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Cocaine use during pregnancy: Maternal depressive symptoms and infant neurobehavior over the first month
INFANT
BEHAVIOR
AND
DEVELOPMENT
16,
83-98
(1993)
Cocaine Use During Pregnancy: Maternal Depressive Symptoms and Infant Neurobehavior Over the First Month NANCI STEWART WOODS, FONDA MARYLOU BEHNKE, AND MICHAEL University
DAVIS
EYLER,
CONLON
of Floridu College of Medicine University of Florida
Research an the effects of prenatal cocaine exposure has produced an inconsistent pattern of results. The goals of this project were (a) to improve upon the methodology of previous research by matching subjects one-to-one on important confounding maternal and infant variables, (b) to tnvestigote a population of rural women not enrolled in an intenswe prenotol intervention program, (c) to ossess the impact of cocaine use on maternal depressive symptoms both immediately and 1 -month postpartum, and (d) to provide longitudinal doto regarding the effect of cocaine exposure and maternal affect on neurobehovioral development of neonotes by assessing the infants in the hospital and at 1 month of age. Cocaine-using mothers hod significantly fewer prenatal visits ond reported more depressive symptoms following delivery than did control mothers. Cocaine-exposed infants had significantly lower brrthweights and shorter gestations. There were no significant differences m neonotol performance on the Brazelton stole ot birth or 1 month of age. These findings demonstrate that not all cocaine-exposed infonts exhibit neurobehovioral deficits in the neanatol period. Longitudinal research is needed to determine if problems will monifest themselves at later ages when greater developmental demands ore placed upon these children.
Brozelton
stole
maternol
depressron infant assessment
prenatal
cocaine
exposure
Currently, there is a great deal of interest in the effects of prenatal cocaine exposure on infants. The examination of this problem during the neonatal period is important because any behavioral or physical abnormalities observed later in development might be the result of interaction among medical, We gratefully wood, and Laurie on Infant Research Pediatric ment
Studies in Child Research.
Correspondence of Psychology.
acknowledge the assistance of Amy Baswell. Tucker. Portions of this article were presented in Montreal. Quebec, Development, Seattle, New Orleans, LA.
Allison Hess, at the International
Canada. April 19YO. the meeting WA, April 1991. and the meeting April 1990.
and requests for reprints should Austin Peay State University,
bc sent Clarksville.
to Nanci Stewart TN 37044.
Christine KirkConference
of the Society of the Society Woods,
for for
Depart-
a3
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EYLER, BEHNKE,
AND
CONLON
maturational, and environmental factors (Riley, Hannigan, & BalazHannigan, 1985). Studies on the teratogenicity of cocaine in animals and humans have produced conflicting results. Some researchers have reported no increase in malformations (Fantel & Macphail, 1982; Giordano et al., 1990; Hadeed & Siegel, 1989; Madden, Payne, & Miller, 1986), whereas others have observed urogenital, urinary, or other types of defects (Chasnoff, W. Burns, Scholl, & K. Burns, 1985; Chasnoff, Chisum, & Kaplan, 1988; Chavez, Mulinare, & Cordero, 1989; Mahalik, Gautieri, & Mann, 1980; Ryan, Ehrlich, & Finnegan, 1987). Research on other effects of prenatal cocaine exposure also has not revealed a consistent pattern of effects. Using mostly retrospective study designs, researchers have reported a diverse and variable set of findings including younger gestational age, reduced birthweight, decreased length or head circumference, increased incidence of intrauterine growth retardation, lower Apgar scores, and higher rates of sudden infant death syndrome. Reported obstetrical problems have included higher rates of abruptio placentae, spontaneous abortion, premature rupture of membranes, and stillbirth (Bingol, Fuchs, Diaz, Stone, & Gromisch, 1987; Frank et al., 1988; Hadeed & Siegel, 1989; Kaye, Elkind, Goldberg, & Tytun, 1989; MacGregor, Keith, Bachichrt, & Chasnoff, 1989; MacGregor et al., 1987; Neerhof, MacGregor, Retsky, & Sullivan, 1989; Ryan et al., 1987; Zuckerman et al., 1989). Infant Neurobehavior
Four published studies have used the Brazelton Neonatal Behavioral Assessment Scale (BNBAS; Brazelton, 1984) to investigate the neurobehavioral development of cocaine-exposed infants (Chasnoff et al., 1985; Chasnoff, Griffith, MacGregor, Dirkes, & Burns, 1989; Eisen et al., 1991; Neuspiel, Hochberg, Greene, & Campbell, 1991). The cocaine-using mothers in the studies conducted by Chasnoff and colleagues were enrolled in a Chicagobased prenatal intervention program providing drug treatment and intensive obstetrical care to substance abusers who voluntarily enrolled prior to the 12th week of pregnancy. The usefulness of their first study is limited due to small group sizes, excessive statistical analyses which may have increased chance findings, and no matching for potentially confounding variables. Chasnoff et al.% (1989) second, larger study used the BNBAS to compare 23 infants exposed to cocaine only during the first trimester, 52 infants exposed throughout gestation, and 40 drug-free infants. Both cocaine-exposed groups showed significantly lower mean cluster scores (Lester, Als, & Brazelton, 1982) in the areas of orientation, motor performance, and state regulation, and a greater number of abnormal reflexes. In Chasnoff et al.‘s (1989) study, the majority of the women in the cocaine groups reported alcohol use during pregnancy; however, none of the women in the control group reported
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using alcohol during pregnancy. In addition, cocaine-exposed infants were more likely to have been born small for gestational age. Although this may have been a result of maternal cocaine use, there are other possible causes of growth retardation including maternal smoking and/or alcohol use. These confounding factors make it difficult to interpret whether the behavioral differences between the groups were a result of cocaine exposure or growth retardation indirectly affected by cocaine, alcohol and/or tobacco exposure. Another concern regarding the second Chasnoff et al. (1989) study is that it is not clear that the target and control groups were tested concurrently (Chasnoff & Griffith, 1989). If, in fact, the groups were not tested concurrently, examiners may have developed suspicions regarding which group of infants were being tested. Even if they were completely blind to group status, testers may have come to expect and exaggerate any real group differences. This possibility is important because the BNBAS is, by design, an interactive, and therefore, potentially subjective assessment. The 26 cocaine-exposed neonates studied by Eisen et al. (1991) showed poorer performance on the habituation cluster when compared to controls who tested negative for both cocaine and marijuana. Matching of control neonates to cocaine-exposed neonates involved a random procedure that stratified the groups on birthweight, gestational age, sex, and race. However, cocaine-using mothers were significantly more likely to smoke tobacco and drink alcohol. Mothers were primarily inner-city, black, low-socioeconomicstatus women. Neuspiel et al. (1991) found a significant difference in the motor cluster scores between 20 cocaine-exposed and 32 comparison infants when a BNBAS exam was conducted at 11 to 30 days following delivery. There were no differences on any of the BNBAS clusters when the exam was conducted at 1 to 3 days. Subjects were recruited from an urban public hospital in Bronx, NY, and cocaine-using mothers were significantly more likely to drink alcohol and smoke marijuana and tobacco. In summary, current research on the neonatal neurobehavior of cocaineexposed infants suggests that shortly followed delivery, neonates may exhibit more abnormal reflexes and less optimal habituation, orientation, motor, and state regulation abilities. Several weeks following delivery these infants may show poorer motor performance. To date, a consistent pattern of neurobehavioral deficits has not been demonstrated. Substance
Abuse
and Maternal
Depression
There are no published data on maternal factors that might affect the caregiving environment of a cocaine-exposed infant. A number of studies have found a relationship between drug use and depression (K. Burns, Melamed, W. Burns, Chasnoff, & Hatcher, 1985; Keeler, Taylor, & Miller, 1979; Ross & Berzins, 1974; Weissman & Myers, 1980). It is not, however, clear whether
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depression promotes drug use or drug use results in depression. There is some evidence that cocaine abusers undergoing treatment have an increased incidence of affective disorders (Gawin, 1986; Weiss, Mirin, Michael, & Sollogub, 1986). Research indicates that children of depressed mothers are at risk for behavioral and emotional problems (Ghodsian, Zajicek, & Wolkind, 1984; Rutter, 1966; Zuckerman & Beardslee, 1987). There is evidence that depressed mothers express flat affect during interaction with their infants, provide less stimulation, and fail to modify their behavior according to the behavior of their infant (Cohn, Matis, Tronick, Connell, & Lyons-Ruth, 1986; Field et al., 1988). Cohn and Tronick (1983) found that even brief experience with simulated maternal depression at 3 months resulted in continued negative infant affect even after the mother returned to normal interaction. In summary, research indicates that children and even infants of depressed parents are at risk for behavioral and emotional problems. In addition, substance abusers and, in particular, cocaine abusersmay be at increased risk of depressive disorders. Currently, there is no published information on the levels of depression experienced by cocaine-using mothers. Our study is the first to investigate the neurobehavioral development Gf infants born to a population of cocaine-using pregnant women who delivered at a rural referral hospital and did not receive intensive prenatal intervention. Improvements over previous studies on the neurobehavioral effects of prenatal cocaine exposure include: (a) explicit procedures for maintaining examiner blindness, including the concurrent testing of cocaine-exposed and control infants and the incorporation of “fake” subjects; (b) samples matched one-to-one on potentially confounding variables; (c) inclusion of a maternal measure assessingdepressive symptoms shortly after birth and 1 month later; and (d) the opportunity to observe any effect of maternal affect on infant neurobehavior at 1 month of age. METHOD Subjects
The subjects in this experiment were drawn from a tertiary-level teaching hospital serving a rural population. The majority of obstetrical patients are at risk for prenatal or perinatal problems and are of low socioeconomic status. The cocaine-exposed group included infants and/or mothers who, for physician-determined clinical reasons, had their urine tested and found positive for cocaine metabolites, aswell as any infants whose mothers admitted to health personnel that they had used cocaine at any time during their pregnancy. Control subjects had no history of illicit drug use during pregnancy. An anonymous prevalence study conducted in the well-baby nursery at our
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institution found that fewer than 2% of infants whose mothers did not admit cocaine use tested positive for cocaine metabolites at delivery (Behnke, Eyler, Conlon, Adams, & Stewart, 1990). The two samples included 35 cocaine-exposed infants and their mothers and 35 infant-mother dyads with no evidence of cocaine or other illicit drug use during pregnancy. The control group matched the cocaine-exposed group one-to-one on the following variables: maternal race, primi- or multiparty, presence or absence of maternal tobacco use, size for gestation (Battaglia & Lubchenco, 1967), and type of delivery. Informed consent was usually not obtained from mothers who delivered infants by Caesarean section until several days following delivery. For this reason, type of delivery was included as a matching variable in order to control for infant age at testing. Preliminary review of the medical records of all neonates born during a 15 day period revealed that only 8% of mothers admitted prenatal use of alcohol to health professionals during routine questioning. Given that this is a much lower rate than that usually reported in obstetric populations, we believed that we could not use medical record reports of alcohol use to match alcohol exposure accurately (Kuzma & Sokol, 1982; Robles & Day, 1990; Tennes & Blackard, 1980). Unfortunately, we were prevented from interviewing subjects regarding prenatal substance use because state law would have required us to report cocaine-using women to the child abuse authorities despite having granted them research confidentiality. All infants participating in this study were admitted to the well-baby nursery following delivery and lived within 80 miles of the hospital. All were born at a gestational age of at least 35 weeks as determined by routine Ballard exam (Ballard, Kazmaier, & Driver, 1977). Mothers were at least 17 years of age and had no adverse medical problems during pregnancy or conditions that would have made it difficult to provide informed consent. Reasons for maternal exclusion from the study included conditions such as diabetes, medicated epilepsy or hypertension, mental retardafion, or deafness. Measures
The BNBAS (Brazelton, 1984) was used because it is the most widely known and utilized neonatal assessment. Furthermore, it was the assessment that had been used in previously published research on cocaine-exposed neonates (Chasnoff et al., 1985; Chasnoff et al., 1989). The BNBAS does not provide one summary score. Therefore, to reduce the data for statistical analysis, individual scores are commonly grouped into the six behavioral clusters established by Lester et al. (1982): habituation, orientation, motor performance, range of state, state regulation, and autonomic regulation. In addition, the total number of abnormal reflexes is recorded. The 1984 version of the BNBAS which was used in this study also includes nine optional supplementary items that were designed to assess the
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fragile infant’s ability to cope with and utilize environmental stimuli. They measure the physiological “cost” to the infant necessary to achieve and maintain an alert state. The Beck Depression Inventory (BDI; Beck, Ward, Mendelson, Mock, & Erbaugh, 1961) has been considered to be the best self-report measure of general depression available for assessing the intensity of depression (Rehm, 1981). The abbreviated 13-item form used in this experiment has been found to correlate .96 with the original (Beck, Steer, & Garbin, 1988). This short version is more appropriate for use with pregnant or recently delivered women because it excludes questions related to issues such as weight gain and frequency of sex which are confounded by pregnancy. Procedures
Medical charts of all admissions to the well-baby nursery were reviewed daily by one of four research assistants. During the course of the 11-month study, 78 cocaine-exposed infants were identified; 4 were not eligible due to maternal retardation, maternal seizure disorder, or gestational age less than 35 weeks; and 13 were discharged before consent could be requested. In the hospital where this experiment was conducted, infants are discharged, on average, about 24 hours after birth. Because records were reviewed each morning, there were often only a few hours during which all infant-mother dyads identified that day could be contacted, enrolled, and assessed. The principal investigator, a certified BNBAS evaluator, carried out all testing of mothers and infants. The following procedures were implemented in an effort to prevent the accidental disclosure of identifying information. The evaluator was not involved in subject selection and carefully avoided interaction with health professionals who might inadvertently disclose a subject’s status. If the evaluator became aware of any identifying information, the subject was dropped from the experiment. Efforts were also taken to prevent any cues regarding group membership. For instance, the evaluator was regularly asked to assess subjects who were not intended to be included in either final sample. The inclusion of these “fake” subjects prevented the evaluator from suspecting that two similar mother-infant dyads might be matched to each other. The evaluator was provided only with the date, type, and time of birth, the mother’s name, infant’s sex, and the estimated time of discharge from the hospital for each subject. The mother was specifically told that the investigator had no knowledge of her substance use history and needed to remain that way throughout the experiment. Mothers were told they would receive a box of diapers at the l-month follow-up visit. The BDI was administered orally to each mother. The BNBAS was conducted in the well-baby nursery when the infant was approximately midway between feedings. Of the 61 cocaine-using mothers who were asked to participate, 42 accepted (68%), compared to 70% acceptance rate for control mothers. In
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accordance with Florida law, all of the cocaine-using women were under investigation by the Department of Health and Rehabilitative Services. A total of 8 infants, 6 cocaine-exposed, were dropped from the experiment due to maternal or staff disclosure of drug-use status. One cocaine-exposed mother-infant dyad could not be matched (a black smoker with no children, who vaginally delivered a large-for-gestational-age infant). Subsequent to the initial testing, mothers were contacted by letter and then called by a research assistant to schedule follow-up. Twenty-one of the 35 cocaine-exposed infants were follow-up tested; however, the matched-control for 1 infant did not return for testing. Two cocaine-exposed infants were brought by their foster parents; therefore, maternal depressive levels could not be assessed. Because subjects could live as far as 80 miles from the hospital, it was not possible to conduct all follow-up testing at the same location. In order to avoid the wide variations in home environments common in this rural population and to provide a nonthreatening location for mothers, half of whom were under child abuse investigation, subjects were tested at restaurants near the location of the family’s home. Avoidance of the home also eliminated environmental cues concerning drug use. Assessments were conducted during the midmorning or midafternoon slow periods, which resulted in distractions and noise levels remarkably similar to the hospital nursery.
RESULTS Subjects were primarily multiparous (74%), black (66%), smokers (74%), who vaginally delivered (91%) average-size-for-gestational-age infants (97%). There were 2 large-for-gestational-age infants (1 cocaine-exposed and 1 matched-control) but no small-for-gestational-age infants included in this study. Cocaine-exposed infants had significantly shorter gestations and lower birthweights than did nonexposed infants (Table 1, p. 90). The infants did not differ on Apgar scores, head circumference, length, ponderal index, or ageat the time of the first or second BNBAS exam. There was no difference in maternal age or socioeconomic status. Finally, cocaine-using women had significantly fewer prenatal visits than did the noncocaine-using women (Table 1). Review of the clinical medical record indicated that based on maternal selfreport and/or a clinically ordered urine toxicology screen positive for cocaine metabolites, 83% of the infants in this experiment were exposed to at least some cocaine beyond the first trimester, and 77% were exposed into the third trimester. Fifteen of the 20 infants (75%) who returned for 1 month follow-up had been exposed into the third trimester. In describing their cocaine use, 80% of the women specifically used the term “crack.” In addition, 23% of the control women and 60% of the cocaine-using women reported alcohol use during pregnancy. The higher use of alcohol in the control group than in our
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for Cocaine-Exposed Descriptive Vanobles
and
TABLE Means
(and
Standard
Deviations] on
Exposed (n = 35) M WI Gestational Birthweight
age
38.2 2949.4 7.8 8.9
Apgor 1 Apgar 5 Heod circumference Ponderal index Hours old (1st Days old (2nd Moternol age No. of prenatal Socioeconomic “n = 34. l p < .05.
BNBAS) BNBAS) visits status
(1.8) (444.8) (1.7) (0.5)
1 Nonexposed
Groups
Nonexposed (n = 35) f
M WI 39.1 3181.6 7.9 8.8
(1.5)
2.23’
(353.2) (1.6) (0.6)
2.42’ 0.07 0.67
33.8 2.5 3:.7
(1.3) (0.4) (21.2)
34.0 (1.3) 2 6 (0.3) 32.3 (9.5)O
0.54 1.18 0.15
28.7 25.4 5.5 16.6
(3.8)” (4.6) (4.8) 14.71
28.0 23.9 8.4 17.7
0.52 1.25 2.46
(4.6)” (5 5) (4.7)” (5.91
0.84
% = 20. ‘*p < .Ol
general obstetric population (7.3%) may have resulted from matching on variables such as maternal tobacco use (Eyler et al., 1990). Analysis of variance (ANOVA) between exposure status and the BNBAS clusters revealed that there were no significant differences between the cocaine-exposed and nonexposed infants on any of the BNBAS clusters when tested shortly after delivery. There were also no significant differences between the groups on the BNBAS supplementary items. Multivariate analysis of variance (MANOVA) was also used in order to utilize the information about the relationships (i.e., correlations) amcng the dependent variables. MANOVA indicated that there was no overall effect of exposure status on BNBAS clusters or the nine supplementary items. There was, however, a significant difference in maternal levels of self-reported depressive symptoms. Cocaine-using women scored significantly higher on the BDI than did women with no evidence of cocaine use. Table 2 presents the means and standard deviations for the BDI and BNBAS clusters following delivery. The average in-hospital BDI score for cocaine-using women who returned for l-month follow-up was 4.1 (SD = 4.1). Cocaine-using women who failed to return for follow-up had an average score of 6.6 (SD = 4.9). Analysis on this sample of 20 cocaine-using women indicated that there was not a statistically significant differential drop-out based on initial depression score. Given this small sample size, however, differential drop-out cannot be ruled out. It is not possible to examine this relationship among the control women because they were only assessed at 1 month if the target to whom they were matched returned.
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TABLE Means
(and
Standard
Deviations)
BDI Hobituation Orientation Motor Ronge of state State regulation Autonomrc regulatron Abnormal reflexes On = 33. ‘p c .05.
‘n
Means
= 21.
‘n
=
(ond
Standard
far
NEONATAL
EFFECTS
91
2 BDI
and
BNBAS
Clusters
at Birth
Exposed (n = 35)
Nanexposed (n = 35)
M (SD)
M WI
5.2 7.0 2.9 4.4
(4.7)” (1.3)b (1.2) (0.8)
3.2 7.4
(2.6) (0.9)’
3.07’ 0.96
3.7 4.5 7.2
(0.6) (1.4) (1.6)
3.2 4.6 3.7 4.8 7.2
(0.5) (0.8) (0.6) (1.6) (1.4)
0.00 1.11 0.11 0.60
2.7
(2.0)
2.1
(2.1)
F
0.00 1.34
16
TABLE 3 for BDI ond
Deviations)
BNBAS
Clusters
at 1 Month
Exposed (n = 20)
Nonexposed (n = 20)
M (SD1
M WI
BDI
2.9
(2.9)”
3.2
(3.2)
0.14
Orientation Motor Ronge of state
3.6 4.9 3.8
(1.2) (0.7) (0.5)
4.7 5.4 3.5
(2.l)b (0.7) (0.9)
1.66 1.42 1.33
State regulotion Autonomic regulotion Abnormal reflexes
4.0 8.6 2.3
(1.3) (0.6) (1.9)
4.4 (1.7) 8.4 (1.6) 1.5 (1.4)
0.63 0.22 1.32
Note. ‘?I =
No 18.
significant differences ?I = 19.
between
F
groups
MANCOVAs on the l-month follow-up data revealed no significant difference between the two groups of infants when controlling for initial BDI score. In addition, the difference in maternal depressive symptomatology found at the time of delivery was no longer apparent at 1 month. The nine supplementary items from the l-month BNBAS were not examined due to missing data and small sample size. Table 3 presents the means and standard deviations for data collected 1 month following delivery. DISCUSSION As documented by previous studies, there are negative effects of prenatal cocaine exposure. A decrease in birthweight has been found in almost every study published, whether prospectively or retrospectively conducted, and it was found in this experiment as well. Many researchers have also documented
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a decrease in gestational age similar to that found here. The lower gestational ages found in our experiment are interesting in that the sample was limited to infants of at least 35 weeks gestational age and healthy enough to have been admitted to the well-baby nursery. This suggests that prenatal cocaine exposure may shorten the length of gestation whether or not an infant is born prematurely. It is intriguing that the cocaine-using women reported more depressive symptoms than the nonusing women immediately following delivery but not l-month postpartum. There are several possible reasons for this change. First, the initial assessment occurred while the cocaine-using women were under investigation for child abuse. Second, cocaine-using women in the hospital may have been suffering from withdrawal-induced depression. Third, cocaine-using women’s initial concern and guilt about the effect of their cocaine use on their infant may have lessened after a month of caregiving. In two of the four previously published studies, cocaine-exposed neonates were found to have less optimal state organization and regulation than nonexposed infants (Chasnoff et al., 1985; Chasnoff et al., 1989). Infants in the later study also exhibited deficits in interactive ability and motor performance. Cocaine-exposed neonates in our experiment were expected to be at even greater risk because their mothers attended fewer prenatal visits than contfols and were not participants in an organized prenatal intervention program. However, they, like the infants examined by Neuspiel et al. (1991), exhibited no differences in neurobehavioral performance when compared to nonexposed neonates shortly after delivery. Our infants did not exhibit poorer motor abilities when tested at 1 month of age, as did those tested by Neuspiel et al. (1991). It is interesting that infants in the Neuspiel et al. study were tested at an average of 19 days of age, whereas ours were tested at an average of 28 days of age. It may be that the subtle motor differences they observed represent transient difficulties experienced by cocaine-exposed infants in the first few weeks following delivery. It is possible that our sample had less heavy cocaine use than a sample of women who voluntarily sought treatment. In Chasnoff et al. (1989), however, even the infants whose mothers stopped using cocaine in the first trimester showed significantly worse orientation, motor, and state regulation. Based on maternal self-report and/or a positive toxicology screen, 83% of the infants in this experiment were exposed to cocaine beyond the first trimester. Other indirect evidence suggests that substantial cocaine exposure may have occurred during pregnancy in the majority of the drug group in this experiment. Twenty-six percent reported previous and/or current participation in some type of drug treatment program. When describing their cocaine use, 80% of the women specifically referred to the use of crack. Crack cocaine is considered to be more quickly addictive than other forms of cocaine due to the intensity of the “high” and the subsequent acute depression produced by
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this method of administration (Perez-Reyes, DiGuiseppi, & Ondusek, 1982). Women not specifically describing crack use reported: (a) a 5-year history of snorting cocaine, (b) use of crank during first trimester followed by treatment, (c) regular use of cocaine throughout pregnancy, and (d) a 1Zyear history of intravenous cocaine use. The three remaining women admitted to cocaine use only in the first 18 weeks of pregnancy. Another factor suggesting significant use is that Florida mandates that all mothers of cocaine-exposed infants be investigated for child abuse. Women appear to be quite aware of this situation, and it is our opinion that the majority of women who are still using in the latter stages of their pregnancy are addicted and are unable to stop regardless of the consequences. In fact, three of the mothers participating in this experiment were known to have previously delivered a cocaine-exposed infant, and a fourth had previously delivered two other exposed infants. Chasnoff et al. (1989) reported similar levels of alcohol use in their two cocaine-exposed groups, but absolutely no alcohol use in the control group. This confounding factor may have contributed to the poorer BNBAS performance of their cocaine-exposed infants. Level of alcohol use is an important factor in this type of research as prenatal alcohol exposure has been found by some researchers to alter the neurobehavioral development of neonates (Coles, Smith, Lancaster, & Falek, 1987; Streissguth, Barr, & Martin, 1983). The most serious problem with our experiment was the inability to match the cocaine-exposed and nonexposed groups on prenatal alcohol use. Because we could not control for the existence or amount of alcohol use, we cannot be certain the significantly decreased birthweight and gestational age found in the target group were due solely to cocaine exposure. However, given the higher rate of alcohol use in our control group (23%) than that reported by the general obstetrical population (7.3%), it may be that controlling for other confounding factors (e.g., maternal tobacco use and size appropriateness) provided an indirect control for maternal alcohol use. Although there remained apparent group differences in alcohol use, the information regarding prenatal alcohol use was not collected in the same manner for the two groups. Women in the control group were asked by nurses about their substance use as a part of routine admission screening. In contrast, once a woman was identified as a cocaine user, she was interviewed in depth by a clinical social worker regarding her substance use and psychosocial history. In addition, women who had already admitted use of an illegal drug may have been less hesitant to admit use of a legal substance. Therefore, true alcohol use may well have been even higher than documented in the controls, and thus closer to the cocaine user’s rate. If differences in neurobehavior had been found between the groups in this experiment, then the inability to match subjects one-to-one on alcohol use during pregnancy would have weakened our behavioral findings. It seems
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highly unlikely, however, that the women in the control group actually had significantly higher levels of alcohol use than the cocaine-using women, and that this imbalance obscured cocaine-related differences in neonatal neurobehavior between the two groups. The issue of examiner blindness to group membership is always relevant in research using subjective measures, but it becomes even more crucial when there are strong initial hypotheses concerning positive or negative impact on measured outcome. The plight of cocaine-exposed infants is currently an extremely emotional and political issue. Researchers studying these infants are likely to have strong expectations about the potentially harmful effects that can result from maternal use of such a potent vasoconstricter. Although hypotheses promote research, it is essential that experiments be designed so that the null hypothesis cannot be falsely rejected (Koren, Graham, Shear, & Einarson, 1989). Maintaining examiner blindness is not a simple issue. It involves complex, coordinated efforts among members of a research team. If one thinks in terms of a continuum of blindness, it is easier to acknowledge that there is a difference between simply not “knowing” the status of a subject and carefully designing procedures and controlling the environment to allow no cues as to group membership. A strength of our findings lies in the efforts made to maintain blindness and optimize objectivity. The most valuable outcome of this experiment may be to remind us that there is likely a continuum of casualty for any developmental toxin or teratogen. Even during the thalidomide tragedy, a significant number of children exposed to this teratogen during the critical period of 20 to 36 days postconception (Lenz, 1965) were born normal (Kajii, Kida, & Takahashi, 1973; Mellin & Katzenstein, 1962; Smithells, 1962). Although it is important to encourage and help all pregnant women to stop using cocaine, it is important to provide careful and accurate information. There is evidence that women overestimate the negative potential of information physicians provided to them about teratogens, and, in fact, are more likely to abort than is warranted by the level of exposure (Koren, Bologa, Long, & Shear, 1989; Koren, Feldman, & MacLeod, 1990; Trichopoulos et al., 1987). Overgeneralization may frighten away prospective parents for those infants who are placed for adoption. It is crucial that we carefully determine the entire range of consequences of prenatal cocaine exposure and work to determine what beneficial effects might result from achieving abstinence at different times during pregnancy. In discussions about cocaine-exposed infants, one of the most commonly stated characteristics is that they tremor and startle more than normal infants. This is a documented characteristic of infants withdrawing from depressants such as heroin; however, there is only one report of this finding when cocaineexposed infants have been prospectively studied (Chasnoff et al., 1985). It is possible that this was a spurious finding due to the number of statistical
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EFFECTS
comparisons. In fact, in the same study there was no difference between the groups on the physiological cluster, which is comprised of only three individual items (tremors, startles, and skin color). The issue of jitteriness is important because many physicians consider increased tremors or startles to be potential indicators of maternal cocaine use and therefore order urine screens to test for cocaine metabolites based on this symptomatology. Interestingly, in a recent study conducted by Parker et al. (1990), it was determined that 44% of 936 healthy, full-term neonates exhibited jitteriness during a IO-min neurological assessment. Analyses revealed that infants prenatally exposed to marijuana, but not those exposed to cocaine, were more likely to jitter. At our own institution, we have found that drug screening based on maternal or infant perinatal risk factors is not effective in accurately identifying prenatal cocaine users (Behnke et al., 1990). More research into the effects of prenatal cocaine exposure is urgently needed. Although cocaine may not be a teratogen, we need information about its potential to alter mother-infant interaction and infant development. Even if future research fails to document any effects in the neonatal period, it is possible that central nervous system damage from the drug or from intrauterine hypoxia related to use might manifest itself at later ages when greater demands are placed upon the child.
REFERENCES Ballard.
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Chasnoff, I.J.. Griffith, D.R., MacGregor, S., Dirkes, K., & Burns, K.A. (1989). Temporal patterns of cocaine use in pregnancy. Journal of the American Medical Associafion. 261, 1741-1744. Chavez, G.F., Mulinare, J., & Cordero. J.F. (1989). Maternal cocaine use during early pregnancy as a risk factor for congential urogenital anomalies. Journal of the American Medical Association. 262. 795-798. Cohn, J.F., Matis, R., Tronick, E.Z.. Connell, D., & Lyons-Ruth, K. (1986). Face-to-face interactions of depressed mothers and their infants. In E.Z. Tronick & T. Field (Eds.), New directions for child development: Vol. 34. Maternal depression and infant disturbance. San Francisco: Jossey-Bass. Cohn, J.F., & Tronick, E.Z. (1983). Three-month-old infants’ reaction to simulated maternal depression. Child Developmen!, 54, 185-193. Coles, C.D., Smith, I.E., Lancaster, J.S., & Falek, A. (1987). Persistence over the first month of neurobehavioral differences in infants exposed to alcohol prenatally. lnfanr Behavior and Development. 10. 23-37. Eisen, L.N., Field, T.M., Bandstra, E.S., Roberts, J.P., Morrow, C.. Larson, S.L., & Steele, B.M. (1991). Perinatal cocaine effects on neonatal stress behavior and performance on the Brazelton Scale. Pediatrics, 88, 477-480. Eyler, F.D., Behnke, M., Conlon, M., Stewart, N., Frentzen, B., & Cruz. A. (1990). Perinatal outcome of cocaine-using mothers compared to controls matched on perinatal risk factors. Pediarric Research, 27, 1440. Fantel, A.G., & MacPhail, B.J. (1982). The teratogenicity of cocaine. Teratology, 26, 17-19. Field, T., Healy. B., Goldstein, S., Perry, S., Bendell, D.. Schanberg, S., Zimmerman, E.A., & Kuhn, C. (1988). Infants of depressed mothers show “depressed” behavior even&with nondepressed adults. Child Development. 59, 15691579. Frank, D.A., Zuckerman, B.S., Amaro, H., Aboagye, K., Cabral, H.. Fried, L., Hingson, R., Kayne. H., Levenson. S.M., Parker, S., Reece, H., & Vinci, R. (1988). Cocaine use during pregnancy: Prevalence and correlates. Pediatrics, 82, 888-895. Gawin, F.H. (1986). New uses of antidepressants in cocaine abuse. Psychosomafics, 27, 27-29. Ghodsian, M.. Zajicek, E., & Wolkind. S. (1984). A longitudinal study of maternal depression on child behavior problems. Journal of Child Psychology and Psychiatry, 25, 91-109. Giordano. M., Moody, C.A., Zubrycki, E.M., Dreshfield, L., Norman, A.B., & Sanberg, P.R. (1990). Prenatal exposure to cocaine in rats: Lack of long-term effects on locomotion and sterotypy. Bulletin of the Psychonomic Society. 28. 51-54. Hadeed, A.J., & Siegel, S.R. (1989). Maternal cocaine use during pregnancy: Effect on the newborn infant. Pediatrics, 84, 205-210. Kajii, T., Kida, M., & Takahashi, K. (1973). The effect of thalidomide intake during 113 human pregnancies. Teratology. 8, 163-166. Kaye, K., Elkind, L., Goldberg, D., & Tytun. A. (1989). Birth outcomes for infants of drug abusing mothers. New York Srare Journal of Medicine, 89. 256-261. Keeler, M.H., Taylor, C.I., & Miller, W.C. (1979). Are all recently detoxified alcoholics depressed? American Journal of Psychiatry. 136. 586588. Koren, G., Bologa. M.. Long, D., & Shear, N. (1989). Their perception of teratogenic risk by pregnant women exposed to drugs and chemicals during the first trimester. American Journal of Obstetrics and Gynecology, 160. 1190-t 194. Koren, G.. Feldman, Y.. & MacLeod, S.M. (1990). Motherisk 11: The first year experience in counseling pregnant women on their teratogenic risk. In G. Koren (Ed.), Maternal fetal foxicology: Clinicians’ guide. New York: Marcel Dekker. Koren. G., Graham, K.. Shear, H., & Einarson, T. (1989). Bias against the null hypothesis: The reproductive hazards of cocaine. Lancer, 1, 1440-1441.
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J.W., & Sokol, R.J. (1982). Maternal drinking behavior and decreased intrauterine growth. Alcoholism: Clinical Experimental Research, 6. 396402. Lenz, W. (1965). Discussion. In J.M. Robson, F.M. Sullivan, & R.L. Smith (Eds.), Embryoparhic activity of drugs. Boston: Little, Brown. Lester, B.M., Als, H., & Brazelton, T.B. (1982). Regional obstetric anesthesia and newborn behavior: A reanalysis toward synergistic effects. Child Developmenr, 53, 687-692. MacGregor, S.N., Keith, L.G., Bachicha, J.A., & Chasnoff, I.J. (1989). Cocaine abuse during pregnancy: Correlation between prenatal care and perinatal outcome. Obsretrics and Gynecology, 74. 882-885. MacGregor, S.N., Keith, L.G., Chasnoff, I.J., Rosner, M.A., Chisum, G.M., Shaw, P., & Minogue, J.P. (1987). Cocaine use during pregnancy: Adverse perinatal outcome. American Journal of Obstetrics and Gynecology. 157, 686-690. Madden, J.D., Payne, T.F., & Miller, S. (1986). Maternal cocaine abuse and effect on the newborn. Pediatrics, 77, 209211. Mahalik, M.P., Gautieri, R.F., & Mann, D.E. (1980). Teratogenic potential of cocaine hydrochloride in CF-1 mice. Journal of Pharmaceutical Sciences. 69, 703706. Mellin, G.W., & Katzenstien, M. (1962). The saga of thalidomide. New England Journal of Medicine, 267, 1184-1244. Neerhof, M.G., MacGregor, S.N.. Retsky, S.S., & Sullivan, T.P. (1989). Cocaine use during pregnancy: Peripartum prevalence and perinatal outcome. American Journal of Obstetrics and Gynecology. 161, 633638. Neuspiel, D.R., Hochberg. H.E., Greene, J., & Campbell, D. (1991). Maternal cocaine use and infant behavior. Neurotoxicology and Teratology, 13, 229-233. Parker, S., Zuckerman, B., Bauchner. H., Frank, D., Vinci, R., & Cabral, H. (1990). Jitteriness in full-term neonates: Prevalence and correlates. Pediatrics. 85, 17-23. Perez-Reyes, M., DiGuiseppi, S., & Ondusek, G. (1982). Freebase cocaine smoking. Clinical Pharmacology and Therapeutics, 32, 45W65. Rehm, L.P. (1981). Self-report depression scales. In M. Herson & A.S. Bellack (Eds.), Eehavioral assessmeni: A praclical handbook (2nd ed). Oxford: Pergamon. Riley, E.P.. Hannigan, J.H., & Balaz-Hannigan. M.A. (1985). Behavioral teratology as the study of early brain damage: Considerations for the assessments of neonates. Neurobehavioral Toxicology and Teratology, 7. 635-638. Robles, N., & Day, N.L. (1990). Recall of alcohol consumption during pregnancy. Journal of Studies on Alcohol, 51, 403-407. Ross, F., & Berzins, J. (1974). Personality characteristics of female addicts on the MMPI. Psychological Reports, 35. 779-784. Rutter, M. (1966). The developmental psychopathology of depression: Issues and perspectives. In M. Rutter, C.E. Izard, & P.B. Read (Eds.). Depression in young people. New York: Guilford. Ryan, L., Ehrlich, S., & Finnegan, L. (1987). Cocaine abuse in pregnancy: Effects on the fetus and newborn. Neuroroxicology and Teratology, 9, 295-299. Smithells, R.W. (1962). Thalidomide and malformations in Liverpool. Lancer, I, 1270-1273. Streissguth, A.P., Barr, H.M., & Martin D.C. (1983). Maternal alcohol use and neonatal habituation assessed with the Brazelton Scale. Child Developmenf, 54, 11091118. Tennes, K., & Blackard, C. (1980). Maternal alcohol consumption, birth weight, and minor physical anomalies. American Journal of Obstetrics and Gynecology, 138. 774780. Trichopoulos, D., Zavitsanos, X.. Koutis. C.. Drogari, P., Proukakis, C., & Petridov, E. (1987). The victims of Chernobyl in Greece: Induced abortions after the accident. Rrifish Medical Journal, 295. 1100. Weiss, R.D., Mirin, S.M., Michael, J.L., & Sollogub, A.C. (1986). Psychopathology in chronic cocaine abusers. American Journal of Alcohol and Drug Abuse, 12. 17-29.
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Weissman. M.M.. & Myers. J.K. (1980). Clinical depression in alcoholics. American Journal of Psychiatry. 137. 372-373. Zuckerman. B.S., & Beardslee, W.R. (1987). Maternal depression: A concern for pediatricians. Pediatrics, 79, 110-l 17. Zuckerman. B.S., Frank, D.A., Hingson. R.. Amaro. H., Levenson, S.M.. Kayne. H.. Parker. S., Vinci, R., Aboagye. K., Fried. L.E., Cabraf. H.. Timperi, R., & Bauchner, H. (19X9). Effects of maternal marijuana and cocaine use on fetal growth. New Ettglattd /owna/ of Medicine, 320, 762-768. 8 May
1991; Revised
31 December
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n
BEHAVIOR
AND
DEVELOPMENT
16,
83-98
(1993)
Cocaine Use During Pregnancy: Maternal Depressive Symptoms and Infant Neurobehavior Over the First Month NANCI STEWART WOODS, FONDA MARYLOU BEHNKE, AND MICHAEL University
DAVIS
EYLER,
CONLON
of Floridu College of Medicine University of Florida
Research an the effects of prenatal cocaine exposure has produced an inconsistent pattern of results. The goals of this project were (a) to improve upon the methodology of previous research by matching subjects one-to-one on important confounding maternal and infant variables, (b) to tnvestigote a population of rural women not enrolled in an intenswe prenotol intervention program, (c) to ossess the impact of cocaine use on maternal depressive symptoms both immediately and 1 -month postpartum, and (d) to provide longitudinal doto regarding the effect of cocaine exposure and maternal affect on neurobehovioral development of neonotes by assessing the infants in the hospital and at 1 month of age. Cocaine-using mothers hod significantly fewer prenatal visits ond reported more depressive symptoms following delivery than did control mothers. Cocaine-exposed infants had significantly lower brrthweights and shorter gestations. There were no significant differences m neonotol performance on the Brazelton stole ot birth or 1 month of age. These findings demonstrate that not all cocaine-exposed infonts exhibit neurobehovioral deficits in the neanatol period. Longitudinal research is needed to determine if problems will monifest themselves at later ages when greater developmental demands ore placed upon these children.
Brozelton
stole
maternol
depressron infant assessment
prenatal
cocaine
exposure
Currently, there is a great deal of interest in the effects of prenatal cocaine exposure on infants. The examination of this problem during the neonatal period is important because any behavioral or physical abnormalities observed later in development might be the result of interaction among medical, We gratefully wood, and Laurie on Infant Research Pediatric ment
Studies in Child Research.
Correspondence of Psychology.
acknowledge the assistance of Amy Baswell. Tucker. Portions of this article were presented in Montreal. Quebec, Development, Seattle, New Orleans, LA.
Allison Hess, at the International
Canada. April 19YO. the meeting WA, April 1991. and the meeting April 1990.
and requests for reprints should Austin Peay State University,
bc sent Clarksville.
to Nanci Stewart TN 37044.
Christine KirkConference
of the Society of the Society Woods,
for for
Depart-
a3
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EYLER, BEHNKE,
AND
CONLON
maturational, and environmental factors (Riley, Hannigan, & BalazHannigan, 1985). Studies on the teratogenicity of cocaine in animals and humans have produced conflicting results. Some researchers have reported no increase in malformations (Fantel & Macphail, 1982; Giordano et al., 1990; Hadeed & Siegel, 1989; Madden, Payne, & Miller, 1986), whereas others have observed urogenital, urinary, or other types of defects (Chasnoff, W. Burns, Scholl, & K. Burns, 1985; Chasnoff, Chisum, & Kaplan, 1988; Chavez, Mulinare, & Cordero, 1989; Mahalik, Gautieri, & Mann, 1980; Ryan, Ehrlich, & Finnegan, 1987). Research on other effects of prenatal cocaine exposure also has not revealed a consistent pattern of effects. Using mostly retrospective study designs, researchers have reported a diverse and variable set of findings including younger gestational age, reduced birthweight, decreased length or head circumference, increased incidence of intrauterine growth retardation, lower Apgar scores, and higher rates of sudden infant death syndrome. Reported obstetrical problems have included higher rates of abruptio placentae, spontaneous abortion, premature rupture of membranes, and stillbirth (Bingol, Fuchs, Diaz, Stone, & Gromisch, 1987; Frank et al., 1988; Hadeed & Siegel, 1989; Kaye, Elkind, Goldberg, & Tytun, 1989; MacGregor, Keith, Bachichrt, & Chasnoff, 1989; MacGregor et al., 1987; Neerhof, MacGregor, Retsky, & Sullivan, 1989; Ryan et al., 1987; Zuckerman et al., 1989). Infant Neurobehavior
Four published studies have used the Brazelton Neonatal Behavioral Assessment Scale (BNBAS; Brazelton, 1984) to investigate the neurobehavioral development of cocaine-exposed infants (Chasnoff et al., 1985; Chasnoff, Griffith, MacGregor, Dirkes, & Burns, 1989; Eisen et al., 1991; Neuspiel, Hochberg, Greene, & Campbell, 1991). The cocaine-using mothers in the studies conducted by Chasnoff and colleagues were enrolled in a Chicagobased prenatal intervention program providing drug treatment and intensive obstetrical care to substance abusers who voluntarily enrolled prior to the 12th week of pregnancy. The usefulness of their first study is limited due to small group sizes, excessive statistical analyses which may have increased chance findings, and no matching for potentially confounding variables. Chasnoff et al.% (1989) second, larger study used the BNBAS to compare 23 infants exposed to cocaine only during the first trimester, 52 infants exposed throughout gestation, and 40 drug-free infants. Both cocaine-exposed groups showed significantly lower mean cluster scores (Lester, Als, & Brazelton, 1982) in the areas of orientation, motor performance, and state regulation, and a greater number of abnormal reflexes. In Chasnoff et al.‘s (1989) study, the majority of the women in the cocaine groups reported alcohol use during pregnancy; however, none of the women in the control group reported
COCAINE:
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EFFECTS
85
using alcohol during pregnancy. In addition, cocaine-exposed infants were more likely to have been born small for gestational age. Although this may have been a result of maternal cocaine use, there are other possible causes of growth retardation including maternal smoking and/or alcohol use. These confounding factors make it difficult to interpret whether the behavioral differences between the groups were a result of cocaine exposure or growth retardation indirectly affected by cocaine, alcohol and/or tobacco exposure. Another concern regarding the second Chasnoff et al. (1989) study is that it is not clear that the target and control groups were tested concurrently (Chasnoff & Griffith, 1989). If, in fact, the groups were not tested concurrently, examiners may have developed suspicions regarding which group of infants were being tested. Even if they were completely blind to group status, testers may have come to expect and exaggerate any real group differences. This possibility is important because the BNBAS is, by design, an interactive, and therefore, potentially subjective assessment. The 26 cocaine-exposed neonates studied by Eisen et al. (1991) showed poorer performance on the habituation cluster when compared to controls who tested negative for both cocaine and marijuana. Matching of control neonates to cocaine-exposed neonates involved a random procedure that stratified the groups on birthweight, gestational age, sex, and race. However, cocaine-using mothers were significantly more likely to smoke tobacco and drink alcohol. Mothers were primarily inner-city, black, low-socioeconomicstatus women. Neuspiel et al. (1991) found a significant difference in the motor cluster scores between 20 cocaine-exposed and 32 comparison infants when a BNBAS exam was conducted at 11 to 30 days following delivery. There were no differences on any of the BNBAS clusters when the exam was conducted at 1 to 3 days. Subjects were recruited from an urban public hospital in Bronx, NY, and cocaine-using mothers were significantly more likely to drink alcohol and smoke marijuana and tobacco. In summary, current research on the neonatal neurobehavior of cocaineexposed infants suggests that shortly followed delivery, neonates may exhibit more abnormal reflexes and less optimal habituation, orientation, motor, and state regulation abilities. Several weeks following delivery these infants may show poorer motor performance. To date, a consistent pattern of neurobehavioral deficits has not been demonstrated. Substance
Abuse
and Maternal
Depression
There are no published data on maternal factors that might affect the caregiving environment of a cocaine-exposed infant. A number of studies have found a relationship between drug use and depression (K. Burns, Melamed, W. Burns, Chasnoff, & Hatcher, 1985; Keeler, Taylor, & Miller, 1979; Ross & Berzins, 1974; Weissman & Myers, 1980). It is not, however, clear whether
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depression promotes drug use or drug use results in depression. There is some evidence that cocaine abusers undergoing treatment have an increased incidence of affective disorders (Gawin, 1986; Weiss, Mirin, Michael, & Sollogub, 1986). Research indicates that children of depressed mothers are at risk for behavioral and emotional problems (Ghodsian, Zajicek, & Wolkind, 1984; Rutter, 1966; Zuckerman & Beardslee, 1987). There is evidence that depressed mothers express flat affect during interaction with their infants, provide less stimulation, and fail to modify their behavior according to the behavior of their infant (Cohn, Matis, Tronick, Connell, & Lyons-Ruth, 1986; Field et al., 1988). Cohn and Tronick (1983) found that even brief experience with simulated maternal depression at 3 months resulted in continued negative infant affect even after the mother returned to normal interaction. In summary, research indicates that children and even infants of depressed parents are at risk for behavioral and emotional problems. In addition, substance abusers and, in particular, cocaine abusersmay be at increased risk of depressive disorders. Currently, there is no published information on the levels of depression experienced by cocaine-using mothers. Our study is the first to investigate the neurobehavioral development Gf infants born to a population of cocaine-using pregnant women who delivered at a rural referral hospital and did not receive intensive prenatal intervention. Improvements over previous studies on the neurobehavioral effects of prenatal cocaine exposure include: (a) explicit procedures for maintaining examiner blindness, including the concurrent testing of cocaine-exposed and control infants and the incorporation of “fake” subjects; (b) samples matched one-to-one on potentially confounding variables; (c) inclusion of a maternal measure assessingdepressive symptoms shortly after birth and 1 month later; and (d) the opportunity to observe any effect of maternal affect on infant neurobehavior at 1 month of age. METHOD Subjects
The subjects in this experiment were drawn from a tertiary-level teaching hospital serving a rural population. The majority of obstetrical patients are at risk for prenatal or perinatal problems and are of low socioeconomic status. The cocaine-exposed group included infants and/or mothers who, for physician-determined clinical reasons, had their urine tested and found positive for cocaine metabolites, aswell as any infants whose mothers admitted to health personnel that they had used cocaine at any time during their pregnancy. Control subjects had no history of illicit drug use during pregnancy. An anonymous prevalence study conducted in the well-baby nursery at our
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institution found that fewer than 2% of infants whose mothers did not admit cocaine use tested positive for cocaine metabolites at delivery (Behnke, Eyler, Conlon, Adams, & Stewart, 1990). The two samples included 35 cocaine-exposed infants and their mothers and 35 infant-mother dyads with no evidence of cocaine or other illicit drug use during pregnancy. The control group matched the cocaine-exposed group one-to-one on the following variables: maternal race, primi- or multiparty, presence or absence of maternal tobacco use, size for gestation (Battaglia & Lubchenco, 1967), and type of delivery. Informed consent was usually not obtained from mothers who delivered infants by Caesarean section until several days following delivery. For this reason, type of delivery was included as a matching variable in order to control for infant age at testing. Preliminary review of the medical records of all neonates born during a 15 day period revealed that only 8% of mothers admitted prenatal use of alcohol to health professionals during routine questioning. Given that this is a much lower rate than that usually reported in obstetric populations, we believed that we could not use medical record reports of alcohol use to match alcohol exposure accurately (Kuzma & Sokol, 1982; Robles & Day, 1990; Tennes & Blackard, 1980). Unfortunately, we were prevented from interviewing subjects regarding prenatal substance use because state law would have required us to report cocaine-using women to the child abuse authorities despite having granted them research confidentiality. All infants participating in this study were admitted to the well-baby nursery following delivery and lived within 80 miles of the hospital. All were born at a gestational age of at least 35 weeks as determined by routine Ballard exam (Ballard, Kazmaier, & Driver, 1977). Mothers were at least 17 years of age and had no adverse medical problems during pregnancy or conditions that would have made it difficult to provide informed consent. Reasons for maternal exclusion from the study included conditions such as diabetes, medicated epilepsy or hypertension, mental retardafion, or deafness. Measures
The BNBAS (Brazelton, 1984) was used because it is the most widely known and utilized neonatal assessment. Furthermore, it was the assessment that had been used in previously published research on cocaine-exposed neonates (Chasnoff et al., 1985; Chasnoff et al., 1989). The BNBAS does not provide one summary score. Therefore, to reduce the data for statistical analysis, individual scores are commonly grouped into the six behavioral clusters established by Lester et al. (1982): habituation, orientation, motor performance, range of state, state regulation, and autonomic regulation. In addition, the total number of abnormal reflexes is recorded. The 1984 version of the BNBAS which was used in this study also includes nine optional supplementary items that were designed to assess the
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CONLON
fragile infant’s ability to cope with and utilize environmental stimuli. They measure the physiological “cost” to the infant necessary to achieve and maintain an alert state. The Beck Depression Inventory (BDI; Beck, Ward, Mendelson, Mock, & Erbaugh, 1961) has been considered to be the best self-report measure of general depression available for assessing the intensity of depression (Rehm, 1981). The abbreviated 13-item form used in this experiment has been found to correlate .96 with the original (Beck, Steer, & Garbin, 1988). This short version is more appropriate for use with pregnant or recently delivered women because it excludes questions related to issues such as weight gain and frequency of sex which are confounded by pregnancy. Procedures
Medical charts of all admissions to the well-baby nursery were reviewed daily by one of four research assistants. During the course of the 11-month study, 78 cocaine-exposed infants were identified; 4 were not eligible due to maternal retardation, maternal seizure disorder, or gestational age less than 35 weeks; and 13 were discharged before consent could be requested. In the hospital where this experiment was conducted, infants are discharged, on average, about 24 hours after birth. Because records were reviewed each morning, there were often only a few hours during which all infant-mother dyads identified that day could be contacted, enrolled, and assessed. The principal investigator, a certified BNBAS evaluator, carried out all testing of mothers and infants. The following procedures were implemented in an effort to prevent the accidental disclosure of identifying information. The evaluator was not involved in subject selection and carefully avoided interaction with health professionals who might inadvertently disclose a subject’s status. If the evaluator became aware of any identifying information, the subject was dropped from the experiment. Efforts were also taken to prevent any cues regarding group membership. For instance, the evaluator was regularly asked to assess subjects who were not intended to be included in either final sample. The inclusion of these “fake” subjects prevented the evaluator from suspecting that two similar mother-infant dyads might be matched to each other. The evaluator was provided only with the date, type, and time of birth, the mother’s name, infant’s sex, and the estimated time of discharge from the hospital for each subject. The mother was specifically told that the investigator had no knowledge of her substance use history and needed to remain that way throughout the experiment. Mothers were told they would receive a box of diapers at the l-month follow-up visit. The BDI was administered orally to each mother. The BNBAS was conducted in the well-baby nursery when the infant was approximately midway between feedings. Of the 61 cocaine-using mothers who were asked to participate, 42 accepted (68%), compared to 70% acceptance rate for control mothers. In
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89
accordance with Florida law, all of the cocaine-using women were under investigation by the Department of Health and Rehabilitative Services. A total of 8 infants, 6 cocaine-exposed, were dropped from the experiment due to maternal or staff disclosure of drug-use status. One cocaine-exposed mother-infant dyad could not be matched (a black smoker with no children, who vaginally delivered a large-for-gestational-age infant). Subsequent to the initial testing, mothers were contacted by letter and then called by a research assistant to schedule follow-up. Twenty-one of the 35 cocaine-exposed infants were follow-up tested; however, the matched-control for 1 infant did not return for testing. Two cocaine-exposed infants were brought by their foster parents; therefore, maternal depressive levels could not be assessed. Because subjects could live as far as 80 miles from the hospital, it was not possible to conduct all follow-up testing at the same location. In order to avoid the wide variations in home environments common in this rural population and to provide a nonthreatening location for mothers, half of whom were under child abuse investigation, subjects were tested at restaurants near the location of the family’s home. Avoidance of the home also eliminated environmental cues concerning drug use. Assessments were conducted during the midmorning or midafternoon slow periods, which resulted in distractions and noise levels remarkably similar to the hospital nursery.
RESULTS Subjects were primarily multiparous (74%), black (66%), smokers (74%), who vaginally delivered (91%) average-size-for-gestational-age infants (97%). There were 2 large-for-gestational-age infants (1 cocaine-exposed and 1 matched-control) but no small-for-gestational-age infants included in this study. Cocaine-exposed infants had significantly shorter gestations and lower birthweights than did nonexposed infants (Table 1, p. 90). The infants did not differ on Apgar scores, head circumference, length, ponderal index, or ageat the time of the first or second BNBAS exam. There was no difference in maternal age or socioeconomic status. Finally, cocaine-using women had significantly fewer prenatal visits than did the noncocaine-using women (Table 1). Review of the clinical medical record indicated that based on maternal selfreport and/or a clinically ordered urine toxicology screen positive for cocaine metabolites, 83% of the infants in this experiment were exposed to at least some cocaine beyond the first trimester, and 77% were exposed into the third trimester. Fifteen of the 20 infants (75%) who returned for 1 month follow-up had been exposed into the third trimester. In describing their cocaine use, 80% of the women specifically used the term “crack.” In addition, 23% of the control women and 60% of the cocaine-using women reported alcohol use during pregnancy. The higher use of alcohol in the control group than in our
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EYLER,
BEHNKE,
AND
CONLON
for Cocaine-Exposed Descriptive Vanobles
and
TABLE Means
(and
Standard
Deviations] on
Exposed (n = 35) M WI Gestational Birthweight
age
38.2 2949.4 7.8 8.9
Apgor 1 Apgar 5 Heod circumference Ponderal index Hours old (1st Days old (2nd Moternol age No. of prenatal Socioeconomic “n = 34. l p < .05.
BNBAS) BNBAS) visits status
(1.8) (444.8) (1.7) (0.5)
1 Nonexposed
Groups
Nonexposed (n = 35) f
M WI 39.1 3181.6 7.9 8.8
(1.5)
2.23’
(353.2) (1.6) (0.6)
2.42’ 0.07 0.67
33.8 2.5 3:.7
(1.3) (0.4) (21.2)
34.0 (1.3) 2 6 (0.3) 32.3 (9.5)O
0.54 1.18 0.15
28.7 25.4 5.5 16.6
(3.8)” (4.6) (4.8) 14.71
28.0 23.9 8.4 17.7
0.52 1.25 2.46
(4.6)” (5 5) (4.7)” (5.91
0.84
% = 20. ‘*p < .Ol
general obstetric population (7.3%) may have resulted from matching on variables such as maternal tobacco use (Eyler et al., 1990). Analysis of variance (ANOVA) between exposure status and the BNBAS clusters revealed that there were no significant differences between the cocaine-exposed and nonexposed infants on any of the BNBAS clusters when tested shortly after delivery. There were also no significant differences between the groups on the BNBAS supplementary items. Multivariate analysis of variance (MANOVA) was also used in order to utilize the information about the relationships (i.e., correlations) amcng the dependent variables. MANOVA indicated that there was no overall effect of exposure status on BNBAS clusters or the nine supplementary items. There was, however, a significant difference in maternal levels of self-reported depressive symptoms. Cocaine-using women scored significantly higher on the BDI than did women with no evidence of cocaine use. Table 2 presents the means and standard deviations for the BDI and BNBAS clusters following delivery. The average in-hospital BDI score for cocaine-using women who returned for l-month follow-up was 4.1 (SD = 4.1). Cocaine-using women who failed to return for follow-up had an average score of 6.6 (SD = 4.9). Analysis on this sample of 20 cocaine-using women indicated that there was not a statistically significant differential drop-out based on initial depression score. Given this small sample size, however, differential drop-out cannot be ruled out. It is not possible to examine this relationship among the control women because they were only assessed at 1 month if the target to whom they were matched returned.
COCAINE:
MATERNAL
AND
TABLE Means
(and
Standard
Deviations)
BDI Hobituation Orientation Motor Ronge of state State regulation Autonomrc regulatron Abnormal reflexes On = 33. ‘p c .05.
‘n
Means
= 21.
‘n
=
(ond
Standard
far
NEONATAL
EFFECTS
91
2 BDI
and
BNBAS
Clusters
at Birth
Exposed (n = 35)
Nanexposed (n = 35)
M (SD)
M WI
5.2 7.0 2.9 4.4
(4.7)” (1.3)b (1.2) (0.8)
3.2 7.4
(2.6) (0.9)’
3.07’ 0.96
3.7 4.5 7.2
(0.6) (1.4) (1.6)
3.2 4.6 3.7 4.8 7.2
(0.5) (0.8) (0.6) (1.6) (1.4)
0.00 1.11 0.11 0.60
2.7
(2.0)
2.1
(2.1)
F
0.00 1.34
16
TABLE 3 for BDI ond
Deviations)
BNBAS
Clusters
at 1 Month
Exposed (n = 20)
Nonexposed (n = 20)
M (SD1
M WI
BDI
2.9
(2.9)”
3.2
(3.2)
0.14
Orientation Motor Ronge of state
3.6 4.9 3.8
(1.2) (0.7) (0.5)
4.7 5.4 3.5
(2.l)b (0.7) (0.9)
1.66 1.42 1.33
State regulotion Autonomic regulotion Abnormal reflexes
4.0 8.6 2.3
(1.3) (0.6) (1.9)
4.4 (1.7) 8.4 (1.6) 1.5 (1.4)
0.63 0.22 1.32
Note. ‘?I =
No 18.
significant differences ?I = 19.
between
F
groups
MANCOVAs on the l-month follow-up data revealed no significant difference between the two groups of infants when controlling for initial BDI score. In addition, the difference in maternal depressive symptomatology found at the time of delivery was no longer apparent at 1 month. The nine supplementary items from the l-month BNBAS were not examined due to missing data and small sample size. Table 3 presents the means and standard deviations for data collected 1 month following delivery. DISCUSSION As documented by previous studies, there are negative effects of prenatal cocaine exposure. A decrease in birthweight has been found in almost every study published, whether prospectively or retrospectively conducted, and it was found in this experiment as well. Many researchers have also documented
92
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CONLON
a decrease in gestational age similar to that found here. The lower gestational ages found in our experiment are interesting in that the sample was limited to infants of at least 35 weeks gestational age and healthy enough to have been admitted to the well-baby nursery. This suggests that prenatal cocaine exposure may shorten the length of gestation whether or not an infant is born prematurely. It is intriguing that the cocaine-using women reported more depressive symptoms than the nonusing women immediately following delivery but not l-month postpartum. There are several possible reasons for this change. First, the initial assessment occurred while the cocaine-using women were under investigation for child abuse. Second, cocaine-using women in the hospital may have been suffering from withdrawal-induced depression. Third, cocaine-using women’s initial concern and guilt about the effect of their cocaine use on their infant may have lessened after a month of caregiving. In two of the four previously published studies, cocaine-exposed neonates were found to have less optimal state organization and regulation than nonexposed infants (Chasnoff et al., 1985; Chasnoff et al., 1989). Infants in the later study also exhibited deficits in interactive ability and motor performance. Cocaine-exposed neonates in our experiment were expected to be at even greater risk because their mothers attended fewer prenatal visits than contfols and were not participants in an organized prenatal intervention program. However, they, like the infants examined by Neuspiel et al. (1991), exhibited no differences in neurobehavioral performance when compared to nonexposed neonates shortly after delivery. Our infants did not exhibit poorer motor abilities when tested at 1 month of age, as did those tested by Neuspiel et al. (1991). It is interesting that infants in the Neuspiel et al. study were tested at an average of 19 days of age, whereas ours were tested at an average of 28 days of age. It may be that the subtle motor differences they observed represent transient difficulties experienced by cocaine-exposed infants in the first few weeks following delivery. It is possible that our sample had less heavy cocaine use than a sample of women who voluntarily sought treatment. In Chasnoff et al. (1989), however, even the infants whose mothers stopped using cocaine in the first trimester showed significantly worse orientation, motor, and state regulation. Based on maternal self-report and/or a positive toxicology screen, 83% of the infants in this experiment were exposed to cocaine beyond the first trimester. Other indirect evidence suggests that substantial cocaine exposure may have occurred during pregnancy in the majority of the drug group in this experiment. Twenty-six percent reported previous and/or current participation in some type of drug treatment program. When describing their cocaine use, 80% of the women specifically referred to the use of crack. Crack cocaine is considered to be more quickly addictive than other forms of cocaine due to the intensity of the “high” and the subsequent acute depression produced by
COCAINE:
MATERNAL
AND
NEONATAL
EFFECTS
93
this method of administration (Perez-Reyes, DiGuiseppi, & Ondusek, 1982). Women not specifically describing crack use reported: (a) a 5-year history of snorting cocaine, (b) use of crank during first trimester followed by treatment, (c) regular use of cocaine throughout pregnancy, and (d) a 1Zyear history of intravenous cocaine use. The three remaining women admitted to cocaine use only in the first 18 weeks of pregnancy. Another factor suggesting significant use is that Florida mandates that all mothers of cocaine-exposed infants be investigated for child abuse. Women appear to be quite aware of this situation, and it is our opinion that the majority of women who are still using in the latter stages of their pregnancy are addicted and are unable to stop regardless of the consequences. In fact, three of the mothers participating in this experiment were known to have previously delivered a cocaine-exposed infant, and a fourth had previously delivered two other exposed infants. Chasnoff et al. (1989) reported similar levels of alcohol use in their two cocaine-exposed groups, but absolutely no alcohol use in the control group. This confounding factor may have contributed to the poorer BNBAS performance of their cocaine-exposed infants. Level of alcohol use is an important factor in this type of research as prenatal alcohol exposure has been found by some researchers to alter the neurobehavioral development of neonates (Coles, Smith, Lancaster, & Falek, 1987; Streissguth, Barr, & Martin, 1983). The most serious problem with our experiment was the inability to match the cocaine-exposed and nonexposed groups on prenatal alcohol use. Because we could not control for the existence or amount of alcohol use, we cannot be certain the significantly decreased birthweight and gestational age found in the target group were due solely to cocaine exposure. However, given the higher rate of alcohol use in our control group (23%) than that reported by the general obstetrical population (7.3%), it may be that controlling for other confounding factors (e.g., maternal tobacco use and size appropriateness) provided an indirect control for maternal alcohol use. Although there remained apparent group differences in alcohol use, the information regarding prenatal alcohol use was not collected in the same manner for the two groups. Women in the control group were asked by nurses about their substance use as a part of routine admission screening. In contrast, once a woman was identified as a cocaine user, she was interviewed in depth by a clinical social worker regarding her substance use and psychosocial history. In addition, women who had already admitted use of an illegal drug may have been less hesitant to admit use of a legal substance. Therefore, true alcohol use may well have been even higher than documented in the controls, and thus closer to the cocaine user’s rate. If differences in neurobehavior had been found between the groups in this experiment, then the inability to match subjects one-to-one on alcohol use during pregnancy would have weakened our behavioral findings. It seems
94
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EYLER, BEHNKE,
AND
CONLON
highly unlikely, however, that the women in the control group actually had significantly higher levels of alcohol use than the cocaine-using women, and that this imbalance obscured cocaine-related differences in neonatal neurobehavior between the two groups. The issue of examiner blindness to group membership is always relevant in research using subjective measures, but it becomes even more crucial when there are strong initial hypotheses concerning positive or negative impact on measured outcome. The plight of cocaine-exposed infants is currently an extremely emotional and political issue. Researchers studying these infants are likely to have strong expectations about the potentially harmful effects that can result from maternal use of such a potent vasoconstricter. Although hypotheses promote research, it is essential that experiments be designed so that the null hypothesis cannot be falsely rejected (Koren, Graham, Shear, & Einarson, 1989). Maintaining examiner blindness is not a simple issue. It involves complex, coordinated efforts among members of a research team. If one thinks in terms of a continuum of blindness, it is easier to acknowledge that there is a difference between simply not “knowing” the status of a subject and carefully designing procedures and controlling the environment to allow no cues as to group membership. A strength of our findings lies in the efforts made to maintain blindness and optimize objectivity. The most valuable outcome of this experiment may be to remind us that there is likely a continuum of casualty for any developmental toxin or teratogen. Even during the thalidomide tragedy, a significant number of children exposed to this teratogen during the critical period of 20 to 36 days postconception (Lenz, 1965) were born normal (Kajii, Kida, & Takahashi, 1973; Mellin & Katzenstein, 1962; Smithells, 1962). Although it is important to encourage and help all pregnant women to stop using cocaine, it is important to provide careful and accurate information. There is evidence that women overestimate the negative potential of information physicians provided to them about teratogens, and, in fact, are more likely to abort than is warranted by the level of exposure (Koren, Bologa, Long, & Shear, 1989; Koren, Feldman, & MacLeod, 1990; Trichopoulos et al., 1987). Overgeneralization may frighten away prospective parents for those infants who are placed for adoption. It is crucial that we carefully determine the entire range of consequences of prenatal cocaine exposure and work to determine what beneficial effects might result from achieving abstinence at different times during pregnancy. In discussions about cocaine-exposed infants, one of the most commonly stated characteristics is that they tremor and startle more than normal infants. This is a documented characteristic of infants withdrawing from depressants such as heroin; however, there is only one report of this finding when cocaineexposed infants have been prospectively studied (Chasnoff et al., 1985). It is possible that this was a spurious finding due to the number of statistical
COCAINE:
MATERNAL
AND
NEONATAL
95
EFFECTS
comparisons. In fact, in the same study there was no difference between the groups on the physiological cluster, which is comprised of only three individual items (tremors, startles, and skin color). The issue of jitteriness is important because many physicians consider increased tremors or startles to be potential indicators of maternal cocaine use and therefore order urine screens to test for cocaine metabolites based on this symptomatology. Interestingly, in a recent study conducted by Parker et al. (1990), it was determined that 44% of 936 healthy, full-term neonates exhibited jitteriness during a IO-min neurological assessment. Analyses revealed that infants prenatally exposed to marijuana, but not those exposed to cocaine, were more likely to jitter. At our own institution, we have found that drug screening based on maternal or infant perinatal risk factors is not effective in accurately identifying prenatal cocaine users (Behnke et al., 1990). More research into the effects of prenatal cocaine exposure is urgently needed. Although cocaine may not be a teratogen, we need information about its potential to alter mother-infant interaction and infant development. Even if future research fails to document any effects in the neonatal period, it is possible that central nervous system damage from the drug or from intrauterine hypoxia related to use might manifest itself at later ages when greater demands are placed upon the child.
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n