By Linda Carroll

(Reuters Health) – Pregnant women who have nicotine in their systems from smoking are more likely to have children who develop attention-deficit/hyperactivity disorder (ADHD), a new study suggests.

And the higher the level of nicotine in a pregnant woman’s blood, the greater her child’s risk of later being diagnosed with ADHD, researchers report in Pediatrics.

While not the first study to find an association between ADHD and in-utero exposure to nicotine, earlier research depended on mothers’ self-reports of cigarette smoking, rather than actual measurements of a nicotine breakdown product in the mothers’ blood.

To tease out any connection between nicotine and ADHD, the researchers turned to national databases kept in Finland, one of which stored blood samples from mothers-to-be and the other kept track of children who developed the attention disorder.

“We found, in a large nationwide sample that mothers who smoked during pregnancy, in particular those who were heavy smokers, had offspring with a fairly high risk for ADHD,” said senior study author Dr. Alan S. Brown, a professor of psychiatry and epidemiology at Columbia University in New York City. “That finding was after we controlled for a lot of potential variables that might account for the association.”

A 2018 government report put the rate of smoking among pregnant women who gave birth in the U.S. in 2016 at 7.2 percent. The rate is similar in Finland, Brown and his colleagues note.

The researchers were able to get data on the pregnant women’s nicotine levels through the Finish Maternity Cohort, which has serum samples collected early in pregnancy from more than 950,000 Finnish women.

For the new study, the researchers analyzed data on 1,079 children born between 1998 and 1999 who had been diagnosed with ADHD and 1,079 age-matched “controls” who did not have the condition.

The serum samples from the mothers of these children were tested for cotinine, a substance created when nicotine breaks down in the body. Along with those data, the researchers were able to gather information on the parents, including any diagnoses of ADHD, psychiatric history and history of drug abuse.

The study found that mothers of kids with an ADHD diagnosis had a mean blood cotinine level more than double that of the mothers of the control children.

And increasing cotinine levels in the samples from the mothers were associated with an increased risk of ADHD in the children, even after taking into account parental socioeconomic status, maternal age, parental mental illnesses and the child’s birth weight.

Dividing the mother-child pairs into three groups according to their cotinine levels, the researchers determined that mothers in the highest nicotine exposure group were 2.21 times as likely as those with the lowest levels to have a child diagnosed with ADHD. When the researchers split the pairs into 10 groups, they found that mothers in the highest nicotine exposure group were 3.34 times as likely as those with the lowest cotinine levels to have a child with ADHD.

Brown doesn’t know for sure how a mother’s smoking would affect her child’s risk of ADHD, but says, “we can speculate a bit since we know that nicotine crosses the placenta. And in animal studies it’s related to increased motor activity.”

“This is a valuable paper and I think it will contribute to the literature in this field, first of all, by showing with a biological measure of serum cotinine levels as opposed to self-reports to measure nicotine exposure prenatally,” said Dr. Christopher Hammond, an assistant professor of psychiatry at the Johns Hopkins University School of Medicine in Baltimore who wasn’t involved in the study.

A “compelling” feature of the new report is the finding that the risk of ADHD goes up with increasing levels of exposure to nicotine, Hammond added. “Other studies have not shown this dose-response in the same way.”

Animal models have suggested that nicotine affects developing brain circuits, resulting in less connectivity between the regions of the brain associated with attention and emotional regulation and those involved with reward and emotional processing, Hammond said. “These studies have suggested that there is a sort of impaired top-down control over reward responses and emotional processing centers,” he added.

SOURCE: Pediatrics, online February 25, 2019.