Polycystic Ovary Syndrome (PCOS) and Autism Solutions exist to lessen your symptoms and minimize your risks of having an autistic child

A new research published in the latest issue of the Journal Molecular Psychiatry (December 2015) puts into light the key role of uterine environment and prenatal exposure to deleterious factors in Autism development.
Indeed, the study shows that Polycystic ovary syndrome (PCOS) could increase your risk of having a child affected by autism by 59%. Although this might sound scary, your risks are still pretty low going from 1.5% in the general population to 2% in patients with PCOS.

  1. What is PCOS?

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting about 6-10% of women of childbearing age depending on ethnicity, with approximately 5 millions of women being concerned in the United States (1).

It is characterized by both gynecological and endocrine symptoms such as:

  • chronic anovulation: missed or absence of period.
  • Hyperandrogenism: higher levels of androgens (male hormones) leading to excess of facial hair growth and acne.
  • Several cysts on the ovaries

In addition, obesity, insulin resistance, and hyperinsulinemia commonly occur in PCOS patients, increasing their susceptibility for metabolic disorders such as type 2 diabetes or hypertension (2).

Being the most common endocrine cause of infertility, a large proportion of women affected by PCOS ignore their condition and are not yet diagnosed, due to subtle or not classical signs, until trying and failing to conceive.
When pregnant, PCOS patients are more prone to obstetrical complications leading to pregnancy losses in 50% of cases (3).

  1. PCOS and Autism in the offspring: facts

A population-based study in Sweden, including almost 24 000 children with ASD and over 208 000 healthy control-matched children shows that PCOS increased significantly the risks of having an autistic child (4). Maternal PCOS was found at a higher rate in mothers of autistic children and increases the risks of having a child with autism by 59%. When combined with obesity, an even higher proportion of mothers with PCOS was found among mothers of autistic children, showing that maternal obesity when combined to PCOS doubles the risks for Autism in the child.
Nevertheless, it is important to underline that the rate of autism remains low even in obese PCOS patients (<3%).

  1. How can PCOS contribute to Autism development in my child?

    a- Maternal inflammation and immune alterations are the prime factors

Immune environment during pregnancy directly impacts fetal development.
When altered, this could have detrimental consequences on fetal health as seen in women suffering from pregnancy complications as miscarriages, pre-eclampsia, preterm delivery or even still birth, events occurring frequently in PCOS pregnant patients (5).

  • HY-restricting alleles

It is very well established that mothers of autistic children have a higher frequency of plasmatic anti-brain autoantibodies (6). 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 and could play a key role in male specific autism development.

  • Dysregulations of inflammatory factors

Dysregulation of cytokine and chemokine levels such as IL4, IL-5, IL-6, IL-8, IFN-γ, TNFα and MCP-1 have been reported in both PCOS patients (7) and in the maternal serum or amniotic fluid during early- or mid-gestation of autistic children (8-9).

Having a key role during the brain development, these factors could be responsible for the increased prevalence of autism in children of PCOS women.

Further, the high estradiol/progesterone ratio due to an anovulatory cycle (no or low progesterone levels with steady levels of estradiol) would likely stimulates the immune system (10).
PCOS is an inflammatory disease as shown by increased levels of white blood cells count (WBC), C reactive protein (CRP) or IL-6 (11) as well as increased oxidative stress (12) and endothelial dysfunctions (13-14).

A recent prospective study comparing immune profiles in pregnant PCOS patients to match-controlled pregnant women showed that the low-grade inflammation, existing before the pregnancy, persists and is exacerbates by pregnancy in PCOS patients. This was associated with obstetrical and neonatal adverse outcomes (15).

The production of inflammatory factors by the maternal immune system could pass through the placenta and attack the fetal brain during a critical time of development thus impairing brain formation and leading toautism.

  • Treg cells

Recent studies showed that PCOS women had lower levels of Treg cells (16), which are key actors of immune tolerance and essential to pregnancy establishment and maintenance. This could be due to a vitamin D deficiency, often found in PCOS and leading to decreased levels of Treg cells (17).

Some patients with insulin resistance may have "suicide" receptors on the Treg cells that tag them to trigger their premature destruction which also lead to failed tolerance and its associate problems in pregnancy (study presented at the ASRI, NYC, 2014).

  • Insulin resistance and hyperglycemia

PCOS is often associated with insulin resistance and hyperglycemia. Maternal glucose can also cross the placenta inducing the production of higher insulin levels by the fetus. Because insulin can directly impact the brain plasticity, it is believed that maternal hyperglycemia could be a contributing cause to autism.

To learn more about maternal inflammation and autism, consult our website www.preventautism.com.

b- Hyperandrogenism

The extreme male brain theory of autism has been developed almost 15 years ago (18). This theory developed the idea that in utero exposure to high levels of testosterone of maternal origin could be responsible for autism development in the offspring.

Mothers of autistic children have been shown to have higher levels of testosterone (19).

Prenatal androgens shape neurons development and could contribute to the development of autism (20). Testosterone also exerts epigenetic influences (regulation of gene expression) that may result in neuronal development alteration and disrupted synapse function and morphology (21). As PCOS is marked by increased androgen levels, this condition could be a possible cause of autism development in the offspring as recently shown (4) although we strongly believe that maternal inflammation and immune alterations are the main factors playing a key role during fetal brain development.

  1. Therapies exist to counteract PCOS symptoms thus minimizing your risks of having a child with autism

    a- Metformin

A large body of evidences is now documenting the efficacy of Metformin in the treatment of PCOS associated with insulin resistance (22-23).

  • Metformin has pleiotropic effects on the endocrine system with:

    - Significant reduction of glucose production
    - Significant increase in glucose utilization
    - Significant reduction in Insulin levels
    - Significant increase in Insulin sensitivity
    - Significant reduction in testosterone levels
  • Metformin restores the ovarian function with:
    - Significant improvement in the frequency of menstrual cycle
    - Significant improvement in ovulation (even in clomiphene-resistant women)
  • Metformin and pregnancy

‚ÄčA multi-center, prospective, randomized, double-blind study showed an increased in pregnancy and live birth rate in Metformin-treated PCOS patients compared to the placebo-treated PCOS pregnant group (23).

Another one showed a significant reduction of miscarriages in PCOS women treated with Metformin during an IVF cycle (24).

Complex interactions between immunological alterations, systemic inflammation and endothelial dysfunction may be responsible for obstetrical complications and autism development in the offspring (25).

By increasing Treg cells (26), lowering inflammatory factor levels (27) and increasing vascularization (28), Metformin has beneficial effects on pregnancy outcome and could minimize your risks of having a child affected by autism.

b- Myo-inositol

Myo-inositol has beneficial effects on oocyte quality and restores ovarian function in women with PCOS (229) helping them conceive (30).

Inositol significantly reduces oxidative status leading to improvements in glucose metabolism. By reducing hyperinsulinemia, Myo-inositol supplementation has been demonstrated to improve pregnancy outcomes in PCOS women (31).

With its anti-inflammatory properties (32), Myo-inositol could help reduce your risks of miscarriages, pregnancy complications and in theory could minimize autism development in your child.

Insulin and glucose alterations as well as immune related and blood clotting issues are commonly associated with PCOS. These imbalances could be accountable for obstetrical complications and autism development as recently shown.
By addressing these symptoms with adequate therapies (a combination of immune therapies and metformin/Myo-inositol), we, at Braverman Reproductive Immunology, can help you maximizing your chances to have an uneventful pregnancy and a healthy baby.

References

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