However, the link was only found for men who are now adult, while a reverse association was seen for boys, researchers report in Thorax.
"Our study contributes to the growing awareness of adverse intergenerational effects of smoking and should stimulate further public health efforts to reduce smoking in the general population in particular before or during pregnancy," write Dr. Gillian Mahon, of University Medical Center Groningen and Beatrix Children's Hospital, in the Netherlands, and colleagues.
For their analysis, the researchers used data from the Lifelines study, which follows three generations in the Netherlands to shed light on chronic disease and healthy aging.
Out of more than 167,000 participants, smoking during pregnancy was confirmed for the grandmothers of 11,544 children (mean age, 10) and 25,747 adults (mean age, 31; maximum age, 50, per study design).
Although the prevalence of asthma was similar (11%) in both groups, a higher prevalence of early childhood asthma (onset before age 6) was seen in children (9.3% vs. 4.4%).
Among men, those whose grandmother smoked while pregnant with their mother had 38% greater odds of having asthma (odds ratio, 1.38; P=0.016) and 49% greater odds of early childhood asthma (OR, 1.49; P=0.023).
Children exposed to maternal grandmaternal smoking during pregnancy had 26% lower odds of both asthma and early childhood asthma (P=0.006 and P=0.011, respectively).
No significant associations were seen for females or between smoking during pregnancy by the paternal grandmother and asthma in grandchildren, in either group.
In stratified analyses in the adult group, maternal grandmaternal smoking was associated with a significantly lower FEV1/FVC % predicted in male grandchildren, as well as in offspring of smoking mothers.
In the children, grandmaternal smoking was associated with a higher FEV1 % predicted and FVC % predicted in male grandchildren, and no change in FEV1/FVC % predicted.
The analysis accounted for maternal smoking and found that the early childhood asthma risk associated with grandmaternal smoking is significant only in those with nonsmoking mothers.
Dr. Mahon told Reuters Health by email that these effects of smoking "are the result of direct exposure, so-called intergenerational inheritance (exposure of the eggs of the fetus which later becomes the grandchild)."
She added, however, that "transgenerational inheritance is another potential mechanism where the effects of indirect exposure to smoking are seen in further generations . . . This raises the question whether the effects of smoking can be observed in generations even further down the line (third-generation offspring)."
As to the opposite effects in children and adults, Dr. Mahon suggested that between the time when the grandmothers of the two study groups lived and gave birth, smoking trends and the social awareness and taboos around smoking changed. As a result, she speculated, the children might have been exposed to smoking in lesser amounts and less often.
Dr. Jean Golding, an emeritus professor of pediatric and perinatal epidemiology at the Centre for Academic Child Health at the Bristol Medical School, in the U.K., told Reuters Health by email that despite a dearth of research, "there is accumulating evidence that some features of a grandmother's pregnancy, including famine, exposure to (diethylstilbestrol) or smoking, can have effects on their grandchildren."
She said of the new work, "This is an interesting study with a complex design which makes the results difficult to interpret."
Dr. Golding, who was not involved in the study, highlighted the opposite links seen for adults and children. "If this is true," she said, "then the intriguing question concerns what differences there may have been in the composition of cigarettes" in the earlier versus the later time periods.
"One candidate could be the formulation of pesticides used on the tobacco crops in earlier years such as DDT (which was banned in the USA in 1972 and in Europe in 1986), but there may be many other explanations," Dr. Golding said.
SOURCE: https://bit.ly/3k0s70z Thorax, online February 4, 2021.
By Scott Baltic
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