Maternal cotinine levels linked to ADHD in offspring

May 1, 2019

Children of women who smoke during pregnancy are more likely to have attention-deficit/hyperactivity disorder (ADHD) than children of nonsmoking mothers, according to the first study to investigate the association between smoking and ADHD based on nicotine serum biomarker levels rather than self-reported smoking. Further, the investigation found that as the amount of smoking increases, so does the likelihood of ADHD.

Children of women who smoke during pregnancy are more likely to have attention-deficit/hyperactivity disorder (ADHD) than children of nonsmoking mothers, according to the first study to investigate the association between smoking and ADHD based on nicotine serum biomarker levels rather than self-reported smoking. Further, the investigation found that as the amount of smoking increases, so does the likelihood of ADHD.

The population-based study was conducted in Finland among 1079 children born between 1998 and 1999 who were diagnosed with ADHD (at a mean age of 7.3 years) and an equal number of children without the diagnosis. Each child with ADHD was matched with a control who had the same birth date (within 30 days), sex, and place of birth. Investigators measured cotinine levels in the blood of maternal participants, using specimens collected during the first and second trimesters of pregnancy. The mean cotinine level among mothers who smoked was 27.4 ng/mL versus 11.3 ng/mL among control mothers.

Maternal cotinine levels were associated with offspring ADHD in analyses that accounted for confounding factors as well as those that did not. In the analyses adjusted for birth weight for gestational age, maternal and paternal psychopathology, and maternal and paternal age, the overall odds ratio (OR) for ADHD in children of mothers who smoked was 1.09. Children born to mothers with the highest cotinine levels (>50 ng/mL) were more than twice as likely to have ADHD (OR, 2.21) than the control children in these analyses. Moderate cotinine levels (20-50 ng/mL) were associated with an OR of 1.27. In the analyses that were not adjusted for confounding factors, heavy and moderate cotinine levels were associated with ORs of 2.95 and 1.92, respectively.

The strongest association between cotinine exposure and ADHD was in children of women whose cotinine levels were in the top 10% (90th to 100th percentile) with unadjusted and adjusted odds for offspring ADHD of 4.9 and 3.34, respectively. For the second highest cotinine levels (80th to 89th percentile), the unadjusted analysis showed an OR of 2.71 and the adjusted analysis of 1.91 (Sourander A, et al. Pediatrics. 2019;143[3]:e20183144).

Thoughts from Dr. Burke

In this study, researchers quantified prenatal smoke exposure by measuring cotinine, a metabolite of nicotine, in blood samples from a Finnish national blood bank of 2 million samples drawn from nearly 1 million expectant mothers beginning in 1983. It could be that the effect on childhood ADHD is due to some other product of cigarette smoking, but other studies the authors cite show nicotine crossing the placenta and changing maturation of central nervous system development. If nicotine is the guilty party, then prenatal nicotine exposure through electronic cigarettes will likely one day be associated with similar findings.

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