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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: 2000 (Cycle 9) Grant #: 9RT-0112 Award: $515,124
Subject Area: General Biomedical Science
Award Type: Research Project Awards

Initial Award Abstract
Maternal cigarette smoking has a severe negative effect on all stages of pregnancy, from conception to birth. Women who smoke cigarettes have a substantially increased risk of a host of serious complications, including spontaneous abortion and premature birth. These complications are responsible for the long-appreciated connection between maternal cigarette smoking and low birth weight—a dose-dependent relationship that has been demonstrated in many populations. 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 the United States, accounting for approximately $250 million in medical costs each year.

In spite of the severe negative consequences of maternal smoking on pregnancy outcome, studies suggest that, depending on the patient population, 16-34% of pregnant women smoke. Results of a recent population-based (29,949 women) 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.

The effects of maternal smoking on the fetus/child and the benefits of quitting are particularly graphic when the statistics are translated into human terms. An annual drop of 1 percentage point in smoking prevalence among pregnant women would prevent the delivery of 1300 low birth weight infants, and save $21 million in direct medical costs during the first year of the program; it would prevent the delivery of 57,200 low birth weight infants and save $572 million in direct medical costs in seven years (Lightfoot et al., 1999).

Currently, little is known about how maternal tobacco use is linked to a dramatic increase in infertility and serious pregnancy complications. We hypothesize 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 conducted in our laboratory and funded by this program show that the placenta is vulnerable to the toxic effects of maternal tobacco use. We have direct evidence that smoking interferes with the way placental cells grow and differentiate. During the present grant period we also discovered that a gene product causally linked to cancers in adults plays an important role in placental development during pregnancy. Thus, the goal of the proposed experiments is to determine whether this important gene product could play a role in mediating the ill effects of maternal smoking on the placenta. If we find that it does, our results may have interesting implications beyond reproduction, extending into cancer biology.

We envision that our results 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 pregnant women reduce or stop cigarette consumption. However, the effectiveness of cessation programs for this group is greatly enhanced when they use materials that are specific to pregnant women. A simple explanation of how smoking harms a child before birth, information our work will provide, 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 benefit.

Human cytotrophoblast expression of the von Hippel-Lindau protein is downregulated during uterine invasion in situ and upregulated by hypoxia in vitro
Periodical: Developmental Biology Index Medicus:
Authors: Genbacev O, Krtolica A, Kaelin W, Fisher SJ ART
Yr: 2001 Vol: 233 Nbr: Abs: Pg: 526-536

Disruption of oxygen-regulated responses underlies pathological changes in the placentas of women who smoke or who are passibely exposed to smoke during pregnancy.
Periodical: Journal of Repro Toxicology Index Medicus:
Authors: Genbacev O, McMaster MT, Zdravkovic T, Fisher SJ ART
Yr: 0 Vol: Nbr: Abs: Pg:

The placenta dilemma.
Periodical: Semin Reprod Med Index Medicus:
Authors: Fisher SL ART
Yr: 2000 Vol: 18 Nbr: Abs: Pg: 321-326