Pregnant women with greater exposure to nicotine were linked to an increased risk of having a child with schizophrenia compared with matched controls, a small case-control study from Finland found.
Overall, women with a higher level of cotinine, a known biomarker of smoking, was associated with a more than two-fold increase of schizophrenia in their offspring (OR 2.69, 95% CI 1.54-4.69, P<0.0001), reported Solja Niemelä, MD, of University of Oulu in Finland, and colleagues.
These associations actually strengthened after adjusting for maternal age, province of birth and any parental psychiatric disorder (OR 3.41, 95% CI 1.86-6.24, P<0.0001), they wrote in the Journal of Psychiatry.
Co-author Alan S. Brown, MD, of Columbia University Mailman School of Public Health in New York City said that surprisingly, little is known about smoking during pregnancy and mental disorders, though he has previously published a paper that showed maternal smoking increases the risk of bipolar disorder.
"There is scant evidence that maternal smoking is related to schizophrenia and no study that has used a maternal chemical (cotinine) in a study of schizophrenia in offspring," he said in an email to MedPage Today. "Although the study requires replication, this adds important evidence that maternal nicotine exposure may be involved in developmental processes that alter the likelihood of developing schizophrenia."
Niemelä's team said that part of the theory behind the association between prenatal nicotine exposure and the development of schizophrenia is that structural brain changes, including cortical thinning and decreased corpus callosal volume occur with both prenatal exposure to smoking and in the mental disorder.
"Prenatal nicotine is associated with abnormal development of cerebral inhibitory neurons, a key pathophysiological defect in schizophrenia," they wrote.
Heavy (as opposed to moderate or light) maternal exposure to nicotine was associated with a 51% increased risk of schizophrenia in offspring (OR 1.51, P<0.0001), and this relationship remained significant in adjusted analyses (OR 1.38, P=0.02).
When asked if these results mean that OB/GYNs should be warning their pregnant patients who are smokers about the potential for mental illness in their offspring, Brown said that further research was necessary.
"While it is premature for OB/GYNs to warn patients about mental illness in their children among smoking mothers, smoking during pregnancy is known to have adverse effects on offspring, including low birthweight," he noted.
In fact, the authors examined low birth weight relative to gestational age as a mediating variable, because of this known relationship between low birth weight and maternal smoking. However, the relationship between maternal nicotine exposure and low birth weight for gestational age was nonsignificant, even after adjusting for multiple confounders.
The Finnish Prenatal Study of Schizophrenia is a population-based nested case-control study that examined 977 cases of schizophrenia in Finland, drawing from the Finnish Maternity Cohort. Controls were matched based on date of birth, sex and residence in Finland at time of diagnosis. Cases and controls were a mean age of 22.3 years (SD=2.2), and maternal and paternal age, parental history of psychiatric disorders, province and municipality of birth were all associated with schizophrenia in offspring. Mean levels of cotinine in case subjects was 35.9 ng/ml, with a mean 23.1 ng/ml in controls.
Limitations to the study include the lack of data on alcohol use during pregnancy, the fact that other biomarker data on the other toxic compounds in nicotine was not available and the potential for residual confounding (for example, adjusting for parental history of schizophrenia, but not other relatives).
The authors conclude that their results "may ultimately have important public health implications for decreasing the incidence of schizophrenia" and suggested the potential for future studies to examine maternal cotinine levels in relation to other psychiatric disorders, such as bipolar disorder and autism.
The study was supported by NIMH grants to Brown.
Niemelä reports receiving speakers' bureau honoraria from Janssen, Lilly, and Lundbeck; as well as travel funds from and serving on advisory panels for Janssen and Lundbeck.
McKeague was partially funded by a grant from the National Institute of General Medical Sciences.
Other co-authors disclose no relevant financial relationships.
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