Heightened risk of adverse neonatal outcomes from prenatal exposure to both cannabis and nicotine

In a recent study published in JAMA Network Open, researchers investigated the perinatal outcomes associated with the prenatal use of cannabis and nicotine products.

Prenatal cannabis use has been increasing in the United States (US). There are concerns for adverse pregnancy outcomes as the primary psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC), can cross the placenta. Reports indicate that prenatal exposure to cannabis is associated with preterm delivery, stillbirth, impaired offspring neurodevelopment, small-for-gestational-age infants, and neonatal intensive care unit (NICU) admissions.

Moreover, half of prenatal cannabis users also use nicotine products or tobacco, and research suggests that cannabis use can aggravate the adverse effects of nicotine exposure. Notably, the combined use of nicotine products and cannabis is associated with poor maternal health outcomes, such as worsened mental health and a higher risk of cannabis use disorder. However, the combined impact of nicotine products and cannabis on maternal and neonatal outcomes is unknown.

Study: Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure. Image Credit: ibragimova / Shutterstock

About the study

In the present study, researchers examined perinatal outcomes associated with prenatal use of both nicotine products and cannabis. They used linked hospital discharge and vital statistics data in California. Pregnant subjects with singleton gestation were included. Those with multiple births and gestational age < 23 weeks or > 42 weeks were excluded.

The primary exposure was the use of nicotine products and cannabis in pregnancy. Subjects were categorized as non-users (controls), nicotine users, cannabis users, and combined or dual users. Maternal outcomes included hypertensive disease and preterm (gestational age < 37 weeks) and very preterm delivery (< 32 weeks).

Patients were classified as having severe maternal morbidity (SMM) if they had aneurysm, myocardial infarction, acute kidney failure, amniotic fluid embolism, acute respiratory distress syndrome, eclampsia, ventricular fibrillation, cardiac arrest, severe anesthesia complications, heart failure, hysterectomy, air and thrombotic embolism, pulmonary edema, puerperal cerebrovascular disorders, or disseminated intravascular coagulation.

Neonatal outcomes were neonatal death (within 28 deaths of birth), infant death (within one year), post-neonatal death (between 28 and 365 days), respiratory distress syndrome, bronchopulmonary dysplasia, hypoglycemia, NICU admission, and small for gestational age. Multivariable Poisson regression models examined the associations of maternal use of cannabis, nicotine products, or both with perinatal outcomes.


In total, 3.12 million pregnant individuals were included. Of these, 53% were Hispanic, 28% were White, 13% were Asian, Native Hawaiian, or other Pacific Islander, and 5% were Black. Overall, 1.8% of subjects used nicotine products, 0.7% were cannabis users, and 0.3% used both. The prevalence of cannabis use increased among pregnant individuals between 2012 and 2019, while that of nicotine use decreased.

Meanwhile, the prevalence of combined use was stable. Dual users were more likely to be White, self-insured, and have < five prenatal visits during pregnancy than controls. Moreover, the proportion of chronic hypertension, diabetes, and mental health disorders was higher among those using both nicotine and cannabis compared to controls.

Increased rates of hypertensive disease were observed in patients using cannabis, nicotine, or both than among non-users. The risk of hypertensive disease was also higher in users than non-users. The rates and risk of preterm delivery were higher in patients using cannabis, nicotine, or both compared to controls. SMM rates were elevated in cannabis, nicotine, and dual users than in controls.

Likewise, SMM risk was also higher in cannabis, nicotine, or dual users. The rate of infant death was four times greater in dual users compared to controls. Further, while the risk of infant deaths was higher in nicotine or cannabis users than in controls, it was much higher in dual users than among those using either substance alone.

Neonatal death rates were 0.3% in cannabis or nicotine users, 0.6% in dual users, and 0.2% in controls. NICU admission rates were more than twice as high in dual users compared to controls. Dual users also had the highest risk of NICU admission, followed by nicotine users and cannabis users. Similarly, the rates for small for gestational age were over twice as high in dual users than in controls.


In sum, combined use of nicotine products and cannabis during pregnancy was associated with significantly higher risks of several adverse maternal and neonatal outcomes compared to the use of either substance alone, suggesting synergistic effects on offspring morbidity and mortality. While abstinence from both substances in pregnancy is the goal, people unable to achieve this would still benefit by ceasing at least one substance. These findings help inform public health policy and clinician counseling, especially regarding cessation benefits.

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