Engs, Ruth C. [Ed.], Controversies in the Addiction's Field. Sterling K. Clarren, M.D. "CHAPTER 18: Drinking In Pregnancy: A Recommendation For Complete Abstinence."
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CHAPTER 18 Drinking In Pregnancy: A Recommendation For Complete Abstinence<
Sterling K. Clarren, M.D.
A teratogen is an environmental agent capable of producing birth defects. As alcohol (ethanol) became established as a human teratogen in the 1970s, the United States Surgeon General was prompted to advise women who were pregnant orplanning to become pregnant that it was best for them to abstain from drinking alcohol containing beverages through out gestation (US Department of Treasury, 1980). I believe, the Surgeon General's simple statement was correct then and now, although it belies issues of great complexity. In order to properly understand the statement, it is necessary to review two topics: what is known about dose-response or the teratogenic threshold for alcohol- related birth defects, and what changes in popular behavior can be expected from public awareness campaigns concerning alcohol consumption in pregnancy based on a professional statement of danger?
The theory of teratogenic threshold explains that environmental substances rarely cause malformations under all circumstances. Danger to the fetus occurs when exposure is above a critical dose at a critical time in gestation, a "period of vulnerability" (Shepard, 1982). When the exposure is above a critical concentration at a vulnerable time then a sensitive organ, tissue line, or cell type (but generally not the fetus as a whole) may be injured or destroyed. For some teratogens the critical dose is sufficiently high and/or the periods of vulnerability are sufficiently limited that little fetal harm is ever done. Other teratogens are effective at low dose exposures in widespread periods of gestation. The teratogenic impact of ethanol seems to fit more closely into the latter category.
Ethanol flows freely through tile placenta and is poorly metabolized by die fetus. Fetal exposure to edhanol is directly reflected in the maternal blood alcohol concentration (BAC). To date, no study has correlated BAC's in pregnant women with fetal outcomes. Such studies would obviously have major methodologic and ethical problems. Consequently, researchers have tried to correlate maternal reported consumption of
alcohol as an indirect measure of BAC to fetal outcomes. Correlating reported maternal alcohol consumption to fetal response can only produce broad estimates of teratogenic threshold for several reasons. First, it is difficult to obtain accurate intake information. Few people measure liquor or wine accurately into a glass. Individuals may report "no more than one drink per night", yet if they are questioned further it is found that "the drink" may have anywhere from one half-ounce to four or five ounces of liquor. People may forget or deny liquor consumption that occurred days, weeks or months prior to an interview. Second, even if people were to have consumed identical volumes of alcohol, absorption and peak blood alcohol concentrations would still vary widely based on the individuals' sizes, their fat/lean body mass ratios, their rates of alcohol consumption, and whether they ate while drinking.
Third, after absorption, degradation of alcohol is primarily determined by the activity of two liver enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. The activity of these enzymes may be varied by racial background, individual genetic background and/or liver disease. Finally there may be other factors that determine ethanol metabolism. In our laboratory, for example, alcohol has been given via nasogastric catheter to non- human primates (M. nemestrina) who were fasted overnight. The animals 'BAC's were sequentially measured over several post consumption hours. Even under these standard conditions peak BAC's varied by 20% to 25% in the same animal given the same dose on different days (Clarren et al., 1987).
Structural malformations are generally regarded as proof of fetal response to teratogenesis. It is probable that there is a specific period of vulnerability for each major or minor malformation during the first trimester, with the exception of the brain which is rapidly developing and changing throughout gestation. The brain must be thought of as a large cotlection of neuronal systems in which each system has its own periods of teratogenic vulnerability (Ailing, 1985). While the brain may be susceptible to alcohol throughout much of gestation, its pattern of alteration may be different in different exposure sequences. Functional as well as structural anomalies of the brain need to be considered as possible teratogenic outcomes. Generalized growth deficiency can also be considered a malformation; length and weight are most severely effected by teratogens in the second half of pregnancy.
Agent concentration and gestational timing can not be the sole determinants of fetal response to alcohol. There are several case reports of fraternal twinning in which one twin was more severely affected than the other (Christoffel and Salasky, 1975). Presumably, fetuses have a genetic resistance to teratogenesis that are not evenly shared. It also remains an
open question to what extent other maternal factors like generalized malnutrition (Fischer et al., l 982), specific vitamin or mineral deficiencies (Dreosti, 1986), or exposures to other drugs (King and Fabro, 1983) might potentials the effects of ethanol exposure at different doses.
Another difficulty in interpreting dose response data in many human studies of alcohol related birth defects is the practice of reporting cohort doses in terms of "averaged consumptions." It is understandable that investigators have used averaged consumption scores which are obtained by dividing daily intake reports by periods of time like weeks or months. After all no two fetuses have ever been exposed to the exact same drinking pattern throughout gestation and consumption data will inevitably be imprecise given the explanations above. However, widely varying drinking patterns may be merged through the averaging approach. A woman drinking 30 gms of alcohol each day and a woman drinking 210 gms of alcohol once per week would have the same averaged weekly consumption score. It is possible that each of these exposure patterns is teratogenic or that only one isóbut surely the impacts of these exposure patterns would be different. When studies report relatively moderate drinking to be associated with a teratogenic impact (Kline et al., 1980; Streissguth et al., 1981), is this true for the cohort over all or are some subgroups in the cohort skewing the results?
At present little is known about the ability of the fetus to repair itself from early gestational teratogenesis. There is evidence that women who stop drinking during pregnancy have larger, healthier babies.(Rosette et al., 1980). But there is also evidence that early gestationa1 alcohol exposure correlates with abnormal behaviors in the offspring independent of later gestational effects by the mother to reduce or eliminate alcohol use (Emhart et al., 1987; Streissguth et al., 1989; Larsson et al., 1985).
One outcome from alcohol teratogenesis is the fetal alcohol syndrome (FAS). This specific disorder is defined by brain dysfunction, growth deficiency, specific minor malformations of the face and other assorted major and minor anomalies (Clarren and Smith, 1978). FAS usually is found in children of chronic alcoholics (Warren, 1981). Alcoholics presumably achieve BAC's above alcohol's teratogenic threshold often enough to affect numerous embryo/fetal vulnerable periods. Not all infants born to alcoholics have FAS, however. Is this because of important difference in consumption patterns, maternal metabolism, fetal resistance, cofactors, or combinations of these? No one yet knows.
Although not all infants born to alcoholics have FAS, this does not mean that they are necessarily "normal." Neither does it mean that fetuses exposed to alcohol in non-alcoholic pregnancies are without teratogenic risk. Physicians or psychologists can never prove an individual is fully
normal, they can only demonstrate that a person is abnormal or normal on the tests given at a specific time. Prospective studies in humans and in animals clearly demonstrate that alcohol can produce isolated malformations or affect brain structure, and/or function without producing the major and minor malformations and growth deficiencies which help to define FAS(Streissguthet al., 1989; Clarrenet al., 1988; Streissguth et al., 1986; West, 1986). Alcohol related brain teratogenesis can be manifest as attention and behavior problems as well as difficulties with memory and learning ( Streissguth et al., 1989). Some, but not all, of these problems would be identified by I.Q. testing. Subtle problems might not be detected until an affected child is well into school (Streissguth et al., l 989). Imaging studies of brain structure are not capable of detecting damage at the cellular or neurochemical level. At this time, virtually no information is available on how many periods of vulnerability for brain teratogenesis exist in humans, or what the specific threshold dose for any necrologic structure or system may be.
In summary, alcohol can produce an identifiable birth defect syndrome, fetal alcohol syndrome, which is generally associated with frequent, heavy alcohol exposures. Binge patterns of drinking or moderate consumption of alcohol may be associated with brain dysfunction in isolation. The limits for dose-response producing central nervous system damage in isolation are not known. Certainly some small amount of liquor taken on only rare days in pregnancy should be below threshold in any pregnancyóbut it is likely that it will never be possible to guarantee an absolutely safe low dose of alcohol for any period of pregnancy for a specific individual.
An official position representing professional opinion on a matter of public health is only the beginning of a campaign to affect public behavior. The issues involved in mounting a campaign concerning the dangers of gestational alcohol use are complex. Who is to be warned? Everyone? Women? High risk women (who are they)? Who is to do the warning? The government, the media, the scientific community, tile liquor manufacturers? Should the campaign be directy aimed at a targeted population of drinkers or should it be aimed at groups like doctors, teachers, or spouses who could then work with tile target population. What fetal problems are to be targeted by the campaign, the prevention of FAS or an alcohol related birth defects? Can a reasonable reduction in fetal morbidity be easily measured? Will the campaign have negative as well as positive consequences? Can the campaign be assessed, sustained and improved over time? Who should take on the responsibility of answering these questions?
The Surgeon General's advice represents, in my opinion, the only responsible professional advice that can be offered for alcohol use in
pregnancy. The only absolutely safe gestational alcohol exposure is no exposure. I believe it is the position from which a public health campaign must be mounted even though it is a most problematic beginning. Alcoholics and intermittent alcohol abusers are the highest risk target populations. Yet the alcoholic woman's denial of her alcohol use and dependence is a primary component of her condition. Public awareness campaigns of simple, direct information are not likely to influence her. However, methods for identifying and confronting pregnant alcoholics and directing them towards treatment are being developed and need to be encouraged (Minor and Van Dort, 1982; Rydberg, 1985; Rosett et al, 1978; May and Hymbaugh, 1989). The non-alcoholic who is concerned about having a healthier baby can team from health recommendations and can alter her behavior. Unfortunately, variations in media and professional advice may confuse her (Little et al., 1981; 1983). Even if an non-alcoholic women understood and accepted the Surgeon General's advice, the situation would be difficult.. Often women do not know they ale pregnant in the first crucial weeks of gestation. In order to fully avoid alcohol's teratogenic impact, women would need to avoid alcohol use in aU periods of unprotected sexual intercourse from menarche to menopause.
The medical profession and the scientific community can not alter the facts to make life less complicated. Alcohol related birth defects will not be prevented by academic wrangling over subtle differences in dhe relative safety of different low dose alcohol exposures. The prevention of FAS and related conditions will only occur when effective methods for identifying and treating alcoholics prior to pregnancy are coupled with convincing advise that helps non-alcoholic women reduce or eliminate their alcohol consumption at times of risk.
Alling, C. (1985). Biochemical maturation of the brain and the concept of vulnerable periods. In Alcohol and the Developing Brain. Rydberg U., (Ed.). Raven Press: New York, pp. 5-10.
Christoffel, K.K and Salasky, I., (1975). Fetal alcohol syndrome in dizygotic twins. Journal of Pediatrics, 87 963-967.
Clarren, S.K. (1981). Recognition of the fetal alcohol syndrome. Journal of theAmerican Medical Association, 245 2436-2439.
Clarren, S.K., Astley, S.J., and Bowden, D.M. (1988). Physical anomalies and developmental delays in non-human primate infants exposed to weekly doses of ethanol during gestation. Teratology, 37 561-570.
Clarren, S.K., Bowden, D.M., and Astley, S.J. (1987). Pregnancy out comes after weekly oral administration of ethanol during gestation in pigtailed macaques (Macaca nemestrina). Teratology, 35 245-254.
Clarren, S.K. and Smith, D.W. (1978). The fetal alcohol syndrome. New England Journal of Medicine, 298 1063-1067.
Dreosti, I.E. (1978). Zinc-alcohol interactions in brain development. In Alcohol and Brain Development. West, J.R. (Ed.). Oxford University Press: New York, pp. 373-405.
Ernhart, C.B., Sokol, R.J., Martier, S., Moron, P., Nadler, D., Ager, J.W., and Wolf, A. (1987). Alcohol teratogenesity in the human.2. Adetailed assessment of specificity critical period and threshold. American Journal of Obstetrics and Gynecology, 156 33-39.
Fischer, S.E.,Atkinson, M., Brunap, J.K., Jacobson, S., Sehgal ,P.K., Scott, W., and Van Thiel, D.H. (1982). Ethanol-associated selective fetal malnutrition: A contributing factor in the fetal alcohol syndrome. Alcoholism: Clinical and Experimental research, 6 197-201.
Kink, J.C. and Fabro, S. (1983). Alcohol consumption and cigarette smoking: effect on pregnancy. Clinical Obstetrics and Gynecology, 26 437-448.
Kline, J., Stein, Z., Shrout, P., Susser, M., and Warburton, D. (1980). Drinking during pregnancy and spontaneous abortion. Lancet, 2 176-180.
Larsson, G., Bohlin, A.V., and Tunell, R. (1985). Prospective study of children exposed to variable amounts of alcohol in utero. Archives of Disease in Childhood, 60 316-321.
Little, R.E., Grathwohti, H.L., Streissguth, S.P., and McIntyre, C.E. (1981). Public awareness and knowledge about the risks of drinking during pregnancy in Multnomah County Oregon. American Journal of Public Health, 71 312-314.
Little, R.E., Streissguth,A.P., Guzinski, G.M., Frathwohl, H.L., Blumhagen, J.M., and McIntyre, C.E. (1983). Change in obstetrician advise following a two year community educational program on alcohol use and pregnancy. American Journal of Obstetrics and Gynecology, 146 23-28.
May, PA. and Hymbaugh, K.J. (1989). A macro-level fetal alcohol syndrome prevention program for Native Americans and Alaska Natives: Description and evaluation. Journal of Studies onAlcohol, 50 508-518.
Minor, M.J. and Van Dort, B. (1982). Prevention research on the teratogenic effects of alcohol. Preventative Medicine, 11 346-359.
Rosett, H.L., Ouellette, E.M., Weiner, L. and Owens, E. (1978). Therapy of heavy drinking during pregnancy. Obstetrics and Gynecology, 51 41-46.
Rosett, H.L., Weiner, L., Zuckerman, B., McKinlay, S., and Edelin, K.C. (1980). Reduction of alcohol consumption during pregnancy with benefits to the newbom. Alcoholism: Clinical and Experimental Research, 4 178-184.
Rydberg, U. (1985). Inpatient treatment of pregnant women with abuse of alcohol and drugs-prognosis for mother and child. The Second Malmo Symposium on Alcohol. Ferrosan, A.B., (Ed.). Department of Alcohol Diseases: Malmo, pp. 69-73.
Shepard, T.H. (1982). Detection of human teratogenic agents. Journal of Pediatrics, 101 810-815.
Streissguth, A.P., Barr, H.M., Sampson, P.D, Bookstein, F.A., and Darby, B.L. (1989). Neurobehavioral effects of prenatal alcohol: Part I. Research Strategy. Neurotoxicology and Teratology, 11 461-476.
Streissguth, A.P., Barr, H.M., Sampson, P.D, Parrish-Johnson, J.C., Kirchner, G.L., and Martin, D.C. (1986). Attention, distraction and reaction time at age 7 years and prenatal alcohol exposure. Neurobehavioral Toxicology and Teratology, 8 717-725.
Streissguth, A.P., Martin, D.C., Martin, J.C, and Barr, H.M. (1981). The Seattle longitudinal prospective study on alcohol and pregnancy. Neurobehavioral, Toxicology and Teratology, 3 223-233.
U.S. Department of the Treasury and the U.S. Department of Health and Human Services. (November, 1980). Report to the President and Congress of health hazards associated with alcohol and methods to infomm the general public of these hazards.
West, J.R. (1986). Alcohol and Brain Development. Oxford University Press: New York.
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