TOPIK 1

Alcohol and Cancer

Cancer kills an estimated 526,000 Americans yearly, second only to heart disease (1). Cancers
of the lung, large bowel, and breast are the most common in the United States. Considerable
evidence suggests a connection between heavy alcohol consumption and increased risk for
cancer, with an estimated 2 to 4 percent of all cancer cases thought to be caused either directly
or indirectly by alcohol (2).
A strong association exists between alcohol use and cancers of the esophagus, pharynx, and
mouth, whereas a more controversial association links alcohol with liver, breast, and colorectal
cancers. Together, these cancers kill more than 125,000 people annually in the United States
(1). The following sections discuss alcohol's role in these cancers.
1. Cancer is a group of diseases characterized by cells that grow out of control; in
many cases, they form masses of cells, or tumors, that infiltrate, crowd out, and destroy
normal tissue. Although the body strictly regulates normal cells to grow within the
confines of tissues, cancer cells reproduce independently, uninhibited by tissue
boundaries. Cancer develops in three stages: initiation, promotion, and
progression. Cancer-causing agents, known as carcinogens, can contribute to the first
two stages.
Cancer initiation occurs when a cell's DNA (the substance that genes are made of) is irreversibly
changed so that, once triggered to divide, the cell will reproduce indefinitely. The "change"
involves mutations to the cell's genes that can occur spontaneously or can be induced by a
carcinogen. In some cancers, it has been shown that the mutations occur in oncogenes, genes
that normally promote cell division, or in suppressor genes, genes that normally suppress cell
division. Thus, it is believed that cancer-causing mutations result in overpromotion or
undersuppression of cell reproduction. During cancer promotion, the initiated cell is stimulated
to divide. The stimulus can be natural, as when tissue damage requires proliferation of new
cells, or it can be caused by a carcinogen. During cancer progression, tumors produced by the
replicating mass of cells metastasize, or spread, from the initial or primary tumor to other parts
of the body, forming secondary
cancers.
Two types of research link alcohol and cancer. Epidemiologic research has shown a dosedependent association between alcohol consumption and certain types of cancer; as alcohol
consumption increases, so does risk of developing certain cancers. More tenuous results have
come from research into the mechanism by which alcohol could contribute to cancer
development.
The strongest link between alcohol and cancer involves cancers of the upper digestive tract,
including the esophagus, the mouth, the pharynx, and the larynx (3). Less consistent data link
alcohol consumption and cancers of the liver, breast, and colon (3).
Upper digestive tract. Chronic heavy drinkers have a higher incidence of esophageal cancer
than does the general population. The risk appears to increase as alcohol consumption
increases (4-6). An estimated 75 percent of esophageal cancers in the United States are
attributable to chronic, excessive alcohol consumption (7).

Nearly 50 percent of cancers of the mouth, pharynx, and larynx are associated with heavy
drinking (7). People who drink large quantities of alcohol over time have an increased risk of
these cancers as compared with abstainers (8,9). If they drink and smok e, the increase in risk
is even more dramatic (5,6).
Liver. Prolonged, heavy drinking has been associated in many cases with primary liver cancer.
However, it is liver cirrhosis, whether caused by alcohol or another factor, that is thought to
induce the cancer (10,11). In areas of Africa and Asia, liver cancer afflicts 50 or more people per
100,000 per year, usually associated with cirrhosis caused by hepatitis viruses. In the United
States, liver cancer is relatively uncommon, afflicting approximately 2 people per 100,000, but
excessive alcohol consumption is linked to as many as 36 percent of these cases by some
investigators (2,12).
The association between alcohol use and liver cancer is difficult to interpret, because liver
cirrhosis and hepatitis B and C virus infections often confound data (13). Studies of the
interactions between alcohol, hepatitis viruses, and cirrhosis will help clarify these associations
with liver cancer (see below).
Breast. Chronic alcohol consumption has been associated with a small (averaging 10 percent)
increase in a woman's risk of breast cancer (14-17). According to these studies, the risk
appears to increase as the quantity and duration of alcohol consumption increases. Other
studies, however, have found no evidence of such a link (18-20).
The inconsistency and weakness of epidemiologic findings suggest that a third confounding
factor, such as nutrition, may be responsible for the link between alcohol and breast
cancer (15). However, studies that adjusted for dietary factors such as fat intake found that the
association between alcohol and breast cancer remained (14,21,22).
Recent studies suggest that alcohol may play an indirect role in the development of breast
cancer. These studies indicate that alcohol increases estrogen levels in premenopausal women,
which, in turn, may promote breast cancer (23).
Colon. Epidemiologic studies have found a small but consistent dose-dependent association
between alcohol consumption and colorectal cancer (15,24), even when controlling for fiber and
other dietary factors (15,25,26). Despite the large number of studies, however, causality cannot
be determined from the available data.
Other cancers. A few studies have linked chronic heavy drinking with cancers of the stomach,
pancreas, and lungs (3). However, the association is consistently weak and the majority of
studies have found no association (3).
The epidemiologic data provide little insight into whether or how alcohol increases the risk for
various cancers. For some cancers, such as mouth and esophageal, alcohol is thought to play a
direct causal role. For others, such as liver and breast cancers, alcohol is thought to play an
indirect role by enhancing mechanisms that may cause cancer. Studies looking at these direct
and indirect mechanisms may shed light on alcohol's role in developing cancers.
Preliminary studies show that alcohol may affect cancer development at the genetic level by
affecting oncogenes at the initiation and promotion stages of cancer. It has been suggested that
acetaldehyde, a product of alcohol metabolism, impairs a cell's natural ability to repair its DNA,

resulting in a greater likelihood that mutations causing cancer initiation will occur (27). It has
recently been suggested that alcohol exposure may result in overexpression of certain
oncogenes in human cells and, thereby, trigger cancer promotion (28).
Although there is no evidence that alcohol itself is a carcinogen, alcohol may act as a
cocarcinogen by enhancing the carcinogenic effects of other chemicals. For example, studies
indicate that alcohol enhances tobacco's abil ity to stimulate tumor formation in rats (29). In
humans, the risk for mouth, tracheal, and esophageal cancer is 35 times greater for people who
both smoke and drink than for people who neither smoke nor drink (30), implying a
cocarcinogenic interaction between alcohol and tobacco-related
carcinogens (29).
Alcohol's cocarcinogenic effect may be explained by its interaction with certain enzymes. Some
enzymes that normally help to detoxify substances that enter the body can also increase the
toxicity of some carcinogens. One of these enzymes is called cytochrome P-450 (31,32).
Dietary alcohol is able to induce cytochrome P-450 in the liver, lungs, esophagus, and intestines
(29,33), where alcohol-associated cancers occur. Subsequently, carcinogens such as those
from tobacco and diet can become more potent as they, too, pass through the esophagus,
lungs, intestines, and liver and encounter the activated enzyme (29,33).
Nutrition. Chronic alcohol abuse may result in abnormalities in the way the body processes
nutrients and may subsequently promote certain types of cancer. Reduced levels of iron, zinc,
vitamin E, and some of the B vitamins, common in heavy drinkers, have been experimentally
associated with some cancers (29). Also, levels of vitamin A, hypothesized to have anticancer
properties (34), are severely depressed in the liver and esophagus of rats during chronic alcohol
consumption (35-37).
A recent study indicates that as few as two drinks per day negates any beneficial effects of a
"correct" diet on decreasing risk of colon cancer (38). Although the study suggests that a diet
high in folic acid, a B vitamin found in fresh fruits and vegetables, decreases the risk for colon
cancer, it also warns that alcohol consumption may counter this protective action and increase
the risk for colon cancer by reducing folic acid levels.
Although epidemiologic studies have found a clear association between alcohol consumption
and development of certain types of cancer, study findings are often inconsistent and may vary
by country and by type of cancer. The key to understanding the association lies in research
designed to decipher how alcohol may promote cancer. Such studies examine
alcohol's metabolic effects at the cellular and genetic levels. Research examining the ways in
which alcohol may induce cancers has found some potential mechanisms, the most promising
of which implicates oncogenes.

TOPIK 2
Alcohol and Stress
The term "stress" often is used to describe the subjective feeling of pressure or tension.
However, when scientists refer to stress, they mean the many objective physiological processes
that are initiated in response to a stressor. As this Alcohol Alert explains, the stress response is
a complex process; the association between drinking and stress is more complicated still.
Because both drinking behavior and an individual's response to stress are determined by
multiple genetic and environmental factors (1-3), studying the link between alcohol consumption
and stress may further our understanding of drinking behavior.
The maintenance of the body's relatively steady internal state, or homeostasis, is essential for
survival. The body's delicate balance of biochemical and physiological function is constantly
challenged by a wide variety of stressors, including illness, injury, and exposure to extreme
temperatures; by psychological factors, such as depression and fear; and by sexual activity and
some forms of novelty-seeking. In response to stress, or even perceived stress, the body
mobilizes an extensive array of physiological and behavioral changes in a process of continual
adaptation, with the goal of maintaining homeostasis and coping with the stress (4).
The stress response is a highly complex, integrated network involving the central nervous
system, the adrenal system, and the cardiovascular system. When homeostasis is threatened,
the hypothalamus gland, at the base of the brain, initiates the stress response by secreting
corticotropin releasing factor (CRF). CRF coordinates the stress response by triggering an
integrated series of physiological and behavioral reactions. CRF is transported in blood within
the brain and in seconds triggers the pituitary gland to release adrenocorticotropin hormone
(ACTH), also referred to as corticotropin. ACTH then triggers secretion of glucocorticoid
hormones (i.e., "steroids") by the adrenal glands, located at the top of the kidneys.
Glucocorticoid hormones play a key role in the stress response and its termination (4).
Activation of the stress response affects smooth muscle, fat, the gastrointestinal tract, the
kidneys, and many other organs and the body functions that they control (4). The stress
response affects the body's regulation of temperature; appetite and satiety; arousal, vigilance,
and attention; mood; and more (4). Physical adaptation to stress allows the body to redirect
oxygen and nutrients to the stressed body site, where they are needed most (4).
Both the perception of what is stressful and the physiological response to stress vary
considerably among individuals. These differences are based on genetic factors and
environmental influences that can be traced back to infancy (5).
Stress is usually thought of as harmful; but when the stress response is acute and transient,
homeostasis is maintained and no adverse effects result. Under chronic stress, however, when
the body either fails to compensate or when it overcompensates, damage can occur (4). Such
damage may include suppression of growth, immune system dysfunction, and cell damage
resulting in impaired learning and memory (4,6).
Human research to clarify the connection between alcohol and stress usually has been
conducted using either population surveys based on subject self-reports or experimental
studies. In many but not all of these studies, individuals report that they drink in response to
stress and do so for a variety of reasons. Studies indicate that people drink as a means of

coping with economic stress, job stress, and marital problems, often in the absence of social
support, and that the more severe and chronic the stressor, the greater the alcohol consumption
(7). However, whether an individual will drink in response to stress appears to depend on many
factors, including possible genetic determinants of drinking in response to stress, an individual's
usual drinking behavior, one's expectations regarding the effect of alcohol on stress, the
intensity and type of stressor, the individual's sense of control over the stressor, the range of
one's responses to cope with the perceived stress, and the availability of social support to buffer
the effects of stress (1,2,7,8). Some researchers have found that high levels of stress may
influence drinking when alternative resources are lacking, when alcohol is accessible, and when
the individual believes that alcohol will help to reduce the stress (1,8).
Numerous studies have found that stress increases alcohol consumption in animals (9) and that
individual animals may differ in the amount of alcohol they consume in response to stress (10).
Such differences may be related in part to an animal's experiencing chronic stress early in life:
Prolonged stress in infancy may permanently alter the hormonal stress response and
subsequent reactions to new stressors, including alcohol consumption (10,11). For example,
monkeys who were reared by peers, a circumstance regarded as a stressor compared to
mother-rearing, consumed twice as much alcohol as monkeys who were mother-reared (10).
According to Viau and colleagues (11), adult rats handled for the first 3 weeks of life
demonstrate markedly reduced hormonal responses to a variety of stressors compared with rats
not handled during this time (11). In humans, Cloninger reported an association between certain
types of alcoholism and adverse early childhood experiences (12).
Animal studies reporting a positive correlation between stress and alcohol consumption suggest
that drinking may take place in response to chronic stress perceived as unavoidable (2,13). For
instance, rats chronically exposed to unavoidable shock learn to be helpless or passive when
faced with any new stressor--including shock that is avoidable--and to demonstrate increased
alcohol preference compared with rats that received only avoidable shock (2). The rats exposed
to unavoidable shock exhibit the hormonal changes indicative of the stress response, including
increased levels of corticosteroid hormones (2).
Whether humans drink in response to uncontrollable stress is less clear, according to Pohorecky
(7). In a review investigating the connection between alcohol consumption and stress,
Pohorecky notes several studies in which researchers sampled individuals from areas affected
by natural disaster. One study found that alcohol consumption increased by 30 percent in the 2
years following a flood at Buffalo Creek, West Virginia. Similarly, there was evidence of
increased drinking in the towns surrounding Mount St. Helens following eruption of the volcano
(7). Following the nuclear plant accident at Three Mile Island, however, alcohol consumption
was infrequently used by those sampled as a means of coping with the resulting stress (14).
In both humans and animals, drinking appears to follow stress (2,3,7,13). Some human
research, however, shows that drinking may take place in anticipation of or during times of
stress (15).
Some studies have reported that acute exposure to low doses of alcohol may reduce the
response to a stressor in animals and humans. For example, low doses of alcohol reduced the
stress response in rats subjected to strenuous activity in a running wheel (3). In humans, a low
dose of alcohol improved performance of a complex mental problem-solving task under stressful
conditions (3). However , in some individuals, at certain doses, alcohol may induce rather than
reduce the body's stress response (16).

Much research demonstrates that alcohol actually induces the stress response by stimulating
hormone release by the hypothalamus, pituitary, and adrenal glands (4,6,17,18). This finding
has been demonstrated in animal studies. In one study with rats, the administration of alcohol
initiated the physiological stress response, measured by increased levels of corticosterone (19).
In addition to stimulating the hormonal stress response, chronic exposure to alcohol also results
in an increase in adrenaline (20).
Stress may be linked to social drinking, and the physiological response to stress is different in
actively drinking alcoholics compared with nonalcoholics (17). Researchers have found that
animals preferring alcohol over water have a different physiological response to stress than
animals that do not prefer alcohol (21). Nonetheless, a clear association between stress,
drinking behavior, and the development of alcoholism in humans has yet to be established.
There may, however, in the already established alcoholic, be a clearer connection between
stress and relapse: Among abstinent alcoholics, personally threatening, severe, and chronic life
stressors may lead to alcohol relapse (15,22). Brown and colleagues (15) studied a group of
men who completed inpatient alcoholism treatment and later experienced severe and prolonged
psychosocial stress prior to and independent of any alcohol use. The researchers found that
subjects who relapsed experienced twice as much severe and prolonged stress before their
return to drinking as those who remained abstinent. In this study, severe psychosocial stress
was related to relapse in alcoholic males who expected alcohol to reduce their stress. Those
most vulnerable to stress-related relapse scored low on measures of coping skills, self-efficacy,
and social support. Stress-related relapse was greatest among those who had less confidence
in their ability to resist drinking and among those who relied on drinkers for social support.
Although many factors can influence a return to drinking, Brown and colleagues note that stress
may exert its greatest influence on the initial consumption of alcohol after a period of abstinence
(15).

TOPIK 3
Pregnancy, Breastfeeding, and Bone Health
Both pregnancy and breastfeeding cause changes and place extra demands on a woman's
body. Some of these may have an affect on her bones. The good news is that most women do
not experience bone problems during pregnancy and breastfeeding. And if their bones are
affected during these times, the problem is often easily corrected. Nevertheless, taking care of
one's bone health is especially important during pregnancy and when breastfeeding for the
good health of both the mother and her baby.
During pregnancy, the baby growing in its mother's womb needs plenty of calcium to develop its
skeleton. This need is especially great during the last 3 months of the pregnancy. If the mother
does not get enough calcium, her baby will draw what it needs from its mother's bones. So, it is
disconcerting to realize that most women of child-bearing years are not in the habit of getting
enough calcium. Fortunately (unless a mother is still a teenager), pregnancy appears to help
protect a woman's calcium reserves in several ways:

Pregnant women absorb calcium better from food and supplements than women who
are not pregnant. This is especially true during the last half of pregnancy, when the baby
is growing quickly and has the greatest need for calcium.

During pregnancy, women produce more estrogen, a hormone that protects bones.

Any bone mass lost during pregnancy is typically restored within several months after
the baby's delivery (or several months after breastfeeding is stopped).

Some studies suggest that pregnancy may be good for bone health overall. There is some
evidence that the more times a woman has been pregnant (for at least 28 weeks), the greater
her bone density and the lower her risk of fracture.
In some cases, women develop osteoporosis during pregnancy and/or breastfeeding, although
this is rare. Osteoporosis is bone loss that is serious enough to result in fragile bones and
increased risk of fracture.
In many cases, women who develop osteoporosis during pregnancy and breastfeeding will
recover lost bone after their pregnancy ends or they stop breastfeeding. It is less clear whether
teenage mothers recover lost bone and are able to go on to optimize their bone mass.
Teenage mothers may be at especially high risk for bone loss during pregnancy and for
osteoporosis later in life. Unlike older women, these mothers are still building much of their total
bone mass during their teenage years. The unborn baby's need to develop its skeleton may
compete with the teenage mother's need for calcium to build her own bones, compromising her
ability to achieve optimal bone mass that will help protect her from osteoporosis later in life.
Pregnant teens should be especially careful to get enough calcium during and after their babies
are born to minimize any bone loss.
Breastfeeding also has an affect on a mother's bones. Studies have shown that women often
lose 3 to 5 percent of their bone mass during breastfeeding, although it is rapidly recovered after
weaning. This bone loss may be caused by the growing baby's increased need for calcium,
which is drawn from the mother's bones. The amount of calcium the mother needs depends on
the amount of breast milk produced and how long breastfeeding continues. Bone loss may also
occur during breastfeeding because the mother produces less estrogen the hormone that

protects bones. The good news is that like the bone lost during pregnancy, bone lost during
breastfeeding is usually recovered within 6 months after breastfeeding ends.
Taking care of your bones is important throughout life, including before, during, and after
pregnancy and breastfeeding. A balanced diet with adequate calcium, regular exercise, and a
healthy lifestyle are good for mothers and their babies.
Calcium: Although this important mineral is important throughout your lifetime, your body's
demand for it is greater during pregnancy and breastfeeding, because both you and your baby
need it. The National Academy of Sciences recommends that women who are pregnant or
breastfeeding consume 1,000 mg (milligrams) of calcium each day. For pregnant teens, the
recommended intake is even higher: 1,300 mg a day.
Good sources of calcium include:

low-fat dairy products, such as milk, yogurt, cheese, and ice cream

dark green, leafy vegetables, such as broccoli, collard greens, and bok choy

canned sardines and salmon with bones

tofu, almonds, corn tortillas

foods fortified with calcium, such as orange juice, cereals, and breads.

In addition, your doctor will probably prescribe a vitamin and mineral supplement to take during
your pregnancy and while breastfeeding to ensure that you get enough of this important mineral.
Exercise: Like muscles, bones respond to exercise by becoming stronger. Regular exercise,
especially weight-bearing exercise that forces you to work against gravity, helps build and
maintain strong bones. Examples of weight-bearing exercise include walking, climbing stairs,
dancing, and lifting weights. Being active and exercising during pregnancy can benefit your
health in other ways, too. According to the American College of Obstetricians and
Gynecologists, it can:

help reduce backaches, constipation, bloating, and swelling

help prevent or treat gestational diabetes

increase energy

improve mood

improve posture

promote muscle tone, strength, and endurance

help you sleep better

help you get back in shape after your baby is born.

It is important to talk to your doctor about your plans before you begin or resume an exercise
program.
Healthy lifestyle: Smoking is bad for your baby, bad for your bones, and bad for your heart and
lungs. Talk to your doctor about quitting. He or she can suggest resources to help you. Alcohol

also is bad for pregnant and breastfeeding women and their babies, and excess alcohol is bad
for bones. So, be sure to follow your doctor's orders to avoid alcohol during this important time.

Effect of Caffeine
Numerous studies have examined the effects of caffeine intake on fertility and
pregnancy. Most studies found that moderate caffeine intake does not affect
fertility or increase the chance of having a miscarriage or a baby with birth
defects; some studies did find a relationship between caffeine intake and
fertility or miscarriages. However, most of those studies were judged to be
inadequate because they did not consider other lifestyle factors that could
contribute to infertility or miscarriages. The Organization of Teratology
Information Services (OTIS) stated that there is no evidence that caffeine
causes birth defects in humans. Groups such as OTIS and Motherisk agree
that low caffeine intake (<150 mg/day or 1 1/2cups of coffee) will not likely
increase a womans chance of having a miscarriage or a low birth weight baby.
Motherisk recommends that caffeine intake by pregnant women not exceed
150 mg/day whereas OTIS stated that moderate caffeine intake of 300 mg/day
(equivalent to about 3 cups of coffee) does not seem to reduce fertility in
women or increase the chances of having a child with birth defects or other
problems. Caffeine can enter breastmilk, and high amounts can cause the
baby to become wakeful and agitated. The American Academy of Pediatrics
recommends that nursing women limit caffeine intake, but states that no harm
is likely to occur in a nursing child whose mother drinks one cup of coffee a
day. OTIS recommends that pregnant and nursing women drink plenty of
water, milk, and juice and not substitute those fluids with caffeinated
beverages.
Caffeine and fertility
Numerous studies have been conducted to determine the effects of caffeine
intake on fertility in women. The International Food Information Council (IFIC)
has described and made conclusions about the following studies (IFIC August
2002).
One small study in 1988 suggested that caffeine, equivalent to the
amount consumed in 1-to 2-cups of coffee daily, might decrease female
fertility. However, the researchers acknowledged that delayed
conception could be due to other factors they did not consider, such as
exercise, stress or other dietary habits. Since then, larger, welldesigned studies have failed to support the 1988 findings.
In 1990, researchers at the Centers for Disease Control and Prevention

and Harvard University examined the association between the length of

time to conceive and consumption of caffeinated beverages. The study
involved more than 2,800 women who had recently given birth and
1,800 women with the medical diagnosis of primary infertility. Each
group was interviewed concerning caffeine consumption, medical
history and lifestyle habits. The researchers found that caffeine
consumption had little or no effect on the reported time to conceive in
those women who had given birth. Caffeine consumption also was not
a risk factor for infertility.
Supporting those findings, a 1991 study of 11,000 Danish women
examined the relationship among number of months to conceive,
cigarette smoking and coffee and tea consumption. Although smokers
who consumed eight or more cups of coffee per day experienced
delayed conception, nonsmokers did not, regardless of caffeine
consumption.
A study of 210 women, published in the American Journal of Public
Health in 1998, examined the differences in fertility associated with
consumption of different caffeinated beverages. This study, prompted
by an inconsistency in previously reported findings, did not find a
significant association between total caffeine consumption and reduced
fertility. In fact, the researchers found that women who drank more than
one-half cup of tea per day had a significant increase in fertility. This
was particularly true with caffeine consumption in the early stages of a
womans attempt at conception. The caffeinated tea and fertility
correlation was supported by a 1994 study; however, those women had
significantly higher consumption levels.
OTIS (OTIS 2001) reviewed the studies examining caffeine effects on fertility
and concluded that, "Low to moderate caffeine consumption (<300 mg/day)
does not seem to reduce a womans chance of becoming pregnant."

Caffeine
Numerous studies have examined the effects of caffeine intake on fertility and
pregnancy. Most studies found that moderate caffeine intake does not affect
fertility or increase the chance of having a miscarriage or a baby with birth
defects; some studies did find a relationship between caffeine intake and
fertility or miscarriages. However, most of those studies were judged to be
inadequate because they did not consider other lifestyle factors that could
contribute to infertility or miscarriages. The Organization of Teratology
Information Services (OTIS) stated that there is no evidence that caffeine
causes birth defects in humans. Groups such as OTIS and Motherisk agree
that low caffeine intake (<150 mg/day or 1 1/2cups of coffee) will not likely
increase a womans chance of having a miscarriage or a low birth weight baby.
Motherisk recommends that caffeine intake by pregnant women not exceed
150 mg/day whereas OTIS stated that moderate caffeine intake of 300 mg/day
(equivalent to about 3 cups of coffee) does not seem to reduce fertility in
women or increase the chances of having a child with birth defects or other
problems. Caffeine can enter breastmilk, and high amounts can cause the
baby to become wakeful and agitated. The American Academy of Pediatrics
recommends that nursing women limit caffeine intake, but states that no harm
is likely to occur in a nursing child whose mother drinks one cup of coffee a
day. OTIS recommends that pregnant and nursing women drink plenty of
water, milk, and juice and not substitute those fluids with caffeinated
beverages.
Caffeine and pregnancy
The March of Dimes (MOD 2002) notes that during pregnancy, caffeine easily
passes from the mother to her unborn child through the placenta. Because the
systems for breaking down and eliminating chemicals are not fully developed
in the unborn child, blood levels of caffeine may remain elevated for longer
periods in the unborn child compared to the mother. OTIS (OTIS 2001) notes
that, "higher amounts of caffeine could affect babies in the same way as it
does adults. Some reports have stated that children born to mothers who
consumed >500 mg/day were more likely to have faster heart rates, tremors,
increased breathing rate, and spend more time awake in the days following
birth."
The effects of caffeine intake on miscarriages, birth defects, and low birth
weight have been studied, and different results were obtained in the various
studies. The International Food Information Council (IFIC) has described and
made conclusions about the following studies (IFIC August 2002).
Recently, researchers from McGill University in Montreal published a

study showing a relationship between caffeine intake and miscarriage.

While caffeine intake before and during pregnancy appeared to be
associated with increased fetal loss, the authors failed to account for a
number of factors that could result in a false association, including
effects of morning sickness or nausea*, the number of cigarettes
smoked and amount of alcohol consumed.
Just prior to the McGill study, a research team from the U.S. National
Institute of Child Health and Human Development conducted a study of
431 women. The researchers monitored the women and the amount of
caffeine they consumed from conception to birth. After accounting for
nausea, smoking, alcohol use and maternal age, the researchers found
no relationship between caffeine consumption of up to 300 mg per day
and adverse pregnancy outcomes, including miscarriage.
Earlier, in 1992, researchers analyzed the effects of cigarettes, alcohol
and coffee consumption on pregnancy outcome in more than 40,000
Canadian women. Although alcohol consumption and smoking tended
to have adverse effects on pregnancy outcome, moderate caffeine
consumption was not associated with low birth weight or miscarriages.
Further, the relationship of caffeine consumption to spontaneous
abortion was investigated in a study of 5,342 pregnant women in 1997
in which researchers concluded that there was no increased risk for
spontaneous abortion associated with moderate caffeine consumption.
Another very comprehensive study, done in Uppsala, Sweden, and
reported in December 2000, concluded reducing caffeine intake during
early pregnancy may be prudent.
Studies published during the 1980s also support the conclusion that
moderate caffeine consumption during pregnancy does not cause early
birth or low birth-weight babies. A review of more than 20 studies
conducted since 1980 found no evidence that caffeine consumption at
moderate levels has any discernible adverse effect on pregnancy
outcome.
A seven-year study of 1,500 women examined caffeine use during
pregnancy and subsequent child development. Caffeine consumption,
equivalent to about 1 1/2 - 2 cups of coffee per day had no effect on
birth weight, birth length or head circumference. Follow-up
examinations at ages eight months, four and seven years also revealed
no effects of caffeine consumption on a child's motor development or
intelligence.
In the early 1980s, the U.S. Food and Drug Administration (FDA)
conducted a study where rats were force-fed very high doses of
caffeine through a stomach tube. While the results prompted an
advisory to pregnant women to avoid caffeine, the study was criticized
as not being representative of the way humans consume caffeine. In

1986, FDA researchers carried out another study, in which rats

consumed high doses of caffeine in their drinking water. At the
conclusion of the second study, the FDA found no adverse effects in
the offspring, contradicting the agency's earlier findings.
A recent study published in 2001 examined the effect of maternal
caffeine consumption throughout pregnancy on fetal growth and found
evidence that caffeine consumption during pregnancy has no adverse
effect on fetal growth. Additionally, a 2002 study entitled "Effect of
caffeine exposure during pregnancy on birthweight and gestational
age," in the American Journal of Epidemiology found no association
between moderate caffeine consumption and reduced birthweight,
gestational age or fetal growth.
Major studies over the last decade have shown no association between
birth defects and caffeine consumption. FDA has evaluated this
scientific evidence and concluded that caffeine does not adversely
affect reproduction in humans. However, as with other dietary habits,
the agency continues to advise pregnant women to consume caffeine
in moderation.
Groups such as OTIS, March of Dimes, and Motherisk reviewed studies
examining caffeine intake during pregnancy and are in agreement that high
caffeine intake (>300 mg/day, equivalent to more than 3 cups of coffee/day)
should be avoided during pregnancy. There is also general agreement that low
caffeine intake (<150 mg/day, about 1 1/2 cups of coffee) during pregnancy is
not likely to harm the unborn child. However, there is some disagreement
regarding moderate caffeine intake.
Following a statistical analysis of studies examining caffeine intake in pregnant
woman, Motherisk (Motherisk 2000) stated, "Our results suggest a small but
statistically significant increase in risk of spontaneous abortion and low birth
weight babies in pregnant women consuming more than 150 mg of caffeine
per day. Pregnant women should be encouraged to be aware of dietary
caffeine intake and to consume less than 150 mg of caffeine a day from all
sources throughout pregnancy."
Subsequent to their review of caffeine studies, OTIS (OTIS 2001) stated that
"Recent reports suggest that low to moderate consumption of caffeine does
not increase the risk for miscarriage. A few studies have shown that there may
be an increased risk for miscarriage with high caffeine consumption (>300
mg/day), particularly in combination with smoking or alcohol, or with very high
levels of caffeine consumption (>800 mg/day)." OTIS (OTIS 2001) goes on to
say that, "In humans, even large amounts of caffeine have not been shown to
cause an increased chance for birth defects." OTIS concluded that (OTIS
2001), "Most experts agree that moderation and common sense are the keys
for consuming caffeinated items during pregnancy. "Moderate" caffeine
consumption is approximately 300 mg/day, which is similar to 3 cups of coffee.

It is also important for pregnant women to drink sufficient quantities of water,

milk and juice. These fluids should not be replaced with caffeinated
beverages."
*Note: The IFIC (IFIC August 2002) stated that, "For some women, nausea
"morning sickness"is a common experience during early pregnancy.
Though this phenomenon is unpleasant, researchers believe it is a normal and
common aspect of early pregnancy. During a normal pregnancy, hormone
levels are high, increasing the likelihood of becoming nauseated. If nauseated,
pregnant women may not desire certain foods and beverages, including those
that contain caffeine. Healthcare professionals often advise pregnant women
who experience nausea to choose bland foods and beverages such as
crackers and water."

TOPIK 4
Air Pollution & Respiratory Disease
Common Chemicals and Safety

Research conducted by NIEHS scientists has shown that long-term exposure to air pollutants
increases the risk of respiratory illnesses such as allergies, asthma, chronic obstructive
pulmonary disease, and lung cancer. Children and the elderly are particularly vulnerable to the
health effects of ozone, fine particles, and other airborne toxicants. This research has resulted in
the development of more stringent air quality standards that promote a higher quality of life,
protect the health of children, the elderly and other vulnerable populations, and reduce the costs
associated with respiratory disease.
One of the first studies to establish a link between air pollution and respiratory health was the
NIEHS-funded Six Cities Study, a long-term study on residents of six U.S. cities to assess the
effects of common air pollutants on the risk of pulmonary and cardiovascular disease. The study
results showed that people living in the more polluted cities had a higher risk of hospitalization
and early death from lung cancer and other respiratory diseases than those living in the less
polluted cities.
Recent data collected by NIEHS-funded scientists at the University of Southern California
suggest that exposure to pollutants in vehicle and fossil fuel emissions may hinder lung
development and limit breathing capacity for a lifetime. Their research shows that children who
live in highly polluted communities are five times more likely to have clinically low lung
functionless than 80% of the lung function normal for their age.
Other studies conducted by the University of Southern California researchers indicate that
increases in ground-level ozone, a highly reactive form of oxygen that is the primary component
of urban smog, may actually cause asthma. Children who were active in outdoor sports in areas
with high ozone concentrations were more than three times as likely to develop asthma as those
who did not engage in outdoor sports during the five-year study.

Lives saved by research on the health

consequences of environmental pollutants can be
counted in the millions. According to the
Environmental Protection Agencys estimates on
air pollution, the commitment to new air quality
standards and cleaner air will prevent 23,000
premature American deaths, 1.7 million cases of
asthma attack or aggravation of chronic asthma,
67,000 new cases of acute and chronic bronchitis,
22,000 respiratory-related hospital admissions, and
42,000 hospital admissions for cardiovascular
disease by the year 2010.
Other benefits of cleaner air, according to a study
by NIEHS-funded researchers at the University of
Washington, include 200 fewer cases of post
neonatal mortality, 10,000 fewer infants of low
birth weight, and 40,000 fewer emergency room
visits for children by 2010. These findings
demonstrate the impact that NIEHS-supported
research and subsequent regulatory actions have
had on protecting the health of our nations
children and other vulnerable populations.