In the most definitive study to date, cigarette smoking during pregnancy was linked to a greater likelihood of schizophrenia in offspring. Those are the findings of a new long-term study which assessed maternal nicotine exposure (via cotinine levels) during pregnancy.

In a first-of-its-kind study, the researchers measured cotinine levels in prospectively drawn, biobanked maternal serum specimens during early to mid-gestation, for nearly all (≥98%) mothers of offspring born in Finland between 1983 and 1998. All serum samples were given unique PINs.

To identify cases of schizophrenia, researchers matched the PINs to records from The Finnish Hospital Outpatient Discharge Registry, which holds diagnoses, hospital admissions and outpatient treatment, and was computerized from 1987 onwards. Cohort records were followed up with until 2009. 

Related Articles

In total 977 cases of schizophrenia were identified, these were matched with 1:1 to control subjects taken from the cohort who didn’t have a diagnosis of schizophrenia.

Results showed an odds ratio of 2.69 between maternal cotinine and schizophrenia, a significant association (95% CI=1.54–4.69, P<0.0001). This association remained significant after adjustments were made for the covariates tied to continine exposure and schizophrenia.

When categorized by quantity of exposure; those with cotinine levels of <20ng/ml, 20–50ng/mL (moderate exposure), and >50ng/mL (heavy exposure), the >50ng/mL offspring group had a 1.38 odds ratio of schizophrenia after covariate adjustments were made (95%CI=1.05–1.82, p=0.02). Whereas the 20–50ng/mL group was associated with schizophrenia only when adjustments for maternal schizophrenia and province were made, but not other multivariate models (OD=1.96, 95% CI=1.04–3.70, p=0.04).

Self-reported prenatal smoking habits correlated with the results. Of the case subjects, 21% of mothers (138 of 656 whose self-reported data was available), reported smoking compared to 15.8% (106 of 670 whose self-reported data was available) of the control group.

The authors highlight how there are several mechanisms by which nicotine exposure can alter fetal brain development by inducing dysregulation of neurotransmitter systems. This neuromorphology persists beyond the fetal period. Such brain anomalies have been demonstrated in schizophrenia.

“Maternal cigarette smoking has been associated with epigenetic effects indicating sensitivity of the methylome and down-regulation of brain-derived neurotrophic factor (BDNF), which is related to schizophrenia,” write the authors.

Study limitations include lack of data on prenatal alcohol use, a comorbidity of smoking. Also, nicotine is only one of several potentially toxic compounds found in cigarettes, however there is substantial evidence in the literature suggesting that nicotine is a biologically plausible dispruptor of fetal development.

The researchers assert the need for further research to address any residual confounders, however they conclude that ”these findings suggest that preventing smoking during pregnancy may decrease the incidence of schizophrenia.”

For more information visit