By linking to some media discussing the inquest findings for Richard Handley (see here) I don't want to trivialise his death or use it as some kind of 'I told you so' example. Here was a man who died as a result of "gross failures" in his care as someone with Down's syndrome who also had a history of bowel issues. His death, linked to chronic constipation and "as a result of choking on his own vomit having inhaled gastric contents following complications with surgery", represents failures on many different levels. Not least is a seeming lack of appreciation of how bowel issues can very much be part of the clinical profile of many conditions / labels / diagnoses considered within the spectrum of intellectual or learning disabilities. Said issues require both regular monitoring and appropriate and timely intervention.
It is perhaps notable then that the paper by Deborah Kinnear and colleagues [1] is published these days, highlighting how various physical conditions are over-represented alongside diagnoses characterised by intellectual (learning) disability. The authors reported that: "The five most prevalent were visual impairment, obesity, epilepsy, constipation and ataxic/gait disorders."
Based on the examination of data for "people with intellectual disabilities living within the geographical area of Greater Glasgow Health Board, Scotland" between 2002 and 2004, researchers reviewed case records and "completed a comprehensive semi-structured health interview and targeted physical examination and followed a phlebotomy protocol, with the person with intellectual disabilities and their carer." This was time consuming affair - the "complete assessment process took about 4 hours per participant" - covering over 1000 people.
Alongside the reporting of those 'top five most prevalent conditions', researchers also observed several other important details. Namely that nearly all of their cohort had a least one co-existing health condition. The average number of comorbid conditions was 11. Yes, that's 11. And some people had over 25 comorbid physical conditions. When also taking into account the presence or not of Down's syndrome, not much changed in relation to the detected physical comorbidity. Similarly, when age and sex/gender were examined, the authors concluded that there only minor differences noted in terms of comorbidity profiles for example.
Relevant to the case of Richard Handley are some discussions in the Kinnear paper about constipation and learning disability. So: "Constipation was the fourth most prevalent physical health condition." Further, they note in another study [2]: "Eight people with chronic constipation had serious side effects (rectal prolapse, diverticula of colon, intestinal obstruction, megacolon and haemorrhoids) and four eventually died of intestinal obstruction... Thus, as well as being painful, constipation may remain undetected for a long time and can cause death due to missed clinical symptoms." Constipation can cause death. It shouldn't in this day and age, but it still does...
In relation to the implications of their findings, the authors make some additional comments. So: "Medical education is also focused on assessment and management of single conditions, yet management of multimorbidity is far more complex." This is important. It implies that outside of the view of one [primary] diagnosis being present per patient, clinicians and others need to have a more plural view, particularly when it comes to something like learning disability. The focus also on 'physical' comorbidities is also important insofar as how various developmental / behavioural / psychiatric conditions can very much manifest other non-developmental / behavioural / psychiatric conditions. This kinda mirrors what has been discussed with autism in mind (see here and see here for examples) and, alongside, the barriers that need to be overcome when it comes to appropriate diagnoses being made in such contexts (see here).
Set within other data indicating that premature mortality is very much over-represented when it comes to learning disability (see here), and that much of that early mortality is due to the presence of physical health conditions, the Kinnear findings should serve as a wake-up call to many sectors of the professional and other communities. Screening, diagnosing and implementing timely and appropriate intervention(s) are key recommendations; with a specific focus on the person as a whole rather than just being the sum of individual somethings like the diagnosis of learning disability. Bear in mind also that guidance on the management of something like constipation in the context of learning disability does exist in the peer-reviewed domain [3].
And finally, just in case you think that today's discussions aren't directly relevant to autism, constipation has also been mentioned in the death of another young person (see here)...
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[1] Kinnear D. et al. Prevalence of physical conditions and multimorbidity in a cohort of adults with intellectual disabilities with and without Down syndrome: cross-sectional study. BMJ Open. 2018; 8: e018292.
[2] Evenhuis HM. Medical aspects of ageing in a population with intellectual disability: III. Mobility, internal conditions and cancer. J Intellect Disabil Res. 1997 Feb;41 ( Pt 1):8-18.
[3] Robertson J. et al. Constipation management in people with intellectual disability: A systematic review. J Appl Res Intellect Disabil. 2017 Nov 23.
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Showing posts with label Down's syndrome. Show all posts
Showing posts with label Down's syndrome. Show all posts
Friday, 9 March 2018
Saturday, 16 December 2017
Mortality patterns in older adults with learning disability
"Older adults with ID [intellectual disability] in Sweden carry a higher mortality risk compared with the general population, mainly attributable to respiratory, nervous and circulatory diseases."
So said the findings reported by Nawi Ng and colleagues [1] (open-access) looking at the records of some 15,000 individuals diagnosed with an intellectual (learning) disability compared with a similar number of control participants with respect to "patterns and risk of mortality." Researchers observed "a 4-fold higher mortality rate and a shorter median survival time among older adults with ID compared with the general older adult population." Such findings add to a growing body of research literature (see here and see here) suggesting that behavioural, cognitive and/or psychiatric diagnoses seem to be accompanied by some significant health inequalities too.
I could go into the details about the Ng study and the various ins-and-outs of how they arrived at their conclusions but to be honest, I'm just not minded to. I say that on the basis that the figures speak for themselves: "the mortality rate among individuals with ID was three times higher than in the control population" and: "Individuals with DS [Down's syndrome] had an 11-fold higher mortality risk than the control population." Sombre reading, perhaps partially reflecting how modern-day society treats some of its most vulnerable citizens.
The ultimate question should be: is there anything that can be done to improve this situation for those with a learning disability? Yes, is the answer; taking into account how a diagnosis of ID for example, means that some might be "more prone to cardiovascular disease risk factors, morbidity and mortality than the general population." The authors add that: "Cardiovascular disease health promotion and prevention programmes should be tailored for individuals with ID, to prevent or delay cardiovascular diseases and premature mortality in this vulnerable group." Corresponding action in relation to deaths resulting from epilepsy for example, should also (and always) be a priority.
"How a society treats its most vulnerable is always the measure of its humanity" is a phrase attributed to many speakers. On the basis of the research from Ng and other study results, society is seemingly failing many of those diagnosed with a learning disability as it is other vulnerable sections of society (see here).
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[1] Ng N. et al. Mortality patterns and risk among older men and women with intellectual disability: a Swedish national retrospective cohort study. BMC Geriatrics. 2017; 17: 269.
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So said the findings reported by Nawi Ng and colleagues [1] (open-access) looking at the records of some 15,000 individuals diagnosed with an intellectual (learning) disability compared with a similar number of control participants with respect to "patterns and risk of mortality." Researchers observed "a 4-fold higher mortality rate and a shorter median survival time among older adults with ID compared with the general older adult population." Such findings add to a growing body of research literature (see here and see here) suggesting that behavioural, cognitive and/or psychiatric diagnoses seem to be accompanied by some significant health inequalities too.
I could go into the details about the Ng study and the various ins-and-outs of how they arrived at their conclusions but to be honest, I'm just not minded to. I say that on the basis that the figures speak for themselves: "the mortality rate among individuals with ID was three times higher than in the control population" and: "Individuals with DS [Down's syndrome] had an 11-fold higher mortality risk than the control population." Sombre reading, perhaps partially reflecting how modern-day society treats some of its most vulnerable citizens.
The ultimate question should be: is there anything that can be done to improve this situation for those with a learning disability? Yes, is the answer; taking into account how a diagnosis of ID for example, means that some might be "more prone to cardiovascular disease risk factors, morbidity and mortality than the general population." The authors add that: "Cardiovascular disease health promotion and prevention programmes should be tailored for individuals with ID, to prevent or delay cardiovascular diseases and premature mortality in this vulnerable group." Corresponding action in relation to deaths resulting from epilepsy for example, should also (and always) be a priority.
"How a society treats its most vulnerable is always the measure of its humanity" is a phrase attributed to many speakers. On the basis of the research from Ng and other study results, society is seemingly failing many of those diagnosed with a learning disability as it is other vulnerable sections of society (see here).
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[1] Ng N. et al. Mortality patterns and risk among older men and women with intellectual disability: a Swedish national retrospective cohort study. BMC Geriatrics. 2017; 17: 269.
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Tuesday, 23 August 2016
Autism and/or ADHD in Down's syndrome
"High rates of ASD [autism spectrum disorder] and ADHD [attention-deficit hyperactivity disorder] were found: 17 (42%) and 14 (34%) of the 41 children met DSM criteria for ASD and ADHD respectively."That was the conclusion reached in the study by Ulrika Oxelgren and colleagues [1] looking at the "prevalence of autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD) in a population-based group of children and adolescents with Down syndrome." The population in this case comprised 60 children and young adults diagnosed with Down's syndrome (Down syndrome if you prefer) and the gold-standards that are the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) were the instruments of choice when arriving at decisions of whether autism might be present or not.
New news? No it's not new news that autism (whether in diagnosis or in traits) may be over-represented when it comes to Down's syndrome (see here and see here for other research-based examples). There has even been a suggestion that regression - a key part of at least some autism - may be part and parcel of some cases of Down's syndrome (see here) too.
Oxelgren et al suggest that the combination of Down's syndrome and the "intellectual disability and medical disorders" that can accompany Down's syndrome added to a possible higher rate of autism potentially make for "a severely disabled group" worthy of far greater attention when it comes to screening and intervention. I don't think anyone would disagree with such sentiments and in particular, how preferential autism screening should once again be added to a growing list of diagnoses and labels. Indeed, such data in particular directs further attention to the link between intellectual (learning) disability and autism (see here and see here).
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[1] Oxelgren UW. et al. Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study. Dev Med Child Neurol. 2016 Aug 9.
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Oxelgren UW, Myrelid Å, Annerén G, Ekstam B, Göransson C, Holmbom A, Isaksson A, Åberg M, Gustafsson J, & Fernell E (2016). Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study. Developmental medicine and child neurology PMID: 27503703
Tuesday, 6 October 2015
Prenatal hormone involvement in autism risk?
The findings reported by Gayle Windham and colleagues [1] caught my eye recently and their observations based on the examination of mid-pregnancy serum hormone and protein markers for some 2500 mothers of children diagnosed with an autism spectrum disorder (ASD) compared with 600,000 controls.Detailing results based on: "Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP)", researchers reported that their results: "further support prenatal hormone involvement in ASD risk."
I perhaps need to do a little 'defining' before progressing any further with this post. Unconjugated estriol (uE3) refers to an estrogen. It becomes the dominant oestrogen during pregnancy; produced by the baby's liver and placenta. Measured levels of uE3 during the 2nd trimester of pregnancy have been linked to various 'outcomes' including the possibility of Down's syndrome and neural tube defects.
Human chorionic gonadotropin (hCG) is another hormone; one that is normally used to confirm pregnancy. During pregnancy, levels of hCG can also be used to determine Down's syndrome. Serum alpha-fetoprotein (MSAFP) is the most abundant plasma protein found in the developing foetus. During pregnancy, extremes in levels of MSAFP can indicate issues in pregnancy. Combined together, these various hormones/proteins make up the so-called triple test, that when added to information such as maternal age and stage of pregnancy, can classify a pregnancy as being high or low risk for chromosomal abnormalities. That being said, the test is by no means perfect.
Windham et al report some rather complicated results based on adjusted odds ratios (AOR) when it came to autism vs control samples. So: "Lower uE3 (AOR for < 10th percentile vs. 25th-74th percentiles = 1.21, 95 % CI 1.06-1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07-1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02-1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05-1.36 for > 90th percentile)." Lower uE3 is a trend found in relation to Down's syndrome. Higher MSAFP however runs slightly counter to what has been discussed in relation to Down's syndrome. By contrast, elevations in MSAFP tend to be more readily linked to pregnancies where neural tube defects may be present. What this all means is that yes, these results could indicate the involvement of prenatal hormones and chromosomal issues in relation to 'some' autism, but science still needs to go a little way before anyone talks about a triple test being applied to autism (and the ethical issues that this might bring).
I think it's also worthwhile briefly bringing in a few caveats to such pregnancy testing that could be pertinent to other autism research findings. As per other information, a mother's weight during pregnancy can affect what results you get - "Serum marker levels tend to be decreased in heavier women, and increased in lighter women." If you map this on to the research talking about maternal obesity linked to some autism (being careful not to generalise here), you can see how adjustments might have been / have to be made. Ethnicity is another factor that needs to be kept in mind. Also: "AFP and uE3 levels tend to be low (about 8% and 6% respectively) in women with insulin dependent diabetes mellitus." This is particularly interesting in view of the quite consistent literature detailing how gestational diabetes seems to show a connection to risk of offspring autism (see here). Various other factors (vaginal bleeding) can similarly affect results.
The Windham results are nevertheless interesting and are strengthened somewhat by the large participant numbers included for study. That other groups have similarly talked about elevations in MSAFP in relation to autism [2] increases the confidence that there may something further to see in this area, at least for some autism.
Music: Al Green - Tired of Being Alone.
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[1] Windham GC. et al. Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California. J Autism Dev Disord. 2015 Sep 14.
[2] Abdallah MW. et al. Autism spectrum disorders and maternal serum α-fetoprotein levels during pregnancy. Can J Psychiatry. 2011 Dec;56(12):727-34.
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Windham GC, Lyall K, Anderson M, & Kharrazi M (2015). Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California. Journal of autism and developmental disorders PMID: 26370672
Friday, 6 March 2015
Hypovitaminosis D is frequent in Down's syndrome
"Hypovitaminosis D is very frequent in DS [Down's syndrome] subjects, in particular in presence of obesity and autoimmune diseases."
That was the conclusion reached in the study by Stefano Stagi and colleagues [1] (open-access here) based on an analysis of their small participant group diagnosed with Down's syndrome looking at vitamin D status among other things. The comment about obesity potentially exacerbating vitamin D deficiency ties in well with another paper independently published around the same time suggesting that obesity may very well impact on vitamin D status [2].
The Stagi paper is open-access so no need for too many details from me. Researchers looked at "calcium, phosphate, parathyroid hormone (PTH), 25(OH)D concentrations, and calcium and 25(OH)D dietary intakes" in 31 children and young adults with DS compared with "99 age- and sex-matched" controls. They reported that as a group, those with DS "showed reduced 25(OH)D levels compared to controls" and significantly higher levels of PTH. Daily supplementation with 400 IU [international units] of cholecalciferol (vitamin D3) did bring levels up over the course of about a year in those with DS but again, as a group, levels were still reduced compared to controls.
What's more to say? Well, we add these results to the growing number of conditions where vitamin D insufficiency or deficiency has been described (see here). As per the discussions about vitamin D and autism, one cannot rule out the issue of comorbidity as playing a role in the Stagi results, particularly if one assumes that DS might confer something of an elevated risk of something like depression [3]. Indeed, the growing research base talking about an increased expression of autism / autistic traits in those with DS is perhaps deserving of a mention too.
In terms of the more typical reasons why one might show issues with the availability of vitamin D - lack of sunshine and/or dietary inadequacy - these are factors that need to be considered. Stagi et al did note that physical activity levels were reported to be lower in the DS group but this needs quite a bit more analysis, based as it was on "questions regarding each child's and adolescent's average number of daily outdoor hours across each season and a prospective daily time-activity diary." Think back to my post on how sitting time might be more objectively measured (see here).
The idea that autoimmune conditions might have also impacted on vitamin D levels in DS is intriguing. Not so long ago I addressed the topic of Down Syndrome Disintegrative Disorder (see here) and the more general association of autoimmune issues with DS in mind. That and my recent post on the Skaaby paper [4] (see here) talking about a "statistically significant inverse associations between vitamin D status and development of any autoimmune disease", and one has a recipe for quite a bit more scientific inquiry into this area.
And to close: Franz Ferdinand with Darts Of Pleasure.
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[1] Stagi S. et al. Determinants of vitamin d levels in children and adolescents with down syndrome. Int J Endocrinol. 2015;2015:896758.
[2] Pereira-Santos M. et al. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev. 2015 Feb 17.
[3] Walker JC. et al. Depression in Down syndrome: a review of the literature. Res Dev Disabil. 2011 Sep-Oct;32(5):1432-40.
[4] Skaaby T. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. 2015 Feb 11.
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Stagi S, Lapi E, Romano S, Bargiacchi S, Brambilla A, Giglio S, Seminara S, & de Martino M (2015). Determinants of vitamin d levels in children and adolescents with down syndrome. International journal of endocrinology, 2015 PMID: 25685147
That was the conclusion reached in the study by Stefano Stagi and colleagues [1] (open-access here) based on an analysis of their small participant group diagnosed with Down's syndrome looking at vitamin D status among other things. The comment about obesity potentially exacerbating vitamin D deficiency ties in well with another paper independently published around the same time suggesting that obesity may very well impact on vitamin D status [2].
The Stagi paper is open-access so no need for too many details from me. Researchers looked at "calcium, phosphate, parathyroid hormone (PTH), 25(OH)D concentrations, and calcium and 25(OH)D dietary intakes" in 31 children and young adults with DS compared with "99 age- and sex-matched" controls. They reported that as a group, those with DS "showed reduced 25(OH)D levels compared to controls" and significantly higher levels of PTH. Daily supplementation with 400 IU [international units] of cholecalciferol (vitamin D3) did bring levels up over the course of about a year in those with DS but again, as a group, levels were still reduced compared to controls.
What's more to say? Well, we add these results to the growing number of conditions where vitamin D insufficiency or deficiency has been described (see here). As per the discussions about vitamin D and autism, one cannot rule out the issue of comorbidity as playing a role in the Stagi results, particularly if one assumes that DS might confer something of an elevated risk of something like depression [3]. Indeed, the growing research base talking about an increased expression of autism / autistic traits in those with DS is perhaps deserving of a mention too.
In terms of the more typical reasons why one might show issues with the availability of vitamin D - lack of sunshine and/or dietary inadequacy - these are factors that need to be considered. Stagi et al did note that physical activity levels were reported to be lower in the DS group but this needs quite a bit more analysis, based as it was on "questions regarding each child's and adolescent's average number of daily outdoor hours across each season and a prospective daily time-activity diary." Think back to my post on how sitting time might be more objectively measured (see here).
The idea that autoimmune conditions might have also impacted on vitamin D levels in DS is intriguing. Not so long ago I addressed the topic of Down Syndrome Disintegrative Disorder (see here) and the more general association of autoimmune issues with DS in mind. That and my recent post on the Skaaby paper [4] (see here) talking about a "statistically significant inverse associations between vitamin D status and development of any autoimmune disease", and one has a recipe for quite a bit more scientific inquiry into this area.
And to close: Franz Ferdinand with Darts Of Pleasure.
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[1] Stagi S. et al. Determinants of vitamin d levels in children and adolescents with down syndrome. Int J Endocrinol. 2015;2015:896758.
[2] Pereira-Santos M. et al. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev. 2015 Feb 17.
[3] Walker JC. et al. Depression in Down syndrome: a review of the literature. Res Dev Disabil. 2011 Sep-Oct;32(5):1432-40.
[4] Skaaby T. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. 2015 Feb 11.
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Stagi S, Lapi E, Romano S, Bargiacchi S, Brambilla A, Giglio S, Seminara S, & de Martino M (2015). Determinants of vitamin d levels in children and adolescents with down syndrome. International journal of endocrinology, 2015 PMID: 25685147
Thursday, 29 January 2015
Autism spectrum symptomatology in individuals with Down syndrome
I was not surprised to read the findings of the paper from Marie Moore Channell and colleagues [1] (open-access) who "identified patterns of ASD [autism spectrum disorder] symptomatology, measured by the SRS [Social Responsiveness Scale], in individuals with DS [Down syndrome] who do not have comorbid ASD."
Harking back to the paper by Georgina Warner and colleagues [2] discussed not-so-long-ago on this blog (see here), the idea that various autistic traits might also overlap into other conditions including that of Down's syndrome, is gaining some research momentum at the moment. Whether such overlap will yield further clues regarding the aetiology of [some] autism or feed into the various discussions about the changing autism numbers game are discussions to be had in future times.
Channell et al report results for a small group of children/young adults diagnosed with DS. Their participant cohort originally started at 54 individuals with DS who met various study criteria. This was subsequently boiled down to 46 participants given that: "Eight participants scored above our predetermined cutoff" based on scores on the Social Communication Questionnaire (SCQ) "and were determined to be at risk for a comorbid ASD diagnosis, and they were referred for a full diagnostic evaluation." The authors importantly add that: "this number should not be used as a prevalence estimate of ASD risk in DS." Not yet at least.
The SRS was the primary assessment tool, a parent/caregiver reporting schedule "that asks caregivers about their child’s behavior over the past 6 months" specifically looking at reciprocal social behaviours. As part of the autism screening arsenal, the SRS is doing pretty well by all accounts [3]. That being said, it has it limitations as was recently mentioned [4] following it's use in that broccoli sprout - autism trial (see here).
Anyhow, the results: "In general, scores were elevated relative to the available normative data on typically developing children and adolescents, suggesting the need for normative data on the SRS for syndrome-specific samples such as those with DS." Indeed, the authors go on to suggest that as more is done in this area looking at any overlap between autism and DS: "It is likely that some of the currently used diagnostic measures also will require modification for ease of use and interpretation in the DS population." Too true although I would perhaps stress the idea that something like issues with social reciprocity might be something in need of further investigation in some cases of DS.
I've got little more to say on this issue over and above what has already been said. I'd like to think that once science has progressed a little further in this specific area, it might also turn its attention to the preliminary data reported by Worley and colleagues [5] and further testing of the concept of 'Down Syndrome Disintegrative Disorder' (see here) as one among other potential links between DS and the presentation of autism.
Music, music, music to close: Limahl - Never Ending Story. Sing it with passion...
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[1] Channell MM. et al. Patterns of autism spectrum symptomatology in individuals with Down
syndrome without comorbid autism spectrum disorder. Journal of Neurodevelopmental Disorders 2015, 7:5.
[2] Warner G. et al. Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales. Autism Res. 2014. March 24. 10.1002/aur.1371
[3] Duvekot J. et al. The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS. J Autism Dev Disord. 2014 Nov 28.
[4] Scahill L. Uncommon use of common measures in sulforaphane trial. PNAS. 2015. Jan 13.
[5] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.
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Marie Moore Channell, B Allyson Phillips, Susan J Loveall, Frances A Conners, Paige M Bussanich, & Laura Grofer Klinger (2015). Patterns of autism spectrum symptomatology in individuals with Down syndrome without comorbid autism spectrum disorder Journal of Neurodevelopmental Disorders : 10.1186/1866-1955-7-5
 |
| You're not going Turbo, are you? |
Harking back to the paper by Georgina Warner and colleagues [2] discussed not-so-long-ago on this blog (see here), the idea that various autistic traits might also overlap into other conditions including that of Down's syndrome, is gaining some research momentum at the moment. Whether such overlap will yield further clues regarding the aetiology of [some] autism or feed into the various discussions about the changing autism numbers game are discussions to be had in future times.
Channell et al report results for a small group of children/young adults diagnosed with DS. Their participant cohort originally started at 54 individuals with DS who met various study criteria. This was subsequently boiled down to 46 participants given that: "Eight participants scored above our predetermined cutoff" based on scores on the Social Communication Questionnaire (SCQ) "and were determined to be at risk for a comorbid ASD diagnosis, and they were referred for a full diagnostic evaluation." The authors importantly add that: "this number should not be used as a prevalence estimate of ASD risk in DS." Not yet at least.
The SRS was the primary assessment tool, a parent/caregiver reporting schedule "that asks caregivers about their child’s behavior over the past 6 months" specifically looking at reciprocal social behaviours. As part of the autism screening arsenal, the SRS is doing pretty well by all accounts [3]. That being said, it has it limitations as was recently mentioned [4] following it's use in that broccoli sprout - autism trial (see here).
Anyhow, the results: "In general, scores were elevated relative to the available normative data on typically developing children and adolescents, suggesting the need for normative data on the SRS for syndrome-specific samples such as those with DS." Indeed, the authors go on to suggest that as more is done in this area looking at any overlap between autism and DS: "It is likely that some of the currently used diagnostic measures also will require modification for ease of use and interpretation in the DS population." Too true although I would perhaps stress the idea that something like issues with social reciprocity might be something in need of further investigation in some cases of DS.
I've got little more to say on this issue over and above what has already been said. I'd like to think that once science has progressed a little further in this specific area, it might also turn its attention to the preliminary data reported by Worley and colleagues [5] and further testing of the concept of 'Down Syndrome Disintegrative Disorder' (see here) as one among other potential links between DS and the presentation of autism.
Music, music, music to close: Limahl - Never Ending Story. Sing it with passion...
----------
[1] Channell MM. et al. Patterns of autism spectrum symptomatology in individuals with Down
syndrome without comorbid autism spectrum disorder. Journal of Neurodevelopmental Disorders 2015, 7:5.
[2] Warner G. et al. Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales. Autism Res. 2014. March 24. 10.1002/aur.1371
[3] Duvekot J. et al. The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS. J Autism Dev Disord. 2014 Nov 28.
[4] Scahill L. Uncommon use of common measures in sulforaphane trial. PNAS. 2015. Jan 13.
[5] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.
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Marie Moore Channell, B Allyson Phillips, Susan J Loveall, Frances A Conners, Paige M Bussanich, & Laura Grofer Klinger (2015). Patterns of autism spectrum symptomatology in individuals with Down syndrome without comorbid autism spectrum disorder Journal of Neurodevelopmental Disorders : 10.1186/1866-1955-7-5
Wednesday, 26 November 2014
The gut microbiome in Down Syndrome
The recent preliminary findings from Elena Biagi and colleagues [1] (open-access) reporting on the constitution of the gut microbiome - the collected bacteria which reside in the deepest, darkest recesses of our gastrointestinal (GI) tract - in a small number of cases of Down's syndrome caught my eye recently.
Perhaps a little bit unusually looking at the gut microbiome because of the link between premature ageing in Down's syndrome (DS) and "human aging... associated with a deterioration of the gut microbiota (GM)-host mutualism" researchers set about characterising the gut microbiota (GM) in 17 participants diagnosed with DS. Profiles from DS participants were "compared with the previously published GM profiles of 16 age-matching healthy adults" indeed previously published by some of the authors [2] which itself has been the topic of some discussion.
The results were not exactly spectacular insofar as: "DS persons and healthy adults showed comparable levels of GM diversity and an overall similarity in the composition of the GM community" again bearing in mind the small participant numbers. Indeed their hypothesis about premature ageing of the gut microbiota did not appear to be borne out by their small scale study.
That being said, one particular finding peaked my interest: "DS persons were enriched in Parasporobacterium and Sutterella, and reduced in Veillonellaceae." It is the Sutterella part and the comment: "The increase of Sutterella and the reduction of Veillonellaceae have been described in autistic children with gastrointestinal symptoms" which made me sit up. I've covered Sutterella a few times on this blog with autism in mind (see here and see here for some replication work). Whilst independent work has suggested that Sutterella (Sutterella wadsworthensis) might be nothing more than "a common commensal" [3] based on analyses of samples from "44 treatment naïve de-novo IBD patients and 42 with normal colons", I am still of the opinion that there may be more to see from this bacteria / bacterium.
The fact that Biagi et al also reported that "the abundance of Sutterella in the GM was positively correlated with the ABC [Aberrant Behavior Checklist] total score in DS persons, suggesting a possible link between this microorganism and ASD [autism spectrum disorder] in DS" is to my mind, worthy of some follow-up as a function of some growing links between DS and the autism spectrum (see here). Whether this extends to the recent suggestion of Down Syndrome Disintegrative Disorder [4] is also a question not yet answered.
Bearing in mind the recent revelation that at least some microbiome analyses might be suffering an XMRV moment as per the paper from Susannah Salter and colleagues [5] on reagent and laboratory contamination potentially affecting results (contaminomics as one commentator has put it), there does seem to be quite a bit more to do in this area with DS in mind. If one takes the collected microbiome work with autism in mind (see here also recently added to by the paper by Tomova et al) as a template, and where that might potentially lead in terms of interventions for example, applying similar logic to findings in relation to DS might offer some similarly intriguing opportunities to impact on quality of life.
Next up on the research menu to complete the gut triad: gut permeability and mucosal immunity in DS? What about gluten 'sensitivity' [7] and/or coeliac disease [8]? Too much?
Music, music, music.... Acceptable in the 80's? (shoulder pads etc.)
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[1] Biagi E. et al. Gut Microbiome in Down Syndrome. PLoS One. 2014 Nov 11;9(11):e112023.
[2] Schnorr SL. et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun. 2014 Apr 15;5:3654.
[3] Hansen R. et al. The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study. PLoS One. 2013;8(3):e58825.
[4] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.
[5] Salter SJ. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biology 2014, 12:87
[6] Tomova A. et al. Gastrointestinal microbiota in children with autism in Slovakia. Physiology & Behavior. 2014. November 6.
[7] Wolters VM. et al. Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability. Hum Immunol. 2010 Apr;71(4):392-6.
[8] Malt EA. et al. Health and disease in adults with Down syndrome. Tidsskr Nor Laegeforen. 2013 Feb 5;133(3):290-4.
----------
Biagi E, Candela M, Centanni M, Consolandi C, Rampelli S, Turroni S, Severgnini M, Peano C, Ghezzo A, Scurti M, Salvioli S, Franceschi C, & Brigidi P (2014). Gut Microbiome in Down Syndrome. PloS one, 9 (11) PMID: 25386941
 |
| It's a funny feeling being taken under the wing of a dragon |
Perhaps a little bit unusually looking at the gut microbiome because of the link between premature ageing in Down's syndrome (DS) and "human aging... associated with a deterioration of the gut microbiota (GM)-host mutualism" researchers set about characterising the gut microbiota (GM) in 17 participants diagnosed with DS. Profiles from DS participants were "compared with the previously published GM profiles of 16 age-matching healthy adults" indeed previously published by some of the authors [2] which itself has been the topic of some discussion.
The results were not exactly spectacular insofar as: "DS persons and healthy adults showed comparable levels of GM diversity and an overall similarity in the composition of the GM community" again bearing in mind the small participant numbers. Indeed their hypothesis about premature ageing of the gut microbiota did not appear to be borne out by their small scale study.
That being said, one particular finding peaked my interest: "DS persons were enriched in Parasporobacterium and Sutterella, and reduced in Veillonellaceae." It is the Sutterella part and the comment: "The increase of Sutterella and the reduction of Veillonellaceae have been described in autistic children with gastrointestinal symptoms" which made me sit up. I've covered Sutterella a few times on this blog with autism in mind (see here and see here for some replication work). Whilst independent work has suggested that Sutterella (Sutterella wadsworthensis) might be nothing more than "a common commensal" [3] based on analyses of samples from "44 treatment naïve de-novo IBD patients and 42 with normal colons", I am still of the opinion that there may be more to see from this bacteria / bacterium.
The fact that Biagi et al also reported that "the abundance of Sutterella in the GM was positively correlated with the ABC [Aberrant Behavior Checklist] total score in DS persons, suggesting a possible link between this microorganism and ASD [autism spectrum disorder] in DS" is to my mind, worthy of some follow-up as a function of some growing links between DS and the autism spectrum (see here). Whether this extends to the recent suggestion of Down Syndrome Disintegrative Disorder [4] is also a question not yet answered.
Bearing in mind the recent revelation that at least some microbiome analyses might be suffering an XMRV moment as per the paper from Susannah Salter and colleagues [5] on reagent and laboratory contamination potentially affecting results (contaminomics as one commentator has put it), there does seem to be quite a bit more to do in this area with DS in mind. If one takes the collected microbiome work with autism in mind (see here also recently added to by the paper by Tomova et al) as a template, and where that might potentially lead in terms of interventions for example, applying similar logic to findings in relation to DS might offer some similarly intriguing opportunities to impact on quality of life.
Next up on the research menu to complete the gut triad: gut permeability and mucosal immunity in DS? What about gluten 'sensitivity' [7] and/or coeliac disease [8]? Too much?
Music, music, music.... Acceptable in the 80's? (shoulder pads etc.)
----------
[1] Biagi E. et al. Gut Microbiome in Down Syndrome. PLoS One. 2014 Nov 11;9(11):e112023.
[2] Schnorr SL. et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun. 2014 Apr 15;5:3654.
[3] Hansen R. et al. The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study. PLoS One. 2013;8(3):e58825.
[4] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.
[5] Salter SJ. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biology 2014, 12:87
[6] Tomova A. et al. Gastrointestinal microbiota in children with autism in Slovakia. Physiology & Behavior. 2014. November 6.
[7] Wolters VM. et al. Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability. Hum Immunol. 2010 Apr;71(4):392-6.
[8] Malt EA. et al. Health and disease in adults with Down syndrome. Tidsskr Nor Laegeforen. 2013 Feb 5;133(3):290-4.
----------
Biagi E, Candela M, Centanni M, Consolandi C, Rampelli S, Turroni S, Severgnini M, Peano C, Ghezzo A, Scurti M, Salvioli S, Franceschi C, & Brigidi P (2014). Gut Microbiome in Down Syndrome. PloS one, 9 (11) PMID: 25386941
Wednesday, 19 November 2014
Down Syndrome Disintegrative Disorder
"Down syndrome disintegrative disorder seems an appropriate name for this newly recognized clinical association, which may be due to autoimmunity."
That was the bottom line of the study published by Gordon Worley and colleagues [1] reviewing a small number of cases (N=11) of children diagnosed with Down's syndrome presenting at clinic "with a history of new-onset... or worsening... autistic characteristics" among other things. Based on some potentially important hunches (see here for a summary of the grant proposal for the project), researchers at Duke University and the Duke Down Syndrome Comprehensive Clinic reported results based on various behavioural and biochemical findings including that: "Ten of 11 cases (91%) had elevated ("positive") thyroperoxidase antibody titers compared to only 5 of 21 (23%) age-matched control subjects with Down syndrome".
As preliminary as these findings were, I was really rather interested to read about this study. Not only because of the link established between Down's syndrome (DS) and the presentation of autistic features harking back to some other important work (see here), but also the idea that autoimmunity might potentially be a driving force to such regressive features. Of course we already have something of a template for such a 'disintegrative disorder' in the description of Heller's syndrome, also known as childhood disintegrative disorder (CDD) (see here for some background). Until recently, CDD was included under the category 'Pervasive Developmental Disorder' roughly translating as part of the autism spectrum; although in the DSM update (DSM-5), the diagnosis no longer appears as such (see here). CDD and autism have a somewhat convoluted history intersecting with one and another during various research times and under different circumstances (see here).
Insofar as those anti-thyroid peroxidase (anti-TPO) antibodies being [positively] reported in quite a few cases of Down syndrome disintegrative disorder (DSDD), my interest is maintained. Issues potentially affecting thyroid function in relation to DS are not uncommonly reported in the research literature [2] and so one might not necessarily be surprised to hear that the presence of anti-TPO antibodies have been recorded previously [3]. Whether this finding overlaps with the Worley results in terms of early evidence for DSDD is a question we can't answer at the moment.
Indeed, autoimmunity in general, has something of a relationship with DS as per reviews such as the one by Chistiakov [4] (open-access). The fact that mention is made of coeliac disease (CD) as part of that autoimmune burden is something of particular interest to me; as the paper by Mårild and colleagues [5] noted: "a sixfold increased risk of CD in individuals with DS". These findings are all the more pertinent given that they also include one Jonas Ludvigsson on the authorship list, he of 'gluten issues not quite coeliac disease linked to some autism' (see here).
Going back specifically to the anti-TPO antibodies, I note that with the 'autistic characteristics' in mind, very little peer-reviewed research has been published in this area. It could be that anti-TPO antibodies are not something commonly seen in relation to autism or perhaps because very few people have actually looked at this issue. I will draw your attention to some of the work by Gustavo Román and colleagues [6] (see this post) which reported: "No [autism] risk was found for children of TPO-antibody–positive mothers".
That would have been all I would have said on the matter had the paper from Alan Brown and colleagues [7] not recently emerged indicating that within their cohort: "The odds of autism were increased by nearly 80% among offspring of mothers who were TPO-Ab + [positive for anti-TPO antibodies] during pregnancy (OR = 1.78, 95% CI = 1.16–2.75, p = 0.009), compared to mothers negative for this autoantibody". As interesting as this finding is, it still tells us very little about anti-TPO antibody status for those diagnosed with autism or an autism spectrum disorder (ASD) and how this might overlay with the DSDD description. I might also add that I have talked previously about research suggesting that such autoantibodies might have some link to certain kinds of depression (see here) which also draw in the possibility of comorbidity playing some role [8].
The Worley results, as preliminary as they are, are certainly worthy of further research consideration. It is a revelation to me even having an extended family member with DS, that beyond the classical presentation, there may be quite a bit more medical comorbidity which may require clinical attention. If Worley et al are indeed correct that for those with DSDD autoimmunity plays such an important role, it strikes me that directing efforts to tackle specific symptoms [9] or even autoimmune processes (as per other autoimmune conditions) might yield quite a few benefits for at least some.
Music: The Clash - Rock the Casbah.
----------
[1] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.
[2] Prasher VP. Down syndrome and thyroid disorders: a review. Downs Syndr Res Pract. 1999 Aug;6(1):25-42.
[3] Chen MH. et al. Thyroid dysfunction in patients with Down syndrome. Acta Paediatr Taiwan. 2007 Jul-Aug;48(4):191-5.
[4] Chistiakov D. Down syndrome and coexistent autoimmune diseases. J Applied Biomed. 2007; 5: 71-76.
[5] Mårild K. et al. Down syndrome is associated with elevated risk of celiac disease: a nationwide case-control study. J Pediatr. 2013 Jul;163(1):237-42.
[6] Román GC. et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013 Aug 13. doi: 10.1002/ana.23976.
[7] Brown AS. et al. Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014. 29 October.
[8] Walker JC. et al. Depression in Down syndrome: a review of the literature. Res Dev Disabil. 2011 Sep-Oct;32(5):1432-40.
[9] Hegedüs L. et al. Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto's thyroiditis. Clin Endocrinol (Oxf). 1991 Sep;35(3):235-8.
----------
Worley G, Crissman BG, Cadogan E, Milleson C, Adkins DW, & Kishnani PS (2014). Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. Journal of child neurology PMID: 25367918
 |
| "Hi, everyone. I'm Olaf and I like warm hugs!" |
That was the bottom line of the study published by Gordon Worley and colleagues [1] reviewing a small number of cases (N=11) of children diagnosed with Down's syndrome presenting at clinic "with a history of new-onset... or worsening... autistic characteristics" among other things. Based on some potentially important hunches (see here for a summary of the grant proposal for the project), researchers at Duke University and the Duke Down Syndrome Comprehensive Clinic reported results based on various behavioural and biochemical findings including that: "Ten of 11 cases (91%) had elevated ("positive") thyroperoxidase antibody titers compared to only 5 of 21 (23%) age-matched control subjects with Down syndrome".
As preliminary as these findings were, I was really rather interested to read about this study. Not only because of the link established between Down's syndrome (DS) and the presentation of autistic features harking back to some other important work (see here), but also the idea that autoimmunity might potentially be a driving force to such regressive features. Of course we already have something of a template for such a 'disintegrative disorder' in the description of Heller's syndrome, also known as childhood disintegrative disorder (CDD) (see here for some background). Until recently, CDD was included under the category 'Pervasive Developmental Disorder' roughly translating as part of the autism spectrum; although in the DSM update (DSM-5), the diagnosis no longer appears as such (see here). CDD and autism have a somewhat convoluted history intersecting with one and another during various research times and under different circumstances (see here).
Insofar as those anti-thyroid peroxidase (anti-TPO) antibodies being [positively] reported in quite a few cases of Down syndrome disintegrative disorder (DSDD), my interest is maintained. Issues potentially affecting thyroid function in relation to DS are not uncommonly reported in the research literature [2] and so one might not necessarily be surprised to hear that the presence of anti-TPO antibodies have been recorded previously [3]. Whether this finding overlaps with the Worley results in terms of early evidence for DSDD is a question we can't answer at the moment.
Indeed, autoimmunity in general, has something of a relationship with DS as per reviews such as the one by Chistiakov [4] (open-access). The fact that mention is made of coeliac disease (CD) as part of that autoimmune burden is something of particular interest to me; as the paper by Mårild and colleagues [5] noted: "a sixfold increased risk of CD in individuals with DS". These findings are all the more pertinent given that they also include one Jonas Ludvigsson on the authorship list, he of 'gluten issues not quite coeliac disease linked to some autism' (see here).
Going back specifically to the anti-TPO antibodies, I note that with the 'autistic characteristics' in mind, very little peer-reviewed research has been published in this area. It could be that anti-TPO antibodies are not something commonly seen in relation to autism or perhaps because very few people have actually looked at this issue. I will draw your attention to some of the work by Gustavo Román and colleagues [6] (see this post) which reported: "No [autism] risk was found for children of TPO-antibody–positive mothers".
That would have been all I would have said on the matter had the paper from Alan Brown and colleagues [7] not recently emerged indicating that within their cohort: "The odds of autism were increased by nearly 80% among offspring of mothers who were TPO-Ab + [positive for anti-TPO antibodies] during pregnancy (OR = 1.78, 95% CI = 1.16–2.75, p = 0.009), compared to mothers negative for this autoantibody". As interesting as this finding is, it still tells us very little about anti-TPO antibody status for those diagnosed with autism or an autism spectrum disorder (ASD) and how this might overlay with the DSDD description. I might also add that I have talked previously about research suggesting that such autoantibodies might have some link to certain kinds of depression (see here) which also draw in the possibility of comorbidity playing some role [8].
The Worley results, as preliminary as they are, are certainly worthy of further research consideration. It is a revelation to me even having an extended family member with DS, that beyond the classical presentation, there may be quite a bit more medical comorbidity which may require clinical attention. If Worley et al are indeed correct that for those with DSDD autoimmunity plays such an important role, it strikes me that directing efforts to tackle specific symptoms [9] or even autoimmune processes (as per other autoimmune conditions) might yield quite a few benefits for at least some.
Music: The Clash - Rock the Casbah.
----------
[1] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.
[2] Prasher VP. Down syndrome and thyroid disorders: a review. Downs Syndr Res Pract. 1999 Aug;6(1):25-42.
[3] Chen MH. et al. Thyroid dysfunction in patients with Down syndrome. Acta Paediatr Taiwan. 2007 Jul-Aug;48(4):191-5.
[4] Chistiakov D. Down syndrome and coexistent autoimmune diseases. J Applied Biomed. 2007; 5: 71-76.
[5] Mårild K. et al. Down syndrome is associated with elevated risk of celiac disease: a nationwide case-control study. J Pediatr. 2013 Jul;163(1):237-42.
[6] Román GC. et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013 Aug 13. doi: 10.1002/ana.23976.
[7] Brown AS. et al. Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014. 29 October.
[8] Walker JC. et al. Depression in Down syndrome: a review of the literature. Res Dev Disabil. 2011 Sep-Oct;32(5):1432-40.
[9] Hegedüs L. et al. Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto's thyroiditis. Clin Endocrinol (Oxf). 1991 Sep;35(3):235-8.
----------
Worley G, Crissman BG, Cadogan E, Milleson C, Adkins DW, & Kishnani PS (2014). Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. Journal of child neurology PMID: 25367918
Tuesday, 18 November 2014
Paediatric congenital heart disease and autism risk?
"Children aged 2-17 with CHD [congenital heart disease] were more likely than those without CHD to have had a diagnosis of autism spectrum disorder (crude OR, 4.6; 95% CI, 1.9-11.0) or intellectual disability (Crude OR, 9.1; 95% CI, 5.4-15.4)".
That was a key conclusion reported in the study by Hilda Razzaghi and colleagues [1] based on their analysis of data from "the 1997-2011 National Health Interview Survey", a US initiative which aims to provide "information on the health of the U.S. civilian noninstitutionalized population through confidential interviews conducted in households" (see here).
I have to say that I was pretty interested in these findings (even though this is not the first time that neurodevelopmental outcomes have been tied to CHD); a view it seems, that was shared by the authors of the paper, bearing in mind the very wide confidence intervals (CIs) detailed for both conditions and the reliance on second-hand reporting over actual independent screening results. I can't readily offer any one 'smoking gun' explanation for the findings specifically in relation to the autism spectrum but will draw your attention to some discussion about the potential causes of congenital heart disease provided by the NHS Choices websites and how they might tie in.
So: various genetic conditions including Down's syndrome are linked to CHD [2] and the net seems to be closing in on some of the underlying genetics around the association [3]. Although still in need of quite a bit more study, there is a growing appreciation that a diagnosis of autism / autistic traits can coexist alongside a diagnosis of Down's syndrome (see here). As per a recent conversation (thanks Marilyn), one also wonders how this autism - Down's syndrome link might also play out with regards to other areas of the autism research landscape such as dietary effects for example...
Next up is maternal diabetes. As per the NHS Choices entry: "It is estimated that 3 to 6% of women with diabetes who become pregnant will give birth to a baby with a heart defect". Autism and maternal diabetes is an interesting topic which has again cropped up in the autism research literature [4]. If you want my take on the Xu meta-analysis paper and related literature, look no further...
After that is a role for alcohol consumption during pregnancy and mention of the condition called foetal alcohol syndrome (FAS). I have talked about FAS and foetal alcohol spectrum disorder (FASD) before on this blog in the context of autism (see here) but can't readily conclude that the links are overly strong between FAS/FASD and autism presentation.
"A rubella infection can cause multiple birth defects, including congenital heart disease". An interesting association given the history of rubella and autism based to quite a large extent on the work from Stella Chess [5]. I don't know enough about the rate of rubella infection in pregnant women to make any informed statement about how this risk factor might tie into both CHD and autism but the numbers of non-immune women do seem to be quite alarming here in the UK [6].
Influenza during pregnancy? "Women who get flu during the first trimester (three months) of pregnancy are twice as likely to give birth to a baby with congenital heart disease than the general population" according to the NHS Choices website. Regular readers of this blog might already know that I tend to talk quite a bit about how infection - immune system response to infection - during pregnancy seems to have some link to subsequent offspring psychology and development (see here). The link is not altogether straight forward with autism in mind and potentially better related to concepts like fever or fever control [7] but still, there might be more to do here.
The final links - certain medications taken during pregnancy, phenylketonuria (PKU) and exposure to organic solvents during pregnancy - have also, to various extents, been linked to autism (see here and see here for example).
I may very well just be plucking at straws trying to link the causes of CHD with some of the suspected 'causes' of autism (some autism at least) but it strikes me that if one was to further pursue the findings reported by Razzaghi et al those would be the places to start (assuming some shared effect). As per the reports of other physiological findings potentially manifesting alongside a diagnosis of autism (see here), some additional screening of children on the autism spectrum where one or more of the correlates of CHD are suspected might be indicated.
Peter Gabriel and Kate Bush with a beautiful song to close: Don't Give Up.
----------
[1] Razzaghi H. et al. Long Term Outcomes in Children with Congenital Heart Disease: National Health Interview Survey. J Pediatr. 2014 Oct 8. pii: S0022-3476(14)00820-8.
[2] Laursen HB. Congenital heart disease in Down's syndrome. Br Heart J. Jan 1976; 38(1): 32–38.
[3] Ramachandran D. et al. Contribution of copy-number variation to Down syndrome-associated atrioventricular septal defects. Genet Med. 2014 Oct 23. doi: 10.1038/gim.2014.144.
[4] Xu G. et al. Maternal diabetes and the risk of autism spectrum disorders in the offspring: a systematic review and meta-analysis. J Autism Dev Disord. 2014 Apr;44(4):766-75.
[5] Chess S. Follow-up report on autism in congenital rubella. J Autism Child Schizophr. 1977 Mar;7(1):69-81.
[6] Skidmore S. et al. Is the MMR vaccination programme failing to protect women against rubella infection? Epidemiol Infect. 2014 May;142(5):1114-7.
[7] Zerbo O. et al. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord. 2013 Jan;43(1):25-33.
----------
Razzaghi H, Oster M, & Reefhuis J (2014). Long Term Outcomes in Children with Congenital Heart Disease: National Health Interview Survey. The Journal of pediatrics PMID: 25304924
 |
| The traveller @ Wikipedia |
That was a key conclusion reported in the study by Hilda Razzaghi and colleagues [1] based on their analysis of data from "the 1997-2011 National Health Interview Survey", a US initiative which aims to provide "information on the health of the U.S. civilian noninstitutionalized population through confidential interviews conducted in households" (see here).
I have to say that I was pretty interested in these findings (even though this is not the first time that neurodevelopmental outcomes have been tied to CHD); a view it seems, that was shared by the authors of the paper, bearing in mind the very wide confidence intervals (CIs) detailed for both conditions and the reliance on second-hand reporting over actual independent screening results. I can't readily offer any one 'smoking gun' explanation for the findings specifically in relation to the autism spectrum but will draw your attention to some discussion about the potential causes of congenital heart disease provided by the NHS Choices websites and how they might tie in.
So: various genetic conditions including Down's syndrome are linked to CHD [2] and the net seems to be closing in on some of the underlying genetics around the association [3]. Although still in need of quite a bit more study, there is a growing appreciation that a diagnosis of autism / autistic traits can coexist alongside a diagnosis of Down's syndrome (see here). As per a recent conversation (thanks Marilyn), one also wonders how this autism - Down's syndrome link might also play out with regards to other areas of the autism research landscape such as dietary effects for example...
Next up is maternal diabetes. As per the NHS Choices entry: "It is estimated that 3 to 6% of women with diabetes who become pregnant will give birth to a baby with a heart defect". Autism and maternal diabetes is an interesting topic which has again cropped up in the autism research literature [4]. If you want my take on the Xu meta-analysis paper and related literature, look no further...
After that is a role for alcohol consumption during pregnancy and mention of the condition called foetal alcohol syndrome (FAS). I have talked about FAS and foetal alcohol spectrum disorder (FASD) before on this blog in the context of autism (see here) but can't readily conclude that the links are overly strong between FAS/FASD and autism presentation.
"A rubella infection can cause multiple birth defects, including congenital heart disease". An interesting association given the history of rubella and autism based to quite a large extent on the work from Stella Chess [5]. I don't know enough about the rate of rubella infection in pregnant women to make any informed statement about how this risk factor might tie into both CHD and autism but the numbers of non-immune women do seem to be quite alarming here in the UK [6].
Influenza during pregnancy? "Women who get flu during the first trimester (three months) of pregnancy are twice as likely to give birth to a baby with congenital heart disease than the general population" according to the NHS Choices website. Regular readers of this blog might already know that I tend to talk quite a bit about how infection - immune system response to infection - during pregnancy seems to have some link to subsequent offspring psychology and development (see here). The link is not altogether straight forward with autism in mind and potentially better related to concepts like fever or fever control [7] but still, there might be more to do here.
The final links - certain medications taken during pregnancy, phenylketonuria (PKU) and exposure to organic solvents during pregnancy - have also, to various extents, been linked to autism (see here and see here for example).
I may very well just be plucking at straws trying to link the causes of CHD with some of the suspected 'causes' of autism (some autism at least) but it strikes me that if one was to further pursue the findings reported by Razzaghi et al those would be the places to start (assuming some shared effect). As per the reports of other physiological findings potentially manifesting alongside a diagnosis of autism (see here), some additional screening of children on the autism spectrum where one or more of the correlates of CHD are suspected might be indicated.
Peter Gabriel and Kate Bush with a beautiful song to close: Don't Give Up.
----------
[1] Razzaghi H. et al. Long Term Outcomes in Children with Congenital Heart Disease: National Health Interview Survey. J Pediatr. 2014 Oct 8. pii: S0022-3476(14)00820-8.
[2] Laursen HB. Congenital heart disease in Down's syndrome. Br Heart J. Jan 1976; 38(1): 32–38.
[3] Ramachandran D. et al. Contribution of copy-number variation to Down syndrome-associated atrioventricular septal defects. Genet Med. 2014 Oct 23. doi: 10.1038/gim.2014.144.
[4] Xu G. et al. Maternal diabetes and the risk of autism spectrum disorders in the offspring: a systematic review and meta-analysis. J Autism Dev Disord. 2014 Apr;44(4):766-75.
[5] Chess S. Follow-up report on autism in congenital rubella. J Autism Child Schizophr. 1977 Mar;7(1):69-81.
[6] Skidmore S. et al. Is the MMR vaccination programme failing to protect women against rubella infection? Epidemiol Infect. 2014 May;142(5):1114-7.
[7] Zerbo O. et al. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord. 2013 Jan;43(1):25-33.
----------
Razzaghi H, Oster M, & Reefhuis J (2014). Long Term Outcomes in Children with Congenital Heart Disease: National Health Interview Survey. The Journal of pediatrics PMID: 25304924
Sunday, 4 May 2014
Autistic behaviours and Down's syndrome
I believe it is obligatory to say 'May the 4th be with you' today given that it is Star Wars Day. If you prefer the Chewbacca version of this greeting, well take yer pick from his many and varied vocalisations... Even better, ponder how Ming the Merciless might approach the greeting (no, really he's [the actor] gonna be in episode VII).
Anyhow... today I want to talk about the paper by Georgina Warner and colleagues [1] and their quite stark finding that: "The pervasiveness of ASD [autism spectrum disorder] in children with DS [Down's syndrome] in England and Wales is substantially higher than in the general population". Indeed, their finding that over a third of children with Down's syndrome (also called Down syndrome) met the cut-off score for an ASD based on the Social Communication Questionnaire (SCQ) is particularly noteworthy. Alongside some related findings based on results from the Strengths and Difficulties Questionnaire (SDQ) suggestive of an ESSENCE-type scenario of comorbidity pertaining in relation to SCQ positive screen DS cases, there is definitely a need for further investigation in this area.
Down's syndrome (DS) is a condition I'm sure most people will have heard of. I've known about it since early childhood as a consequence of having an extended family member with DS. In more recent times, I've also become interested in John Langdon Down, the physician who gave his name to the condition and how science is progressing when it comes to issues like pregnancy screening for the condition and the implications thereafter (see here) (something which autism research may one day have to face).
Looking at some of the other peer-reviewed literature on the overlap between DS and ASD, a few other details caught my eye:
Outside of the requirement for further examination of the possible relationship between DS and autism, the Warner results also have some very practical implications such as the potential need for greater screening for autism in cases of DS. As the authors note: "the profile of their [DS] autism characteristics on the SCQ was atypical compared with individuals with idiopathic ASD" which might imply that similar to the topic of sex differences in autism presentation, a one-size-fits-all approach is probably not going to be particularly useful. Also, if at all possible, I'd also like to see if the prevalence of autism in DS is showing the same time trend differences as autism witnessed in the general population...?
Music to close. Did you know there ain't no flour in a hundred dollar bill... so said Tex Richman.
----------
[1] Warner G. et al. Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales. Autism Res. 2014. March 24. 10.1002/aur.1371
[2] Magyar CI. et al. An initial evaluation of the Social Communication Questionnaire for the assessment of autism spectrum disorders in children with Down syndrome. J Dev Behav Pediatr. 2012 Feb;33(2):134-45.
[3] Moss J. et al. Prevalence of autism spectrum disorder symptomatology and related behavioural characteristics in individuals with Down syndrome. Autism. 2013 Jul;17(4):390-404.
[4] DiGuiseppi C. et al. Screening for autism spectrum disorders in children with Down syndrome: population prevalence and screening test characteristics. J Dev Behav Pediatr. 2010 Apr;31(3):181-91.
[5] Lowenthal R. et al. Prevalence of pervasive developmental disorder in Down's syndrome. J Autism Dev Disord. 2007 Aug;37(7):1394-5.
[6] Kent L. et al. Comorbidity of autistic spectrum disorders in children with Down syndrome. Dev Med Child Neurol. 1999 Mar;41(3):153-8.
[7] Ghaziuddin M. et al. Autism in Down's syndrome: a family history study. J Intellect Disabil Res. 2000 Oct;44 ( Pt 5):562-6.
[8] Zafeiriou DI. et al. Autism spectrum disorders: the quest for genetic syndromes. Am J Med Genet B Neuropsychiatr Genet. 2013 Jun;162B(4):327-66.
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Warner, G., Moss, J., Smith, P., & Howlin, P. (2014). Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales Autism Research DOI: 10.1002/aur.1371
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| Pizza the Hutt @ cyclonebill @ Wikipedia |
Anyhow... today I want to talk about the paper by Georgina Warner and colleagues [1] and their quite stark finding that: "The pervasiveness of ASD [autism spectrum disorder] in children with DS [Down's syndrome] in England and Wales is substantially higher than in the general population". Indeed, their finding that over a third of children with Down's syndrome (also called Down syndrome) met the cut-off score for an ASD based on the Social Communication Questionnaire (SCQ) is particularly noteworthy. Alongside some related findings based on results from the Strengths and Difficulties Questionnaire (SDQ) suggestive of an ESSENCE-type scenario of comorbidity pertaining in relation to SCQ positive screen DS cases, there is definitely a need for further investigation in this area.
Down's syndrome (DS) is a condition I'm sure most people will have heard of. I've known about it since early childhood as a consequence of having an extended family member with DS. In more recent times, I've also become interested in John Langdon Down, the physician who gave his name to the condition and how science is progressing when it comes to issues like pregnancy screening for the condition and the implications thereafter (see here) (something which autism research may one day have to face).
Looking at some of the other peer-reviewed literature on the overlap between DS and ASD, a few other details caught my eye:
- The Warner paper results, whilst interesting, have to be viewed with some caution insofar as their reliance on the SCD as a screening tool for autism; slightly different from making an actual diagnosis of autism. You may also argue that the presentation of DS might complicate matters when screening/assessing for ASD, but according to the results from Magyar and colleagues [2], the SCD in particular does seem fit for purpose.
- Joanna Moss, one of the co-authors on the Warner paper, has previously looked into the presentation of ASD in DS [3], again relying on the SCD. Whilst the numbers reaching the SCD cut-offs for autism and ASD were quite a few percentage points lower on that occasion compared with the recent data, they are still eye-catching.
- Just on the topic of the estimated prevalence of autism/ASD in DS, the paper by DiGuiseppi and colleagues [4] makes for some interesting reading: "Weighted prevalences of autistic disorder and total ASD were 6.4% (95% confidence interval [CI]: 2.6%-11.6%) and 18.2% (95% CI: 9.7%-26.8%), respectively". These figures aren't a million miles away from other data such as that reported by Lowenthal and colleagues [5] and the estimate by Kent and colleagues [6] who stated: "The comorbid occurrence of autism and DS is at least 7%".
- Perhaps one of the most useful research points to take from the suggestion of a heightened risk of autism in cases of DS is the possibility that there may be shared genetic or biological variables which predispose a person to both conditions. The paper by Ghaziuddin [7] kinda hints at this when reporting participants "with both DS and autism had an excess of first-degree relatives who met the description of the broader phenotype of autism". The fact however that autism is not universally detected in DS means that we have to be a little careful not to inflate this argument too much. That also autism has been linked to other genetic conditions such as NF1 (see here) and SLOS (see here) to name but a few [8], means that fragility is probably going to a bigger factor over and above certainty. That and the increasingly important pluralisation(?) of autism to take into account.
Outside of the requirement for further examination of the possible relationship between DS and autism, the Warner results also have some very practical implications such as the potential need for greater screening for autism in cases of DS. As the authors note: "the profile of their [DS] autism characteristics on the SCQ was atypical compared with individuals with idiopathic ASD" which might imply that similar to the topic of sex differences in autism presentation, a one-size-fits-all approach is probably not going to be particularly useful. Also, if at all possible, I'd also like to see if the prevalence of autism in DS is showing the same time trend differences as autism witnessed in the general population...?
Music to close. Did you know there ain't no flour in a hundred dollar bill... so said Tex Richman.
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[1] Warner G. et al. Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales. Autism Res. 2014. March 24. 10.1002/aur.1371
[2] Magyar CI. et al. An initial evaluation of the Social Communication Questionnaire for the assessment of autism spectrum disorders in children with Down syndrome. J Dev Behav Pediatr. 2012 Feb;33(2):134-45.
[3] Moss J. et al. Prevalence of autism spectrum disorder symptomatology and related behavioural characteristics in individuals with Down syndrome. Autism. 2013 Jul;17(4):390-404.
[4] DiGuiseppi C. et al. Screening for autism spectrum disorders in children with Down syndrome: population prevalence and screening test characteristics. J Dev Behav Pediatr. 2010 Apr;31(3):181-91.
[5] Lowenthal R. et al. Prevalence of pervasive developmental disorder in Down's syndrome. J Autism Dev Disord. 2007 Aug;37(7):1394-5.
[6] Kent L. et al. Comorbidity of autistic spectrum disorders in children with Down syndrome. Dev Med Child Neurol. 1999 Mar;41(3):153-8.
[7] Ghaziuddin M. et al. Autism in Down's syndrome: a family history study. J Intellect Disabil Res. 2000 Oct;44 ( Pt 5):562-6.
[8] Zafeiriou DI. et al. Autism spectrum disorders: the quest for genetic syndromes. Am J Med Genet B Neuropsychiatr Genet. 2013 Jun;162B(4):327-66.
----------
Warner, G., Moss, J., Smith, P., & Howlin, P. (2014). Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales Autism Research DOI: 10.1002/aur.1371
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