When grandmothers smoked during pregnancy...

Please, do not smoke during pregnancy

ALSPAC - the Avon Longitudinal Study of Parents and Children - continues to give in research terms as today I want to mention the findings reported by Jean Golding and colleagues [1] (open-access) observing "an association between maternal grandmother smoking in pregnancy and grand daughters having adverse scores in Social Communication and Repetitive Behaviour measures that are independently predictive of diagnosed autism."

The study results have garnered quite a bit of media interest (see here for example) with calls for quite a bit more research to be carried out on this important topic. I might also give a hat-tip to Jill Escher and the Escher Fund for Autism who were instrumental in this study. Indeed, her analysis of the Golding results (see here) will no doubt trump my contribution.

The Golding paper is open-access but a few details are worth mentioning:

• As I noted, ALSPAC provided the source data for the study (as it has on quite a few autism research occasions). This time around researchers looked at autistic traits among some of their 14,000 strong cohort comprising "a social communication score, a speech coherence score, a sociability temperament scale, and a repetitive behaviour score." 
• Mothers and fathers of children involved in ALSPAC also provided information about pregnancy including answering questions on whether mothers themselves were/had smoked during pregnancy and also whether their mother (the child's grandmothers on both sides) smoked during pregnancy.
• The data obtained from the autistic traits measures (delivered at various times of the child's development) and the smoking histories were analysed. Data on some 170 participating children actually diagnosed with an autism spectrum disorder (ASD) were also thrown into the statistical mix.
• Results: "We found that two of the four autistic traits in the grandchild (F2) were increased in prevalence if the maternal grandmother (F0) smoked in pregnancy especially if the mother herself (F1) did not herself smoke." Researchers also noted a particular association between grandmother pregnancy smoking and grand-daughters over grandsons, and several potentially important confounding variables were also taken into account. They also concluded that "diagnosed autism was also associated with the maternal grandmother smoking in pregnancy" but express some caution in light of the smaller numbers included in this part of the analysis.

"These results are intriguing" say the authors. Indeed they are. Accepting the reliance on parental report, acceptance of the myriad of other factors that might affect any relationship and the fact that "sets of trait questions were not designed as measures of autistic traits but rather to identify the child’s performance in regard to a large number of attributes at different ages" as a consequence of researchers not originally expecting the prevalence of autism to be anything like it is today(!), further research is indicated. I say this in the context that research looking at any link between maternal pregnancy smoking and offspring autism risk has not consistently found any correlation (see here).

Then to the question of mechanism of effect. Well, researchers talk about "two plausible candidate mechanisms" to account for results. First is "transmission of damage to mitochondrial DNA (mtDNA)" where mitochondria DNA is subject to 'mutation' as a result of exposure to tobacco smoke. The researchers noted that: "Mitochondrial transmission across the generations is exclusively via the mother, so is compatible with our observed associations between maternal prenatal tobacco exposure and adverse scores on Social Communication and Repetitive Behaviour measures in her granddaughters." The second possible mechanism is that of "epigenetic inheritance from one generation to the next." This builds upon something of a continuing debate where structural DNA issues (i.e. mutations) are put to one side in favour of chemical alterations to genes (e.g. the addition of methyl groups) affecting gene expression. It's a topic that has been talked about quite a bit on this blog with reference to autism (see here for example) but still needs a lot more science done on it specifically on transgenerational epigenetic inheritance. Smoking is known to have effects on DNA methylation (see here) but the suggestion is that these or other epigenetic effects could continue down into future generations.

The potential effects of tobacco smoking during pregnancy in relation to second (or even third generation) autism or autistic traits risk requires quite a bit more study. Importantly, if such results are confirmed in future investigations, it opens up a whole myriad of possibilities in terms of how other previous generational exposures outside of just tobacco smoking during pregnancy might have affected future generations. This research area could get very, very complicated indeed.

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[1] Golding J. et al. Grand-maternal smoking in pregnancy and grandchild's autistic traits and diagnosed autism. Sci Rep. 2017 Apr 27;7:46179.

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Golding J, Ellis G, Gregory S, Birmingham K, Iles-Caven Y, Rai D, & Pembrey M (2017). Grand-maternal smoking in pregnancy and grandchild's autistic traits and diagnosed autism. Scientific reports, 7 PMID: 28448061