Children whose maternal grandmother smoked during pregnancy are more likely to be diagnosed with autism, a study of UK children has found. There's an even greater discrepancy in the proportion of girls who show certain autism-like traits. Given the enormous problems associated with inaccurate reports of autism's causes, much care needs to be taken before assuming causation. However, if the connection is confirmed, it would have profound implications for thinking both about autism itself and about the effect of smoking on developing embryos.

Studies looking for an association between smoking during pregnancy and ASD have produced mixed results. Since smoking can affect both mitochondrial and nuclear DNA in eggs being produced in an early embryo, and ASD is associated with increased mutation rates, Professor Marcus Pembrey of the University of Bristol thought it worth looking back a generation at whether mothers were exposed to tobacco in the womb.

In a sample of 14,500 children born in the 1990s, children whose grandmother smoked while pregnant with the child's mother were 53 percent more likely to be diagnosed with autism spectrum disorder (ASD) than those whose grandmothers did not. The effect, published in Scientific Reports, was stronger with granddaughters than grandsons, and, after controlling for other factors, girls were 67 percent more likely to have poor social communication skills and repetitive behaviors if their grandmother smoked.

“In terms of mechanisms, there are two broad possibilities. There is DNA damage that is transmitted to the grandchildren or there is some adaptive response to the smoking that leaves the grandchild more vulnerable to ASD,” Pembrey said in a statement. “More specifically, we know smoking can damage the DNA of mitochondria – the numerous "power-packs" contained in every cell, and mitochondria are only transmitted to the next generation via the mother's egg. The initial mitochondrial DNA mutations often have no overt effect in the mother herself, but the impact can increase when transmitted to her own children.”

The authors admit they cannot explain the sex differences in the outcomes.

ASD is diagnosed at far higher rates than just a few decades ago. Some, and possibly all, of this increase is a result of changed definitions and greater awareness, leading to children being diagnosed for symptoms that would have been ignored in previous generations. Nevertheless, it's not just anti-vaccine campaigners who think some of the increase is real, leading to a search for environmental causes.

The proportion of UK women smoking has fallen more slowly, as in most of the developed world, than that of men. Nevertheless, it has dropped by more than 50 percent since the early 1970s. For health effects that take at least a generation to show up, however, we may not see the consequences for some time.