New research out of the Yale School of Medicine is the first to link prenatal nicotine exposure with impaired reading skills, the most recent finding in a large body of literature urging mothers not to smoke while pregnant.

Study authors analyzed more than 5,000 young children tracked through the Avon Longitudinal Study of Parents and Children (ALSPAC), a well-known database of children born in 1991 and 1992 in Bristol, England. After controlling for other factors that affect reading ability, such as socio-economic status and alcohol consumption, the researchers concluded that the more a mother smokes while pregnant, the more likely her child will struggle relative to peers on a broad range of reading tests, including comprehension, accuracy and speed. The paper first appeared online in The Journal of Pediatrics on Nov. 5.

The ALSPAC data includes genetic information about every one of its subjects, and Jeffrey Gruen, senior study author and professor of pediatrics and genetics at the Yale School of Medicine, said he initially engaged with the data set to elucidate the genetic underpinnings of dyslexia. The nicotine findings arose as his team identified possible factors that may underlie genetic effects of reading disorders. Gruen said he was “very surprised” to find that heavy maternal smoking of more than a pack a day could decrease reading performance by over 15 percent.

“It was such an important finding that we decided to go ahead and publish it all by itself,” he said.

The paper did not investigate the mechanism that translated prenatal exposure to nicotine into impaired reading ability. But Gruen said he suspects multiple factors may be at play, given that nicotine can cross the placenta and interact in complex ways with the developing baby. Nicotine binds easily with nicotinic receptors, which may cause permanent damage to the baby’s developing central nervous system. Alternatively, Gruen said that since nicotine can change the genes of a developing baby, this prenatal exposure may cause epigenetic changes that impact future cognitive function.

Study co-author and professor of child and youth studies at Brock University Jan Frijters said he also suspects nicotine interacts with the child’s genome to affect reading ability years later.

“The most tantalizing and suggestive outcome of the paper is to wonder what exactly the mechanism is,” Frijters said.

The strength of the paper comes from the size of the ALSPAC data set and the rigorous statistics analysis the authors used, said Shelley Smith, a professor of pediatrics at the University of Nebraska who was not involved in the study. She added that the data set does not sufficiently quantify parental literacy, which prevents the authors from more thoroughly controlling for some confounding genetic factors.

Frijters said the paper amplifies the call to women to quit smoking cigarettes as soon as they become pregnant.

“It’s not a ‘feel bad’ story,” he said. It’s a “‘you can do something to change the outcome’ story.”

According to the Centers for Disease Control and Prevention, roughly 13 percent of women smoke during the last trimester of pregnancy.