The quote titling this post - "Physical and mental health issues were highly prevalent among children with obesity" - comes from the findings reported by Stasia Hadjiyannakis and colleagues [1].
Researchers set out to "examine the association between BMI [body mass index] class and EOSS-P [Edmonton Obesity Staging System for Pediatrics] stage" on the basis that measures such as BMI "do not always accurately and reliably identify children and youth with obesity-related health risks or comorbidities" [2] and issues like obesity don't typically appear in a "metabolic, mechanical, mental health and social milieu" vacuum.
As you might have already noted, Hadjiyannakis and colleagues have some 'research form' in this area. This time around data on nearly 850 children "with obesity aged 5-17 years" attending one of a number of weight management clinics were the source material. They observed that most of their cohort - about two-thirds of them - were described as having severe obesity according to their BMI score. When it came to their EOSS-P staging scores, 80% fell into the categories of a 2 or 3 denoting moderate to severe issues with regards to health issues such as metabolic complications either requiring pharmacotherapy or being described as "uncontrolled".
Of particular note to this blog and the focus on the intersection between physical and mental health parameters, researchers describe how "mental health concerns were most common" among their participant group. By 'mental health concerns' they specifically talk about anxiety and attention-deficit hyperactivity disorder (ADHD) as being present and "equally distributed across BMI classes." I was particularly intrigued with the ADHD bit because despite the focus on hyperkinetic behaviours in ADHD, the emerging research picture is suggesting that ADHD and obesity *might* actually be connected (see here) under quite a few different circumstances (see here).
What's more to say? Well, the Hadjiyannakis results perhaps imply that preferential screening for various physical and mental / behavioural are indicated when obesity is present. Specifically, and bearing in mind that "mental health risks were high across BMI classes" the results suggest that the possibility of an elevated risk of mental / behavioural diagnoses is not something confined to those with more or less severe obesity but rather, potentially, a universal issue.
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[1] Hadjiyannakis S. et al. Obesity class versus the Edmonton Obesity Staging System for Pediatrics to define health risk in childhood obesity: results from the CANPWR cross-sectional study. Lancet Child Adolesc Health. 2019 Apr 2. pii: S2352-4642(19)30056-2.
[2] Hadjiyannakis S. et al. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for paediatric obesity. Paediatr Child Health. 2016;21(1):21–26.
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News and views on autism research and other musings. Sometimes uncomfortable but rooted in peer-reviewed scientific research.
Showing posts with label body mass index (BMI). Show all posts
Showing posts with label body mass index (BMI). Show all posts
Friday, 10 May 2019
Wednesday, 24 April 2019
"Maternal diabetes, especially GDM, is probably a risk factor for ADHD"
It's coincidental that as I write this post about the findings reported by Lifeng Zhao and colleagues [1] talking about how "Maternal diabetes, especially GDM [gestational diabetes mellitus], is probably a risk factor for ADHD [attention-deficit hyperactivity disorder]" so the BBC news website highlights how screening for gestational diabetes here in Blighty is still a bit of a hit-and-miss affair (see here).That news report mentions how about a quarter of those mums-to-be who are most at risk of developing pregnancy diabetes - "having a high BMI [body mass index] or being of South Asian or Black Caribbean ethnicity" - did not get screened at all. Left untreated, gestational or pregnancy diabetes can increase the risk of various adverse events including "a baby that grows larger than usual, leading to problems in labour; premature birth; pre-eclampsia and stillbirth."
The Zhao findings - a meta-analysis - continue a theme suggesting that exposure to maternal diabetes, including pregnancy diabetes, seems to increase the risk of various other developmental and behavioural diagnoses also being present in offspring. The primary source material of this blog - autism - has been talked about on various occasions as being one of those developmental/behavioural diagnoses (see here and see here). That ADHD is quite often mentioned in the diagnostic mix when it comes to autism (see here) is another point to make.
The basics of the Zhao paper: a search of the peer-reviewed science literature was undertaken revealing nine studies that fitted the inclusion criteria including "7,218,903 participants." The quality of most studies was ranked as high. The results were interesting in that researchers "did not find significant association between maternal diabetes and ADHD risk (OR: 1.20, 95% CI: 0.96–1.49)." This observation is slightly at odds with the quote titling this post, which Zhao et al put down to the "high heterogeneity" detected among the included studies and their subgroup analysis of case-control studies (n=3).
Also... when it came to looking at another type of study - a cohort study (n=6) - "the meta-analysis demonstrated that maternal diabetes increased the risk of ADHD in offspring by 40%." Further, and bearing in mind the description 'diabetes' covers quite a bit of diagnostic ground, authors zoomed in on one particular 'type of diabetes', that called gestational diabetes (GDM) and looked at any effect. This is where things got a little more interesting as their results, based on four studies, indicated that "GDM exposure increased the risk of ADHD for children by 164%" in Caucasian children. Ergo, although a little mixed, the existing research literature at the time of analysis indicated that maternal diabetes during pregnancy, particularly GDM, *might* have some important effect on risk of offspring ADHD.
I'm not going to say much more at this point in time in terms of potential mechanisms that *might* elevate the risk of ADHD in offspring exposed to pregnancy diabetes. It's likely to be pretty complicated. Given also that GDM appears more often than not alongside other conditions (see here), it's not going to be easy to tease apart what might be the more important issues. Is it inflammation? Is something to do with blood sugar or insulin? At the moment, we just don't know enough...
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[1] Zhao L. et al. The association of maternal diabetes with attention deficit and hyperactivity disorder in offspring: a meta-analysis. Neuropsychiatr Dis Treat. 2019;15:675–684.
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Friday, 25 May 2018
Exercise may protect against the development of depression
"Available evidence supports the notion that physical activity can confer protection against the emergence of depression regardless of age and geographical region."So said the findings reported by Felipe Schuch and colleagues [1] who undertook a review of the existing peer-reviewed research literature looking at whether physical activity a.k.a exercise *might* provide some important protection against the development of depression. Such a review took place in the context that NHS Choices, the go-to place for health and medical information here in Blighty, already has an entry called 'exercise for depression'.
The authors - many of whom are quite recognisable names in the area of science looking at the physical and the mental coexisting together - located almost 50 studies labelled as prospective cohort studies including over a quarter of a million participants residing across the globe. They undertook a meta-analysis - combining all the data from the various studies together and coming up with a sort of consensus finding - and concluded that yes, physical activity does seem to have a positive effect on reducing the risk of depression. The level of the decrease in risk of depression from participation in physical activity seemed to vary slightly according to age, amount of exercise and geographical region, but the trend was most definitely in the protective direction across such variables and remained even after potentially important variables such as body mass index (BMI) and tobacco smoking were taken into account. The authors also reported that: "Although significant publication bias was found, adjusting for this did not change the magnitude of the associations" indicating that although there was a tendency for results 'friendly' to the 'physical activity might reduce depression' hypothesis to be published over less positive results, this did not seemingly affect the findings in any particularly meaningful way.
Accepting that there is a further scheme of work required on this topic in terms of things like what physical activities might be 'best' for depression or depressive symptoms (see here), how to measure physical activity more objectively (ahem, actigraphy) and what the mechanism(s) of effect might be, these are important results. I can think of many, many different areas that the Schuch results could be pertinent to; several already covered on this blog (see here and see here). Many of those areas / conditions / labels reflect states where either physical activity seems to be reduced by choice (see here) or through necessity (see here) but the net result could be the same in terms of elevated risk of depression.
Still, the general message emerging from the Schuch paper is: if you can, move more, and perhaps not just for the physical benefits that accompany physical activity.
And just in case you need some more reading material on this topic, you could do a lot worse than the paper by Brett Gordon and colleagues [2] who concluded that: "Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength."
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[1] Schuch FB. et al. Physical Activity and Incident Depression: A Meta-Analysis of Prospective Cohort Studies. Am J Psychiatry. 2018 Apr 25:appiajp201817111194.
[2] Gordon BR. et al. Association of Efficacy of Resistance Exercise Training With Depressive Symptoms. JAMA Psychiatry. 2018. May 9.
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Saturday, 23 December 2017
"people with a diagnosis of schizophrenia have an increased hazard of being obese"
Warm but not hot on the heels of a previous post potentially turning upside-down our understanding of inflammatory markers in the context of schizophrenia (see here) I'm bringing the paper by Isobel Cameron and colleagues [1] to the blogging table.What's the link you may ask?
Well, if one assumes that the Hartwig findings [2] on inflammatory markers in schizophrenia could be 'influenced' by the presence of increasing body mass index (BMI) talked about in other research [3] one should, most definitely, be looking at how weight and/or BMI issues manifest in relation to schizophrenia as Cameron et al did.
So with the aim of estimating levels of obesity "in a national population sample by comparing patients with schizophrenia with matched controls" nearly 5000 adult cases of schizophrenia and "19 752 controls matched by age, gender and practice" were initially identified from a database covering Scotland. Further: "Patients with a recorded BMI were classified as obese (BMI ≥30 kg/m2) or not obese (BMI <30 kg/m2)."
Results: bearing in mind that other population statistics point to obesity not being an unfamiliar health issue in Scotland (see here) as in many other parts of the world, authors reported that: "people with a diagnosis of schizophrenia have an increased hazard of being obese when compared with adults matched by age, gender and practice attended." Taking into account occasions where "no BMI, height and weight were recorded in the 3 years before entry into the PCCIU database" researchers presented two different statistics. One where missing data were treated "as not obese following the logic that as there was no weight or BMI recorded the GP saw no clinical need to obtain these measures" and the other where records were excluded when BMI was not recorded. Both ways were associated with "an increased obesity hazard" to a similar sort of degree.
"Our analyses show that even within a nation with a substantial obesity prevalence, patients with schizophrenia are significantly more likely to be obese." This isn't of course the first time that issues with weight (or BMI) have been noted in the peer-reviewed science domain with schizophrenia in mind [3] and I doubt it will be the last.
The question should then be: what can be done about overweight and obesity in the specific context of schizophrenia? For potential answers to that, I'll refer you to some of the collected works of Dr Brendon Stubbs and colleagues (see here) and their very thorough reviews and meta-analyses on all-manner of topics that potentially tie into such a weighty issue...
This is my last post before Christmas, and so includes a traditional(?) song to send best wishes to all (hopefully not from the drunk tank)...
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[1] Cameron IM. et al. Obesity in individuals with schizophrenia: a case controlled study in Scotland. British Journal of Psychiatry Open. 2017; 3: 254-256;
[2] Hartwig FP. et al. Inflammatory Biomarkers and Risk of Schizophrenia: A 2-Sample Mendelian Randomization Study. JAMA Psychiatry. 2017 Nov 1.
[3] Annamalai A. et al. Prevalence of obesity and diabetes in patients with schizophrenia. World J Diabetes. 2017 Aug 15;8(8):390-396.
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Wednesday, 6 September 2017
Metformin to tackle medication induced weight gain in autism continued
The results of the open-label extension trial on the use of "Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism" reported by Benjamin Handen and colleagues [1] is blogging fodder for today. Continuing a research interest from this group (see here), the idea that weight and related side-effects from certain antipsychotic medicines can be managed by a drug readily used to treat type 2 diabetes receives yet more support.Last time around [2] researchers showed that under double-blind, placebo controlled conditions, metformin was fairly well-tolerated and did aid in "decreasing weight gain associated with atypical antipsychotic use" in children and young adults diagnosed with an autism spectrum disorder (ASD). This latest publication detailed what happened when everyone - well, 85% of the original cohort - went on metformin in terms of their body mass index (BMI) and "additional body composition and metabolic parameters" for an additional 16 weeks.
Results: well, as would probably be expected, "participants initially taking placebo during the RCT [randomised controlled trial] had reduced BMI z-scores" when metformin was introduced. For those who were already taking metformin during the original trial, prior reductions in BMI were maintained but they "did not experience additional weight loss." I might also add that 'fairly well-tolerated' meant that: "Three participants discontinued treatment due to an adverse event."
These are important findings and add to other preliminary research findings in this area [3]. I know many people (including myself) have some reservations about adding in medicines to treat the side-effects of other medicines (as well as the conditions for prescribing antipsychotics in the first place [4]), but given what elevated BMI scores can mean to physical health and associated health risks, this is one occasion where intervention might be truly life-saving (with appropriate clinical monitoring assumed). Further studies are indicated.
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[1] Handen BL. et al. A Randomized, Placebo-Controlled Trial of Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorder: Open-Label Extension. Journal of the American Academy of Child & Adolescent Psychiatry. 2017. Aug 19.
[2] Anagnostou E. et al. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Sep 1;73(9):928-37.
[3] Wink LK. et al. Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder. J Autism Dev Disord. 2017 Jul;47(7):2290-2294.
[4] Jackel C. et al. Factors Associated with Developmental Behavioral Pediatricians Prescribing Psychotropic Medication to Children with Autism Spectrum Disorder: A Study of Three DBPNet Sites. J Dev Behav Pediatr. 2017 Aug 10.
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Saturday, 5 August 2017
Pre-pregnancy weight and risk of offspring ADHD
"Compared to normal weight mothers, the risk of having a child with ADHD [attention-deficit hyperactivity disorder] was significantly increased if the mother was overweight..., obese... or severely obese."So said the findings reported by Andersen and colleagues [1] examining data from some 80,000 mother and child pairs "participating in the Danish National Birth Cohort (DNBC)." The name of the research game was to look-see whether maternal weight before pregnancy might be an important factor when it comes to offspring developmental and behavioural outcomes specifically with ADHD and/or autism in mind.
The results showing a possible relationship between maternal pre-pregnancy weight and ADHD were to some extent mirrored in relation to offspring autism albeit not showing the 'dose trend' of hazard ratios - overweight, obese, severely obese - noted in relation to ADHD. Indeed authors noted that: "Regarding ASD [autism spectrum disorder], an increased risk was observed in underweight... and obese... mothers" illustrating a less confident pattern of possible association.
This is not the first time that this topic has been discussed on this blog (see here). One still has to be a little careful with such 'observational' research so as not to assume that only pre-pregnancy maternal weight is a risk factor for offspring ADHD or anything else. I'm also minded to suggest that the continued use of the body mass index (BMI) statistic is not without difficulties. That and the fact that we're also no further forward when it comes to talking about possible mechanisms behind any association given the myriad of effects that excess weight can potentially cause to mother and any children to be (see here).
What we can however take from this and other independent data [2] is that the physical health of mothers (and fathers) might be quite important to offspring even when the prospect of children is still a twinkle in the eyes of parents. We're all constantly being told to eat well, exercise regularly and cut out or cut back on certain things to achieve optimal health and wellbeing. This and other research if true, suggest that heeding such advice might have inter-generational implications too, for lots of different reasons [3]...
Music to close, and sorry Your Majesty, but some of my brood find the alternative 'God Save the Queen' much more entertaining than the original...
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[1] Andersen CH. et al. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. Eur Child Adolesc Psychiatry. 2017 Jul 15.
[2] Van Lieshout RJ. et al. Pre-pregnancy and pregnancy obesity and neurodevelopmental outcomes in offspring: a systematic review. Obes Rev. 2011 May;12(5):e548-59.
[3] Jensen ET. et al. The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm. J Pediatrics. 2017. March 21.
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Tuesday, 25 April 2017
Who'd have thunk it: physical activity inversely associated with BMI and body fat percentage
"In this sample of middle-aged adults, drawn from the general population, physical activity was inversely associated with BMI [body mass index] and body fat percentage. For people with the same BMI, those who were more active had a lower body fat percentage."Those were the conclusions made by Kathryn Bradbury and colleagues [1] (open-access) drawing on data derived from "cross-sectional analysis of participants recruited into UK Biobank in 2006–2010." Said results continue a research theme where physical activity figures in the aforementioned dataset.
So: "119 230 men and 140 578 women aged 40–69 years, with complete physical activity information, and without a self-reported long-term illness, disability or infirmity" were included for study - not an under-powered study by any means. Height and weight of participants were measured by trained staff "using standardised techniques." Physical activity estimates were gathered via self-report; specifically the use of 'touchscreens' as information gatherers regarding "walking, moderate physical activity and vigorous physical activity" and how often in a typical week participants "did each of the activities for 10 min or more" then onward for how many minutes during a day. Such data was number-crunched to provide something called "excess metabolic equivalent (MET)-hours/week of physical activity during work and leisure time." The authors also report on some efforts to off-set the potential unreliability of self-reported physical activity and several other variables (whether occupation involved primarily sitting or standing, tobacco smoking status, alcohol consumption, etc) were also thrown into the statistical mixer.
Results: well, who'd have thunk it? Those reporting higher levels of physical activity (via questionnaire responses) tended to have a lower BMI and a lower body fat percentage. They were also likely to eat more fruit and vegetables that those with low levels of physical activity. Diet, occupation type and education level did not however seem to affect the primary findings.
Accepting again that self-reported physical activity is not a great substitute for more objective measures and that BMI, whilst a good rough-and-ready indication of weight status, tends not to differentiate between fat and muscle, these are important results. They imply that far from not being able to outrun a bad diet (see here) physical activity still has an important place in maintaining a sensible weight and thus reducing the risk of a myriad of adverse health outcomes. Added to other findings indicating that we all really need to move quite a bit more (see here), the message seems to be that the human body was made for moving so move it. And the latest figures on obesity and physical activity highlight the challenges being faced in this area.
And so to close, a song to help with that 'move it' sentiment...
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[1] Bradbury KE. et al. Association between physical activity and body fat percentage, with adjustment for BMI: a large cross-sectional analysis of UK Biobank. BMJ Open 2017; 7: e011843.
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Tuesday, 4 April 2017
Autism, ageing and comorbidity
I'm not spending too much time today on the findings published by Elizabeth Wise and colleagues [1] but did want to bring them to your attention. Looking at the presentation of "comorbidities and behavioral and neuropsychiatric symptoms" in relation to autism in the context of ageing, some important details were noted. Not least that "GI [gastrointestinal] disorders (68.9%) and seizure disorders (23%) were common, and 25.7% of the sample had a BMI [body mass index] >30" when looking at their 74 strong cohort of adults diagnosed with autism (DSM-5 autism by all accounts).It's not new news that the label of autism rarely exists in some sort of diagnostic vacuum (see here and see here for other examples). The fact that GI disorders (whether functional or more pathological), epilepsy and/or seizure disorder and excess BMI have been picked out by Wise et al ties into an extensive peer-reviewed research body highlighting such issues. What is still missing from quite a lot of that literature is the hows-and-whys of such over-represented comorbidity and importantly, what can be done to manage/ameliorate them (see here for example) given that sometimes they can be just as 'disabling' as a diagnosis of autism itself.
Wise and colleagues also noted that: "the point prevalence of behavioral and neuropsychiatric symptoms (BNPS) declined significantly for 12 of 13 BNPS over a mean of 25 years while many other features of ASD remained stable." Accepting the relatively small cohort studied, this is an interesting finding and ties into other research looking at what happens to something like psychiatric comorbidity in the context of ageing and autism (see here). There is a caution attached to the idea that behavioural and psychiatric comorbidity might be quite fluid across the lifespan in relation to autism insofar as sex/gender potentially being an important variable (see here).
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[1] Wise EA. et al. Aging and Autism Spectrum Disorder: A Naturalistic, Longitudinal Study of the Comorbidities and Behavioral and Neuropsychiatric Symptoms in Adults with ASD. J Autism Dev Disord. 2017. Mar 16.
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Monday, 3 April 2017
Decreased urinary creatinine levels associated with autism (again)
One finding in particular stood out from those reported by Lussu and colleagues [1] following some nifty metabolomic investigations: decreased levels of urinary creatinine in their cohort of participants diagnosed as on the autism spectrum (n=21) compared with "controls (n = 21), these being siblings of autistic patients."Based on the "use of 1 H-NMR metabolomics to analyze the global biochemical signature of ASD [autism spectrum disorder] patients" researchers turned again to a favourite topic of this blog - metabolomics - and how the detection and identification of small molecules in various biofluids (urine, blood, saliva, etc) might be particularly informative. Metabolomics is, in essence, all about two things: (i) the analytical technology used to analyse a sample and (ii) the statistical technology used to make sense of the chemical analysis. If one assumes that a biofluid like urine literally contains thousands of compounds and small molecules, you get a flavour for the task facing researchers in this area.
I've talked metabolomics a few times on this blog with autism in mind (see here and see here for examples) but have chosen to zoom in on the Lussu findings in relation to an interesting compound called creatinine. Creatinine is a break-down product of creatine phosphate typically found in muscle. It's generally used as a rough-and-ready guide to the dilution of a urine sample given that it is produced at quite constant rate (see here).
In my day job, I continue to have some interest when it comes to creatinine (urinary) in the context of autism as per some research published a decade or so back [2]. My colleagues and I reported: "Controlling for sample pH and body mass index [BMI], a significant decrease in urinary creatinine concentration was found in the PDD [pervasive developmental disorder] group compared to controls." Other [independent] researchers have also reported similar things [3] when it comes to blood levels of creatinine in the context of autism.
Unfortunately I don't yet have a good explanation as to why creatinine seems to be on the low side when it comes to at least some autism bearing in mind issues such as BMI can seemingly affect values. I do find in interesting that muscle mass may have a bearing on urinary creatinine excretion and could perhaps stretch an association with [some] autism on the basis of more generalised issues with muscle function or tone (see here). That low urinary creatinine *may* also point to issues with kidney function is also interesting and invites quite a bit more study on this organ in relation to autism...
Music: Acceptable in the 80's.
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[1] Lussu M. et al. The urinary 1 H-NMR metabolomics profile of an italian autistic children population and their unaffected siblings. Autism Res. 2017 Mar 11.
[2] Whiteley P. et al. Spot urinary creatinine excretion in pervasive developmental disorders. Pediatr Int. 2006 Jun;48(3):292-7.
[3] West PR. et al. Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children. PLoS One. 2014 Nov 7;9(11):e112445.
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Friday, 10 March 2017
I would walk 500 miles... or maybe just 8 miles (a day).
"Desk-bound workers should ‘walk EIGHT miles a day’ to slash risk of heart attacks or stroke" went one headline talking about the findings reported by William Tigbe and colleagues [1]. Drawing on data from over 110 postal workers - "(55 office-workers, 5 women, and 56 walking/delivery-workers, 10 women)" - who wore "activPAL physical activity monitors for seven days", researchers observed some potentially important trends.Alongside wearing their activity monitors, participants were also assessed on the basis of weight, height, and blood pressure; also providing blood samples pertinent to analyses for cholesterol and triglycerides. Such collected data were used to assess cardiovascular risk based on the PROCAM risk calculator.
Results: those who were described as office workers and had a 'desk job' were generally larger at the waist and showed a slightly larger body mass index (BMI) score. They were also deemed to have an elevated risk of cardiovascular disease (over 10 years) compared with the walking/delivery workers. These observations were discussed in terms of the sedentary behaviours associated with their desk job. By contrast, those who delivered post (i.e. were active for large parts of the day) fared quite a bit better than their desk-bound colleagues, bearing in mind that all study participants were fairly healthy to begin with in terms of being non-smokers for example and not being in current receipt of blood pressure or glucose lowering medicines at time of study.
The 'walk 8 miles a day' headline that followed the Tigbe study was derived from the observation(s) that: "Those with no metabolic syndrome features walked >15 000 steps/day, or spent >7 h/day upright." Metabolic syndrome refers to a collection of symptoms - "a combination of diabetes, high blood pressure and obesity" - that increases the risk of adverse events associated with cardiovascular (dys)function. It seems that being active, or at least not being sedentary, is important for our health - a shocker indeed!
I've covered some of the other research in this area before (see here and see here for examples) and so the Tigbe results really don't come as a surprise. The strengths of the study are multiple in terms of objective measuring of activity (not reliant on the 'how much activity/exercise did you do today' type questionnaires) and all those biochemical measurements taken for participants to complement such findings. Yes, the sample size is OK but not particularly large and yes, these were pretty healthy participants to start with, but the results are nonetheless important.
Obviously one has to be a little careful so as not to imply that being active is the only thing that leads to good health and wellbeing. Science has already heard about how 'you can't outrun a bad diet' [2] and for some people, walking 15,000 steps every day or even standing up for 7 hours a day is going to be a big ask. But as part of a package of 'interventions' to potentially ward off metabolic syndrome or related issues [3], the idea that we should all be quite a bit more active is one that really should be given a lot more consideration...
Music to close, and with the title to this post, what else could I offer?
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[1] Tigbe WW. et al. Time spent in sedentary posture is associated with waist circumference and cardiovascular risk. Int J Obes (Lond). 2017 Jan 31.
[2] Malhotra A. et al. It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet. Br J Sports Med. 2015 Aug;49(15):967-8.
[3] Alexander DD. et al. A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk. Mayo Clinic Proceedings. 2017; 92: 15-29.
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Monday, 17 October 2016
Maternal obesity and offspring autism meta-analysed (again)
Meta-analyses eh? You spend ages waiting for one and two come along in quick succession. Well today I'm posting about yet another meta-analysis of the peer-reviewed scientific literature suggesting that "excessive maternal BMI [body mass index] is associated with an increased ASD [autism spectrum disorder] risk in offspring." [1]The review by Ying Wang et al follows hot on the heels of the meta-analysis by Li and colleagues [2] (see here for my take) but further looked at "the potential association of different category of BMI including overweight and underweight with ASD risk" among other things. BMI by the way, is a rough and ready way to quantify how much of a person there is according to height and weight. Whilst a useful statistic, it is not without its issues.
After taking into account data from "6 cohort studies and 1 case-control study involving 8,403 cases and 509,167 participants" the authors unsurprisingly came to the same conclusion as Li and colleagues that a higher BMI seems to confer more [relative] risk for offspring autism as an outcome. Authors even included a nice graphic (see here) suggesting something of a dose-response relationship between the two variables (based on data from four of the studies included in their meta-analysis).
What's more to say? Well, 'The maternal body as environment in autism science' returns into the frame and questions about possible mechanisms need to be asked/answered. No, such findings don't mean (a) every mum with a child with autism was overweight or obese before or during pregnancy or (b) every overweight or obese mum will have a child with autism: "Compared with children whose mothers were at normal weight, children born to overweight and obese mothers have a 28% and 36% higher risk of developing ASD, respectively." Such data does however open the door to the idea of foetal programming when it comes to potential offspring outcomes and how elevated BMI as possibly linking to facets of metabolic syndrome for example, might have some role to play for some (see here).
More investigations are indicated.
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[1] Wang Y. et al. Maternal Body Mass Index and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis. Scientific Reports. 2016; 6: 34248.
[2] Li YM. et al. Association Between Maternal Obesity and Autism Spectrum Disorder in Offspring: A Meta-analysis. J Autism Dev Disord. 2016 Jan;46(1):95-102.
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Thursday, 8 September 2016
Metformin to tackle medication induced weight gain in autism?
"Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD [autism spectrum disorder]."So said the paper by Evdokia Anagnostou and colleagues [1] (open-access) tackling an increasingly important health issue related to the pharmacological 'management' of some aspects of some autism.
Metformin is the treatment of choice when it comes to the management of type 2 diabetes (the one where "the pancreas doesn't produce enough insulin or the body's cells don't react to insulin"). It is thought to work by helping the liver to stop producing new glucose and also helping insulin carry more glucose into muscle cells more effectively. Alongside, an increasing body of research has also suggested that metformin might be a useful intervention measure to offset one of the quite well-known side-effects associated with various antipsychotic agents: weight gain.
So Anagnostou et al set about looking to "assess the safety, tolerability, and efficacy of metformin to decrease weight gain associated with the use of atypical antipsychotic medication in children with ASD." They did this using the gold-standard in clinical trial designs: the "double-blind, placebo-controlled, randomized clinical trial" where some 60 children and young adults diagnosed with an ASD and receiving a stable dose of an atypical antipsychotic received either metformin (Riomet) or a placebo over the course of 16 weeks. "The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables." The study protocol was also registered with ClinicalTrials.gov.
As per the opening sentence, there were some important differences in body mass index (BMI) z-scores suggestive that compared with a placebo, those prescribed metformin saw decreases in weight gain. The range of decrease in BMI were in some cases between about 8-9% over the course of the 16 week study period (most of the benefits seemed to be apparent after about 8 weeks of metformin use). Insofar as those secondary variables also examined during the course of the study (glucose levels, insulin, triglycerides, etc.) no significant differences were noted across the study. When it came to the important issue of side-effects, the authors noted that gastrointestinal (GI) effects seemed to be more apparent in the group taking metformin during treatment days. Aside from that, short-term side-effects seemed to be few and far between.
The authors note that their trial "did not address the question of whether coadministration of metformin at the onset of atypical antipsychotic use prevents initial weight gain" but rather whether metformin use after weight gain associated with antipsychotic use could be effective. In that light, these are important results that very much require further independent investigation.
Quite a few times on this blog I've talked about how the physical health of those on the autism spectrum is sometimes neglected as a function on the focus on mental health or behaviour. There is a growing recognition that autism, or at least some of the important comorbidities associated with autism, might somehow predispose to a more sedentary lifestyle and the accompanying health issues that this can bring. Throw into the mix the possibility that some of the pharmacotherapy used in autism might also contribute to something like weight issues [2], and you have a recipe for some pretty severe health issues potentially building up in later life. These latest findings are therefore welcomed as a way to potentially lower the burden of an elevated BMI in cases where such medication is prescribed.
I do have questions however about this approach and how one perhaps needs to be slightly cautious about slipping into the old 'medication to tackle medication side-effects' routine with autism in mind (something noted in an accompanying editorial to the Anagnostou study). Metformin, whilst a very useful drug, is not without side-effects as was noted in the Anagnostou study and given the quite high rates of GI issues noted in cases of autism (see here), one really does not want to make this any worse. I would also like to see more data on the use of metformin in antipsychotic-induced weight gain in autism with a focus on other parameters thought to be altered by such antipsychotic use such as the issue of prolactin levels for example (see here). Yes, there is data to suggest that metformin might more generally work on prolactin levels too [3] but does this similarly apply to children on the autism spectrum? And then also there is the issue of sleep [4]...
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[1] Anagnostou E. et al. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder. JAMA Psychiatry. 2016. Aug 24.
[2] Shedlock K. et al. Autism Spectrum Disorders and Metabolic Complications of Obesity. Journal of Pediatrics. 2016. Sept 2.
[3] Krysiak R. et al. The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia. Eur J Intern Med. 2016 May;30:94-8.
[4] Kajbaf F. et al. The relationship between metformin therapy and sleep quantity and quality in patients with Type 2 diabetes referred for potential sleep disorders. Diabet Med. 2014 May;31(5):577-80.
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Wednesday, 13 April 2016
Vitamin D deficiency and psychosis
In amongst my various ramblings about how vitamin D - the sunshine vitamin/hormone - might show more than a few connections to conditions/labels outside of just the English disease (see here), I've covered some science on a possible connection with psychosis (see here) and schizophrenia (see here). There are still gaps in terms of the hows and whys of vitamin D insufficiency and deficiency when it comes to this area of psychiatry, but I believe there is enough science in this area to initially warrant screening of vitamin D levels as and when a diagnosis is received. This similarly extends to other labels too (see here and see here).The paper by Lally and colleagues [1] (open-access) puts a little more scientific flesh on the bones about how vitamin D insufficiency/deficiency might manifest in cases of psychosis, with a particular focus on "increased cardiovascular disease risk factors and in particular metabolic syndrome [MetS]."
With thanks to Brendon Stubbs (one of the authors of the paper) for bringing the findings to my attention, researchers set about looking at "the prevalence of vitamin D deficiency in a cohort of community patients with established psychotic illnesses" (N=324). Given my earlier mention of the 'English disease', the cohort were indeed all living in England and drawn from a larger study initiative. Vitamin D levels were assayed via a chemiluminescence immunoassay based on the examination of serum samples. Various other measures were also included for study around the issue of cardiovascular risk factors including body mass index (BMI), waist circumference, blood pressure, serum cholesterol levels and glucose levels. High sensitivity serum C-reactive protein (HS-CRP) was also included.
Results: "Almost half of the sample (48.8 %, n = 158) were deficient in vitamin D while only 13.9 % (n = 45) had sufficient vitamin D." Ethnicity seemed to play a role in those determinations of deficiency/sufficiency with vitamin D levels generally lower in those who were black African or black Caribbean. Likewise the season of testing showed an effect. When it came to determining whether there was an association between vitamin D status and mental state, researchers reported nothing significant based on the use of the Positive And Negative Syndrome Scale (PANSS) and related measures.
But... there might be quite a bit more to look at when taking into account those cardiovascular disease risk factors and vitamin D levels as the authors reported various significant correlations. So: "those with the highest levels of vitamin D have a lower prevalence of MetS (20.5 %), compared to those in the lowest (39.1 %), second (48.3 %) and third quartile (43.1 %) of vitamin D." Indeed, just about every measure of cardiovascular risk showed an association with measured serum vitamin D levels when controlling for "age, gender, ethnicity and season of 25-OHD blood sampling." The authors also add that: "Those engaging in low intensity physical activity over the week prior to sampling... had significantly lower 25-OHD levels... than those who engaged in moderate or high intensity physical activity."
Teasing apart what might actually be doing what is a difficult task in such studies where various outcome measures might be implicated. The authors do speculate on how for example, their finding of "raised CRP and vitamin D deficiency in established psychosis" might tie into other research on inflammation or inflammatory processes with both variables in mind (see here and see here). Indeed, this might also tie in with calls for further integration of immunopsychiatry with psychotic disorders in mind [2]. But there remains more to do, including the intriguing question: "would the supplementation of vitamin D in psychosis prevent and/or ameliorate cardiovascular and metabolic risk?"
I do have some small points to make about the study that might also require attention in follow-up work, not least the idea that immunoassay for determining functional vitamin D levels might not be the most accurate method [3]. Indeed, the authors make this point in their conclusions. One might also hope that comparisons with other patient groups might offer some further information about how specific the findings are to just psychosis or other psychiatric groupings. If found in a more general sense, the idea that vitamin D is related to variables affecting cardiovascular risk in such groups could make lots and lots of waves.
For now however, this research extends the ideas that: (a) preferential screening for vitamin D might be indicated for this group/label, and (b) the focus on psychiatric presentation should not be made at the expense of somatic presentation. Parity of esteem and all that; or rather just making sure that health inequality does not follow from receipt of a psychiatric label...
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[1] Lally J. et al. Clinical correlates of vitamin D deficiency in established psychosis. BMC Psychiatry. 2016; 16: 76.
[2] Leboyer M. et al. Is it time for immunopsychiatry in psychotic disorders? Psychopharmacology (Berl). 2016 Mar 18.
[3] 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.
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Tuesday, 24 November 2015
Secondary conditions impacting on obesity stats in autism?
"Decision makers, clinicians, and researchers developing interventions for children with ASDs [autism spectrum disorders] should consider how secondary conditions may impact obesity and related activities."That was the conclusion reached in the study by Kathryn Corvey and colleagues [1] looking to: "examine obesity, overweight, physical activity, and sedentary behavior among children and youth with and without ASD using nationally representative data and controlling for secondary conditions, including intellectual and learning disabilities, ADHD, developmental delay, and other mental, physical, and medical conditions, as well as medication use."
Detailing results based on information gathered from the 2011-2012 National Survey of Children's Health whereby households of some 65,000 children between the ages of 6 and 17 years were quizzed about various physical and emotional health related matters, researchers specifically focused on some 1300 children with a reported diagnosis of ASD. Various confounding variables including those 'secondary conditions' were taken into account in their quite detailed analyses.
Results: following a trend noted in other peer-reviewed research (see here), the authors reported that a diagnosis of ASD was associated with elevated odds of being obese. But... when it came to adjusting their analyses for the presence of some of those secondary conditions "ASD diagnosis was no longer associated with obesity."
This is interesting stuff. In line with some of the shifts in thinking about autism these days - including plurality, comorbidity clusters and the idea of differing developmental trajectories - the Corvey results imply that more care is needed before making sweeping generalisations about how 'all' autism is linked to obesity or related issues. This comes at a time when other research has talked about the timing of weight issues when it comes to autism [2]. Allied to previous research more generally looking at obesity in learning disability [3] the message is becoming a little clearer that a variety of factors 'around' autism might be the important risk issues for something like obesity or being overweight including various social factors linked to physical activity levels too (see here).
Quite recently I've also become rather interested in the peer-reviewed research related to ADHD (attention-deficit hyperactivity disorder) and obesity (see here) and some of the clues emerging there that are potentially relevant to some autism. Allied to what is known about the 'anthropometric' effects of certain types of medication used by some on the autism spectrum (see here), and it appears that risk of obesity and being overweight in relation to autism is at last getting the 'no sweeping generalisations needed' handling that it truly deserves.
Music: Pick A Part That's New - Stereophonics.
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[1] Corvey K. et al. Obesity, Physical Activity and Sedentary Behaviors in Children with an Autism Spectrum Disorder. Matern Child Health J. 2015 Oct 29.
[2] Hill AP. et al. Obesity and Autism. Pediatrics. 2015. Nov 2.
[3] de Winter CF. et al. Overweight and obesity in older people with intellectual disability. Res Dev Disabil. 2012 Mar-Apr;33(2):398-405.
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Tuesday, 24 February 2015
Maternal recall vs. medical records: implications for autism research
I don't want to dwell too much on the findings reported by Paula Krakowiak and colleagues [1] talking about the accuracy of "maternally-reported diabetes and hypertensive disorders, and reliability of BMI [body mass index] measurements during periconception and pregnancy compared with medical records when mothers are interviewed 2-5 years after delivery" but they are potentially important.
With authors such as Krakowiak and Irva Hertz-Picciotto on the paper in question, those who follow the autism research scene might have already made the connection back to the CHARGE (CHildhood Autism Risks from Genetics and the Environment) study (beincharge!) as the source of the current data. Indeed from CHARGE, findings such as a link between maternal obesity and offspring autism risk (see here) and maternal diabetes and autism (see here) have been previously discussed on this blog. For the most part, examination of such factors linked to subsequent offspring autism diagnosis has been through self-report and post-event questioning which potentially opens up such studies to various forms of bias.
The results from Krakowiak et al seemed to suggest when questioned about such issues: "self-reported diabetes and hypertensive disorders during periconception and pregnancy show high validity among mothers." Further: "Recall of pre-pregnancy BMI is reliable compared with self-reported values in medical records." In other words, still with some caution, families involved in initiatives such as CHARGE can and do quite accurately communicate their medical history. Of course this is not the first time that science has shown parentally-derived medical information to be pretty accurate when it comes to autism as per the Gorrindo findings [2]: "sensitive to the existence, although not necessarily the nature of" gastrointestinal issues related to autism (see here). That being said, developmental history recall is still subject to some forms of bias (see here).
There's little more for me to say about this topic aside from highlighting how: "Multiparity was associated with higher discrepancies in BMI and misreporting of hypertensive disorders" suggestive that 'the state of having borne a number of children' might interfere with recall in these areas. Still, when it comes to asking parents about their health and wellbeing before, during and after the birth of their children with autism research in mind and without over-generalising, one might be a little less critical of the value of the information received.
Music to close: The Flaming Lips and Race For The Prize. Scientists... don't race for the prize!
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[1] Krakowiak P. et al. Maternal Recall Versus Medical Records of Metabolic Conditions from the Prenatal Period: A Validation Study. Matern Child Health J. 2015 Feb 6.
[2] Gorrindo P. et al. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012 Apr;5(2):101-8.
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Krakowiak P, Walker CK, Tancredi DJ, & Hertz-Picciotto I (2015). Maternal Recall Versus Medical Records of Metabolic Conditions from the Prenatal Period: A Validation Study. Maternal and child health journal PMID: 25656730
With authors such as Krakowiak and Irva Hertz-Picciotto on the paper in question, those who follow the autism research scene might have already made the connection back to the CHARGE (CHildhood Autism Risks from Genetics and the Environment) study (beincharge!) as the source of the current data. Indeed from CHARGE, findings such as a link between maternal obesity and offspring autism risk (see here) and maternal diabetes and autism (see here) have been previously discussed on this blog. For the most part, examination of such factors linked to subsequent offspring autism diagnosis has been through self-report and post-event questioning which potentially opens up such studies to various forms of bias.
The results from Krakowiak et al seemed to suggest when questioned about such issues: "self-reported diabetes and hypertensive disorders during periconception and pregnancy show high validity among mothers." Further: "Recall of pre-pregnancy BMI is reliable compared with self-reported values in medical records." In other words, still with some caution, families involved in initiatives such as CHARGE can and do quite accurately communicate their medical history. Of course this is not the first time that science has shown parentally-derived medical information to be pretty accurate when it comes to autism as per the Gorrindo findings [2]: "sensitive to the existence, although not necessarily the nature of" gastrointestinal issues related to autism (see here). That being said, developmental history recall is still subject to some forms of bias (see here).
There's little more for me to say about this topic aside from highlighting how: "Multiparity was associated with higher discrepancies in BMI and misreporting of hypertensive disorders" suggestive that 'the state of having borne a number of children' might interfere with recall in these areas. Still, when it comes to asking parents about their health and wellbeing before, during and after the birth of their children with autism research in mind and without over-generalising, one might be a little less critical of the value of the information received.
Music to close: The Flaming Lips and Race For The Prize. Scientists... don't race for the prize!
----------
[1] Krakowiak P. et al. Maternal Recall Versus Medical Records of Metabolic Conditions from the Prenatal Period: A Validation Study. Matern Child Health J. 2015 Feb 6.
[2] Gorrindo P. et al. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012 Apr;5(2):101-8.
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Tuesday, 21 October 2014
Antibiotics and childhood obesity: a weighty correlation
It's been a few weeks since the publication of the paper by L. Charles Bailey and colleagues [1] correlating early multiple exposure to broad spectrum antibiotics with obesity in infancy. On purpose I've left it a while before talking about this research so as to let the scientific dust settle a little and get a flavour for some of the discussions about this research (see here and see here).
A few details about the Bailey study first:
The Bailey results are interesting insofar as the association being made between early antibiotic use and obesity but, as always, a little caution needs to be applied before reading too much into the findings. I note the BBC coverage of this article mentions limitations: "they were not able to look at the children's weight or exercise regimes" so correlation not necessarily being the same as causation comes into play. I might also add that whilst antibiotic stewardship is still a developing area, many/most antibiotic prescriptions are not just given willy-nilly as any parent with a young child suffering from an ear infection for example, will probably be able to attest.
I have kinda talked around this area of antibiotics and weight before on this blog (see here) and the implication that antibiotics, broad spectrum, by their very nature have a pretty profound effect on the trillions of bacterial beasties which inhabit places like the gastrointestinal (GI) tract. Carl Zimmer's post on swallowing a grenade (not literally) is a good starting point. The idea being that as well as helping digest our food, said bacteria (whether individual strains or through a more collective action) might also be able to influence a variety of issues like energy homoeostasis, weight management and even our risk of disease (see here and see here). If I take you back to some work looking at a particular bacterium called Akkermansia muciniphila you might get a flavour for this possible connection with weight in mind (at least in rodents).
I'm going to finish with another quote included with the BBC report on the Bailey findings. It comes from an independent commentary of the paper and sums up some important issues arising from reading this work:
"It would be a concern if parents took from this that they ought to be reluctant to allow antibiotic use in their children. The key risk factors for childhood obesity are over-consumption of high energy, nutrient-poor foods and lack of exercise."
Whilst I would perhaps suggest that 'energy in - energy out' is too simplistic an explanation of weight management issues (see here) I would agree that under the right circumstances, antibiotics still make a valuable contribution to the medicines cabinet, and obesity is, very much, a multi-faceted condition.
Music... Stevie Wonder and Superstition.
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[1] Bailey LC. et al. Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA Pediatr. 2014. 29 Sept.
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Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, & DeRusso PA (2014). Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA pediatrics PMID: 25265089
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| You're a true vulgarian, aren't you? |
A few details about the Bailey study first:
- Looking at the electronic records for a large cohort of children (~65,000), researchers picked out "Treatment episodes for prescribed antibiotics" based on prescription data before the age of 2 years.
- Anthropometric (growth) data was also determined from visits to healthcare providers between the ages of 2 and 5 years and compared with body mass index (BMI) norms derived from a large US-based survey, NHANES.
- Results: "Sixty-nine percent of children were exposed to antibiotics before age 24 months" with a rough average of 2 antibiotic prescriptions per child. For those who received 4 or more courses of antibiotics, the risk of obesity during early childhood was slightly elevated (11%) compared with those receiving fewer courses.
- The authors specifically focused on broad spectrum antibiotics as being correlated with infant weight issues; antimicrobials acting against a broad range of bacteria rather than more targeted pharmaceutics.
- They concluded: "Repeated exposure to broad-spectrum antibiotics at ages 0 to 23 months is associated with early childhood obesity". That being said, they also noted that various other factors seemed to correlate with infant obesity including: "Steroid use, male sex, urban practice, public insurance, Hispanic ethnicity, and diagnosed asthma or wheezing".
- I'm also minded to pull in a few other findings which did not get so many media headlines such as the reporting that at 4 years of age, 15% of the cohort were found to be obese and 33% overweight (source here).
The Bailey results are interesting insofar as the association being made between early antibiotic use and obesity but, as always, a little caution needs to be applied before reading too much into the findings. I note the BBC coverage of this article mentions limitations: "they were not able to look at the children's weight or exercise regimes" so correlation not necessarily being the same as causation comes into play. I might also add that whilst antibiotic stewardship is still a developing area, many/most antibiotic prescriptions are not just given willy-nilly as any parent with a young child suffering from an ear infection for example, will probably be able to attest.
I have kinda talked around this area of antibiotics and weight before on this blog (see here) and the implication that antibiotics, broad spectrum, by their very nature have a pretty profound effect on the trillions of bacterial beasties which inhabit places like the gastrointestinal (GI) tract. Carl Zimmer's post on swallowing a grenade (not literally) is a good starting point. The idea being that as well as helping digest our food, said bacteria (whether individual strains or through a more collective action) might also be able to influence a variety of issues like energy homoeostasis, weight management and even our risk of disease (see here and see here). If I take you back to some work looking at a particular bacterium called Akkermansia muciniphila you might get a flavour for this possible connection with weight in mind (at least in rodents).
I'm going to finish with another quote included with the BBC report on the Bailey findings. It comes from an independent commentary of the paper and sums up some important issues arising from reading this work:
"It would be a concern if parents took from this that they ought to be reluctant to allow antibiotic use in their children. The key risk factors for childhood obesity are over-consumption of high energy, nutrient-poor foods and lack of exercise."
Whilst I would perhaps suggest that 'energy in - energy out' is too simplistic an explanation of weight management issues (see here) I would agree that under the right circumstances, antibiotics still make a valuable contribution to the medicines cabinet, and obesity is, very much, a multi-faceted condition.
Music... Stevie Wonder and Superstition.
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[1] Bailey LC. et al. Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA Pediatr. 2014. 29 Sept.
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