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Effect of maternal smoking on human placental development

Institution: University of California, San Francisco
Investigator(s): Susan Fisher, Ph.D.
Award Cycle: 1997 (Cycle 6) Grant #: 6RT-0304 Award: $450,000
Subject Area: General Biomedical Science
Award Type: Research Project Awards

Initial Award Abstract
Maternal cigarette smoking significantly increases the risk of serious pregnancy complications. Estimates suggest that each year tobacco use is responsible for 19,000 to 141,000 abortions, 32,000 to 61,000 low birth weight infants, 14,000 to 26,000 infants who require admission to neonatal intensive care units, and 1,900 to 4,800 infant deaths. Thus, it is not surprising that maternal cigarette smoking is unequivocally the largest and most important known, modifiable risk factor for low birth weight and infant death.

In spite of the severe negative consequences of maternal smoking on pregnancy outcome, studies suggest that approximately 20-30% of pregnant women in this country smoke. Results of a recent population-based epidemiological study conducted in California highlight the problem locally. Prevalence of prenatal tobacco use was 9% in the general population, and 29% among mothers who did not receive prenatal care. It is important to note that in this study cigarette smoking was self-reported, i.e. not verified by biochemical testing. Thus, the actual rates of prenatal smoking are likely to be far greater.

Currently, little is known about how maternal tobacco use is linked to a dramatic increase in serious pregnancy complications. We are testing the theory that smoking harms the placenta. The placenta is a transient organ that exists only during pregnancy. Its short life span belies its unique functions which are vital to human development before birth. For example, pregnancy begins when placental cells attach the embryo to the mother's uterus. Once pregnancy is established, a child must develop in the uterus for many months before its organ systems can function on their own. During this time the placenta carries out, for the child, the roles played by many important organs including the heart, lungs, digestive system and kidneys. Thus, throughout this critical period toxic substances that harm the placenta likewise harm the developing child. Results of experiments we published during the previous grant period showed that the placenta is vulnerable to the toxic effects of maternal tobacco use. Smoking interferes with the way placental cells attach to the uterus, and subsequently, the way they function. Our findings suggest that the problems are primarily due to the negative effects of maternal smoking on placental growth, the focus of our current application.

We envision that the results of our study could be used in cessation studies to help women quit smoking during pregnancy. Research suggests that pregnancy is an ideal time to intervene, since many women reduce or stop cigarette consumption on learning they are pregnant. However, the effectiveness of cessation programs in this population is greatly enhanced when they use materials that are specific to pregnant women. A simple explanation of how smoking harms a child before birth, one possible outcome of our work, could be an important part of these specially designed materials. It is likely that a subset of mothers who smoke during pregnancy will be more likely to quit if they better understand the added risk their infants incur as a result of their cigarette use. In addition, if the mother is able to stop smoking permanently, her own health will greatly benefit.

Final Report
When a mother smokes, she puts the health of her unborn child at risk. The most obvious problem that has been widely publicized is growth retardation. If the pregnancy proceeds for the usual time of nine months, then the babies born at term to mothers who smoke cigarettes weigh about 10% less than the babies born to mothers who do not smoke. Although this difference is not usually large enough to determine whether the baby lives or dies, there are nonetheless many profound consequences. Recent studies by the National Institutes of Health, and in other countries, show that impaired growth before birth leads to a variety of adult medical conditions such as obesity and diabetes. This unexpected and surprising result again highlights the importance of eliminating tobacco use during pregnancy in order to allow the baby to grow normally.

The outcome for the baby is more dire if a woman who smokes has additional pregnancy complications that lead to preterm birth, i.e. before the normal nine-month period is over. Modern obstetrical and pediatric care now allows very small babies to survive when they are born up to four months earlier than normal. If the mother smokes, then the 10% lower weight of a baby born prematurely can literally make the difference between life and death.

Why are the babies born to mothers who use tobacco so much smaller than normal? Work from our research group has focused on the role of the placenta. The reason we are interested in this organ is that it is literally the lifeline between the baby and the mother. The placenta provides air and food to the baby and removes harmful waste products. Therefore, factors that harm the placenta also harm the baby. This basic principle has been proven many times by our group and by many other researchers, here in the United States and around the world.

What happens to the placenta when a woman smokes? Our work shows that the placenta has a great deal of functional similarity to the heart. Therefore, it is not surprising that smoking, which harms the heart, also damages the placenta. During the previous grant period we investigated the exact nature of this damage. First, we used the time-honored method of using a microscope to find and characterize the kinds of damage that smoking produces in placental tissue. We found several very obvious problems that affected the placental cells that carry out the organ’s most important functions. This led us to the second part of the study in which we showed that maternal smoking harms the growth of the placenta even before it harms the growth of the baby. Surprisingly, in the same population of placental cells, we also found that the rate of cell death substantially increased. In essence we uncovered a domino effect in which a damaged placenta does not support normal development of the baby in the womb.

We want very much to use the information from our work to help smoking obstetrical patients give up cigarettes, and thereby avoid harming the growth of their babies. Our studies are producing a great deal of very specific information about the exact nature of the placental problems that ensue. This information, including facts about slower growth and acceleration of cell death, could be included in simple diagrammatic form in materials that are used by health professionals to help their patients stop smoking during pregnancy. The information from our study also suggests that these women should stop smoking even before they become pregnant, an important concept from a public health point of view. Finally, understanding the need to stop cigarette smoking during pregnancy could help at least some of the woman realize why smoking is bad at any stage of life, laying the groundwork for permanent cessation.

Regulation of human placental development by oxygen tension
Periodical: Science Index Medicus:
Authors: Genbacev O, Zhou Y, Ludlow W, Fisher SJ ART
Yr: 1997 Vol: 277 Nbr: Abs: Pg: 1669-1672

Concordant in situ and in vitro data show that maternal cigarette smoking negatively regulates placental cytotrophoblast passage through the cell cycle
Periodical: Reproductive Toxicology Index Medicus:
Authors: Genbacex O, McMaster MT, Lazic J, Nedeljkovic S, Cvetkovic M, Fisher SJ ART
Yr: 2000 Vol: 14 Nbr: Abs: Pg: 495-506