How maternal inflammation during pregnancy could affect fetal brain development and lead to Autism?

Posted By Dr. Braverman || 18-Dec-2014

What is autism?

Autism, as part of the Autism Spectrum Disorders (ASD), is a neurodevelopmental disorder characterized by:

  • deficits in social interactions
  • deficits in verbal and non-verbal communication
  • restrictive and repetitive stereotyped behaviors

This disorder manifests during early childhood, affecting up to 1 in 68 births in USA and is five times more likely to occur in males. Autism has multifactorial causes. Among them, genetic predispositions in the fetus clearly contribute to the development of the disease as seen by the concordance rate between monozygotic twins (40-90%) versus dizygotic twins (0-10%). Other factors such as the fetal environment in utero, a history of familial autoimmunity may play a role in the development of autism.

Inflammation in utero and increased risk of developing autism in the offspring.

Facts and statistics:
During pregnancy, a favorable uterine environment is crucial for harmonious fetal growth.

In the womb, the fetus interacting with its environment can undergo permanent and dramatic impairments at very sensitive and crucial periods. In particular, the cognitive functions could be affected by prenatal factors such as inflammation, causing structuring abnormalities as seen by patch of brain cells that did not develop properly, thus leading to long-lasting brain dysfunction especially during the second and third trimester of gestation.

Imbalance in maternal immune homeostasis during pregnancy (in response to disease or other environmental influences) could impact fetal development and particularly brain maturation during crucial period of development.

Maternal autoimmune diseases have also been shown to increase the risks of autism in children with 40% of autistic children having at least one relative affected by an autoimmune disease. Maternal celiac disease or rheumatoid arthritis significantly increase autism risk in the offspring (by 350% and 80% respectively).

Maternal immune dysregulation during pregnancy: the "cytokine theory" of autism.

A healthy pregnancy switches the maternal immune system toward a more tolerant, low inflammatory state. Cytokines and chemokines are proteins that control the type of immune response, they are involved in pregnancy maintenance and have a strong role in neurodevelopment.

Dysregulations of inflammatory cytokine and chemokine levels such as IL4, IL-5, IL-6, IL-8 IFN-γ, TNFα and MCP-1 have been reported in the maternal serum or amniotic fluid during early- or mid-gestation of autistic children.

The high prevalence of autoimmune diseases in mothers of autistic children suggests that these disorders may also affect the developing fetus in utero.

Mothers of autistic children have a higher frequency of plasmatic anti-brain autoantibodies, this is associated with maternal autoimmune diseases in particular rheumatoid arthritis and systemic lupus erythematosus. Moreover, we strongly believe that patients showing reactivity to fetal antigens by failing to generate proper tolerance to paternal antigen may produce these anti-brain antibodies. Indeed, the high prevalence of autism in males could be explained by an altered maternal immune response against male-specific minor histocompatibility (HY) antigens. These antigens are found in women following a first pregnancy with a boy and are responsible of secondary recurrent miscarriage and other pregnancy complications. Braverman IVF & Reproductive Immunology runs testing of HY restricting allele to determine maternal population at risks.

Because human autoantibodies have been shown to be neurotoxic to the developing brain and induce autistic-like behavior in mice, we suspect that HY restricting allele and antigens could be involved in brain formation impairment of autistic children.

Inflammatory conditions during pregnancy are a serious matter that require a screening, particularly for autoimmune patient, a close monitoring and an adequate treatment to avoid the deleterious impact that they can have on fetal brain formation.

To date, there is no scientific evidences clearly showing that autism could be prevented by the regulation of inflammation during pregnancy. Nevertheless, based on our knowledge, we strongly believe that it should play a part in lowering the risk of autism.

Brain inflammation impacts its development.

During pregnancy, the placenta allows maternal antibodies, such as immunoglobulin G (IgG), to reach the fetus and provide passive immunity throughout the pregnancy. In addition to the passage of protective antibodies, maternal antibodies reactive to fetal antigens could also reach and harm the fetus. Because the central nervous system is in formation during fetal life, maternal antibodies can have direct access to the brain during gestation.

Maternal autoantibodies targeting fetal brain as well as inflammatory cytokines have been detected in autistic children brain highlighting the transfer of these factors from the maternal to the fetal blood stream to finally reach fetal brain. These factors induce irreversible perinatal brain alterations that can be morphologically assessed by scan or MRI especially in the cerebellum and cortical region.

At Braverman IVF & Reproductive Immunology, we recently launched a website to display information on autism.

If you had a prior history of miscarriages and have a child diagnosed with ASD, you will be able to read the latest research facts on fetal predispositions, maternal and environmental influences that trigger autism and find answers to your questions.

Categories: News
Share Post