Although the effects of smoking and exposure to secondhand smoke during pregnancies are relatively well-known, new Duke research suggests that being exposed to secondhand smoke even before conception could still affect fetal development. 

The scientists mimicked the effects of secondhand smoke exposure in female rats before mating, in early gestation and in late gestation. Detrimental effects on fetal brain development were greatest after the pregnant rats were exposed during late gestation, but surprisingly, the team found that certain brain circuits in the fetus were still impaired when rats were exposed before they had even mated. 

The research also concluded that exposure to secondhand smoke during any of the time periods did not significantly change the proportion of pregnant rats that gave birth, the amount of weight the mothers gained or the number of babies born to each mother—but instead that the major effects happened to brain development. 

“The study emphasizes the need for parents to avoid secondhand smoke exposure even before pregnancy, as well as throughout the term of pregnancy," wrote Theodore Slotkin, first author and a professor of pharmacology and cancer biology, psychiatry and behavioral sciences and neurobiology, in an email. "To our knowledge, this is the first study to demonstrate that vulnerability extends to the period prior to conception, not just during gestation itself."

The research team—with senior author Frederic Seidler, an assistant research professor of pharmacology and cancer biology—created a tobacco smoke extract with low nicotine concentrations to mimic secondhand smoke. This extract was introduced into the rats during the three different periods, each 10 days apart. The rats were then tracked during a period of 150 days to assess the long-term effects of the smoke exposure. 

At all three exposure times, acetylcholine circuit activity was impaired in the brain and acetylcholine receptors were reduced—nicotine is known to affect these receptors. Moreover, the study also found that there was no “critical period” for smoking—smoking can affect the fetus even before conception.  

"That has important implications for public health—women need to avoid secondhand smoke exposure not just while they are pregnant, but in the period prior to conception as well," Slotkin wrote. "As we state in the paper, basically this warning then extends to women of childbearing age, regardless of whether they are pregnant or even planning a pregnancy."

The study pointed out several potential reasons for why exposure to secondhand smoke before a pregnancy could result in developmental changes down the road. Remnants of nicotine even after it has metabolized could linger in the body, the mother's physiology could be altered somehow, the smoke could cause epigenetic changes in the eggs or the effects on the fetal brain could be related to nicotine withdrawal. 

Epigenetics refers to changes in the regulation of gene expression in an individual, and studies have linked maternal exposure to tobacco smoke and epigenetic changes during pregnancy. However, as Slotkin's study points out, there may be a link to tobacco exposure even before conception and epigenetic alterations. If these pre-conception changes are proven to be due to epigenetics, this could provide the link between secondhand smoke exposure before birth and fetal developmental problems. 

Slotkin noted that he plans to investigate these epigenetic links in new ways. 

“Prior studies of smoking and epigenetic changes have involved sampling blood, and there is no guarantee that these changes (or lack of changes) are reflective of what is going on in the developing brain,” Slotkin wrote. “Uniquely, we’ll be looking at changes in the brain and comparing them to what is found in the blood, to see if the peripheral markers are predictive or related to what happens in the brain.”

Such a study could provide key insights into the effects of the mother's exposure between conception and early pregnancy to the chemicals and agents that can affect the fetus.

Correction: This article was updated to include that the researchers measured acetylcholine circuit function, not just receptors. The Chronicle regrets the error.