Mothers Who Smoke During Pregnancy Could Risk Child’s Brain Development


Children may have suboptimal long-term brain development if their mother smokes tobacco consistently during pregnancy.

Consistent maternal smoking during pregnancy may be associated with suboptimal long-term brain development for the offspring, according to a recent study published in JAMA Network.

The study authors noted that there is mounting evidence indicating tobacco use during pregnancy creates suboptimal neurodevelopment in offspring. These issues include impaired cognitive abilities, bipolar disorder, and schizophrenia spectrum disorders.

The study explored the association between a mother who uses tobacco during her pregnancy and preadolescent brain development, including its mediating pathways. Paternal smoking was used as a negative control for family confounding and shared genetics.

This study joined the larger population-based Generation R Study, based in the Netherlands. The Generation R Study recruited 9778 pregnant women who delivered between April 2002 and January 2006. Of these children, 2047 were included in the study.

Researchers first administered questionnaires to the mothers about their tobacco use during each trimester. Investigators then used magnetic resonance imaging to assess the preadolescent’s brain morphology, collecting information on brain volume and surface-based cortical measures. They quantified DNA methylation using a weighted methylation risk score.

Consistent tobacco use during pregnancy was positively associated with the offspring having lower global and regional brain volumes, which remained when the child grew to 9-11 years of age. The offspring also had noticeably smaller surface areas of their brain, and further imaging revealed less gyrification among 10-year-old participants. Even though tobacco exposure is a significant environmental factor associated with DNA methylation, no evidence associates maternal smoking with DNA methylation at birth, according to the investigators.

These findings suggest that children consistently exposed to tobacco in utero had compromised brain development 10 years later. Nicotine could be a factor for this finding, as it has been shown in animal models to induce apoptotic cell death that can shrink a fetal brain and cause it to stay shrunken as the offspring grows up. Additionally, recent studies have linked tobacco to reducing skull capacity, which could restrict long-term brain development.

Researchers observed no association between paternal tobacco use and child brain morphology. Thus, family factors or shared genetics were not believed to contribute to this suboptimal preadolescent brain development.

The study authors speculated that consistent tobacco use during pregnancy impacted brain development more than early-on tobacco use only. Researchers now recommend quitting tobacco before a planned pregnancy or when a pregnancy is discovered to protect optimal brain development for the child.

This study was limited because information on tobacco was based on a questionnaire without biomarkers. Further, the study authors said they may misjudge paternal figures who smoke before pregnancy about their smoking during pregnancy. The research is also generalized to White children only and confounding could have occurred because of the study’s observational nature.

Future studies could look at the neurocognitive outcomes to find the clinical relevance of brain morphology and smoking, according to the investigators.


Zou, Runyu. Boer, Olga D., Felix, Janine F. et al. Association of Maternal Tobacco Use During Pregnancy With Preadolescent Brain Morphology Among Offspring. JAMA Netw Open. 2022;5(8):e2224701. doi:10.1001/jamanetworkopen.2022.24701

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