This report investigated the relationship between PCE and growth, cognitive development, and behavior at 7 years of age. First trimester cocaine use predicted reduced 7-year weight and height. There was a direct effect between PCE and 7-year weight that was not solely due to the effects of PCE on birth weight [64
]. Head circumference was not significantly predicted by PCE in these analyses, although we previously reported that PCE was a predictor of head circumference at 7 years [60
]. However, that was a report using longitudinal modeling across four phases and had a different sample size than the current report, which likely accounts for the different findings. Most other research groups have not found effects of PCE on child growth [5
]. However, most of those groups defined PCE as any use during pregnancy. We found that 7-year weight and height were both affected by first trimester use, which is consistent with the idea that symmetric growth retardation results from exposure early in pregnancy [10
Prenatal cocaine use did not predict performance on the cognitive, learning and memory, achievement, or neuropsychological assessments. The lack of a significant association between PCE and global cognitive development is consistent with other reports [5
], and is an indication that the effects of PCE on cognitive function may be subtle and therefore not detectable by global measures. We also did not find specific neuropsychological effects at this age. While there have been some reports of significant effects of PCE on neuropsychological measures, there is no one domain that is consistently affected. It may be that effects in these domains will not become evident until there is development of more advanced cognitive abilities, such as occurs in middle childhood [35
Consistent with our hypothesis, we found associations between PCE and child behavior problems that were evident on both mother and teacher ratings. Third trimester use, which reflects use throughout pregnancy, was associated with significantly more externalizing behavior problems, such as aggressive behavior and attention problems, and with increased activity, inattention, and impulsivity, controlling for prenatal and current maternal substance use, sociodemographic and environmental factors, and child characteristics. Our findings of increased behavior problems are also consistent with other reports [6
]. There were no interactions between PCE and gender or home environment, although there was an interaction between PCE and maternal age on the TRF internalizing scale. The effect of PCE on total behavior problems at age 7, as measured by the CBCL, was mediated by the effects of PCE on total behavior problems at 3 years, but the effects of PCE on CBCL externalizing behaviors and on TRF total and externalizing behaviors were direct.
At 3 years, we found that first trimester exposure was associated with more mother-rated externalizing behavior problems [62
]. At 7 years, third trimester exposure, but not first, predicted the mother’s rating of externalizing problems. Thus, the affected domains remained the same across time, but the time of exposure differed with maturation. There could be several reasons for this: One, there could have been selective subject loss among the children who were affected and exposed only early in gestation. However, we have shown that there was no selective drop-out, so this possibility is not likely. Two, women who used cocaine throughout pregnancy may differ from women who did not on significant characteristics that we did not measure and thus were not able to control for. While we controlled for socioeconomic, psychological, and home environment characteristics, we did not have measures of exposure to violence or community characteristics at the 7-year assessment. We have added these measures to later follow-up phases. Three, children who were exposed in the first trimester only may have been able to compensate for the effects of exposure by age 7. This possibility, particularly in a population of offspring with low to moderate levels of exposure, is supported by literature on plasticity in development [75
], and is likely the best explanation.
PCE affects fetal development through a number of mechanisms, including: 1) neurochemical changes in the dopamine, norepinephrine, and serotonin systems; 2) indirect vasoconstrictive effects; and 3) disruptions in fetal programming [44
]. In animal models, there are effects of PCE on behaviors that are regulated by the dopamine and norepinephrine neurotransmitter systems, including cognitive abilities, motor performance, reward, mood, and stress reactivity [36
]. In humans, PCE effects would be expected to occur in brain regions such as the prefrontal cortex that express dopamine receptors and receive dopaminergic projections from the midbrain [34
]. Behaviorally, changes would be expected in domains that rely on the function of the dopamine systems in the brain such as attention, arousal, mood, state regulation, and executive functioning [18
]. Our findings and the reports of others show that, during childhood, PCE affects the capacity to control behavior and regulate emotion, reflecting disturbances in the prefrontal cortex as well as other brain regions. The behavioral effects of PCE could be due to direct effects on neurotransmitter systems, consistent with the first mechanism, or they could be indirect effects mediated through changes in the HPA axis, consistent with the third mechanism [13
A potential limitation of the study is that biological measures were not used to document drug use. While it is possible that some women who used drugs denied use and were misclassified, this would reduce the differences between groups and would not affect the significant findings. Moreover, biological screening fails to detect many cocaine users because of the short time period for detection [39
]. Our interviews identified a higher percentage of users than did urine screening [64
], a finding also reported by others [43
]. Thus, detailed, confidential interviewing is an effective way to identify users and to characterize the quantity, timing, and pattern of use [58
Another issue to consider is whether maternal ratings of behavior reflect the child’s behavior or the mother’s perception of the child’s behavior. Women who use cocaine might be more depressed than women who do not use cocaine and therefore they may perceive their child’s behavior differently. However, PCE and maternal depression were not related in our study or in others [47
]. Maternal hostility was associated with child behavior, but when we controlled for maternal hostility, PCE was still a significant predictor of behavior. In addition, PCE was a significant predictor of teacher-rated behavior problems, a further indication that the reported behavior changes are not a reflection of the mother’s perception.
The strengths of this study include its prospective design, large number of subjects, good follow-up rates, and statistical control for confounding factors, including other drugs and current environmental influences on child development. We can assess the effects of light to moderate levels of PCE and of the timing and duration of exposure on development. Women enrolled in this study received prenatal care by their fourth or fifth month of pregnancy. They were interviewed at defined time points and at frequent intervals to minimize recall bias. We have also established that the instruments were reliable and valid [23
]. This prenatal care sample represents the typical pattern of substance use in a general population of pregnant women and allows us to study the effects of exposure to cocaine early in pregnancy, as well as throughout pregnancy.
In conclusion, this is a unique study of women from a prenatal clinic who used low to moderate amounts of cocaine early in pregnancy. We have shown previously that PCE is a significant predictor of neurobehavioral and neurophysiological changes at birth [63
], temperament at 1 year [61
], and memory, temperament, and behavior at 3 years [62
]. We have now documented increased mother- and teacher-rated behavior problems at 7 years. The extent of the teacher-rated problems in the continuously-exposed group was comparable to that in a clinical sample [4
]. This continuing pattern of behavior problems associated with PCE, a reflection of behavioral dysregulation, is important because temperament, externalizing behaviors, and inattention are predictors of adolescent psychopathology, including substance use, delinquent behaviors, ADHD, anxiety, and depression [13
]. The identification of this pattern will allow targeted early intervention with children who are vulnerable because of their prenatal cocaine exposure in order to disrupt this potential pathway to adolescent psychopathology.