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an Substance Use and Abuse During Pregnancy The use of substances such as tobacco, alcohol and illicit drugs during pregnancy has important general health implications both for the mother and the fetus. A Food and Nutrition Board report entitled Alternative Dietary Practices and Nutritional Abuses in Pregnancy (NRC, 1982) consid- ered at length the adverse reproductive effects of cigarette smoking and alcohol abuse as well as the teratogenic potential of caffeine in animals. The present report briefly summarizes the influence of tobacco, alcohol, caffeine, marijuana, and cocaine on the fetus and reviews the data on how these substances may affect dietary intake and nutritional status during pregnancy. Marijuana use is included because of its relatively common occurrence and because of concern about its possible adverse effect on fetal growth and development. Cocaine is also discussed because of the recent dramatic increase in its use and its potentially devastating effect on the health and well-being of the mother and the fetus. Coverage of other types of substances was considered to be beyond the scope of work of this subcommittee, even though illicit and certain prescription drugs are known to have detrimental effects on nutrition and pregnancy outcome. Use of such substances should be actively assessed when counseling women regarding nutrition and ways to promote a healthy pregnancy. 390
SUBSTANCE USE AND ABUSE 391 CIGARETTE SMOKING Prevalence Although the prevalence of cigarette smoking in the general U.S. population has declined over the past two decades, it is still a common addiction among pregnant women. The proportion of women of child- bearing age (20 to 44 years) who smoke has decreased from about 40% in 1965 to 30% in 1987 (NCHS, 1989~. Smoking rates among girls aged 12 to 17 increased during the mid-1970s but subsequently declined-from 24% in 1974 to 11% in 1988 (NCHS, 1989; NIDA, 1989~. Smoking during pregnancy also appears to have decreased. Data from the 1967 and 1980 National Natality Surveys indicate that among married pregnant women aged 20 or older, the proportion of smokers declined from 40 to 25% for white mothers and from 33 to 23% for black mothers (Kleinman and Kop- stein, 1987~. This decline was limited largely to those who had completed high school; no change was reported in the prevalence of smoking among mothers under age 20. The 1980 National Natality Survey showed that the overall proportion of married mothers who smoked was 25% (Prayer et al., 1984), the highest rates occurring among white women, followed by black and Hispanic women. Smoking was also considerably more common among teenage mothers and those who had not completed high school as compared with the older or more educated mothers. Data from the 26 states in the Behavioral Risk Factor Surveillance System in 1985 and 1986 indicate that the overall prevalence of smoking in pregnancy was 21% with higher rates for unmarried (36~) as compared with married (18%) pregnant women (Williamson et al., 1989~. Effects on the Developing Fetus and Child The effects of maternal smoking on pregnancy and on the developing fetus and child have been reviewed extensively (Abel, 1980b; Berkowitz, 1988; DHEW, 1979; DHHS, 1980~. The most consistent observation is the reduction in birth weight (on average 200 g) among infants of smokers. A recent review of the literature on the determinants of low birth weight has, like previous reviews, concluded that cigarette smoking is by far the single most important modifiable factor responsible for fetal growth retardation in developed countries (Kramer, 1987~. Other adverse effects include a mod- erately increased risk of preterm delivery (Fedrick and Anderson, 1976; Meyer et al., 1976; Shiono et al., 1986), perinatal mortality (DHEW, 1979; Meyer and Fascia, 1977; Meyer et al., 1976), and, possibly, spontaneous abortion (Alberman et al., 1976; Kline et al., 1980b; Kullander and Kallen, 1971~. A sizable proportion of perinatal deaths and preterm births appears
392 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS to be mediated through a smoking-related increase in the incidence of placenta previa and abruptio placentae (premature separation of the pla- centa) (Andrews and McGarry, 1972; DHEW, 1979; Meyer and Fascia, 1977; Naeye, 1979~. In addition, children of mothers who smoke during pregnancy may have slight but measurable deficits in long-term physical growth, intellectual performance, and behavioral development (Butler and Goldstein, 1973; Dunn et al., 1977; Naeye and Peters, 1984; Rantakallio, 1983~. Interpreting the long-term effects of maternal smoking is prob- lematic, however, since it is difficult to separate the effect of in utero exposure from postnatal passive exposure and other characteristics of the home environment of smoking parents. The adverse effects have been found to be proportional to the fre- quengy of smoking and appear to be prevented or reduced if The mother does not smoke during a subsequent pregnancy (Abel, 1980b; DHEW, 1979; DHHS, 1980; Naeye, 1978~. The smoking-related effects have also been found to be independent of other factors, such as race, parity, prepregnancy weight, maternal weight gain, and socioeconomic status. These observa- tions support the generally accepted conclusion that the adverse effects of smoking represent a cause-and-effect relationship and are not a reflection of different characteristics of smokers and nonsmokers. Nutr~tion-Related Effects of Smoking Cigarette smoke contains approximately 2,000 different compounds. The exact mechanism behind the detrimental effects of smoking on the fetus and newborn have not been established. The most widely accepted explanation is that smoking causes intrauterine hypoxia through increased carboxyhemoglobin levels or reduced uteroplacental blood flow (Abel, 1980b; Longo, 1982~. Other nutrition-related factors may also play a role. Cyanide, a constituent of tobacco smoke, and thiocyanate levels in the blood and urine of smokers and their infants are higher than those of controls (Meberg et al., 1979; Pettigrew et al., 1977~. Since vitamin BE and sulfur-containing amino acids are utilized in the detoxification of cyanide, the depletion of these important nutrients may adversely affect the growth and development of the.fetuses of smokers. Other studies show statisti- cally significant reductions in the plasma levels of several amino acids and carotene in pregnant women who smoke compared with levels in pregnant nonsmokers (Crosby et al., 1977~. The maternal plasma carotene level in smokers has, in turn, been positively associated with birth weight (Metcoff et al., 1989~. Cigarette smoking also appears to be related to reduced vitamin C levels. Data from the Second National Health and Nutrition Examination Survey (NHANES II) revealed that serum vitamin C levels in nonpregnant female smokers were lower than in nonsmokers (Woteki et al.,
SUBSTANCE USE AND ABUSE 393 1986), and serum levels were found to be significantly reduced among smok- ers after adjusting for vitamin C intake in a small-scale study of adolescent females (Keith and Mossholder, 1986~. Smokers have also been reported to have decreased plasma ascorbate levels, which in turn are associated with increased metabolism of vitamin C rather than alterations in absorption or urinary excretion (Kallner et al., 1981~. Nonpregnant, adult heavy smokers (>20 cigarettes/day) may require up to twice as much vitamin C to maintain a body pool of vitamin C similar to that in nonsmokers. In NHANES II (1976-1980), the prevalence of low serum and ery- throcyte folate levels was significantly higher for female smokers than for nonsmokers (LSRO, 1984~. In addition, hemoglobin concentrations in smokers were found to be higher than those in nonsmokers-a finding that presumably reflects a response to the conversion of hemoglobin to carboxyhemoglobin in smokers. This finding was not confirmed in the data from the Collaborative Perinatal Project, but elevated hemoglobin and hematocrit levels were found in the neonates of smokers (Garn et al., 1978~. Because the presence of carboxyhemoglobin in the blood results in elevated hemoglobin concentrations in smokers, the Centers for Disease Control recently recommended higher hemoglobin and hematocrit cutoff values for identifying the risk of anemia for smokers as compared with risk for nonsmokers (CD C, 1989~. There is also evidence that smokers may have decreased placental zinc-to-cadmium ratios, which in turn have been related to reduced birth weight (Kuhnert et al., 1987, 1988~. Caloric intake may modify the relationship between smoking and re- duced birth weight. Smokers have generally been found to have a some- what lower prepregnancy weight and weight gain during pregnancy than nonsmokers (Butler et al., 1972; Garn et al., 1979; Rush, 1974~. It would therefore be expected that smokers consume less food than nonsmokers; however, data from the National WIC (Supplemental Food Program for Women, Infants, and Children) Evaluation (Rush et al., 1988) and other studies (Haworth et al., 1980a; Picone et al., 1982) have shown that dietary intakes of smokers during pregnancy are higher than those of nonsmokers. Since cigarette smoking has been demonstrated to increase the metabolic rate (Perkins et al., 1989), the lower prepregnancy weight and weight gain in smokers presumably reflect a reduced availability of calories for weight gain. An increase in the nutritional intake of pregnant smokers may coun- teract some of the smoking-related effects on birth weight (Garn et al., 1979; Metcoff et al., 1985; Rush et al., 1980), but some data show that infants of obese smokers will still weigh significantly less than infants of obese nonsmokers (Haworth et al., 1980b). Thus, it appears that improving the food intake of pregnant smokers does not completely compensate for the negative effect of smoking on birth weight.
394 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS In summary, cigarette smoking may affect maternal nutrition (and con- sequently, fetal nutrition) in two important ways: the increased metabolic rate in smokers can lead to the lower availability of calories, and exposure to tobacco may increase iron requirements and decrease the availability of certain nutrients such as vitamin Bit, amino acids, vitamin C, folate, and zinc. In addition, the hypothesized reduction in uteroplacental blood flow in smokers could restrict nutrient and oxygen flow to the fetus. As a result, mothers who smoke may need special counseling regarding dietary intake and may benefit from multiv~tamin-mineral supplementation, but this has not been investigated. Furthermore, compensatory intakes should not replace strategies for persuading women to give up smoking. Some smoking cessation programs during pregnancy have been found to be effective in increasing infant birth weight (Sexton and Hebel, 1984), and pregnancy may be a particularly opportune time to introduce antismoking assistance (Sexton and Hebel, 1984; Windsor et al., 1985~. ALCOHOL Effects on the Developing Fetus and Child Although the fetal alcohol syndrome (FAS) was not described until 1973 (Jones and Smith, 1973), alcohol is now recognized as a potent terato- gen. FAS is estimated to affect approximately one to two infants per 1,000 live births in the United States (Abel and Sokol, 1987) and is characterized by prenatal or postnatal growth retardation, distinct facial anomalies, and mental deficiency (Rosett, 1980~. Other potential alcohol-related birth de- fects include cardiac and genitourinary abnormalities (Ernhart et al., 1985; Hanson et al., 1976), but it is difficult to attribute isolated anomalies to alcohol exposure. In addition to FAS, alcohol has been associated with a spectrum of adverse effects that range from spontaneous abortion (Harlap and Shiono, 1980; Kline et al., 1980a) to subtle behavioral effects in the absence of physical anomalies (Aronson et al., 1985; Shaywitz et al., 1980~. The effect of alcohol on central nervous system dysfunction is of partic- ular concern, since some degree of intellectual impairment is frequently reported for children with FAS, especially those having the most severe dysmorphogenesis (Streissguth et al., 1983~. Definitions and Prevalence of Alcohol Use and Abuse According to national surveys of women aged 18 or older, the propor- tion who drink alcohol at least occasionally has decreased slightly between 1971 (58%) and 1985 (55%), and the proportion who consume 30 cc (1
SUBSTANCE USE AND ABUSE 395 oz) or more of pure alcohol per day has dropped from 5 to 3% during the same period (NCHS, 1989~. Among women aged 18 to 25, the proportion who reported that they consumed alcohol in the preceding month increased from 58% in 1976 to 68% in 1979 and then declined to 57% in 1988 (NCHS, 1989; NIDA, 1989~. Precise estimates of alcohol abuse cannot easily be obtained because of underreporting of alcohol intake and the difficulty of accurately quantifying alcohol exposure. Nor has any consistent criterion been used for defining alcohol abuse. In the 1980 National Natality Survey, it was found that among 4,405 married women who delivered live infants, 39% consumed some alcohol during the pregnancy and 3% drank three or more servings of alcoholic beverages per week (Prayer et al., 1984~. Alcohol consumption was highest among white mothers, followed by Hispanic and black mothers. Age and education were both positively related to drinking; i.e., drinking was most prevalent among older and better educated mothers. Other studies have estimated that anywhere from 0.8% (Streissguth et al., 1983) to 9% (Ouellette et al., 1977) of pregnant women are heavy drinkers; most studies report a range of 2 to 3%. Although the definition of heavy use has varied, consumption of two or more drinks per day has commonly been used for identifying heavy alcohol intake. It is not known whether alcohol consumption during pregnancy has declined since the 1977 and 1981 Surgeon General's reports on alcohol and pregnancy, but at least one study found no significant decrease in the relative proportion of heavy drinkers among Pregnant women in Seattle. Washington, between 1974-1975 and ~~= r--c~--~ ---, 1980-1981 (Streissguth et al., 1983~. Although FAS is believed to be limited to chronic alcohol abusers, growth retardation has been observed at lower levels of alcohol consumption (approximately 30 to 60 cc, or 1 to 2 oz. of absolute alcohol daily) (Hanson et al., 1978; Little, 1977; Wright et al., 1983~. Another study showed a significantly increased risk of delivering a growth-retarded infant for women who consumed one to two drinks per day (Mills et al., 1984~. Still other studies have demonstrated no or inconsistent associations between moderate levels of alcohol consumption and fetal growth (Brooke et al., 1989; Kline et al., 1987; Marbury et al., 1983; Rosett et al., 1983; Tennes and Blackard, 1980~. Thus, the evidence concerning the effects of low levels of alcohol consumption is both limited and inconsistent. The possibility that maternal binge drinking may adversely affect the fetus has also been suggested by data on both humans and animals (Clarren et al., 1978, 1988~. Nutrition-Related Effects of Alcohol Use The exact mechanism by which alcohol adversely affects fetal growth and morphogenesis has not been established. Animal studies have docu
396 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS mented direct dose-response effects of alcohol on fetal growth and devel opment and have shown that these effects were not attributable to other factors such as malnutrition (Randall et al., 1981~. Alcohol may also affect the fetus indirectly through its effect on maternal nutrition. Since ethanol is a source of energy, chronic alcoholics may have a relatively low intake of proteins, essential fats, vitamins, and minerals. In a prospective study of alcohol use during pregnancy and neonatal outcome in Cleveland, Ohio, investigators compared 24-hour dietary intake histories of patients with positive and negative scores on the Michigan Alcoholism Screening Test (Sokol et al., 1981~. Those with positive scores had significantly lower intakes of meat and vegetable protein, dairy foods, cereal and bread, calcium, certain B vitamins, and vitamin D. However, dietary intake was not significantly different among rare, moderate, and heavy drinkers in another study (Ouellette et al., 1977~. There are few data on the effect of alcohol on maternal nutrition. In one study maternal and umbilical cord blood zinc levels were found to be lower in alcoholic than in nonalcoholic pregnant women (Flynn et al., 1981), although the importance of these findings has been questioned (Kiely, 1981~. Other studies suggest that alcohol may impair placental transport of amino acids, which in turn may adversely affect fetal nutrition (Fisher et al., 1981~. Animal studies have similarly shown that ethanol inhibits placental transport of certain amino acids (Henderson et al., 1981; Lin, 1981) and zinc (Ghishan et al., 1982~. Ethanol can also interfere with the intestinal transport of several es- sential nutrients including calcium, amino acids, and some vitamins (Wilson and Hoyumpa, 1979~. The adverse effects of ethanol on liver function may lead to abnormalities in metabolism and nutrient utilization (Lieber, 1985~. However, evidence concerning the adverse effects of alcohol on specific nutritional indices comes largely from studies of nonpregnant hospitalized alcoholics, many of whom had hepatic damage. Specifically, chronic alcohol abuse has been linked to increased urinary zinc excretion and low serum zinc concentrations (Fredricks et al., 1960; McClain and Su, 1983; Vallee et al., 1957), decreased levels of hepatic vitamin A (Leo and Lieber, 1982), impaired uptake and utilization of folate (Halsted et al., 1971), and possibly thiamin malabsorption (Camilo et al., 1981; Hoyumpa, 1983~. Thus, zinc, vitamin A, folate, and thiamin deficiencies may occur with chronic alcohol consumption. However, supplementation with fat-soluble vitamins, partic- ularly vitamin A, may not be advisable, partly because of general concerns regarding toxicities, but also because data on animals suggest that vitamin A supplementation combined with ethanol consumption may enhance hepatic toxicity (Leo and Lieber, 1983~.
SUBSTANCE USE AND ABUSE 397 There is evidence from experiments in animals that nutritional factors may act synergistically with alcohol exposure in producing adverse effects. For example, low protein and caloric intakes have been hypothesized to interact with alcohol exposure, leading to higher blood alcohol levels and more severe growth retardation in rats (Wiener et al., 1981~. However, inconsistent results have been obtained when the protein content of the diet was increased (Weinberg, 1985; Wiener et al., 1981~. Zinc deficiency has also been postulated to be a coteratogen with alcohol. Studies in rats have shown that low zinc intake plus alcohol had more severe effects on the fetus than did either alcohol or low zinc intake alone (Keppen et al., 1985; Ruth and Goldsmith, 1981~. Plasma zinc levels and increased urinary zinc excretion were significantly lower in six infants with FAS as compared with levels in controls (Assad) and Ziai, 1986~. Zinc supplementation has been suggested as a way to prevent or lessen adverse alcohol-related effects; however, a study in rats produced no evidence that supplementation of a high-ethanol diet with zinc increased the placental transport of zinc (Ghishan and Greene, 1983~. In summary, alcohol may be related to decreased dietary intake, im- paired metabolism and absorption of nutrients, and altered nutrient activa- tion and utilization. Interactions between alcohol and deficiencies of such nutrients as protein and zinc may also play a role in the etiology of alcohol- related effects in the fetus. Although there is no convincing evidence that nutritional supplementation will counteract the adverse effects of alcohol, multivitamin-mineral supplementation (excluding vitamin A) may be indi- cated for women who are known or suspected alcohol abusers. However, since alcohol abuse has clearly been shown to be detrimental to the fetus, nutritional supplementation should not replace efforts to encourage women to limit or eliminate alcohol intake during pregnancy. CAFFEINE Caffeine along with theophylline and theobromine are methylxanthines found in coffee, tea, cola, and cocoa beverages. Caffeine is also a common additive in many non-prescription preparations, especially mild analgesics (Graham, 1978~. The Food and Nutrition Board's GRAS (Generally Rec- ognized as Safe) Survey Committee estimated in 1977 that 74% of pregnant females consumed some caffeine and that the mean intake for the entire group was 144 mg/day (approximately 1.5 cups of coffee) (NRC, 1977~. In a more recent study of pregnant women in Connecticut, the average daily caffeine intake was found to be slightly lower (102 ma) (Bracken et al., 1982~.
398 DIETARY INTAKE; AND NUTRIENT SUPPLEMENTS Pharmacologic Effects of Caffeine and Other Methylxanthines The three xanthines share several pharmacologic properties; namely, they stimulate the central nervous system and the cardiac muscle, act on the kidney to produce diuresis, and relax smooth muscle (Rail, 1985~. Of the three xanthines, caffeine is believed to be the most active central nervous system stimulant and the most extensively studied. Caffeine passes readily to the fetus, but the fetus cannot metabolize caffeine effectively, nor can the infant do so until several months after birth (Aldridge et al., 1979~. Maternal consumption of two cups of coffee significantly increases maternal epinephrine concentrations and decreases intervillous placental blood flow (Kirkinen et al., 1983~. Possible Effects on the Developing Fetus Although there is substantial evidence that caffeine is teratogenic in animals (Bertrand et al., 1965; Collins et al., 1982), there is no convinc- ing evidence that it is associated with birth defects in humans (Heinonen et al., 1977; Kurppa et al., 1982; Linn et al., 1982; Nelson and Forfar, 1971; Rosenberg et al., 1982~. Coffee and caffeine consumption have been associated with a reduction in birth weight and an increased risk of low- birth-weight infants, especially among full-term deliveries (Hogue, 1981; Martin and Bracken, 1987; Man and Netter, 1974; Munoz et al., 1988; van den Berg, 1977; Watkinson and Fried, 1985), but it is not clear in some of these studies whether the effects were due to caffeine, some other con- stituent of coffee, or other characteristics of coffee drinkers. Furthermore, most of the studies only assessed coffee consumption (Heinonen et al., 1977; Hogue, 1981; Kurppa et al., 1982; Linn et al., 1982; Mau and Netter, 1974; van den Berg, 1977), while others included additional sources of caffeine (Martin and Bracken, 1987; Nelson and Forfar, 1971; Rosenberg et al., 1982; Watkinson and Fried, 1985~. In addition, the level at which adverse effects have been reported ranges from a total daily caffeine intake greater than 150 mg (equivalent to 1.5 or more cups of coffee) (Martin and Bracken, 1987) to seven or more cups of coffee per day (Hogue, 1981~. An increased risk of late first- and second-trimester spontaneous abortions in women consuming more than 150 mg of caffeine daily after adjustment for other risk factors has also been reported (Srisuphan and Bracken, 1986~. In contrast, other studies have found no significant association between maternal caffeine or coffee consumption and reduced birth weight (Brooke et al., 1989; Hingson et al., 1982; Linn et al., 1982; Tennes and Blackard, 1980) or preterm delivery (Berkowitz et al'., 1982; Linn et al., 1982~.
SUBSTANCE USE AND ABUSE Nutr~tion-Related Effects of Caffeine or Coffee 399 Little is known about the nutritional status of pregnant women who consume caffeine. One study noted that women who consumed more than 300 mg of caffeine daily during pregnancy had lower weight for height and lower average intakes of calories, protein, calcium, vitamin A, thiamin, riboflavin, and vitamin C than those of women who consumed less than or equal to 300 mg daily (Watkinson and Fried, 1985~. The differences, however, were based on a small number of heavy caffeine users and were not statistically significant. Coffee and caffeine intakes have been reported to affect the status of some nutrients in nonpregnant populations. Specifically, caffeine intake has been observed to increase urinary calcium excretion (Massey and Hollingbery, 198%a,b) and coffee consumption has been related to decreased urinary thiamin excretion (Lewis and Inoue, 1981) and depressed zinc and iron absorption (Morck et al., 1983; Pecoud et al., 1975~. In a prospective study of pregnant women in Costa Rica, investigators found that consumption of three or more cups of coffee a day was associated with significantly lower maternal and neonatal hemoglobin and hematocrit levels (Munoz et al., 1988~. Since all the women in that study reportedly took prenatal supplements containing iron, supplemental iron did not appear to prevent the hematologic deficits among the coffee consumers. However, coffee consumption may facilitate calcium intake, particularly for Hispanic populations, who tend to dilute the coffee with a substantial amount of milk. Thus, although there is no convincing evidence that coffee or caffeine causes birth defects in humans, there is some limited evidence that moderate to heavy use of coffee and caffeine may lower infant birth weight. The latter finding has not been reported in all studies and needs to be confirmed by additional investigations. In 1980, the U.S. Food and Drug Administration recommended that the most prudent action for pregnant women and those who may become pregnant was to avoid caffeine-containing products or to use them sparingly (FDA, 1980~. Although it appears sensible to limit coffee and caffeine intake during pregnancy, the subcommittee concluded that the data are not sufficient for making a specific recommendation. Information regarding the influence of coffee and caffeine on maternal nutrition is very limited, and it is not known whether nutrient supplements would be necessary or beneficial for those who continue to consume caffeine ounng pregnancy. MARIJUANA Prevalence of Marijuana Use National surveys estimate that the proportion of women between the ages of 18 and 25 who had used marijuana in the previous month increased
400 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS from 19% in 1976 to 26% in 1979 and subsequently declined to 11% in 1988 (NCHS, 1989; NIDA, 1989~. According to the 1988 survey, the proportions were lower for teenage girls (7%) and for women aged 26 to 34 (7%~. In the 1985 survey, usage among the 18 to 25 year aids was substantially higher for whites (18%) and blacks (17%) compared with that for Hispanics (9%) (NIDA, 1987~. Although there are no national data on the prevalence of marijuana use during pregnancy, estimates from hospital- based studies have ranged from approximately 10% (Hatch and Bracken, 1986; Linn et al., 1983) to 27% (Zuckerman et al., 1989~. Variations in population characteristics as well as differences in methods of ascertaining marijuana use are likely explanations for the wide range. For example, a recent study showed that self-reported maternal marijuana use is lower than the estimate obtained from a combination of interviews and urine assays (Zuckerman et al., 1989~. Underreporting was also more common for self-reported marijuana use than for self-reported cigarette or alcohol use during pregnancy (Hingson et al., 1986~. Pharmacologic Effects of Marijuana The main active ingredient of marijuana, /~9-tetrahydrocannabinol, crosses the placenta (Indanpaan-Heikkila et al., 1969~. Because marijuana is fat-soluble and is excreted at a slow rate (Jones, 1980), the exposure of the fetus to the drug may be prolonged. Marijuana smoking, like tobacco smoking, is also associated with increased carboxyhemoglobin levels (Wu et al., 1988), which in turn may impair fetal oxygenation and, consequently, fetal growth. Indeed, the increase in carboxyhemoglobin levels has been found to be substantially higher for marijuana smoking than for tobacco smoking (Wu et al., 1988~. Furthermore, marijuana use tends to increase the heart rate and blood pressure (Foltin et al., 1987), which may lead to reduced uteroplacental blood flow to the fetus. Effects on the Developing Fetus and Child Animal experiments indicate that marijuana may have a fetotoxic potential, including increased fetal resorption and reduced birth weight (Harclerode, 1980), but some of these effects may have been related to reductions in food and water consumption (Abel, 1980a). Data on the influence of marijuana on pregnancy outcomes in humans are both limited and inconsistent. Adverse effects that have been reported include decreased birth weight (Hingson et al., 1982; Zuckerman et al., 1989) and body length (Zuckerman et al., 1989), increased frequency of preterm delivery (Gibson et al., 1983), shortened length of gestation (Fried et al., 1984), higher rates of precipitate labor and meconium passage (Greenland et al., 1982),
SUBSTANCE USE AND ABUSE 401 increased risk of infant features compatible with the fetal alcohol syndrome (Hingson et al., 1982), and altered neurobehavioral responses in neonates (Fried, 1980; Scher et al., 1988~. Other studies, however, have reported no effect on either birth weight or length of gestation (Linn et al., 1983; Rosett et al., 1983) or produced inconsistent results. For example, one study found that white, but not nonwhite, women who used marijuana at least two to three times monthly during the pregnancy were at an increased risk of delivering a low-birth- weight, small-for-gestational-age, and preterm infant (Hatch and Bracken, 1986~. Another investigation, which was based on two pregnancy cohorts followed over different periods, found a reduction in birth weight with increasing frequency of marijuana use during the second, but not the first phase of the study (Kline et al., 1987~. Furthermore, a recent study found no association between marijuana use during pregnancy and features compatible with fetal alcohol effects at age 4 (Graham et al., 1988~. Possible explanations for the inconsistent findings include differences in the ascertainment and classification of marijuana use, variations in the underreporting of marijuana or other illicit drug use, and the difficulty of controlling for highly interrelated factors such as abuse of other substances. Possible Nutrition-Related Effects of Marijuana Use There are few data on the nutritional status of pregnant marijuana users, nor is it known what effect marijuana exposure may have on specific nutrients. Although marijuana reportedly stimulates the appetite (Abel, 1971), studies of women who have consumed marijuana during pregnancy have provided conflicting results regarding their nutritional status. One study found that marijuana users consumed significantly more calories and protein and gained slightly more weight during the pregnancy than did their controls (O'Connell and Fried, 1984~. Another study reported that women who had a positive assay for marijuana use weighed slightly less before the pregnancy and gained significantly less weight during the pregnancy as compared with those who had a negative assay (Zuckerman et al., 1989~. A third investigation found no consistent relationship between obesity (ponderal index >30) and the frequency of marijuana usage during pregnancy (Linn et al., 1983~. Since it appears that prepregnancy weight and maternal weight gain were not controlled for in all investigations (Hatch and Bracken, 1986), it is unclear to what extent nutritional factors may have contributed to some of the reported effects of marijuana. Despite the relatively high prevalence of marijuana use during preg- nancy, no conclusive data are available on the effect of marijuana on the developing fetus. There is, however, suggestive evidence that marijuana use during pregnancy may impair fetal growth.
402 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS COCAINE Prevalence of Cocaine Use Cocaine use has grown to epidemic proportions during the past decade in the United States. Although cocaine was previously believed to be a relatively safe, nonaddictive euphoriant agent, it is now recognized that cocaine use is associated with substantial morbidity and mortality (Cregler and Mark, 1986; Gawin and Ellinwood, 19884. The National Household Survey on Drug Abuse in 1988 estimated that more than 20 million people in the United States had tried cocaine, including 20% of those between the ages of 18 and 25 (NIDA, 1989~. The proportion of women aged 18 to 25 years who had used cocaine in the past month increased from 4.7% in 1982 to 6.3% in 1985 but declined to 3% in 1988 (NCHS, 1989; NIDA, 1989~. Among teenage girls, however, the proportion has remained constant between 1985 and 1988 (NIDA, 1987; NIDA, 1989~. While earlier surveys have indicated that cocaine usage was more common among whites than nonwhites, rates of recent usage in the 1988 survey were higher for Hispanic and black women as compared with white women (Abelson and Miller, 1985; NIDA, 1989~. The subcommittee was unable to find any representative data on the prevalence of cocaine use among pregnant women, but a recent prospective study of consecutive prenatal patients from a poor inner-city population reported that 18% had used cocaine at least once during the pregnancy (Zuckerman et al., 1989~. Cocaine addiction Is believed to be five times more common than heroin addiction (Gawin and Ellinwood, 1988~. Cocaine is an alkaloid prepared from the plant Erythroxylon coca. When used in the free-base form (i.e., crack), it is more potent because it is almost pure cocaine. Cocaine acts as a central nervous system stimulant, causing increased heart rate, hypertension, and vasoconstriction (Cregler and Mark, 1986; Woods et al., 1987~. Because of its low molecular weight and high solubility In water and lipids, cocaine readily crosses the placenta (Anonymous, 1988~; however, the vasoconstrictive effect of cocaine may reduce placental transport (Fantel and MacPhail, 1982~. Effects on the Developing Fetus and Infant An association between cocaine exposure and abruptio placentae is fairly well established (Acker et al., 1983' Bingol et al., 1987; Chasnoff and MacGregor, 1987; Chasnoff et al., 1985; Landy and Hinson, 1988; Livesay et al., 1987; Oro and Dixon, 1987~. There is also growing evidence that co- caine abuse may be associated with premature labor and intrauterine growth retardation (Chasnoff and MacGregor, 1987; Chouteau et al., 1988; Dixon and Oro, 1987; LeBlanc et al., 1987; Oro and Dixon, 1987; Zuckerman et
SUBSTANCE USE AND ABUSE 4~)3 al., 1989) as well as spontaneous abortion (Chasnoff et al., 1985; Livesay et al., 1987~. The teratogenic potential of cocaine is less clear, although there are reports suggesting an increase in congenital anomalies (Bingol et al., 1987; Chasnoffetal., 1988; Koborietal., 1989~. A mild withdrawal syndrome (Chasnoff et al., 1985; Doberczak et al., 1988; Oro and Dixon, 1987) and transient electroencephalogram abnormalities (Doberczak et al., 1988) have been described in some infants born to cocaine-abusing mothers. Of great concern are recent case reports of cerebral infarction in neonates who had been exposed to cocaine in utero (Chasnoff et al., 1986; Ferriero et al., 1988~. Possible Nutr~tion-Related Effects of Cocaine Use As is true for marijuana, little is known about the nutrition-related effects of cocaine use. Cocaine's vasoconstrictive ability may lead to fetal hypoxia (Woods et al., 1987) and reduced nutritional supply to the fetus. Since cocaine, like amphetamines, acts as an appetite suppressant (Cregler and Mark, 1986; Gawin and Ellinwood, 1988; Resnick et al., 1977), an inadequate maternal diet may play a role in the growth retardation seen in fetuses of cocaine abusers. In one study, pregnant women with urine assays positive for cocaine weighed significantly less before the pregnancy, had lower hematocrit levels at the time of prenatal registration, and gained slightly less weight during the gestation than did those with negative assays (Frank et al., 1988; Zuckerman et al., 1989~. Although the deficit in birth weight did not achieve significance when prepregnancy weight and maternal weight gain were controlled for in the analysis, significant decreases in birth length and head circumference remained (Zuckerman et al., 1989~. Thus, these data suggest that the association between cocaine use and growth retardation may be partially but not completely mediated by nutritional factors. Other factors, such as cigarette smoking, alcohol consumption, and other drug abuse, which were not controlled for in all the studies, may also have confounded some of the reported adverse effects. Since the origin of the current cocaine epidemic is recent, further stud- ies should be conducted to provide more definitive evidence on the effects of cocaine on the course of pregnancy and neonatal outcome. Isolating the influence of cocaine from other factors will nevertheless be difficult, since cocaine use is often accompanied by abuse of other substances as well as other life-style patterns that may be detrimental to the fetus. SUMMARY AND RECOMMENDATIONS FOR FUTURE RESEARCH Although the adverse reproductive effects of tobacco, alcohol, and many illicit drugs are well established and there is some, albeit limited and conflicting, evidence that moderate to heavy use of coffee and caffeine may
404 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS decrease birth weight, the underlying mechanisms responsible for these effects are generally not well understood. Much also remains to be learned concerning critical periods of exposure, dose-response thresholds, factors that modify susceptibility to the adverse effects, and influences of substance abuse on maternal and fetal nutrition. Similarly, little is known about the effects of specific patterns of substance abuse such as binge, as opposed to chronic, alcohol consumption. Furthermore, the factors underlying or associated with substance abuse, including the role of genetic predisposition, need to be delineated. CLINICAL IMPLICATIONS · Highest priority should be given to efforts to prevent or stop substance abuse by pregnant women since there is clear evidence that cigarette smoking and alcohol and drug abuse adversely affect the health of the mother and the fetus. Since nutritional deficiencies can be expected, especially among heavy substance abusers, diet counseling and other efforts (e.g., referral to a social worker) to improve food intake are recommended. · Because heavy substance abusers may have difficulty in taking the steps needed to improve their dietary intake, the subcommittee recom- mends the use of multivitamin-mineral supplements of the type outlined in Chapter 1. REFERENCES Abel, E.L 1971. Effects of marihuana on the solution of anagrams, memory and appetite. Nature 231:260-261. Abel, E.L. 1980a. Prenatal exposure to cannabis: a critical review of effects on growth, development, and behavior. Behav. Neurol. Biol. 29:137-156. Abel, E.L" 1980b. Smoking during pregnancy: a review of effects on growth and development of offspring. Hum. Biol. 52 593-625. Abel, E.L, and RJ. Sokol. 1987. Incidence of fetal alcohol syndrome and economic impact of FAS-related anomalies. Drug Alcohol Depend. 19:51-70. Abelson, H.I., and J.D. Miller. 1985. A decade of trends in cocaine use in the household population. -Natl. Inst. Drug Abuse Res. Monogr. Ser. 61:35-49. Acker, D., B.P. Sachs, KJ. Tracey, and WE. Wise. 1983. Abruptio placentae associated with cocaine use. Am. J. Obstet. Gynecol. 146:220-221. Alberman, E., M. Creasy, M. Elliott, and C. Spicer. 1976. Maternal factors associated with fetal chromosomal anomalies in spontaneous abortions. Br. J. Obstet. Gynaecol. 83:621-627. Aldridge, A., J.V. Aranda, and A.H. Neims. 1979. Caffeine metabolism in the newborn. Clin. Pharmacol. Ther. 25:447-453. Andrews, J., and J.M. McGar~y. 1972. A community study of smoking in pregnancy. J. Obstet. Gynaecol. Br. Commonw. 79:1057-1073. Anonymous. 1988. Perinatal toxicity of cocaine. The Med. Lett. 30:59~0. Aronson, M., M. Kyllerman, K.G. Sabel, B. Sandin, and R. Olegard. 1985. Children of alcoholic mothers. Developmental, perceptual and behavioral characteristics as compared to matched controls. Acta Paediatr. Scand. 74:27-35.
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406 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS Dixon, S.Z., and A. Oro. 1987. Cocaine and amphetamine exposure in neonates: perinatal consequences. Pediatr. Res. 21:359A. Doberczak, T.M., S. Shanzer, R.T. Senie, and S.R. Kandall. 1988. Neonatal necrologic and electroencephalographic effects of intrauterine cocaine exposure. J. Pediatr. 113:354-358. Dunn, H.G., A K. McBurney, S. Ingram, and C.M. Hunter. 1977. Maternal cigarette smoking during pregnancy and the child's subsequent development: II. Neurological and intellectual maturation to the age of 6 l/2 years. Can. J. Public Health 68:4~50. Ernhart, C B., AW. Wolf, P.L. Linn, RJ. Sokol, M.J. Kennard, and H.F. Filipovich. 1985. Alcohol-related birth defects: syndromal anomalies, intrauterine growth retardation, and neonatal behavioral assessment. Alcoholism 9:447453. Fantel, A G., and BJ. MacPhail. 1982. The teratogenicit,v of cocaine. Teratology 26:17-19. FDA (Food and Drug Administration). 1980. Caffeine and Pregnancy. FDA Drug Bull. 10:19-20. Fedrick, J., and AB.M. Anderson. 1976. Factors associated with spontaneous pre-term birth. Br. J. Obstet. Gynaecol. 83:342-350. Ferriero, D.M., J.C. Partridge, and D.F. Wong. 1988. Congenital defects and stroke in cocaine-exposed neonates. Ann. Neurol. 24:348-349. Fisher, S.E., M. Atkinson, D.H. Van Thiel, E. Rosenblum, R. David, and I. Holzman. 1981. Selective fetal malnutrition: the effect of ethanol and acetaldehyde upon ~n v~iro uptake of alpha amino isobutyric acid ~y human placenta. Life Sci. 29:1283-1288. Flynn, A., S.I. Miller, S.S. Martier, N.L" Golden, RJ. Sokol, and B.C. Del Villano. 1981. Zinc status of pregnant alcoholic women: a determinant of fetal outcome. Lancet 1:572-575. Foltin, RW., M.W. Fischman, JJ. Pedroso, and G.D. Pearlson. 1987. Marijuana and cocaine interactions in humans: cardiovascular consequences. Pharmacol. Biochem. Behav. 28:459-464. Frank, D.A., B.S. Zuckelman, H. Amaro, K Aboagye, H. Bauchner, H. Cabral, ~ Fried, R. Hingson, H. Kayne, S.M. Levenson, S. Parker, H. Reece, and R. Vinci. 1988. Cocaine use during pregnancy: prevalence and correlates. Pediatrics 82:888-895. Fredricks, R.E., KR. Tanaka, and W.N. Valentine. 1960. Zinc in human blood cells: normal values and abnormalities associated with liver disease. J. Clin. Invest. 39:1651-1656. Fried, P.A. 1980. Marihuana use by pregnant women: neurobehavioral effects in neonates. Drug Alcohol Depend. 6:415424. Fried, P.A., B. Watkinson, and A. W~llan. 1984. Marijuana use during pregnancy and decreased length of gestation. Am. J. Obstet. Gynecol. 150:2~27. Garn, S.M., H.A. Shaw, and KD. McCabe. 1978. Effect of maternal smoking on hemoglobins and hematocrits of the newborn. Am. J. ain. Nutr. 31:557-558. Garn, S.M., K. Hoff, and K.D. McCabe. 1979. Is there nutritional mediation of the "smoking effect" on the fetus. Am. J. Clin. Nutr. 32:1181-1187. Gawin, F.H., and E.H. Ellinwood, Jr. 1988. Cocaine and other stimulants: actions, abuse, and treatment. N. Engl. J. Med. 318:1173-1182. Ghishan, F.K., and H.L~ Greene. 1983. Fetal alcohol syndrome: failure of zinc supplemen- tation to reverse the effect of ethanol on placental transport of zinc. Pediatr. Res. 17:529-531. Ghishan, F.K, R. Patwardhan, and H.L~ Greene. 1982. Fetal alcohol syndrome: inhibition of placental zinc transport as a potential mechanism for fetal growth retardation in the rat. J. Lab. Clin. Med. 100:45-52. Gibson, G.T., P.A. Baghurst, and D.P. Colley. 1983. Maternal alcohol, tobacco and cannabis consumption and the outcome of pregnancy. Aust. N.ZJ. Obstet. Gynaecol. 23:15-19. Graham, D.M. 1978. Caffeine its identity, dieta~y sources, intake and biological effects. Nutr. Rev. 36:97-102. Graham, J.M., Jr., J.W. Hanson, B.L~ Darby, H.M. Barr, and ~P. Streissguth. 1988. Independent dysmorphology evaluations at birth and 4 years of age for children exposed to va~ying amounts of alcohol in utero. Pediatrics 81:772-778.
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