The Effects of Tobacco on the Fetal Brain - makes it smaller?

From Medscape Pediatrics > Viewpoints
William T. Basco, Jr., MD

J Pediatr. 2010;156:185-190

Study Summary
In the introduction to this report, the investigators review the multiple clinical effects attributed to intrauterine exposure to maternal smoking, but little is known about how fetal tobacco and nicotine exposure affect actual brain development.

This study evaluated a cohort of children born in Finland at a single hospital from 2001 to 2006. The patients were all very-low-birthweight or born < 32 weeks gestational age (very-low gestational age). This analysis included 232 infants. The maternal information was collected at enrollment, or at birth of the infant.

The infants underwent head ultrasound at predetermined points, and cranial magnetic resonance imaging when the infants were at term (by corrected age). The investigators used computer programming to determine volume measurements. Analyses determined the contribution of smoke exposure to brain volume, controlling for multiple prenatal and postnatal clinical features, including gestational age, presence of intraventricular hemorrhage, other clinical complications of prematurity, and maternal factors including alcohol use during pregnancy.

Of the 232 mothers, 42 had smoked during their pregnancy (18.1%), and they smoked a median of 10 cigarettes per day. Of those infants exposed prenatally via maternal smoking, 13% were exposed to more than 20 cigarettes per day. Boys comprised 66.7% of the exposed infants but only 54.2% of the nonexposed infants. The mean gestational age was 29 weeks. Clinical conditions of the infants did not differ between groups, including neonatal inflammatory diseases (septicemia, lung disease, etc), rates of patent ductus arteriosi, or intraventricular hemorrhage.

Mothers who smoked during pregnancy were more likely to drink alcohol during pregnancy (16.7% vs 5.8% of those who didn't smoke). They were also more likely to use illicit drugs during pregnancy, but this difference did not quite reach statistical significance (4.8% of moms who smoked used illicit drugs, compared to 0.5% of those who did not smoke, P = .08).

Although the mean total brain volume did not differ between the 2 groups (390.8 mL in exposed infants, compared with 398.4 mL in nonexposed infants, P = .09), the infants exposed to prenatal smoking had smaller frontal lobe volumes and cerebellar volumes.

The mean frontal lobe volume among infants exposed to prenatal smoking was 117.9 mL compared with 127.3 mL in nonexposed infants, and the cerebellar volume was 23.1 mL compared with 24.5 mL. The differences between frontal lobe and cerebellar volumes remained significant after adjusting for all confounding variables.

Maternal smoking was not associated with different head circumference at birth or at later time points. The authors conclude that prenatal smoking exposure is associated with a smaller frontal lobe and cerebellar volumes.

Viewpoint
I doubt that the results of this study will surprise many practitioners, most of whom (I assume) believe prenatal smoke exposure to be detrimental to a developing fetus, but actually finding brain volume associations is really eye-opening. Sadly, even these striking findings may not be enough to persuade women with nicotine addiction to not smoke during pregnancy, but it is always nice to have those discussions take place from a basis of data.

The investigators caution that it is unclear what clinical implications can be drawn from lower frontal lobe or cerebellar volumes, because this study did not report on development or functioning of the children as they aged. However, the discussion section reviews other studies that show lower frontal lobe or cerebellar volume in children and adults with behavioral problems, including attention-deficit/hyperactivity disorder, suggesting that intrauterine smoke exposure might be related to attention-deficit/hyperactivity disorder. Again, this study could raise

Because of the degree to which mothers who smoked in this study were also more likely to use alcohol during pregnancy, and have a higher rate of illicit drug use, this study points out the importance of statistically controlling for other factors that occur along with smoking, because several of these variables would also be hypothesized to have adverse effects on the developing brain.