0892-0362/92 SS.00 + .OO

Neurotoxicolo~ and Teratologv. Vol. 14, pp. 407-414, 1992 Printedin the U.S.A. All rightireserved.

Copyright0 1992PergamonPressLtd.

The Effects of Prenatal Tobacco and Marijuana Use on Offspring Growth From Birth Through 3 Years of Age N. DAY,*’

M. CORNELIUS,* L. GOLDSCHMIDTt G. RICHARDSON,* N. ROBLESt AND P. TAYLOR*

*Deparfmenf of Psychiatry, Universityof Piffsburgh School of Medicine, Pittsburgh, PA t Western Psychiatric Institute and Clinic, Universityof Pittsburgh School of Medicine, 3811 O’Hara Street, Pittsburgh, PA 15213-2593 SPediafricsand Obsfefrics and Gynecology, Magee Womens Hospital, Universityof Pitfsburgh School of Medicine, Pittsburgh, PA Received 15 November

1991; Accepted 5 August 1992

DAY, N., M. CORNBLIUS, L. GOLDSCHMIDT, G. RICHARDSON. N. ROBLES AND P. TAYLOR. The #fecLs of prenatal tobacco and marzjuana use on offspring growth from birth through 3 years of age. NBUROTOXICOL TERATOL M(6) 407-414, 1992.-This is a prospective study of prenatal substance use. Women were interviewed during their fourth and seventh months of pregnancy, at delivery, and at 8, 18, and 36 months postpartum. At birth, there were 763 liveborn. singleton offspring in the sample. At each phase. the offspring were examined and measured for growth. Data are presented on the relationship between tobacco and marijuana use and the size of the offspring at birth, 8, 18, and 36 months of age. At birth, there was a significant inverse relationship between tobacco use and weight, length. and head circumference. At 8 months of age, only length continued to be associated with prenatal tobacco exposure. By 18 months of age, there was no relationship between prenatal tobacco exposure and size of the offspring. Prenatal marijuana exposure was only associated with decreased length at birth. Neither tobacco nor marijuana use predicted gestational age or morphological abnormalities. Tobacco

Marijuana

Pregnancy

Growth

Morphology

ing during pregnancy was significantly correlated with low birth weight among nonsmoking women and estimated that, on average, full-term newborns exposed to passive smoke were 24 g lighter. However, passive smoking did not significantly affect the birthweight of children of smoking women. In contrast to the data on the effects of tobacco use on neonatal growth, reports on the effects of prenatal exposure to marijuana on birth size are conflicting. Although most studies have not reported a relationship between growth de% ciencies and prenatal exposure (9,23), some have (15.30). An earlier report from this study found that there was a correlation between exposure during the Fist two months of pregnancy and decreased length at birth (4). These findings are reassessed in this analysis with a larger cohort. There was also an unexpected relationship between exposure during the third trimester and increased birth weight. Follow-up studies of marijuana-exposed offspring are rare. Fried and Watkinson (10) found that prenatal marijuana use was associated with an increase in weight at 12 months and

MATERNAL tobacco use during pregnancy has been associated with growth retardation in the offspring (13,20). Biweight decreases in direct proportion to the number of cigarettes smoked (25,29) and on average, smokers’ babies are 150 to 250 g lighter than the offspring of nonsmokers (28). The longer-term effects of prenatal tobacco exposure on the offspring are not as clear. Naeye (23). analyzing data from the Collaborative Perinatal Project, detected a very small difference in height and head circumference in exposed offspring at age 7. Rantakallio (26) found that exposed offspring were shorter at age 14 and Fogehnan and Manor (8) reported decreased height at ages 7, 11, and 23. In the latter study, the differences in height at age 23 were mediated by biihweight. Others have found no growth retardation longitudinally (7, 9,12). The fetus and the subsequent offspring of even nonsmoking mothers can also be exposed to tobacco through passive exposure or the presence of tobacco within the environment. Martin and Bracken (22) found that passive exposure to smok-

’ Requests for reprints should be addressed to Nancy L. Day, Ph.D., Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213-2593. 407

408

DAY ET AL.

height at 24 months. However, other studies reported either no effect of fetal exposure on height and weight at 12 months of age (27) or a decrease in length at 8 months with no change in weight or head circumference (2). Only recently have reports of the effect of tobacco use adjusted for alcohol exposure during pregnancy, and few of the studies have controlled for the exposure to illicit drugs. In the few studies that have looked at alcohol, tobacco and illicit drugs, however, there have been reports of interactions. Haste et al. (14), for example, found that the combination of tobacco and alcohol resulted in smaller offspring than either separately. Similar findings were reported by Olson et al. (24). Fried and O'Connell (9) reported that marijuana use offset the negative effects of tobacco on birthweight. Therefore, it is essential to consider the effects of polydrug exposure in the assessment of the effects of either tobacco or marijuana. This study assesses the effects of prenatal tobacco and marijuana use on the offspring at birth and ages 8, 18, and 36 months. Outcomes include growth, gestational age, morphological abnormalities, and mortality. METHOD

Sample Selection and Study Design A random sample of women who attended an outpatient prenatal clinic was interviewed when the women came in for their fourth prenatal month appointment. All subjects were at least 18 years of age. The initial refusal rate was 15070, resulting in a screening sample of 1360 women who were interviewed at Time 1. From the initial sample of 1360, two separate cohorts were selected using stratified sampling. In the first cohort, any woman who reported having drunk alcohol at the rate of three or more drinks a week during the first trimester, and the next woman who drank less than this amount were selected for the study. A second cohort was selected in the same manner by taking all women who reported marijuana use at the rate of two or more joints per month and again the next woman interviewed who used less than this amount. The sampling for both cohorts was done with replacement, so that women could be in either or both cohorts depending on their patterns of substance use. These two study cohorts have been combined for this analysis to be able to evaluate all of the tobacco-using women. Given the sampling scheme, all marijuana users who used ~ 2 joints per month were already in the marijuana cohort, so combining the two samples did not increase the number of heavier marijuana users. The combined sample (n = 829) did not significantly differ in demographic characteristics from either of the individual cohorts. The women were interviewed again at the seventh month of pregnancy. At delivery, the women were interviewed and their offspring were examined. Follow-ups were at 8, 18, and 36 months of age; children and their mothers are currently being seen at 6 years. At each follow-up, the mothers were interviewed with a standardized instrument that assessed marijuana and other illicit drug use, tobacco, alcohol use, life style, current environment, medical history, and demographic status. During pregnancy, data were collected for the preceding trimester and each postpartum interview covered the time from the last study interview. Intake for the study was between 1982 and 1985. Sample Characteristics At birth, 763 live singleton offspring were examined, a completion rate of 97070. In the original sample of 829 preg-

nancies, there were 18 deaths, 8 refusals, 16 women were missed, 21 moved out of the region, 1 baby was placed for adoption, and 2 pregnancies resulted in twins. At 8 months postpartum, we examined 81070 of the eligible birth cohort of 763 infants and at 18 months we assessed 90% of the eligible mother-child dyads from the birth cohort. At 36 months, the completion rate was 95°]0 of those who were eligible for assessment. Subjects were ineligible if the child died or was placed for adoption, if they moved more than 150 miles away, or if the mother refused two successive study phases. There were no significant differences in demographic characteristics or in the patterns of substance use during pregnancy between the women who were interviewed at each phase compared to those who were not. These women were selected from an outpatient prenatal clinic and were healthy and generally of lower social status. Overall, 74°70 of the women had finished high school and 60070 had incomes of less than $400 per month. The sample was evenly divided between black and white women reflecting the composition of the clinic population. Ages ranged from 18 to 42 years with a mean of 23. Most of the subjects were single (67070) and 32070were primigravidas. During the first trimester, 40.3% of the women reported marijuana use, 54.3070 were tobacco users, 64.5070 reported alcohol use, and 11070reported use of illicit drugs other than marijuana. By the third trimester, 17.807o of the women used marijuana, 52.60]0 tobacco, 31.8070 alcohol, and only 1.3070 of the sample reported other illicit drug use. The average birthweight of the offspring was 3198 g; 10.2070 were low birth weight (_< 2500 g). The rate of prematurity ( < 37 weeks gestation) was 8.5070 and 13.6070 of the infants were small-for-gestational age (SGA; < 10th percentile for growth). Only 1.6070of the infants had major anomalies; 5.1 070 of the offspring had more than one minor physical anomaly. At 8 months of age, the children weighed on average, 8.9 kg, and at 18 and 36 months, they weighed 11.6 and 14.8 kg, respectively.

Measurement o f Substance Use Tobacco use. Tobacco use was measured at each study point. Pattern of smoking was described for both current and ex-smokers by the number of cigarettes used dally. In the questionnaire, use was categorized as: occasional (less than dally), less than half a pack, half a pack but less than 1 pack per day, 1 pack but less than 2 packs per day, 2 but less than 3 packs per day, and 3 or more packs per day. In the regression analyses, the mean of the category was used to estimate the average number of cigarettes smoked per day. Cigarette use was categorized into four categories for descriptive purposes: (a) nonsmoker, did not smoke at time of interview, (b) light smoker, smoked occasionally but less than half a pack per day, (c) moderate smoker, one half to less than 1 pack per day, and (d) heavy smoker, at least 1 pack per day. Marijuana use. The marijuana questions have been described in detail elsewhere (6). Usual quantity and frequency, minimum and maximum quantity, and frequency were obtained for marijuana use at each time point. Marijuana use was expressed as average daily joints (ADJ). Hashish and sensemiUa were calculated into the marijuana use score. Hashish use was given the equivalence of 3 joints of marijuana and sensemilla was counted as 2 joints. These estimates were made based on the relative amounts of A-9-THC in each of the compounds ( 11,16,19). The rate of marijuana use was calculated for each month

TOBACCO AND M A R I J U A N A USE A N D OFFSPRING G R O W T H o f the first trimester and was measured retrospectively over the whole trimester for the second and third trimesters. For subsequent study phases, recall was from the time since last study interview. Other substance use. Alcohol use was measured in the same way as marijuana use, with information on the usual, maximum and minimum quantity and frequency. Use of illicit drugs other than marijuana was ascertained for each individuai drug in terms of quantity, frequency, amount, and mode of use. For these analyses, however, illicit drug use was dichotomized to reflect any use/no use.

Pediatric Assessments At each study point, children were examined by study pediatric nurse clinicians who were trained to reliability with each other and with the study pediatrician and who were blind to maternal substance use. Growth and morphology were assessed and a physical exam and medical history were completed at each phase. Reports of hearing, vision, and speech problems were noted. Minor physical abnormalities (MPAs) were also assessed at each study visit. Gestationai age was estimated by the nurse clinician using the Dubowitz exam (1). Ponderai index was calculated as the ratio of birthweight (g) x 100/birth length 3 (cm). An infant was defined as SGA if his/her birthweight was less than the tenth percentile for gestational age (3).

Statistical Methods Data analyses used stepwise and logistic regression. Analysis o f covariance (ANCOVA) was used to illustrate findings in the tables. Covariates were maternal age, education, gravidity, marital status, work status, income, race, life events, social support, depression and anxiety, weight gained during pregnancy, maternal height, and use of alcohol and illicit drugs other than marijuana. Several variables were dichotomized: work status (work or school/neither), race (White/ non-White), illicit drug use other than marijuana (any use during the trimester/none). In the analysis of the effects of cigarette smoking, we controlled for alcohol, marijuana, and other drug use in the corresponding time period and for use of each of the substances, including tobacco, currently. All analyses of the effects of marijuana were controlled for other substance use during the target study phase and current substance use including marijuana. A stepwise linear regression model was used to assess the dose-response relationship between tobacco or marijuana use and the outcome measures. Outcomes were run separately,

409

and included weight, length, head, and chest circumference. Log transformations o f tobacco and marijuana use were used for the regression analyses. T h e outcome measures SGA, LBW, and MPA's (dichotomized at > 3 / < 3) were analyzed with logistic regressions. To test for interactions between the effects of tobacco, marijuana, and alcohol, we used two statistical techniques. In the first, we entered interaction terms into the regression models to test for a potentiation of effects. As a second step, we compared selected contrasts. The contrasts selected were high tobacco use and high alcohol use compared to high tobacco use and no alcohol use; high tobacco use and high marijuana use compared to high tobacco use and no marijuana use. High tobacco use was defined as 1 or more packs per day, high alcohol use was an average daily volume of 1 or more drinks, and high marijuana use was an average use of 1 or more joints per day. The contrast comparison was done by ANCOVA with significant covariates entered. These analyses were conducted only when there were significant main effects. A test for parallelism of the regression equation between the two racial groups (Black/White) was conducted. Although the regression lines did not coincide, the slopes did not differ significantly. The regressions were also run separately by race. The relationships between predictor and outcome variables did not vary between racial groups. Thus, although Black infants were smaller than White infants, the relationships between the predictor and outcome variables were similar for each race. RESULTS

Demographic Predictors o f Tobacco and Marijuana Use During Pregnancy Tobacco. Tobacco was used by a majority of this population. Fifty-four percent of the women reported tobacco use in the first trimester and this rate remained relatively stable throughout pregnancy (Table 1). Between the first and third trimester, the proportion of light smokers dropped from 20.5070 to 15.9070, while the proportion of heavy smokers increased from 15.2070 to 18.5°70. Tobacco use increased to 62.6070 by the eighth postpartum month and was relatively constant at 61.5070 at three years. More women smoked after the birth of the target offspring and those who had smoked previously smoked more heavily. Women who smoked tobacco were significantly more likely to be White (Table 2). The heavy smokers were significantly less likely to have a high school education, although they were

TABLE 1 TOBACCO USE AT EACH STUDY PHASE (~a REPORTING USE) Trimesterof Pregnancy TobaccoUse

First

Second

Third

8 Months

18 Months

36 Months

None* Lightt Moderate~ Heavy§ N

45.7 20.5 18.6 15.2 763

47.3 19.5 16.8 16.5 692

47.4 15.9 18.2 18.5 763

37.4 16.2 19.6 26.9 591

37.8 16.4 17.4 28.4 645

38.4 14.4 18.3 29.0 662

*None: no use during the time period, tLight: less than ½ pack/day. ~/Moderate: > ½ but < 1 pack/day. §Heavy: >_ 1 pack/day; N = sample size.

410

DAY ET AL. TABLE 2 CHARACTERISTICSOF NON-TOBACCOUSERS AND HEAVY TOBACCOUSERS DURING THE FIRST AND THIRD TRIMESTERS First Trimester

Demographic Age (mean) Marital status (e/s married) Race (e/o white) Education (e/s ~ 12 years) Income (e/e ~- $400/month) Primigravida (%) Drug use Alcohol (drinks/day) Marijuana (joints/day) Other illicit drugs (e/e)

ThirdTrimester

None n = 349

Heavy n = 116

None n = 362

Heavy n = 141

22.8 34.4 40.4 81.1 39.3 36.1

23.7 40.5 78.4t 58.6t 45.6 24.1"

22.8 36.2 42.3 81.2 39.2 38.1

23.3 41.1 80.1t 57.4t 44.5 43.8'

.26 .27 4.6

1.09"* .44* 22.4**

.08 .09 .3

.11 .18 3.5

*p = 0.05. tp < 0.005. Statistical significance is determined by Chi-square and t tests.

slightly better off in terms of monthly income. Neither age nor gravidity were significantly different by smoking category. Women who increased their smoking during pregnancy were less likely to be married and had less education. Tobacco users were also much more likely to use other substances (Table 2). At Time 1, the fourth prenatal month, nearly a quarter of the heavy smokers reported illicit drug use other than marijuana, compared to only 4.6re of the nonsmokers. Similarly, at Time 1, the mean number of drinks/ day was four times higher among the heavy smokers compared to the nonsmokers. For both alcohol and illicit drugs other than marijuana, the relationship was linear; there was a direct relationship between the amount of tobacco use and the amount of alcohol or illicit drug use. Women who smoked tobacco compared to non-tobacco users, were twice as likely to use marijuana. However, the relationship was not linear; moderate tobacco users were more likely than heavy tobacco users to use marijuana heavily. Tobacco use between each of the trimesters of pregnancy was highly correlated. Because of this, it was not possible in this data set to assess the separate effects of smoking during each of the trimesters. Marijuana. Marijuana use followed a much different pat-

tern than tobacco use during pregnancy. Marijuana use decreased from 40.3% in the first trimester to 17.8% in the third trimester (Table 3). By the eighth postpartum month, marijuana use had increased to 39.3% and by 36 months, the rate of marijuana use in the study population was 35.1%. Hashish and sensemilla use were rare. Ten women reported sensemilla use during the first trimester, 6 during the second and 4 during the third. Three women used hashish during the first trimester and there was one report during each of the other two trimesters. At follow-up, sensemilla use was more common with use reported by 6re, 10re, and 7% of the mothers at 8, 18, and 36 month follow-ups, respectively. Hashish use was reported by 2, 4, and 8 women at the 8, 18, and 36 month follow-ups, respectively. Women who reported marijuana use during the first trimester were significantly more likely to be single and Black (Table 4). Marijuana users had significantly higher rates of tobacco use compared to non-marijuana users. Women who used marijuana were significantly more likely to use other illicit drugs compared to non-marijuana users (16% vs. 7re) and had a significantly higher mean rate of alcohol use (0.9 vs. 0.4 drinks/day). During the third trimester, marijuana users were significantly more likely to be tobacco users and to

TABLE 3 MARIJUANA USE AT EACH STUDY PHASE (~0 REPORTINGUSE) Trimesterof Pregnancy MarijuanaUse

First

Second

Third

8 Months

18Months

36 Months

None* Lightt Moderate~ Heavy§ Any use N

59.7 19.2 7.6 13.5 40.3 761

78.3 13.2 3.5 5.1 21.7 692

82.2 9.7 3.3 4.8 17.8 763

60.7 18.6 6.9 13.7 39.3 591

62.9 20.6 6.5 9.9 37.1 645

64.9 20.4 5.9 8.8 35.1 661

*None: no use during the time period, tLight: > 0 and ~ 0.4 joints/day. ~Moderate: > 0.4 joints/ day and < 1 joint/day. §Heavy: ~ 1 joint/day.

TOBACCO AND MARIJUANA USE AND OFFSPRING GROWTH

411

TABLE 4 CHARACTERISTICSOF NON-MARIJUANAUSERS AND HEAVY MARIJUANAUSERS DURING THE FIRST AND THIRD TRIMESTERS First Trimester

Demographic Age (mean) % Married e/e White Education (We ~ 12 years) Income (We ~ $400/month) Primigravida (%) Drug use Alcohol (drinks/day) Tobacco (cigarettes/day) Other illicit drugs (%)

ThirdTrimester

None n = 454

Heavy n = 307

None n = 627

Heavy n = 136

23.2 38,5 55.1 75.6 42.4 32.4

22.8 24.4t 38.8t 72.3 32.8* 31.6

23.0 37.0 51.4 43.0 40.9 32.9

23.1 26.5* 34.5t 47.0 26.7t 28.7

.4 7.6 7.5

.9* 9.4* 15.9'*

.1 8.8 1.0

.3* 11.0" 3.0

*p < 0.05. tP < 0.005. Statistical significance is determined by Chi-square and t tests.

drink alcohol. At 36 months postpartum, 21% of the current marijuana users reported illicit drug use compared to 7% of the non-marijuana users. Twice as many marijuana users used alcohol and tobacco compared to women who did not use marijuana at 36 months and the current marijuana users were more likely to use each substance heavily.

Effects of Prenatal Tobacco and Marijuana Use on the Offspring at Birth Growth. There was a highly significant relationship between tobacco use during pregnancy and measurements of the infant at birth. The ANCOVA illustrates the differences in the adjusted means of the growth parameters between the extreme smoking categories for weight, length, head, and chest circumference. Compared to nonsmokers, women who smoked an average of 1 or more packs of cigarettes per day in the third trimester had infants who weighed 204 g less at birth, were 10 mm shorter, and whose head circumference was 4 ram less (Table 5)~ Ponderal index did not differ between the tobacco exposure groups. Gestational age also was not significantly affected by prenatal tobacco exposure. Stepwise multiple regression analyses on each of the growth parameters demonstrated that maternal smoking was a consistent and significant predictor of lower birthweight, shorter birth length, and smaller head and chest circumference. This effect held for each trimester of pregnancy. Because there was such a high correlation between smoking from one trimester to the next r > 0.9), we did not test for the separate effects of smoking during any one trimester independent of use during other trimesters. Maternal smoking in the third trimester accounted for 4% of the variance for birthweight, 3% of the variance for birth length and chest circumference, and 1% of the variance for head circumference. A stepwise logistic regression was performed to determine the effect of tobacco exposure during each trimester on the risk of fetal growth retardation. Tobacco smoking was a significant predictor of having an infant that was SGA. The relative risk of having an SGA baby was 2.03 for women who smoked 1 pack or more per day in the third trimester compared to women who were nonsmokers.

The results for the effect of marijuana on growth at birth have been presented elsewhere for the marijuana cohort (4). The analyses in this article that used the combined data sets do not differ from the earlier report. As reported earlier, there were no significant effects of marijuana use during any trimester on the birthweight, head or chest circumference of the offspring. We did f'md that women who smoked marijuana during the first trimester at the rate of 1 or more joints per day had infants that were shorter by 1.5 mm compared to the offspring of non-marijuana users. The ponderal index was also significantly different, reflecting the asymmetry of growth. There was no significant effect of marijuana use on gestational age, nor were the infants more likely to be SGA. Morphology. For both tobacco and marijuana, there were no effects on the number of minor or major physical anomalies at birth.

TABLE 5 GROWTH AT BIRTH AND EIGHT MONTHS BY THIRD TRIMESTERTOBACCO USE Birth

8Monks

Outcome

None*

Heavyt

None

Heavy

Weight (g) Length (mm) Head circumference (mm) Ponderal index Gestational age (Dubowitz)

3320 497

3116"* 487**

9001 725

8813 715~/

343 2.7

339§ 2.7

453 2.4

452 2.4

39.8

40.0

-

--

Adjusted for maternal age, education, gravidity, marital status, work status, income, race, weight gain during pregnancy, maternal height, alcohol, marijuana, illicit drugs, gestational age. *No use during the third trimester, t ~e 1 pack/day. ~Significantat < 0.03. §Significantat < 0.001. ]lStatisticaltest was ANCOVA.

412

DAY ET AL.

Effects of Tobacco and Marijuana Use at Follow-up Growth. At 8 months of age, in the regression analyses, length was significantly predicted by prenatal tobacco exposure during each trimester o f pregnancy, but prenatal tobacco exposure no longer had a significant effect on weight, head, or chest circumference. This is illustrated in Table 5 using ANCOVA. At 18 and 36 months of age, tobacco use during pregnancy was not significantly associated with any growth parameter. In parallel with other analyses that we have done, we included measures of current substance use in the regression model for each postpartum study phase. The relationships between prenatal tobacco use and outcome became unstable, and the tolerance became very low due to the high correlations between prenatal and postpartum tobacco use. Therefore, it was not possible to separate the effects o f prenatal tobacco use from the effects of current tobacco exposure. This was not a problem with marijuana use and we were able to assess the effects of prenatal use while controlling for current exposure to the infant. By 8 months o f age, the previously reported relationship between first trimester marijuana use and infant length (4) was no longer significant. Current maternal marijuana use at 8 months postpartum was significantly and positively associated with head circumference at 8 months in the infant. There were no other significant relationships between prenatal or current marijuana use and growth at any o f the follow-up phases. We assessed interactions between substances in two ways. One was by introducing an interaction term into the regression and the second was a series of planned contrasts. None of the interaction terms was significant nor were any of the planned contrasts. However, both at birth and at 8 months, although the findings were not significant, the offspring who were exposed to high tobacco (1 or more packs per day) and high marijuana use (l or more joints per day), were longer in length than those infants who were exposed to high tobacco use but not to high marijuana use. This relationship was consistent for exposure during each trimester of pregnancy. In comparison, the offspring who were exposed to alcohol and tobacco were consistently, though not significantly, smaller than infants who were exposed to either tobacco or alcohol. Mortality. There were 10 fetal deaths among pregnancies that were 28 weeks or greater; 8 of these were to women who smoked tobacco throughout pregnancy. Marijuana was used by 5 of these women in the first trimester and 2 during the third trimester. Alcohol use was reported by 6 and 2 of the 10 for the first and third trimesters, respectively. There were 3 deaths from sudden infant death syndrome (SIDS) in the cohort. The mothers of these three infants all smoked heavily throughout pregnancy. One mother reported heavy alcohol use and light marijuana use during the first trimester, one reported light alcohol use throughout pregnancy and the third reported neither marijuana nor alcohol use during pregnancy. DISCUSSION

These analyses have demonstrated that, after controlling for other substance use, there is a significant relationship between prenatal tobacco exposure during each trimester of pregnancy and infant size at birth. Decreased birthweight, length, and head circumference were all significantly associated with tobacco use. In addition, there was a significant relationship between tobacco exposure and the risk of being

SGA. There was no effect of tobacco use on either gestational age or morphological abnormalities. These findings are consistent with reports in the literature (13,20,25,29) and the decrease in birthweight is within the range of most other reports (28). The marked initial effects of tobacco exposure had largely disappeared by 8 months when exposed infants were still shorter in length but not in any other growth parameter. By 18 and 36 months of age, there were no significant differences in growth parameters related to tobacco exposure. These findings agree with some reports in the literature (7,9,12) but differ from others (8,26). One reason for this may be that we were able to control for the effects of prenatal alcohol exposure and other factors in the environment that are known to affect the growth of infants and children. Few of the studies that demonstrated a long-term effect o f tobacco exposure controlled for such variables. The finding o f a tobacco effect at 8 months must be interpreted with some caution. Because of the high rates of multicollinearity between prenatal tobacco use and current tobacco use at each phase of the study, it is not possible to determine whether the relationships noted at follow-up are associated with prenatal exposure or whether they reflect the effect of continuing exposure within the household. In this sample, because tobacco use is so highly correlated at each time point, this cannot be separated. Given this high rate of confounding, studies that attribute long-term growth deficits to prenatal exposure may be assigning the effect incorrectly and conversely, studies that detect an effect of passive exposure after birth must consider the effects of prenatal exposure. Marijuana use, as we have reported earlier, had no effect on growth at birth, with the exception of a significant relationship between use during the early part of pregnancy and decreased length (4). This effect had disappeared by the 8th month and no other significant relationships between prenatal marijuana use and growth retardation were found. There were also no significant relationships between marijuana exposure and gestational age, the risk of being SGA, or MPAs. There were also no significant two-way interactions between marijuana, tobacco, and alcohol, indicating that polydrug use did not have a significant multiplicative effect. We have reported the findings for the contrasts, even though they were not significant because they are consistent with other reports in the literature. Fried and O'Connell (9) noted earlier that marijuana seemed to offset the negative effects of tobacco use on birthweight. We found the same relationship in our study for length at birth and at 8 months, although it was not statistically significant. Similarly, in the present study, the effects of alcohol and tobacco seemed to be cumulative and doubly exposed infants were consistently smaller, although not significantly so. One of the problems with an interview study such as this is the correct ascertainment of both use and exposure. This study of women who attended an outpatient prenatal clinic reflects the pattern of substance use in a low-income urban population. In the initial representative sample o f 1,360 women from which the study cohorts were selected, we found that 48% of the women used tobacco during the first trimester and 31% reported using marijuana. These findings are slightly higher than the annual prevalence rates of 38% for tobacco use and 28% for marijuana use that are reported for women between the ages of 19 and 30 by the Monitoring the Future Project (18) and reflect the higher rates of use in a lower income population. It is also the case that the amount of A-9-THC in street marijuana has increased over time, so the current dose

TOBACCO AND MARIJUANA USE AND OFFSPRING GROWTH may be greater than the exposure during the time period 19821985 when these data were collected (17). However, given that we have used a linear model for our analyses, thisq:hange in strength should not affect the reported relationships but would affect any estimates of the effects by the number of joints smoked. These women were also exposed to passive smoke prenatally, which may also affect growth of the fetus. Martin and Bracken (22) reported that the passive smoke was only detectable, in their sample, among the offspring of nonsmokers. If this is the case, then this would serve to reduce the difference noted in this study between the smokers and the nonsmokers. Therefore, the significant differences that we have reported might be even larger if we were able to adjust for passive exposure. Little is known about either the long-term effects of passive exposure during pregancy or the effects on the child's growth of current passive exposure in the household. Therefore, it is not possible to estimate the bias that this exposure would introduce. Another issue that must be considered is the small number of women who continued marijuana use during the second and third trimesters of pregnancy and the precision of the estimates that can be made from these small numbers. Within this combined study cohort was a cohort of women selected

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to study the effects of alcohol use during pregnancy. The rates of alcohol exposure during the second and third trimesters were similar to the rates of marijuana use (5). In the analyses of the data from the alcohol cohort, we have found significant effects of prenatal alcohol use on growth at each phase of the study through 36 months of age (5). Therefore, the sample size and the techniques for measuring substance use and outcomes are sufficient to detect subtle effects of teratogens. In summary, although there was a significant effect of tobacco exposure during pregnancy on the size of the infant at birth, by 18 months of age there was no relationship between any of the growth parameters and prenatal tobacco exposure. In contrast, marijuana use had little effect on birth size, and at all subsequent phases of the study, there was no relationship between marijuana exposure either prenatal or current and growth deficits. ACKNOWLEDGEMENTS This work was done at the University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, and the MageeWomens Hospital. Support was from the National Institute on Drug Abuse, grants DA03209, DA0090, DA03874, and the National Institute on Alcohol Abuse and Alcoholism AA06390 and AA06666 (N. Day, Principal Investigator).

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