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Prenatal Exposure to Cocaine and Other Drugs: Outcome at Four to Six Yearsa
Annals of the New York Academy of Sciences
Abstract
In a longitudinal, prospective study, 95 children born to mothers who used cocaine and other drugs during pregnancy and 75 matched, nonexposed children born to mothers who had no evidence of alcohol or illicit substance use during pregnancy were evaluated for cognitive and behavioral outcome at 6 years of age. Prenatal exposure to cocaine and other drugs had no direct effect on the child's cognitive outcome (measured as IQ), but it had an indirect effect as mediated through the home environment. However, prenatal exposure to cocaine and other drugs did have a direct effect on the child's behavioral characteristics at 4–6 years of age, with the home environment having little impact. This study helps us to understand the fragile interaction of biological and environmental factors affecting the cognitive and behavioral development of children prenatally exposed to cocaine and other drugs.
... 15 Most recently, Chasnoff and colleagues' (1998) longitudinal study (completed after the review by ) concluded that behavioral characteristics of 4 -6 year olds were directly affected by prenatal exposure, resulting in higher rates of depression and anxiety; social, thought, and attention problems; delinquent and aggressive behaviors; and impulsivity and distractibility among prenatally exposed children. In terms of cognitive effects, the researchers found that while prenatal exposure did not directly affect the IQ scores of these children, their IQ scores were indirectly affected through the quality of their home environments: children living in homes in which there was prenatal substance use had poorer quality home environments, a factor that was related to lower IQ scores (Chasnoff et al. 1998). ...
... 16 In contrast, prenatally exposed children often develop poorly when faced with inadequate care from a mother whose functioning is affected by the ''stress and chaos'' that are associated with long-term drug abuse (Mathias 1992, p. 15). Studies have found that prenatal exposure and the postnatal environment have similar effects on the intelligence of 3 year olds (Azuma and Chasnoff 1993) and that maternal postpartum drug use is correlated with IQ and behavioral problems for children at age 6 (Chasnoff et al. 1998). ...
... An alternative to mandatory testing, proposed by Chasnoff, is that primary-care physicians screen every family with infants or young children as a means of promoting early detection of exposure. He recommends that whenever an infant or young child is born with or presents with a positive urine toxicology or whenever a young child's family is identified as abusing alcohol or illicit drugs, the family be referred for appropriate treatment but not referred to CPS unless the family refuses or fails to comply with treatment (Chasnoff 1998). This proposal has numerous advantages over a testing proposal but is also not entirely problem free, as we address below. ...
In this article, we review the literature regarding prenatal cocaine exposure and child development. We then reexamine current child welfare policies in light of that literature, paying particular attention to laws that mandate reporting substance-exposed newborns and substance use during pregnancy as well as policies that view such reports as prima facie evidence of child maltreatment Finally, we reassess the utility of such policies, given our current knowledge of the long-term effects of prenatal exposure, and consider alternative approaches to protecting children who are born to parents who are using crack cocaine.
... Aggression [25,35], anxiety, decreased socialization [42] , predisposition to drug seeking [23], alterations in regulatory and coping behavior, and elevated responsivity to acute and chronic stress, are behaviors found in prenatally cocaine-exposed animals565758. Early research using caregiver report on preschool children prenatally exposed to cocaine also indicates higher rates of behavioral problems [10,43] compared to non-cocaine-exposed children. Several studies have found that hyperactivity and externalizing behaviors are increased among prenatally cocaine-exposed children. ...
... The findings raise some important methodological issues and potential limitations. Previous studies have indicated that prenatal cocaine exposure was related to increased negative behaviors in children ages 1–6 years [4,6,10,43]. This study design extends previous findings by examining specific behavioral domains of cocaine-exposed children longitudinally through age 10 while also exploring the association of elevated blood lead on behavioral outcomes and controlling for prenatal drug exposures and environmental conditions. ...
Children prenatally exposed to cocaine may be at increased risk for behavioral problems due to disruptions of monaminergically regulated arousal systems and/or environmental conditions.
To assess behavioral outcomes of cocaine (CE) and non-cocaine-exposed (NCE) children, 4 through 10 years old, controlling for other prenatal drug exposures and environmental factors.
Low socioeconomic status (SES), primarily African American children (n=381 (193 (CE), 188 (NCE)) were recruited from birth. Generalized Estimating Equation (GEE) analyses were used to assess the predictive relationship of prenatal cocaine exposure to odds of caregiver reported clinically elevated behavioral problems at 4, 6, 9 and 10y ears of age, controlling for confounders.
Prenatal cocaine exposure was associated with increased rates of caregiver reported delinquency (OR=1.93, CI: 1.09-3.42, p<0.02). A significant prenatal cocaine exposure by sex interaction was found for delinquency indicating that only females were affected (OR=3.57, CI: 1.67-7.60, p<0.001). There was no effect of cocaine on increased odds of other CBCL subscales. Higher prenatal tobacco exposure was associated with increased odds of externalizing symptoms at 4, 9 and 10 years of age. For CE children, those in foster or adoptive care were rated as having more behavior problems than those in biologic mother or relative care. Greater caregiver psychological distress was associated with increased behavioral problems. There were no independent effects of elevated blood lead level on increased behavior problems after control for prenatal drug exposure and other environmental conditions.
Prenatal cocaine and tobacco exposure were associated with greater externalizing behavior after control for multiple prenatal drug exposures, other environmental and caregiving factors and lead exposure from 4 through 10 years of age. Greater caregiver psychological distress negatively affected caregiver ratings of all CBCL domains. Since cocaine and tobacco use during pregnancy and maternal psychological distress have the potential to be altered through prenatal educational, drug treatment and mental health interventions, they warrant attention in efforts to reduce rates of problem behaviors in children.
Background/objectives
Maternal illicit drug use is associated with negative physical and developmental outcomes for their born children. We aim to find out the incidence of different developmental problems in a cohort of Chinese children born to drug-abusing mothers, compare the physical health and developmental outcomes of the subjects recruited in the Integrated Program to the Comprehensive Child Development Service (CCDS), and to study the potential factors on their associations.
Methods
A retrospective longitudinal cohort study with frequent clinical assessments of the children’s physical and developmental outcomes in a HKSAR’s regional hospital from birth until 5 years old. 123 Children in Integrated Program were compared with 214 children in CCDS between 1 January 2008 and 28 February 2019. Cox regression analysis was performed to determine the possible factors associated with the developmental outcomes.
Results
Developmental delay was detected in 129 children (38.9%). CCDS group has significantly higher incidence of cognitive delay ( p = < 0.001), language delay ( p = < 0.001), motor delay ( p = < 0.001), social delay ( p = 0.002), and global delay ( p = 0.002). On Cox multivariable regression analysis, integrated program (HRadj 0.53, 95% C. I. 0.34–0.84), social support (HRadj 0.45, 95% C.I. 0.25–0.80), and maternal abstinence from drug use up to 2-year post-delivery (HRadj 0.62, 95% C.I. 0.40–0.95) were significant protective factors, while male gender (HRadj 1.73, 95% C.I. 1.18–2.54) was a significant risk factor.
Conclusion
CCDS achieves early engagement of drug-abusing expectant mothers during pregnancy, and an early integrated program with multidisciplinary collaboration was an independent factor in improving the developmental outcomes of these vulnerable children.
An experimental, community‐based, residential program, focused on health promotion, was established in 1990 for incarcerated pregnant women with short‐term sentences and histories of drug abuse in a large, midwestern metropolitan area in the United States. Infants resided with mothers after birth. Prenatal care, delivery, postpartum, and family‐planning services were initiated and provided by a nurse‐midwifery service. Community‐based health care, job training, and drug rehabilitation were provided for women during pregnancy through the fourth postpartum month. Program participants' prenatal, delivery, postpartum, and neonatal health outcomes are presented and compared with those of incarcerated women in the same state prison system who experienced usual correctional facility care and support. Program participants represented a group of obstetrically high‐risk women. Health outcomes for both groups of incarcerated women and their infants were similar and more optimal than would have been expected given their preexisting health conditions and risk factors.
Prenatal substance exposure is a growing public health concern worldwide. Although the opioid crisis remains one of the most prevalent addiction problems in our society, abuse of cocaine, methamphetamines, and other illicit drugs, particularly amongst pregnant women, are nonetheless significant and widespread. Evidence demonstrates prenatal drug exposure can affect fetal brain development and thus can have long-lasting impact on neurobehavioral and cognitive performance later in life. In this review, we highlight research examining the most prevalent drugs of abuse and their effects on brain development with a focus on endoplasmic reticulum stress and oxidative stress signaling pathways. A thorough exploration of drug-induced cellular stress mechanisms during prenatal brain development may provide insight into therapeutic interventions to combat effects of prenatal drug exposure.
This study investigated the design and impact of a matrix-aided performance system (MAPS) to support teachers' performance in developing intervention strategies for classroom behavior management. The design concept of MAPS is based on Ausubel's (1963, 2000) advance organizers theoretical framework with the addition of electronic performance support system (EPSS) technology and matrix metaphor interface design principles. The MAPS design framework is described to demonstrate how the advance organizer concept can be exemplified through interactive multimedia and database technology to facilitate the problem-solving process and to offer a design instrument for EPSSs. A formative field evaluation was conducted to better understand the system's applicability in the real world environment. Five inservice special education and resource teachers from two elementary schools and one junior high school participated in the evaluation. Participants used this system for four weeks, as often as they desired. Interviews were held after the four-week trial period to explore possible barriers to use and to identify potential performance improvements to enhance the system. Three EPSS design considerations—performance scaffolding, interface cues, and content comprehension—are offered to create true pedagogy-driven, usable EPSSs. Suggestions for future research conclude the paper.
Fifteen percent of the US population—47 million people—was living at or below the poverty line in 2013. However, 22 % of the nation’s 74 million children were living in poverty, making them the poorest residents of our nation. The chapter defines poverty and explores the nature and extent of poverty in the USA, including trends in poverty rates by age group and region as well as by race, ethnicity, and immigrant status. Also examined are the impact of family economic hardship on child health, the research on the social determinants of health, and the effects of US antipoverty policies as well as early child development programs on poor children. It concludes with recommendations for advancing poverty reduction efforts that promote child health, with a focus on policies and programs that address the needs of both parents and their children. Because an examination of poverty and child health is inherently multidisciplinary, data are drawn from the fields of economics, maternal and child health, developmental psychology, public policy, sociology, and social welfare.
Compared with other illicit substances, stimulants are not commonly used by adolescents; however, they represent a serious concern regarding substance use among youths. This article uses methamphetamine as a model for stimulant use in adolescents; cocaine and prescription stimulants are also mentioned. Methamphetamine use among adolescents and young adults is a serious health concern with potentially long-term physical, cognitive, and psychiatric consequences. Brain development and the effects of misusing stimulants align such that usage in adolescents can more dangerous than during adulthood. It seems helpful to keep in mind the differences between adolescents and young adults when implementing interventions.
Rats exposed to cocaine prenatally were administered a series of 3-choice visual attention tasks. with the most pronounced deficits seen in a task in which the onset time. location, and duration of a visual cue varied unpredictably between trials. The cocaine-exposed rats were less accurate than controls but did not differ in the rate of premature responses or omission errors. The pattern of errors, coupled with response latency data, implicated deficits in the ability to rapidly engage attention and maintain a high level of alertness to the task. The cocaine-exposed rats also exhibited a blunted reaction to an error on the previous trial, possibly reflecting air alteration in emotional regulation and/or error monitoring. Implications for underlying neuropathology are discussed.
Although research methodology in study of the effects of prenatal cocaine exposure has markedly improved as this complex field has matured, there remain vexing methodological difficulties. Comparing findings across different cohort studies is challenging because of variations in how samples are described or because important sample characteristics are not documented. A few studies of prenatal poly-drug exposure with problems in sample design continue to be published, the implications of sample design for research questions need consideration, and sample attrition is a continuing problem. This paper explains these problems, and suggests some practical solutions. Examples are drawn from the current literature and the authors' experience with the Seattle Cocaine and Pregnancy Study, an early cohort study of cocaine effects.
Previous Studies of children with in-utero drug exposure (IUDE) raise concerns that decreased head circumference (HC) at birth increases the child's risk for later compromised cognitive functioning The purpose ofthis StUdy was to determine il'HC at birth and HC growth change are associated with cognitive. functioning (IQ) at 36 months of age in children with IUDE. In-utero drug exposed infants (N = 204) identified following delivery at two Urban hospitals were cornpared with a group of non-exposed children (N = 34) matched for maternal ape, gestational age and socioeconomic status. The IUDE infants had significantly smaller HC at birth than the non-exposed infants. however, by age 36 months the HC was comparable between the two groups. At age 36 months, there was no difference detected in the IQ between the IUDE and non-exposed groups, yet both groups scored almost one standard deviation below the mean for IQ and both groups were below but approached the US standard HC mean at the same age. Further Studies of the more subtle effects of prenatal drug exposure such as attention, impulse control and state regulation oil developmental outcomes are recommended as these children mature.
Objective:
Given its prevalence and impact on health and well-being, children's exposure to traumatic experiences is of growing importance to pediatricians and other medical providers. Little is known, however, about the traumatic experiences profiles, trauma-related sequelae, and service use patterns of youth with chronic or recurrent medical problems/disabilities. This study aimed to fill this research gap.
Method:
Participants were children less than 18 years of age who were referred for assessment and/or treatment services at one of the 56 National Child Traumatic Stress Network centers from 2004 to 2010 across the United States and had experienced at least one of 13 types of traumatic experience(s) (n = 9885; mean = 11 years, SD = 4.3; 52.3% girls). Generalized linear mixed models were used to examine associations among types of trauma, emotional and behavioral problems, and rates of service utilization adjusting for treatment center-level random effects, demographic characteristics, and the total number of types of trauma exposures.
Results:
Among children seeking treatment for traumatic stress, those with comorbid medical problems/disabilities had different demographic characteristics, different types of trauma exposure, and more service utilization in multiple sectors before trauma treatment entry than those without comorbid medical problems/disabilities. Those without comorbid medical problems/disabilities had higher levels of some types of traumatic exposures, associated symptoms, and higher levels of behavioral problems at home, school, or day care. Those with medical disorders/disabilities were at 30% to 40% higher odds of meeting clinical criteria for hyperarousal and re-experiencing posttraumatic stress disorder symptoms, used more medical and mental health services for trauma, and had more emotional and behavioral concerns.
Conclusion:
Given that pediatricians are more likely to see children with medical disabilities and concerns than those without, there is an opportunity to ask directly about traumatic exposures and associated symptoms and provide support and interventions to promote resilience. Integrating trauma screening and mental health services into medical care could be especially beneficial for children with chronic medical conditions.
This longitudinal study examines links among adolescent internalizing and externalizing symptoms, the prenatal environment (e.g., nicotine exposure) and pre/perinatal maternal health, and cardiovascular risk factors. Girls (N = 262) ages 11-17 reported internalizing and externalizing behaviors and mothers reported about the prenatal environment and maternal health during pregnancy and 3 months post-pregnancy. Adolescent cardiovascular risk included adiposity, smoking, blood pressure, and salivary C-reactive protein. Internalizing symptoms mediated relations between prenatal exposures/maternal health and adiposity; externalizing symptoms mediated relations between prenatal exposures and adolescent smoking. Health care providers who attend to internalizing and externalizing symptoms in girls may ultimately influence cardiovascular health, especially among those with pre/perinatal risk factors.
We examined physical growth and behavioral outcomes in 226 10-year-old children who were participants in a longitudinal study of prenatal cocaine exposure (PCE), while controlling for other factors that affect development. During the first trimester, 42% of the women used cocaine, with use declining across pregnancy. At the 10-year follow-up, the caregivers were 37 years old, had 12.8 years of education, and 50% were African American. First trimester cocaine exposure predicted decreased weight, height, and head circumference at 10 years. First trimester cocaine use also predicted maternal ratings of less sociability on the EAS Temperament Survey and more withdrawn behavior problems on the Child Behavior Checklist, more anxious/depressed behaviors on the Teacher Report Form, and more self-reported depressive symptoms on the Children's Depression Inventory. In addition, exposure to violence mediated the effect of PCE on child and teacher reports of depressive symptoms, but not of maternal reports of sociability and withdrawn behaviors. These behaviors may be precursors of later psychiatric problems.
SUMMARY This manuscript describes the key components for establishing collaborative partnerships in the delivery of services to children who have been traumatized by abuse, neglect, and prenatal exposure to alcohol. Specifically, the manuscript addresses: the national need for such collaborative partnerships; the effects of abuse, neglect, and prenatal exposure to alcohol on developmental and educational outcomes; the process used to develop the children's trauma assessment center (CTAC) including discussion on the family centered and transdisciplinary nature of the center; and the accomplishment and future goals of CTAC. The members of the CTAC team currently include the disciplines of counseling, occupational therapy, pediatric medicine, social work, and speech-language pathology. Future goals include expanding the core team to include the nursing and educational psychology disciplines.
In the past 10 years, behavioral neuroscience research has revealed that prenatal exposure to cocaine results in a specific constellation of cognitive impairments, primarily within the domains of selective attention, sustained attention, and emotional reactivity. In this time, numerous animal models have been developed in an attempt to understand the biological basis of these cognitive and affective changes. However, several inconsistencies in key methodologies and experimental procedures utilized by these models have hindered the formulation of conclusions from this animal data. In this commentary, these procedural differences are discussed, and numerous criteria are proposed for evaluating the validity of animal models of prenatal cocaine exposure.
This chapter discusses prenatal drug exposure and mental retardation. Prenatal exposure to cocaine is a behavioral teratogen. The early “rush to judgement” that occurred with crack cocaine can be replaced by sound research. As is evident from studies of cocaine exposure, even in cases where no birth defects are obvious, long-term follow-up may be needed to detect and ameliorate neurobehavioral effects. At both the individual and the societal levels, even in situations where etiology and pathogenesis are well-known, developmental disorders such as mental retardation do not emerge as a result of a single factor or at a single point in development. Neither a prenatal teratogenic environment nor a postnatal rearing environment model of development following prenatal cocaine exposure has total explanatory power. At each stage in development, the human brain is uniquely susceptible to exposure of teratogenic compounds. It is also readily apparent that prevention and treatment of conditions arising from exposure to teratogenic substances will be largely dictated by the stage or stages in which the exposure occurs. The chapter discusses several drawbacks of the traditional etiological classification of mental retardation—prenatal, perinatal, or postnatal.
Recent advances in our understanding of the human brain suggest that adolescence is a unique period of development during which both environmental and genetic influences can leave a lasting impression. To advance the goal of integrating brain and prevention science, two areas of research which do not usually communicate with one another, the Annenberg Public Policy Center's Adolescent Risk Communication Institute held a conference with the purpose of producing an integrated book on this interdisciplinary area. Contributors were asked to address two questions: What neurodevelopmental processes in children and adolescents could be altered so that mental disorders might be prevented? And what interventions or life experiences might be able to introduce such changes? The book deals with the following: biological and social universals in development; characteristics of brain and behavior in development; effects of early maltreatment and stress on brain development; effects of stress and other environmental influences during adolescence on brain development; and reversible orders of brain development.
Recent advances in the brain sciences have dramatically improved our understanding of brain function. As we find out more and more about what makes us tick, we must stop and consider the ethical implications of this new found knowledge. Will having a new biology of the brain through imaging make us less responsible for our behavior and lose our free will? Should certain brain scan studies be disallowed on the basis of moral grounds? Why is the media so interested in reporting results of brain imaging studies? What ethical lessons from the past can best inform the future of brain imaging? These compelling questions and many more are tackled by a group of contributors to this book on neuroethics. The wide range of disciplinary backgrounds that this book represents, from neuroscience, bioethics and philosophy, to law, social and health care policy, education, religion, and film, allow for profoundly insightful and provocative answers to these questions, and open up the door to a host of new ones. The contributions highlight the timeliness of modern neuroethics today, and assure the longevity and importance of neuroethics for generations to come.
The purpose of the study was to examine cognitive development (using the Bayley MDI) and mother–child interaction (using the Emotion Availability Scales, 3rd edition) among infants of opioid‐abusing mothers. Participants were 87 dyads (15 opioid‐exposed, 15 maternal depression and 57 unexposed mother–infant dyads). The study group included 15 infants (mean age=7.0 months, sd=2.8 months) of mothers who participated in buprenorphine‐replacement therapy. Study variables were evaluated during the second half of the first year and compared with the infants of depressed (mean age = 8.06 months, sd =2.4 months) and nonabusing mothers (mean age = 9.96 months, sd =2.9 months). The opioid‐exposed infants earned the lowest Bayley‐II MDI scores. Furthermore, they scored the lowest in infant involvement. The role of environmental risk factors, in turn, was highlighted in that the opioid‐abusing mothers scored the lowest in maternal sensitivity, structuring and nonintrusiveness. Maternal childhood foster care and criminal record were significantly related to lower sensitivity and higher intrusiveness. Finally, the environmental risk status of the opioid‐exposed infants was further underlined in that there were more separations from the mother in the end of the first year as well as an elevated risk for physical abuse.
Objective. The purpose was to compare emotional availability, maternal self-efficacy beliefs, and child developmental status in caregiver–child relationships with prenatally buprenorphine-exposed and nonexposed 3-year-old children. Design. We compared prenatally buprenorphine-exposed children living either with the biological mother (n = 7) or in foster care (n = 14) to nonexposed participants (n = 13). Emotional availability was coded from videotaped parent-child free-play interactions. Results. After controlling for covariates, buprenorphine-exposed children scored lower on maternal Sensitivity and Nonhostility and child Responsiveness and Involvement as well as lower on the Bayley Cognitive and Language scales than did nonexposed children. As compared to foster mothers, biological mothers scored lower on Sensitivity and Nonhostility and self-efficacy beliefs, and their children scored lower on Responsiveness and the Bayley Cognitive Scale. Regardless of group status, the parenting variables were meaningfully related to child socioemotional variables. Conclusions. Buprenorphine-exposed children experienced more environmental risks in emotional availability and parental self-efficacy and performed worse on the Bayley as compared to nonexposed children.
Previous studies of children with in-utero drug exposure (IUDE) raise concerns that decreased head circumference (HC) at birth increases the child's risk for later compromised cognitive functioning. The purpose of this study was to determine if HC at birth and HC growth change are associated with cognitive functioning (IQ) at 36 months of age in children with IUDE. In-utero drug exposed infants (N = 204) identified following delivery at two urban hospitals were compared with a group of non-exposed children (N = 34) matched for maternal age, gestational age and socioeconomic status.The IUDE infants had significantly smaller HC at birth than the non-exposed infants, however, by age 36 months the HC was comparable between the two groups. At age 36 months, there was no difference detected in the IQ between the IUDE and non-exposed groups, yet both groups scored almost one standard deviation below the mean for IQ and both groups were below but approached the US standard HC mean at the same age. Further studies of the more subtle effects of prenatal drug exposure such as attention, impulse control and state regulation on developmental outcomes are recommended as these children mature.
Children in out-of-home care due to abuse and neglect are at disproportionately high risk for disabling conditions. The reasons for the over-representation of children with disabilities in the child welfare system are reviewed and discussed in this chapter. Factors discussed include impact of abuse and neglect, the impact risk factors such as exposure to community and domestic violence and poverty, risk of abuse or neglect associated with disability, and child welfare system factors. In addition, the need for greater efficacy in identification of disability, identification of service needs, and linkage with and delivery of services to serve the needs of children with disabilities in out-of-home care is addressed. Recommendations for policy review at State and Federal levels are offered along with direction for future research.
Prenatal substance exposure poses a significant public health problem in terms of both its economic costs to society and the health and development of those children affected. While substance abusing pregnant women and their children could benefit from early identification and appropriate interventions, drug testing of infants is controversial, and there is currently no national policy regarding the drug testing of infants, nor substance abuse screening for pregnant women. This paper provides a cost-benefit analysis of a universal substance abuse screening and treatment referral policy for pregnant women. Results suggest that the monetary benefits of such a policy will only outweigh its costs if it does little to increase post-birth child protective services reporting and/or foster care placement rates. Thus, additional policies regarding the ways in which screening results are utilized may be important factors in determining the effects of a universal substance abuse screening policy for pregnant women.
This review starts with a discussion of what is meant by developmental change. It is concluded that development is an inherently “fuzzy” concept but that it constitutes a useful framework for research into psychopathology. Some of the major changes over the last four decades in the approach taken for the study of development are noted. Ten key developmental issues are discussed: (1) prenatal influences; (2) sensitive period effects; (3) mechanisms mediating long-term effects of experiences; (4) age of onset differences; (5) sex differences; (6) normality and disorder; (7) connections among different psychological domains; (8) psychopathological progressions; (9) resilience; and (10) gene – environment interplay. It is concluded that developmental research is a rich field of high potential but it needs to be process-oriented rather than norm-oriented, it needs to focus on interconnections between brain and mind, and it needs to have a major interest in individual differences.
Intrauterine illicit drug exposure may lead to a variety of adverse neurobehavioral and neurodevelopmental outcomes. Providing early intervention to reduce the impact of maternal substance abuse on the developing fetus may have significant benefits for the child and family. In this article, we report on 3 promising intervention programs designed to improve the well-being of parents with drug dependence and their children. The initiation of these programs spans from pregnancy through early childhood. All 3 programs are community-based, using comprehensive culturally relevant developmental models. The first program was developed to provide comprehensive care for pregnant women with drug dependence and their newborns. Project STRIVE (Support, Trust, Rehabilitation, Initiative, Values, and Education) provided substance abuse treatment, intensive center- and home-based social work, and parent education onsite at a high-risk obstetric and pediatric clinic. The second program, the Early Infant Transition Center, enrolled newborns with a history of neonatal abstinence syndrome and their mothers. Based in a renovated rowhouse in East Baltimore, one block away from a major urban hospital, the Early Infant Transition Center provided 24-hour nursing care, oncall physicians and nurse practitioners, social workers, parent education, and onsite sleeping accommodation for parents during their infant's recovery. The third program, Home-U-Go Safely, used community-based nurses to give home-based health monitoring, education, and support to new mothers with a history of cocaine and/or opiate dependence.
We studied the uptake, transport and metabolism of cocaine in human intestine using the colonic T-84 monolayers as a model. T-84 cells were grown in DMEM/Ham's F-12 medium containing 6 % newborn calf serum at 37 ° C on 1.0 μm collagen inserts. The cells develop into a polarized monolayer with the apical surface facing the upper chamber and the basolateral surface facing the lower. The monolayers develop a transepithelial resistance of ≥ 600 Ω cm2 in 7 days. Varying concentrations of cocaine HCl was added in a serum free medium to the luminal side only, and after 30 min and 60 min samples from the luminal and serosal aspect were removed for analysis. Cocaine and its metabolites were measured by G C/MS. Cocaine transport across T-84 monolayers increased linearly with increasing concentration of cocaine, with no significant difference between 30 min and 60 min of exposure. Transepithelial resistance did not change even at 800 ng of cocaine suggesting no effect on monolayer viability. The metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME) but not norcocaine were detected in both luminal and serosal side. The concentrations of BE and EME in the luminal side were significantly higher than in the serosal. Combined recovery of cocaine, BE and EME from luminal and serosal sides were 52 – 80 % of total added cocaine. While fresh medium did not metabolize cocaine, media previously exposed to the monolayer (cell-free medium) caused a significant breakdown into BE and EME, suggesting that esterases may be released into the medium. These results indicate transfer of cocaine across this model of intestinal epithelial cell line is by simple diffusion and is concentration dependent. These studies imply that cocaine in swallowed amniotic fluid can be absorbed by the fetal gastrointestinal tract.
Substance use among pregnant women continues to be a major public health concern, posing potential risk to their drug-exposed children as well as burdens on society. This review is intended to discuss the most recent literature regarding the association between in utero cocaine exposure and developmental and behavioral outcomes from birth through adolescence across various domains of functioning (growth, neurobiology, intelligence, academic achievement, language, executive functioning, behavioral regulation and psychopathology). In addition, methodological limitations, associated biological, sociodemographic and environmental risk factors and future directions in this area of research are discussed. Given the large number of exposed children in the child welfare system and the increased need for medical, mental health and special education services within this population, more definitively documenting associations between prenatal cocaine exposure and later child outcomes is essential in order to be able to prospectively address the many significant public health, economic and public policy implications.Journal of Perinatology advance online publication, 12 July 2012; doi:10.1038/jp.2012.90.
This study examined the impact of maternal cocaine use and associated risk factors such as polysubstance use, maternal functioning, and caregiving on affect regulation during infancy. Participants were 45 mother-infant dyads (19 cocaine exposed and 26 control infants) recruited at birth. Observations and maternal reports of infant behavior were obtained at 2 and 7 months of age, along with measures of pre- and postnatal substance use, maternal functioning, and caregiving stability. Maternal cocaine use accounted for significant variance in infant positive affect at 2 months. Other substance use and gestational age predicted infant distress to novelty and arousal during developmental assessments. At 7 months, the impact of prenatal cocaine exposure on infant affect regulation was mediated by postnatal alcohol use and caregiving stability. These findings, if replicated, suggest that 1 pathway to later problem behavior reported among substance-exposed children may be through early regulatory problems and the quality of postnatal caregiving.
A group of 78 children with polysubstance exposure in utero and a comparison group of 58 children with no known risk status were followed from infancy to age 3 years. Sixty-six children (84.6%) in the exposed group were taken into custody, and were either placed in foster homes or adopted. The foster parents were specially recruited to provide care to infants at risk. The substance-exposed group exhibited significantly lower birthweight, gestational age, and head circumference than the comparison group. The perinatal data demonstrated no gender differences. The children were assessed on the Bayley-II Scales of Infant Development at 1, 2, and 3 years of age. The results yielded a significant group by gender interaction on the Bayley-II MDI. The boys, but not the girls who had been prenatally exposed to polydrugs, alcohol, and tobacco earned significantly lower MDI scores at 1, 2, and 3 years of age than the comparison group at the corresponding ages. The gender differences were still statistically significant when controlling for the effects of prematurity and the caregivers' socioeconomic status. This suggests a special vulnerability in prenatally substance-exposed boys, perhaps because of cumulative risk. However, this group of exposed children did show a developmental catch-up across the first 3 years of life. We suggest that the optimized caregiving environment had a buffering effect, and may have compensated for initial developmental lags in this group of children. ©2001 Michigan Association for Infant Mental Health.
Background : Individuals with comorbid alcohol and drug use disorders are at particularly high risk for a variety of problems, including other psychiatric disorders. In general, patients with comorbid alcohol and drug dependence tend to have more severe dependence problems and often have poorer treatment outcomes than individuals with single disorders. For treatment-seeking pregnant women, psychiatric comorbidity can lead to relapse and premature treatment dropout, with adverse consequences to mother and infant.
Methods: Psychopathology, as measured by the Minnesota Multiphasic Personality Inventory–Revised (MMPI-2), was examined in 170 pregnant women admitted to a comprehensive treatment program for cocaine or opiate dependence. Most were single (75%) and African American (80%), with a mean age of 29 years. Thirty-six met DSM-III-R criteria for both alcohol and drug dependence (alcohol positive), whereas 134 were drug dependent only (alcohol negative).
Results: Alcohol-positive women had higher levels of psychopathology than alcohol-negative women, with higher scores on scales 2 (Depression), 4 (Psychopathic Deviance), 8 (Schizophrenia), and 0 (Social Introversion;p < 0.05). The mean MMPI-2 profile for alcohol-positive women was 2-4-8 (Depression-Psychopathic Deviance-Schizophrenia; all T-scores > 65), whereas alcohol-negative women had only a scale 4 increase.
Conclusions: Results suggest that pregnant, drug-dependent women with comorbid alcohol dependence present for treatment with greater psychopathology and thus may require more intense interventions than pregnant, drug-dependent women without comorbid alcohol dependence. Alcohol use by pregnant women is particularly important to address in treatment, because alcohol is a known teratogen associated with mental retardation and behavioral problems.
Cognitive neuroscience offers an important perspective on the persistence of poverty by illuminating the ways in which the
experience of growing up poor reduces people’s ability to escape poverty. Neuroscience research on the effects of early experience
on animal brain development suggests how childhood poverty might constrain human brain development. Specifically, the reduced
opportunities for stimulating experience and increased stress of poverty would be expected to exert a negative influence on
neurocognitive development. Without good neurocognitive development, intellectual and educational attainments are limited,
which in turn limits upward socioeconomic mobility. The research summarized in this chapter by Farah and others is aimed at
understanding the ways in which childhood poverty, including experiences prior to school entry, affects cognitive development.
A better understanding of the ways in which childhood experience and classroom instruction shape brain function will suggest
new ways of preventing and remediating some of the disadvantages suffered by poor children.
EINLEITUNG: Da in Europa während der letzten Jahre ein stetiger Anstieg des Kokainund Crackkonsums beobachtet werden konnte,
wurde im Rahmen einer multizentrischen Querschnittuntersuchung der Missbrauch dieser Substanzen in verschiedenen Zielgruppen
erhoben. Die Studie wurde an der Universitätsklinik für Psychiatrie, Medizinische Universität Wien und neun weiteren europäischen
Städten durchgeführt. METHODEN: Die Daten wurden mittels strukturierter Interviews erhoben. Insgesamt wurden 211 KokainkonsumentInnen
befragt, wobei diese einer von drei Zielgruppen zugeteilt wurden: (1) der Behandlungsgruppe (BG), die sich zum Zeitpunkt der
Befragung in Opioiderhaltungstherapie befand, (2) der marginalisierten Szenegruppe (SG) oder (3) der sozial integrierten Partygruppe
(PG). Neben soziodemographischen Daten wurden monatliche Ausgaben für Kokain/Crack, das Konsummuster, wie auch körperliche
und psychische Gesundheit erhoben als auch Fragen zur Selbsteinschätzung den eigenen Kokainkonsum betreffend. Zudem wurden
toxikologische Analysen hinsichtlich der Veränderung des Kokainkonsums in der BG als Indikator herangezogen. ERGEBNISSE: Von
den drei Zielgruppen war die Szenegruppe mit durchschnittlich 29,35 Jahren die älteste und wies innerhalb des letzten Monats
die höchste Arbeitslosigkeit (im Mittel 25,11 Tage) und die längste Dauer des Kokainkonsums (im Mittel 5,80 Jahre) auf. Im
letzten Monat hatten sie den höchstfrequenten Kokainkonsum mit durchschnittlich 22,32 Tagen und verbrauchten durchschnittlich
1969 Euro/Monat für den Erwerb. Die Behandlungsgruppe hingegen hatte mit durchschnittlich 10,36 Jahren die geringste Schulbildung,
wohingegen die Personen der Partygruppe am jüngsten waren (durchschnittliches Alter 25,64 Jahre), am wenigsten für die Beschaffung
des Suchtgiftes ausgaben, immerhin aber durchschnittlich 588,99 Euro/Monat, und die schlechteste Selbsteinschätzung durch
die Kokain- bzw. Crackproblematik abgaben. Über den Zeitraum von 1996–2002 findet man zudem in der Analyse kokain-positiver
Harnanalysen bei PatientInnen in einer Opioiderhaltungstherapie (BG) einen signifikanten Anstieg (1996: 33,1%; 2002: 40,2%;
p = 0,044). DISKUSSION: Der europäische Trend des steigenden Kokainkonsums bestätigt sich auch in Wien. Eine der größten Schwierigkeiten
in der Behandlung dieser Substanzabhängigengruppe besteht darin, die betroffene Population zu erreichen. Als Hauptcharakteristikum
der KokainkonsumentInnen ist das häufige Auftreten eines polytoxikomanen Substanzmusters zu nennen, wobei diesem Aspekt in
der Behandlung eine wesentliche Rolle zukommen sollte (SG u. BG – Zusatzkonsum von Heroin und Benzodiazepinen; PG – Zusatzkonsum
von Alkohol). Die Wiener Ergebnisse spiegeln im Wesentlichen die europäische Situation wieder, jedoch stellen Crack-Konsum
und Binge-Abusus, im Vergleich zu beispielsweise Hamburg oder London, in Wien derzeit kein vorrangiges Problem dar.
INTRODUCTION: As cocaine consumption seems to have increased over the last decades, the EU has funded this multi-center, cross-sectional
survey to investigate cocaine consumption in three different target groups. The study was conducted by the Addiction Clinic,
Department of Psychiatry, Medical University Vienna and other nine European cities. METHODS: Data were collected by structured
face-to-face interviews. The sample was composed of 211 cocaine abusers out of three target groups: (1) treatment group undergoing
opioid maintenance therapy, (2) marginalized scene group and (3) integrated party group. Sociodemographic data such as age,
education, employment, monthly expenses on cocaine/crack, data on consumption patterns, physical and mental health and personal
needs regarding cocaine consumption were evaluated. Urine toxicology results for cocaine in the treatment group completed
the analysis. RESULTS: The marginalized scene group was the oldest with a mean age of 29.35 years, with the highest unemployment
rate (mean 25.11 days) and the longest duration of cocaine consumption (mean 5.80 years). They had the highest cocaine consumption
pattern with a mean of 22.32 days within the last month. On average 1969 Euros/months was spent for their addiction. The treatment
group had the lowest school education with a mean of 10.36 years, but showed a sufficient insight in their cocaine problem.
However, the party group (with the lowest mean age, 25.64 years) highly underestimated their drug problem, the mean amount
of money they spent for their addiction was 588.99 Euro/months. Structured urine toxicology between 1996 and 2002 in patients
undergoing opioid maintenance therapy ("treatment group") revealed a significant increase of concomitant cocaine consumption
(1996: 33.1%; 2002: 40.2%; p = 0.044). DISCUSSION: The European trend of increased cocaine use could also be observed in Vienna.
One of the greatest barriers for establishing adequate treatment settings for this target group is the difficulty to reach
this population. In addition, multiple substance abuse seems to be one of the predominating patterns of cocaine consumption
and this aspect should be integrated within treatment (in the treatment and scene groups additional heroin and benzodiapzepines
abuse is observed, in the party group intensive alcohol consumption). The Viennese results are in line with those of the other
European cities; however, it could not be confirmed that consumption of crack cocaine and binge play a similarly significant
role as in cities such as Hamburg or London.
Children who are prenatally exposed to drugs may be at risk for emotion dysregulation, including childhood anxiety/depression and aggression, potentially increasing their risk for peer victimization. The objectives of this study were to investigate how prenatal drug exposure relates to adolescent peer victimization and the mediating effects of childhood anxiety/depression and aggression.
Seventy-six prenatally drug exposed (PDE) and 38 nonexposed (NE) adolescent-caregiver dyads followed since birth and middle childhood, respectively, participated in an evaluation during adolescence. In middle childhood, caregivers reported on their child's anxiety/depression and aggression, and children reported on violence exposure. In adolescence, caregivers and adolescents responded to a parallel single-item measure of peer victimization. Analyses were conducted using multivariate linear and logistic regression models, adjusting for covariates, including violence exposure.
One-third (33.3%, n = 35) of the sample endorsed peer victimization: 40.8% PDE and 17.6% NE, p = .01. In middle childhood, PDE youth had more aggressive behaviors (11.92 vs 7.45, p < .01) and anxiety/depression symptoms (3.43 vs 1.76, p < .01) than NE youth. Anxious/depressed behavior during childhood mediated the association between prenatal drug exposure and adolescent peer victimization. Aggression was not a significant mediator.
The consequences of prenatal drug exposure extend into adolescence. Prenatal drug exposure may interfere with emotion regulation, resulting in anxious/depressed behavior during childhood and significantly increasing the risk for peer victimization during adolescence, even in the presence of violence exposure. Strategies to reduce anxious/depressed behavior among children with a history of prenatal drug exposure may reduce adolescent peer victimization.
In the United States, exposure to maternal use of drugs and alcohol, pre- and/or postnatally, is one of the most common risk factors associated with children's negative behavioral and developmental outcomes. Despite evidence linking alcohol and tobacco to fetal damage and warnings from public health campaigns, currently, at least 10% of women drink alcohol during pregnancy (Centers for Disease Control and Prevention, 2004) and 11% smoke cigarettes (Martin, Kochanek, Strobino, Guyer, & MacDorman, 2005). Although these reported rates have declined in recent years, they may not reflect exposure early in the pregnancy before women know they are pregnant. For instance, recently the Centers for Disease Control and Prevention (2004) reported that over 50% of women of childbearing age who were not using birth control drank alcohol and were, therefore, at risk for pregnancy complicated by fetal risk. Maternal substance use also includes marijuana, "hard drugs" (heroin, cocaine, and methamphetamines), and pre- scription medications, either through medical advice or misuse. As evidence has accumulated about the terato- genic risk associated with such use, professionals and the public have become aware of the need to understand the impact on pregnancy outcomes and children's devel- opment. Initial concerns regarding the presumed, but undocumented, effects of substance exposure on chil- dren's development have given way to a more balanced approach that examines how substances interact with environmental factors to influence children's develop- ment. Information from current studies demonstrates the importance of developing strategies to promote the health and development of exposed children, to implement effective prevention programs, and to avoid the unnec- essary anxiety that can stigmatize mothers and children. The knowledge base regarding the effects of prenatal exposure to substances of abuse is growing, often in response to interest by scientists and the support available from federal funding sources. Research on the effects of prenatal exposure to substances of abuse has occurred in response to the scientific awareness of the dangers to chil- dren, as when fetal alcohol syndrome was first described in 1973 (Jones and Smith, 1973), and to public health concerns regarding "epidemics" of drug use, such as her- oin in the 1960s, and cocaine and crack in the late 1980s and early 1990s. Currently, there is a great deal of atten- tion being paid to the effects of pre- and postnatal expo- sure to tobacco and to methamphetamines. Much of the recent research on the effects of prena-
To determine whether young children involved with child welfare (CW) have gross motor (GM) delay; to examine relationships between GM skills and the influence of multiple factors on GM skills.
One hundred seventy-six children involved with CW received GM assessment, physical examinations, and caseworker interviews. Descriptive statistics, correlations, t tests, analysis of variance and covariance, and multiple regression analyses were completed.
GM scores, lower than population norms, were associated with growth parameters. Children in kinship care had significantly higher GM scores compared with children in foster care and those with in-home protective services when adjusted for differences in time in CW. Abuse/neglect, medical neglect, and parental substance abuse produced lower scores; referral for abandonment produced higher scores. Age was most strongly related to GM outcome, with multiple regression explaining 19% of GM variance.
Children involved with CW have lower mean GM scores than population norms. Several factors specific to CW experiences may influence GM outcome.
To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.
Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.
At birth cocaine-exposed infants (n=364) had significantly lower growth parameters compared to non-exposed children (n=771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).
Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.
Prenatal cocaine exposure has been linked to increased child behavior difficulties in some studies but not others.
The primary aim was to estimate the relationship between in utero cocaine exposure and child behavioral functioning at age 7 years with ratings made by blinded examiners during a structured testing session. A second aim was to examine whether caregiver drug use and psychological problems might mediate suspected relationships between prenatal cocaine exposure and aspects of examiner-rated behavior.
407 children (212 cocaine-exposed, 195 non-exposed) participating in the longitudinal Miami Prenatal Cocaine Study (MPCS) were rated with regard to their behavior during a neuropsychological assessment conducted at age 7 years. Raters were trained research psychometricians blinded to drug exposure status. Individual behavioral items were summarized and the cocaine-behavior relationship was estimated within the context of latent variable modeling, using Mplus software.
Two latent variables, Behavioral Regulation and Sociability, were derived via exploratory latent structure analysis with promax rotation. Prenatal cocaine exposure, statistically controlling for child sex, test age, and prenatal exposure to alcohol, tobacco, and marijuana, was associated with Behavioral Regulation (estimated slope ß=-0.25; 95% CI=-0.48, -0.02; p=0.04) but not Sociability (estimated slope ß=-0.03; 95% CI=-0.26, 0.20; p=0.79). Neither postnatal drug use by caregivers nor the severity of their psychological problems at age 5 follow-up predicted levels of child Behavioral Regulation or Sociability at age 7 years (p>0.10).
Examiner ratings of child behavior at age 7 revealed less optimal behavioral regulation for prenatally cocaine-exposed compared to non-exposed children, in contrast with what had been previously found from parent-report data. This evidence highlights the potential value of trained observers in assessing behavioral outcomes of children exposed in utero to drugs and other toxicants.
Cognitive functioning was compared in 29 children diagnosed with fetal alcohol syndrome (FAS), 35 children with fetal alcohol effects (FAE), and 66 psychotropic drugs-exposed (PDE) children using Wechsler tests and the neuropsychological test battery NEPSY. In the FAS group, verbal IQ (VIQ=78), performance IQ (PIQ=77), and full scale IQ (FSIQ=75) were significantly lower as compared to the FAE and PDE groups. In the PDE group VIQ and FSIQ were significantly higher than in the FAE group. In the FAS group, processing speed (PS) was significantly lower than the other three factors. In the FAE group, perceptual organization (PO) was significantly higher, whereas PS was significantly lower than the other factors. In the PDE group, verbal comprehension (VC) was significantly higher than the other factors. Attention subscales on the NEPSY were significantly lower in all the three groups. Prenatal alcohol exposure affects IQ levels more than exposure to psychotropic drugs. Attentional problems were found in all children when tested with the NEPSY in all groups.
Treatment programs for women who use drugs during pregnancy have developed out of a backdrop of punitive policies and the psychosocial complexities of this population, which include psychological comorbidities and consideration of the needs of their children. In this literature review, we examine evidence-based approaches to treatment for these women and some promising newer initiatives. We also discuss limitations of this research and issues that need to be addressed. The increasing understanding and acceptance of substance abuse as a treatable mental health disorder brings renewed optimism to this field.
Effects of prenatal cocaine exposure on special education in school-aged children . Levine T. P., Liu J., Das A., Lester B., Lagasse L., Shankaran S., Bada H. S., Bauer C. R. & Higgins R. ( 2008 ) Pediatrics . Published online . DOI: 10.1542/peds.2007-2826 .
Objective The objective of this study was to evaluate the effects of prenatal cocaine exposure on special education at age 7 with adjustment for covariates.
Methods As part of the prospective, longitudinal, multi-site study of children with prenatal cocaine exposure (Maternal Lifestyle Study), school records were reviewed for 943 children at 7 years to determine involvement in special education outcomes: (1) individualized education plan; (2) special education conditions; (3) support services; (4) special education classes; and (5) speech and language services. Logistic regression was used to examine the effect of prenatal cocaine exposure on these outcomes with environmental, maternal and infant medical variables as covariates, as well as with and without low child IQ.
Results Complete data for each analysis model were available for 737–916 children. When controlling for covariates including low child IQ, prenatal cocaine exposure had a significant effect on individualized education plan. When low child IQ was not included in the model, prenatal cocaine exposure had a significant effect on support services. Male gender, low birthweight, white race and low child IQ also predicted individualized education plan. Low birthweight and low child IQ were significant in all models. White race was also significant in speech and language services. Other covariate effects were model specific. When included in the models, low child IQ accounted for more of the variance and changed the significance of other covariates.
Conclusions Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan and support services, with adjustment for covariates. Low birthweight and low child IQ increased the likelihood of all outcomes. The finding that white children were more likely to get an individualized education plan and speech and language services could indicate a greater advantage in getting educational resources for this population.
Ribonuclease protection assays (RPA) were performed to quantify mu-opioid receptor mRNA expression in specific brain regions of day 70 Rhesus Macaque fetuses that were exposed to cocaine (3 mg/kg) or saline from days 22-70 of gestation. The content of mu-receptor mRNA was high in the diencephalon and moderate in the mesencephalon. In contrast, mu-receptor mRNA was lightly expressed in areas such as the frontal cortex, striatum and the temporal lobe. The content of mu-opioid receptor mRNA was significantly higher in the diencephalon than in other brain regions (P < 0.001; n = 4). Cocaine exposure significantly decreased the expression of mu-receptor mRNA in the fetal diencephalon (P < 0.05; n = 4 in each group). Our data would indicate that prolonged gestational cocaine exposure causes mu-opioid receptor mRNA down-regulation in specific brain regions of the fetus.
Scientific study of prenatal drug exposure and child outcome began a period of substantial growth in the 1970s with a focus on exposure to opiates. By the mid-1980s, attention shifted to cocaine. Most of this research has involved cohort studies in which groups of children are followed up longitudinally from birth. Significant progress has been made regarding the assessment of child outcome (greater range of outcome areas and greater specificity of measures) and regarding attention to and analysis of confounding factors that travel with prenatal exposure. As progress has been made, investigators are tackling new and continuing challenges inherent in these complex studies. Considerable effort is being devoted to determining the level of severity of exposure. Interest is increasing regarding the use of neuroimaging assessments as well as the identification of possible biologic and environmental mechanisms underlying associations between prenatal exposure and subtle child outcomes.
A meta-analysis was performed of the research published from 1985 to 1998 examining the effect of in utero exposure to cocaine on infant neurobehavioral outcome. The initial search for articles to include in the meta-analysis identified 18 studies with potentially meta-analytic variables. Of the studies originally retrieved, 13 failed to meet all of the inclusion criteria and were excluded from the meta-analysis. A total of 14 meta-analyses were performed comparing cocaine-exposed infants to nonexposed infants on NBAS cluster scales at birth and at 3-4 weeks of age. While the meta-analytic combination of studies produced a large enough sample size to drive statistical significance in a small majority of the tests of difference between the cocaine-exposed and nonexposed infants both at birth and soon after, the magnitude of all effects was small. The largest reliable differences appeared for the motor performance and abnormal reflexes clusters. Both also demonstrated a slight trend for increasing standard differences from birth to measures obtained at 3-4 weeks. The orientation and autonomic regulation clusters produced small, significant effects at both time periods, but the trend was for reduced effect sizes over time. All other effects appear truly negligible.
We have reported previously prenatal cocaine-induced functional deficits in serotonergic terminals, and gender-specific supersensitivity of postsynaptic 5-HT(1A) receptor-mediated hormone responses in offspring. This study investigates the effects of prenatal exposure to cocaine on postsynaptic 5-HT(2A) receptor-mediated responses in prepubescent male and female offspring. Pregnant rats were administered saline or (-)cocaine (15 mg/kg, s.c., b.i.d) from gestational day 13 through 20. Changes in 5-HT(2A) receptor function in offspring were assessed by differences in the ability of DOI [4-iodo, 2,5-dimethoxyphenyl-isopropylamine; 2. 0 mg/kg, s.c.] to elevate plasma levels of the hormones ACTH, corticosterone and renin. Basal hormone levels in male and female progeny were unaffected by prenatal cocaine exposure. However, prenatal exposure to cocaine significantly potentiated the magnitude of the ACTH response to DOI in both male (+19%) and female (+43%) progeny. Similarly, the DOI-induced elevation of plasma renin was markedly potentiated in male (+51%) and female (+83%) cocaine-exposed offspring. Although DOI significantly elevated corticosterone levels in both male and female offspring, the magnitude of corticosterone responses was not altered by prenatal exposure to cocaine. Densities of agonist ((125)I-DOI)-labeled receptors in hypothalamus and cortex were unaltered by prenatal exposure to cocaine. These data indicate prenatal cocaine-induced supersensitivity of postsynaptic 5-HT(2A) receptor function in male and female offspring without changes in receptor density. Synapse: 35:163-172, 2000.
In this article, the authors provide a conceptual framework in which to consider alternative approaches to identify the developmental consequences of exposing the developing brain to neurotoxic substances. Concepts underlying brain development and issues regarding neurobehavioral testing in children are reviewed. In addition, the authors selectively review preclinical data identifying mechanisms contributing to neurobehavioral compromise, and clinical data identifying deficits resulting from exposure to two classes of neurotoxins: exposure to drugs of abuse, including alcohol, nicotine, and cocaine; and exposure to environmental agents, including lead, methyl-mercury, PCBs, and organophosphorus compounds.
This study assessed the effects of prenatal cocaine exposure on cognitive functioning, using an intravenous (IV) rodent model that closely mimics the pharmacokinetics seen in humans after smoking or IV injection and that avoids maternal stress and undernutrition. Cocaine-exposed males were significantly impaired on a 3-choice, but not 2-choice, olfactory serial reversal learning task. Both male and female cocaine-exposed rats were significantly impaired on extradimensional shift tasks that required shifting from olfactory to spatial cues; however, they showed no impairment when required to shift from spatial to olfactory cues. In-depth analyses of discrete learning phases implicated deficient selective attention as the basis of impairment in both tasks. These data provide clear evidence that prenatal cocaine exposure produces long-lasting cognitive dysfunction, but they also underscore the specificity of the impairment.
To investigate the effects on infants of the use of marijuana and cocaine during pregnancy and to compare the importance of urine assays with that of interviews in ascertaining drug use, we prospectively studied 1226 mothers, recruited from a general prenatal clinic, and their infants. On the basis of either interviews or urine assays conducted prenatally or post partum, 27 percent of the subjects had used marijuana during pregnancy and 18 percent had used cocaine. When only positive urine assays were considered, the corresponding values were 16 percent and 9 percent, respectively. When potentially confounding variables were controlled for in the analysis, the infants whose mothers had positive urine assays for marijuana, as compared with the infants whose mothers were negative according to both interviews and urine assays, had a 79-g decrease in birth weight (P = 0.04) and a 0.5-cm decrement in length (P = 0.02). Women who had positive assays for cocaine, as compared with nonusers, had infants with a 93-g decrease in birth weight (P = 0.07), a 0.7-cm decrement in length (P = 0.01), and a 0.43-cm-smaller head circumference (P = 0.01). To compare our findings with those of other investigators who did not use urine assays, we repeated the analyses, considering only self-reported use of marijuana (23 percent) and cocaine (13 percent). There were no significant associations between such use as determined by interviews alone and any of the measures of outcome. We conclude that the use of marijuana or cocaine during pregnancy is associated with impaired fetal growth and that measuring a biologic marker of such use is important to demonstrate the association.
To assess the neurodevelopment of adopted children who had been exposed in utero to cocaine.
A case-control observational study.
Twenty-three children aged 14 months to 6.5 years exposed in utero to cocaine and their adoptive mothers, and 23 age-matched control children not exposed to cocaine and their mothers, matched with the adoptive mothers for IQ and socioeconomic status.
The Motherisk Programme at The Hospital for Sick Children, Toronto, a consultation service for chemical exposure during pregnancy.
Height, weight and head circumference at birth and at follow-up, and achievement on standard tests of cognitive and language development.
Compared with the control group, children exposed in utero to cocaine had an 8-fold increased risk for microcephaly (95% confidence interval 1.5 to 42.3); they also had a lower mean birth weight (p = 0.005) and a lower gestational age (p = 0.002). In follow-up the cocaine-exposed children caught up with the control subjects in weight and stature but not in head circumference (mean 31st percentile v. 63rd percentile) (p = 0.001). Although there were no significant differences between the two groups in global IQ, the cocaine-exposed children had significantly lower scores than the control subjects on the Reynell language test for both verbal comprehension (p = 0.003) and expressive language (p = 0.001).
This is the first study to document that intrauterine exposure to cocaine is associated with measurable and clinically significant toxic neurologic effects, independent of postnatal home and environmental confounders. Because women who use cocaine during pregnancy almost invariably smoke cigarettes and often use alcohol, it is impossible to attribute the measured toxic effects to cocaine alone.
Objective. To determine the effect of prenatal cocaine exposure on 3-month infant information processing and developmental assessments.
Methods. One hundred and eight infants, 61 cocaine-exposed and 47 controls, participated at 3 months of age in an infant-control habituation and novelty responsiveness procedure and in a developmental assessment using the Bayley Scales of Infant Development both administered by experimenters blind to the drug exposure status of the infant.
Results. Compared to the non-drug-exposed group, infants exposed prenatally to cocaine were significantly more likely to fail to start the habituation procedure and, for those who did, significantly more likely to react with irritability early in the procedure. The majority of infants in both groups reached the habituation criterion, and among those who did there were no significant difference between cocaine and non-cocaine-exposed infants in habituation or in recovery to a novel stimulus. Infants who were cocaine-exposed showed comparatively depressed performance on the motor (Psychomotor Developmental Index) but not the mental (Mental Developmental Index (MDI)) scales of the Bayley. These results obtained for habituation and Bayley MDI controlling for both perinatal and sociodemographic factors.
Conclusions. Differences in reactivity to novelty but not in information processing between cocaine-exposed and non-cocaine-exposed infants suggest that the effects of prenatal cocaine exposure may be on arousal and attention regulation rather than early cognitive processes.
The impact of cocaine on pregnancy and neonatal outcome has been well documented over the past few years, but little information regarding long-term outcome of the passively exposed infants has been available. In the present study, the 2-year growth and developmental outcome for three groups of infants is presented: group 1 infants exposed to cocaine and usually marijuana and/or alcohol (n = 106), group 2 infants exposed to marijuana and/or alcohol but no cocaine (n = 45), and group 3 infants exposed to no drugs during pregnancy. All three groups were similar in racial and demographic characteristics and received prenatal care through a comprehensive drug treatment and follow-up program for addicted pregnant women and their infants. The group 1 infants demonstrated significant decreases in birth weight, length, and head circumference, but by a year of age had caught up in mean length and weight compared with control infants. The group 2 infants exhibited only decreased head circumference at birth. Head size in the two drug-exposed groups remained significantly smaller than in control infants through 2 years of age. On the Bayley Scales of Infant Development, mean developmental scores of the two groups of drug-exposed infants did not vary significantly from the control group, although an increased proportion of group 1 and 2 infants scored greater than two standard deviations below the standardized mean score on both the Mental Developmental Index and the Psychomotor Developmental Index compared with the control infants. Cocaine exposure was found to be the single best predictor of head circumference. Across all infants in the study, a significant correlation between small head size and developmental scores was found. The present study demonstrates that intrauterine drug exposure may place infants at risk for developmental outcome and that head growth after birth may be an important biological marker in predicting long-term development in children exposed in utero to cocaine and other drugs.
To study the association of maternal cocaine use during early pregnancy with the occurrence of congenital urogenital anomalies, we analyzed data from the population-based Atlanta Birth Defects Case-Control Study. We identified 276 and 791 case-babies with urinary and genital anomalies, respectively, who were live born and stillborn to residents of metropolitan Atlanta from 1968 through 1980. There were 2835 and 2973 respective control-babies born without birth defects randomly selected through birth certificates. Maternal cocaine use during early pregnancy was defined as reported use at any time from 1 month before the pregnancy began through the first 3 months of pregnancy. We found a statistically significant association of reported cocaine use with an increased risk for urinary tract defects (crude odds ratio, 4.39; 95% confidence interval, 1.12 to 17.24) and no statistically significant association with genital organ defects (odds ratio, 2.26; confidence interval, 0.67 to 7.62). The findings from this study were consistent with a previously reported association of maternal cocaine use and urinary tract anomalies in animal and clinical studies.
(JAMA. 1989;262:795-798)
Seventy-five cocaine-using women enrolled in a comprehensive perinatal care program were divided into two groups: those who used cocaine in only the first trimester of pregnancy (group 1 [N = 23]) and those who used cocaine throughout pregnancy (group 2 [N = 52]). Perinatal outcomes of these pregnancies were compared with perinatal outcomes of a matched group of obstetric patients with no history or evidence of substance abuse (group 3 [N = 40]). Group 2 women had an increased rate of preterm delivery and low-birth-weight infants as well as an increased rate of intrauterine growth retardation. Group 1 women had rates of these complications similar to the drug-free group. Mean birth weight, length, and head circumference for term infants were reduced in only the group 2 infants. However, both groups of cocaine-exposed infants demonstrated significant impairment of orientation, motor, and state regulation behaviors on the Neonatal Behavioral Assessment Scale.
(JAMA 1989;261:1741-1744)
Compared to (+)-cocaine, (−)-cocaine was 20 times more potent in inhibiting uptake of 3H-norepinephrine (3HNE) by cortical synaptosomes and 66 times more potent with respect to 3H-dopamine (3HDA) uptake by striatal synaptosomes. Although the tropacocaine isomers were equipotent as inhibitors of 3HNE uptake in the cortex, tropacocaine was 3.9 times more potent as an inhibitor of 3HDa uptake in the striatum than tropococaine. A major known cocaine metabolite, benzoylecgonine failed to inhibit the accumulation of 3HNE and 3HDA by synaptosomes from the cortex and striatum, respectively. The implications of these findings in relation to the motor stimulation seen with (−)-cocaine, (+)-cocaine and benzoylecgonine in rats are discussed.
The effects of cocaine (20 mg/kg s.c.) on 5‐hydroxytryptamine (5‐HT) turnover were examined in rats.
In vivo cocaine administration resulted in decreased turnover of 5‐HT, as indicated by the decreased accumulation of 5‐HT after pargyline administration and the decreased accumulation of 5‐hydroxyindoleacetic acid (5‐HIAA) following probenecid injection.
A time‐related decrease in 5‐HIAA concentrations and a small fall in 5‐HT concentrations in the whole brain were observed following the acute administration of cocaine hydrochloride (20 mg/kg). Tryptophan levels were found to be slightly decreased in the brain.
Enhanced reactivity, but neither stereotypy nor hyperthermia, was observed following cocaine injection (20 mg/kg).
It is concluded that cocaine inhibits the turnover of brain 5‐HT and that this action of cocaine may be responsible for the differences in a number of pharmacological effects between cocaine and amphetamine.
A scoring system for the neonatal abstinence syndrome has been devised and implemented as both a clinical and investigative tool. The score monitors the passively addicted infant in a more comprehensive and objective fashion, and facilitates a more precise evaluation of the clinical status of the infant undergoing withdrawal. In addition, the scoring system has been applied in research designed to test the comparative usefulness of various pharmacologic agents currently recommended for the neonatal abstinence syndrome, and has been found useful in following the progression and diminution of withdrawal symptomatology before, during, and after therapy. Furthermore, the scoring system provides a basis ofr developing uniform criteria for the assessment and treatment of the neonate born to the addicted mother.
This study examined relations between parents' ratings of children's behavioral/emotional problems, family variables, and stressful experiences as predictors of 3-year outcomes in a nationally representative sample of American children. Outcomes were measured by time 2 parent, teacher, and self ratings on eight empirically derived cross-informant syndromes. Path analyses indicated that parent ratings of each time 1 syndrome predicted parent ratings of the same time 2 syndrome. Family variables and intervening stressful experiences predicted parent and self ratings, but not teacher ratings of syndromes. The number of family members receiving mental health services was the family variable that predicted the most time 2 syndromes. Parent reports of stress predicted parent ratings of time 2 syndromes, whereas child reports of stress predicted self-ratings of time 2 syndromes.
Fifty-two newborns were assessed for the effects of maternal cocaine use on their performance on the Brazelton Neonatal Behavior Assessment Scale and on their stress behaviors during the Brazelton as tapped by the Neonatal Stress Scale. The cocaine-exposed newborns experienced more obstetric complications, had smaller head circumferences, showed more limited habituation abilities on the Brazelton Scale, and exhibited more stress behaviors than control newborns.
The number of infants born to cocaine-using mothers has continued to rise during the past 5 years. Maternal cocaine use during pregnancy is associated with medical and life-style characteristics detrimental to fetal and infant development. Cocaine exposure has been independently linked to growth retardation and impaired fetal oxygenation even when polydrug use and other confounding factors are considered. Neurologic and neurobehavioral abnormalities noted in the immediate neonatal period have also been associated with fetal cocaine exposure. The direct and indirect toxic effects of cocaine, per se, have not yet been independently linked to specific behavioral outcomes because of small sample sizes, confounding factors, and lack of long-term follow-up. The impoverished environments and increased risk for out-of-family placement of cocaine-exposed infants are known independent correlates of negative developmental outcomes. Poor maternal nutrition, lack of prenatal care, and other health and life-style factors related to maternal cocaine use during pregnancy also appear to be factors mediating the developmental problems of cocaine-exposed infants. The cocaine-using mother often uses other drugs, particularly alcohol, independently known to be linked to growth and behavioral impairments similar to those proposed for cocaine-exposed infants. Accounting for these multiple confounding variables in studies of the specific effects of cocaine on neurobehavioral outcome may be scientifically appropriate, but in clinical practice these factors cannot be "isolated," and their statistical consideration in studies does not diminish clinical risk. Finally, currently available studies of behavioral outcome have restricted their samples to term infants. It is possible that preterm infants may be less affected by prenatal cocaine exposure because of decreased exposure. However, because epidemiologic studies suggest that prematurity is a sequelae of maternal cocaine use, restriction of samples to term or appropriately sized infants may underestimate the spectrum of morbidity associated with cocaine exposure. We believe that maternal cocaine use during pregnancy is a "marker" variable for early impairments in infant growth and behavioral functioning that have long-term implications for later developmental outcome, especially for learning disabilities and behavioral disorders. Critically assessing the independent contribution of cocaine to negative developmental outcome and determining whether early neonatal abnormalities are permanent or modifiable may allow clinical intervention and improved social policy. Assessing the independent effects of cocaine on child developmental outcome will require carefully designed, long-term, longitudinal, population-based studies with samples large enough to allow multivariate data analyses and statistical control of confounding medical and social variables.
The effects of fetal cocaine exposure on newborn cry characteristics were studied in 80 cocaine-exposed and 80 control infants. The groups were stratified to be similar on maternal demographic characteristics and maternal use of other illegal substances and alcohol during pregnancy. The hypothesis was that excitable cry characteristics were related to the direct effects of cocaine, while depressed cry characteristics were related to the indirect effects of cocaine secondary to low birthweight. Structural equation modeling (EQS) showed direct effects of cocaine on cries with a longer duration, higher fundamental frequency, and a higher and more variable first formant frequency. Indirect effects of cocaine secondary to low birthweight resulted in cries with a longer latency, fewer utterances, lower amplitude, and more dysphonation. Cocaine-exposed infants had a lower birthweight, shorter length, and smaller head circumference than the unexposed controls. Findings were consistent with the notion that 2 neurobehavioral syndromes, excitable and depressed, can be described in cocaine-exposed infants, and that these 2 syndromes are due, respectively, to direct neurotoxic effects and indirect effects secondary to intrauterine growth retardation.
The relationship of maternal use of marijuana and cocaine during pregnancy to measures of neonatal body proportionality and body composition was assessed in a multiethnic sample of 1082 newborn infants. Maternal use of marijuana and cocaine during pregnancy was ascertained by self-report and by an enzyme-multiplied immunoassay technique for screening of urine samples obtained prenatally and again post partum. After each substance was analytically controlled for use of the other and for other potentially confounding variables, detection of marijuana metabolites in maternal urine was associated (p less than 0.05) with depressed mean arm muscle circumference and nonfat area of the arm but not with any measure of neonatal fatness. In contrast, detection of cocaine in maternal urine was associated (p less than 0.05) with decrements of subscapular fat folds and of the fat and nonfat areas of the arm. Although both substances were associated with depressed birth weight, there was no decrement of neonatal ponderal index or of the arm circumference/head circumference ratio in association with exposure to either substance. We conclude that both marijuana exposure and cocaine exposure during pregnancy are associated with symmetric intrauterine growth retardation, but that deficits are in differing compartments of intrauterine growth. These findings suggest that marijuana may retard fetal growth through maternal-fetal hypoxia, whereas cocaine may alter nutrient transfer to the fetus and fetal metabolism.
Aspects of neurobehavioral development were examined in 133 36-month- and 130 48-month-old children for whom prenatal exposure to marijuana, cigarettes, and alcohol had been previously ascertained and who have been assessed since birth. Parallelling earlier observations made with this sample at 12 and 24 months, prenatal exposure to cigarette smoking was significantly associated with poorer language development and lower cognitive scores at both 36 and 48 months after statistically controlling for confounding factors. Relatively low levels of maternal alcohol consumption, which had measurable effects at 24 and 36 months, no longer had significant relationships with outcome variables at 48 months of age. At 48 months, significantly lower scores in verbal and memory domains were associated with maternal marijuana use after adjusting for confounding variables. This negative relationship is the first reported association beyond the neonatal stage, and may represent a long-term effect of the drug upon complex behavior that, at a younger age, had not developed and/or could not be assessed.
As a preface to the pharmacokinetic analysis of cocaine in pregnant and lactating rats (using oral administration of drug), young Long-Evans rats were used to compare the relative concentrations of cocaine in blood, brain, and liver after administering cocaine by iv or oral routes. Cocaine and its metabolites were determined using 3H-cocaine as a tracer, followed by homogenization and solvent extraction of tissues, and quantitative analysis by HPTLC and LSC. From 30 min postinjection to several hrs later, the concentration of cocaine was higher in brain (3-4 fold) and liver (3-5 fold) than in blood, using the iv route. Using the oral route, the concentration in brain was 2-3 fold higher than in blood, and in liver, 10-20 fold higher. The metabolites of cocaine were largely excluded from entry into brain tissue, whereas the accumulation of metabolites in liver was typically an order of magnitude higher, or more, than in blood (iv or oral route). The ratio of cocaine to metabolites increased in all three tissues, as the dosage increased, indicating that more and more of an administered dose actually reaches the tissues as cocaine as the dosage level increases. During the period from 30 to 90 min following the administration of cocaine to pregnant dams, cocaine appeared in fetal brain at a rate of 50-90% of the concentration in the dam's brain (presumably because of the lower lipid content in fetal brain compared to adult), but still at a rate of 109-151% of the concentration in the dam's blood. Cocaine is sufficiently stable in milk to assume that any cocaine entering breast milk from the blood stream will be available to the suckling infant, and after administering radioactive cocaine to lactating dams, the milk/blood ratio for cocaine averaged 7.8. These data indicate that both the fetus and suckling infant are at considerable risk from cocaine use by the mother.
Hypoxia-ischemia, hypoglycemia, and status epilepticus damage specific regions in the developing brain. The factors which determine selective neuronal vulnerability have remained obscure but recent research suggests that the patterns may be related to dysfunction of specific sets of synapses. An important current hypothesis suggests that hyperactivity of excitatory synapses, which use neurotransmitters such as glutamate, may cause excessive transmitter release and lead to damage of adjacent neurons. Excessive stimulation of excitatory neurotransmitter receptors triggers a cascade of biochemical reactions and potentially lethal ionic shifts. Recent observations suggest that drugs acting at these receptors could be used to reduce brain injury caused by a variety of insults to the developing brain.
Seventy-five cocaine-using women enrolled in a comprehensive perinatal care program were divided into two groups: those who used cocaine in only the first trimester of pregnancy (group 1 [N = 23]) and those who used cocaine throughout pregnancy (group 2 [N = 52]). Perinatal outcomes of these pregnancies were compared with perinatal outcomes of a matched group of obstetric patients with no history or evidence of substance abuse (group 3 [N = 40]). Group 2 women had an increased rate of preterm delivery and low-birth-weight infants as well as an increased rate of intrauterine growth retardation. Group 1 women had rates of these complications similar to the drug-free group. Mean birth weight, length, and head circumference for term infants were reduced in only the group 2 infants. However, both groups of cocaine-exposed infants demonstrated significant impairment of orientation, motor, and state regulation behaviors on the Neonatal Behavioral Assessment Scale.
Extracellular microelectrode studies were conducted to test the effects of cocaine HCl on the activity of spontaneously firing single serotonergic dorsal raphe (DRN), noradrenergic locus coeruleus (LC) and dopaminergic ventral tegmental (VTA) and zona compacta (ZC) neurons, and cerebellar Purkinje neurons (PC) in urethane anesthetized rats in vivo. Cocaine (0.0625-4 mg/kg) predominantly inhibited all of the central monoaminergic neurons and predominantly activated cerebellar Purkinje neurons. Cocaine (1 mg/kg, IV) failed to potentiate the inhibitory effects of LC stimulation on PC neurons. The temporal effects of intravenous cocaine on arterial pressure (i.e., pressor response) were not directly correlated with the effects on neurons. Cocaine did not decrease the amplitude or slope of neuron action potentials, and the effects of cocaine on firing rate were not shared by similar doses of procaine. Reserpine pretreatment (10 mg/kg, IP) attenuated the effects of cocaine (1 mg/kg, IV) on DRN, LC, and PC neurons. Specific adrenoceptor antagonists antagonized the inhibitory effects of cocaine on LC (piperoxane, yohimbine) and VTA (haloperidol) neurons. These results suggest that the central effects of cocaine on presynaptic monoaminergic neurons may in part be mediated by augmented monoamine neurotransmission at autoreceptors and that the effects of cocaine on postsynaptic target cells (PC) may be more complex, requiring the analysis of both pre- and postsynaptic elements.
To study teratogenicity of cocaine in humans, we studied three groups of pregnant women and their offspring: group 1, 50 women who abused cocaine only; group 2, 110 women who were polydrug abusers; and group 3, 340 who were drug free. All three groups were similar for socioeconomic status, cigarette smoking, and ethnicity. Maternal age of group 1 was similar to that of group 3, but group 2 mothers were significantly older. Gravidity was significantly higher in groups 1 and 2 compared with group 3. No statistical difference was found in spontaneous abortion rate among the three groups, but the stillbirth rate was significantly higher in group 1 (chi 2 = 6.89, P less than or equal to 0.01). All stillbirths were related to abruptio placentae. Birth weight, length, and head circumference were significantly decreased in infants in groups 1 and 2 compared with group 3 (P less than or equal to 0.0001), but no statistical difference was found between groups 1 and 2. The congenital malformation rate was significantly higher in group 1 compared with group 3 (chi 2 = 7.07, P less than or equal to 0.01). We conclude that cocaine abuse in humans significantly reduces weight of the fetus, increases the stillbirth rate related to abruptio placentae, and is associated with a higher malformation rate.
With the increasing use of cocaine in the United States, there has been growing concern regarding its effects on the fetuses and neonates of pregnant cocaine abusers. Twenty-three cocaine-using women enrolled in a comprehensive perinatal-addiction program were divided into two groups: those using cocaine only and those using cocaine plus narcotics. These two groups were compared with a group of women who had used narcotics in the past and were maintained on methadone during pregnancy, and with a group of drug-free women. All four groups were similar in maternal age, socioeconomic status, number of pregnancies, and cigarette, marijuana, and alcohol use. Their medical histories indicated that the cocaine-using women had a significantly higher rate of spontaneous abortion than the women in the other two groups. In the pregnancies under study, four cocaine-using women had onset of labor with abruptio placentae immediately after intravenous self-injection of cocaine. Neonatal gestational age, birth weight, length, and head circumference were not affected by cocaine use. However, the Brazelton Neonatal Behavioral Assessment Scale revealed that infants exposed to cocaine had significant depression of interactive behavior and a poor organizational response to environmental stimuli (state organization). These preliminary observations suggest that cocaine influences the outcome of pregnancy as well as the neurologic behavior of the newborn, but a full assessment will require a larger number of pregnancies and longer follow-up.
PIP
Case histories are presented of 8 unrelated children born to mothers who were chronic alcoholics. These children showed a similar pattern of craniofacial, limb, and cardiovascular defects associated with prenatal-onset growth deficiency and developmental delay. This is the 1st report to document an association between maternal alcoholism and aberrant morphogenesis in the offspring. The mean duration of maternal alcoholism was 9.4 years. 3 of the cases were black, 3 were Native American, and 2 were white. The mean gestational age was 38 weeks. The degree of linear growth deficiency was more severe than the deficit of weight at birth, suggesting that a factor other than maternal undernutrition alone affected prenatal growth. Developmental delay, prenatal and postnatal growth deficiency, and short palbebral fissures were observed in all 8 children. 7 of the 8 children also demonstrated microcephaly and maxillary hypoplasia with relative prognathism. 6 had an altered palmar crease pattern, 5 showed cardiac and joint anomalies, and 4 had epicanthal folds. Although adequate nutrition was provided to the children during hospital admission and/or foster care placement, no catch-up growth was observed. After 1 year, the average linear growth rate was 65% of normal and the average rate of weight gain was only 38% of normal. By 1 year, head circumference fell below the 3rd percentile for height and chronological age in 5 of the 6 children in whom measurements were taken. Fine motor dysfunction was present in 5 of the 6 children tested, and most were delayed in gross motor performance as well. The similarity in pattern of malformation noted among these 8 children suggests a singular mode of etiology related to an as yet unknown effect of maternal alcoholism. Direct ethanol toxicity is the most likely possibility.
The levels of dopamine and norepinephrine were determined in the brains of fetal and newborn rats by means of a sensitive, radiometric-enzymatic assay. Catecholamines were converted to their 3-O-methylated derivatives in the presence of catechol-O-methyl transferase (EC 2.1.1.1) and [3 H-methyl]S-adenosylmethionine; and the [3H]-derivatives were isolated by selective extraction. The assay had a sensitivity for dopamine and norepinephrine of 100 picograms and was linear to at least 30 nanograms of catecholamines. Both amines were present at 15 days of gestation and increased 15-fold in content during the last week of gestation. The regional distribution of these neurotransmitters in the brain of the newborn rat correlated with the distribution of their biosynthetic enzymes. An investigation of the effects of reserpine, pheniprazine, α-methyl-para-tyrosine, diethyldithiocarbamate and l -DOPA on the levels of dopamine and norepinephrine in the brains of the 18-day gestational fetus indicated that the levels of these neurotransmitters are under controls similar to those known to occur in the brain of the adult rat.
The onset of cell differentiation in the locus coeruleus, dorsal and medial raphe nuclei, and substantia nigra (zona compacta) was studied using the technique of long-survival H3-thymidine autoradiography to date neurogenesis. Pregnant female rats were injected with isotope on day 10, 11, 12, 13, 14, 15, 16 or 17 of gestation. Litters were born on day 22 and allowed to survive for 30 days. Brains were prepared for the fluorescence histochemical demonstration of monoamines or fixed by formalin perfusion. Autoradiography was carried out on sections adjacent to those in which monoamine-nuclear groups were identified by the fluorescence method and also on sections from perfused brains, which were used to facilitate cell counting. The norepinephrine cells of the locus coeruleus began to differentiate (presence of heavily labelled cells) on days 10–13 of gestation, with a peak of heavy labelling on day 12, whereas the 5-HT cells of the raphe nuclei and the dopamine cells of the substantia nigra began differentiating on days 11–15. In the dorsal raphe nucleus, the peak of heavy labelling occurred on day 14, whereas in the medial nucleus this took place on days 13–14. The substantia nigra, on the other hand, peaked on day 13.
Cell differentiation was also studied in the cerebellar Purkinje cells and hippocampal macroneurons (pyramidal and polymorph cells) of areas CA3 and CA4, to which the locus coeruleus has been reported to project. Differentiation of these cells commenced on days 14–15 (Purkinje cells) and 13–18 (hippocampal cells), with both cell types peaking on day 15, a full three days after the peak of heavy labelling in the locus coeruleus.
Evidence is discussed for the possible neurotrophic role of monoamine neurons in the neurogenesis of monoaminergic receptive cells.
Cocaine and other drug use during pregnancy continues to be a major health concern. With increasing use of cocaine by women of childbearing age, large numbers of children have been exposed to this and other substances in utero. Currently, very little information regarding the long-term developmental implications of cocaine/polydrug exposure exists. The purpose of this study is to present 3-year cognitive and behavioral data on infants exposed to cocaine and other drugs during gestation.
The subjects and controls in this study are currently enrolled in a longitudinal, prospective evaluation. At 3 years of age, 92 children exposed to cocaine and other drugs, 25 children exposed to multiple drugs but no cocaine, and 45 drug-free controls were evaluated using the Stanford-Binet Intelligence Scale (fourth edition), the Child Behavioral Checklist, the Home Screening Questionnaire, and a Summative Perseverance Scale. The data were analyzed using an a priori model and path analytic procedures.
The results indicate that prenatal drug exposure has significant direct and indirect effects on 3-year cognitive functioning as measured on the Stanford-Binet scale. The fit indices indicated that overall, the hypothesized model accurately reflected the actual data.
The findings of the study provide specific evidence elucidating the nature of long-term developmental risk associated with intrauterine drug exposure. Drug exposure was found to have a direct effect on cognitive ability at 3 years of age. However, the effects of drug exposure are also mediated indirectly through head circumference, home environment, and level of perseverance at a task. Future explorations should continue to utilize path analysis techniques to further clarify the ramifications of drug exposure on the development of the growing child.
To determine the effect of prenatal cocaine exposure on 3-month infant information processing and developmental assessments.
One hundred and eight infants, 61 cocaine-exposed and 47 controls, participated at 3 months of age in an infant-control habituation and novelty responsiveness procedure and in a developmental assessment using the Bayley Scales of Infant Development both administered by experimenters blind to the drug exposure status of the infant.
Compared to the non-drug-exposed group, infants exposed prenatally to cocaine were significantly more likely to fail to start the habituation procedure and, for those who did, significantly more likely to react with irritability early in the procedure. The majority of infants in both groups reached the habituation criterion, and among those who did there were no significant differences between cocaine and non-cocaine-exposed infants in habituation or in recovery to a novel stimulus. Infants who were cocaine-exposed showed comparatively depressed performance on the motor (Psychomotor Developmental Index) but not the mental (Mental Developmental Index (MDI)) scales of the Bayley. These results obtained for habituation and Bayley MDI controlling for both perinatal and sociodemographic factors.
Differences in reactivity to novelty but not in information processing between cocaine-exposed and non-cocaine-exposed infants suggest that the effects of prenatal cocaine exposure may be on arousal and attention regulation rather than early cognitive processes.
Data concerning alcohol and drug abuse and dependence, depression, and antisocial behaviors, among both subjects and their parents, were obtained from a community sample of 1,201 young adults. Although 35% of the sample exhibited alcohol abuse or dependence, 14% marijuana or cocaine abuse or dependence, and 22% reported a parent positive for alcoholism, evidence of comorbidity with depression or antisocial personality was generally rare among both parents and subjects. Over one third of the subjects were negative both for family history and any disorder of their own and 20% reported a problem in both themselves and in one or both parents. These findings lend only partial support for Winokur's depression spectrum disease hypothesis, in that diagnosed children of depressed-only families have a 30% chance of exhibiting substance abuse or dependence alone, whereas diagnosed children of alcoholic-only families have only a 7% chance of exhibiting depression alone.
Cocaine‐exposed children: Follow‐up through 30 months
- Hurt H.
Neurobehavioral syndromes in cocaine-exposed newborn infants
- Lester
The Home Screening Questionnaire Reference Manual
- C E E C Coons
- A W Gay