Detrimental Effects of Prenatal Cocaine Exposure: Illusion or Reality?

Detrimental Effects of Prenatal Cocaine Exposure: Illusion or Reality? GALE A. RICHARDSON, PH.D., AND NANCYL. DAY, PH.D.

ABSTRACT Objective: The primary purpose of this study is to investigate the impact of prenatal cocaine exposure, while controlling for other factors that influence infant outcome. Method: These preliminary data are from an ongoing prospective study of prenatal cocaine and/or crack exposure. Detailed information is collected about the use of cocaine, crack, alcohol, tobacco, marijuana, and other drugs during each trimester of pregnancy. Results: Women who use cocaine and/or crack during pregnancy differ from those who do not. The women who use cocaine are older, more likely to be black, and less likely to be married. They also use more tobacco, alcohol, and marijuana during pregnancy than do nonusers of cocaine. When these differences between the exposure groups are controlled, preliminary analyses indicate there is no significant effect of prenatal cocaine use on infant growth and morphology. Conclusions: Future research needs to address the effects of prenatal cocaine and/or crack exposure on central nervous system development and on the long-term development of exposed offspring. J. Am. Acad. Child Ado/esc. Psychiatry, 1994, 33, 1:28-34. Key Words: prenatal cocaine exposure, infant growth and morphology, lifestyle characteristics.

A number of reports have suggested there are negative effects of prenatal cocaine use including growth deficits (Chasnoff, 1988; Coles et al., 1992), changes in the central nervous system (Dixon and Bejar, 1989), and differences in behavior (Chasnoff et al., 1987). However, other studies have reported no effects of prenatal cocaine use (McCalla et al., 1991; Neuspiel et al., 1991; Richardson and Day, 1991). Methodological limitations that contribute to the lack of consistency among studies include the method of case selection, the failure to control for use of other drugs (such as alcohol and tobacco), the lack of appropriate comparison groups, and the failure to control for other covariates of drug use (such as prenatal care and lifestyle characteristics) (Richardson and Day, 1991; Richardson et al., 1993). Accepted May 12, 1993. From the Program in Epidemiology, Western PsychiatricInstitute and Clinic, University ofPittsburgh School ofMedicine. An earlier version ofthis paper was presented at the American Academy of Pediatrics, San Diego, California, March 1991. This research was supported by NIDA: The Effect ofPrenatal Cocaine Use on Infimt Outcome (DA05460) and Prenatal Cocaine Use: A Longitudinal Epidemiologic Study (DA06839), G. Richardson, Principal Investigator. The authors also thank Lidush Goldschmidt and Young ]hon for their assistance with data analysis. Reprint requests to Dr. Gale A. Richardson, Program in Epidemiology, Western Psychiatric Institute & Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213.

0890-8567/94/3301-0028$03.00/0©1994 by the American Academy of Child and Adolescent Psychiatry.

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Although many researchers have not considered the differences between women who use cocaine and those who do not, some studies have shown that women who use cocaine during pregnancy are different from women who do not. They more often use alcohol, tobacco, marijuana, and other illicit drugs during pregnancy (McCalla et al., 1991; Richardson and Day, 1991; Streissguth et al., 1991). Tobacco and alcohol, in particular, have well-documented effects on infant outcome (Day et aI., 1989, 1992) that must be taken into account when evaluating the effect of cocaine use. In addition, women who use cocaine during pregnancy are older, of higher gravidity and/or parity, and more likely to be black (Gillogley et al., 1990; McCalla et al., 1991). Each of these factors is, by itself, a risk factor for a more problematic pregnancy outcome and must be considered in the analysis. A review of the literature demonstrated that when women who use cocaine and other drugs during pregnancy are compared with drug-free women, the offspring of the cocaine users are significantly different from the offspring of the controls (Richardson et al., 1993). However, when women who use cocaine are compared with women who use drugs other than cocaine, the offspring do not appear significantly different. This would imply that the effects of prenatal cocaine exposure are not specific to cocaine and that they reflect the poor environments in which the pregnancies occur and in which the children are raised.

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994

PRENATAL COCAINE EXPOSURE

This paper describes an ongoing prospective, longitudinal study of the effects of prenatal cocaine and crack use, which was designed to overcome the previously cited methodological problems. The sample includes women who use cocaine and/or crack at light to moderate levelsduring early pregnancy and who receive prenatal care. Detailed information is collected regarding the pattern ofall prenatal drug use for each trimester of pregnancy. Information also is collected regarding other aspects of the pregnancy and social environment that might influence outcome. Preliminary data are presented to illustrate the thesis that it may not be cocaine per se that affects infant outcome (the illusion), but a multitude of factors including sociodemographic characteristics and the use of other drugs (the reality). METHOD Study Design This is an ongoing, prospective study of women attending a medical assistance prenatal clinic. Written consent is obtained by project interviewers for both mothers and infants according to guidelines established by the University's Institutional ReviewBoard for Biomedical Research and the Research Review and Human Experimentation Committee of Magee-Womens Hospital. The women are a representative group attending a prenatal clinic. They are not in drug treatment. Women who are at least 18 years of age are initially interviewed during their fourth or fifth prenatal month by trained research interviewers not associated with the medical staff. If a woman has not sought prenatal care by 23 weeks of gestation, she is not eligible for the study. Women who meet the eligibility requirements are approached randomly by the interviewers, who are initially blind to her substance use status. That is, no information is obtained from the medical charts about a woman's drug use before her being asked to participate in the study. During the first interview, women are asked detailed questions about their use of cocaine, crack, alcohol, marijuana, tobacco, and other drugs for the year preceding pregnancy and for the first trimester. They are asked about their usual, maximum, and minimum quantity and frequency of use. The women are interviewed about the quantity and frequency oftheir cocaine use and separately about their crack use. They are also asked how they used cocaine: the mode or method of administration. In addition, questions are asked about drug use during specific periods of the first trimester. Each woman is asked to indicate on a calendar three time points: (1) when she actually conceived, (2) when she first realized she was pregnant (recognition), and (3) when she had a positive pregnancy test (confirmation). The interviewers are trained to accurately elicit this information by using holidays or other special events to help the woman remember these time points. The woman is then asked for the period between conception and pregnancy recognition whether her drug use resembled what she reported for the year before pregnancy or whether it resembled what she reported for first trimester use. This question is repeated for the time between pregnancy recognition and confirmation.

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994

The answers to the questions are used to create a calculated first trimester variable that takes into account the fact that women often use at their prepregnancy levels until they realize they are pregnant. These methods of ascertainment were adapted from those used previously in studies of prenatal alcohol and marijuana exposure (Day et al., 1985; Robles and Day, 1990). All women who report using any cocaine or crack during the first trimester are enrolled. The next woman interviewed who reports no cocaine or crack use during the first trimester and the year before pregnancy also is enrolled. Ninety percent ofthe women eligible to be interviewed consent to participate in the study. Medical chart reviews of a random sample of women who refused to participate indicated only 5% of the women who refused had a history of drug use during pregnancy. Women are interviewed again at 7 months about their substance use during the second trimester and again at 24 to 48 hours postdelivery, when they are asked about third trimester substance use. (Second trimester data will not be presented in this paper.) Information also is obtained at each phase regarding sociodemographic (age, education, race, income, occupation) and lifestyle (life events, household composition, church attendance) characteristics, social support (number of friendslrelatives in support system, satisfaction with support), and psychiatric symptomatology (depression, self-esteem, hostility, anxiety). Information regarding maternal medical history, pregnancy, labor, and delivery conditions is abstracted from the medical charts by research nurse clinicians after the physical examination is completed. All newborns receive comprehensive physical examinations, generally within 24 to 48 hours of delivery, by the research nurse clinicians who are blind to prenatal exposure. Physical status, growth parameters, and morphologic abnormalities are assessed. In addition, full-term infants are assessed with the Brazelton Neonatal Behavioral Assessment Scale (Brazelton, 1984) and observed with their mothers during a feeding (Osofsky and Danzger, 1974). A 2- to 3-hour EEG sleep study is also obtained on a subset of fullterm infants. Because of the time and expense involved in conducting EEG sleep studies, two groups of infants are selected for these studies: (1) offspring of women who used cocaine/crack more than once a week during the first trimester and (2) offspring of women who did not use cocaine/crack during the first trimester. Women are reinterviewed and their offspring are assessed with physical, cognitive, and behavioral measures at 12 and 36 months postpartum. This report presents preliminary data only from the newborn physical examinations.

Subjects Data are available currently on 267 women who are enrolled in the study. It is anticipated that a total of 400 women will be enrolled. Fifty-two percent of the women are white, 47% are black, and 1% are Hispanic. This ethnic distribution in the sample reflects the distribution of women who attend the prenatal clinic. At the initial interview, the mean age was 24.6 years (range 18 to 41), the mean years of education was 11.9 (range 8 to 16), and the median monthly family income was $500 (range $0 to $2,800). Forty-one percent of the women worked or went to school during the first trimester; 13% did so during the third trimester. Twentyone percent were married at the initial interview; an additional 1% married before delivery. Data are available on 227 infants. Fifty-three percent of the infants were males. The mean 1- and 5-minute Apgars were 7.9 (range 2 to 10) and 8.9 (range 4 to 10), respectively. The mean

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RICHARDSON AND DAY gestational age, as measured by a modification of the Dubowitz assessment (Ballard et al., 1979), was 39.6 weeks (range 21 to 44). Approximately 8% of the infants were preterm (<37 weeks), 10% were low birth weight (<2,500 g), and 9% were small-for-gestational age (Brenner et al., 1976).

Statistical Analysis The usual, maximum, and minimum quantity and frequency of cocaine and crack use are combined into one variable reflecting the average daily use of the drug. An average daily use variable is calculated for each trimester. Alcohol is analyzed as average number ofdrinks per day, marijuana as average joints per day, and tobacco as average cigarettes per day. These are also trimester-specific variables. For descriptive purposes, two extreme levels of cocaine/crack use, no use and frequent use, were compared. No use was defined as no cocaine or crack use during the specified period. Frequent use was defined as using one or more lines of cocaine per day (or an equivalent amount of crack) during the specified trimester. Initial comparisons between the groups were evaluated with ttests for continuous variables and X2 for categorical variables. Analysis of covariance (ANCOVA) was then used to compare the exposure groups while controlling for other variables of interest. In ANCOVA, covariates (e.g., tobacco and alcohol use) are entered to adjust for the effects on the outcome variable (birth weight) that are due to the covariates. The purpose of ANCOVA is to adjust the outcome to what it would be if all subjects were equal on particular covariates. It is a statistical procedure for controlling the variation among subjects that cannot be experimentally manipulated (Tabachnick and Fidell, 1989).

RESULTS

Patterns of Cocaine Use

Twenty-two percent of the women selected for the sample were frequent users during the year before pregnancy, 17% were frequent users during the first trimester, and 5% of the women were still using daily in the third trimester. The average use for the frequent group was 0.5 g per day during the first trimester (approximately 15 lines of cocaine per day or 2 to 3 rocks of crack per day), with use ranging up to 3 g per day during the first trimester. The women who used frequently during the third trimester averaged 0.04 g per day, or approximately one line per day, with use ranging up to 0.5 g per day. Ninety-two percent of the women who used frequently during the third trimester had used at that level first trimester. When the reported mode of cocaine use was examined, a discrepancy in the frequency of cocaine and crack use was found. Eighty-five percent of the women reported using only a drug they called "cocaine," 7% reported using a drug they called "crack," and 7% reported using both drugs. However, when the mode

30

of use was analyzed, 55% of the women reported they snorted cocaine in powder form, 35% freebased or smoked the drug with marijuana or tobacco cigarettes (that is, they were using crack), 8% used both methods, and 2% were intravenous users. Therefore, by report of the name of the drug alone, 14% reported crack use, but in reality 43% were smoking crack rather than using cocaine.

Correlates of Cocaine Use

Women who were frequent users of cocaine/crack during the first trimester were older, more likely to be black, less often married, and had a lower family income (Table 1). The frequent users also had more pregnancies, more births, and more abortions than the women who did not use cocaine/crack, and these differences persisted after controlling for maternal age. There were no differences between frequent users and nonusers in the number of miscarriages, in prepregnancy weight, or in the amount of weight gained during pregnancy. Gestational age at first prenatal visit did not differ, although the frequent users had fewer prenatal visits. Frequent users had more medical problems and difficulties with their pregnancies, but they did not differ in the rate of labor or delivery complications. The frequent users were significantly more likely to have notations on their medical charts about alcohol and drug problems, both prep regnancy and during the current pregnancy. Women who used cocaine were also more likely to use other drugs. Women who used cocaine frequently (one or more lines/day) were significantly more likely to use tobacco during the first and third trimesters (Table 2). During the first trimester, 82% of the frequent cocaine users were tobacco smokers compared with 46% of the noncocaine users. Frequent users of cocaine were also significantly more likely to drink alcohol during the first and third trimesters and to drink more heavily. Fifty-five percent of the frequent cocaine users drank one or more drinks per day first trimester compared with 16% of the nonusers. The frequent cocaine users also used more marijuana first trimester and reported more use of other illicit drugs during the first and third trimesters.

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994

PRENATAL COCAINE EXPOSURE

TABLE 1 Maternal Characteristics

Demographic Characteristics Mean age** (years) Mean education (years) Race** White Black Marital status at delivery** Single Married Neither work nor go to school 1st trimester Family income l st trimester < $500 per month** Obstetrical Characteristics Mean prepregnancy weight (lb) Mean weight gain during pregnancy (lb) Mean gravidiry** Mean pariry* Mean no. miscarriages Mean no. abortions* First prenatal visit (week) Total prenatal visits**

Frequent Cocaine Users' N= 44

Nonusers' N=I65

27.5 (18-36) 11.9 (9-16)

24.0 (18-41) 11.9 (8-16)

30% 70%

56% 44%

87% 13% 67% 69%

71 % 29% 57% 42%

138.6 (98-185) 34.5 (-14-81) 4.2 (1-13) 2.5 (1-6) 0.70 (0-5) 0.98 (0-5) 14.9 (8-26) 8.0 (1-18)

143.2 (85-270) 33.8 (-22-72) 2.9 (1-14) 2.0 (1-7) 0.38 (0-7) 0.50 (0-5) 13.8 (5-27) 10.3 (1-19)

"First trimester.

*p < .05, **p < .001.

Infant Outcome

The difference in birth weights between offspring of nonusers and frequent users of cocaine is 307 g, almost 3/4 of a pound, which is statistically significant (Table 3). As was illustrated in Tables 1 and 2, however, a number of other factors correlate with cocaine use. These variables are also predictors of infant outcome and therefore must be controlled in the analysis. Furthermore, gestational age and birth weight are highly correlated. When the effect of gestational age on birth weight is removed, the difference between the nonusers and frequent users is reduced to 128 g, a nonsignificant difference (Table 3). By also controlling for the difference in tobacco use between the two groups, the difference is reduced to 96 g. By controlling for alcohol, the difference is reduced to 82 g. When race and gender are added to the model, the difference between the groups is reduced to 33 g or only about one ounce. Thus, when the effects of these other variables are removed, there is no significant difference between the groups. If one did not control for the other factors that differ between the exposure groups, it would appear that prenatal cocaine exposure decreases birth weight. These analyses are with women who used

]. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994

frequently during the first trimester. Although there were too few women who used frequently during the third trimester to detect significant differences, the same pattern of findings was found. The same findings held true for other outcomes as well. When the appropriate confounding variableswere included in the analysis of covariance, there were no significant differences between infants of women who were frequent users of cocaine and those of women who were nonusers. As shown in Table 4, infants did not differ in gestational age, Apgar scores, birth weight, length, head circumference, or the number of minor physical anomalies. Logistic regression analyses indicated that cocaine use during the first trimester was also not associated with prematurity «37 weeks), low birth weight (<2,500 g), or being small-for-gestational age after alcohol, tobacco, marijuana, and other illicit drug use were controlled. First and third trimester alcohol use significantly predicted prematurity and first and third trimester alcohol and tobacco use significantly predicted low birth weight. Stepwise regression analyses showed that birth weight, length, and head circumference were all predicted by gestational age, gender, race, and maternal

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RICHARDSON AND DAY

TABLE 2 Maternal Substance Use (%) During First and Third Trimesters of Pregnancy

3rd Trimester*

1st T rimester" Tobacco Nonsmokers Less than .5 to 1 pack/day More than 1 pack/day Cigarettes/day Median Range

Freq" 18 64 18

None 54 30 16

b

Freq' 08 67 25

Noned 50 33 17

10 0-30

07 0-40

09 0-25

07 0-40

Freq 11 34 55

None 42 42 16

Freq 42 16 42

None 60 36 03

2.1 2.8 0-14

0.6g 1.6 0-10

1.6 2.3 0-06

0.2 b

1st Trimester** Alcohol Abstainers Light/moderate' Heavy! Drinks/day Mean Standard deviation Range

3rd Trimester'?"

1st Trimester** Marijuana Abstainers Light/moderate' Heavy! Joints/day Mean Standard deviation Range Other illicit drugs (Excluding cocaine) "N = 44, bN = 165, 'N = 12, dN month, Jless than l/mo. *p < .05, **p < .001.

3rd Trimester

Freq 41 36 23

None 78 17 05

Freq 75 25 00

None 90 08 02

0.9 2.0 0-10

o.r

0.1 0.2 0-01

o.ov

0.3 0-01 None 04

Freq 08

Ist Trimester* Freq 16

= 212, 'light/moderate

DISCUSSION

These preliminary data are from an ongoing prospective, longitudinal study of prenatal cocaine and/or crack exposure. Detailed information is collected about the use of cocaine, crack, alcohol, tobacco, marijuana, and other drugs during each trimester of pregnancy. Women who use cocaine/crack differ from those who do not in aspects other than cocaine/crack use. The women who use cocaine/crack are older, more likely to be black, and less likely to be married. They use more tobacco, alcohol, and marijuana than nonusers of cocame,

0.3 0-03 3rd Trimester*

= > 0 and < 1 per day, fheavy

height. In addition, birth weight and length were predicted by first trimester tobacco use. These findings are in agreement with reports from studies of prenatal alcohol and marijuana exposure, using similar methods and with a larger sample size (Day et al., 1989, 1991).

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1.1

0-14

None 01

= ;:: 1 per day, K3-4/week, hl-2/week, i2-3/

Factors that covary with cocaine use are, in themselves, risk factors for poorer outcome. If a direct comparison is made of cocaine-exposed offspring with nonexposed offspring, the exposed offspring do less well in all aspects. However, when other risk factors are considered, the effects of cocaine use on infant outcome were an illusion. The reality is that the lifestyle and covariates of cocaine use combine to affect the infant's status. There are several methodological advantages of this study. This is a sample of women who sought prenatal care early in pregnancy, thus minimizing the negative effects of poor health care. All women are interviewed at set intervals at the end of each trimester of pregnancy to minimize recall bias. Detailed quantity and frequency information is obtained about all licit and illicit drugs, with special attention paid to early first-trimester exposure. We have demonstrated that women who use cocaine prenatally also use more alcohol, marijuana,

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994

PRENATAL COCAINE EXPOSURE

TABLE 3 Adjusted Mean' Binh Weight (g) by Level of First Trimester Cocaine Use Adjusted for No adjustments Gestational age (GA) GA, tobacco GA, tobacco, alcohol GA, tobacco, alcohol, race, gender

Frequent Users

Nonusers

Difference

p

3,024 3,157 3,176 3,186 3,227

3,331 3,285 3,272 3,268 3,260

307 128

.00 .17 .30 .40 .73

96 82 33

'Derived from analysis of covariance.

We have only discussed the effects ofprenatal cocaine use on a limited number of outcomes at birth. We know less about the impact of cocaine on the central nervous system, which might affect behavior and cognition , effectsmore difficult to measure. It is also difficult to speak to the long-term outcome of cocaine-exposed infants, as longitudinal studies are rare. It is possible that as the children develop increasingly complex cognitive skills, differences will be noted due to cocaine exposure. This awaits additional study. However, we believe the effects of prenatal cocaine exposure reported to date reflect the impact of polydrug use and a disadvantaged lifestyle, rather than the direct effects of cocaine use. Future research should focus on the cumulative effects of substance use and the associated lifestyle characteristics.

and tobacco, information that is needed to properly separate the effects of potential teratogens. A large sample of women allows statistical control ofconfounding variables (or covariates) to clarify the real effects of prenatal cocaine use. A limitation of the study is that women were recruited from a prenatal clinic, and thus we have not studied women who were heavy users of cocaine/crack and who were hesitant to seek medical care. This is a preliminary analysis of data from a large longitudinal study. This analysis used a portion of our data, the average daily amount of cocaine/crack used (a variable that combines quantity and frequency information) , and described neonatal growth effects in two extreme exposure groups. Few other researchers have collected such detailed information regarding the pattern of drug use during pregnancy. These data are essential to properly evaluate the potential teratogenic impact of prenatal cocaine exposure. Future analyses from this study will investigate the impact of cocaine use across the entire range of exposure as well as the differential impact of cocaine and crack.

REFERENCES Ballard ]L, Novak KK, Driver BA (1979), A simplified score for assessment of fetal maturation of newly born infants. ] Pediatr, 95:769-774 Brazelton TB (1984), Neonatal Behavioral Assessment Scale. (2nd ed.), Philadelphia: ]B Lippincott Company

TABLE 4 Neonatal Characteristics

Percent male Mean Dubowirz score" (wks) Mean 1 min Apgar Mean 5 min Apgar Mean birth weight (g)' Mean length (ern)' Mean head circumferernce (em)' Mean number minor physical anomalies

Frequent Cocaine Users'

Nonusers'

50% 38.9 (21-44) 8.0 (3-9) 8.9 (7-10) 3,227 (930-4,500) 49.9 (39- 56) 34.5 (30- 37) 1.2 (0-5)

53% 39.8 (34-44) 7.8 (2-10) 8.8 (4-10) 3,260 (2,140-5,600) 49.6 (45- 55) 34.5 (31- 39) 1.0 (0-6)

'First trimester bMeans were adjusted for first trimester tobacco and alcohol use, race, and infant gender with analysis of covariance. 'Means were adjusted for gestational age, first trimester tobacco and alcohol use, race, and infant gender with analysis of covariance.

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RICHARDSON AND DAY Brenner WE, Edelman DA, Hendricks CH (1976), A standard of fetal gro wth for the Un ited St at es of America. Am] Obstet Gynecol 126:555-564 Chasnoff 1] (1988), Cocaine: effects on pregnancy and the neonate. In: Drugs, Alcohol; Pregnancy and Parenting, ed IJ Chasnoff. Boston: Kluwer Academic Publishers, pp. 97-103 Chasnoff IJ, Burns KA, Burns WJ (1987), Cocaine use in pregnancy: perinatal morbidity and mortality. Neurotoxicol TeratoI9:291-293 Coles CD , Plarzman KA, Smith I, James ME, Falek A (1992), Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status. Neurotoxicol Teratol 14:23-33 Day NL, Cornelius MD , Goldschmidt L, Richardson GA, Robles N , Taylor PM (1992), The effects of prenatal tobacco and marijuana use on offspring growth from birth through three years of age. Neurotoxicol

TeratoI14:407-414 Day NL, Jasperse D, Richardson GA et al. (1989), Prenatal exposure to alcohol: effect on infant growth and morphologic characteristics. Pediatrics 84:536-541 Day NL, Sambamoorthi U, Taylor P et al. (1991), Prenatal marijuana use and neonatal outcome. Neurotoxicol TeratoI13:329-334 Day NL, Wagener DK, Taylor PM (1985), Measurement of substance use dur ing pregnancy: methodologic issues. In: Consequences of Maternal Drug Abuse, ed TM Pinkerr. NIDA Research Monograph No. 59, pp. 36-47

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Dixon SD, Bejar R (1989), Echoencephalographic finding s in neonates associatedwith maternal cocaine and methamphetamine use: incidence and clinical correlates. ] Pediatr 115:770-778 Gillogley KM, Evans AT, Hansen RL, Samuels SJ, Batra KK (1990), The perinatal impact of cocaine, amphetam ine, and opiate use detected by universal intrapartum screening. Am] Obste: GynecoI163:1535-1542 McCalla S, Minkoff HL, Feldman et al. (1991), The biologic and social consequences of perinatal cocaine use in an inner-city population : results of an anonymous cross-sectional study. Am ] Obstet Gynecol 164:625-630 Neuspiel DR, Hamel SC, Hochberg E, Greene J, Campbell D (1991), Maternal cocaine use and infant behavior. Neurotoxi col Teratol 13:229-233 OsofskyJ, Danzger B (1974), Relationships between neonatal characteristics and mother-infant characteristics. Developmental Psychology 10:124-130 Richardson GA, Day NL (1991), Maternal and neonatal effectsof moderate cocaine use during pregnancy. Neurotoxicol Teratol13:455-460 Richardson GA, Day NL, McGauhey PJ (1993), The impact of prenatal marijuana and cocaine use on the infant and child. Clin Obstet Gyne-

col36:302-318 RoblesN, Day NL (1990), Recallof alcohol consumption during pregnancy. ] Stud Alcohol 51:403-407 Streissguth AP, Grant TM , Barr HM et al. (1991), Cocaine and the use of alcohol and other drugs during pregnancy. Am ] Obstet Gynecol 164:1239-1243 Tabachnick BG, Fidell 15 (1989), UsingMu/tivariate Statistics (2nd Edition). New York: Harper Collins Publishers, Inc

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