Severity of autism symptoms is correlated to the presence of copy number variations and exposure to first trimester ultrasound

Many people regard prenatal ultrasound as part of the routine care of any pregnancy. They probably base this view on the fact that in our modern society, even for low risk pregnancies, ultrasound is used numerous times without a real medical reason. This practice exists in spite numerous safety committees having stated that ultrasound should be used under the ALARA principle, that is, using energy levels and time of exposure “As Low As Reasonably Achievable”. Furthermore, regulatory boards decry its use for dating purposes during the first trimester and have called for the close monitoring of the better known injurious mechanisms of ultrasound by implementing safety levels for both the thermal and mechanical effects of this technique.

Back in the 1990’s energy levels for ultrasound were increased by an eight-fold with little in terms of studies to warrant its safety. This level of medical complacency is the result of numerous studies in humans that have found no consistent relationship to congenital anomalies nor to any particular mental disorder. Those few studies claiming speech delay and increased prevalence of left handedness as a result of prenatal ultrasound have been criticized in the literature.  However, human studies can’t control for variables that are essential in any ultrasound study, e.g., exact energy transfer when considering different practitioners using different equipment.  It is in this regard that animal studies that effectively control many experimental variables are better suited than human studies to uncover the potential dangers of ultrasound.

Animal studies of ultrasound have, in effect, shown disrupted patterns of brain myelination and altered migration of cells during the stage in which the cerebral cortex is formed (Ellisman et al., 1987). Another study showed how 20 minutes of ultrasound in rats changed their mRNA and protein expression levels in their hippocampi while damaging their cellular connections (Li et al., 2015). Other studies have found that prenatal exposure to ultrasound has effects on behaviors. e.g., decreased motor and exploratory activities as well as decreased learning abilities (Surech et al, 2008; Li et al., 2015). Recently Pierre Mourad’s group at the University of Washington reported that as little as 30 minutes of prenatal exposure to ultrasound resulted in juvenile mice exhibiting decrease socializing behavior and more hyperactivity. The latter study proposed the use of ultrasound as a risk factor for autism-like behaviors McClintic et al. 2013).

Sara Jane Webb in collaboration with Pierre Mourad and others have now published a follow up study using data derived from humans in the journal Autism Research. Their intent, in part, was to prove whether or not ultrasound was part of a “triple hit” that conferred vulnerability to autism in humans. In essence, the triple hit hypothesis of autism says that the autism spectrum is an expression of an exogenous stressor acting during a particular time of gestation in a genetically susceptible individual (see http://bit.ly/2bR6txn ). Although the original triple hit hypothesis of autism was meant to establish a causal link to the pathology of autism, Webb’s study addressed whether the same factors could help explain the presence and severity of autism-like symptoms in children diagnosed with the condition. In this particular instance the authors collected data from the Simon’s Simplex Collection on 2,644 families from across the United States. The families had one child diagnosed with autism according to a number of different screening techniques. In this group of children 1,000 of them had received ultrasound during their first trimester. From the group that had received ultrasound during the first trimester, 100 had genetic errors (so-called copy number variants) and 70 of them could be said to have “severe” autism. Data derived from individuals that had ultrasound during the second or third trimester showed no correlations. Overall the study found that the combination of common number variants or mutations and ultrasound during the first trimester of gestation in male children correlated to poorer cognitive outcomes and increased repetitive behaviors.  The authors concluded that, “…heterogeneity in ASD symptoms may result in part, from exposure to diagnostic ultrasound during early prenatal development of children with specific genetic vulnerabilities” (Webb et al., 2016).

Sara Jane Webb

Figure: The leading author of the study was Sara Jane Webb PhD. She is an Associate Professor at the University of Washington’s Department of Psychiatry and Behavioral Sciences. The focus of research for Dr. Webb is the functional neurobiology and development of information processing in individuals with autism spectrum disorder and other developmental disorders.

These results also add weigh to on-going concerns expressed by the FDA about non-medical use of diagnostic ultrasound during pregnancy. In effect there are about 900 ultrasound boutiques spread across the Unites States offering ultrasound as keepsake images. Since ultrasound is not closely regulated by the federal or state government any individual can buy the equipment and monitor their pregnancy. More recently there has been a promotion of baby shower parties where rental of an ultrasound machine allows all of those in attendance to watch the baby. Given the available evidence, partaking in such activities is not recommended. Ultrasound may be non-invasive but the assertion that it carries no risk needs to be further investigated.

Other previous blogs on ultrasound and autism in cortical chauvinism include:

Ultrasound and autism http://bit.ly/2c0Dpht

Mice exposed to ultrasound during gestation show autistic behaviors http://bit.ly/2bPiByW

The need for more studies on the safety of prenatal ultrasound http://bit.ly/2cA9d21

Ultrasound exposure and autism: Dr. Manuel Casanova cautions against the overuse of ultrasound http://bit.ly/2cl9WQ1

References

Ellisman MH, Palmer DE, Andre MP. Diagnostic levels ofultrasound may disrupt myelination. Experimental Neurology 98: 78-92, 1987.

Li P, Wand PJ, Zhang W. Prenatal exposure to ultrasound affects learning and memory in young rats. Ultrasound in Medicine and Biology 41:644-653, 2015.

McClintic AM, King BH, Webb SJ, Mourad PD. Mice exposed todiagnostic ultrasound in utero are less social and more active in social situations relative to controls. Autism research, 7:295-304, 2013.

Surech R, Ramesh Rao T, Davis EM, Ovchinnikow N, McRae A. Effect of diagnostic ultrasound during the fetal period on learning and memory in mic. Annals of Antomy Anatomischer Anzeiger 190: 37-45, 2008.

Webb SJ, Garrison MM, Bernier R, McClintic AM, King BH, Mourad PD. Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound. Autism Research 2016 Sep 1. doi: 10.1002/aur.1690. [Epub ahead of print] PMID: 27582229

 

8 responses to “Severity of autism symptoms is correlated to the presence of copy number variations and exposure to first trimester ultrasound

  1. This is very interesting given how many twin Mamas I know who have children with ASDs. When pregnant with my own twins, I had numerous US. Being aware of the work by the Rakic and Schwartz groups at Yale I was concerned, but it seemed that the reasons for US were endless, especially with early bleeding and difficulty conceiving. I was taking progesterone to maintain the pregnancy in the first weeks and I was high risk, being over 35 and pregnant with twins. I had multiple high risk screenings, checks for cervical length (used to monitor the risk of premature birth), and screenings for developmental abnormalities. If I think back, I had about 5 in the first trimester, the first being at 7 weeks. I met an online group of twin mothers all due in the same month or two. We have stayed in touch for 6 years and have a FB group. We’ve shared the ups and downs of twin pregnancy (including multiple Ultrasounds) and the challenges of raising twins. Of 44 live births, we have 3 ASD diagnoses, all from different pairs (that’s almost 7%, or 1 out of 15). Among some twin Moms, it is strongly suspected that just being a twin, puts you at higher risk of having ASDs. Maybe it’s the stress of the pregnancy/placental issues, and a twin pregnancy is TOUGH, but maybe the multiple ultra sounds are also a factor.

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  2. Good comment. I was not aware of the FB on twins. The statistics are quite striking. I have an FB on ultrasound.
    It may be that certain risk factors for autism such as older age, obesity, multiple pregnancies, threatened abortion are all linked by the same commonality, i.e., an increased number of ultrasounds.

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  3. Good point about the commonality of high risk factors leading to multiple ultra sounds, and early ultrasounds. I had not thought of it that way, but there is something to that. By “FB”, I meant Face book, and we have our own private group. We are/were 22 Moms that were due in the same time frame. We had met on the website Babycenter, but our experiences were so different from the regular babycenter birth-club group, we decided to chat among ourselves. As our kids developed, we compared milestones. Some of the Mom’s became concerned very early on, some a bit later. Given the family history of ASDs on both my husband’s side of the family, and mine, I feel we lucked out because our kids did not end up with ASD. ADHD on the other hand…Well, let’s just see how kindergarten goes, but we’ve already started the conversation with our pediatrician. Among our twins mom group, many are concerned with ADHD symptoms in their kids. It also brings to mind the potential confounder of MZ vs DZ twin studies. How much can you trust them for a condition, if there mere fact of having a twin pregnancy can skew the results. As most science goes, multiple lines of evidence are important when trying to arrive at the truth.

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  4. Thank you for clarfying. I did understand the FB reference. The ultrasound page that I made reference to is in Facebook: Fetal sonograms safe? I wish it had another title.

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  5. Hello, I would just like to ask, hypothetically, what would be easier to change in a person’s brain?

    Homosexuality or autism?
    Now, I am not comparing the two, they are not equivalents at all.
    But since we here talks of cures for autism (or at least treatments, both of which I am in favor of), how difficult would it be compared to changing sexuality of a person looking at the physical differences in the brain?(Homosexual people have different brain structures as well, and also like autism, there are some genetic components which increase the risk but a strong support for epigenetic factors that cause it to happen or not and then the brain develops differently).

    Do you know?

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    • Thank you for the comment. I don;t believe anybody has talked about a cure for autism as one demanding a change in a person’s cognitive style. Accomodations and treatment are sought for those issues that may handicap the autistic individual including social anxiety, affective disorders, sensory abnormalities, sleep disturbances, seizures, etc.

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  6. Thank you, Dr. Casanova, for your articles on this — I am thankful that I just found your blog. I’m at 13 weeks in my first pregnancy, and thanks to articles I’ve read quoting you and Dr. Pasko Rakic, I’ve opted out of all the ultrasounds and Dopplers that have been offered thus far (2 ultrasounds and 1 Doppler already, in just the first trimester.)

    I get pushback from my Ob each time though, and I can foresee the pressure getting worse in the months ahead. She is especially adamant about suggesting the 20 week anatomy scan, and Doppler heartbeat scans after 30 weeks. I’m quite torn on how to proceed, and whether I should search for a new doctor — but I have a hunch that all providers I meet will have the same attitude.

    I know you likely don’t want to prescribe specific behaviors, but I’m curious: If your wife were carrying a child right now, would you recommend she have any ultrasounds at all? In your opinion, the 20 week scan far enough along in development to be less damaging, or is the entire prenatal period potentially delicate?

    Liked by 1 person

    • Most safety boards tell physicians to provide ultraound exams only when medically needed. Ask your physician about the need of the scan. If possible, also ask the physician to see if he/she can provide some literature as to the need of the ultrasound for the purpose that he/she is requesting the same.

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