Nicotine exposure and offspring ADHD (yet again)

The study findings reported by Andre Sourander and colleagues [1] talking about "an association with and a dose-response relationship between nicotine exposure during pregnancy and offspring ADHD [attention-deficit hyperactivity disorder]" continue an important research theme (see here and see here).

What was different about the Sourander results compared with some of the other studies in this area was their focus on the measurement of cotinine levels - cotinine being a biomarker for exposure to tobacco smoke - in mums-to-be as "measured by using quantitative immunoassays from maternal serum specimens collected during the first and second trimesters of pregnancy and archived in the national biobank." Indeed, such a biological marker measurement protocol mimics other research from members of this authorship group when looking at maternal nicotine exposure and offspring risk of schizophrenia for example (see here).

Based on the analyses of samples from over a thousand participants born in the late 1990s and diagnosed with ADHD compared with samples from a similar number of non-ADHD control participants, researchers came to their possible *link* observation. They mention how the relationship between maternal cotinine levels and offspring ADHD diagnosis was statistically significant even when other important, potentially confounding, variables were taken into account. When categorising their maternal cotinine results into bands approximating light to heavy nicotine exposure and the possibility of a link with offspring ADHD diagnosis, researchers also reported something that looked like a dose-response relationship. Ergo, a biomarker of nicotine exposure during pregnancy *looked* to be potentially linked to offspring risk of ADHD.

Although important work, my first thought when reading this research was about how these results are 'set' within the context that historically, smoking rates or tobacco exposure rates during pregnancy were so much larger decades ago than they are now (see here), but ADHD is seemingly showing only quite a recent rise in numbers (see here). Although no expert on pregnancy tobacco consumption during the 20th century, I'm assuming that all those adverts about smoking being 'healthy' in the 1940s and beyond (see here) probably meant that quite a few women smoked during their pregnancy in the belief that it was 'healthy'. At the very least, it probably meant that they were exposed to a lot more second-hand tobacco smoke as a result of smoking being allowed in various public places and also more likely to be observed in the home environment. Surely then we would have seen an explosion of ADHD diagnoses at that point in time if the link was so simple? That is, assuming that the tobacco of today is the same as the tobacco of yesteryear.

I'm also intrigued that within the various potentially confounding variables which Sourander and colleagues adjusted for - "maternal socioeconomic status, maternal age, maternal psychopathology, paternal age, paternal psychopathology, and child’s birth weight for gestational age" - there's another variable that could exert an effect on ADHD risk: relative age (see here and see here). Relative age refers to the observation that the youngest children in the school classroom compared to their older classmates, are more likely to be diagnosed with ADHD. It strikes me that alongside something like tobacco or nicotine exposure, so age and other effects could be important.

I'm not trying to poo-poo the link that Sourander and various other research teams have independently observed. I'm also not trying to downplay the harms that tobacco (nicotine) exposure can have for the unborn child. I merely suggest that with typically falling rates of (reported) tobacco exposure during pregnancy in many countries (see here) and increasing levels of childhood (and adulthood) ADHD being reported, there must be other factors at work in any such relationship (see here for example).

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[1] Sourander A. et al. Prenatal Cotinine Levels and ADHD Among Offspring. Pediatrics. 2019. Feb 25.

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Maternal tobacco smoking and offspring ADHD risk again

"ADHD [attention-deficit hyperactivity disorder] and movement disorders were found to be more common in hospitalized children of smoking mothers."

That was one of the details recorded in the research findings published by Gil Gutvirtz and colleagues [1] adding to a growing research 'trend' suggesting that maternal tobacco smoking during pregnancy seemingly does little for mum's health and also probably not a great deal for her offspring's health and wellbeing either (see here).

Based on results analysing "all deliveries of mothers who reported smoking during pregnancy and non-smoking mothers between 1991 and 2014 at a single tertiary medical center" researchers included almost 250,000 children in their study. Quite a small proportion - "2861 (1.2%)" - were children of mothers who smoked during pregnancy. When researchers looked at these children they noted "higher rates of movement, eating and developmental disorders as well as attention deficit hyperactive disorder" as compared with the larger non-smoking group. "Maternal smoking during pregnancy is an independent risk factor for long-term neurological morbidity of the offspring" was the conclusion.

Allowing for the fact that observational studies, even population-based ones, aren't great for 'proving' cause-and-effect, the volume of such studies independently reaching the conclusion that maternal smoking during pregnancy *might* have an important connection to risk of offspring ADHD is growing. Indeed, alongside all the other adverse outcomes seemingly connected to smoking during pregnancy (see here) I don't think it would be out of place for regulators and health-related agencies to start informing the population at large that ADHD or ADHD-related behaviours as an outcome is at least possible; as some agencies seem to be doing (see here)...

Another research step could be some further investigations actually looking at something like cotinine levels (and important marker of tobacco smoke exposure) in both mums and offspring to see whether 'the dose makes the poison' as other recent studies have hinted at [2].

Tobacco smoking ain't good for anyone it seems, and children seem to be particularly vulnerable to its effects.

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[1] Gutvirtz G. et al. Maternal smoking during pregnancy and long-term neurological morbidity of the offspring. Addictive Behaviors. 2018. Aug 16.

[2] Kim KM. et al. Associations between urinary cotinine and symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder. Environ Res. 2018 Jun 26;166:481-486.

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Maternal tobacco smoking and offspring ADHD risk

"The results showed that either prenatal exposure to MSDP [maternal smoking during pregnancy] or smoking cessation during first trimester was significantly associated with childhood ADHD [attention-deficit hyperactivity disorder] after adjusting for parental psychiatric history and social socioeconomic status."

and:

"With our meta-analysis, we provide evidence for an association between maternal smoking and offspring ADHD but do not solve the causality issues concerning potential confounding by other risk factors."

Those quotes were taken from the findings reported by Tianyu Dong and colleagues [1] and Lan Huang and colleagues [2] respectively, both applying the 'top of the methodological tree' analysis that is a meta-analysis to the collected data looking at whether maternal smoking during pregnancy might impact on offspring risk of a diagnosis of ADHD. Their combined answer: very possibly but...

Having previously covered the non-association between maternal smoking during pregnancy and offspring autism before on this blog (see here), the recent results from Dong and Huang highlight how tobacco smoking during pregnancy is still something to be avoided for the sake of the child(ren). The fact that Huang et al also observed something of a dose-response relationship: "The risk of ADHD was greater for children whose mothers were heavy smokers (OR: 1.75; 95% CI: 1.51-2.02) than for those mothers were light smokers (OR: 1.54; 95% CI: 1.40-1.70)" kinda adds to the strength of their argument for an *association* between smoking during pregnancy and adverse offspring developmental outcome(s).

It's true that even with such meta-analytical prowess, it's still a little difficult to say conclusively that 'smoking causes offspring ADHD'. I'm also minded to state how "different assessment tools of ADHD and a lack of objective biological measures for maternal smoking" were picked up by the authors as other reasons to be cautious about their [collected] findings. I will also direct you to other research published not-so-long-ago that did not find such a strong connection between maternal smoking during pregnancy and offspring ADHD [3] (or at least "indicating that the association between maternal smoking during pregnancy and offspring ADHD is not directly causal, but confounded by unmeasured factors.")

Still, even if maternal smoking during pregnancy represents just one of a number of factors potentially impacting on offspring risk of ADHD, it is worth reducing that risk by nudging mums-to-be (and perhaps even dads-to-be) to quit smoking for the sake of their children. This on top of the myriad of other reasons that parental tobacco smoking during conception, pregnancy and offspring childhood is something that really needs to be stamped out once and for all...

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[1] Dong T. et al. Prenatal Exposure to Maternal Smoking during Pregnancy and Attention-deficit/hyperactivity Disorder in Offspring: A Meta-analysis. Reprod Toxicol. 2017 Dec 30. pii: S0890-6238(17)30599-3.

[2] Huang L. et al. Maternal Smoking and Attention-Deficit/Hyperactivity Disorder in Offspring: A Meta-analysis. Pediatrics. 2018 Jan;141(1). pii: e20172465.

[3] Gustavson K. et al. Smoking in Pregnancy and Child ADHD. Pediatrics. 2017 Feb;139(2). pii: e20162509.

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