effect of prenatal marijuana exposure on the cognitive development of offspring at age three

~ Pergamon Neurotoxicology and Teratology, Vol. 16, No. 2, pp. 169-175, 1994

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Effect of Prenatal Marijuana Exposure on the Cognitive Development of

Offspring at Age Three

N. L. DAY, *l G. A. R I C H A R D S O N , * L. G O L D S C H M I D T , I " N. R O B L E S , t P. M. TAYLOR,~: D. S. S T O F F E R , § M. D. C O R N E L I U S * A N D D. GEVA*

Department o f Psychiatry, University o f Pittsburgh School o f Medicine, ~f Western Psychiatric Institute and Clinic, University o f Pittsburgh School o f Medicine,

t~Pediatrics, Obstetrics and Gynecology, Magee-Womens Hospital, University o f Pittsburgh School o f Medicine, §Department o f Mathematics and Statistics, University o f Pittsburgh,

3811 O'Hara Street, Pittsburgh, PA 15213-2593

Received 23 November 1992; Accepted 25 October 1993

DAY, N. L., G. A. RICHARDSON, L. GOLDSCHMIDT, N. ROBLES, P. M. TAYLOR, D. S. STOFFER, M. D. CORNELIUS AND D. GEVA. Effect of prenatai marijuana exposure on the cognitive development of offspring at age three. NEUROTOXICOL TERATOL 16(2) 169-175, 1994. --Marijuana is the most commonly used illicit substance among pregnant women. Although there has been substantial concern about the effects of substance use during pregnancy, few studies have assessed the effects of prenatal exposure to marijuana and even fewer have provided longitudinal data on the developmental outcome of offspring. This is a report from a longitudinal study of substance use during pregnancy. The women in the cohort were of lower socioeconomic status, most were single, half were white and half were African-American. Women were interviewed at the fourth and seventh prenatal months, and women and children were assessed at delivery, 8, 18, and 36 months. Pediatric assessment included physical and cognitive development. At each study phase, mothers were interviewed about life style, living situation, current substance use, sociodemog~aphic, and psychological status. Findings are reported on 655 women and children who were assessed at the third year. There were significant negative effects of prenatal marijuana exposure on the performance of 3-year-old children on the Stanford-Binet Intelligence Scale. The effects were associated with exposure during the first and second trimesters of pregnancy. Among the offspring of white women, these effects were moderated by the child's attendance at preschool/day-care at age three.

Marijuana Pregnancy Stanford-Binet Intelligence Scale Cognitive development

MARIJUANA is the illicit drug most commonly used by pregnant women (6), yet little is known about the effects of prenatal exposure to marijuana on the offspring. Several studies have assessed the relationship between marijuana use and fetal growth (9,12,23,33), but few have followed the exposed children to evaluate the relationship between exposure and developmental outcomes.

The few reports of the effects of prenatal marijuana exposure on the central nervous system (CNS), or on cognitive and behavioral development, have been provocative but not def'mitive. Fried and Makin (11) reported a significant relationship between prenatal marijuana exposure, altered visual

responsiveness, and increased startles and tremors on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS). These findings persisted through 30 days of age on neurological examination (15). Other studies found no relationship between marijuana exposure and performance at birth on the BNBAS (19,26,31).

Researchers, using other methodologies, have demonstrated other effects of prenatal marijuana exposure on the integrity of the CNS. An assessment of the sleep-EEG patterns of a subset of newborns from the Maternal Health Practices and Child Development Project (MHPCD) found significant differences in the sleep cycling and motility of marijuana-

Requests for reprints should be addressed to Nancy L. Day, Western Psychiatric Institute and Cfinic, 3811 O'Hara Street, Pittsburgh, PA 15213-2593.

169

170 DAY ET AL.

exposed compared with nonexposed newborns (28). These effects remained consistent over time, and at 3 years of age, disturbed sleep patterns were still significantly associated with prenatal marijuana exposure (4). In another evaluation of po- tential CNS effects, Lester and Dreher (22) explored the acoustic characteristics of infant cries, comparing a Jamaican sample of 20 ganja users with 20 nonusers. The exposed infants' cries were significantly different from the cries of nonexposed infants on a number of parameters, which, the authors argued, may be due to the direct effects of prenatal marijuana exposure on the brain stem or higher regions of the brain.

Effects of marijuana exposure on the CNS have also been reported at older ages. The Ottawa Prenatal Prospective Study (OPPS) (14) reported that, at 48 months, using the McCarthy Scales of Children's Abilities, maternal mari juana use during pregnancy was significantly associated with lower scores in both the verbal and memory domains. In contrast, Streissguth et al. (30) did not find any significant effect of prenatal marijuana exposure on the development of 4-year-olds. A later analysis from the OPPS (24) reported on 28 six- to 9-year old children born to regular marijuana users and 28 control children matched on other prenatal drug history. Although the findings were not significant, children who were exposed to marijuana prenatally did less well on visual-perceptual tasks, language comprehension, and distractibility, as well as on parental ratings of behavior problems. A newer analysis of a larger cohort of the OPPS (13) reported no significant effects of prenatal mari juana exposure on cognitive or receptive language development in 5- and 6-year-old children. Signifi- cant effects of prenatal marijuana exposure were found in the OPPS on omission errors on a vigilance task and on maternal reports of impulsive and hyperactive behavior in 6-year-old children (16). Thus, the current findings are equivocal, although there are suggestions that marijuana use during pregnancy may affect development. Significant effects have been noted on the BNBAS, measures of the sleep-EEG, cry analyses, and at older ages, on measures of cognitive development and behavior.

This is an analysis of the effects of prenatal marijuana use on the development of offspring in the MHPCD study when they were 3 years old. The outcome is performance on the Stanford-Binet Intelligence Scale (32).

METHODS

Sample Selection and Study Design

Women attending an outpatient prenatal clinic were interviewed when they came in for their fourth-month appoint- ment. All were at least 18 years of age. A refusal rate of 15% resulted in a total of 1360 interviews. Two cohorts were selected from this initial sample to study the effects of prenatal marijuana and alcohol exposure on the offspring. In the first cohort, every woman who reported using mari juana at the rate of 2 or more joints per month during the first trimester and the next woman who used less than this amount were selected for the study. In the second cohort, each woman who reported drinking at the rate of 3 or more drinks a week during the first trimester and the next woman interviewed who drank less than this amount were selected. The sampling for each cohort was with replacement, so women could be in ei- ther or both samples depending on their patterns of substance use. The two samples have been combined for this analysis resulting in a combined cohort of 829 women.

Women were interviewed at the fourth and seventh months

of pregnancy and at delivery. Offspring were examined at delivery and at 8 and 18 months, 3 and 6 years of age. Mothers were interviewed at these time points utilizing a standardized instrument to assess marijuana and other illicit drug use, tobacco and alcohol use, psychological status of the mother, life style, current environment, medical history, and demographic status. During pregnancy, data were collected for the preced- ing trimester. The 3-year interview covered the time from the 18-month interview through the third year. Initial recruitment for the study was between 1983 and 1985.

Sample Characteristics

Description. The characteristics of the women in the sample are listed in Table 1. The women were generally of lower social status with a high school education. The sample was evenly divided by race, reflecting the composition of the prenatal clinic population. The mean age at first interview was 23, most of the subjects were unmarried and 31% were primi- gravidas. The majority reported alcohol and tobacco use, 11% reported use of illicit drugs other than marijuana (Table 2). By the third trimester, the use of alcohol and illicit drugs had decreased, although tobacco use remained constant. At 3 years, the rates of substance use had returned to the higher levels o f the first trimester.

The average birthweight of the offspring was 3222 g (range 1040 to 4990) and 9% were low birth weight (<2500 g). The rate of prematurity ( < 37 weeks gestation) was 8% and 10% of the infants were small-for-gestational age (SGA; growth < 10th percentile for gestational age). At the 3-year follow-up, the average age of the children was 38 months (range 35.5 to 56.3). Ninety-one percent of the children were seen by 42 months of age.

At age 3, 21% of the children attended preschool/day-care. Of these, 27% attended Head Start Programs, preschools or nursery schools, 21% were in family day-care, and the rest were in organized day-care facilities. Time spent in preschool/ day-care ranged from 2 to 60 h per week with a median of 20 hours. Ninety-four percent of the children who attended preschool/day-care attended regularly, the remainder attended on a drop-in basis. African-American women were more likely to have their children in preschool/day-care than were white women.

TABLE 1 CHARACTERISTICS OF THE STUDY COHORT

Range

Maternal age at first trimester (mean) 23 years 18-42

Race % White 48.2 e/e African-American 51.8

Primigravidous (%) 31.0 Maternal education at

first trimester (mean) 12 years 8-18 Monthly personal income at

first trimester (mean) $340 $0-1000 Monthly family income at

3 years (mean) $520 $0--1000 Married at 3 years (%) 36.4 Worked or attended school

at three years (%) 56.0

EFFECT OF PRENATAL MARIJUANA ON IQ 171

TABLE 2 SUBSTANCE USE OF THE STUDY COHORT

Percent Mean Range Users Use in Use

Alcohol First trimester 64.7 Third trimester 31.5 3 years 81.4

Tobacco First trimester 52.2 Third trimester 52.2 3 years 61.3

Illicit substance use~ First trimester 10.7 Third trimester 1.0 3 years 11.6

Cocaine First trimester 3.3 Third trimester 0.4 3 years 6.9

.58" 0-19.6" 0.15 0-24.7 0.91 0-18.8

8.2t 0-50t 9. l 0-70

12.7 0-70

*Mean drinks/day; tMean cigarettes/day; ~Illicit drugs other than marijuana but including cocaine.

Cohort size. There were 829 women in the combined cohort. We examined 763 live singleton offspring at birth, a completion rate of 92%. Subject loss was from fetal death (n = 18), refusal (n = 8), lost to follow-up (n = 16), moved out of the region (n = 21), adoption (n = 1), and multiple births (n = 2).

At 3 years, we interviewed 95% of the eligible subjects (n = 672), which represented 88% of the birth cohort. Losses between birth and 3 years of age occurred because subjects had moved (n -- 50), been placed for adoption (n = 3), refused further participation (n = 17), died (n = 3) or were lost to follow-up (n = 18). There were no significant differences in demographic characteristics or in the patterns of substance use during pregnancy between the women who were interviewed at year three and those who were not.

The final size of the cohort used for the analysis was 655. One child was assessed too late for inclusion in the analysis. Six children were missed, although we interviewed their mothers, and five children refused to do the Stanford-Binet. In addition, 5 children had physical impairments and were un- testable on the Stanford-Binet; 2 of these had cerebral palsy, 2 had visual problems, and 1 was deaf. The substance use of these mothers did not differ from the mothers of children who were able to participate.

Measurement

Marijuana use. The development of the mari juana ques- tions has been described elsewhere (7). Usual quantity and frequency, and minimum and maximum quantity and frequency were obtained at each time-point. Mari juana use was expressed as average daily joints (ADJ). Hashish and sen- semiila were calculated into the mari juana score. Hashish use was considered equivalent to three joints of mari juana and sensemilla was counted as two joints based on the relative amounts of A-9-THC in each (17,18,21).

The rate of mari juana use was calculated for each month of the first trimester and was reported 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 for each bev- erage type. Tobacco use was calculated as cigarettes per day. The quantity, frequency, amount, and mode of use was ascer- tained for each illicit drug. For these analyses, however, illicit drug use was dichotomized as any use/no use. Most commonly, the drugs used in the first trimester were amphet- amines (6%), tranquilizers (3%), and cocaine (3%).

Stanford-Binet Intelligence Scale. Cognitive development at 3 years was assessed with the Fourth Edition of the Stanford- Binet Intelligence Scale (32). Assessment personnel were trained to reliability and were supervised by a developmental psychologist. All were blind to maternal substance use.

The composite score and four area scores were obtained: verbal reasoning, abstract/visual reasoning, quantitative reasoning, and short-term memory. The average composite score for the cohort was 96 (SD = 10.9) with a range of 72 to 131. The quantitative reasoning subscale was very difficult for our subjects and only 55% of the children completed this portion of the evaluation. When we assessed the differences between those children who did and did not complete this subscale, we found a significant relationship between noncompletion and age at assessment. The noncompleters were, on average, 37.2 months of age compared with the completers who were 38.5 months. The groups did not differ by prenatal marijuana exposure.

Current environment. The current environment was measured by variables that covered multiple domains (Table 3). Socioeconomic status was assessed by maternal education, current work status, and family income. The psychological environment was measured by maternal levels of depression using the Center for Epidemiologic Studies-Depression Scale (25), anxiety and hostility with the Spielberger State-Trait Anxiety Inventory (29), self-esteem with the Rosenberg Self- Esteem Scale (27), and the mother's perception of how difficult the child was. The structure of the environment was assessed using a measure of household structure that reflected who resided in the household, the number and distance in age between siblings. The Pediatric Review of Children's Environ- mental Support and Stimulation Inventory (PROCESS) (2) was used to evaluate the child's social and physical home environment. This scale assesses organization and stimulation in the environment. It also includes a toy list and an observer- scored assessment of the mother/child interaction.

The social environment was measured by the social support and life events of the mother. These instruments were adapted for the study from an instrument used in the Human Popula- tion Laboratory studies (1) and the PERI (10), respectively. A measure of the child's social environment, attendance at preschool, nursery school, or day-care was also used. A dichotomized variable was created to represent preschool/day-care attendance versus no preschool or day-care attendance.

Data Analysis

A regression model was used to assess the relationship between prenaial marijuana exposure and performance on the Stanford-Binet Intelligence Scale at age 3. Stepwise and back- ward elimination models were used and gave comparable results. The results of the stepwise regressions are reported.

All significant predictors identified in the regression were inspected for interaction by testing for the homogeneity of

172 DAY ET AL.

TABLE 3 COVARIATES CONSIDERED IN THE REGRESSION ANALYSES

Demographic factors *Race Maternal age

*Parity Sex of child

*Marital status

Socioeconomic status *Maternal education Maternal work status Family income

Environmental factors (assessed at 3 years postpartum) Psychological environment

*Depression (CES-D) *Anxiety (Spielberger State-Trait Anxiety Inventory) Hostility (Spielberger State-Trait Anxiety Inventory) Self-esteem (Rosenberg Self-Esteem)

*Maternal perception of the child's difficultness

Structural factors in the environment Household structure Number of sibfings Distance between sibfings Organization of the household (PROCESS) Stimulation in the household (PROCESS)

Social factors in the environment *Social support Life events

*Child's school and/or day-care attendance

Substance Use Use of marijuana, alcohol, tobacco, and other illicit drugs at 3 years postpartum Trimester-specific use of marijuana, alcohol, tobacco, and

other illicit drugs

*Indicates that this variable was a significant predictor of the Stanford-Binet Intelligence Scale composite score in the total cohort in the regression model.

the regression slopes between marijuana users and nonusers. Variables for which the test indicated a significant interaction, those that had different effects on the outcome for the exposed versus the nonexposed groups, were treated as modera- tors. Only two variables, race and preschool/day care attendance, met this criterion.

Prenatal marijuana exposure was used as a continuous variable, expressed as average daily joints (ADJ). The ranges in ADJ were from 0 to 8.8, from 0 to 6.5, and from 0 to 9.4 for the first, second, and third trimesters, respectively. The regression coefficients are presented as the amount of change associated with a one unit change in ADJ, or a change of one joint/day.

Analyses were run separately for each trimester. In each, substance use (marijuana, other illicit drugs, alcohol, tobacco) specific to the trimester and maternal substance use at the current 3-year assessment were included in the analysis. The correlations between marijuana use at each trimester and use at 3 years were moderate (0.40-0.44), so it was possible to include both variables in the same regression model. The toler- ances were high at all times.

The covariates listed in Table 3 were used for the initial

model development. These covariates were selected from an initial bivariate screen of relationships between variables. They also correspond to a list of covariates recommended for consideration in studies of teratogenic exposures (20). The final models included only the significant covariates. In general, the regression model for each trimester contained the covariates listed as significant predictors of the composite score (Table 3). All p values are presented as one-tailed values because we were testing a hypothesis of negative effect.

As a final step, the adequacy of the fitted regression model was tested. The residuals were examined for any violations of the assumptions. In addition to residuals, Mahalanobis distance and Cook's statistics were screened to identify possible outliers or influential observations (3).

RESULTS

The distribution of marijuana use during pregnancy and at each follow-up phase of the study is described in Table 4. Use decreased over the pregnancy, but by the third year postpartum had returned to higher levels.

Women who used marijuana during pregnancy were significantly more likely to be African-American and unmarried. Of the women who used marijuana heavily during the first trimester (ADJ > I), 78% were African-American, compared with 45% of the nonusers (/7 ~ 0.0001). Nineteen percent of the heavy users were married compared with 42% of the nonusers (p = 0.0001). Heavy users were also significantly more likely to report use of alcohol (p = 0.0007) and illicit drugs other than marijuana (p = 0.0003) at each study interview, although there were no differences in tobacco use.

There were no significant effects of marijuana use during any trimester of pregnancy on the composite score of the Stanford-Binet. There also was no effect of current maternal marijuana use on the composite score. The variables that significantly predicted the composite score in regression analysis were child's sex and preschool/day-care attendance at age 3, maternal race, education, marital status, parity, mother's perception of the child, depression, anxiety, and social support at 3 years postpartum (Table 3). These variables explained 22% of the variance.

When the subscale scores were used as outcome variables, there were marginally significant, negative relationships between marijuana use during the second trimester of pregnancy and short-term memory (coefficient = - 1.5; p = 0.06) and between short-term memory and the mother's current use of marijuana (coefficient = - 1 .3 ; p = 0.06). There were no other significant relationships between marijuana use during any phase on any of the subscales of the Stanford-Binet.

TABLE 4 PREVALENCE OF MARIJUANA USE DURING PREGNANCY

AND AT 3 YEARS POSTPARTUM (%)

Trimester of Pregnancy 3 Years

Marijuana Use First Second Third Postpartum

None 59.1 78.5 82.1 64.9 Light 19.9 13.3 10.1 20.2 Moderate 7.4 3.5 3.5 5.7 Heavy 13.6 4.7 4.3 9.2 Sample size 653 594 655 652

None: No use; Light: ADJ > 0 and ~0.4; Moderate: ADJ > 0.4and <1; Heavy:ADJ ~e 1.

E F F E C T OF P R E N A T A L M A R I J U A N A ON IQ 173

Mar i juana use was more prevalent among the African- American women and the covariates o f use differed by race. In the Afr ican-American sample, there were significant differences between users and nonusers on education (11.7 vs. 12 years; p = 0.01) and marital status (17.1% vs. 26% married; p = 0.05), al though these variables did not predict use among white women. A m o n g white women, mar i juana users reported significantly more illicit drug use during pregnancy (29% vs. 10% among the nonusers; p < 0.001) and at 3 years (22% vs. lleTe among nonusers; p < .001). This was not the case for Afr ican-American women. Because o f these differences between the two racial groups, an interaction term (ADJ x race) was entered into the regression models. This interaction term was significant. To explore this further, the analyses were run separately by race. The quanti tat ive reasoning subscale was not used in this analysis because o f the large number o f children who failed to complete this part o f the assessment.

A m o n g the offspring o f Afr ican-American women, first trimester mar i juana use significantly predicted a decrease o f 1.3 IQ points per jo in t smoked per day on the verbal reasoning subscale (19 = 0.007). Mar i juana use during the second trimester was a significant predictor o f per formance on the short- term memory subscale ( - 1 . 6 po in t s / jo in t /day ; p = 0.05). In each case, more mar i juana use predicted a lower score. In the white populat ion, there were no significant effects o f prenatal mar i juana exposure during any trimester o f pregnancy on the composi te score or the subscales.

Preschool /day-care at tendance was a significant predictor o f better performance on the Stanford-Binet Intelligence Scale. The rate o f preschool /day-care at tendance varied between racial groups and with prenatal mar i juana exposure. More Afri-

can-American and more mari juana-exposed children attended preschool /day-care . The presence o f an interaction between mar i juana and preschool/day-care attendance on the Stanford- Binet was explored by entering an interaction term (ADJ x child's preschool /day-care at tendance at age 3) into the regressions for the total cohort and the two racial groups.

In the total cohort , the interaction o f first trimester marijuana use by preschool/day-care attendance was significant and positive for the composite score and the verbal reasoning subscale (Table 5), while both the interaction and the main effect o f first trimester mari juana use predicted short-term memory. The main effect o f second trimester mari juana use on short- term memory remained significant for the total cohort and ac- counted f o r a d e c r e a s e o f 2 . 3 p o i n t s / j o i n t / d a y ( p = 0.02). The significant relationship reported earlier between short-term memory and mari juana use at 3 years postpar tum was not significant when the interaction term was entered.

Among Afr ican-American offspring, first trimester marijuana use had significant, negative main effects on the composite score ( - 0 . 9 po in ts / jo in t /day; p = 0.05), the short- term memory subscale ( - 1 . 1 po in t s / jo in t /day ; p = 0.05), and the verbal reasoning subseale ( - 1 . 5 po in t s / jo in t /day ; p = 0.005) (Table 5). There was also a main effect o f second trimester exposure on short-term memory, predicting a decrease o f 1.8 po in t s / jo in t /day (17 = 0.05). The interaction between mari juana use and preschool/day-care attendance was not a significant variable in predicting scores among the Afr ican-American offspring.

The results for the white offspring were very different. Both the interaction term and the main effect o f second trimester exposure were significant predictors o f the composite

T A B L E 5

PRENATAL MARIJUANA USE AND SCHOOL ATTENDANCE AS PREDICTORS OF PERFORMANCE ON THE STANFORD-BINET INTELLIGENCE SCALE

Stanford-Binet Scale Total Cohort African-American White

Composite score First trimester Interaction* (1.6)t Main~t ( - 0.9) - § Second trimester - - Interaction (8.9)I and Main ( - 8.9)¶ Third trimester -- - -

Short-term memory First trimester Interaction (3.0) and Main ( - 1.1) Main ( - 1.1) Interaction (3.6) Second trimester Main ( - 2.3) Main ( - 1.8) - Third trimester - - Interaction (13.8) and Main ( - 8.9)

Verbal reasoning First trimester Interaction (1.9) Main ( - 1.5) -- Second trimester - - Interaction (8,9) and Main ( - 8.6) Third trimester - - -

Abstract/visual First trimester - - - Second trimester - - Main ( - 7.6) Third trimester - - -

Quantitative¶ First trimester - # # Second trimester -- # # Third trimester - # #

*Only the interaction of marijuana use x presehool/day-care attendance was significant; tTheregressioneocfficient (in parentheses) represents the effect associated with a change of 1 joint/day; ~Only the main effect of marijuana use was significant; §No significant effect; IBoth the interaction marijuana use x preschool/day-care and the main effect of marijuana use were significant in the same regression; #Analysis not done separately by rare.

174 DAY ET AL.

score. There was a decrease of 8.9 points / jo in t /day (p = 0.007) for children who did not attend preschool/day-care which was offset by an increase in the IQ score among the children who attended preschool/day-care (Table 5). Short- term memory was significantly predicted by the interaction term for the first trimester and by both the interaction term and the main effect for third trimester mari juana exposure. In addition, second trimester mari juana exposure had a significant interaction and main effect on the verbal reasoning subscale. There was a significant main effect on the abstract/ visual reasoning subscale, representing a decrease of 7.6 points / jo in t /day (p = 0.03), after controlling for the effect of the interaction.

Although measures of the current environment were entered into the regression model as covariates, for descriptive purposes we conducted one further assessment of the effects of prenatal marijuana exposure compared with current maternal mari juana use at 3 years postpartum. Marijuana use was dichotomized into a higher (ADJ ~0.5) and a lower (ADJ < 0.5) level of use. Scores on the Stanford-Binet were adjusted for the significant covariates identified in the regression analyses. The adjusted composite score among children who were currently exposed to a higher amount of marijuana but who had been exposed to the lower amount during the second trimester of pregnancy was 98 (n = 47). In contrast, children who were currently exposed to a lower amount but who had been exposed to the higher amount during the second trimester had a composite score of 93 (n = 17). We assessed the composite and short-term memory scores for the total cohort, African-Americans and whites separately, and within racial groups, by preschool/day-care attendance. In each comparison, the impact of prenatal exposure was greater than the effect of current mari juana use, although it was not always significantly different because of small cell sizes.

DISCUSSION

In the total cohort, there were no overall effects of marijuana exposure on the composite score of the Stanford-Binet Intelligence Scale. There was a significant negative effect of marijuana use on the short-term memory subscale. When the two racial groups were analyzed separately, negative effects of marijuana use during pregnancy were found on the verbal reasoning and short-term memory subscales only for African- American offspring.

An interaction term, ADJ x preschool/day-care attendance, was added to the model to explore the effects of preschool/day-care attendance on cognitive development. When this term was entered, significant and positive interactions were found for white offspring on the composite score, short- term memory, and verbal reasoning subscales. These significant, positive interaction terms, in general, were coupled with a significant, negative main effect for mari juana use. Thus, for white children, there was a significant negative effect of prenatal marijuana exposure on performance on the Stanford- Binet Intelligence Scale, which was offset by the positive effect of preschool/day-care attendance. For African-American children, significant main effects were found on the composite score, short-term memory, and verbal reasoning subscales and the effects of prenatal marijuana use were not moderated by preschool/day-care attendance. In summary, for both white and African-American offspring, prenatal marijuana exposure was associated with significantly decreased scores on the Stanford-Binet. For the white children, however, the decrease in performance on the Stanford-Binet was offset by preschool/day-care attendance.

These findings parallel the report from the OPPS on 4- year-olds. In that study, using the McCarthy Scales of Chil- dren's Abilities, the authors reported significant effects of prenatal marijuana exposure on both the verbal and memory domains (14). That study, however, did not assess the effects separately by race or by preschool and day-care attendance. It is noteworthy, however, that in the OPPS sample, the effects of prenatal exposure to marijuana were no longer significant when the children reached school age (13).

A competing hypothesis that must be considered is that factors in the current environment of the child may be corre- lated with prenatal marijuana use and that these may be deter- mining the findings. However, the regression model contained variables that represented the social, economic, psychological, and structural components of the current environment, as well as current substance use (Table 3). The effects of prenatal marijuana exposure remained significant after controlling for these factors. In an additional analysis, after adjusting for the significant covariates, we demonstrated that children who had been exposed to higher levels of marijuana prenatally but who were not currently exposed to higher amounts, had lower composite scores than those who were currently exposed to higher amounts but had not been heavily exposed to marijuana prenatally. Therefore, although factors in the child's environment significantly affect their performance on the Stanford-Binet, the effect of prenatal marijuana exposure was still significant after taking current environment into account.

Thus, in this study, we have found a significant negative effect of prenatal exposure to marijuana on the performance of both African-American and White children on the Stan- ford-Binet Intelligence Scale. This negative relationship was predicted by marijuana exposure in the first and second trimesters. It was not detected in the initial regression models because of significant interactions between race, prenatal marijuana exposure, and preschool/day-care attendance at age 3. For white children who attended preschool/day-care, the effects of prenatal exposure were ameliorated. For white children who did not attend preschool/day-care, the significant negative effects of prenatal exposure remained. Among the African-American children, there were direct effects of prenatal marijuana exposure and there were no significant interactions between preschool/day-care attendance and prenatal marijuana exposure.

The effects that are reported are small and would not be clinically significant for an individual. However, the effects that we are reporting are differences between populations not between individual cases. The results indicate that, on average, children exposed prenatally to marijuana will have a lower IQ compared with children who were not exposed. These results were found when the effects of current environmental factors were controlled. Although small, these differences mark the long-term effect of a teratogen.

These findings have important implications for planning for the care of children prenatally exposed to marijuana. Our data demonstrate that, at least for some children, enhancing their environment with preschool and day-care can mitigate the negative effects of prenatal exposure to marijuana.

ACKNOWLEDGEMENTS

This work was done at the University of Pittsburgh School of Medicine, Western Psychiatric Institute and Cfinic, and the Magee- Womens Hospital. Support was from the National Institute on Drug Abuse Grants DA03209 and DA03874 and the National Institute o n

Alcohol Abuse and Alcohofism, Grants AA06390 and AA06666 (N. Day, Principal Investigator).

EFFECT OF PRENATAL M A R I J U A N A ON IQ 175

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