A study of over 6,000 mothers and their newborn children--one of the largest studies of its kind--solidifies the evidence that smoking cigarettes while pregnant chemically modifies a fetus' DNA, mirroring patterns seen in adult smokers. The researchers also identify new development-related genes affected by smoking. The work, published March 31 in the American Journal of Human Genetics, suggests a potential explanation for the link between smoking during pregnancy and health complications in children.
"I find it kind of amazing when we see these epigenetic signals in newborns, from in utero exposure, lighting up the same genes as an adult's own cigarette smoking. There's a lot of overlap," says co-senior author Stephanie London, an epidemiologist and physician at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. "This is a blood-borne exposure to smoking--the fetus isn't breathing it, but many of the same things are going to be passing through the placenta."
Links between smoking and chemical modifications to DNA, or methylation, have been found for developing fetuses in smaller studies, but the larger analysis gives scientists more power to uncover patterns. An international team of researchers pooled results from 6,685 newborns and their mothers around the world. Based on questionnaires, mothers were labeled as "sustained smokers" who smoked cigarettes daily throughout most of pregnancy (13 percent), "non-smokers" (62 percent), or those with "any smoking" during pregnancy (25 percent), which captured mothers who were occasional smokers or who quit smoking early on.
To analyze methylation in the newborns' DNA, researchers collected samples mainly from blood in the umbilical cord after delivery. For the newborns whose mothers fell into the "sustained smoker" category, the research teams identified 6,073 places where the DNA was chemically modified differently than in the "no smoking" newborns. About half of these locations could be tied to a specific gene.
London and her colleagues found that this collection of genes related to lung and nervous system development, smoking-related cancers, birth defects such as cleft lip and palate, and more. "Many signals tied into developmental pathways," says Bonnie Joubert, an epidemiologist at the NIEHS and a co-first author on the paper. In a separate analysis, many of these DNA modifications were still apparent in older children whose mothers had smoked during pregnancy.
Next steps include building on the preliminary gene-expression analyses conducted by the research team to better understand how these DNA modifications might influence child development and disease. For example, London says, "We already knew that smoking is related to cleft lip and palate, but we don't know why. Methylation might be somehow involved in the process."
This is the first paper from the international Pregnancy and Childhood Epigenetics (PACE) consortium. PACE is applying the "consortium approach" to additional studies, bringing large teams of scientists together on questions such as the impact of a mother's body weight, alcohol intake, and air pollution on her child's epigenetic marks--and the effects of those marks on the child's health. "It's important to recognize the many people involved and the work that they did," says Joubert.
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