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Cigarette Smoking |
[Maternal
Weight and Weight Gain During Pregnancy][Constitutional
Theory][Chromosomal Analysis]
The fetus is in a very precarious position; it has very little control over its environment, especially what it is fed and what chemicals and toxins it is exposed to. For many years, we have become painfully aware of the potential for severe harm to the fetus if it is exposed to injurious substances, especially during the first trimester when many body organs are in their critical stages of development. Exposure to alcohol throughout pregnancy may produce the so-called "fetal alcohol syndrome", characterized by mental retardation, congenital abnormalities, and an unusual looking face. Exposure to cocaine during fetal life can produce severe withdrawal syndromes, abnormal brain development, and even death to the fetus. Other chemicals can increase the chance of miscarriage, or produce severe congenital abnormalities as were seen with the widely prescribed drug, thalidomide. What is so tragic is that most of these exposures could have been prevented - there is no need for them to occur. An innocent life becomes severely affected, or even extinguished. We now know most of the chemicals most likely to cause severe
congenital abnormalities, have catalogued them, and many have become public
knowledge. Most pregnant women are counseled to contact their physician
before taking any new medications - or even to cut back or stop drugs they
could take with impunity before they became pregnant. Doctors are
very careful when drugs are prescribed during pregnancy to weigh the benefit
to the mother against the potential harm to the fetus. New
drugs undergo extensive testing in the laboratory before they are ever
released to the general public. Often this testing takes many years
and countless millions of dollars to be sure the drugs holds no surprises
in the toxicity it can cause to the public. We have become a very
concerned society about protecting the unborn - giving it the best possible
chance to develop normally and attain its full potential after birth -
with one exception.
They often continue to smoke after they become pregnant with the full realization that they may be harming their unborn child. The risk of maternal smoking to the fetus has only fairly recently been studied - and the results of these rigorous scientific investigations are alarming. There appears to be a fairly clear-cut association between maternal smoking and fetal development. This association should probably not be too much of a surprise considering the thousands of toxins in cigarette smoke, that most of these toxins are quickly dissolved in the bloodstream from the lungs, and that the fetus receives nourishment and exposure to these toxins from the mother's blood. Some of these toxins include carbon monoxide (the same gas produced in car exhaust) and hydrogen cyanide, a very poisonous gas that can be used in chemical warfare. It is not too surprising, therefore, to suppose that these repeated exposures to poisonous gases might exact some toll. Indeed, this appears to be the case. The fetus exposed to these gases throughout pregnancy has a much more difficult time than those who are fortunate to co-exist with mothers who do not smoke. There is a higher incidence of spontaneous abortion, growth retardation, increased infant mortality and morbidity, and behavioral defects in children of mothers who smoke during pregnancy. Low birth weight is a well documented although somewhat poorly understood complication of maternal smoking. This low birth weight does not seem to be due to prematurity (being born before full maturity), but rather appears to be secondary to intrauterine growth retardation. The fetus has spent the standard nine months in the mother's womb, but is still smaller than usual. This smallness is likely due to repeated daily exposure to the many toxic substances produced by the burning cigarette, and/or to reduced exposure of the fetus to life sustaining substances such as nutrition and oxygen. The various hypotheses that have been proposed to explain what these toxic byproducts are and how they might affect fetal and childhood development will be discussed next. Maternal Weight and Weight Gain During Pregnancy Smoking women experience diminished appetite, decreased food consumption, and often decreased weight gain during pregnancy. Some investigators have proposed that this reduced weight gain by the mother may be somehow related to the fetal developmental abnormalities previously discussed. Perhaps the reduced maternal nutrition could adversely affect fetal development through some mechanism. Maybe, if the mother becomes malnourished, the growing fetus will also become malnourished. However, Davies et al. (1) have pointed out that the 8 percent reduction in birth weight observed in smoking women is similar to the 9 percent reduction in birth weight observed in women during the Dutch famine of 1944 to 1945 under Nazi occupation in the worst of times. The population of this occupied country were literally being starved by their brutal invaders. This starvation and malnutrition lead to a reduction in the birth weight of children born during this period of approximately 10 percent, the same degree of reduced birth weight seen in smoking mothers. While smoking mothers certainly may have reduced appetite, it is highly doubtful if they voluntarily under the degree of starvation found in the occupied countries of Europe during World War 2! Davis concluded in his investigation that "If a reduced food intake alone is responsible, then the diets of our women who smoked would have to be nearly as inadequate as those of the wartime Dutch. Clearly this is most unlikely to have been so. Additionally, some recent investigations have even observed a reduced fetal weight in the absence of a reduction in maternal weight. Thus, it is not even necessary to lose any weight during pregnancy for the baby to have a low birth weight. The Ontario Perinatal Mortality Study (2) failed to demonstrate any relationship between maternal weight gain during pregnancy and birth weight in conjunction with smoking. A German study (3) involving more than 6200 women also failed to uncover any relationship between cigarette smoking and weight gain during pregnancy. Hajeri (4) matched smokers and nonsmokers on the basis of maternal age, height, parity, duration of pregnancy, sex of the infants, and gestational age. While there was a twofold greater increase in small birth weight children born to smoking women, there were only minimal differences in maternal weight gain during pregnancy. While the fetal birth weight does not seem to be related to maternal weight gain during pregnancy, Garn et al. (5) did find that maternal weight gain during pregnancy is affected by smoking. They find that women who do not smoke during pregnancy weigh about 3 to 4 pounds greater prior to pregnancy and gain more weight during their pregnancy than do smoking women. It is doubtful that differences in pre-pregnancy and pregnancy weight can have any significant affect on pre-natal development. The differences in fetal weight between those born to smoking mothers and non-smoking mothers may instead be due to many other possible factors introduced by the smoking habit. One such possibility that has received some recent interest is the effect maternal smoking has on blood vitamin levels. Recently, it has been established that smoking cigarettes may reduce the blood vitamin levels in the mother (or any other smoker for that matter).. This theory then proposes that the reduced vitamin stores by the mother then produces a reduction of important vitamins to the fetus during its development, and that this reduced exposure may have a harmful effect upon the its growth and future development. To substantiate this claim. Crosby et al. (6) demonstrated a reduced concentration of 14 amino acids (the building blocks of proteins) and carotene (similar to Vitamin A) in mothers who smoked. Although the differences were rather small (in the range of 10 to 20 percent) this reduction may be significant enough to produce developmental abnormalities when present in early embryonic stages. Vitamin C (ascorbic acid) has rather consistently been found to be lower in the white blood cells (leukocytes) of women who smoke compared to other women. Vitamin C has many important functions in the body, such as possibly helping to fight infection and helps the body produce strong connective tissue. Scurvy, a common disease among English sailors prior to the introduction of citrus fruits upon sea-faring vessels, is caused by a reduced intake of Vitamin C resulting in fragile tissues that can be easily injured. Schorah et al. (7) have hypothesized that the lower ascorbic acid levels in the maternal blood may be a factor in fetal growth development and in the increased incidence of premature rupture of membranes among women who smoke. Possibly, the low level of Vitamin C in these smoking mothers prevented them from producing placental membranes of the same integrity as non-smoking mothers. Nonetheless, it is difficult to substantiate the possibility that maternal malnutrition induced by cigarette smoking can have any real significance in fetal development. When remembering the work of Davies (1), it is impossible to believe that the starvation of American smokers can approach that of Dutch farmers during WW2, yet the reduction in birth weight in the two populations is rather similar. Because of these reasons, the theory that the reduced birth weight of children born to mothers who smoke is due to nutritional factors has fallen into disfavor. Another hypothesis that has been proposed to explain the reduced birth weight of children born to maternal smokers is that there is a constitutional difference between those mothers who choose to smoke and those who do not. In other words, the fact that children born to smoking mothers are small is not due to cigarette toxicity, but rather to some inherent deficiency in the mother; the cigarette smoking habit serving only as a marker for that deficiency. This hypothesis was proposed by Yerushalmy (8,9) when he said that: Smokers...may represent a group of people whose reproductive experience would have duplicated the observed pattern whether or not they smoked. In other words, the smoking may be considered an index which characterizes the smokers, but smoking per se is only incidental and not essential as a causal factor in the observed phenomenon. Support for the constitutional theory comes from several studies. Hickey et al. (10-13) contents that smoking is symptomatic of a psychological deficiency that nicotine tends to alleviate. People who smoke need the nicotine it provides to alleviate some psychological deficiency. There are several other more psychological deficiencies that smoking may help to alleviate. A possible deficiency which has recently been proposed is the metabolic rate. The metabolic rate can be loosely thought of as the thermostat we all have that determines how quickly we burn our calories and generate energy. Those who have high metabolic rates burn their calories more quickly and are more energetic than others with lower metabolic rates. The constitutional theory states that women who smoke have a different "constitution" than non-smokers; they tend to have a lower metabolic rate. These women smoke, the constitutional theory states, for the nicotine (and possibly other substances), which will act as a nerve stimulant and give them more energy. Most smokers also tend to be avid coffee drinkers' the caffeine they get from coffee also (as with nicotine) increases their "bioenergy" and gives them more pep. As Hickey said (12), "If smoking is, for some, a symptoms of a deficient bioenergetics, such a deficiency may cause a limitation of the metabolism or detoxification of chemicals that nicotine can alleviate." Hickey goes on to hypothesize that one possible deficiency in patients who smoke may be in their level of catecholamines (one type of catecholamine is epinephrine, or adrenalin - the familiar drug that makes your heart beat faster and increases alertness and wakefulness). Certainly, it is known that nicotine can increase catecholamine release by the adrenal gland, and that this epinephrine can then act on the liver to increase glucose production. The hypothesis that smoking behavior may be in some part related to glucose metabolism is strengthened by the observation that there is a greater incidence of smoking among diabetic men than among non-diabetic control subjects. Additionally, men who smoke have a higher fasting glucose blood level than men who do not smoke (10). As further evidence that there may be some genetic predisposition to smoking, Hickey offers the observation that smoking is more common among monozygotic twins (identical) than among dizygotic twins (non-identical) (10). Therefore, there seem to be basic physiological differences between smokers and non-smokers; it is possible that it is this physiological difference that predisposes to smoking behavior. As Hickey said (13), "Is it smoking that causes afflictions associated statistically with smoking or is smoking symptomatic of a physiological deficiency that nicotine tends to alleviate?" These observations by Hickey and associates tend to substantiate the constitutionality hypothesis by asserting that there is something intrinsically (and perhaps genetically) different among smokers when compared to their non-smoking counterparts (as judged by greater incidence of smoking among diabetics, their greater need for neural stimulation as substantiated by their greater coffee consumption, and inheritance factors). It is this intrinsic difference (rather than cigarette smoking) that leads to nicotine craving and increased cigarette consumption. Finally, it may be that it is this intrinsic, inherited, physiologic difference between smokers and non-smokers that also predisposes pregnant women who smoke to have lower birth weight children rather than their cigarette smoking. However, this theory is not without its detractors. For instance, Rantakallio (14) and Schwartz et al. (15) demonstrated that mothers who discontinue smoking prior to their pregnancy will have less reduction in birth weight than those who continue to smoke (although not as large as mothers who were non-smokers). This finding seems to demonstrate that the reduction in birth weight may be more related to the smoking habit and not to some constitutional genetic factor predisposing these children to lower birth weight. Naeye (16) also compared the weights of babies born to mothers who smoked during one pregnancy but not during another. These unique observations were very important in establishing whether low birth weights were due to a constitutionality factor, or to some toxin reducing fetal growth. If the reduced birth weight were due to a genetically described constitutionality factor, then there should be a reduced birth weight in both pregnancies regardless of whether the mother smoked or not. However, if the reduced birth weight were due to toxins, then there would be a reduced birth weight primarily in those pregnancies during which the mother smoked. The results from this interesting investigation revealed a reduction in birth weights primarily among children born to mothers while they were smoking and not to those born while the mothers were not smoking. Thus, while the constitutionality hypothesis is difficult to disprove completely, there does seem to be substantial evidence that the reduction in birth weight of children born to mothers who smoke is due to some toxic byproduct rather than to some undefined difference among smokers. It has been hypothesized that cigarette smoke may damage the fetus (and possibly also the parent) through damage to its chromosomal make-up, and that this chromosomal damage might have a harmful effect upon in-utero growth. At this point, it is probably important to introduce a brief digression for a discussion about chromosomes and DNA. DNA is the genetic material that carries information from one generation to the next, such as blood type, hair color, height, etc. DNA is contained within even more complicated structures called chromosomes. There are 46 chromosomes in each human cell which are arranged in 23 pairs. In addition to the DNA, chromosomes have another major constituent called histones which are believed to be intimately associated with the DNA molecule, possibly stabilizing its structure. Additionally, the histones may be important in controlled which DNA genes are activated and which ones are not. This incredibly complex structure, like anything very complex, is subject to breakdown and malfunction. There can be too many of a certain chromosome or part of a chromosome, resulting in fetal and childhood defects, such as Down's syndrome. There may be too little of a portion of a chromosome or an entire missing chromosome, resulting for instance in Turner's syndrome. Or the chromosome may be malformed forming rings or interconnections which may then lead to difficulties in transmitting genetic information to the next generation. Perhaps more importantly, these chromosomal abnormalities may be important in the production of tumors and cancers in the adult. There have been many investigations on the effect of cigarette smoke upon the chromosomes in blood cells of smokers. The investigations by Obe and Herba (17) demonstrated a significantly greater incidence of chromosomal aberrations among smokers than others. Murthy (18) examined the lymphocytes (a special type of white blood cell from smokers and demonstrated a greater incidence of chromosomal abnormalities. There was even a relationship between the exposure to tobacco smoke and the incidence of these aberrations. Those who had been smoking for less than 10 years had the same incidence of these abnormalities as non-smokers, but those who had been smoking for more than this period of time had a significant increase. Other studies have also been done which tend to corroborate the assertion that smoking is associated with a greater incidence of chromosomal abnormalities in the smoker. However, there is no evidence that these chromosomal abnormalities also occur in germ cells (the egg in the female or the sperm in the male) to carry them on to the next generation. Alberman et al. (19) and Boue et al. (20) were both unable to demonstrate an increased incidence of chromosomal abnormalities among spontaneously aborted fetuses from mothers who smoked, arguing against a significant increase of genetic abnormalities in these children. Thus, it seems unlikely that chromosomal abnormalities produced by cigarette smoking are responsible for the reduction in birth weight in children born to smoking mothers. Because the reduction in birth weight in children born to mothers who smoke appears to be secondary to intra-uterine growth retardation rather than prematurity, a logical place to look as a possible explanation is the placenta. The placenta is the physiological link between the mother and her unborn infant. Through the placenta go the nutrients (and possible the contaminants) from the mother to the infant, including life sustaining oxygen. There is exchange of waste products from the infant back to the mother for excretion also. Thus, owing to this crucial link between the two, several investigations had been performed to study whether there are placental abnormalities in women who smoke. First, just the gross appearance and weight of the placenta were looked at. Even though the placental weight was not reduced in smokers, there is an elevation in the placental ratio, or the ratio between placental weight and infant birth weight. Thus, for a given placental weight, the infant weight is not as great as normal (21-24). The realization that there is a reduction in the placental ratio in smoking mothers is consistent with the hypothesis that smoking results in hypoxia. This is true because one of the ways the placenta compensates for reduced oxygen transfer to the fetus is through hypertrophy, or enlargement. By increasing in size, there is greater vascularity and diffusion area for oxygen transfer to occur. If this theory were true, then there should be an increased placental ratio in women living at high altitudes to compensate for the hypoxia resulting from great elevation (21), and in mothers with anemia to compensate for reduced oxygen delivery (21). Indeed, it does turn out that the placental ratio is increased in both of these situations. However, while with smoking the elevated placental ratio results from a decrease in birth weight in relation to a placenta of normal weight, the elevated placental ratio in women living at high altitude or with anemia is due to a both a reduction in birth weight and an elevation in placental weight. Another way that the placenta might be affected in smoking women is through an alteration in the activity of enzymatic reactions within the placenta necessary for its function. For example, one of the major responsibilities of the placenta is the uptake of amino acids (the building blocks of protein). Rowell (25) has examined the activity of certain enzymes in the human placenta in relation to maternal smoking. He was able to demonstrate a significant 24 percent reduction in the uptake of the amino acid a-aminoisobutyric acid in the placentas of mothers who smoked 20 or more cigarettes per day. Similarly, exposure of nicotine to a rat during pregnancy has been shown to significantly inhibit transport of iron across the placenta to the fetus. Thus, one way that maternal cigarette exposure might reduce birth weight could be through reduced function of the placenta. Additionally, smoking has been demonstrated to actually structurally damage the placenta, which may result in both a reduction of nutrient flow to the fetus, but also a reduction of blood flow and oxygen. Christianson (22) examined over 7000 pregnancies and noted that the placentas from smokers were more calcified and contained subchorionic fibrin deposits than did those from non-smokers. These changes were apparently found to be primarily related to smoking exposure even after adjustment for maternal age, gestation, and birth weight. Spira et al. (26) also reported increased "signs of hypoxia" in placentas from mothers who smoked, including decreased intervillous space, buds, nuclear clumps, ischemic necrosis, retroplacental hematomas, infarctions, and abnormal uteroplacental vessels. Naeye (27) noted that there was an increased incidence of necrosis and inflammation of the placental margins in the placentas from mothers who smoked when data from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke were analyzed. In addition to increased placental ratios and signs of placental damage in smoking women, other even more significant alterations also be more frequent (27). Abruptio placentae and placenta previa are also more common in women who smoke. Abruptio placentae is the premature separation of the placenta from the uterine wall which can be very hazardous both to the mother as well as to the infant. Placenta previa is the implantation of the placenta at an abnormal position in the uterus. A comparison of the frequency of these disorders during pregnancy shows that the incidence is lowest in women who never smoked, higher in those women who smoked but stopped before pregnancy, and highest in women who smoking throughout their pregnancy. Significantly, Naeye (27) demonstrated that in women who smoked for greater than six years, the incidence of placenta previa, abruptio placentae, and large placental lesions increased by 143, 72, and 37 percent respectively. Thus, there is a direct correlation between cigarette smoking in women and serious placental abnormalities that may lead to miscarriage, maternal death, and reduced fetal birth weight. Studies have also demonstrated abnormalities in the placental
vessels from smoking mothers. Asmussem et al. (28) showed evidence
of blood vessel damage from women who smoked. There were abnormalities
in the umbilical arteries and veins, as well as placental capillaries from
mothers who smoked, while such damage was not present in women who did
not smoke. Additionally, another study demonstrated blood vessel
damages unique to smokers and not seen in women living at high altitudes
suggesting that these abnormalities are not just due to low oxygen exposure,
but rather to other factors, possibly toxins, unique to cigarette exposure.
Another way that placental abnormalities may induce reduced birth weight may be through reduced uterine blood flow. Suzuki et al. (29) were able to demonstrate that infused nicotine to pregnant monkeys during the latter part of their pregnancy induced a drop of their uterine blood flow by approximately 38 percent. This uterine blood flow reduction was associated with significant distress by the fetus with a reduction in fetal oxygenation. Resnik et al. (30) also demonstrated a reduction in uterine blood flow in pregnant ewes after nicotine infusion. The resistance to blood flow through the ewe's uterine blood vessels was increased by 203 percent. Likewise, Bruce and Parkinson (31) observed an increase in uterine vascular resistance to blood flow in the pregnant rat and a reduction in uterine blood flow of approximately 51 percent after nicotine infusion. The reduction in uterine blood flow in these experiments offer another mechanism whereby nicotine (and hence smoking) may induce a reduction in fetal weight. This reduced uterine blood flow means that less blood, and therefore less oxygen, will be delivered to the developing fetus possibly resulting in reduced size and development. Even though the reduced blood flow through the uterus after nicotine exposure is rather transient, repeated exposure may produce significant periods of rather significant blood flow reduction. One of the ways that nicotine may induce reduced uterine blood flow is through release of substances called catecholamines from the adrenal glands. Catecholamines such as epinephrine (also known as adrenalin) and norepinephrine have many physiologic effects upon the body, and especially upon the cardiovascular system. It has been demonstrated by Quigley (32), for instance, that catecholamines induce significant increases in blood levels of both epinephrine and norepinephrine after about 2.5 minutes of smoking. Further support for this hypothesis comes from the work of Resnik et al. (30) who showed that while the infection of nicotine directly into the uterine artery did not cause uterine artery vasoconstriction, if the nicotine were injected into the general circulation instead, uterine vasoconstriction was produced. This suggests that nicotine produces its effect upon the uterus not directly, but indirectly as through catecholamine release. Additionally, Resnik et al. (30) reported an increase in epinephrine levels of about 60 percent. Harrison and McKenna (33) have offered an alternative hypothesis
as to how nicotine exposure may reduce uterine blood flow. They note
that blood from umbilical cord samples from infants born to smoking mothers
is more viscous, or thicker, than blood samples from other infants.
They suggested that this thicker blood may travel more slowly through the
maternal uterus, therefore carrying less oxygen to the growing fetus than
would normally be the case in the non-smoking mother.
In this section, we have seen how smoking can seriously reduce the amount of blood that gets to the developing fetus. But the blood that does get through may be carrying chemicals from cigarette smoke that can, over a period of several months, cause severe harm to the vulnerable fetus. There are chemicals contained within cigarette smoke that become absorbed into the mother's bloodstream that are poisons in the truest sense of the word. One of these poisons is carbon monoxide. Carbon monoxide is a colorless, tasteless gaseous substance produced by the burning cigarette. It is the same lethal molecule produced by the burning car engine that can kill the driver who keeps the garage door closed, or whose car exhaust leaks into the cabin slowly suffocating him. The reason carbon monoxide is so dangerous is that it binds to the hemoglobin molecule much more tenaciously than does oxygen. Hemoglobin cannot carry oxygen nearly as well when it has carbon monoxide attached to it, so the person may become severely oxygen deficient even though the air that is breathed in may be otherwise normal. When hemoglobin is carrying carbon monoxide, another molecule is formed: carboxyhemoglobin. Cigarette smoking has been shown to reduce the oxygen carrying capacity of the blood by as much as 12 percent (34) primarily through the production of this toxic substance. There is a small amount of carbon monoxide that is produced by the body's normal metabolism. Sjostrand first demonstrated the major pathway of carbon monoxide production in the body as being the breakdown of a molecule called protoporphyrin, into carbon monoxide and bilirubin (53). (Bilirubin is the molecule that becomes significantly elevated in patients with advanced liver disease, turning them yellow). Additionally, there is an increased carbon monoxide production in the body during a normal pregnancy, coming from both the mother and from the fetus; this increased level during pregnancy then rapidly decreases after birth (54). The normal fluctuations in carbon monoxide level in the non-smoking pregnant woman varies from 0.4 to 4.4%; however, in heavy smokers, the carboxyhemoglobin level may reach as much as 14 percent (35). This maternal increase also translates into increased infant carboxyhemoglobin. Carbon monoxide rapidly crosses the placenta from the mother into the fetus where it combines with fetal hemoglobin forming carboxyhemoglobin. The same poison that is formed in the mother is also formed in the developing fetus. The situation in the fetus is even worse than in its mother, however, because carbon monoxide is concentrated in the fetus; the fetal carboxyhemoglobin concentration is normally about 10 to 15% greater than that of the mother. Since fetal hemoglobin is somewhat different from maternal hemoglobin, carbon monoxide takes longer to be eliminated from the fetus than from the mother. While the mother can generally get rid of half her carbon monoxide in two hours, the fetus may take up to 6 or 7 hours to reduce its level by half. So the fetus develops a higher carbon monoxide level than its mother, and tends to hold onto the carbon monoxide for a longer time, all else being equal. But the situation becomes even worse for the poor fetus because its carbon monoxide contaminated hemoglobin, being different from its mother, holds onto its oxygen more strongly and releases it to oxygen hungry tissues at a slower rate. In other words, the fetal hemoglobin contaminated with carbon monoxide becomes more "sticky" for the oxygen that is being carried on it. Therefore, not only is there less oxygen being carried by fetal hemoglobin due to interference from carbon monoxide, but less of the little remaining oxygen is released from the hemoglobin molecule to the tissues. Oxygen transfer from the mother to the developing fetus is also reduced for similar reasons. Maternal hemoglobin contaminated with carbon monoxide also becomes more sticky for oxygen; therefore, less oxygen is released from maternal hemoglobin to cross the placenta to the fetus. Since fetal hemoglobin normally carries considerably less oxygen than does maternal hemoglobin (maternal hemoglobin is about 95% saturated with oxygen, whereas fetal hemoglobin is only about 50% saturated, any further reduction in oxygen delivering capacity in the fetus can be critical. Reduction in oxygen levels during the critical phases of the fetus could conceivably lead to difficulties in pregnancy, developmental difficulties during childhood, or even increased fetal death. [Developmental
Abnormalities][Blood Vessel
Disease in Children][Fetal Breathing
Activity]
Several studies have reported an increased incidence of significant complications during the pregnancies of women who smoke compared to pregnancies of women who do not smoke. These complications include an increased incidence of stillbirth (55,56), placenta previa (abnormal positioning of the placenta within the uterus), increased bleeding during pregnancy (57,58), increased incidence of premature rupture of the fetal membranes (premature "water breakage") (59), abnormal breathing movements of the fetus (60,61), delayed onset of crying and irregular respiration immediately after delivery (62). Naturally, these severe complications during pregnancy could have an impact upon the future life of the fetus. Low levels of carbon monoxide can produce subtle changes in young adults. Carboxyhemoglobin levels as low as 4 to 5%, certainly achievable in urban dwellers, can cause a reduction in mental function (67), visual acuity (68), and metabolism (69,70). The results of these experimenters have alerted other investigators to the possibility that a nine-month exposure of the developing fetus to even higher levels of carbon monoxide may seriously interfere with that child's future developmental progress. The effect of carbon monoxide exposure during pregnancy upon the surviving children is an area of active current research. On study of over 5000 children was performed in the British National Child Development Study. This group found that the reading attainment of 7 year olds of mothers who smoked during their pregnancy was different from the children of mothers who did not smoke (63,64). When these same children were then restudied 4 years later when they were 11 years old, the children of mothers who smoked had significantly poorly developmental achievement in school than their peers. Specifically, there was a retardation of 3 months in general ability, 4 months in reading ability, and 5 months retardation in mathematics (65). Another study showed that the mothers of hyperactive children smoked more frequently than other mothers (66). While these preliminary studies need confirmation from other investigators, there is at least preliminary evidence that smoking during pregnancy may lead to developmental difficulties and lower achievement in the surviving children. Blood Vessel Disease in Children There is little doubt that smoking over many years will increase the chances of developing significant heart and peripheral blood vessel disease. Indeed, cigarette smoking is one of the major risk factors in the development of a heart attack. Recently, it has become clear that these increased risks also extend to children of mothers who smoke during pregnancy. What is even more startling and worrisome is that maternal smoking during pregnancy may also damage blood vessels in the fetus. To examine this possibility, researchers examined the umbilical artery from children born to mothers who smoked. The umbilical artery is the artery connecting the placenta to the fetus and presumably is a good reflection as to what is going on in the fetus. They examined 13 umbilical arteries from smoking mothers and found there were marked changes in the arterial intima - or the inner part of the artery - that looked suspiciously like early changes of atherosclerosis, or hardening of the arteries. Many structural damages were seen, especially under the powerful electron microscope, that further emphasizes the potential vulnerability of the fetus while lying helplessly in the mother's womb. We know, for example, that many young, teenage American soldiers killed in Vietnam showed hardening of the arteries leading to their heart at autopsy. Presumably, these soldiers would have developed heart disease if they had survived. Now, it appears possible that exposure to carbon monoxide in the uterus from maternal cigarette smoking may provide the same danger to the fetus. Certainly, more study is needed before it can be stated with certainty that carbon monoxide exposure in the uterus will make the fetus more prone to develop coronary artery disease or peripheral vascular disease later in life, these preliminary investigations make this conclusion a definite possibility. The occurrence of hypoxia in the infant born to mothers who smoke can be manifested in the infant through several mechanisms. Recent advances in medical technology have made it possible to analyze the infant in ways that were simply impossible even in recent years. We can now determine how much the fetus is breathing and regularity of the fetal heart beat among other things. This technology has been used to investigate the unborn fetus in smoking mothers. Using this new technology, a significant increase in fetal apnea periods (periods of no breathing efforts) which may persist for as long as 90 minutes after smoking. Manning et al. (39) monitored 19 pregnant women before during and after smoking cigarettes. It was demonstrated that within five minutes of smoking two cigarettes, there was a 50 percent reduction in fetal breathing movements that took one hour to return to normal levels. The longest period of apnea was 20 seconds. Interestingly, while cigarette smoking has these profound effects upon fetal breathing patterns, herbal cigarettes (which contain no nicotine but similar amounts of carbon dioxide as regular cigarettes) did not have this suppressive action (40,41). Additionally, when nicotine alone was administered to pregnant women, there was again this reduction in fetal breathing pattern. Apparently, then, it is the nicotine which reduces fetal breathing patterns and not carbon dioxide (or perhaps other elements contained in cigarette smoke). It is still unknown, however, how nicotine has this effect on the breathing pattern of infants since it stimulates breathing in the newborn and adult. Nevertheless, the facts seem to indicate that in the fetus, exposure to nicotine from maternal cigarette smoking has a profound effect on fetal respiration produced increased episodes of reduced breathing patterns. The reduced breathing patterns will worsen fetal hypoxia because they will be exposed to less oxygen in the uterus. Thus, the reduced breathing patterns seen in these infants will worsen the hypoxia produced by the other pre-term insults hurled against the developing fetus such as carboxyhemoglobin and placental abnormalities. This worsening hypoxia can then lead to the reduced birth weight that we have previously noted is so common in children born to women who smoke. The reduced birth weight is not the only complication of fetal hypoxia. Cardiovascular changes in the fetus can also occur suggestive of hypoxia (42,43,). There is an increased fetal heart rate and increased beat irregularity in these infants. These irregularities may be due to stimulation from nicotine and the effect of hypoxia. Additionally, the hematocrit, a measure of the amount of red blood cells contained in a given volume of blood, is increased (36). This increase may be in response to fetal hypoxia as the infant tries to make more oxygen-carrying blood to compensate for their reduced oxygen environment. As though being exposed to less oxygen with a defective placenta with blood containing high levels of carbon monoxide, the developing fetus is also exposed to cyanide contained in tobacco smoke (44-46). Cyanide is a very potent poison that can be extremely lethal in rather small doses. It works by poisoning certain enzymes needed for metabolism and can make cells starve for oxygen even in an oxygen-rich environment. In the fetus, B12 is used to detoxify cyanide to thiocyanate. Since this reaction uses up vitamin B12, it is possible that a deficiency can result from constant exposure (46). When blood from newborn infants is analyzed, there are increased cyanide and thiocyanate levels which resemble the elevated levels found in their mothers (44,45). Additionally, these increased levels correlate very well with reduced birth weight such that the higher the levels, the lower the infant birth weight (45). It has been suggested by some that cyanide may produce reduced fetal growth and development by interfering with the activity of certain enzymes (sulfur-containing enzymes) that are required for normal development (44). Certainly, no mother would consider administering cyanide to her unborn infant. Yet this is exactly what she does when she puffs away on a cigarette. Is there any wonder, then, that these children may have subsequent developmental differences compared to those born without this exposure? Additional Complications of Pregnancy As if all of the above complications from smoking cigarettes during pregnancy were not enough, there are many other complications of pregnancy including increased bleeding, amniotic fluid infections, and premature rupture of membranes. Underwood et al. (47) noted that premature rupture of membranes occurred regardless of socioeconomic status or race, and that there is a dose-relationship with smoking. In other words, the greater the mother smokes, the larger her chances of suffering from this complication. Persson et al. (48) also noted this relationship, and in his studies there was an incidence of premature rupture of membranes in 0.3 percent of nonsmokers, 0.6 percent in women smoking less than 5 cigarettes per day, but a 1.4 percent chance when women smoked more than a pack a day. While these are not large percentages, they represent approximately a three-fold increased risk of premature rupture of membranes in women who smoke. As we have previously noted, at least part of this increased risk may be due to a deficiency of Vitamin C in many women who smoke. Andrews and McGarry (49) have studied the increased incidence of antenatal (prebirth) maternal bleeding among cigarette smokers. They found that the danger of this complication was especially high among women who had had 4 prior births. Cope et al. (50) noted an increase from 3.5 percent in non-smokers to 5.6 percent in smokers. Similar results were reported by Russel et al. (51), and by the Ontario Perinatal Mortality Study (52). In the latter study, bleeding during pregnancy after 20 weeks gestation was the greatest factor contributing to fetal death among smokers' babies. It should not be too surprising that with all the toxic compounds present in cigarette smoke, there should be some adverse effects upon fetal development. When a pregnancy mother smokes, she takes these compounds into her system through her very efficient absorptive units, the lungs. Part of the normal function of the lungs is to take in enough oxygen from the air to support life. To do this effectively, they have a very large surface area constantly exposed with each breath to the outside environment. Unfortunately for the women smoker and her infant, this efficient gas exchanging capacity allows the absorption of many toxic compounds from the inspired air. As we have seen, cigarette smoke contains many especially toxic compounds such as carbon monoxide and cyanide, which can be especially harmful to the developing infant with its delicate susceptible organs. Let's now review some of these toxic effects.
It seems clear that a pregnant women who smokes is not only endangering her own life and health, but also the life of her unborn child. She alone has to make the decision as to which is more important in her life, the cigarette smoking habit or the life and health of her unborn infant. In the final analysis, she alone bears the responsibility for that decision because it is hers to make alone.
References
1. Davies, D.P., Gray, O.P., Effwood, P.C., et al. Cigarette Smoking
in Pregnancy: Association with Maternal Weight Gain and Fetal Growth.
Lancet, 1, 385, 1976.
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