Study highlights:
• Smoking while pregnant has been shown to reduce the production of a chemical that relaxes blood vessels and can lead to lowered blood flow to the fetus, resulting in lower birth weight, shorter length and smaller head circumference.
• The study is one of the first to pinpoint the mechanism linking maternal smoking to low birth weight.
• If an expectant mother stops smoking early in pregnancy, enzyme levels return to normal and the infant is born at normal birth weight, researchers said.
 
DALLAS, Feb. 2, 2009 — Smoking during pregnancy has been shown to reduce the production of a chemical substance that relaxes blood vessels which leads to lowered blood flow to the fetus — resulting in lower birth weight, shorter length and smaller head circumference — Danish researchers report in Circulation: Journal of the American Heart Association.

“This study is one of the first to show a biochemical measurement of what is going on to cause the lower birth weight,” said Malene Rohr Andersen, M.Sc., Ph.D., lead author of the study and project manager of the Department of Clinical Biochemistry at Gentofte University Hospital in Denmark. “We have known for 50 years that infants born to mothers who smoke during pregnancy have lower birth weights. But this study provides a possible explanation of why there is restricted blood flow to the fetus.
Reduced production of the vasodilator nitric oxide may lower the blood flow to the fetus.”

Researchers also found that if the expectant mother quits smoking early in pregnancy, the enzyme that produces nitric oxide returns to normal levels and the infant is born at normal birth weight.

The study included 266 healthy pregnancies of 182 non-smokers, 43 smokers and 41 women who had stopped smoking early (approximately six weeks) in the pregnancy. Women who had cardiovascular disease, gestational diabetes, pre-eclampsia or delivered before 37 weeks of gestation were excluded. To assess smoking activity, the researchers measured levels of cotinine, the major metabolite of nicotine that indicates levels of tobacco exposure.

The inner cell lining of the fetal umbilical cord (endothelial cells) was isolated immediately after delivery and stored frozen. At the end of the study the eNOS activity and concentration were quantified.

Newborns of mothers who smoked had not only reduced activity but reduced concentrations of the enzyme endothelial nitric oxide synthase (eNOS), which produces nitric oxide regulating the blood flow through the vessels. Activity of eNOS in the fetal umbilical cord of smokers was 36 percent less than in non-smokers and the eNOS concentration was 47 percent lower in smokers. Furthermore, high-density lipoprotein (HDL) — good cholesterol — was found to be 18 percent lower in the newborns of smoking mothers.

Researchers found that the number of cigarettes smoked each day during the pregnancy was negatively associated with eNOS activity and concentration. Furthermore, higher eNOS activity was associated with higher newborn weight and the association persisted after adjustment for body mass index (BMI) of the women before pregnancy, parity, gestational age and infant gender (all possible factors for low birth weight).

Researchers found the average difference in newborn weight between infants of nonsmokers and smokers was approximately 350 grams, with about 25 percent of the reduction in newborn weight explained by the differences in eNOS activity between smoking and non-smoking mothers. A reduced production of nitric oxide in the fetal vessels causes restriction in the vessels, lowering the blood flow in the umbilical cord which exclusively supplies the fetus with oxygen and nutrients prior to birth. The reduction in blood flow may thus result in retarded fetal growth and low birth weight when the infant is born.

“Women who smoke should stop smoking if they plan to become pregnant, or at the very least should stop smoking as soon as they find out they are pregnant,” Andersen said. “Women should also not start smoking again once they have delivered. Some women stop smoking during pregnancy, only to start up again after the baby is delivered and the child is then exposed to environmental smoke, which also affects vascular function.”

Scientists still don’t know whether the compromised vascular system before birth carries into adulthood, making these infants more vulnerable to cardiovascular disease.

“Are these children predisposed to atherosclerosis later in life because of the endothelial dysfunction before birth?,” asked Andersen, whose research team hopes to follow some of the children in this study through childhood and into adulthood to get the answer to the question.

Co-authors are: Ulf Simonsen, M.D., Ph.D.; Niels Uldbjerg, M.D., Ph.D.; Christian Aalkjaer, M.D., Ph.D.; and Steen Stender, M.D., Ph.D. Individual author disclosures are available on the manuscript.

The study was funded by the Faculty of Health Science and the Clinical Institute (Aarhus University); the Master Cabinetmaker Sophus Jacobsen and Wife Astrid Jacobsen’s Fund; the National Association for Controlling Circulatory Diseases Foundation; and the Marie Dorthea and Holger From, Haderslev Fund.

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NR09 – 1012 (Circ/Andersen)