmental
factors contribute to autism development.
A subset of autism cases are linked to rare genetic variation such as
copy-number variation (CNV), which are structural alterations of the DNA
in the genome resulting in more (duplication) or fewer (deletion) number
copies on certain chromosomes.
A recent study, grouping multiple laboratories over the world (8 countries
including USA) under the
Autism Genome Project, analyzed 2,446 ASD-affected families. The results showed an increase
of specific genetic deletions and duplications in affected versus control
groups associated with ASD and intellectual disability.
Several animal studies have demonstrated that maternal inflammation during
pregnancy, in particular the secretion of IL-6, could alter fetal neurodevelopment
and lead to autism in the offspring. More interestingly, other studies
investigated the effects of maternal immune activation (MIA) on pups of
control mothers (typical strain with no predisposition to behavioral impairment)
and pups from an inbred strain predisposed to exhibit ASD-like behaviors.
Results showed greater impairments in pups with both genetic susceptibility
and exposure to MIA than in pups with either risk factor alone. This strongly
highlights the fact that genetic predisposition when combined with a strong
immune reaction (inflammation) during gestation result in a higher risk
to develop ASD and an increase in autism severity.
In human, a new study published in the latest issue of the
Journal of Developmental and Behavioral Pediatrics
, clearly demonstrates that
maternal immune activation
genetic predispositions such as CNV
to induce the
development of autism
. In that report, they analyzed 1971 children of the Simons Simplex Collection
Sample with a diagnosis of ASD and explore the relation of ASD-associated
copy number variants (CNVs) with environmental risks for the condition
such as prenatal maternal infection inducing
Maternal infections and febrile episodes during pregnancy were reported
by parent interview.
Results showed a strong correlation between the presence of ASD-related
CNV and maternal infection. But most mothers who experienced fever or
infections during pregnancy do not give birth to a future autistic child.
This suggests that individuals carrying these specific genetic variants
are more susceptible to the effects of maternal infection and are at higher
risk to develop severe autism behaviors.
These recent works clearly demonstrate and confirmed our postulate “
Maternal systemic inflammation resulting from an infection or an autoimmune
disease could disrupt fetal neurodevelopment, which is more severely affected
when combined to genetic predisposition and could lead to autism”.
Thus the prevention or reduction of maternal inflammation during pregnancy,
through an early immune profile screening and subsequent therapies, could
minimize the risks of having a future autistic child.