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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News and views on autism research and other musings. Sometimes uncomfortable but rooted in peer-reviewed scientific research.
Showing posts with label caesarean section. Show all posts
Showing posts with label caesarean section. Show all posts
Friday, 11 January 2019
Wednesday, 4 October 2017
Can a 'disturbed gut microbiota' explain a cognitive performance dip in those born by C-section?
In answer to the question posed in the title of this post - Can a 'disturbed gut microbiota' explain a cognitive performance dip in those born by C-section? - I have to say that I don't know. I was however, rather intrigued by the findings reported by Cain Polidano and colleagues [1] (open-access) who observed that "cesarean-born children perform significantly below vaginally-born children, by up to a tenth of a standard deviation in national numeracy test scores at age 8–9" when allowing for "a large range of confounders."Based on data derived from the Longitudinal Study of Australian Children (LSAC), a sort of Aussie equivalent to ALSPAC here in Blighty, researchers set about examining whether the growth in Caesarean sections might have some long-term implications for child cognitive development. The question of whether those trillions of wee beasties (bacteria and the like) that call our gastrointestinal (GI) tract home might be implicated in the cognitive findings stems from previous research talking about how, theoretically, said bacteria might be doing so much more than just helping us to digest our food or producing the odd nutrient here and there (see here for example). This also bearing in mind that those born by C-section have been suggested to show a different gut bacteria profile from those not. I say all that acknowledging that gut bacteria doing this, that and t'other is going through something of a period of reflection at the moment (see here).
It is the size of the Polidano participant sample (N=3,666) and the "internationally recognized and widely-used longitudinal" nature of the LSAC that interested me in these findings. The authors provide quite a bit of detail on how the initiative works and what measures have been put in place to potentially rule out mediating and/or confounding variables. Even missing data has been discussed and accounted for: "non-random attrition does not appear to be seriously biasing our results."
What is unfortunately missing from the Polidano paper is any measure of 'gut bacteria' to substantiate the possibility of a connection between C-section birth, gut bacteria and academic outcome(s). I say this bearing in mind that whilst there is extensive literature talking about *associations* between C-section birth and a variety of cognitive and developmental outcomes, the details are still a little scarce insofar as whether any association is tied to a specific family of bacteria or indeed, something like overall bacterial diversity. One also has to bear in mind that other factors also affect newborn gut bacterial make-up such as breastfeeding and seemingly specific components of breastfeeding [2]. I note that other authors are also not sold on the ideas generated from the Polidano paper (see here) and caution that C-sections are not somehow demonised as a result (not everyone is 'too posh to push').
"While the magnitude of our estimated difference in outcomes is not large, up to a tenth of a standard deviation in national test scores in numeracy, they are large enough to warrant action." The authors note that their observations might not seem to show a particularly large contribution to cognitive development, they are nonetheless still potentially important. Indeed: "A tenth of a standard deviation in national test scores is comparable in size to differences related to gender, class size and teacher quality that are the focus of policy effort." In other words, don't discount this potentially important area of investigation just yet...
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[1] Polidano C. et al. The relation between cesarean birth and child cognitive development. Scientific Reports. 2017; 7: 11483.
[2] Toscano M. et al. Impact of delivery mode on the colostrum microbiota composition. BMC Microbiology. 2017; 17: 205.
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Saturday, 2 July 2016
The gut microbiome and coeliac disease risk
"Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD [coeliac disease] onset during childhood, suggesting the role of dysbiosis during early life."
Those were some of the rather surprising findings reported by Fredinah Namatovu and colleagues [1] (open-access) following their pretty well-powered study covering "1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age" living in Sweden. With the aim of exploring "how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood" quite a few variables were thrown into the statistical mix with some rather interesting results. Indeed, researchers also reported that: "High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style."
Aside from the rather large participant numbers included for study "based on the entire child population in Sweden born during between 1991 and 2009" Namatovu et al were also able to accumulate enough cases of CD so as to ensure "high precision in [their] estimates and enabled adjustment for several variables." Said CD cases were also rigorously confirmed, being "identified through the Swedish National Childhood CD Incidence Register reported from all paediatric departments across the country."
The idea that although there is a pretty well-defined course of genetic and biological events tied into CD (see here) onset might also be moderated by some impact of those trillions of wee beasties that call us home (the gut microbiome) for example, is not a new one. I've already covered the peer-reviewed idea that antibiotic use potentially 'altering' the gut microbiome might have implications for CD on this blog (see here). I note also that a recent review by Simon Murch [2] also mentions a possible role for the gut microbiome too, and with it the requirement for greater scrutiny of this important organ [3]. This all falling under the general suggestion that antibiotics during infancy 'might change their gut microbes for years'.
"In future, preventive strategies could benefit by taking measures to prevent gut dysbiosis." Further: "Reduced prescription of antibiotics is one way that would also work to counteract the enormous problem with development of bacterial resistance to antibiotics. Promoting normal delivery would also be in line with goals in the field of maternal and child health." I, personally, would like to see a little more investigation done on such variables before anyone jumps to too many conclusions. The jury is for example, currently out when it comes to infant feeding and risk of CD [4] on the basis of the suggestion by Namatovu et al that: "older mothers are more likely to practise prolonged and exclusive breastfeeding." There is slightly more support for the idea that a child's mode of entry into the world might influence the development of CD [5] but the absolute risk seems to be rather small.
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[1] Namatovu F. et al. Maternal and perinatal conditions and the risk of developing celiac disease during childhood. BMC Pediatrics. 2016;16:77.
[2] Murch S. Recent Advances in Celiac Disease. Indian J Pediatr. 2016 Jun 8.
[3] Baquero F.& Nombela C. The microbiome as a human organ. Clin Microbiol Infect. 2012 Jul;18 Suppl 4:2-4.
[4] Silano M. et al. Infant feeding and risk of developing celiac disease: a systematic review. BMJ Open. 2016 Jan 25;6(1):e009163.
[5] Mårild K. et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. 2012 Jan;142(1):39-45.e3.
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Namatovu, F., Olsson, C., Lindkvist, M., Myléus, A., Högberg, U., Ivarsson, A., & Sandström, O. (2016). Maternal and perinatal conditions and the risk of developing celiac disease during childhood BMC Pediatrics, 16 (1) DOI: 10.1186/s12887-016-0613-y
Those were some of the rather surprising findings reported by Fredinah Namatovu and colleagues [1] (open-access) following their pretty well-powered study covering "1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age" living in Sweden. With the aim of exploring "how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood" quite a few variables were thrown into the statistical mix with some rather interesting results. Indeed, researchers also reported that: "High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style."
Aside from the rather large participant numbers included for study "based on the entire child population in Sweden born during between 1991 and 2009" Namatovu et al were also able to accumulate enough cases of CD so as to ensure "high precision in [their] estimates and enabled adjustment for several variables." Said CD cases were also rigorously confirmed, being "identified through the Swedish National Childhood CD Incidence Register reported from all paediatric departments across the country."
The idea that although there is a pretty well-defined course of genetic and biological events tied into CD (see here) onset might also be moderated by some impact of those trillions of wee beasties that call us home (the gut microbiome) for example, is not a new one. I've already covered the peer-reviewed idea that antibiotic use potentially 'altering' the gut microbiome might have implications for CD on this blog (see here). I note also that a recent review by Simon Murch [2] also mentions a possible role for the gut microbiome too, and with it the requirement for greater scrutiny of this important organ [3]. This all falling under the general suggestion that antibiotics during infancy 'might change their gut microbes for years'.
"In future, preventive strategies could benefit by taking measures to prevent gut dysbiosis." Further: "Reduced prescription of antibiotics is one way that would also work to counteract the enormous problem with development of bacterial resistance to antibiotics. Promoting normal delivery would also be in line with goals in the field of maternal and child health." I, personally, would like to see a little more investigation done on such variables before anyone jumps to too many conclusions. The jury is for example, currently out when it comes to infant feeding and risk of CD [4] on the basis of the suggestion by Namatovu et al that: "older mothers are more likely to practise prolonged and exclusive breastfeeding." There is slightly more support for the idea that a child's mode of entry into the world might influence the development of CD [5] but the absolute risk seems to be rather small.
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[1] Namatovu F. et al. Maternal and perinatal conditions and the risk of developing celiac disease during childhood. BMC Pediatrics. 2016;16:77.
[2] Murch S. Recent Advances in Celiac Disease. Indian J Pediatr. 2016 Jun 8.
[3] Baquero F.& Nombela C. The microbiome as a human organ. Clin Microbiol Infect. 2012 Jul;18 Suppl 4:2-4.
[4] Silano M. et al. Infant feeding and risk of developing celiac disease: a systematic review. BMJ Open. 2016 Jan 25;6(1):e009163.
[5] Mårild K. et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. 2012 Jan;142(1):39-45.e3.
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Saturday, 27 February 2016
C-section and the microbial transplant
I'm pretty sure that the paper by Maria Dominguez-Bello and colleagues [1] speaks for itself when describing the results of "a pilot study in which infants delivered by C-section [Caesarean section] were exposed to maternal vaginal fluids at birth." If you need a graphic, some coverage of the research in the New York Times helpfully provides a visual aid (see here).
The long-and-short of it is that following some concerns that infants delivered via C-section might be missing out on some valuable exposure to their mother's microbial passengers [2] as a function of their by-passing the birth canal and beyond, the use of a "vaginal microbial transfer" might be an option. Detailing results based on a small number of births - 11 born by C-section (planned or elective) and 7 via the more traditional route - researchers report what happened when 4 of the C-section infants were swabbed with previously collected gauze containing mum's bacterial passengers. Swabbing by the way, was done on various parts of the infant's body.
The authors concluded that: "Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns [swabbed C-section infants] during the first 30 d[ays] of life was enriched in vaginal bacteria—which were underrepresented in unexposed C-section–delivered infants." That being said, the results appeared to show that whilst swabbing was good at delivering a microbial transplant for C-section infants, it was no substitute for the real thing (a vaginal birth) bacterially-speaking. I might also add that important variables such as breastfeeding (or not) can also influence the constitution of our gut bacteria (see here).
There is some media chatter about this study and onwards what the longer-term effects might be in terms of health and well-being in the context of how our bacterial masters may show various health/disease links [3]. I'd be interested to see how this cohort and other larger ones fare as a result. I do however, have a word of caution to add to proceedings alongside others it seems (see here).
Accepting that a vaginal microbial transfer is not the same as the more 'popular' talking point that is a faecal microbiota transplant, and that the bacteria that colonise the gut may not necessarily be the same as that colonising other parts of the body, I'm minded to direct readers to a post not-so-long-ago covering weight gain following poo(p) transplant (see here). I don't think the specific 'obesogenic' bacteria were isolated in the case report by by Neha Alang and Colleen Kelly [3] or indeed, whether other elements such as the gut virome may have exerted some effect on patient weight gain following "receiving stool from a healthy but overweight donor." But one question might be to ask whether a similar 'process' could potentially be pertinent to the swabbing of C-section infants?
OK, I appreciate that there has been some research discussion about how C-section babies *might* be slightly more prone to obesity in later life (see here). But if one assumes that outside of the typical risk factors linked to obesity, there may be a microbial link too, is it not inconceivable that an early-days microbial transplant from a mum who is herself overweight or obese at the time of birth might potentially 'transmit' the basis of such weight problems to offspring too? Indeed, with all the chatter about microbes and mood these days (see here for example) one could potentially stretch the 'bacterial association' even further...
I'll leave you with those thoughts and some (new) music from the Leppard (hopefully really not a "nuclear waste of time").
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[1] Dominguez-Bello MG. et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature Medicine. 2016. Feb 2.
[2] Biasucci G. et al. Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr. 2008 Sep;138(9):1796S-1800S.
[3] Alang N. & Kelly CR. Weight Gain After Fecal Microbiota Transplantation. Open Forum Infect Dis. 2015; 2: 1.
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Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R, & Clemente JC (2016). Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature medicine PMID: 26828196
The long-and-short of it is that following some concerns that infants delivered via C-section might be missing out on some valuable exposure to their mother's microbial passengers [2] as a function of their by-passing the birth canal and beyond, the use of a "vaginal microbial transfer" might be an option. Detailing results based on a small number of births - 11 born by C-section (planned or elective) and 7 via the more traditional route - researchers report what happened when 4 of the C-section infants were swabbed with previously collected gauze containing mum's bacterial passengers. Swabbing by the way, was done on various parts of the infant's body.
The authors concluded that: "Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns [swabbed C-section infants] during the first 30 d[ays] of life was enriched in vaginal bacteria—which were underrepresented in unexposed C-section–delivered infants." That being said, the results appeared to show that whilst swabbing was good at delivering a microbial transplant for C-section infants, it was no substitute for the real thing (a vaginal birth) bacterially-speaking. I might also add that important variables such as breastfeeding (or not) can also influence the constitution of our gut bacteria (see here).
There is some media chatter about this study and onwards what the longer-term effects might be in terms of health and well-being in the context of how our bacterial masters may show various health/disease links [3]. I'd be interested to see how this cohort and other larger ones fare as a result. I do however, have a word of caution to add to proceedings alongside others it seems (see here).
Accepting that a vaginal microbial transfer is not the same as the more 'popular' talking point that is a faecal microbiota transplant, and that the bacteria that colonise the gut may not necessarily be the same as that colonising other parts of the body, I'm minded to direct readers to a post not-so-long-ago covering weight gain following poo(p) transplant (see here). I don't think the specific 'obesogenic' bacteria were isolated in the case report by by Neha Alang and Colleen Kelly [3] or indeed, whether other elements such as the gut virome may have exerted some effect on patient weight gain following "receiving stool from a healthy but overweight donor." But one question might be to ask whether a similar 'process' could potentially be pertinent to the swabbing of C-section infants?
OK, I appreciate that there has been some research discussion about how C-section babies *might* be slightly more prone to obesity in later life (see here). But if one assumes that outside of the typical risk factors linked to obesity, there may be a microbial link too, is it not inconceivable that an early-days microbial transplant from a mum who is herself overweight or obese at the time of birth might potentially 'transmit' the basis of such weight problems to offspring too? Indeed, with all the chatter about microbes and mood these days (see here for example) one could potentially stretch the 'bacterial association' even further...
I'll leave you with those thoughts and some (new) music from the Leppard (hopefully really not a "nuclear waste of time").
----------
[1] Dominguez-Bello MG. et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature Medicine. 2016. Feb 2.
[2] Biasucci G. et al. Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr. 2008 Sep;138(9):1796S-1800S.
[3] Alang N. & Kelly CR. Weight Gain After Fecal Microbiota Transplantation. Open Forum Infect Dis. 2015; 2: 1.
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Tuesday, 20 October 2015
No wait... C-sections are NOT linked to autism
A quote to begin: "There was no association between planned CS [Caesarean section] and ASD [autism spectrum disorder]... or ADHD [attention-deficit hyperactivity disorder]." And further: "There was no association between mode of delivery and ASD or ADHD in this cohort."Those were the conclusions reached in the paper by Eileen Curran and colleagues [1] who sought to look at whether the route of entry into the world may influence offspring risk of autism or ADHD. Based on data derived from The Millennium Cohort Study (MCS), a longitudinal survey covering the birth period and "including 13,141 children", researchers dived into the treasure trove of collected information to see whether "birth by Cesarean section (CS) and induction of labor (IOL)" correlated with later childhood outcomes. Probably not was the answer coming back, or at least not in any generalisable sense. Indeed, other recent research has also suggested similar things [2].
This is interesting research. Not least because I've discussed other work from this research group on this topic before on this blog (see here) based on their systematic review and meta-analysis of the available data up to February 2014 [3]. Up until then, the message was a cautious: "Delivery by CS is associated with a modest increased odds of ASD, and possibly ADHD, when compared to vaginal delivery."
At this point I'd also like to introduce another recent paper from this authorship group [4] further adding to this debate about birth method and offspring risk (or not) of autism. Based on data derived from the "Swedish Medical Birth Register and the Swedish National Patient Register" providing information on perinatal factors and ASD diagnosis respectively, the authors concluded that whilst "children born by CS are approximately 20% more likely to be diagnosed as having ASD", this association dwindled somewhat when "using sibling controls." Ergo, the correlation between birth by C-section and autism diagnosis is likely "confounding by genetic and/or environmental factors." A good write-up of the study can be seen here.
So, based on two pretty large (participants in the thousands) studies, geographically separate (UK vs. Sweden), the suggestion that birthing method might affect autism risk turns out to be not as strong as originally suggested and with it a reminder that meta-analyses are only as strong as the data they include. I know most people with their eyes and ears to the autism research scene probably won't be shocked by these results and the almost pantomime-like state ('oh yes it is, oh no it's not') of various aspects of autism research. As has been noted on some occasions, autism research seems to have a reproducibility crisis of its own to contend with.
But in all of that a few reminders: autism is a very heterogeneous condition (remember the autisms) and just because there is not population-wide effect does not mean that variable A, B or C is all bunk when it comes to 'some' autism (see here). Oh, and baby and bathwater - as in, don't throw them both out - should also be remembered [5]...
And now... Star Wars.
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[1] Curran EA. et al. Obstetrical Mode of Delivery and Childhood Behavior and Psychological Development in a British Cohort. J Autism Dev Disord. 2015 Sep 28.
[2] Robson SJ. et al. Childhood Health and Developmental Outcomes After Cesarean Birth in an Australian Cohort. Pediatrics. 2015. October 12.
[3] Curran EA. et al. Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry. 2015 May;56(5):500-8.
[4] Curran EA. et al. Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study. JAMA Psychiatry. 2015 Sep 1;72(9):935-42.
[5] Chien LN. et al. Risk of autism associated with general anesthesia during cesarean delivery: a population-based birth-cohort analysis. J Autism Dev Disord. 2015 Apr;45(4):932-42.
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Friday, 31 October 2014
Caesarean section births and autism risk?
It was a familiar story. Big media headlines such as: Caesarean sections 'may increase risk of autism' appearing all over, but when it came to finding the study behind the headlines, the publishing journal seemed to be trailing a little way behind. We've been in a similar situation before.
Anyhow, the paper by Eileen Curran and colleagues [1] (open-access) has finally made it to the research table and hence is fodder for today's ramblings with the suggestion that the way we make our grand entrance into the world might correlate with some heightened risk for autism spectrum disorder (ASD).
I have to say that I was initially quite interested in the Curran findings for quite a few reasons. Primary among them is some curiosity I have about the gut microbiota in relation to quite a few states and diagnoses (see here) and how our mode of entry into the world can seemingly impact on our first exposure to the bacterial passengers which eventually call us home. It is perhaps one of the lesser known observations, that the voyage down our dear mothers birth canal is also a great meet-and-greet opportunity for baby and bacteria. For those who don't get to experience such wonders, there is a suggestion that different types of bacteria might make friends which are then 'programmed' to be accepted by our developing immune systems [2] with onwards possible significance for future health and wellbeing. That being said, there is still a way to go to understanding such a relationship more thoroughly despite some intriguing results specifically with autism and the gut microbiome in mind (see here). I might also add that some of the authors on the Curran paper seemingly have some interest in the whole gut bacteria - behaviour relationship as per another recent paper [3].
The Curran paper is a systematic review of the literature which looked at: "mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD)". They concluded that: "Thirteen studies reported an adjusted estimate for CS-ASD [Caesarean section-ASD], producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40)". Said studies were analysed up to February 2014. The population attributable fraction calculated by authors implied that: "5.36% of cases of ASD may be attributable to delivery by CS assuming the observed association is causal".
The lead author is rightly cautious about their findings, as per some other comment in the media: “Parents should be reassured that the overall risk of a child developing ASD (Autism Spectrum Disorder) is very small and that Caesarean section is largely a very safe procedure and when medically indicated, it can be lifesaving,”. I wouldn't disagree with those sentiments allowing for the fact that (a) a fair proportion of deliveries these days are by C-section, and (b) not every child diagnosed with autism is delivered via C-section.
That being said, there does seem to be more to do in this area of science. Subsequent studies published after the cut-off point set by Curran have reported C-sections as a 'risk factor' for autism. The paper by Salhia and colleagues [4] for example, looking at the epidemiology of autism in [some] Arab Gulf countries found as much, alongside some other quite frequently reported variables potentially influencing autism risk (e.g. advanced maternal and paternal age).
I'm going to drop in a few additional papers and then I'm done. Chien and colleagues [5] also talked about C-sections as a risk factor for autism but with the added twist that the use of a general anaesthetic during said procedure might be implicated in any relationship. You might scoff at the suggestion that anaesthetic has anything to do with autism but before you do, perhaps have a read through the paper by DiMaggio and colleagues [6] first and slightly more speculatively, the paper by Johnson and colleagues [7]. The study by Chudal and colleagues [8] - mentioned by Curren et al - looking at various perinatal factors in the context of bipolar disorder is also worthwhile introducing bearing in mind that interest in such comorbidity is increasing in the context of some autism (see here). As with many other variables 'correlated' to autism risk, to shut the door on any association with comorbidity outside of just the diagnosis of autism is foolhardy.
Irrespective of your opinion about whether C-sections might be linked to autism risk and the other possible reasoning behind said suggestion [9], the Curran paper joins a growing list of variables potentially associated with autism. Systematic reviews and meta-analyses are consolidating quite a bit of this data, although as always the heterogeneity covered under the label of autism and the important issue of comorbidity need to be kept in mind. As with the growing idea that many small genetic issues might cumulatively be linked to [some] autism further compounded by more recent data [10] (see here for some media), so one might assume that multiple small contributions from the 'environment' might likewise also influence offspring risk of autism too. Determining how and when these genetic and environmental variables come together seems to be to be the next logical step...
Music to close: The Specials and Ghost Town. Have a spooky day!
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[1] Curran EA. et al. Research Review: Birth by Caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Journal of Child Psychology and Psychiatry. 2014. October 27.
[2] Weng M. & Walker WA. The role of gut microbiota in programming the immune phenotype. J Dev Orig Health Dis. 2013 Jun;4(3):203-14.
[3] Stilling RM. et al. Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front. Cell. Infect. Microbiol. 2014. October 29.
[4] Salhia HO. et al. Systemic review of the epidemiology of autism in Arab Gulf countries. Neurosciences (Riyadh). 2014 Oct;19(4):291-6.
[5] Chien LN. et al. Risk of Autism Associated With General Anesthesia During Cesarean Delivery: A Population-Based Birth-Cohort Analysis. J Autism Dev Disord. 2014 Sep 26.
[6] DiMaggio C. et al. Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort. Anesth Analg. 2011 Nov;113(5):1143-51.
[7] Johnson B. et al. Fibromyalgia, autism, and opioid addiction as natural and induced disorders of the endogenous opioid hormonal system. Discov Med. 2014 Oct;18(99):209-20.
[8] Chudal R. et al. Perinatal factors and the risk of bipolar disorder in Finland. J Affect Disord. 2014 Feb;155:75-80.
[9] Gialloreti LE. et al. Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders? Med Hypotheses. 2014 Jun;82(6):713-8.
[10] Iossifov I. et al. The contribution of de novo coding mutations to autism spectrum disorder Nature. 2014. October 29.
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Curran EA, O'Neill SM, Cryan JF, Kenny LC, Dinan TG, Khashan AS, & Kearney PM (2014). Research Review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Journal of child psychology and psychiatry, and allied disciplines PMID: 25348074
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| "As the flames rose to her Roman nose" |
Anyhow, the paper by Eileen Curran and colleagues [1] (open-access) has finally made it to the research table and hence is fodder for today's ramblings with the suggestion that the way we make our grand entrance into the world might correlate with some heightened risk for autism spectrum disorder (ASD).
I have to say that I was initially quite interested in the Curran findings for quite a few reasons. Primary among them is some curiosity I have about the gut microbiota in relation to quite a few states and diagnoses (see here) and how our mode of entry into the world can seemingly impact on our first exposure to the bacterial passengers which eventually call us home. It is perhaps one of the lesser known observations, that the voyage down our dear mothers birth canal is also a great meet-and-greet opportunity for baby and bacteria. For those who don't get to experience such wonders, there is a suggestion that different types of bacteria might make friends which are then 'programmed' to be accepted by our developing immune systems [2] with onwards possible significance for future health and wellbeing. That being said, there is still a way to go to understanding such a relationship more thoroughly despite some intriguing results specifically with autism and the gut microbiome in mind (see here). I might also add that some of the authors on the Curran paper seemingly have some interest in the whole gut bacteria - behaviour relationship as per another recent paper [3].
The Curran paper is a systematic review of the literature which looked at: "mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD)". They concluded that: "Thirteen studies reported an adjusted estimate for CS-ASD [Caesarean section-ASD], producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40)". Said studies were analysed up to February 2014. The population attributable fraction calculated by authors implied that: "5.36% of cases of ASD may be attributable to delivery by CS assuming the observed association is causal".
The lead author is rightly cautious about their findings, as per some other comment in the media: “Parents should be reassured that the overall risk of a child developing ASD (Autism Spectrum Disorder) is very small and that Caesarean section is largely a very safe procedure and when medically indicated, it can be lifesaving,”. I wouldn't disagree with those sentiments allowing for the fact that (a) a fair proportion of deliveries these days are by C-section, and (b) not every child diagnosed with autism is delivered via C-section.
That being said, there does seem to be more to do in this area of science. Subsequent studies published after the cut-off point set by Curran have reported C-sections as a 'risk factor' for autism. The paper by Salhia and colleagues [4] for example, looking at the epidemiology of autism in [some] Arab Gulf countries found as much, alongside some other quite frequently reported variables potentially influencing autism risk (e.g. advanced maternal and paternal age).
I'm going to drop in a few additional papers and then I'm done. Chien and colleagues [5] also talked about C-sections as a risk factor for autism but with the added twist that the use of a general anaesthetic during said procedure might be implicated in any relationship. You might scoff at the suggestion that anaesthetic has anything to do with autism but before you do, perhaps have a read through the paper by DiMaggio and colleagues [6] first and slightly more speculatively, the paper by Johnson and colleagues [7]. The study by Chudal and colleagues [8] - mentioned by Curren et al - looking at various perinatal factors in the context of bipolar disorder is also worthwhile introducing bearing in mind that interest in such comorbidity is increasing in the context of some autism (see here). As with many other variables 'correlated' to autism risk, to shut the door on any association with comorbidity outside of just the diagnosis of autism is foolhardy.
Irrespective of your opinion about whether C-sections might be linked to autism risk and the other possible reasoning behind said suggestion [9], the Curran paper joins a growing list of variables potentially associated with autism. Systematic reviews and meta-analyses are consolidating quite a bit of this data, although as always the heterogeneity covered under the label of autism and the important issue of comorbidity need to be kept in mind. As with the growing idea that many small genetic issues might cumulatively be linked to [some] autism further compounded by more recent data [10] (see here for some media), so one might assume that multiple small contributions from the 'environment' might likewise also influence offspring risk of autism too. Determining how and when these genetic and environmental variables come together seems to be to be the next logical step...
Music to close: The Specials and Ghost Town. Have a spooky day!
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[1] Curran EA. et al. Research Review: Birth by Caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Journal of Child Psychology and Psychiatry. 2014. October 27.
[2] Weng M. & Walker WA. The role of gut microbiota in programming the immune phenotype. J Dev Orig Health Dis. 2013 Jun;4(3):203-14.
[3] Stilling RM. et al. Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front. Cell. Infect. Microbiol. 2014. October 29.
[4] Salhia HO. et al. Systemic review of the epidemiology of autism in Arab Gulf countries. Neurosciences (Riyadh). 2014 Oct;19(4):291-6.
[5] Chien LN. et al. Risk of Autism Associated With General Anesthesia During Cesarean Delivery: A Population-Based Birth-Cohort Analysis. J Autism Dev Disord. 2014 Sep 26.
[6] DiMaggio C. et al. Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort. Anesth Analg. 2011 Nov;113(5):1143-51.
[7] Johnson B. et al. Fibromyalgia, autism, and opioid addiction as natural and induced disorders of the endogenous opioid hormonal system. Discov Med. 2014 Oct;18(99):209-20.
[8] Chudal R. et al. Perinatal factors and the risk of bipolar disorder in Finland. J Affect Disord. 2014 Feb;155:75-80.
[9] Gialloreti LE. et al. Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders? Med Hypotheses. 2014 Jun;82(6):713-8.
[10] Iossifov I. et al. The contribution of de novo coding mutations to autism spectrum disorder Nature. 2014. October 29.
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Monday, 19 December 2011
C-sections and obesity
This is an extension post to a topic previously discussed on this blog and its sister blog in relation to your route of entry into the world potentially being correlated with later health and ill-health risk.
The header in the UK Sunday Times on 20 November 2011 was 'caesarean babies have greater risk of obesity'. We are told through this article that babies born through planned c-sections are more likely to become obese. The reason: higher levels of fats in the liver as a result of a malfunction of the metabolic processes which allows people to handle fats according to one of the authors, Prof. Neena Modi of Imperial College, London. It appears that the often traumatic journey from snug warm cocoon to big wide world via the birth canal, and all the hormones and chemicals involved in this process, might have lots of different lasting effects on baby. That's before you even reach the stage of cord clamping and when to do it.
I can't post a link to the study in question reporting these findings because I can't find it (yet). What we do know is that scanning livers of 62 babies and correlating with maternal body mass index (BMI) and birth route (vaginal, emergency c-section, planned c-section) revealed some interesting trends. So, mum's weight seemed to have an effect on liver fat content but only when birth was by planned c-section. This might have some interesting implications for the message being put out about larger mums predisposing to larger offspring.
The Imperial team (no, not that Imperial) are no strangers to this type of research as evidenced by a recent paper of theirs suggesting that fat in liver (intrahepatocellular lipid) of babies might be correlated with maternal body mass index (BMI). I assume that this latest research is an extension of their tried and tested investigative techniques.
Going back to my previous posts on c-sections, it is interesting that a few trends seem to be appearing. Labour and all the biochemical changes a woman's body makes when it is time to give birth seem to be important when it comes to a baby's subsequent risk of obesity (fatty liver anyway) and coeliac disease. Distinguishing emergency c-sections from planned c-sections, where one would assume that many of those biochemical changes are already starting to take place despite the fact that entry into the world is via a different port, also seems to be important.
I do also wonder about that favourite topic of mine 'bacteria' and whether babies who need to be delivered by emergency c-section might have already taken a few mouthfuls of the good stuff as a result of their partial journey down the birth canal? Does this mean that a good dose of mum's bacteria should accompany all planned c-sections? (Not that I'm offering any clinical advice!)
The header in the UK Sunday Times on 20 November 2011 was 'caesarean babies have greater risk of obesity'. We are told through this article that babies born through planned c-sections are more likely to become obese. The reason: higher levels of fats in the liver as a result of a malfunction of the metabolic processes which allows people to handle fats according to one of the authors, Prof. Neena Modi of Imperial College, London. It appears that the often traumatic journey from snug warm cocoon to big wide world via the birth canal, and all the hormones and chemicals involved in this process, might have lots of different lasting effects on baby. That's before you even reach the stage of cord clamping and when to do it.
I can't post a link to the study in question reporting these findings because I can't find it (yet). What we do know is that scanning livers of 62 babies and correlating with maternal body mass index (BMI) and birth route (vaginal, emergency c-section, planned c-section) revealed some interesting trends. So, mum's weight seemed to have an effect on liver fat content but only when birth was by planned c-section. This might have some interesting implications for the message being put out about larger mums predisposing to larger offspring.
The Imperial team (no, not that Imperial) are no strangers to this type of research as evidenced by a recent paper of theirs suggesting that fat in liver (intrahepatocellular lipid) of babies might be correlated with maternal body mass index (BMI). I assume that this latest research is an extension of their tried and tested investigative techniques.
Going back to my previous posts on c-sections, it is interesting that a few trends seem to be appearing. Labour and all the biochemical changes a woman's body makes when it is time to give birth seem to be important when it comes to a baby's subsequent risk of obesity (fatty liver anyway) and coeliac disease. Distinguishing emergency c-sections from planned c-sections, where one would assume that many of those biochemical changes are already starting to take place despite the fact that entry into the world is via a different port, also seems to be important.
I do also wonder about that favourite topic of mine 'bacteria' and whether babies who need to be delivered by emergency c-section might have already taken a few mouthfuls of the good stuff as a result of their partial journey down the birth canal? Does this mean that a good dose of mum's bacteria should accompany all planned c-sections? (Not that I'm offering any clinical advice!)
Monday, 6 June 2011
Caesarean section and coeliac disease?
"Here I go again on my own". So went the lyrics to the song from Whitesnake, a band formed in the bracing breeze of the North East of England. Hair, yes they had lots of that. The Bruce Willis muscle vest, yes they had that too and the spandex trousers. Despite confessing a degree of infatuation with the 1980's rock scene, I am not devoting another post to it. Rather this is another post (hence, here he goes again) on risk and possible association with that old favourite, coeliac disease; this time with birth by caesarean section (c-section).
The papers in question are this one published in Pediatrics (full-text) and this more descriptive article published in the journal Gut Microbe (again full-text here) from the same author group which suggested that those born by c-section were at greater risk of developing coeliac disease. I hopefully am not going to gross out my (male) readers too much with my brief description of the c-section: an incision made in the front wall of the abdomen and womb to gain access (and give exit) to the infant, all under appropriate anaesthetic of course. Planned c-sections are not normally done under epidural or spinal block, and generally accompanied by the words "you might feel a bit of pulling and tugging" as operation 'delivering baby' commences. There are lots of different reasons for a c-section; not least multiple births (twins, triplets, etc), a breech presenting baby or in emergency cases, where for example, labour is not progressing or there is some immediate risk to the baby.
C-section born babies tend to be a little more 'baby-like' when they make an appearance because they don't have to travel through the rather cramped birth canal where they can sometimes get a bit of a 'conehead' and some bruising (which is not generally permenant I might add). One of the bonuses however of this often quite difficult journey, aside from clearing the airways, is that baby picks up quite a bit of mum on the way down in the form of various bacteria colonising the route some of which has been suggested to be protective against a few things in later life. It is with this in mind that the studies of interest have focussed on.
Getting back to those studies then. The main Pediatrics paper did the science-y bit analysing data from nearly 2000 live births. They compared the birth experience of several groups: those diagnosed with coeliac disease (CD), those with Crohn's disease, those with ulcerative colitis, those with GI disease (not otherwise specified) and asymptomatic controls free of gastrointestinal disease. There is a slightly different detail to this paper in that they use the acronym CD to denote Crohn's disease whereas I use it to denote coeliac disease.
The authors report a few important findings:
There are a few elements of these results which are perhaps slightly counter-intuitive and have been highlighted by the study authors. The main ones being the fact that picking up mum's bacteria via a natural delivery may offer some degree of protection against CD above and beyond other inflammatory bowel diseases given the links that have been made between bacteria and such conditions. Also is the issue of breastfeeding, which despite being highest and longest for the CD group did not seem to offer very much in the way of enhanced protection against developing CD. I should perhaps add at this point that timing of gluten introduction may also have played a role here.
I have already posted on breastfeeding in relation to autism and so am not going to make too much more of this side of the data. The possible protective effects of a non c-section birth against developing CD are interesting and coincide with similar data. Other studies have for example, looked specifically at the bacterial differences between c-section and non c-section babies and reported higher levels of total gut bacteria and, in particular, higher levels of Bifidobacteria. There is also some initial evidence that certain strains of Bifidobacteria might have the ability to alter the inflammatory effects caused by gliadin (at least in the petri dish) which would fit in with the results obtained in the Pediatrics study. Added to the fact that CD is associated with perturbed Bifidobacterial colonisation, the link perhaps gets stronger (at least with regards to Bifidobacteria).
This for me is a very interesting area of research, which provides a fascinating look into how mother nature and our environment shape our very complicated lives from beginning to end. I have touched upon the concept of 'risk' before and the obvious caveat that risk is by no means equivalent to certainty. In this case, non c-section delivery reduced the risk of developing CD but so might lots of other variables, known and unknown; not least the fact that we all seem to host our own unique(?) bacterial profile influenced by lots of different things including our environment and psychology.
The papers in question are this one published in Pediatrics (full-text) and this more descriptive article published in the journal Gut Microbe (again full-text here) from the same author group which suggested that those born by c-section were at greater risk of developing coeliac disease. I hopefully am not going to gross out my (male) readers too much with my brief description of the c-section: an incision made in the front wall of the abdomen and womb to gain access (and give exit) to the infant, all under appropriate anaesthetic of course. Planned c-sections are not normally done under epidural or spinal block, and generally accompanied by the words "you might feel a bit of pulling and tugging" as operation 'delivering baby' commences. There are lots of different reasons for a c-section; not least multiple births (twins, triplets, etc), a breech presenting baby or in emergency cases, where for example, labour is not progressing or there is some immediate risk to the baby.
C-section born babies tend to be a little more 'baby-like' when they make an appearance because they don't have to travel through the rather cramped birth canal where they can sometimes get a bit of a 'conehead' and some bruising (which is not generally permenant I might add). One of the bonuses however of this often quite difficult journey, aside from clearing the airways, is that baby picks up quite a bit of mum on the way down in the form of various bacteria colonising the route some of which has been suggested to be protective against a few things in later life. It is with this in mind that the studies of interest have focussed on.
Getting back to those studies then. The main Pediatrics paper did the science-y bit analysing data from nearly 2000 live births. They compared the birth experience of several groups: those diagnosed with coeliac disease (CD), those with Crohn's disease, those with ulcerative colitis, those with GI disease (not otherwise specified) and asymptomatic controls free of gastrointestinal disease. There is a slightly different detail to this paper in that they use the acronym CD to denote Crohn's disease whereas I use it to denote coeliac disease.
The authors report a few important findings:
- The rate of caesarean section deliveries is on the rise (15% increase between 1991 and 2007).
- Rates of c-section delivery were elevated in CD compared with the control sample (OR: 1.83, CI: 1-18-2.85).
- Whilst breastfeeding rates were fairly similar across the groups, children with CD showed the highest rates of breastfeeding (86.6%) and for the longest period too (mean 5.18 months) despite birth by c-section being associated with a decreased likelihood of being breastfed.
- The male:female ratio was quite a bit less even across the CD group compared with the other groups (65% female).
There are a few elements of these results which are perhaps slightly counter-intuitive and have been highlighted by the study authors. The main ones being the fact that picking up mum's bacteria via a natural delivery may offer some degree of protection against CD above and beyond other inflammatory bowel diseases given the links that have been made between bacteria and such conditions. Also is the issue of breastfeeding, which despite being highest and longest for the CD group did not seem to offer very much in the way of enhanced protection against developing CD. I should perhaps add at this point that timing of gluten introduction may also have played a role here.
I have already posted on breastfeeding in relation to autism and so am not going to make too much more of this side of the data. The possible protective effects of a non c-section birth against developing CD are interesting and coincide with similar data. Other studies have for example, looked specifically at the bacterial differences between c-section and non c-section babies and reported higher levels of total gut bacteria and, in particular, higher levels of Bifidobacteria. There is also some initial evidence that certain strains of Bifidobacteria might have the ability to alter the inflammatory effects caused by gliadin (at least in the petri dish) which would fit in with the results obtained in the Pediatrics study. Added to the fact that CD is associated with perturbed Bifidobacterial colonisation, the link perhaps gets stronger (at least with regards to Bifidobacteria).
This for me is a very interesting area of research, which provides a fascinating look into how mother nature and our environment shape our very complicated lives from beginning to end. I have touched upon the concept of 'risk' before and the obvious caveat that risk is by no means equivalent to certainty. In this case, non c-section delivery reduced the risk of developing CD but so might lots of other variables, known and unknown; not least the fact that we all seem to host our own unique(?) bacterial profile influenced by lots of different things including our environment and psychology.
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