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Research Review: Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental Disorders

A guest post by Sana Johnson-Quijada, MD

Autism is a syndrome, not a disease, with multiple genetic and non-genetic causes (Muhle, Trentacoste and Rapin; 2004). Current research has not been able to clearly define a definite cause of autism.

A recent study has added to our body of knowledge about autism. Krakowiak et al (2012) has published collaborative research showing a correlation between a mother’s health during pregnancy,  i.e. Maternal Metabolic Conditions, such as diabetes, hypertension and obesity, and neurodevelopmental disorders in children. The correlative evidence related to autism is listed below:

Etiology of Autism – Correlative Evidence

  • Maternal Metabolic Conditions (Krakowiak et al, 2011)
  • Toxins (oxidative stress) (Garecht and Austin, 2011)
  • Multiple interacting genetic factors (a specific gene has not been identified) (Muhle, Trentacoste and Rapin, 2004)
  • Sibling pairs (Greenberg, Hodge Sowinski and Nicoll, 2001)
  • Medications (Garecht and Austin, 2011)
  • Birth order (Turner, Pihur, and Chakravarti, 2011; Durkin et al, 2010)
  • Parental age (Turner, Pihur, and Chakravarti, 2011; Durkin et al, 2010)

Can the information from the study of Krakowiak et al (2012) help reduce the incidence of autism? Importantly, the information is correlative and does not demonstrate causality. The study, Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental Disorders, is simply done, makes sense, and is consistent with other studies that demonstrate that a healthy Mom helps produce a healthy fetus.

Let’s take a look at this specific study. In California, between 2003- 2010, Krakowiak et al (2012) enrolled 689 children (ages 2 – 5 years old) with a diagnosis of autism spectrum disorder or developmental delay, along with 315 children in a control group, in the CHARGE study (Children Autism Risks from Genetics and the Environment). The children were diagnosed by using standardized testing. The mothers were diagnosed by medical records and structured interviews.

The researchers found that all Maternal Metabolic Conditions, such as diabetes, hypertension and obesity, were more prevalent among the case mothers than the control mothers. The researchers note their findings are consistent with other studies linking maternal diabetes to impairments in their children.

Maternal diabetes, hypertension and obesity are associated with the maternal conditions of increased insulin resistance, poorly regulated glucose levels and chronic inflammation, which all adversely fetal development.

Prolonged exposure of the fetus to maternal elevated glucose levels can result in chronic fetal hyperinsulemia, which then results in increased fetal oxygen consumption and metabolism, which induces chronic intrauterine tissue hypoxia and possibly, downstream fetal iron deficiency. Both fetal tissue hypoxia and fetal iron deficiency can profoundly affect neurodevelopment in humans, such as aberrations in myelination, cortical connectivity and hippocampal neurons (Krakowiak et al, 2012).

Maternal chronic inflammation is associated with excess production of pro-inflammatory interleukin and cytokines in the mother. These substances cross the placenta and can adversely affect fetal development. Cytokine interleukin-6 has been associated with adverse development of the hippocampus and seizures in animal studies (Krakowiak et al, 2012). Other studies have found a correlation with inflammation and autism, including the studies on mercury fueling the oxidative stress found in autism (Garecht and Austin, 2011).

What do we know about inflammation? Inflammation triggers expression of cancer genes, depression genes, irritable bowel syndrome and so forth. Genes start talking and moving when they are pushed. Remember the research we have demonstrating familial inheritence in autism? Krakowiak et al (2012) believe inflammation may be a voice that is heard during pregnancy as well.

Does this study give us enough evidence to use when advising mothers to be healthy during pregnancy? The studies are not conclusive. But they make sense.

In participating with patients (clients) in their health care, life choices and treatments, ultimately, we all know, the patient (client) is accountable to him or herself. We present them with information and let them make their choices.

This study is consistent with life “sense,” and is empowering to all of us. We find in the idea of caring for our bodies and our children that we must do the friendly thing, starting with good self-care.

References:

Autistic children: diagnosis and clinical features. Rapin I. Pediatrics. 1991 May;87(5 Pt 2):751-60. Review.

Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental Disorders, Paula Krakowiak, Cheryl K. Walker, Andrew A. Bremer, Alice S. Baker,Sally Ozonoff, Robin L. Hansen, and Irva Hertz-Picciotto. Pediatrics peds.2011-2583; published ahead of print April 9, 2012,doi:10.1542/peds.2011-2583

The Genetics of Autism.Rebecca Muhle, Stephanie V. Trentacoste, and Isabelle Rapin. Pediatrics 2004; 113:5 e472-e486

Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci.Hedges DJ, Hamilton-Nelson KL, Sacharow SJ, Nations L, Beecham GW, Kozhekbaeva ZM, Butler BL, Cukier HN, Whitehead PL, Ma D, Jaworski JM, Nathanson L, Lee JM, Hauser SL, Oksenberg JR, Cuccaro ML, Haines JL, Gilbert JR, Pericak-Vance MA. Mol Autism. 2012 Apr 2;3(1):2.

The plausibility of a role for mercury in the etiology of autism: a cellular perspective.Garrecht M, Austin DW. Toxicol Environ Chem. 2011 May;93(5-6):1251-1273

Effect of Prenatal Valproic Acid Exposure on Cortical Morphology in Female Mice.Hara Y, Maeda Y, Kataoka S, Ago Y, Takuma K, Matsuda T. J Pharmacol Sci. 2012 Mar 22.

Quantifying and modeling birth order effects in autism. Turner T, Pihur V, Chakravarti A.PLoS One. 2011;6(10):e26418. Epub 2011 Oct 19.

Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Greenberg DA, Hodge SE, Sowinski J, Nicoll D. Am J Hum Genet. 2001 Nov;69(5):1062-7

Advanced Parental Age and the Risk of Autism Spectrum Disorder. Durkin, MS, Maenner, MJ, Newschaffer, LL, Cunniff, CM, Daniels, JL, Kirby, RS, Leavitt, L., Miller, L., Zahorondy, W., Schieve, LA. American Journal of Epidemiology. 2010, 168(11);1268-1276.

Sana Johnson-Quijada, MD, is a board certified psychiatrist who completed her psychiatry residency and fellowship in Primary Medicine between Loma Linda University and Harvard South Shore in 2002. She is in private practice in the areas of outpatient clinical, ECT, and serves as the Medical Director of the Loma Linda University Behavioral Medical Center Partial Hospital of Murrieta, California. Along with her husband, she parents her three children. She never gets tired of talking about becoming a friend to yourself. She’d love to hear from you via her website, Friend to Yourself.

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  1. April 23rd, 2012 at 08:19 | #1

    Thanks for a very informative article.

    I would think that polycystic ovarian syndrome (PCOS) would be an interesting confounder for obesity, which I understand had a higher correlation than diabetes and hypertension in the study. PCOS has been missing from the discussions I have seen about this, and was not addressed in the original article. Autism has been linked to higher levels of androgens in people living with autism spectrum disorder. PCOS is strongly associated with obesity, and part of its diagnostic criteria includes high androgen levels. Higher maternal androgen levels during pregnancy may be a possible environmental risk factor for development of autism in the fetus.

  2. April 23rd, 2012 at 10:26 | #2

    Hilary,

    Thank you for raising that important point. One question that came to mind for me was how to best support women with PCOS, diabetes, or other conditions who may feel frightened or discouraged about pregnancy when faced with a study like this. I don’t think that the take-away needs to be that they shouldn’t become pregnant, but needs to focus on empowering women to be active stewards of their health.

    Warmly,
    Ann

  3. April 23rd, 2012 at 13:38 | #3

    @Hilary Gerber
    Hi Hilary – I re-read the study very carefully. I havent seen any reference to PCOS in this study, only to diabetes, hypertension and obesity. Perhaps you are thinking of another study? The link to the full study is provided. Thanks for your input to this important topic, Kathy

  4. April 23rd, 2012 at 13:41 | #4

    @Ann Becker-Schutte, Ph.D.
    Hi Ann – Yes it is important that women don’t feel shamed about this issue. And self-care is a broad topic most people can use some encouragement with. I wanted to mention that I have carefully re-read the stud and I cannot find any reference to PCOS. I just dont want the wrong impression to be conveyed. The link tot he full study has been generously provided by Dr. Johnson-Quijada. thanks, Ann! warmly, Kathy

  5. April 23rd, 2012 at 15:33 | #5

    This is an excellent overview. Thank you.

  6. April 23rd, 2012 at 15:50 | #6

    Hi Hilary. That makes sense. PCOS goes w the 3 F’s – fat, fecund, forty. Obesity increases androgen levels, in part because of the hormones stored in the fat cells and because our organs that produce hormones might get fatty too, within themselves, and stop working the way they were designed.
    In the neighborhood, is how the organs in our body system also get fatty and then work less than their design intended – such as the pancreas which regulates sugar levels. We know that’s why people with diabetes get foot ulcers, impotence, blindness and so forth – unharnessed sugar floating around in the blood is destructive, inflammatory and compounds damage on damage.
    So…. I’m ok w PCOS as a comorbidty to autism, high androgen levels as a comorbidity and so forth. Inflammation comes into town on many a craft. keep on.
    @Hilary Gerber

  7. April 23rd, 2012 at 15:52 | #7

    three cheers! u cut to the nucleus. keep on.@Ann Becker-Schutte, Ph.D.

  8. April 23rd, 2012 at 15:53 | #8

    Walker Karraa :
    This is an excellent overview. Thank you.

    - u bet. great to connect w u.@Walker Karraa

  9. April 23rd, 2012 at 19:54 | #9

    My mind immediately went to the embryonic environment the unborn suffer whose mother is alcoholic/addict. The maladies and intensities increase exponentially. It makes me think of advocating the arrest and detention and treatment of such addicted mothers suspending civil rights for duration of pregnancy and requiring a mandatory 2 year parole/counseling enrollment. Poisoning the unborn is a criminal act and may even lead to the distasteful pragmatism of abortion which is an issue that may further complicate treatment options. The post birth world is ugly enough without the unfavorable pre birth conditions that lessen the ability to function and grow to adulthood and function in adulthood. I applaud this kind of research in the particular area you have studied. And our government, starting with food stamps, continues to cut funding for the underclass of women that desperately need services such as Planned Parenthood and other pre birth education and care.

  10. April 24th, 2012 at 07:56 | #10

    I love the “sense” part of Science & Sensibility. Thanks for this informative post.

  11. April 24th, 2012 at 09:57 | #11

    @Preconceptionist
    Thank you for kind support. We hope to make sense of all the research otu there and simplify relevant topics for our readers.

  12. May 3rd, 2012 at 18:49 | #12

    Carl, Perspective is your other name. If we lived in biblical days, maybe u’d b renamed some hebrew version of that.
    @Carl D’Agostino

  1. April 23rd, 2012 at 15:58 | #1