DRINKING DURING PREGNANCY AND SPONTANEOUS ABORTION

176

thermore, previous studies in humans indicate that moderate drinking is associated with growth retardation and fetal abnormalities,6,1l,12 suggesting that alcohol has a teratogenic and/or fetotoxic effect. Our data do not enable us to compare different types of drinks, to estimate the dangers of occasional drinking sessions as opposed to regular light or moderate drinking, or to establish whether there is a maximum safe amount of alcohol. We are also unable to assess whether there was any significant degree of under-reporting of alcohol use in our population. These results should not be taken to imply with certainty that alcohol has no effect in the first trimester. This study was not designed for research into spontaneous abortions, and the women who initiated antenatal care early in pregnancy (and therefore entered the study early) would have been a selected group, perhaps at higher risk for miscarriage. We have no way of knowing whether these women were also less likely to be alcohol users, so that it is possible that our findings for early pregnancy contain biases which could invalidate our conclusions about the effect of alcohol at that time. Our work also confirms in a prospective study an association between smoking and spontaneous losses, previously noticed in several retrospective investigations.8 The association is less strong than that observed for alcohol, and in our population is less clearly related to the number of cigarettes smoked daily. Previous studies of smoking and spontaneous losses have not taken into account the effects of drinking, and it is possible that the larger relative risks observed in these studies, compared with ours, can be partly explained by alcohol. Data obtained from Kaiser-Permanente Birth Defects

Study.

This work was supported by contract number N01-HD-4-2861 from the Center for Population Research, NICHD.

Requests for reprints should be addressed to S. H., Department of Ecology, Hebrew University of Jerusalem, PO Box 1172, Jer-

Medical

usalem, Israel.

REFERENCES

298: 1063-67.

Streissguth AP. Fetal alcohol syndrome J Epidemiol 1978, 107: 467-78

an

epidemiologic perspective.

Amer

N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. N Nat Cancer Inst 1959; 22: 719-48. 5. Klatsky AL, Friedman GD, Siegelaub AB, Gerard MJ. Alcohol consumption among White, Black or Oriental men and women: Kaiser-Permanente Multiphasic Health Examination data. Am J Epidemiol 1977; 105: 311-23. 6 Little RE. Moderate alcohol use during pregnancy and decreased infant birth

4 Mantel

weight Am J Publ Health 1977; 67: 1154-56. J, Stein ZA, Susser M, Warburton D. Smoking:

7. Kline 8.

A risk factor for spon-

taneous abortion. N Engl J Med 1977, 297: 793-96. Harlap S, Davies AM. Characteristics of pregnant women reporting previous

induced abortion. Bull WHO 1975; 52: 149-54. 9. Chernoff G. A mouse model of the fetal alcohol syndrome. Teratology 1975; 11: 14A. 10. Tze WJ, Lee M. Adverse effects of maternal alcohol consumption on pregnancy foetal growth in rats Nature 1975; 257: 479. 11. Hanson JW, Streissguth AP, Smith DW. The effects of moderate alcohol consumption during pregnancy on fetal growth and morphogenesis. J Pediat 1978, 92: 457-60. 12. Ulleland C, Wennberg RP, Igo RP, Smith NJ the offspring of alcoholic mothers. Pediat Res 1970, 4: 474. 13. Stein Z, Susser M, Watburton D, Wittes J, Kline J. Spontaneous abortion as a screening device: the effect of fetal survival on the incidence of birth

defects. Am J Epidemiol 1975; 102: 275-90. 14. Luce BR, Schweitzer SO

economic consequences

AND

SPONTANEOUS ABORTION

PATRICK SHROUT MERVYN SUSSER DOROTHY WARBURTON

JENNIE KLINE ZENA STEIN

New York State Psychiatric Institute; and Sergievsky Centre, School of Public Health, and Department of Human Genetics and Development, Columbia University, New York

drinking alcohol who aborted spontaneously (cases) was compared with that among 632 women who delivered after at least 28 weeks gestation (controls). 17·0% of cases reported drinking twice a week or more during pregnancy whereas among controls, only 8·1% of women reported drinking twice a week or more. The hypothesis that drinking during pregnancy is associated with spontaneous abortion was tested by maximum-likelihood logistic regression analysis. The adjusted-odds ratio for this association was 2·62. We estimate that more than one-quarter of pregnant women drinking twice a week or more are likely to abort, compared with about 14% among women who drink less often. Consideration of wine, beer, and spirits separately suggested that the minimum harmful dosage was one ounce of absolute alcohol. Several potentially confounding variables, including maternal age, gestation, prior spontaneous abortions, smoking, and nausea/vomiting, were controlled in the analysis. The association between drinking during pregnancy and spontaneous abortion did not vary with these factors. Even moderate consumption of alcohol during pregnancy is a risk factor for, and may be a cause of, spontaneous abortion. Among the possible mechanisms, acute fetal poisoning seems the most likely, although chronic poisoning is also

Summary

The

frequency

among 616

of

women

possible.

1. Jones KL, Smith DW, Hanson JW. The fetal alcohol syndrome: Clinical delineation. Ann New York Acad Sci 1976; 272: 130-37. 2. Classen SK, Smith DW. The fetal alcohol syndrome. N Engl J Med 1978; 3.

DRINKING DURING PREGNANCY

Smoking and alcohol abuse A comparison of their

N Engl J. Med 1978; 298: 569-71.

Introduction EPIDEMIOLOGICAL and animal studies suggest that

high alcohol intake may affect the fetus in a variety of ways. In man, heavy drinking has been associated with the fetal alcohol syndrome,2-15 minor and major malformations,16 stillbirths,t7 prematurity, 16 and low birthweight,16-19 placental weight,17 and birth length.16 Fetal breathing movements can be suppressed by moderate quantities of alcohol.20,21 Although in pregnant mice exposure to alcohol resulted in dose-related increases in malformations and resorptions,22 an effect on spontaneous abortion in man has not been shown. Neither have the effects of drinking before conception and during pregnancy been studied separately in man; nor have the effects of different doses been considered. We compared drinking habits before and during pregnancy in 616 women who aborted spontaneously (cases) and in 632 women who delivered after at least 28 weeks gestation (controls). The amount and type of alcohol, frequency of drinking, and time of exposure were considered.

177

Methods

-

Cases These comprised a consecutive series of spontaneous abortions collected in the public facilities of three Manhattan hospitals from April, 1974, to May, 1978. (Women in the private facilities were excluded from this analysis because the sample size (179) was too small to control for potentially confounding variables.) We tried to interview each woman, and to collect the abortus for pathological and karyotypic examination. 1899 women had spontaneous abortions; 80% (1514) were interviewed. The uninterviewed group comprised mainly women who refused to participate (155), or who could not be traced (117). Interviewed and uninterviewed women were similar in race, marital status, and gravidity; maternal age was slightly higher (mean 26.4 vs 25.4 years) and gestational age slightly longer (mean 92.8vs 84.1days) among the women interviewed.

Controls

Statistical Analysis The relationships between alcohol use (the independent variable), the control variables, and spontaneous abortion (the dependable variable) were examined by maximum-likelihood logistic regression -methods.24,25 This technique enables the relationships of each independent variable with the dependent as well as their interactions with each of the control variables to be tested. The parameters used in the logistic models correspond to the logarithm of the adjusted odds ratios associated with each independent variable. Goodness of fit of the logistic model can be tested by the likelihood ratio or the Pearson chi-square statistic.26

variable,

Selection of controls began towards the end of 1975, when funding for the full study was obtained and procedures to identify cases had been fully developed. At each hospital, con.trols for a consecutive series of spontaneous abortion were recruited over a 2-year period. Eligible controls registered for prenatal care before 22 weeks and delivered no earlier than 28 weeks gestation. Each control was matched to a case on two variables: age (within 2 years) at last menstrual period, and hospital. Controls were selected for 1053 cases; 909 (86%) were interviewed. Of the 144 uninterviewed controls, 109 refused participation. Interviewed and uninterviewed controls did not differ in gravidity, but differed slightly in age (mean 25.7vs 27.0years), and in ethnic and marital characteristics.

Pairs Included in the Analysis The analysis included 657 case-control pairs where both members of the pair were aged 15-40 years at last menstrual period, both consented to be interviewed, both contributed only one pregnancy each to the series, and neither used heroin or methadone. We excluded 13 pairs with a member over 40 years of age (since at this age there were too few controls to control for maternal age in the desired intervals), 121 pairs where the case was interviewed but the matched control was not, 158 pairs where the control was interviewed but the matched case was not, 41 pairs in which one of the pair was already represented by a previous pregnancy among the 657 pairs to be analysed, and 40 pairs in which one member took heroin or methadone. The 657 cases and their matched controls did not differ significantly in age at last menstrual period (mean 25.7 vs 25-6 years), language spoken at interview, marital status, ethnic group, place of birth, the level of education, current religion or occupation of either the patient or her mate. The fact that fewer cases (28%) than controls (38%) had welfare as the primary source of income probably reflects differences in payment requirements for prenatal care and for spontaneousabortion admissions.23 The interval between last menstrual period and the interview was longer among controls (131.4 days) than among cases (109.6 days). The mean length of gestation of cases at abortion was 94.6days.

Measures

drink?" Amount per day was coded in eight-ounce units for wine, in twelve-ounce units for beer, and in one ounce-units for spirits. Frequency, for the three types of beverage combined, was generally considered in five categories: never, twice a month and less, less than twice a week, 2-6 days a week, and every day. In 99%, the frequency category for the beverage drunk most often was the same as that for all beverages combined. We noted that there was no bias in the frequency distribution of alcohol consumption among those excluded from the analysis because the other member of the pair was not interviewed. The distribution was identical to that among the 657 pairs included in the study

usually

of Alcohol

Use

We asked about the frequency and amount of wine, beer, rye, scotch, vodka etc) consumed during pregnancy and before pregnancy. For each beverage, and for each phase two questions were asked: "How often do you drink?" and "When you drinkhow much do you

spirits (bourbon, gin,

Results

Frequency of drinking during pregnancy.-17 .0% of and only 8-1% of controls reported drinking twice a week or more (table I). The adjusted odds ratio was 2.62 (95% confidence limits=1.62 to 4.24). The odds ratio were adjusted for three variables. Maternal age cases

control variation in drinking habits with of age. Length gestation (at time of abortion for cases and at interview for controls) was entered to control variation in drinking habits with stage of gestation. Drinking before pregnancy was entered to control for effects of pre-conception drinking on spontaneous abortion.

was

entered

to

Dose-response Relationships.-With non-drinkers as comparison group, the adjusted odds ratio for drink-

the

TABLE .

I-FREQUENCY

(%) OF ALCOHOL CONSUMPTION AMONG

CASES AND CONTROLS

*Table excludes 7 cases and 11 controls with unknown frequencies of alcohol consumption either before or during pregnancy, 34 cases with unknown gestations at time of spontaneous abortion, and 14 controls with unknown gestations at time of interview. tEach odds ratio is computed by comparing each frequency category with the "never consumed alcohol" category. Odds ratios are conditional on a model which included three effects: (1) an interaction between maternal age (15-19, 20-29, 30-40 years), gestation (15 weeks, 16 weeks), alcohol consumption before pregnancy (never, twice a month,
178

ing daily (2-58) was higher than that for drinking twice weekly or more (2-33). The chi-square statistics for both the linear and quadratic components were significant, indicating a dose-response effect. Matched-pair analysis gave almost identical results.27

TABLE II-PERCENTAGE DRINKING TWICE A WEEK AND MORE DURING PREGNANCY WITHIN CATEGORIES OF POTENTIALLY

CONFOUNDING VARIABLES

Pre-conception and post-conception drinking.Maternal age and length of gestation were controlled by taking account of their associations with both the dependent and independent variables. Both drinking before pregnancy (X==ll-2, 4 degrees of freedom (df), p<0.025), and drinking during pregnancy (X=27-3, 4 when taken separately, showed statistidf, p<0-0001) cally significant associations with spontaneous abortion. There was substantial overlap between these two variables ; the usual drinking habits of the women influenced their drinking during pregnancy. When the overlap was controlled by entering both variables simultaneously into the log-linear model, only the association of spontaneous abortion with drinking during pregnancy remained statistically significant. Moreover, among women who drank at least twice a week before pregnancy, 62% of the 152 cases and only 35% of the 113 controls maintained that level during pregnancy (table 11). and controls

levels for differences within categories between cases were calculated in bivariate tables with Yates corrected

X2; *p<0.05,

fp<0.01, tP<0-001.

confounding variables.-A further series of was performed to see whether the asanalyses logistic

Significance

sociation between spontaneous abortion and alcohol consumption during pregnancy could be explained by other factors. Nine variables were tested: four variables (table 11)—gestational age*, smoking,28 previous spon-

Number of cases and controls (in parentheses) varies with each variable since women with an unknown value for a variable are omitted.

Possible

taneous

abortion, and

nausea

were controlled, although beer less strongly than wine and spirits. The adjusted odds ratio for wine, independent of the effects of beer and spirits, was 3.15 (95% confidence limits=1.53, 6.51); for beer, independent of the effects of wine and spirits, 1-58(95% confidence limits=1.02, 2.44); and for spirits, independent of the effects of wine and beer, 2.26 (95% confidence limits=1.13, 4.51). None of the interactions between beverages, and between beverages and maternal age,

beverages

and/or vomiting during

spontaneous abortion, and the other variables-maternal age, maternal race, pre-pregnant weight, marijuana use and caffeine use-were tested because they might explain the association between drinking and reproductive outcome. The variables were added to the analysis individually and also in

pregnancy-related

to

pairs. There were no statistically significant interactions (at p
Type of beverage.-To assess whether each beverage had an independent effect, their associations were examined both separately and together. In this logistic model, frequency of drinking for each beverage was entered as a dichotomous variable (less than twice a week vs twice a week or more). Maternal age was a control variable. Each beverage, drunk twice a week or more, was significantly associated with spontaneous abortion when other *30’c of

later after their sponinterviewed prior to delivery. Since the case was asked about drinking during pregnancy, we defined gestational age by gestation at abortion for cases and at interview for controls. The frequency of drinking twice a week or more did not vary with the length of gestation of controls at the time of interview.

taneous

cases were

interviewed 1 week

or

abortion, whereas nearly all controls

were

were _

statistically significant.

and amount.-To separate the effects of of alcohol consumed per occasion from frequency, we made an analysis of variance. We stratified frequency into six levels to control for the conflation of frequent drinking with amount: thus for each beverage, a 6 x 2 nonorthogonal analysis of variance was performed.24 Amount was estimated in ounces of absolute alcohol (allowing 0.50% for spirits; 0.125% for wine; 0.04% for beer). There was no significant difference for wine, beer, or spirits between cases and controls in the amount of alcohol consumed per occasion. There was one significant interaction-that between the amount of beer per occasion and frequency-in relation to sponIn other taneous abortion (F=2.6, df=5413; p<0.05). words, only among daily beer drinkers did cases consume significantly more absolute alcohol than controls. It is noteworthy that only in this category of beer drinkers did the mean amount of absolute alcohol per occasion exceed one ounce, a level exceeded by wine drinkers in every category and by those drinking spirits

Frequency

amount

in most categories.

179 TABLE III-MEAN ABSOLUTE ALCOHOL

CONSUMPTION(ounces) ON EACH OCCASION AND FREQUENCY OF DRINKING DURING PREGNANCY

Number of women in parentheses.

Discussion There is thus a strong association between spontaneous abortion and drinking during pregnancy, which is evident for drinking as seldom as twice a week, and becomes stronger with more frequent drinking. For wine and spirits, where the average amount drunk per occasion generally exceeds one ounce of absolute alcohol, the association is stronger than for beer, where the average amount is less than one ounce, except for daily drinkers. If we assume that cases and controls did not underreport the amount of alcohol they’consumed on each occasion, the data suggest that a mean of one ounce of absolute alcohol twice weekly is the minimum threshold for producing an abortion. We believe that drinking and spontaneous abortion are causally associated. A bias in the reporting of alcohol use, with better recall among cases than controls because of the adverse outcome, is unlikely to account for the association. If adverse outcomes induce better recall, cases with previous spontaneous abortions might be expected to be particularly attentive to events during pregnancy. No such variation was found. The analysis of the average amount of absolute alcohol taken on each occasion provides good evidence against recall bias. Cases and controls differed in the frequency with which they drank, but except for daily beer drinkers, they did not differ in the amount they drank. (A more direct test of recall bias came from analyses of the karyotype of the abortus [unknown at the time of interview to both questioner and respondent and thus not subject to bias]. We hypothesised that drinking during pregnancy raised the risk of aborting euploid conceptions. Karyotype analyses, recently completed, showed that drinking during pregnancy was associated with the abortion of euploid, and not aneuploid, conceptions.29) Under-reporting of alcohol consumption by our controls is unlikely to account for the association between spontaneous abortion and drinking during pregnancy. The proportion of heavy drinkers in our control group was only slightly lower than in other series from prenatal clinics studied in the U.S.A.6,16,30 5% of controls had a mean consumption of one ounce or more of absolute alcohol per day before pregnancy, and 1-2% during pregnancy. It is more likely that the reproductive process is highly sensitive to alcohol, and that spontaneous abortion is by far the most frequent manifestation of this sensitivity. The newborn with congenital malformations, or fetal alcohol syndrome can then be considered

rare survivors among

conceptions heavily exposed

to

alcohol. 31 We have been able to separate the effects of drinking before and during pregnancy. Although in our data drinking before pregnancy contributed no effect, it is possible that the effects of drinking during pregnancy somehow depend on drinking before pregnancy, because of the considerable overlap in women who do both. The mechanisms in spontaneous abortion may or may not be the same as those that underlie the reported associations of chronic alcoholism with fetal alcohol syndrome and congenital malformations, and of daily drinking with decreased birthweight. Unlike these associations, the effect seen here is not confined to either chronic alcoholism or to daily drinking. Drinking during pregnancy could bring about spontaneous abortion by acting as a teratogen, abortifacient, or fetotoxin, of which the latter seems the most likely. If teratogenesis was the primary mechanism, alcohol drinking would be most strongly associated with abortions early in gestation, the time when most malformations occur. In fact the association was unrelated to gestation at abortion (table 11), and mean gestational age did not vary among cases, whether they never drank (92.5 days), drank less than twice a week (96-4 days), or drank twice a week or more (95-1 days). The pathological data which describe the abortuses in this series should show whether alcohol is teratogenic or not. If alcohol was mainly an abortifacient, which caused premature labour, then spontaneous abortions might be expected to occur shortly after episodes of drinking. This seems unlikely since no such coincidence in timing has previously been noted. On estimates from our data, at least a quarter of pregnant women who drink twice a week or more will have a spontaneous abortion, half which will relate to alcohol. (In making this estimate we assumed the following: 15% of all conceptions end in spontaneous abortion; 17% of women experiencing spontaneous abortion drink twice a week or more [as in our sample]; and that the odds ratio for the association of drinking with abortion is 2.62. Under these assumptions we estimate a 13-6% abortion rate among women drinking less than twice a week and a 29.3% abortion rate

among

women

drinking more frequently.) However,

rule out the possibility that a heavy dose of alcohol may sometimes induce labour. If alcohol was mainly a chronic fetotoxin gradually causing a cumulative effect in the fetus such as retarded we cannot

180

frequency of drinking could be a good indiunequivocally that frequency of drinking is consistently associated with spontaneous abortion provided that an average of

growth,

the

cator, of the process. Our results show

least one ounce of absolute alcohol is consumed per occasion. If the effect was due to chronic exposure, however, we would also expect more frequent drinking among women who have spontaneous abortion early in gestation, so that the necessary dose could be accumulated. The data do not support this prediction. If alcohol was mainly an acute fetotoxin and the fetus was at risk of death at each exposure, then provided the actual intake of alcohol on any occasion varied randomly during the observed gestation period and fetal susceptibility did not, the risk of abortion would rise with frequency of drinking; this is compatible with our results. Furthermore, one moderate dose of alcohol (e.g., one ounce of vodka) late in gestation seems to suppress fetal respiratory movements observed by ultrasonography.2o,21 Unlike an abortifacient mechanism, abortion need not follow fetal death immediately; studies of spontaneous abortion suggest that there may be an interval of several weeks before expulsion of a dead fetus.32 Our results imply that alcohol causes spontaneous abortion by acting as a fetal poison, most likely acute, and that the developing fetus is highly sensitive to alcohol throughout the first and second trimesters. Drinking as little as twice a week, above a minimum dosage of one ounce of absolute alcohol, is probably enough to endanger the fetus. at

We thank Dr Frank Seixas for his advice; Mr A. Mark, Ms M. Topal, and Mr R. Cautin for programming and data processing; Ms Callery, Ms Jozak, Ms Kornhauser, Ms Lambert, and Ms Silverstein, who performed the fieldwork; and Prof. R. Vande Wiele, Dr R. Neuwirth, Dr T. F. Dillon, and Dr A. Risk and their colleagues for facilitating our work on their services. This work was supported by grants from the New York State Department of Mental Hygiene and by grants (5ROI-HD-08838 and 5T32-HD07040) from the National Institute of Health. Reprint requests should be addressed to J. K., Sergievsky Center, Columbia University, 630 West 168th Street, New York, New York 10032. REFERENCES 1. Strobino BR, Kline J, Stein Z. Chemical and physicial exposures of parents: Effects on human reproduction and offspring. Early Human Development

1978; 1: 371-99. P, Harousseau H, Borteyru JP,

2. Lemoine

et

al. Les enfants des parents alcoo-

liques: anomalies observées. Quest Médicale 21: 476-482, 1968. 3. Jones KL, Smith DW: Recognition of the fetal alcohol syndrome fancy. Lancet 1973; ii. 999-1001.

in

early

Jones KL, Smith DL, Ulleland CN,

weight. Am J Public Health 1977; 67:1154-56. 20. Fox

HE, Steinbrecher M, Pessel D, et al. Maternal ethanol ingestion and the of human fetal breathing movements. Am J Obstet 1978; 132:

occurrence

354-58. 21. Lewis PJ, Boylan P. Alcohol and fetal breathing. Lancet 1979; i: 338. 22. Randall CL, Taylor WJ, Walker DW. Ethanol induced malformations in mice. Alcoholism: Clin Exp Res 1977; 1(3): 219-24. 23. Kline J. Shrout P, Stem Z, et al. II. An epidemiological study of the role of gravidity in spontaneous abortion. Early Human Development 1978; 1: 345-56. 24. Bock RD. Multivariate analysis of qualitative data. Multivariate Statistical Methods in Behavioral Research. New York: McGraw-Hill, 1975. 25. Fienberg SE. The Analysis of Cross-Classified Categorical Data, Cambridge: MIT Press, 1977. 26. Bishop YMM, Fienberg SE, Holland PW. Discrete Multivariate Analysis: Theory and Practice. Cambridge: MIT Press, 1975. 27. Holford TR, White C, Kelsey JL: Multivariate analysis for matched casecontrol studies. Am J Epidemiol 1978; 107: 245-56. 28. Kline J, Stein ZA, Susser M, et al. Smoking: a risk factor for spontaneous abortion. N Engl J Med 1977; 297: 793-96. 29. Kline J, Stein Z, Susser M, Warburton D. Environmental influences on early reproductive loss in a current New York City Study. Human embryonic and fetal death. In: Porter IH, Hook EB, eds. Academic Press: New York, 1980 (in press). 30. Kusma JW, Phillips RL. Characteristics of drinking and non-drinking mothers. Paper presented at National Council on Alcoholism Meetings, Washington DC, May, 1976. 31. Stein ZA, Susser M, Warburton D, et al. Spontaneous abortion as a screening device: The effect of fetal survival on the incidence of birth defects.

Am J Epidemiol 1975; 102: 275-90. 32. Boulé J, Boulé A. Anomalies chromosomiques dans les avortements spontanes. In: Boulé A. Thibault C, eds Les Accidents Chromosomiques de la Reproduction. Paris: INSERM, 1973:29-55.

Preliminary

Communications

PROPRANOLOL—A MEDICAL TREATMENT FOR PORTAL HYPERTENSION?

DIDIER LEBREC MICHÈLE CORBIC

OLIVIER NOUEL

JEAN-PIERRE BENHAMOU Unité de Recherches de Physiopathologie Hépatique (INSERM), Hôpital Beaujon, 92118 Clichy, France

in-

al. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1973; i. 1267-71. 5. Jones KL, Smith DW, Streissguth AP, et al. Outcome in offspring of chronic alcoholic women Lancet 1974, i: 1076-78. 6. Mulvihill JJ, Klimas JT, Stokes DC, et al Fetal alcohol syndrome: Seven new cases. Am J Obstet Gynecol 1976; 125: 937-44. 7. Hanson JW, Streissguth AP, Smith DW. The effects of moderate alcohol consumption during pregnancy on fetal growth and morphogenesis. J

4.

15. Fabro SE. The Fabro Report; Alcoholic beverage consumption and outcome of pregnancy. In: The Fetal Alcohol Syndrome Public Awareness Campaign Progress Report. Department of the Treasury and Bureau of Alcohol, Tobacco and Firearms, February, 1979. 16. Ouellette EM, Rossett HL, Rosman NP, et al. Adverse effects on offspring of maternal alcohol abuse during pregnancy. N Engl J Med 1977; 297: 628-30. 17. Kaminski M, Rumeau C, Schwartz D. Alcohol consumption in pregnant women and the outcome of pregnancy. Alcoholism: Clin Exp Res 1978; 2: 155-63. 18. Russell M. Intrauterine growth in infants born to women with alcoholrelated psychiatric diagnoses. Alcoholism: Clin Exp Res 1977; 1: 225-31. 19. Little RE. Moderate alcohol use during pregnancy and decreased infant birth

et

Pediatr 1978, 92 (3): 457-60. 8. Majewski F, Bierich JR, Loser H. Zur Klinik und Pathogenese der AlkoholEmbryopathie. Munch med Wschr 1976; 188 (50): 1635-42. 9. Clarren SK, Alvord EC, Sumi SM, et al. Brain malformations related to prenatal exposure to ethanol. J Pediatr 1978; 92: 63-67. 10. Streissguth AP, Martion DC, Buffington VE. Test-retest reliability of three scales derived from quantity-frequency-variability assessment of selfreported alcohol consumption. Ann N Y Acad Sci 1976; 273: 458-66. 11. Streissguth AP, Herman CS, Smith DW. Intelligence, behavior, and dysmorphogenesis in the fetal alcoholism syndrome: A report on 20 patients. J Pediatr 1978; 92 (3) : 363-67. 12. Kessel N. The fetal alcohol syndrome from the public health standpoint. Health Trends 1977; 9: 86-89. 13. Warren KR, ed. Critical review of the fetal alcohol syndrome. National Institute on Alcohol Abuse and Alcoholism, 1977. 14. Clarren SK, Smith DW. The fetal alcohol syndrome. N Engl J Med 1978; 298:1063-67.

Summary

Continuous, oral administration of pro-

pranolol at doses which reduced the heart-rate by 25% produced a sustained decrease in portal venous pressure in cirrhotic patients with portal hypertension. This effect of propranolol might be useful in preventing recurrent bleeding due to ruptured œsophageal varices in patients with portal hypertension. INTRODUCTION

SURGICAL portal-systemic shunting is used to obtain a permanent decrease in portal venous pressure in patients with portal hypertension. Vasopressin and somatostatin, which require intravenous administration and have a short biological life, induce only transient decrease in portal venous pressure.1,2 We investigated the effect on portal venous pressure of continuous, oral administration of propranolol in cirrhotic patients with portal

hypertension.