Autism has undoubtedly a genetic component but recent accumulation of evidences
shows a clear association between autism and pregnancy complications,
revealing that the
prenatal period is a time of
very high susceptibility to noxious factors
; when compromised this leads to irreversible consequences on fetal health.
Pregnancy success relies on a tight regulation between the
placenta and the
maternal immune system. Pre-eclampsia (PE) is a complex disease that occurs in 3–5% of
all pregnancies and contributes significantly to maternal and neonatal
mortality and morbidity. Although the initial events that lead to pre-eclampsia
occur during the first 12 weeks of pregnancy, i.e. inadequate trophoblast
invasion and poor spiral artery remodeling that affect the delivery of
blood to the placenta, the symptoms don’t manifest until at least
18 weeks of gestation and often not until the third trimester, many times
leading to preterm delivery.
The cause of poor placental implantation is usually due to failed maternal
tolerance for the paternal genetics and the risk factors for this are
many. They are autoimmune disease in the mother, immunologic incompatibility
between the parents, underlying inflammatory disease in the mother such
as PCOS or endometriosis to name a few and these are the most common presentations
to our center. The placental hypoxia caused by the poor implantation creates
placental and vascular injuries (main cause of both pre-eclampsia and
intra uterine growth restriction: IUGR) and induces the secretion of a
number of circulating factors such as TNF-α, IL-6, IL-1 creating a
systemic inflammatory environment.
Most importantly, it is crucial to note that these immune alterations are
treatment may prevent the pregnancy complications that are a result of
these inflammatory changes.
These early environmental damages may predispose subjects to autistic
disorders by affecting fetal brain development apparently during the second
trimester of the pregnancy. There is no evidence at this time that treatment
for miscarriages will also prevent autism but as they seem to have
the same root cause in cases of inflammation this is an area that must be investigated carefully.
The Childhood Autism Risks from Genetics and the Environment (CHARGE),
a recent study recruited young children in California (24-60 months of
age) who are autistic (n=517), who are developmental delayed (n=194) or
healthy controls (n=350). The CHARGE study reported that autistic children
were twice as likely to have been exposed to pre-eclampsia, while developmental
delay was correlated to IUGR.
These results were confirmed with another study that linked the prevalence
of autism in adolescent born preterm with a weight of less than 2kg.
In a Swedish study involving n=1216 autistic and n=6080 healthy controls
children, pre-eclampsia was also associated with a 50% increased risk
of having an autistic child. A strong correlation between a low Apgar
score (common in preterm birth occurring frequently in pre-eclamptic women)
and severe cases of autism has also been reported.
Altogether, these recent studies strongly suggest that
an impaired embryo implantation
and the subsequent obstetrical complications lead to a systemic inflammation and can cause dramatic effects on
fetal neurodevelopment indicating that
root causes of autism are likely to take place