Smoking During Pregnancy Associated with Increased Risk of Schizophrenia

A study by researchers at Columbia University’s Mailman School of Public Health, Columbia University Medical Center (CUMC), New York State Psychiatric Institute and colleagues in Finland reports an association between smoking during pregnancy and increased risk for schizophrenia in children. Results show that a higher maternal nicotine level in the mother’s blood was associated with an increased risk of schizophrenia among their offspring. Findings are published online in the American Journal of Psychiatry.

The paper evaluated nearly 1,000 cases of schizophrenia and matched controls among offspring born in Finland from 1983-1998 who were ascertained from the country’s national registry.  Heavy maternal nicotine exposure was associated with a 38-percent increased odds of schizophrenia. The findings persisted after adjusting for factors, including maternal and parental psychiatric history, socioeconomic status, and maternal age.

“To our knowledge, this is the first biomarker-based study to show a relationship between fetal nicotine exposure and schizophrenia,” said Alan Brown, MD, MPH, senior author and Mailman School professor of Epidemiology and professor of Psychiatry at CUMC. “We employed a nationwide sample with the highest number of schizophrenia cases to date in a study of this type.”

Researchers analyzed data from a large national birth cohort of pregnant women who participated in the Finnish Prenatal Study of Schizophrenia and their offspring from the Finnish Maternity Cohort, which archived over 1 million prenatal serum specimens since 1983. Blood was collected during the first and early second trimesters. The Finnish Hospital and Outpatient Discharge Registry was used to identify all recorded diagnoses for psychiatric hospital admissions and outpatient treatment visits.

Heavy smoking based on cotinine, a reliable marker of nicotine in maternal blood sera, was reported by 20 percent of the mothers of cases, but only 15 percent of the mothers of controls.

Smoking during pregnancy is known to contribute to significant problems in utero and following birth, including low birth weight and childhood attention deficits. Nicotine readily crosses the placenta into the fetal bloodstream, specifically targets fetal brain development, causing short- and long-term changes in cognition, and potentially contributes to other neurodevelopmental abnormalities.

“These findings underscore the value of ongoing public health education on the potentially debilitating, and largely preventable, consequences that smoking may have on children over time,” said Brown.

In a previous study from a different birth cohort, also reported in the American Journal of Psychiatry, Brown and colleagues found that offspring of mothers who reported smoking during pregnancy have an increased risk of bipolar disorder.

Funding for the study was provided by the National Institute of Mental Health, grants R01 MH082052, K02 MH065422, and grant 2R01 GM095722-05 from the National Institute of General Medical Sciences.

Co-authors: Solja Niemelä, MD, PhD, University of Oulu, Finland; Andre Sourander, MD, PhD, and Susanna Hinkka-Yli-Salomäki, PhLic., University of Turku, Finland; Heljä-Marja Surcel, PhD, National Institute of Health and Welfare, Finland; and Ian W. McKeague, PhD, and Keely Cheslack-Postava, PhD, of Columbia. Within the past 36 months, Niemelä has received honoraria from Janssen, Lilly, and Lundbeck. The other authors report no financial relationships with commercial interests.