"Suicidal spectrum behaviors" and ADHD meta-analysed

"Awareness of the association between ADHD [attention-deficit hyperactivity disorder] and SSBs [suicidal spectrum behaviors] should contribute to more effectively prevent SSBs."

That was the conclusion reached in the study published by Mathilde Septier and colleagues [1] and the results of their "first meta-analysis on the association between ADHD and SSBs taking possible confounders into account." Their systematic review and meta-analysis was preregistered (see here) so we knew it would be coming.

Starting with nearly 3000 references, the available data was whittled down to just over 50 studies. The data were analysed and boiled down to reveal "a significant association between ADHD and suicidal attempts..., suicidal ideations..., suicidal plans..., and completed suicide."

What's more to say? Well such results although stark are not completely unexpected given what has already been discussed on this blog on this topic (see here and see here and see here). They serve to confirm that a diagnosis of ADHD (or even the presentation of subclinical ADHD symptoms?) should really set in motion some preferential screening for suicidal spectrum behaviours and appropriate support offered as and when detected. Minus any sweeping generalisations, such results also invite further inquiry into how certain intervention options indicated for ADHD *might* also affect risk of suicidality in the context of ADHD (see here).

If you need someone to talk to, there are organisations out there...

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[1] Septier M. et al. Association between suicidal spectrum behaviors and Attention-Deficit/Hyperactivity Disorder: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2019 May 23. pii: S0149-7634(18)30941-2.

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Managing ADHD: pharmacotherapy use and quality of life

"The QoL [quality of life] of the children with ADHD [attention-deficit hyperactivity disorder] and the subjective well-being of the parents improved significantly after introducing pharmacotherapy."

That was the research 'bottom line' described by Hanife Temizsoy and colleagues [1] following the publication of their study results designed to "investigate the changes of QoL of children with ADHD and their parents' subjective well-being before and after starting pharmacotherapy." Pharmacotherapy is the fancy word for medication; and the Temizsoy findings add to quite a large bank of peer-reviewed research suggesting that some medicines 'for ADHD' have a pretty good benefit-risk profile (see here). Indeed, the use of indicated medicines for ADHD seems to have some good potential for decreasing various future risks that seem to follow a diagnosis of ADHD (see here and see here).

"We assessed the QoL and the parental well-being in 60 children and adolescents with ADHD between the ages of 6 and 12 years." Various questionnaires were utilised, including the KINDL designed to assess "Health-Related Quality of Life in children and adolescents aged 3 years and older" and "the World Health Organization (WHO) Big Five Questionnaire", a short questionnaire on (current) well being. The results obtained were encouraging.

Bearing in mind that the Temizsoy was a straightforward 'before and after' study lacking important methodological features such as blinding and objective measures from physicians or other objective viewers for example, the results are important. I'm also minded to add that whilst certain medicines indicated for ADHD do seem to have quite a good track record for improving features of the condition, they are not without potential side-effects as per just about every other medicine in existence.

But... if children with ADHD and their parents/carers are reporting that their quality of life is getting better with medication compared to times without medication, surely this counts for something. With regular monitoring, good medicines management and possibly alongside the use of other potential intervention options (see here and see here for examples), ADHD for many people, is a condition that can be managed and managed well.

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[1] Temizsoy H. et al. Influence of Psychopharmacotherapy on the Quality of Life of Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2019 Mar 29.

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"This study provides important information about psychiatric comorbidity in adult ASD" (again)

The quote titling this post - "This study provides important information about psychiatric comorbidity in adult ASD [autism spectrum disorder]" - comes from the findings published by Jack Underwood and colleagues [1] (open-access available here).

The Underwood study is a bit of a mash-up paper because, alongside examining things like psychiatric comorbidity and other features accompanying or allied to 'adult autism', it also ventures into the possible genetics of autism. Unfortunately, the relatively small sample size - "105 eligible individuals were matched to 76 healthy controls" (authors words not mine) - means that the genetic results in particular need to be treated with some caution. With this in mind, I'm not going to go further into this side of the Underwood report.

So: "105 individuals were all confirmed to have an ASD diagnosis consistent with ICD-10 criteria by case-note review" were the cohort included for study, all derived from the National Centre for Mental Health institution based in Wales. Interviews and questionnaires were disseminated, covering topics like marriage and employment status alongside questions on 'biological offspring' (children, to you and me). Participants were questioned about psychiatric comorbidity (as in, did they have any diagnoses) as well as medication use and substance use/abuse. We are told that: "By definition, control participants did not have psychiatric morbidity and were not using any psychotropic medication."

"Comorbid psychiatric diagnosis was reported by 89.5% (n = 94) of individuals with ASD." If you would have told me that statistic about 10 or 15 years ago I might have been shocked. These days such figures, high figures, on psychiatric comorbidity accompanying autism seem to be reported on almost a weekly basis. I don't say that to downplay the effects of such high comorbidity; just that there is little novelty in their discovery (see here and see here) particularly the high rates of depression and anxiety that were picked up (see here). Oh, and once again I'll question whether the word 'comorbidity' is entirely accurate in the context of various issues appearing alongside autism (see here).

Medication use? Yes, as probably expected, there was quite a bit of that, particularly antidepressants, anxiolitics (for anxiety) and antipsychotics in the autistic group. Again, there's little novelty in those findings (see here) but they do reiterate the need for regular monitoring and good medicines management (see here).

Onward: "Adults with ASD were significantly less likely to be currently working..., to be married or cohabiting..., to be currently off work because of sickness or disablement... and to have alcohol-related problem." Yes, there was more overlap with other independent findings in some of those areas (see here and see here for examples) but also some quite important details. Take for example the category termed 'problems due to alcohol use' which was reported by 36% of the autistic group compared with 8% of controls. Although not exactly great PR for the label of autism, there is an emerging understanding that alcohol use and abuse does seem to be over-represented alongside a diagnosis of autism (see here). The authors opine that this "could be usage to self-medicate for the aforementioned anxiety as suggested by other authors, or to facilitate social interactions" but really we need lots more data about this and the long-term effects of such 'self-medication' if that's what it truly is.

Another details also stuck out for me: "Forty-one (42.7%) individuals with ASD reported lifetime history of migraine headaches compared with 15 (20.5%) control participants." Migraine headaches (or even just headaches) have been talked about before on this blog in the context of autism (see here). With such a large percentage of participants with autism talking about this issue, I'm minded to suggest that a lot more investigation is needed in this area.

There is little in the way of new, novel findings in the Underwood paper but I don't want readers to think that this is a not a valuable addition to the peer-reviewed science literature. It is, simply because it continues important conversations about (a) the presentation of autism into adulthood (see here), (b) the idea that autism rarely appears in some sort of diagnostic vacuum (see here), and (c) the various inequalities - health and social - faced by those on the autism spectrum. What however I would like to see more of is research on 'what helps' to iron out some of these important issues and how services can be effectively delivered. Alongside we need some debates about funding too.

And just before I go, the focus on autism "and no self-report comorbid intellectual disability" in the Underwood paper did not go unnoticed. Autism science also needs to make sure that all voices on the autism spectrum are equally heard (see here). Indeed, another recent paper [2] makes the point very eloquently: "We found selection bias against ID [intellectual disability] throughout all fields of autism research. We recommend transparent reporting about ID and strategies for inclusion for this much marginalised group." I wouldn't disagree...

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[1] Underwood JFG. et al. Autism spectrum disorder diagnosis in adults: phenotype and genotype findings from a clinically derived cohort. Br J Psychiatry. 2019 Feb 26:1-7.

[2] Russell G. et al. Selection bias on intellectual ability in autism research: a cross-sectional review and meta-analysis. Molecular Autism. 2019; 10: 9.

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"parental asthma was associated with slightly elevated risk of ASD in offspring"

The paper by Tong Gong and colleagues [1] provides the blogging fodder today and the finding that "parental asthma was associated with slightly elevated risk of ASD [autism spectrum disorder] in offspring."

As unusual as it might sound to some people that a condition primarily affecting the lungs *might* show a connection to a developmental diagnosis in offspring, this is not the first time that asthma and autism has been talked about on this blog (see here and see here). Granted, much of that previous peer-reviewed research has been looking at the possible *connection* between asthma and autism diagnosed in the same person (albeit not necessarily always describing a link). But there is some research history connecting the two labels. Indeed, one of the primary comorbidities that can follow a diagnosis of autism - attention-deficit hyperactivity disorder (ADHD) - seems to have an even stronger *association* with asthma (see here).

Gong et al set out to investigate a few important issues: "the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to β2-agonists, other asthma medications and offspring ASD." It would be difficult to describe the Gong study as 'underpowered' given that their use of those fabulous Scandinavian population registries - this time in Sweden - covering "all children (N=1,579,263) born in Sweden 1992-2007." From the total population, researchers identified some 22,000 children diagnosed with an ASD. They looked at their exposure to "parental asthma or prenatal asthma medications" and compared the data with other populations (not diagnosed with autism) including various degrees of siblings and extended family members.

As per the title of this post, a possible *association* was revealed between parental medical history of asthma and offspring risk of a diagnosis of ASD. Asthma in either parent seemed to show a connection, but maternal asthma showed the stronger connection. Also: "The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings... full-cousins... and half-cousins." This suggests that familial factors were not 'confounding' factors. Another detail is important to mention: "Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD." This is an important detail. It mirrors the findings reported in the paper by Su and colleagues [2] looking at another Scandinavian cohort, and their conclusion: "children born to women who used β2AA [β2-adrenoreceptor agonist] during pregnancy have an increased risk of ASDs in later life" with the caveat that risk of offspring autism was "more likely due to underlying maternal diseases rather than the exposure to β2AA itself."

Implications? Well, several. Not least that more study is required looking at the biological and genetic links between autism and asthma. Y'know, something along the lines of the fact that 'autism genes are probably not just genes for autism' (see here) and how autism has been previously studied in the context of lung architecture too (see here).

What else? How about examining the possibility of some shared biological mechanisms also at work? Perhaps start with inflammation for example [3] and work through other potential immune-related issues as well (see here). And how about also thinking about the possibility of shared 'exposure' events being potentially important? Asthma is a condition affecting the lungs. Something like air pollution is therefore a prime suspect when it comes to the development and continuation of the condition. Likewise, air pollution is no stranger to the autism peer-reviewed research landscape (see here for example). Is it possible that air pollution might be implicated in asthma and autism?

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[1] Gong T. et al. Parental asthma and risk of autism spectrum disorder in offspring: a population and family based case-control study. Clin Exp Allergy. 2019 Feb 11.

[2] Su X. et al. Prenatal exposure to β2-adrenoreceptor agonists and the risk of autism spectrum disorders in offspring. Pharmacoepidemiol Drug Saf. 2017 Jul;26(7):812-818.

[3] Murdoch JR. & Lloyd CM. Chronic inflammation and asthma. Mutat Res. 2010;690(1-2):24-39.

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Treating ADHD: better school results, less risk of crime and better sleep?

I

I had already written and scheduled in this blog post before an important - very important - headline appeared on the BBC News website: "ADHD [attention-deficit hyperactivity disorder] testing after 'impulsive crime' arrests should be mandatory, MPs say." The news piece covered, amongst other things, some of the peer-reviewed research findings suggesting that a diagnosis of ADHD appears to place someone at various enhanced risk for adverse life outcomes. And that potentially includes offending behaviour and prison time.

So...

Today's post is a bit of a mash-up insofar as bringing together three pieces of independent peer-reviewed research pertinent to the important idea of managing or 'treating' ADHD when it arises. I appreciate that not many people would want their nearest-and-dearest 'medicated' for example in the long-term. But when it comes to something like ADHD the case is indeed growing strong for how pharmacological intervention in particular, could literally be a life-saver for some (see here)...

The papers: first there are the findings reported by Andreas Jangmo and colleagues [1] who "analyzed school performance in students with ADHD compared to students without ADHD, and the association between pharmacological treatment of ADHD and school performance." This continues a research theme (see here). The second paper is that from Christina Mohr-Jensen and colleagues [2] which looked at "the risk of long-term conviction and incarceration associated with childhood attention-deficit/hyperactivity disorder (ADHD), and to identify risk and protective factors including associations with active treatment with ADHD medication." Again, this is a topic that has previously received quite a bit of study before (see here). Finally, I'd like to bring the paper by Stephen Becker and colleagues [3] to the blogging table, investigating whether "sleep duration is causally linked to sleepiness, inattention, and behavioral functioning in adolescents with ADHD." The answer: yes, yes it was, in line with other independent research (see here). And that potentially opens the door to intervention (see here).

Minus any sweeping generalisations from me or anyone else, the net result of these studies suggest that intervention for ADHD - primarily pharmacotherapy along the lines of what is currently indicated for ADHD - seems to have an important positive effect for many people diagnosed with ADHD. Some examples of this in action:

• School performance and ADHD: "ADHD was associated with substantially lower school performance independent of socioeconomic background factors." But the good news: "Treatment with ADHD medication for 3 months was positively associated with all primary outcomes" including higher grades and improving access to education. Such data was derived from a total sample size in the hundreds of thousands.
• Crime and ADHD: "Out of n=4,231 individuals with ADHD, n=1,355 (32.0%) had received at least one conviction compared to n=3,059 (15.6%) of the n=19,595 participants without ADHD." But... "The crime rates increased with the number of associated risks but were reduced during periods of taking ADHD medication."
• Sleep and ADHD: "Compared to the extended sleep week, parents reported more inattentive and oppositional symptoms during the restricted sleep week." The Becker study did not specifically talk about the use of intervention for sleep issues in the context of ADHD but it wouldn't be a giant leap to look at 'options' for improving sleep parameters in that context (and what knock-on effects this might have for behaviour).

Caveats? Well, correlation is not the same as causation, so even despite the 'strong' connections noted across these various studies mentioning ADHD, one cannot rule out other confounding variables playing a role. There's also the issue of balancing efficacy and safety to consider as and when any form of pharmacotherapy is introduced, something that is still being looked at with for example, methylphenidate and ADHD (paediatric ADHD) in mind [4]. I'm also minded to suggest that more fundamental work on the basis for ADHD should continue, alongside examination of the hows-and-whys of certain medicines *working* in the context of the biology of ADHD too. That, and an acceptance that medication might be but one tool in the arsenal (see here and see here and see here) to help prevent ADHD from negatively affecting a person's life and/or life chances.

But still the combined results are important. And they may well be important to those who don't quite reach all the thresholds for ADHD as a diagnosis [5] too... 

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[1] Jangmo A. et al. Attention-Deficit/Hyperactivity Disorder, School Performance, and Effect of Medication. J Am Acad Child Adolesc Psychiatry. 2019 Feb 1. pii: S0890-8567(19)30059-0.

[2] Mohr-Jensen C. et al. Attention-Deficit/Hyperactivity Disorder in Childhood and Adolescence and the Risk of Crime in Young Adulthood in a Danish Nationwide Study. J Am Acad Child Adolesc Psychiatry. 2019 Feb 11. pii: S0890-8567(19)30105-4.

[3] Becker SP. et al. Shortened Sleep Duration Causes Sleepiness, Inattention, and Oppositionality in Adolescents With ADHD: Findings From a Crossover Sleep Restriction/Extension Study. J Am Acad Child Adolesc Psychiatry. 2018 Nov 1. pii: S0890-8567(18)31914-2.

[4] Inglis SK. et al. Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study. BMJ Open. 2016;6(4):e010433.

[5] Kirova AM. et al. Are subsyndromal manifestations of attention deficit hyperactivity disorder morbid in children? A systematic qualitative review of the literature with meta-analysis. Psychiatry Res. 2019 Feb 3;274:75-90.

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Psychiatric and seizure medicines for autism: what 'works' best

The paper by Devon Coleman and colleagues [1] represents pretty good scientific value for money by my reckoning. Describing the results of a 'survey' called the "National Survey on Treatment Effectiveness for Autism" created by the researchers, the aim was to provide "separated... scales for overall benefits and overall AEs [adverse effects]" for a wide range of interventions used in the context of autism.

The focus this time around was on "Psychiatric and Seizure medications data" but it looks like there may be quite a bit more to see from this group in future with regards to data on "supplements, diets, therapies, and educational interventions" also collected during this initiative. Before continuing on with this paper I have to hat-tip the authors for mentioning a great and much under-valued resource in autism circles: "the Parent Ratings of Behavioral Effects of Biomedical Interventions Survey,... conducted by the Autism Research Institute (ARI) and published in 2008." Indeed, in other posts talking about the medicines cabinet and autism (see here) I've expressed my positive views of the ARI resource albeit with caveats.

Anyhow: "we report ratings of 26 psychiatric and seizure medications by 505 participants." Researchers actually noted that nearly 900 people completed their survey; most of whom were described as the "Primary caregiver of an individual with autism." Some people might um-and-ah about the lack of 'authentic autistic representation' in this study, but one needs to bear in mind that most participants - about three-quarters - were under 18 years of age, most diagnosed with autism and not autism spectrum disorder (described as "less severe than a diagnosis of autism") and most were currently described as having mild, moderate or severe autism. I know this won't be enough for some people, but there you have it.

Then to the medicines that were 'graded', which fell into "five general categories: stimulants (four medications), SSRIs [selective serotonin reuptake inhibitors] (five medications), antipsychotics (four medications), seizure (nine medications), and other (four medications)." There's a lot of data included in the Coleman paper which really is too much for a blog post. I'll direct you to Figure 8 of the Coleman paper which provides a handy 'net benefit score' taking into account an 'overall benefit score' and an 'overall adverse score' for each medicine. When it came to SSRI medicines - typically indicated for treating depression - sertraline came top. When it came to antiepileptic medicines - primarily used to manage epilepsy and/or seizures - lamotrigine came top. When it came to antipsychotic medicines, aripiprazole came top. I was also interested to see that buspirone, a medicine typically indicated for anxiety, also did pretty well according to the Coleman results, which kinda ties in with some continuing research interest in this medicine with autism in mind (see here). Researchers also provide a handy 'medications for symptoms' overview as a consequence of their results (see Table 7) covering various symptoms from aggression/agitation to tics/abnormal movements. I can see this being particularly useful when it comes to physicians having to make big medication decisions (which should never be entered into lightly).

There's a couple of other details that are also mentioned in the Coleman paper outside of those 'how was medicine rated?' sentiments. Some details are not likely to make many friends in some quarters. So, around 2% of participants were described as follows: "No current diagnosis, but he/she was on the autism spectrum previously." Yes folks, such data once again harks back to the idea that for some people at least, autism is not a lifelong diagnosis (see here and see here). And also: "Thirty-four percent of participants had early onset of symptoms, but 56% had normal development followed by a plateau or regression." Regression accompanying autism is not the 'dirty' concept that it used to be (see here). Indeed, in the few years that I've been blogging about autism research, I've seen it become a lot more commonplace to talk about regression and autism (see here) even to the point that some now talk about it being 'the rule rather than the exception' (see here). Interesting.

And then there's something even more controversial in the Coleman paper: "The perceptions of possible causes of the regression are listed in Table 2." So we have things like high fever, illness, seizure and then... vaccination. I know this takes us into some uncomfortable territory, but the authors report that 51% of respondents to their survey who cited regression as part of the clinical picture mentioned vaccination as the 'perceived cause' whether singly or in conjunction with other factors. Of course I'm going to provide a link to what the population-based science says on this matter (see here) with the caveat that such 'perceived cause' data perhaps needs objective and dispassionate follow-up (see here and see here).

The Coleman results are not without their limitations as per author comments such as: "The survey is retrospective and based on respondent memory which reduces the accuracy" and "The results are subject to “placebo effect” since it represents clinical data without a placebo control, so the real benefit is likely less than the perceived benefit." But let's not take too much away from the findings and how they may, as well as informing clinical practice, also hopefully lead to further inquiry to make medicines safer and more reliable for those on the autism spectrum who access them.

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[1] Coleman DM. et al. Rating of the Effectiveness of 26 Psychiatric and Seizure Medications for Autism Spectrum Disorder: Results of a National Survey. J Child Adolesc Psychopharmacol. 2019 Feb 6.

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"Are women with autism at an increased risk of adverse pregnancy outcomes?"

The paper by Heléne Sundelin and colleagues [1] provides the blogging fodder today, and research pertinent to the question: "Are women with autism at an increased risk of adverse pregnancy outcomes?" The short answer to the question is yes: "Maternal autism is associated with preterm birth, likely due to an increased frequency of medically indicated preterm births, but also with other adverse pregnancy outcomes, suggesting a need for extra surveillance during prenatal care."

It was refreshing to read the results from Sundelin et al (a research group who are no strangers to autism research) because this was a study devoted to looking at women with autism / autistic women and their pregnancy outcomes. It was distinct from other research on maternal pregnancy outcomes and offspring autism more traditionally seen in the peer-reviewed research literature and covered on this blog (see here and see here for examples).

The source material for the Sundelin study was the Swedish Medical Birth Registry (yes, one of those fantastic Scandinavian population registries again) and records of "2,198 births to 1,382 women with autism and 877,742 births to 503,846 women never diagnosed with autism." When comparing the groups across various different measures including preterm delivery ("defined as <37 completed weeks of gestation"), tobacco smoking during pregnancy and the use of various prescription medicines during pregnancy, some interesting trends were observed.

"Women with autism were at an increased risk of preterm birth..., which after stratification, remained for moderately (32 to <37 weeks) preterm birth." Also: "Maternal autism was also linked with an increased risk of elective cesarean delivery in births to women with autism" and "Preeclampsia was more prevalent in mothers with autism."

Although not seemingly affecting many of the 'adverse' pregnancy outcomes examined, researchers also noted that rates of tobacco smoking (light and heavy use) during early pregnancy were elevated in mums with autism, alongside prescription medicine use (antiepileptics, antipsychotics, hypnotics/anxiolytics, antidepressants) being more frequently reported before and during pregnancy compared to non-autistic pregnant mums. Authors reported that "there was no increased risk of adverse pregnancy outcomes except for induction of delivery" but one has to remember that the focus was on pregnancy outcomes - "completed weeks of gestation, mode of delivery, 5-minute Apgar scores, intrauterine growth, stillbirth, and maternal complications (preeclampsia and gestational diabetes)" - and does not say anything about longer term post-pregnancy outcomes. I say this with a few potential 'issues' in mind (see here and see here and see here).

The Sundelin study is by no means perfect - a "limitation is the lack of information on life circumstances" - but does carry the research weight that comes from those extremely well-categorised Scandinavian population registries. The authors conclude that their: "results suggest a need for individual prenatal care for women with autism, weighing pros and cons for continuation of psychotropic medication, with a better understanding of the difficulties related to autism, especially regarding the communication with health care professionals." Who am I to argue with them?

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[1] Sundelin HE. et al. Pregnancy outcomes in women with autism: a nationwide population-based cohort study. Clin Epidemiol. 2018 Nov 30;10:1817-1826.

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SEED says... risk of overweight/obesity in autism is heightened

SEED - The Study to Explore Early Development - provides yet more discussion fodder today as I bring the findings reported by Susan Levy and colleagues [1] to the blogging table. This time around the focus was on the risk of being overweight and/or obese in relation to a diagnosis of autism and the conclusion that: "Prevention of excess weight gain in children with ASD [autism spectrum disorder], especially those with severe symptoms, and in children with developmental delays/disorders represents an important target for intervention" on the basis of results observed.

It's not exactly a new thing to observe that those diagnosed with autism are perhaps at a greater risk of being overweight and/or obese (see here). There are a multitude of possible reasons behind such statistics covering everything from research showing those on the autism spectrum to typically be more sedentary than peers (see here) (bearing in mind the idea that 'you can't outrun a bad diet'), to a heightened risk of receiving medicines that list weight issues as a side-effect (see here) to a possible role for over-represented comorbidity (see here) with regard to weight issues. The net results however is the same: being diagnosed with an autism spectrum disorder places someone at a heightened risk of being overweight or obese.

Levy et al compared three groups of young children - "2-5 years of age" - classified by a diagnosis of autism spectrum disorder (ASD) or developmental delay/disorder or classed as a general population controls (i.e. asymptomatic). Importantly they describe how height and weight were "measured during a clinical visit" thus removing the reliance on 'at home' or routine records measurements [2] and the risk of bias that they can sometimes bring. Researchers also gathered background information on various co-occurring conditions/diagnoses.

Results: "The odds of overweight/obesity were 1.57 times... higher in children with ASD than general population controls and 1.38 times... higher in children with developmental delays/disorders than general population controls." One needs to be bear in mind the quite young age of participants when putting that last sentence into some context. Also: "Among children with ASD, those with severe ASD symptoms were 1.7 times... more likely to be classified as overweight/obese compared with children with mild ASD symptoms."

There's little more to say about such findings other than autism or autistic traits, yet again, seems to place someone as a quite significant disadvantage when it comes to their physical health and wellbeing. Now, the important question: what can be done about it?

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[1] Levy SE. et al. Relationship of Weight Outcomes, Co-Occurring Conditions, and Severity of Autism Spectrum Disorder in the Study to Explore Early Development. The Journal of Pediatrics. 2018. 9 Oct.

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On 'definite ADHD' and an "overall increase in caseness"

Consider this post a short continuation of an entry not-so-long-ago (see here) talking about the rates of attention-deficit hyperactivity disorder (ADHD) in the United States (US) going in only one direction. The findings reported by MinKyoung Song and colleagues [1] observed a similar trend - an increase in rates of ADHD - but added that the trend was noted in "Definite" ADHD" caseness: ""Definite" ADHD in caseness in 2007/2008 was 4.04%, increasing to 5.49% in 2011/2012."

The definition of 'definite' ADHD caseness? Authors "stratified identification of ADHD by current status, severity, psychiatric comorbidity, and ADHD medication usage". Alongside, they also talk about 'probable, doubtful and no' ADHD using data from the (US) National Survey of Children's Health (NSCH), an initiative that "provides rich data on multiple, intersecting aspects of children’s lives—including physical and mental health, access to quality health care, and the child’s family, neighborhood, school, and social context."

Accepting that different information sources are perhaps likely to produce slightly different results, the Song findings based on the NSCH don't exactly overlap with the Xu findings [2] previously blogged about, derived from the National Health Interview Survey (NHIS). The Song 'definite' ADHD caseness figures for 2007/2008 came in at about 4%. The rival Xu figures were more like 8%. The Song figures for 2011-2012 were 5.5%. The Xu figures for that period were approaching 10%. You can perhaps see the differences and trend.

Either way you can however still see that the direction of the figures - up - and once again perhaps appreciate that with data showing that a diagnosis of ADHD is associated with greater odds of various adverse life events occurring (see here and see here), so it's imperative that those who are diagnosed receive all the support that they need. I'd also suggest that science should be doing its utmost to focus on why the figures are increasing and what can be done to curb them.

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[1] Song M. et al. Addressing Discrepancies Between ADHD Prevalence and Case Identification Estimates Among U.S. Children Utilizing NSCH 2007-2012. J Atten Disord. 2018 Sep 28:1087054718799930.

[2] Xu G. et al. Twenty-Year Trends in Diagnosed Attention-Deficit/Hyperactivity Disorder Among US Children and Adolescents, 1997-2016. JAMA Network Open. 2018; 1: e181471.

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SEED says... opioid prescription before or in early pregnancy may impact on 'child neurodevelopment'

One has to be a little careful with a few things associated with the findings reported by Eric Rubenstein and colleagues [1] but they are interesting.

In it, researchers talk about analysing for various opioid based medicines prescribed over the period 3 months before conception up to the point of childbirth and onward any subsequent correlation with "child’s risk of ASD [autism spectrum disorder], developmental delay/disorder (DD) with no ASD features, or ASD/DD with autism features." Readers may have already heard about this study as a function of its inclusion in the 2018 INSAR (IMFAR) meeting (see here).

Outside of the old tenet 'correlation is not the same as causation', the authors specific focus was on 'opioid prescription', referring to a range of opiate-based medicines that are typically indicated for pain relief and supplied under medical consultation/supervision. This was not a study looking at other types of opioid 'drug' use that seem to be making a lot of news headlines in recent times (see here), despite the inclusion of methadone and buprenorphine in their list of watched-for prescriptions in maternal medical records. Authors do however mention that opioid use among pregnant women is increasing for various different reasons...

The use of the SEED - Study to Explore Early Development - initiative was the starting point for the Rubenstein study. As per the title of this post - 'SEED says' - it's yet another research venture (see here and see here for other examples) that seems to be producing some important data covering various aspects of autism and related developmental disorders (see here). At first glance, I was a little confused about the categorisation of 'ASD/DD with autism features' included in the study but readily accepted that this was a grouping distinct from another categorisation: 'developmental delay/disorder without features of ASD'. The authors were specifically looking at autistic features with such a division of the groups.

Taking into account the various medicines that are listed as opiates (including medicines containing codeine and fentanyl), authors scoured maternal medical records looking for opioid prescriptions. The also looked at time of use covering pregnancy trimesters, their use 3 months prior to conception and 'peri-pregnancy', all as a function of those diagnostic bandings.

Results: "Preconception opioid prescription was associated with 2.43 times the odds of ASD [95% confidence interval (CI) 0.99, 6.02] and 2.64 times the odds of ASD/DD with autism features (95% CI 1.10, 6.31) compared to mothers without prescriptions." CI refers to confidence interval and although I'm no statistics expert, I noted that the first finding on preconceptual opioid prescription being *associated with* an increased odds of offspring ASD (as in a diagnosis of ASD) did cross the magical '1' number: "95% confidence interval (CI) 0.99, 6.02." Combined with quite a large CI interval, and some might say that the 'precision' of that finding was less than convincing in a statistical sense. The other 'autistic traits' finding is a little more robust but there's still a need for further investigations in this area, including the use of some biological testing parameters perhaps?

I'm not saying that medicines taken during pregnancy can't have a possible impact on offspring neurodevelopment. The still-emerging data for example, on paracetamol (see here) or valproate (see here) seem to underline that point; albeit with a scheme of work to follow in those areas too. I'm also not saying that opioid-based medicines might not have some effect on offspring development [2], quite a few effects by all accounts [3], bearing in mind the pressing need to look at this issue in the context of the opioid crisis seemingly affecting many nations these days. But, at the present time, we have to be a little careful with the still-emerging-picture in this area so as not to make big claims or unduly tarnish what is an important class of prescription medicines when it comes to pain relief and beyond. And I say that as someone who has done his fair share of using the words 'opioid' and 'autism' down the [research] years [4]...

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[1] Rubenstein E. et al. Brief Report: Maternal Opioid Prescription from Preconception Through Pregnancy and the Odds of Autism Spectrum Disorder and Autism Features in Children. J Autism Dev Disord. 2018. Aug 21.

[2] Hans SL. & Jeremy RJ. Postneonatal mental and motor development of infants exposed in utero to opioid drugs. Infant Mental Health Journal. 2001. May 9.

[3] Fill M-MA. et al. Educational Disabilities Among Children Born With Neonatal Abstinence Syndrome. Pediatrics. 2018. Aug 30.

[4] Shattock P. & Whiteley P. Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets. 2002 Apr;6(2):175-83.

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Risk of poisoning in ADHD: meta-analysed

There was something inevitable about the results published by Maite Ruiz-Goikoetxea and colleagues [1] looking at the currently amassed scientific data "quantifying the risk of poisoning in children/adolescents with ADHD [attention-deficit hyperactivity disorder]."

Inevitable, because the results of their meta-analysis observing that "ADHD is associated with a significantly higher risk of poisoning" kinda tallies with other enhanced risk(s) in relation to general injury coinciding with this diagnosis, mentioned by the same authorship group (see here).

Poisoning - "defined by the World Health Organization as “an injury that results from being exposed to an exogenous substance that causes cellular injury or death”" - covers quite a bit of ground. The authors headed into this particular topic on the basis of their previous research foray (which I blogged about) on meta-analysing injury risk in the context of ADHD [2]. They started out with the premise that "a plausible hypothesis is that ADHD symptoms (inattention, hyperactivity and impulsivity) could lead to a similar increase in the risk of poisoning."

Nine studies including some 85,000 children and adolescents diagnosed with ADHD and 1.4 million not-ADHD controls, were included in their meta-analysis. Diagnosis of ADHD were garnered from various sources but most commonly 'administrative coding' on the basis of diagnosis and/or medication being dispensed for ADHD. Exposure to a poisoning event was also analysed; predominantly based on the use of registry data and predominantly utilising the ICD classification of poisoning.

"Overall, poisoning cases were uncommon" is an important point made by the authors; indicating that the absolute numbers of poisoning cases in ADHD and not-ADHD were actually low. So: "The median number per study of poisoned individuals that suffered from ADHD was 14..., whereas the median number per study of poisoned individuals who did not suffer from ADHD was 29." Bearing in mind there were more not-ADHD participants than diagnosed ADHD participants cumulatively reviewed by Ruiz-Goikoetxea et al, the calculated prevalence rates (per 1000) of poisoning "ranged between 3.5 and 60 (median 16) in children and adolescents with ADHD and between 0.8 and 37.3 (median 4.8) in children and adolescents without ADHD."

Still, the calculated risk - relative risk - was elevated in relation to poisoning events in those diagnosed with ADHD to the tune of something like them being three times more likely to suffer a poisoning event. Authors also noted that: "the relative risk of poisoning in individuals with ADHD compared to individuals without it was statistically higher than the overall relative risk of physical injuries" thus hat-tipping their previous research efforts.

There are some other details included in the Ruiz-Goikoetxea that are noteworthy insofar as age-effects - "poisoning incidence has two peaks across the child life span" - and how "the poly-pharmacy status in many ADHD patients could increase the likelihood of an accidental poisoning." But the bottom line is that, yet again, a diagnosis of ADHD seems to put someone as some significantly heightened risk of injury, and we should be doing everything we can to minimise any additional risks to those diagnosed.

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[1] Ruiz-Goikoetxea M. et al. Risk of poisoning in children and adolescents with ADHD: a systematic review and meta-analysis. Sci Rep. 2018 May 15;8(1):7584.

[2] Ruiz-Goikoetxea M. et al. Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: a systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews. 2018; 84: 63-71.

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One in five 8-year olds "received a psychiatric diagnosis"

"Question: What is the cumulative incidence of psychiatric diagnosis and use of psychotropic medications in a Medicaid-insured birth cohort by age 8 years?"

Answer: About 1 in 5 children were in receipt of a psychiatric diagnosis at age 8, and about 10% were in receipt of psychotropic medication.

So said the findings reported by Dinci Pennap and colleagues [1] who relied on "Medicaid claims data for newborns in a mid-Atlantic state in 2007... and followed up for 96 months or less through December 31, 2014." As per the focus on Medicaid - an initiative that 'helps with medical costs for some people with limited income and resources' - this was a study conducted in the United States, and included data for over 35,000 infants/children. The sorts of psychiatric diagnoses examined by Pennap et al included "ADHD [attention-deficit hyperactivity disorder], disruptive disorders, learning disorder (LD), adjustment disorder, anxiety disorders, depression, ASD [autism spectrum disorder], and other psychiatric diagnoses" all diagnosed by a clinician, but also requiring "2 or more diagnosis claims on separate days."

Venturing further into the study results, we learn some potentially important details. So, across the years of study, approaching two-thirds of the diagnoses received were defined as 'behavioural'. As probably expected (see here), a diagnosis of ADHD was the most popular label - "accounted for 43.9% (1999 of 4550)" - followed by a learning disorder (disability) diagnosis received by just over 30% of the group. White children were seemingly more likely to receive any psychiatric diagnosis than African American children or Hispanic children, and there were some important sex/gender differences noted across various diagnostic labels. If I'm also reading the results correctly with regards to the label of ASD (autism spectrum disorder) (see here), it looks like about 2-2.5% of boys had received a diagnosis, bearing in mind that this is a figure showing as a percentage of those who had received a psychiatric diagnosis. As a function of the entire cohort (N=35,244), the cumulative incidence of ASD across the years (2007-2014) and across the genders was 0.89%.

Then to the issue of pharmacotherapy or medication prescription. Bear in mind that Pennap and colleagues were looking at psychotropic medication being delivered to infants and young children; a group where even greater caution than usual should be expected. They reported that just over 10% of the entire cohort had some history of psychotropic medication use. Alongside those stats on ADHD as a diagnosis, so the medicines classed as stimulants (indicated for ADHD) made up the biggest class of medication used. The authors also zoomed in on a few particular parts of their medication findings. First: "girls were twice as likely as boys to initiate treatment with anxiolytics and hypnotics (25.2% [173 of 686] vs 13.2% [199 of 1510]; P < .001)", also noting that "there is insufficient evidence to support the use of anxiolytics and hypnotics as first-line treatment for pediatric mental health conditions." Second, they discuss evidence suggesting that: "antipsychotics are largely used for off-label behavioral management in the birth cohort, highlighting the need for a delicate benefit-risk balance." Yes, indeed there is a need for exploring that 'delicate benefit-risk balance' (see here and see here). The other rather important finding concerned the use of more than one psychotropic medicine over a prolonged period of time: "approximately 20% of medicated children (433 of 2196 [percentage adjusted for right censoring]) received 2 or more classes concomitantly for 60 days or more." Remember again, these were young children that were under study.

The picture painted by Pennap et al is an important one. It adds to other independent evidence to suggest that across different geographies, psychiatric disorders including behaviourally and emotionally-defined conditions, are prevalent, dare I even say frequent (see here and see here). I'd also add in the 'yet newer' recent US CDC 'estimates' of autism in 8-year olds in this context too (see here).

In relation to the medication side of things, well, 10% of their total population have had some exposure to psychotropic medication, which is important. Accepting that (very) careful medicines management is required given the young age of the group, I'm gonna stick to a line that I've mentioned before regarding the clinical need for such medicines [generally] outweighing the risk(s). I say this on the basis that prescribing clinicians know their clinical population and know something about the risk-benefit profile of the medicines they're administering. I'd also add that when it comes to something like stimulants as a class of medicines, the clinical profile of such medicines is typically 'safe' (benefits outweighing risks) and can, in a few cases, literally be a life-saver (see here and see here). But all that does not mean that science shouldn't be looking to other avenues for intervention for various labels (see here and see here for examples), alongside keeping a sharp eye on ways and means of making such medicines even safer for such younger populations...

And just in case you thought the figure 1 in 5 only holds for the United States, you're wrong and resources and services here in Blighty are seemingly still struggling...

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[1] Pennap D. et al. Patterns of Early Mental Health Diagnosis and Medication Treatment in a Medicaid-Insured Birth Cohort. JAMA Pediatrics. 2018. April 30.

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"ADHD was a risk factor for suicide attempt"

The findings reported by Kai-Lin Huang and colleagues [1] continue an important research theme (see here) on how a diagnosis of attention-deficit hyperactivity disorder (ADHD) may increase the risk of suicidal behaviours (see here). Further, that timely management of the symptoms of ADHD via indicated pharmacological means in particular, may provide some important risk-reduction from such behaviours; again substantiating previous investigations in this area (see here).

Based, yet again, on the fabulous but now sadly non-functional resource that is/was the National Health Insurance Research Database (NHIRD) in Taiwan, researchers undertook a "longitudinal cohort study [that] enrolled 20 574 adolescents and young adults with ADHD and 61 722 age- and gender-matched controls between 2001 and 2009." This is yet another example of Taiwanese 'big data' in action on the important topic of suicide (see here and see here). Alongside detailing any psychiatric comorbidities accompanying the diagnosis of ADHD, Huang and colleagues looked for diagnostic codes indicating suicide attempt(s) and whether or not medication(s) clinically indicated for ADHD were prescribed.

Results: "ADHD was an independent and direct risk factor for any suicide attempt, and an even stronger risk factor for repeated suicide attempts." As per my previous blogging forays into this topic, such news is by no means novel. The use of "long-term methylphenidate treatment" being associated with "a significantly decreased risk of repeated suicide attempts in men with ADHD" is also not new news, but does once more, provide yet more evidence for the use of such strategies and their seeming effects well beyond just symptom reduction/management.

What's more to say? Well, one might need to delve a little more into what it is about ADHD that *might* predispose to such extremes of behaviour. Whether this be a heightened risk of other comorbidity occurring as a function of ADHD (see here) impacting on suicidal behaviour(s) or something rather more directly linked to ADHD (see here), there is a schedule of further research to continue. I'm also minded to direct your attention to the findings reported by Mars and colleagues [2] and how general population 'risk factors' might also provide some clues. Minus any medical or clinical advice given or intended, I'll reiterate how the use of something like lithium seems to be quite useful in the context of potentially reducing suicide risk (see here) and how further work perhaps needs to be done on this compound with specific focus on suicide risk and ADHD. I say this, bearing in mind that lithium has a risk profile of its own.

Oh, and need I remind you that ADHD as being an 'over-represented' feature of autism for quite a few people (see here) might also imply some 'association' in the very serious statistics talking about suicide risk in the context of autism (see here)...

Again, if anyone needs to talk to someone, there are organisations out there willing to listen.

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[1] Huang KL. et al. Risk of suicide attempts in adolescents and young adults with attention-deficit hyperactivity disorder: a nationwide longitudinal study. Br J Psychiatry. 2018 Mar 4:1-5.

[2] Mars B. et al. What distinguishes adolescents with suicidal thoughts from those who have attempted suicide? A population-based birth cohort study. J Child Psychol Psychiatry. 2018 Mar 1.

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Chronic kidney disease is over-represented in cases of serious mental illness

The findings reported by Masao Iwagami and colleagues [1] observing that "CKD [chronic kidney disease] is identified more commonly among patients with SMI [serious mental illness] than in the general population" are not entirely novel. I've touched upon this topic before (see here), set within the broader perspective that physical / somatic ailments experienced by those with a psychiatric and/or behavioural diagnosis can sometimes be 'downplayed' in light of their receipt of a 'primary' psychiatric / behavioural label. It stretches across various different labels (see here for example) with sometimes catastrophic outcomes.

Iwagami et al started out with the premise that risk factors for CKD - "a long-term condition where the kidneys don't work as well as they should" - including tobacco smoking and diabetes, are more frequently reported in those diagnosed with an SMI, hence their risk of CKD may be greater. To see if there was any heightened association between SMI and CKD here in Blighty, they relied on data from a resource called the Clinical Practice Research Datalink (CPRD). CPRD allows researchers to access various details from patient records based on the accrual of primary healthcare data. Importantly, as well as containing read codes for SMI, the database also includes laboratory test results pertinent to CKD: "CKD was based on two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 separated by 3 months or longer; calculated from serum creatinine." The combined data was analysed and 'adjusted' for various potentially confounding variables including lithium use (lithium can affect kidney function).

From a starting population of some 2.5 million people (records), authors identified a diagnosis of SMI in about 28,000 (~1%). Most of those 28,000 or so diagnosed with a SMI had no history of lithium use (24,101 / 28,396). The prevalence of CKD was 14.6% in those with a SMI and history of lithium use. The prevalence of CKD was 3.3% in those with a SMI and no history of lithium use. This compares with a CKD prevalence rate of 2.1% in the population not diagnosed with a SMI (N=2,387,988). Ergo: "patients with SMI had a greater prevalence of CKD compared to the general population." Authors also mention how risk of renal replacement therapy (RRT) was also increased in those with a SMI.

This is important data. It's not foolproof data insofar as "a greater prevalence of CKD among patients with SMI may, in part, be influenced by surveillance or ascertainment bias. Patients with SMI take medications, such as lithium and other psychotropic drugs, which need regular monitoring." It does however suggest that regular screening for CKD needs to be a priority for those diagnosed with a SMI particularly given that "CKD is strongly and independently associated with mortality and cardiovascular risk" (something else mentioned in the context of certain psychiatric diagnoses). But there is also something rather uncomfortable in the Iwagami results: that possibility of an advanced risk of CKD in cases of SMI with a history of lithium use.

Minus any clinical or medical advice given or intended on this blog, I can see why the authors haven't overplayed the potential effect of lithium use on their results. Lithium, in the context of various psychiatric disorders and beyond, is an important medication, particularly when it comes to its proposed properties as an 'anti-suicidal' agent (see here). It really does save lives. But as with just about every medicine available, there is an important cost-benefit ratio to take into account when prescribing this medication and ensuring regular monitoring is available to minimise any side-effects. I might also add that there are *possibilities* [2] when it comes to potentially reducing some of the effects that lithium use might have on kidney function but I'll leave such discussions to the experts.

For now, we have further evidence that for whatever reason(s), being diagnosed with a SMI has the potential to impact on many areas of health, both mental and physical.

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[1] Iwagami M. et al. Severe mental illness and chronic kidney disease: a cross-sectional study in the United Kingdom. Clin Epidemiol. 2018 Apr 16;10:421-429.

[2] Lodin M. & Dwyer J. The role of amiloride in managing patients with lithium‐induced nephrogenic diabetes insipidus. J Pharmacy Practice & Research. 2017; 47(5): 389-392.

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Treating anxiety and depression in the context of autism: is 'talk therapy' cutting the mustard?

The findings reported by Brenna Maddox and colleagues [1] caught my eye recently, talking about "community treatment" patterns for co-occurring anxiety or depression in the context of autism.

Researchers concluded that talking therapy such as cognitive behavioural therapy (CBT) typically indicated for such mental health issues, is utilised in the context of autism but perhaps not as frequently as experienced in a not-autistic group. That finding covered various types of talk therapy such as individual therapy for anxiety/depression and case management. Alongside: "Adults with ASD [autism spectrum disorder] are more likely to be prescribed multiple medications concurrently."

Drawing on "Pennsylvania Medicaid claims data", researchers were able to identify adults with ASD who also presented with defined depression and/or anxiety. They matched this group (numbering about 270) with other adults presenting with depression and/or anxiety but not diagnosed with autism (N=1072). They then compared psychiatric treatment experiences between the groups.

"Adults without ASD were more likely to receive talk therapy for anxiety/depression." I added the bolding to the text so that we are clear that the Maddox results suggested that talking therapies for co-occurring depression and/or anxiety were less likely to be used when autism was mentioned. The authors further explain that these results are consistent with the idea that "they [those diagnosed with autism] often experience difficulty accessing mental health services." That being said, when talk therapy was accessed by adults with autism, researchers reported that they "averaged more individual talk therapy visits per month than did adults without ASD." I'll come back to this point in a moment...

Going back to the experiences of pharmacotherapy for those with and without autism, Maddox et al observed that: "the ASD group had a significantly higher number of days per month prescribed for all medication classes" covering medicines such as antidepressants, antipsychotics, benzodiazepines (anxiolytic) and CNS stimulant. Polypharmacy - where more than one medicine is dispensed - was also a more frequent occurrence for autistic adults too (nearly half were taking two or more psychotropic medicines).

What could all this mean? Well, going back to the observation that when they were able to access talk therapy, more visits per month were noted for the adults with autism, there is one possibility entertained by the authors to account for this: "talk therapy in the community is less effective with adults with ASD, who therefore stay in therapy for a longer period in pursuit of greater symptom relief." That possibility alongside the higher rates of 'multiple medicine use' noted in that group, adds weight to the idea that whilst talking therapy is useful for some cases of anxiety and depression, in the context of autism it might not necessarily be 'cutting the mustard'. The words "having more “treatment refractory” or complex constellations of symptoms" are also mentioned by Maddox and, well, have been discussed before (see here for example).

Further research is required on this issue before any sweeping generalisations are made by me or anyone else. For the record, I'm not adverse to the idea that talking therapy could be useful for depression/anxiety in the context of autism, but am open to the idea that the presentation of such mental health issues alongside autism might not be the same in form or for the same reason(s) as that in other non-autistic contexts. Indeed, in these days of ESSENCE and 'autism plus', I'm fast coming around to the idea that anxiety and depression could well be a core part of [some] autism (see here) as per what other - often forgotten names - had previously suggested (see here). Contrary then to the idea being promulgated among some (mainly psychological) quarters of the autism research and practice scene, that anxiety and depression develop in the most part as a consequence of external sources (see here for some chatter on 'social acceptance'), such mental health issues could be more fundamental characteristics of autism [2]. By saying that, I'm not discounting *some* influences like the contributions of loneliness and self-esteem (see here) but would also look to more intrinsic (biological and genetic) variables as also exerting something of a powerful effect. Similar sentiments have also been voiced when it comes to some other extremes of behaviour and their possible 'core' link to autism (see here).

"Our results suggest the need both for more granular and sophisticated assessment of community treatment for adults with ASD and anxiety/depression, and for better training for clinicians working with this population." I don't think many people would disagree with such conclusions. What I would like to see, under scientifically controlled circumstances, is some further comparisons of talking therapy for anxiety/depression in autism vs. not autism. I'm not talking about CBT vs no CBT with autism in mind [3] but rather research comparisons taking into account whether a diagnosis of autism might mean rethinking particularly talking therapy strategies for managing such quality-of-life-draining issues such as depression and anxiety.

The implication is also, yet again, that to really positively impact on the presentation of such issues, one needs to consider 'targeting' the core symptoms of autism themselves, as per what other research has similarly hinted at (see here). I can see conflicts arising following such sentiments...

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[1] Maddox BB. et al. Treatment utilization by adults with autism and co-occurring anxiety or depression. Research in Autism Spectrum Disorders. 2018; 51: 32-37.

[2] Spain D. et al. Social anxiety in autism spectrum disorder: A systematic review. Research in Autism Spectrum Disorders. 2018; 52: 51-68.

[3] Kilburn TR. et al. Rationale and design for cognitive behavioral therapy for anxiety disorders in children with autism spectrum disorder: a study protocol of a randomized controlled trial. Trials. 2018 Apr 2;19(1):210.

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Pregnancy exposure to paracetamol and offspring developmental outcomes meta-analysed

Yes, I'm yet again talking about pregnancy paracetamol (acetaminophen) use and offspring developmental outcomes on this blog (see here and see here for other discussions on this topic). As I mentioned on another recent blogging occasion, the news regarding pregnancy paracetamol use and offspring outcomes seems to be getting worse and worse, as associations galore keep appearing in the peer-reviewed science arena. Of course one has to be a little cautious about the nature of the studies that are emerging (i.e. observational, not readily designed to look at 'cause-and-effect') but the volume of research is growing at a significant pace potentially suggestive of something to see.

Now we have the results of a "Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies" published by Reem Masarwa and colleagues [1] on the topic of pregnancy paracetamol use and "the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy." All that meta-analysis stuff means that authors boiled down the current, existing peer-reviewed research into some sort of coherent whole. Their paper also comes complete with some lay media attention too (see here).

The findings? Well, taking into account various studies published "up to January 2017" and including some "132,738 mother and child pairs and with a follow-up period of 3-11 years", you probably won't be surprised to here that prolonged paracetamol use during pregnancy did seem to increase the risk of ADHD and/or autism in offspring to the tune of about 20-30% compared with those who did not take such medicine during pregnancy. That's not an unimportant percentage in anyone's book.

Reiterating the observational nature of the studies reviewed and boiled down (in a statistical sense) by Masarwa et al and the need for further investigations on things like possible mechanisms and indeed, whether the conditions for which paracetamol as pain relief was being taken *might* exert an effect on offspring risk, the results add to the concern. Much like other areas where various pregnancy medications are seemingly being implicated in relation to offspring outcome (see here and see here) such findings reiterate the importance of the nine months that made us and the need for much more sound research on this topic...

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[1] Masarwa R. et al. Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies. American Journal of Epidemiology. 2018. April 24.

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