Pregnancy vitamin D supplementation and offspring autism risk

Although I'm pretty interested in the idea that the sunshine vitamin/hormone known as vitamin D might have quite a few more biological effects than previously appreciated (see here), I accept that the findings reported by Gene Stubbs and colleagues [1] are probably not going to be everyone's cup of tea.

With the aim of testing the hypothesis of "whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD [autism spectrum disorder] in the offspring" based on some external findings (see here), researchers set about the task. I think I might have mentioned this trial protocol in a post not-so-long-ago (see here). They relied on a prospective study method to follow 20 mothers "who had one or more children who had been diagnosed with autism by a physician or psychologist and who were pregnant in the first, second or early third trimester." The risk of familial recurrence for autism by the way, is estimated at around about 10% (see here) with some important caveats (see here).

Said mothers were initially tested for "25 hydroxy D3 levels (25 OHD) and serum calcium levels" and then prescribed "5000 IU [international units] D3/day during the pregnancy and 7000 IU D3/day while breastfeeding." Various birth outcomes were assessed, and at 18 months and 3 years of age researchers relied on a couple of screening instruments pertinent to the presentation of autism: the Modified Checklist for Autism in Toddlers (M-CHAT) and the Pervasive Developmental Disorder Behavior Inventory (PDDBI).

What happened? Well, one mother and child pair withdrew from the study so the final participant number was 19. In terms of vitamin D deficiency during pregnancy: "Only two [mothers] were in the deficient range of less than 20 ng/ml of 25 OHD when starting vitamin D." At the second time of vitamin D testing (2 months after the first testing occasion), none of the mums where data were available (n=18) were in that deficient range defined as less than 20ng/ml. Interestingly though, I counted at least three mothers whose second vitamin D test scores were lower than the first testing occasion. You could quibble about pregnancy effects on vitamin D levels or the reliability of the vitamin D assay, but on that last point at least, these were all measured "using liquid chromatography/mass spectrometry (LC–MS/MS) methodology" so the 'gold-standard' for assaying assuming accurate measurement [2]. The question about compliance to the prescribing regime is one area however, not commented on in the publication.

In terms of those autism screens at 18 months and 3 years of age: "17 of 19 (89%) pass the MCHAT screening test at 18 months of age, that is, they were negative for autism." Further: "17 of 19 (89%) pass the PDDBI diagnostic questionnaire at 3 years of age. Eighteen of 19 (95%) had a final diagnosis as not having autism." The authors concluded that their findings were evidence of "a reduction in the recurrence rate of autism in newborn siblings compared to the reported recurrence rate in the literature of about 20%." A 20% recurrence rate? Well, as I've previously mentioned, I'd put it closer to 10% but am willing to accept some variation listed in the peer-reviewed literature [3].

There are some other very interesting details included in the Stubbs data; dare I say even more important than the main findings. So: "The two children in our study who developed autism as diagnosed by the PDDBI, both regressed following an infection." Illness including "bilateral ear infections" is mentioned, tapping into another potentially really important area of the autism research landscape (see here) and including the issue of regression (see here). That gastrointestinal (GI) issues are also mentioned - "The symptoms of autism seemed to coincide with the severity of GI problems. As the GI symptoms got more severe, the symptoms of autism got more severe. As the GI symptoms improved, so did the autism symptoms" - is something crying out for much more detailed study beyond the subjective descriptions offered in this paper. As regular readers might know, GI issues accompanying autism are no longer the taboo subject they used to be (see here) but still require lots more study particularly with a view to the hows and whys and what options for management are available. And yes, this is on top of the Buie et al guidance (see here) already available and more recent findings [4] (blog post to follow on these soon).

From a methodological point of view, the small number of participants and the lack of any 'control' group reported on, means the Stubbs study/results are not perfect and easy to pick holes in. I'm sure some people will do just that; even pointing out the publishing journal too (see here). I personally am interested to see how this area progresses further from a scientific point of view. Similar to other suggestions that pregnancy use of folic acid for example, *might* affect offspring risk of autism (see here), I don't envisage a straight-forward relationship appearing but this may not be unexpected in these times of plural autisms (see here). I'm also mindful of the implications of a potential 'screening test for autism' where vitamin D may, at some point, be potentially included (see here) and what this might mean to quite a few people on the autism spectrum and their families.

Research into vitamin D and autism seemingly continues at a pace [5]...

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[1] Stubbs G. et al. Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? Medical Hypotheses. 2016; 88: 74-78.

[2] Yang Y. et al. High-throughput measurement of 25-hydroxyvitamin D by LC-MS/MS with separation of the C3-epimer interference for pediatric populations. Clin Chim Acta. 2016 Feb 15;454:102-6.

[3] Wood CL. et al. Evidence for ASD recurrence rates and reproductive stoppage from large UK ASD research family databases. Autism Res. 2015 Feb;8(1):73-81.

[4] Kushak RI. et al. Evaluation of Intestinal Function in Children with Autism and Gastrointestinal Symptoms. J Pediatr Gastroenterol Nutr. 2016 Feb 20.

[5] Shan L. et al. Research advances in the role of vitamin D in autism spectrum disorders. Zhongguo Dang Dai Er Ke Za Zhi. 2016 Feb;18(2):183-8.

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Stubbs, G., Henley, K., & Green, J. (2016). Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? Medical Hypotheses, 88, 74-78 DOI: 10.1016/j.mehy.2016.01.015

SCQ vs. M-CHAT for autism screening: no winner

"While screening tests may provide useful information, their accuracy is moderate. Screening information in isolation should not be used to make referral decisions regarding specialized ASD [autism spectrum disorder] assessment."

That was the findings of the study published by Tony Charman and colleagues [1] who sought to "test the accuracy of two screening instruments in UK Community health services: Modified Checklist for Autism in Toddlers (M-CHAT) and Social Communication Questionnaire (SCQ) for autism spectrum disorder (ASD)."

Looking at referrals to "speech and language therapy services in two London districts over a 12-month period between September 2004 and September 2005" researchers initially had screen data for over 540 children (aged between 18 and 48 months) which was subsequently whittled down to a "stratified subsample of 120 children" who then  received an in-depth assessment for possible ASD based on ICD-10 criteria. We are also told that: "Community clinician judgement of likely ASD was available for 98 out of the 120 children."

Based on that in-depth assessment for ASD, data is presented on the performance of the SCQ and/or M-CHAT as part of the instigator of said assessment. The data don't read particularly well. Measures of sensitivity and specificity (also called the 'true positive' and 'true negative' rate) were mediocre at best; for example, the specificity of the M-CHAT came in at 50% (33-64%). The SCQ did slightly better on that particular parameter but it has to be said, still not great. The authors conclude: "The screening tests did not perform well to confirm preliminary clinical judgement to refer (in series), nor as an alternative indicator for referral (in parallel)."

I've been interested in autism screening (early autism screening) for quite a while on this blog. The peaks and troughs of autism research in this area are quite evident (see here) and have perhaps been contributory to recent going-ons in the United States for example, with the Preventive Services Task Force asking for more evidence to support universal screening for autism in young children who show no developmental issues.

There are issues to iron out here, based on what questions to ask (see here) when considering screening as well as understanding that variables such as regression can influence age of onset (see here); particularly relevant to the removal of specific age of onset limits with the latest manifestation of DSM (see here). One factor that I would also perhaps like to see more attention given to is parents as agents of screening and referral (see here). That and further consideration of the how good/bad (delete as appropriate) the pre-diagnostic experience might be (see here) and lots more questions need to be answered.

And as I write, lo and behold a possible new player in the autism screening stakes [2]?

Music: Robert Palmer - Addicted To Love.

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[1] Charman T. et al. Testing two screening instruments for autism spectrum disorder in UK community child health services. Dev Med Child Neurol. 2015 Aug 25.

[2] Grodberg D. et al. A Simplified Diagnostic Observational Assessment of Autism Spectrum Disorder in Early Childhood. Autism Res. 2015 Aug 25.

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Charman T, Baird G, Simonoff E, Chandler S, Davison-Jenkins A, Sharma A, O'Sullivan T, & Pickles A (2015). Testing two screening instruments for autism spectrum disorder in UK community child health services. Developmental medicine and child neurology PMID: 26303216

Screening for autism in young children: 6 questions to ask

Question 1: Does your child ever point with their index finger to ask for something?
Question 2: Is your child able to imitate you or your actions, for example if you pull a face?
Question 3: Does your child ever use pretend play, for example to talk on a phone or take care of a doll?
Question 4: Does your child look at something across a room when you point to it?
Question 5: Does your child understand what people say?
Question 6: Does your child ever bring an object to you to show you something?

The paper from Yoko Kamio and colleagues [1] (open-access) suggests that these 6 questions taken from the 23-item M-CHAT Japanese version (JV) might have the methodological strength to screen for possible autism in toddlers -- at least in Japan. M-CHAT by the way, is one of the instruments of choice when it comes to screening for possible autism and has seen some developments in recent times (see here).

Based on data derived from "two prospective community cohorts in Japan, Fukuoka (cohort 1) and Tokyo (cohort 2)" cumulatively including some 2500 children "who received health check-ups when aged 18 months", researchers analysed data using a model of discriminant function analysis based on groupings of those who were eventually diagnosed with an autism spectrum disorder (ASD) compared with those who weren't. They concluded that their study "identified a highly discriminative 6-item set from the 23-item M-CHAT-JV and demonstrated its reliability and validity with cohort data from 2 geographically different regions in Japan." The results, I might add, were not 100% reliable in terms of the 6-item screening method used, but this is real life and, as far as I am aware, we don't have a perfectly reliable autism screen at the moment.

These are interesting results as a function of the important autism science on the best way to 'red flag' autism in its very earliest days (see here). Indeed, the focus on social-communicative functions (including pointing) follows a trend in the peer-reviewed research literature in this area, as something to focus on when it comes to early screening for autism. I say this bearing in mind that within the very heterogeneous label of autism, there are cases of regression into autism at a time later than 18 months.

"Considering the tight time constraints in primary care settings, a brief screening tool might be helpful in facilitating the integration of autism-specific screening within routine general developmental screening." These are noble sentiments from the authors and kinda accords with some increasing moves in autism practice to make things more streamlined in these resource-austere times that we live in (see here). Obviously we await further research in this area on whether the Kamio findings cross cultures and geographies with other infant cohorts or not. If they do however, combined with the rise and rise of telemedicine for example, the days of the [often] long and expensive autism screening and diagnosis process might be numbered. Oh, and screening might just start to be interactive too [2] (see here for more information on the RITA-T).

Music: iLL BLU - Lonely People ft. James Morrison.

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[1] Kamio Y. et al. Brief Report: Best Discriminators for Identifying Children with Autism Spectrum Disorder at an 18-Month Health Check-Up in Japan. Journal of Autism and Developmental Disorders. 2015. July 19.

[2] Choueiri R. & Wagner S. A New Interactive Screening Test for Autism Spectrum Disorders in Toddlers. J Pediatr. 2015 Aug;167(2):460-466.

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Kamio, Y., Haraguchi, H., Stickley, A., Ogino, K., Ishitobi, M., & Takahashi, H. (2015). Brief Report: Best Discriminators for Identifying Children with Autism Spectrum Disorder at an 18-Month Health Check-Up in Japan Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2527-1

Screening for autism in preterm infants

"A positive screen on the M-CHAT [Modified Checklist for Autism in Toddlers] occurs more commonly in very preterm infants than those born at term."

So said the study by Peter Gray and colleagues [1] as the topic of preterm status - that is, babies born alive before 37 weeks of pregnancy - potentially being linked to a greater risk of autism or at least, increased risk of screening positive for autism, crops up yet again on this blog (see here).

Gray et al examined a cohort of children born at the very boundaries of the definition of preterm ("≤30weeks gestation") when aged 2 years old, questioning mums of preterm children (n=97) and mums of term infants (n=77) with a whole range of questionnaires / schedules including the M-CHAT and the Child Behaviour Checklist (CBCL) among other things. "Previously collected data from the mothers at 12months - the Edinburgh Postnatal Depression Scales (EPDS)" were also analysed.

Authors reported that a higher percentage of preterm kids "screened positive on the M-CHAT" compared with term controls (13.4% vs. 3.9% respectively). These statistics decreased somewhat as a consequence of "an M-CHAT follow-up interview by phone" with only one child with membership of the preterm group subsequently receiving a diagnosis of autism from the entire cohort. The authors discuss some of the whys and wherefores of those pretermers who initially screened positive on the M-CHAT and how they were: "born to younger, non-Caucasian mothers and were of lower birth weight and had a higher incidence of being small for gestational age."

As per my discussion on the paper by Alexa Guy and colleagues [2] (see here again), the message coming through about using M-CHAT with the preterm population is again one of 'use with caution'. Indeed, the Gray paper illustrates how the follow-up consultation is a pretty important part of M-CHAT, something further developed on by the findings from Diana Robins and colleagues [3] and the whole M-CHAT-R/F thing (see here). I wouldn't necessarily say that M-CHAT is completely useless as a screen for autism under certain conditions. Merely that looking for the early red flags that might denote autism is very much still a work in progress potentially confounded by length of gestation. YouTube video anyone?

Music: PJ Harvey- The Words That Maketh Murder.

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[1] Gray PH. et al. Screening for autism spectrum disorder in very preterm infants during early childhood. Early Hum Dev. 2015 Mar 9;91(4):271-276.

[2] Guy A. et al. Infants Born Late/Moderately Preterm Are at Increased Risk for a Positive
Autism Screen at 2 Years of Age. J Pediatrics. 2014. 5 December.

[3] Robins DL. et al. Validation of the modified checklist for Autism in toddlers, revised with follow-up (M-CHAT-R/F). Pediatrics. 2014 Jan;133(1):37-45.

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Gray PH, Edwards DM, O'Callaghan MJ, & Gibbons K (2015). Screening for autism spectrum disorder in very preterm infants during early childhood. Early human development, 91 (4), 271-276 PMID: 25766314

Late/moderately preterm kids at risk for a positive autism screen

If you're sick of the sight of tinsel and/or turkey (delete as appropriate), I promise no more mention of them in this post. Just a brief introduction to the the paper by Alexa Guy and colleagues [1] (open-access) who concluded that: "LMPT [late and moderately preterm] infants are at significantly increased risk for positive autistic screen."

Megamind, incredibly handsome criminal
genius and master of all villainy!

Based on the [final] analysis of data from some 600 LMPT infant and 760 term-born infants taking part in a study initiative here in the UK, researchers looked at M-CHAT (Modified Checklist for Autism in Toddlers) scores derived from parental questioning when the child was 2 years old. They found: "LMPT infants were at significantly increased risk for a positive M-CHAT questionnaire screen compared with term-born infants, and this remained significant after application of the follow-up interview and exclusion of infants with neurosensory impairments." Further that their findings: "provide empirical evidence that screening for ASD is especially confounded in preterm populations" as a function of the the high false-positive rate found compared against the term-born controls.

M-CHAT has cropped up a few times on this blog (see here for example). In recent times, the schedule has undergone a bit of (further) revision, evolving into the M-CHAT-R/F [2] (see here for further details) to further improve on its sensitivity statistics when it comes to assessing risk of an autism spectrum disorder (ASD). Indeed, as per the Guy quote: "An M-CHAT follow-up interview is essential as screening for autism spectrum disorders is especially confounded in preterm populations" one can perhaps see where M-CHAT R/F might be particularly handy for further study of this important group.

These results add to an already sizeable volume of peer-reviewed research literature hinting that the timing of our very earliest introduction into the world might influence risk of neurodevelopmental issues such as autism and/or a positive screen for potential autism. That being said, the various factors linked to time in-utero such as birth weight as potentially impacting on development illustrate how complex an issue this might be. How we screen for autism in among the various complexities of preterm births (and lower birth weight) remains a question on many people's minds, including the possibility of using more than one instrument [3].

Music to close: Norwegian Wood.

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[1] Guy A. et al. Infants Born Late/Moderately Preterm Are at Increased Risk for a Positive
Autism Screen at 2 Years of Age. J Pediatrics. 2014. 5 December.

[2] Robins DL. et al. Validation of the modified checklist for Autism in toddlers, revised with follow-up (M-CHAT-R/F). Pediatrics. 2014 Jan;133(1):37-45.

[3] Dudova I. et al. Comparison of three screening tests for autism in preterm children with birth weights less than 1,500 grams. Neuropsychiatr Dis Treat. 2014 Nov 17;10:2201-2208.

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Guy, A., Seaton, S., Boyle, E., Draper, E., Field, D., Manktelow, B., Marlow, N., Smith, L., & Johnson, S. (2014). Infants Born Late/Moderately Preterm Are at Increased Risk for a Positive Autism Screen at 2 Years of Age The Journal of Pediatrics DOI: 10.1016/j.jpeds.2014.10.053

Vitamin D supplement improves autistic behaviours?

I don't want to get too ahead of myself with this post talking about the paper by Feiyong Jia and colleagues [1] (open-access) who concluded: "Vitamin D supplementation may be effective in ameliorating the autistic behavioral problems in children with autism spectrum disorders [ASDs]".

The idea however that issues with vitamin D seemingly present in quite a few cases of ASD [2] (see here too) but not all [3] might actually have more direct consequences for behavioural presentation is something which is deserving of quite a bit more experimental study. I'm minded to suggest that the paper by Frighi and colleagues [4] might also be relevant here given the heightened prevalence of intellectual disability associated with (some) autism.

"The light that burns twice as
bright burns half as long"

I'll admit that I have not been able to fully take in all the details of the Jia paper given that it is published in Chinese. But looking at the abstract and using a translation tool for the full-text version ("OK Google, translate..."), a few things were seemingly apparent:

• This is a case report detailing the clinical experiences of a young boy aged 32 months who fitted the DSM-IV criteria for an ASD. Apparently there is some interest in vitamin D and autism at the authors' affiliated institution (see here).
• As part of some biological work-up the young boy was found to present with low levels of vitamin D (serum 25 (OH) D) (14.3 ng/ml). Depending on how you would define adequate vitamin D levels, this value would probably reflect deficiency (see here).
• Treatment of the vitamin D deficiency followed involving an injection of 150,000 IU (international units) of vitamin D3 combined with daily 400 IU of vitamin D3 administered by mouth. The authors note that no other treatment was provided at this time.
• At 2 months, behaviour was reassessed by CARS and M-CHAT among things, and serum 25 (OH) D levels examined again. Vitamin D levels had increased to 51.8 ng/ml which put him within the normal concentration range. Allied to this increase, autistic symptoms were also noted to have improved. The authors suggest that their results warrant further, larger and more controlled, study, something which appears to have already started [5].

Before anyone gets the idea that I'm advocating vitamin D3 injections for autism or anything else, I would very much like to reiterate the authors' point about needing further research in this area bearing in mind the more typical relationship between vitamin D and something like bone health for example. The recent guidance from the American Academy of Pediatrics (AAP) on optimising bone health in children and adolescents [6] might also be pertinent. The use of 150,000 IU of vitamin D has also been discussed previously in the more general peer-reviewed literature [7] particularly if and when compliance to an oral treatment regime might be poor. But that still does not mean that I'm advocating anything at this time.

I'm afraid that I cannot readily offer any specific biological reasons why vitamin D supplementation might tie into the symptom improvements noted in the Jia study given the seemingly wide range of systems showing some involvement for the sunshine vitamin/hormone. I could speculate about certain processes being potentially affected (see here) which might be relevant to cases of autism but won't say too much more about that at this time. This might be a good point to also drop in the paper by Sarah Hanieh and colleagues [8] (open-access) talking about maternal vitamin D levels and offspring language scores as potentially being pertinent.

I should reiterate that the Jia paper was based on an individual case report so one has to perhaps be slightly weary of any effect being potentially applicable to others nor solely due to vitamin D. This, particularly given the receipt of a diagnosis of ASD at baseline and what this might have meant for things like education and the use of less-formal intervention options over the course of the study period.

That all being said, I continue to find the reported results interesting [9] if not just from the perspective of autism to more general health and wellbeing...

Classical music to close and since we're not so far from there: remember, remember the 5th of November, the gunpowder treason and plot... (and the world according to 'V').

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[1] Jia F. et al. Vitamin D Supplementation Improves Autistic Symptoms in a Child with Autism
Spectrum Disorder. Asian Case Reports in Pediatrics. 2014; 2: 21-24.

[2] Pioggia G. et al. Autism and lack of D3 vitamin: A systematic review. Research in Autism Spectrum Disorders. 2014; 8: 1685-1698.

[3] Uğur C. & Gürkan CK. Serum vitamin D and folate levels in children with autism spectrum disorders. Research in Autism Spectrum Disorders. 2014; 8: 1641-1647.

[4] Frighi V. et al. Vitamin D deficiency in patients with intellectual disabilities: prevalence, risk factors and management strategies. Br J Psychiatry. 2014 Sep 25. pii: bjp.bp.113.143511.

[5] Ucuz II. et al. The relationship between Vitamin D, autistic spectrum disorders, and cognitive development: do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship? International Journal of Developmental Disabilities. 2014. DOI: http://dx.doi.org/10.1179/2047387714Y.0000000054

[6] Golden NH. et al. Optimizing Bone Health in Children and Adolescents. Pediatrics. 29 Sept.

[7] Munns C. et al. Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement. Med J Aust. 2006 Sep 4;185(5):268-72.

[8] Garland CF. et al. Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Public Health. 2014 Aug;104(8):e43-50.

[9] Hanieh S. et al. Maternal vitamin D status and infant outcomes in rural Vietnam: a prospective cohort study. PLoS One. 2014 Jun 26;9(6):e99005.

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贾, �. (2014). Vitamin D Supplementation Improves Autistic Symptoms in a Child with Autism Spectrum Disorder Asian Case Reports in Pediatrics, 02 (03), 21-24 DOI: 10.12677/ACRP.2014.23005

The [universal] early identification of autism or not?

As I might have already intimated, whilst I'm all in favour of the very early identification of autism and the potential effects this might bring to a child in terms of something like benefiting from early intervention, I'm not overly enthused by the collected evidence which has been amassed so far in this area despite some promising data.

Under my umbrellas @ Wikipedia 

Most people with some knowledge of autism will know that it is an extremely heterogeneous condition, with presentation also seemingly tied up with the risk of various other comorbidity appearing alongside. That autism also seems to include an element of regression for quite few on the spectrum, means that the holy grail that is very early red flags hinting at the earliest manifestation(s) of autism is going to be a difficult universal concept to find. Also complicated by various other factors including ethnicity, issues around the possible stability of symptoms in the early years and the possibility of plural autisms. Oh and healthcare providers can, on occasion, be barriers themselves too (see here).

Two papers recently caught my eye on this topic, coming to quite different conclusions.

The first paper by Samango-Sprouse and colleagues* based on an impressive participant number (N=1024) reported that their "study demonstrates an efficient means to identify infants at risk for autism spectrum disorder by 9 months of age and serves to alert primary care providers of infants who are vulnerable for autism spectrum disorder before symptoms are discernible by clinical judgment of primary care providers, parental concerns, or by screening questionnaires". They arrived at this conclusion on the basis of "abrupt head circumference acceleration and the absence of head tilt reflex by 9 months were used to identify infants at risk for autism spectrum disorder". So, with some more work to do, looking at head size and the head tilt reflex might be something to watch for in subsequent publications.

The second paper by Stenberg and colleagues** including an authorship list of the great and good of autism research (including Drs Hornig and Lipkin) came to a rather different conclusion based on the behavioural identification of children aged 18 months as likely having autism: "results imply that it might not be possible to detect all children with ASD at this age". Their participant size was even more impressive.

Of course I am kinda looking at apples and pears in comparing these two findings. The Samango-Sprouse study looking at something rather more physiological than behavioural, as compared to the Stenberg findings which was putting the M-CHAT (Modified Checklist for Autism in Toddlers) screening tool through it's paces based to a large part on the MoBa cohort. Again, with ear to the autism research ground, some people might remember that M-CHAT (itself a revision of the CHAT) has gone through even more adaptation fairly recently with the Diana Robins paper*** talking about M-CHAT-R/F (see here for more details). One therefore wonders if the Stenberg findings are already out-of-date even before they were published?

Insofar as the issue of rapid head circumference acceleration being potentially linked to the development of autism, well, we know the topic of head size and autism is a complicated one (see this previous post). I'm also thinking back to the work that came out the MIND Institute a couple of years back, which suggested that brain enlargement in relation to autism might show some link to the issue of regression (see here) at least for some types of autism. Quite how this data (if reproduced) would impact on the Samango-Sprouse findings is still unclear.

Don't get me wrong, the issue of early red flags potentially pointing to autism is a very, very important area of autism research. Every once in a while one hears about some ground-breaking research that a new marker for autism is on the horizon - see Jon Brock's post one example of this a few months back - but more often than not, nothing further comes of such research. What perhaps I would like to see more of in this area are a few things:

• some better appreciation for 'the autisms' over the singular concept of autism (and different developmental profiles / red flags potentially being present across different sub-groups?),
• greater amalgamation of various sources of information, behavioural and physiological, to see if looking at overt signs and symptoms together with something like head growth charts, might actually yield more real-world effects in combination. Although seemingly forgotten, the issue of airway anatomy and autism (no, really) might also be something to include here alongside other early markers that have been previously suggested.

Oh, and remember that at least one of the diagnostic schedules to denote autism or not has recently gone through a bit of a change, so one waits to see how this might affect all this early identification talk too.

Music to close. Having seen the Lego Movie not-so-long ago with some of my brood, I can very much recommend it for all ages. And just remember: everything is awesome...

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* Samango-Sprouse CA. et al. Identification of infants at risk for autism spectrum disorder and developmental language delay prior to 12 months. Autism. 2014 Feb 18.

** Stenberg N. et al. Identifying Children with Autism Spectrum Disorder at 18 Months in a General Population Sample. Paediatr Perinat Epidemiol. 2014 Feb 18.

*** Robins DL. et al. Validation of the modified checklist for Autism in toddlers, revised with follow-up (M-CHAT-R/F). Pediatrics. 2014 Jan;133(1):37-45.

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Samango-Sprouse CA, Stapleton EJ, Aliabadi F, Graw R, Vickers R, Haskell K, Sadeghin T, Jameson R, Parmele CL, & Gropman AL (2014). Identification of infants at risk for autism spectrum disorder and developmental language delay prior to 12 months. Autism : the international journal of research and practice PMID: 24550549



Stenberg N, Bresnahan M, Gunnes N, Hirtz D, Hornig M, Lie KK, Lipkin WI, Lord C, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Surén P, Susser E, Svendsen BK, von Tetzchner S, Oyen AS, & Stoltenberg C. (2014). Identifying Children with Autism Spectrum Disorder at 18 Months in a General Population Sample Paediatr Perinat Epidemiol. DOI: 10.1111/ppe.12114