Smoking in pregnancy can damage the unborn child
They believe the key is the way that certain genes interact with cigarette smoke.
These genes - called CYP1A1 and GSTTI - control the way the body breaks down the chemical components of cigarette smoke.
Dr Xiaobin Wang and her colleagues studied 741 pregnant women who gave birth at Boston Medical Center during 1998-2000.
The lowest birth weights and shortest gestations were seen in babies of those women who smoked throughout pregnancy and had variant forms of both genes.
Among women who had never smoked, there was no independent increased risk of low birth weight or prematurity from the same genetic variations.
Writing in the Journal of the American Medical Association, the authors say: "Our data demonstrate that a subgroup of pregnant women with certain genotypes appeared to be particularly susceptible to the adverse effect of cigarette smoke, suggesting an interaction between metabolic genes and cigarette smoking."
However, Dr Wang said low birth weight was a very complex problem, and many different environmental and genetic factors might be involved.
Breakthrough
She said: "This is the first study to demonstrate a link between cigarette smoking, specific genes, and low birth weight.
"Although this finding needs to be confirmed, it is solid, innovative science and we hope it will lead to better ways to recognise and treat those women at high risk of having a low birth weight baby.
"For example, in the future, smoking prevention or cessation could be more strenuously targeted to those women with this genetic profile."
Dee Beresford, executive officer of the UK's Neonatal Nursing Association, said all women who were considering getting pregnant should be given help and advice to quit or reduce their smoking.
She told BBC News Online: "The general message has to be that smoking in pregnancy can harm babies."
Dr Wang is seeking to identify specific genetic traits that make women more likely to give birth to a low birth weight or premature baby.
She has chosen 51 genes to study, including those involved in the body's responses to stress and infection, in hormonal changes related to pregnancy, and in ways in which the body handles a wide variety of environmental toxins.