Previous studies have demonstrated that children born to mothers who smoke during pregnancy are at increased risk for attention-deficit/hyperactivity disorder (ADHD).  In a recent review, Huang and colleagues looked at data from 15 cohort studies and 5 case-control studies which included a total of 50,044 children with ADHD and 2,998,059 controls.  Maternal smoking during pregnancy was associated with an increased risk of ADHD in the exposed offspring (OR: 1.60; 95% CI: 1.45-1.76). The risk of ADHD was greater for children born to mothers who were heavy smokers (OR: 1.75; 95% CI: 1.51-2.02) compared to children whose mothers were light smokers (OR: 1.54; 95% CI: 1.40-1.70).

Most of these studies have relied on maternal self-report of smoking which makes it difficult to correlate level of exposure with risk.  A recent study measures maternal cotinine levels as a means of quantifying exposure. Cotinine levels in the blood reflect recent exposure to nicotine in tobacco smoke and can be used to distinguish heavy smokers from lighter smokers and nonsmokers.  

In this population-based study, 1079 children born between 1998 and 1999 who were  diagnosed with ADHD (according to the International Classification of Diseases) and 1079 age-matched controls were identified using Finnish nationwide health registers. Maternal cotinine levels were measured during the first and second trimesters of pregnancy.

There was a significant association between maternal cotinine levels and offspring ADHD. The odds ratio was small but statistically significant (OR=1.09, 95% confidence interval [CI] 1.06-1.12), after adjusting for maternal socioeconomic status, maternal and paternal age, maternal and paternal psychopathology, and child’s birth weight for gestational age.

The researchers then quantified risk of ADHD according to cotinine levels.  Heavy nicotine exposure (cotinine level > 50 ng/mL) was associated with the highest risk of offspring ADHD, with an odds ratio of 2.21 (95% CI 1.63-2.99) in the adjusted analyses. Looking at the ten percent of women with the highest cotinine levels, the risk for ADHD was even higher, with an odds ratio of 3.34 (95% CI 2.02-5.52).

While this study identifies an association with and a dose-response relationship between nicotine exposure during pregnancy and offspring ADHD, it is important to note that correlation is not the same as causation.  In populations of pregnant women, we cannot do randomized controlled studies, where one group of women are exposed to tobacco smoke and another group of women with no exposure serve as a control. We must rely on what happens naturalistically and must contend with the complication that the women who smoke during pregnancy may differ considerably from the women who do not smoke with regard to other factors which may modulate risk for ADHD.  Similarly, women who are heavy users most likely differ from lighter users.

It is possible that mothers who smoke are “self-medicating” with nicotine, which has stimulant effects.  We know that people with ADHD are more likely to smoke, perhaps in part to improve attention and concentration.  Women with mood and anxiety disorders are also more likely to smoke than women without these disorders. If we take a group of women who smoke, we may be looking at a group of women who have higher rates of ADHD and other psychiatric illness than we would see in a group of non-smokers.  Thus, the children born to smokers may be at increased risk to ADHD as a result of genetic vulnerability, and exposure to nicotine during pregnancy may play a less important role.

The researchers did attempt to control for maternal and paternal psychopathology which would theoretically help to separate the effects of prenatal exposures from increased genetic vulnerability. It does appear that the magnitude of risk observed in this study is lower than observed in the above-mentioned meta-analysis (OR 1.09) which did not control for maternal psychopathology.

However, the maternal diagnoses made in this study rely upon diagnoses indicated in the medical record.  Women who have not been diagnosed with a particular disorder or who are not in treatment would not be identified, and this may make it impossible to fully adjust for maternal psychiatric illness.  To better elucidate the connection between maternal tobacco use and risk for ADHD in exposed children, future studies including data on environmental, genetic, and epigenetic factors are warranted.


Ruta Nonacs, MD PhD


Huang L, Wang Y, Zhang L, Zheng Z, Zhu T, Qu Y, Mu D.Maternal Smoking and Attention-Deficit/Hyperactivity Disorder in Offspring: A Meta-analysis.  Pediatrics. 2018 Jan;141(1). Free Article

Sourander A, Sucksdorff M, Chudal R, Surcel HM, Hinkka-Yli-Salomäki S, Gyllenberg D, Cheslack-Postava K, Brown AS.  Prenatal Cotinine Levels and ADHD Among Offspring.  Pediatrics. 2019 Mar;143(3). pii: e20183144.





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