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Cocaine Babies: Does Prenatal Exposure to Cocaine Affect Development?
SPECIAL
Assistant Editor: John E. Schowalter, M.D.
SECTION
Cocaine Babies: Does Prenatal Exposure to Cocaine Mfect Development? GUEST EDITORS: NILDA M. GONZALEZ, M.D., AND MAGDA CAMPBELL, M.D.
INTRODUCTION
In the past decade the use of cocaine and "crack" by women of childbearing years has created a great deal of concern among clinicians and society at large. This concern is because of possible long-term effects of a potentially neurotoxic agent in the offspring, somewhat analogous to the recognition two decades ago of the fetal alcohol syndrome (jones et al., 1973). Considerable media attention has been directed toward the emergence of a new group of children at risk: the so called "crack babies." Children who were exposed intrautero to these substances are being referred to nurseries, schools, and developmental clinics as they approach their second to seventh year of life. Th~re has been considerable press coverage of prenatal cocaine exposure and its detrimental effects on development; anecdotal reports suggest these children may present with distractibility, hyperactivity, impulsivity, aggressiveness, and language delays. There seems to be a tendency to cite studies with positive findings (Finnegan, 1991; Koren et al., 1989). Recent reports by the Senate Judiciary Committee indicate that there are almost 2,200,000 cocaine addicts in this country. It is estimated that 325,000 prenatally drug-exposed babies are born per year in the United
Accepted May 12, 1993. At the time thispaper was written, Dr. Gonzalez was a Research Fellow and Clinical Instructor at the Department ofPsychiatry, New York University Medical Center, New York; currently sheisInstructor ofPsychiatry, Department ofPsychiatry, New York Hospital/Cornell University M~dical College, West~hes terDivision, WhitePlains, New York. Dr. Campbell ts Professor ofPsychtatry, Department of Psychiatry, New York University Medical Center. This work was supported in part by NIMH grants MH-40177 (Dr. Campbeli) and MH-18915 (Drs. Campbell and Gonzalez). Reprint requests to Dr. Campbell; Department of Psychiatry, New York University Medical Center, 550 FirstAvenue, New York, NY 10016. 0890-8567/94/3301-0016$03.00/0©1994 by the American Academy of Child and Adolescent Psychiatry.
16
States; approximately 100,000 were exposed to cocaine (cited from the U.S. General Accounting Office, June 1990), although cocaine alone is rarely used. Thus, these babies usually were exposed intrautero to other illicit substances (Chasnoff et al., 1992) as well as to alcohol. Underreporting of drug use is common (Matera et al., 1990; Zuckerman et al., 1989) and constitutes a major problem with retrospective studies (Chasnoff et al., 1992). The high rate of cocaine abuse as well as simultaneous abuse of other illicit substances and of alcohol has been reported across all socioeconomic classes (Bingol et al., 1987; Chasnoff and Griffith, 1989; Chasnoff et al., 1989) and throughout most communities in the country. However, there are only a few carefully designed long-term studies designed to critically ascertain the effects, if any, of prenatal cocaine exposure in children. Systematic research is required to identify any cognitive/ behavioral delays or deviations in children with prenatal cocaine exposure and to develop appropriate educational and therapeutic interventions. In planning a study with any population of children, it is important to address methodological issues. In this population, the multiple psychosocial and biological variables make the study of the effects of prenatal cocaine exposure very difficult. Among these variables are the effects. of polysubstance use, the trimester ofexposure, the quality and quantity ofsubstances abused, the effects of malnutrition and poor prenatal care; maternal psychopathology; family dysfunction; child neglect; and the effects of multiple caregivers in foster care placement. Of greatest importance is the selection of the sample and the selection of controls. Cocaine is a central nervous system (CNS) stimulant derived from the Erythroxylon coca plant. Cocaine blocks presynaptic dopamine (DA) and norepinephrine (NE) reuptake into the presynaptic region acting, therefore, as an indirect agonist to both substances. Cocaine
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994
COCAINE BABIES: INTRODUCTION '
can be administered orally, intranasally, by IV injection, or smoked. The rapid onset, short duration, and euphoric state caused by cocaine seems to be the reason for its high addictive potential (for reviewsee Fischman, 1987). Onset of action of cocaine used intravenously or if smoked as crack (an alkaloidal base form of cocaine) is within 1 to 2 minutes; intranasal intake has a slower onset and produces less euphoria. Cocaine is metabolized primarily by liver and plasma cholinesterases; in adults, close to 70% of the metabolites can be recovered in the urine up to 3 days after drug use (Hawks and Chiang, 1986). Pregnant women (Evans er al., 1988; Jones, 1984) and fetuses (jones, 1984) may have decreased cholinesterase activity and cocaine metabolites, specificallybenzolecgonine, have remained in human babies up to 120 hours after delivery (Chasnoff er al., 1989). In laboratory animals, cocaine crosses the placenta rapidly resulting in fetal tachycardia and hypertension and uterine artery vasoconstriction with concomitant fetal hypoxemia (Woods et al., 1987, 1989), but there is disagreement as to the long-term effects of prenatal cocaine exposure. Hyperactivity (Dow-Edwards, 1989; Spear, 1989) and learninglretention deficits (Spear, 1989) were reported in rats with prenatal cocaine exposure. Only minimal delays in physical maturation and developmental deficits and a trend toward hypoactive behavior (Church et al., 1990; Church and Overbeck, 1990a,b) as well as improvement with maturation (Church et al., 1990a,b) were reported by others. Effects of cocaine in human neonates were evaluated by Richardson and Day (1991). Thirty-four mostly low-income pregnant women (described as moderate cocaine users) attending a prenatal clinic were studied. This group reported using 2 to 3 g of cocaine per month during the first trimester. Cocaine use decreased to 0.4 and 0.2 g per month during the second and third trimester, respectively. There were no significant differences in this sample of 34 prenatally cocaine exposed neonates as compared with the 600 controls in regard to minor physical anomalies, head circumference, length, or birth weight when adjusting for parity, race, alcohol, tobacco, and other drug exposure. The sample was studied between 1983 and 1986; there were no reports of crack use in the mothers. The use of highly addictive crack is likely to be associated with a deterioration in functioning of the mother, with concomitant increasing drug exposure,
J. AM. ACAD . CHILD ADOLESC . PSYCHIATRY, 33:1, JANUARY 199 4
poor prenatal care, and higher risk to the ferus. Cocaine and/or crack is rarely the sole drug used: most early reports are based on offspring of mothers who were polydrug users in addition to cocaine and/or crack. In these reports, high rates of abruptio placentae and growth retardation intrautero (Chasnoff and Griffith , 1989) were reported; at birth, withdrawal symptoms (Chasnoff et al., 1988) and cerebral infarctions (Chasnoff et al., 1986), low weight, congenital malformations (Kim et al., 1989); microcephaly (Bingol et al., 1987; Chasnoffand Griffith , 1989; Yoon et al., 1989); genitourinary tract malformations (Chasnoff et al., 1988) and transient abnormalities of electroencephalogram (EEG) were found (Doberczack et al., 1988). Disturbances of feeding, sleep, and vision also have been reported. The frequency and total amount of cocaine intake influences the outcome (Chasnoff et al., 1989; Richardson and Day, 1991). The frequent association of cocaine and alcohol use during pregnancy makes the possibility of toxicity secondary to cocaethylene arise; cocaethylene, and ethyl homologue of cocaine produced by the liver has a long half-life (2 hours), and in rats can be lethal. The long-term effects of cocaethylene in children are not known. The effects of alcohol and nicotine in infants of mothers who were heavy users of these drugs are well documented. Such effects of alcohol include dysmorphology in the form of fetal alcohol syndrome (jones et al., 1973), growth abnormalities (Fried and O'Connell, 1987), cognitive and language deficits (Fried and Watkinson, 1990), aggression and hyperactivity (Brown et al., 1991). Heavy cigarette smoking during pregnancy was reported to be associated with perinatal complications, low birth weight (Fried and O'Connell, 1987), and impairment in language and cognitive development in offspring as compared with controls at ages 36 and 48 months (Fried and Watkinson, 1990). Long-term follow-up studies of children exposed intrautero to other drugs (such as heroin and methadone) have, not surprisingly, been inconclusive. Language delays (Van Baar, 1990), low weight and head circumference, presence of soft neurological signs, impulsivity, and poor peer relationships (Wilson et al., 1979) compared with controls have been reported in preschoolers. No significant differences between preschoolers with opiate exposure and controls were found by others (Kaltenbach and Finnegan, 1989; ' Lifschitz et al., 1985).
17
GONZALEZ AND CAMPBELL
Based on a retrospective chart review, a variety of developmental and growth delays and behavioral symptoms were identified in 70 children with prenatal polydrug exposure: all had a history of prenatal cocaine exposure and/or positive toxicology report at birth (Davis et al., 1992). In addition to cocaine, alcohol (47%) and opiates (14%) were among the drugs used by the mothers. The children, ranging from neonates to older than 3 years (mean, 19.2 months), were referred to a developmental clinic of a large municipal hospital. Hyperactivity, language delays, and behavioral disorders were reported; although the mean percentile of weight and height was within the normal range, the number of small children was excessive both for height and weight (Davis et al., 1992). Eleven percent of the children were diagnosed as autistic disorder by DSM-III-R criteria (American Psychiatric Association, 1987). However, because this is a biased sample, the high number of children with autistic disorder as well as with other developmental delays or behavioral problems may be a function of the nature of the clinic and not necessarily of cocaine exposure. Because of the absence of a control group (without prenatal cocaine exposure), these findings cannot be generalized. In another study, the effectsof prenatal exposure to multiple drugs was assessed in a sample of 18 infants at 13 months of age (Rodning et al., 1989). Most of the sample had been exposed to cocaine, and all infants were drug positive at birth. When compared with preterm high-risk infants matched for age and without history of drug exposure, the drug-exposed group had poor representational play even though it was within the average range developmentally. Chasnoff et al., (1992) reported a 2-year follow-up of 106 infants with prenatal cocaine as well as alcohol and marijuana exposure (Group 1) and of 45 infants with alcohol/marijuana exposure but without cocaine (Group 2). Periodic assessments were carried out in the same fashion in both groups as in the control group of 81 infants whose mothers were free of alcohol and illicit drugs during pregnancy (Group 3). At 24 months of age both groups with prenatal drug exposure had significantly smaller head circumferences and developmental delays as evidenced on Bayley Mental and Psychomotor Indices than did the controls who had no prenatal drug exposure. However, only the children with prenatal cocaine exposure were significantly shorter than the control group. The sample sizes had
18
decreased at 24 months: Group 1 to 41 children, Group 2 to 23, and Group 3 (the controls) to 77. There is, as yet, no answer to the question posed by the title of our section. This special section will present on-going prospective follow-up studies with the objective of shedding light on this difficult topic. Our goal is to generate clinical interest and to promote research and discussion in the child psychiatry community concerning this serious public health problem.
REFERENCES American PsychiatricAssociation (1987), Diagnostic and Statistical Manual ofMental Disorders 3rd edition-revised (DSM-IlI-R). Washington, DC: American Psychiatric Association BingolN, Fuchs M, Diaz V, Stone RK, Gromisch DS (1987), Teratogenicity of cocaine in humans. ] Pediatr 110:93-96 Brown RT, Coles CD, Smith IE et al. (1991), Effects of prenatal alcohol exposure at school age. II. Attention and behavior. Neurotoxicol Teratol 13:369-376 Chasnoff IJ, Bussey ME, Savich R, Stack CM (1986), Perinatal cerebral infarction and maternal cocaine use. ] Pediatr 108:456-459 Chasnoff IJ, Chisum GM, Kaplan WE (1988), Maternal cocaine use and genitourinary tract malformations. Teratology 37:201-204 Chasnoff I, Griffith D (1989), Cocaine: clinical studies of pregnancy and the newborn. Ann NY Acad Sci 562:260-266 Chasnoff IJ, Griffith DR, Freier C, Murray J (1992), Cocaine/polydrug use in pregnancy: two-year follow-up. Pediatrics89:284-289 Chasnoff IJ, Lewis DE, Griffith DR, Willey S (1989), Cocaine and pregnancy: clinical and toxicological implications for the neonate.
Clinical Chemistry 35:1276-1278 Church MW, Overbeck GW, Andrzejczak AL (1990), Prenaral cocaine exposure in the Long-Evans rat: I. Dose-dependent effects on gestation, mortality and postnatal maturation. Neurotoxicol TeratoI12:327-334 Church MW, Overbeck GW (1990a), Prenatal cocaine exposure in the Long-Evans rat: II. Dose dependent effects on offspring behavior.
Neurotoxicol TeratoI12:335-343 Church MW, Overbeck GW (1990b), Prenaral cocaine exposure in the Long-Evans rat: III. Developmental effects on the brainstem auditoryevoked potential. Neurotoxicol TeratoI12:345-351 Davis E, Fennoy I, Laraque D, Kanem N, Brown G, Mitchell J (1992), Autism and developmental abnormalities in children with perinatal cocaine exposure. ] Natl Med Assoc 84:315-319 Doberczack TM, Shanzer S, Senie RT, Kandall SR (1988), Neonatal neurologic and electroencephalographic effects of intrauterine cocaine exposure. ] Pediatr 113:354-358 Dow-Edwards DL (1989), Long-term neurochemical and neurobehavioral consequences of cocaine use during pregnancy. Ann N Y Acad Sci 562:280-289 Evans RT, O'Callaghan J, Norman A (1988), A longitudinal study of cholinesterase changes in pregnancy. Clinical Chemistry 34:2249-2252 Finnegan LP (1991), Cocaine abuse in pregancy: the toll on fetus and newborn. Paper presented at the Eighth Annual Einstein Symposium in Psychiatry, The War Against Cocaine: Scientific Insights, Clinical 6Societal Implications. New York Academy of Medicine, New York City, November 22, 1991 Fischman MW (1987), Cocaine and the amphetamines, In: Psychopharmacology: The Third Generation of Progress, ed H Y Meltzer, New York, Raven Press Fried, PA, O'Connell CM (1987), A comparison of the effects of prenatal exposure to tobacco, alcohol, cannabis, and caffeine on birth size and subsequent growth. Neurobehavioral Toxicology and Teratology 9:79-85
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994
COCAINE BABIES: INTRODUCTION Richardson GA, Day NL (1991), Maternal and neonatal effectsof moderate cocaine use during pregnancy. Neurotoxicol Teratol13:455-460 Rodning C, Beckwith L, Howard J (1989), Prenatal exposure to drugs: behavioral distortions reflecting CNS impairment? NeuroToxicology 10:629-634 Spear LP, Kirstein CL, Frambes NA (1989), Cocaine effects on the developing central nervous system: behavioral, psychopharmacological and neurochemical studies. Ann N Y Acad Sci 562:290-307 van Baar A (1990), Development of infants of drug dependent mothers. J Child Psychol Psychiatry 31:911-920 Wilson GS, McCreary R, Kean J, Baxter JC (1979), The development of preschool children of heroin-addicted mothers: a controlled study.
Fried PA, Watkinson B (1990), 36- and 48- month neurobehavioral followup of children prenatally exposed to marijuana, cigarettes, and alcohol. J Deu Behav Pediatr 11:49-58 Hawks RL, Chiang CN (1986), Examples of specific drug assays. Urine Testing for Drugs of Abuse. NIDA Res Monogr 73:84-112 Jones KL, Smith OW, Ulleland CN (1973), Pattern of malformation in offspring chronic alcoholic mothers. Lancet 1:1267-1271 Jones R (1984), The Pharmacology of Cocaine. NIDA Res Monogr 50:34-53 Kaltenbach K, Finnegan LP (1989), Children exposed to methadone in utero: assessment of developmental and cognitive ability. Ann N Y
Acad Sci 562:360-362 Kim M, Checola RT, Noble LM, Yoon JJ (1989), Cocaine and congenital malformations. Pediatr Res Proc 25(part 2):77A Koren G, Shear H, Graham K, Einarson T (1989), Bias against the null hypothesis: the reproductive hazards of cocaine. Lancet 1440-1442 Lifschitz MH, Wilson GS, Smith EO, Desmond MM (1985), Factors affecting head growth and intellectual function in children of drug addicts. Pediatrics 75:269-274 Matera C, Warren WE, Moomjy M, Fink OJ, Fox HE (1990), Prevalence of the use of cocaine and other substances in an obstetric population.
Pediatrics 63:135-141 Woods JR, Plessinger MA, Clark KE (1987), Effect of cocaine on uterine blood flow and fetal oxygenation. JAMA 257:957-961 Woods JR, Plessinger MA, Scott K, Miller RK (1989), Prenatal cocaine exposure to the fetus: a sheep model for cardiovascular evaluation. Ann
NY Acad Sri 562:267-279 Yoon JJ, Kim M, Checola RT, Noble LM (1989), Maternal cocaine abuse and microcephaly. Pediatr Res Proc 25(parr 2):79A Zuckerman B, Frank DA et al. (1989), Effects of maternal marijuana and cocaine use in fetal growth. N EnglJ Med 320:762-768
Am J Obstet GynecolI63:797-801
Coming in February: Special Article: Confidentiality in Custody Disputes CarlP. Malmquist
•
ADD Symptoms in Adolescence Elizabeth Schaughency et al.
•
Suicidal Children Grow Up: Effects of Treatment Cynthia R. Pfeffer et al.
•
Follow-up of Youth Exposed to Suicide David A. Brentet al.
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Behavioral Disorders in Male Carriers of Fragile X Margaret B. Dorn et al.
•
Thyroid Function and ADHD Josephine Elia et al.
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994
19
Assistant Editor: John E. Schowalter, M.D.
SECTION
Cocaine Babies: Does Prenatal Exposure to Cocaine Mfect Development? GUEST EDITORS: NILDA M. GONZALEZ, M.D., AND MAGDA CAMPBELL, M.D.
INTRODUCTION
In the past decade the use of cocaine and "crack" by women of childbearing years has created a great deal of concern among clinicians and society at large. This concern is because of possible long-term effects of a potentially neurotoxic agent in the offspring, somewhat analogous to the recognition two decades ago of the fetal alcohol syndrome (jones et al., 1973). Considerable media attention has been directed toward the emergence of a new group of children at risk: the so called "crack babies." Children who were exposed intrautero to these substances are being referred to nurseries, schools, and developmental clinics as they approach their second to seventh year of life. Th~re has been considerable press coverage of prenatal cocaine exposure and its detrimental effects on development; anecdotal reports suggest these children may present with distractibility, hyperactivity, impulsivity, aggressiveness, and language delays. There seems to be a tendency to cite studies with positive findings (Finnegan, 1991; Koren et al., 1989). Recent reports by the Senate Judiciary Committee indicate that there are almost 2,200,000 cocaine addicts in this country. It is estimated that 325,000 prenatally drug-exposed babies are born per year in the United
Accepted May 12, 1993. At the time thispaper was written, Dr. Gonzalez was a Research Fellow and Clinical Instructor at the Department ofPsychiatry, New York University Medical Center, New York; currently sheisInstructor ofPsychiatry, Department ofPsychiatry, New York Hospital/Cornell University M~dical College, West~hes terDivision, WhitePlains, New York. Dr. Campbell ts Professor ofPsychtatry, Department of Psychiatry, New York University Medical Center. This work was supported in part by NIMH grants MH-40177 (Dr. Campbeli) and MH-18915 (Drs. Campbell and Gonzalez). Reprint requests to Dr. Campbell; Department of Psychiatry, New York University Medical Center, 550 FirstAvenue, New York, NY 10016. 0890-8567/94/3301-0016$03.00/0©1994 by the American Academy of Child and Adolescent Psychiatry.
16
States; approximately 100,000 were exposed to cocaine (cited from the U.S. General Accounting Office, June 1990), although cocaine alone is rarely used. Thus, these babies usually were exposed intrautero to other illicit substances (Chasnoff et al., 1992) as well as to alcohol. Underreporting of drug use is common (Matera et al., 1990; Zuckerman et al., 1989) and constitutes a major problem with retrospective studies (Chasnoff et al., 1992). The high rate of cocaine abuse as well as simultaneous abuse of other illicit substances and of alcohol has been reported across all socioeconomic classes (Bingol et al., 1987; Chasnoff and Griffith, 1989; Chasnoff et al., 1989) and throughout most communities in the country. However, there are only a few carefully designed long-term studies designed to critically ascertain the effects, if any, of prenatal cocaine exposure in children. Systematic research is required to identify any cognitive/ behavioral delays or deviations in children with prenatal cocaine exposure and to develop appropriate educational and therapeutic interventions. In planning a study with any population of children, it is important to address methodological issues. In this population, the multiple psychosocial and biological variables make the study of the effects of prenatal cocaine exposure very difficult. Among these variables are the effects. of polysubstance use, the trimester ofexposure, the quality and quantity ofsubstances abused, the effects of malnutrition and poor prenatal care; maternal psychopathology; family dysfunction; child neglect; and the effects of multiple caregivers in foster care placement. Of greatest importance is the selection of the sample and the selection of controls. Cocaine is a central nervous system (CNS) stimulant derived from the Erythroxylon coca plant. Cocaine blocks presynaptic dopamine (DA) and norepinephrine (NE) reuptake into the presynaptic region acting, therefore, as an indirect agonist to both substances. Cocaine
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994
COCAINE BABIES: INTRODUCTION '
can be administered orally, intranasally, by IV injection, or smoked. The rapid onset, short duration, and euphoric state caused by cocaine seems to be the reason for its high addictive potential (for reviewsee Fischman, 1987). Onset of action of cocaine used intravenously or if smoked as crack (an alkaloidal base form of cocaine) is within 1 to 2 minutes; intranasal intake has a slower onset and produces less euphoria. Cocaine is metabolized primarily by liver and plasma cholinesterases; in adults, close to 70% of the metabolites can be recovered in the urine up to 3 days after drug use (Hawks and Chiang, 1986). Pregnant women (Evans er al., 1988; Jones, 1984) and fetuses (jones, 1984) may have decreased cholinesterase activity and cocaine metabolites, specificallybenzolecgonine, have remained in human babies up to 120 hours after delivery (Chasnoff er al., 1989). In laboratory animals, cocaine crosses the placenta rapidly resulting in fetal tachycardia and hypertension and uterine artery vasoconstriction with concomitant fetal hypoxemia (Woods et al., 1987, 1989), but there is disagreement as to the long-term effects of prenatal cocaine exposure. Hyperactivity (Dow-Edwards, 1989; Spear, 1989) and learninglretention deficits (Spear, 1989) were reported in rats with prenatal cocaine exposure. Only minimal delays in physical maturation and developmental deficits and a trend toward hypoactive behavior (Church et al., 1990; Church and Overbeck, 1990a,b) as well as improvement with maturation (Church et al., 1990a,b) were reported by others. Effects of cocaine in human neonates were evaluated by Richardson and Day (1991). Thirty-four mostly low-income pregnant women (described as moderate cocaine users) attending a prenatal clinic were studied. This group reported using 2 to 3 g of cocaine per month during the first trimester. Cocaine use decreased to 0.4 and 0.2 g per month during the second and third trimester, respectively. There were no significant differences in this sample of 34 prenatally cocaine exposed neonates as compared with the 600 controls in regard to minor physical anomalies, head circumference, length, or birth weight when adjusting for parity, race, alcohol, tobacco, and other drug exposure. The sample was studied between 1983 and 1986; there were no reports of crack use in the mothers. The use of highly addictive crack is likely to be associated with a deterioration in functioning of the mother, with concomitant increasing drug exposure,
J. AM. ACAD . CHILD ADOLESC . PSYCHIATRY, 33:1, JANUARY 199 4
poor prenatal care, and higher risk to the ferus. Cocaine and/or crack is rarely the sole drug used: most early reports are based on offspring of mothers who were polydrug users in addition to cocaine and/or crack. In these reports, high rates of abruptio placentae and growth retardation intrautero (Chasnoff and Griffith , 1989) were reported; at birth, withdrawal symptoms (Chasnoff et al., 1988) and cerebral infarctions (Chasnoff et al., 1986), low weight, congenital malformations (Kim et al., 1989); microcephaly (Bingol et al., 1987; Chasnoffand Griffith , 1989; Yoon et al., 1989); genitourinary tract malformations (Chasnoff et al., 1988) and transient abnormalities of electroencephalogram (EEG) were found (Doberczack et al., 1988). Disturbances of feeding, sleep, and vision also have been reported. The frequency and total amount of cocaine intake influences the outcome (Chasnoff et al., 1989; Richardson and Day, 1991). The frequent association of cocaine and alcohol use during pregnancy makes the possibility of toxicity secondary to cocaethylene arise; cocaethylene, and ethyl homologue of cocaine produced by the liver has a long half-life (2 hours), and in rats can be lethal. The long-term effects of cocaethylene in children are not known. The effects of alcohol and nicotine in infants of mothers who were heavy users of these drugs are well documented. Such effects of alcohol include dysmorphology in the form of fetal alcohol syndrome (jones et al., 1973), growth abnormalities (Fried and O'Connell, 1987), cognitive and language deficits (Fried and Watkinson, 1990), aggression and hyperactivity (Brown et al., 1991). Heavy cigarette smoking during pregnancy was reported to be associated with perinatal complications, low birth weight (Fried and O'Connell, 1987), and impairment in language and cognitive development in offspring as compared with controls at ages 36 and 48 months (Fried and Watkinson, 1990). Long-term follow-up studies of children exposed intrautero to other drugs (such as heroin and methadone) have, not surprisingly, been inconclusive. Language delays (Van Baar, 1990), low weight and head circumference, presence of soft neurological signs, impulsivity, and poor peer relationships (Wilson et al., 1979) compared with controls have been reported in preschoolers. No significant differences between preschoolers with opiate exposure and controls were found by others (Kaltenbach and Finnegan, 1989; ' Lifschitz et al., 1985).
17
GONZALEZ AND CAMPBELL
Based on a retrospective chart review, a variety of developmental and growth delays and behavioral symptoms were identified in 70 children with prenatal polydrug exposure: all had a history of prenatal cocaine exposure and/or positive toxicology report at birth (Davis et al., 1992). In addition to cocaine, alcohol (47%) and opiates (14%) were among the drugs used by the mothers. The children, ranging from neonates to older than 3 years (mean, 19.2 months), were referred to a developmental clinic of a large municipal hospital. Hyperactivity, language delays, and behavioral disorders were reported; although the mean percentile of weight and height was within the normal range, the number of small children was excessive both for height and weight (Davis et al., 1992). Eleven percent of the children were diagnosed as autistic disorder by DSM-III-R criteria (American Psychiatric Association, 1987). However, because this is a biased sample, the high number of children with autistic disorder as well as with other developmental delays or behavioral problems may be a function of the nature of the clinic and not necessarily of cocaine exposure. Because of the absence of a control group (without prenatal cocaine exposure), these findings cannot be generalized. In another study, the effectsof prenatal exposure to multiple drugs was assessed in a sample of 18 infants at 13 months of age (Rodning et al., 1989). Most of the sample had been exposed to cocaine, and all infants were drug positive at birth. When compared with preterm high-risk infants matched for age and without history of drug exposure, the drug-exposed group had poor representational play even though it was within the average range developmentally. Chasnoff et al., (1992) reported a 2-year follow-up of 106 infants with prenatal cocaine as well as alcohol and marijuana exposure (Group 1) and of 45 infants with alcohol/marijuana exposure but without cocaine (Group 2). Periodic assessments were carried out in the same fashion in both groups as in the control group of 81 infants whose mothers were free of alcohol and illicit drugs during pregnancy (Group 3). At 24 months of age both groups with prenatal drug exposure had significantly smaller head circumferences and developmental delays as evidenced on Bayley Mental and Psychomotor Indices than did the controls who had no prenatal drug exposure. However, only the children with prenatal cocaine exposure were significantly shorter than the control group. The sample sizes had
18
decreased at 24 months: Group 1 to 41 children, Group 2 to 23, and Group 3 (the controls) to 77. There is, as yet, no answer to the question posed by the title of our section. This special section will present on-going prospective follow-up studies with the objective of shedding light on this difficult topic. Our goal is to generate clinical interest and to promote research and discussion in the child psychiatry community concerning this serious public health problem.
REFERENCES American PsychiatricAssociation (1987), Diagnostic and Statistical Manual ofMental Disorders 3rd edition-revised (DSM-IlI-R). Washington, DC: American Psychiatric Association BingolN, Fuchs M, Diaz V, Stone RK, Gromisch DS (1987), Teratogenicity of cocaine in humans. ] Pediatr 110:93-96 Brown RT, Coles CD, Smith IE et al. (1991), Effects of prenatal alcohol exposure at school age. II. Attention and behavior. Neurotoxicol Teratol 13:369-376 Chasnoff IJ, Bussey ME, Savich R, Stack CM (1986), Perinatal cerebral infarction and maternal cocaine use. ] Pediatr 108:456-459 Chasnoff IJ, Chisum GM, Kaplan WE (1988), Maternal cocaine use and genitourinary tract malformations. Teratology 37:201-204 Chasnoff I, Griffith D (1989), Cocaine: clinical studies of pregnancy and the newborn. Ann NY Acad Sci 562:260-266 Chasnoff IJ, Griffith DR, Freier C, Murray J (1992), Cocaine/polydrug use in pregnancy: two-year follow-up. Pediatrics89:284-289 Chasnoff IJ, Lewis DE, Griffith DR, Willey S (1989), Cocaine and pregnancy: clinical and toxicological implications for the neonate.
Clinical Chemistry 35:1276-1278 Church MW, Overbeck GW, Andrzejczak AL (1990), Prenaral cocaine exposure in the Long-Evans rat: I. Dose-dependent effects on gestation, mortality and postnatal maturation. Neurotoxicol TeratoI12:327-334 Church MW, Overbeck GW (1990a), Prenatal cocaine exposure in the Long-Evans rat: II. Dose dependent effects on offspring behavior.
Neurotoxicol TeratoI12:335-343 Church MW, Overbeck GW (1990b), Prenaral cocaine exposure in the Long-Evans rat: III. Developmental effects on the brainstem auditoryevoked potential. Neurotoxicol TeratoI12:345-351 Davis E, Fennoy I, Laraque D, Kanem N, Brown G, Mitchell J (1992), Autism and developmental abnormalities in children with perinatal cocaine exposure. ] Natl Med Assoc 84:315-319 Doberczack TM, Shanzer S, Senie RT, Kandall SR (1988), Neonatal neurologic and electroencephalographic effects of intrauterine cocaine exposure. ] Pediatr 113:354-358 Dow-Edwards DL (1989), Long-term neurochemical and neurobehavioral consequences of cocaine use during pregnancy. Ann N Y Acad Sci 562:280-289 Evans RT, O'Callaghan J, Norman A (1988), A longitudinal study of cholinesterase changes in pregnancy. Clinical Chemistry 34:2249-2252 Finnegan LP (1991), Cocaine abuse in pregancy: the toll on fetus and newborn. Paper presented at the Eighth Annual Einstein Symposium in Psychiatry, The War Against Cocaine: Scientific Insights, Clinical 6Societal Implications. New York Academy of Medicine, New York City, November 22, 1991 Fischman MW (1987), Cocaine and the amphetamines, In: Psychopharmacology: The Third Generation of Progress, ed H Y Meltzer, New York, Raven Press Fried, PA, O'Connell CM (1987), A comparison of the effects of prenatal exposure to tobacco, alcohol, cannabis, and caffeine on birth size and subsequent growth. Neurobehavioral Toxicology and Teratology 9:79-85
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994
COCAINE BABIES: INTRODUCTION Richardson GA, Day NL (1991), Maternal and neonatal effectsof moderate cocaine use during pregnancy. Neurotoxicol Teratol13:455-460 Rodning C, Beckwith L, Howard J (1989), Prenatal exposure to drugs: behavioral distortions reflecting CNS impairment? NeuroToxicology 10:629-634 Spear LP, Kirstein CL, Frambes NA (1989), Cocaine effects on the developing central nervous system: behavioral, psychopharmacological and neurochemical studies. Ann N Y Acad Sci 562:290-307 van Baar A (1990), Development of infants of drug dependent mothers. J Child Psychol Psychiatry 31:911-920 Wilson GS, McCreary R, Kean J, Baxter JC (1979), The development of preschool children of heroin-addicted mothers: a controlled study.
Fried PA, Watkinson B (1990), 36- and 48- month neurobehavioral followup of children prenatally exposed to marijuana, cigarettes, and alcohol. J Deu Behav Pediatr 11:49-58 Hawks RL, Chiang CN (1986), Examples of specific drug assays. Urine Testing for Drugs of Abuse. NIDA Res Monogr 73:84-112 Jones KL, Smith OW, Ulleland CN (1973), Pattern of malformation in offspring chronic alcoholic mothers. Lancet 1:1267-1271 Jones R (1984), The Pharmacology of Cocaine. NIDA Res Monogr 50:34-53 Kaltenbach K, Finnegan LP (1989), Children exposed to methadone in utero: assessment of developmental and cognitive ability. Ann N Y
Acad Sci 562:360-362 Kim M, Checola RT, Noble LM, Yoon JJ (1989), Cocaine and congenital malformations. Pediatr Res Proc 25(part 2):77A Koren G, Shear H, Graham K, Einarson T (1989), Bias against the null hypothesis: the reproductive hazards of cocaine. Lancet 1440-1442 Lifschitz MH, Wilson GS, Smith EO, Desmond MM (1985), Factors affecting head growth and intellectual function in children of drug addicts. Pediatrics 75:269-274 Matera C, Warren WE, Moomjy M, Fink OJ, Fox HE (1990), Prevalence of the use of cocaine and other substances in an obstetric population.
Pediatrics 63:135-141 Woods JR, Plessinger MA, Clark KE (1987), Effect of cocaine on uterine blood flow and fetal oxygenation. JAMA 257:957-961 Woods JR, Plessinger MA, Scott K, Miller RK (1989), Prenatal cocaine exposure to the fetus: a sheep model for cardiovascular evaluation. Ann
NY Acad Sri 562:267-279 Yoon JJ, Kim M, Checola RT, Noble LM (1989), Maternal cocaine abuse and microcephaly. Pediatr Res Proc 25(parr 2):79A Zuckerman B, Frank DA et al. (1989), Effects of maternal marijuana and cocaine use in fetal growth. N EnglJ Med 320:762-768
Am J Obstet GynecolI63:797-801
Coming in February: Special Article: Confidentiality in Custody Disputes CarlP. Malmquist
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ADD Symptoms in Adolescence Elizabeth Schaughency et al.
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Suicidal Children Grow Up: Effects of Treatment Cynthia R. Pfeffer et al.
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Follow-up of Youth Exposed to Suicide David A. Brentet al.
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Behavioral Disorders in Male Carriers of Fragile X Margaret B. Dorn et al.
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Thyroid Function and ADHD Josephine Elia et al.
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:1, JANUARY 1994
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