Children with a common genetic variant who were exposed to maternal cigarette smoke in the womb were significantly more likely to have asthma, wheezing and emergency room visits due to breathing problems than other similar children, according to a study in the Aug. 15 issue of the American Journal of Respiratory and Critical Care Medicine.
Frank D. Gilliland, M.D., Ph.D., professor of preventive medicine, and colleagues conducted their study with 2,950 school children in 4th, 7th and 10th grades in Southern California. They asked parents about maternal smoking while pregnant and about respiratory health problems currently or previously experienced by children.
The children were participants in the expansive Children's Health Study, led by USC researchers. Scientists have monitored levels of major pollutants in 12 Southern California communities since 1993 while carefully following the respiratory health of thousands of children in these areas.
Previous research has shown that environmental tobacco smoke impairs lung growth and development in children, and recent reports have suggested exposure in the womb is associated with deficits in lung function at birth that may persist into young adulthood.
This study pinpoints for the first time a group of children who appear genetically susceptible to the effects of smoke from their very beginnings.
"The study illustrates that experiences during the period in the womb are very important for long term health, especially among genetically susceptible children, and emphasize the importance of pregnant women not smoking," Gilliland said.
Researchers collected cell samples from the mouth of each child and analyzed their DNA. They looked for variation in a gene called glutathione S-transferase M1, or GSTM1. This gene is responsible for creating an enzyme the lung uses to protect itself from pollutants. It helps the lungs detoxify some of the products of tobacco and it defuses oxidants before they can cause damage to delicate lung tissue.
This gene occurs in two common forms in the population-either present or null. Differences between present and null genes are small, but they mean a lot. When children are born with two of the null form of the gene, known as the GSTM1 null genotype, their bodies cannot produce the protective enzyme at all.
Among children in the study, more than 16 percent had a mother who smoked while the child was still in the womb. More than 45 percent of all children had the GSTM1 null variant genotype.
When researchers looked only at children with the GSTM1 null genotype, they found that in utero exposure to smoke was associated with increased prevalence of numerous respiratory symptoms:
- 3.7-fold risk increased risk for emergency room visits during the past year;
2.2-fold and 2.1-fold increased risks for wheezing with exercise and wheezing requiring medication, respectively;
80 percent increased risk for lifetime history of wheezing; and
70 percent and 60 percent increased risks for asthma with current symptoms and early onset asthma, respectively.
In contrast, researchers found no increased risk for respiratory problems among exposed children with the GSTM1 present genotype (at least one copy of the GSTM1 present allele).
Researchers warn that further studies are needed to confirm findings. The group hopes to examine links between other genes and respiratory disease risk. They already have shown that a variant in the glutathione S-transferase P1 gene is linked to decreased risk of respiratory illness-related school absences.
"Findings show that exposure to smoke in the womb for certain genetically susceptible children may have long-term health effects," Gilliland says. "Maternal smoking is common, and the null genotype is found in nearly half of the population, so this high-risk group might be an important population to target for prevention."
The research was funded by the California Air Resources Board, the National Institute of Environmental Health Sciences, the Environmental Protection Agency, the National Heart, Lung and Blood Institute and the Hastings Foundation.
Frank D. Gilliland, Yu-Fen Li, Louis Dubeau, Kiros Berhane, Edward Avol, Rob McConnell, W. James Gauderman and John Peters. "Effects of GSTM1, Maternal Smoking during Pregnancy, and Environmental Tobacco Smoke on Asthma and Wheezing in Children," American Journal of Respiratory and Critical Care Medicine, Aug. 15, 2002, Vol. 166, No. 3.