Prenatal Cocaine Exposure

Richard J. Konkol, George D. Olsen

• Éditeur: CRC Press
• Année: 2020
• ISBN:
  9781000151763
• Édition: 1
• Sujet: Medizin
• Sous-sujet: Gynäkologie, Geburtshilfe & Hebammen

Prenatal Cocaine Exposures addresses the timely problem of maternal cocaine abuse and its effects on exposed infants, including growth retardation, learning, cardiovascular effects, and seizures. The impact of substance abuse on this and future generations presents an ongoing challenge to medical science. This comprehensive and authoritative volume reviews both animal and clinical studies to explain implications for treatment and long-term outcomes of early exposure.
Prenatal Cocaine Exposures investigates the specific role of cocaine in altering fetal development. Discussions of current studies and state-of-the-art techniques provide a basis for informed clinical decisions. Pediatricians, medical specialists, basic scientists, educators, and policy makers will all benefit from the comprehensive research gathered in this volume.

Chapter 1

Cocaine and the Fetus: Methodological Issues and Neurological Correlates

Chiriboga Claudia, A. MD, MPH

1.0 INTRODUCTION

In the 1980s a drop in cocaine prices coupled with the introduction of “crack” cocaine fueled an unprecedented degree of cocaine abuse. During the peak of the cocaine epidemic 30% of adults between the ages of 19 and 28 years reported using cocaine at least once.¹ Although cocaine use declined abruptly in 1987, it is still a major public health problem, as an unfortunately high level of abuse continues unabated. Infants born to women using crack/cocaine, the so-called “crack/cocaine babies,” have been stigmatized by the media because of their potential burden to society. The pendulum of the medical and lay press has swung away from its initially fatalistic outlook that doomed such children from birth to the current nihilistic climate that tends to minimize any possible cocaine effects, despite the lack of solid information on the long-term consequences of fetal cocaine exposure.

Efforts to determine whether prenatal exposure to cocaine damages the human nervous system are fraught with methodological difficulties. Unlike the experimental model where variables are fixed by the investigator, the clinical setting is laden by the many factors that act in concert to influence the fetal or postnatal environment. Although epidemiological methods offer some control over these extraneous or “confounding” variables, the erratic high-risk behaviors associated with drug use introduce additional elements that make inferences in clinical studies regarding cocaine-related associations more vulnerable to bias, e.g., selection bias resulting from a high level of attrition. This chapter focuses on the methodological problems that have arisen in the clinical research of fetal cocaine exposure and provides a broad overview of the salient clinical findings associated with cocaine exposure (Table 1.1), with the exception of strokes and seizures, which are discussed elsewhere.

1.1 BACKGROUND

Cocaine is obtained from Erythroxylon coca, a plant indigenous to the mountainous regions of South America. For centuries the natives of this region have used coca leaves in religious rituals or for its medicinal properties to treat a variety of ailments, notably fatigue and mountain sickness. In these settings coca is administered by either chewing on coca leaves or by preparing an infusion of coca leaves, coca tea.

Table 1.1 Fetal Cocaine Effects and Associations

Pregnancy

Spontaneous abortions

Abruptio placentae

Stillbirths

Premature delivery

Growth

Low birth weight

Intrauterine growth retardation

Small head size

Infections

Perinatal HIV

Congenital syphilis

Malformations

Urogenital

Brain

Midline defects (agenesis of corpus callosum, septo-optic dysplasia)

Skull defects, encephaloceles

Ocular

Vascular disruption (limb reduction, intestinal atresia)

Cardiac

Neurodevelopmental findings

Neonates

Impaired organizational state

Hypertonia, tremor

Strokes, porencephaly

Seizures

Brainstem conduction delays

Sudden infant death syndrome

Infants and children

Hypertonia in infancy

Abnormal behaviors (?)

(Adapted with permission from Chiriboga, C.A., Abuse of children: Pediatric AIDS, fetal alcohol syndrome, fetal cocaine effects, and the battered child syndrome, in Merritt’s Textbook of Neurology, 9th ed., Baltimore, Williams & Wilkins, Lea & Febiger, 1995.)

In the United States, legal cocaine use was barred following the Harrison Narcotic Act in 1914. Thereafter, because of its high cost, illegal cocaine use continued mostly among the affluent. In recent times, however, cocaine has become much less expensive and widely available. This combination of factors has resulted in an alarming increase in cocaine use by the less affluent, especially among individuals of lower socioeconomic status. Thus, cocaine traffic has flourished in inner cities, bringing with it the infamous “drug dealer,” as well as escalating violence? Regrettably, no geographical area in the United States has been totally immune to its spread.

The two most common forms of cocaine used by addicts on the street are cocaine hydrochloride, a water soluble salt, and crack/cocaine, a free-base alkaloid. Cocaine hydrochloride can be used by either snorting a line, applying it to various mucosal membranes (oral or genital), or injecting it intravenously. Crack/cocaine is volatile and is administered by smoking.

1.2 PHARMACOLOGY

Cocaine is a highly psychoactive substance with numerous effects³: it inhibits postsynaptic reuptake of catecholamines, leading to an increase in postsynaptic norepinephrine and epinephrine, which produce hypertension and tachycardia and have vasoconstrictive effects; it increases postsynaptic dopamine levels, which is thought to mediate cocaine addiction at the mesolimbic and mesocortical levels; it inhibits tryptophan reuptake, thus altering serotonin pathways, which presumably mediate cocaine effects on sleep; and it blocks sodium ion permeability, thus acting as a local anesthetic agent. In addition to the multiple effects exerted by the parent compound, cocaine breaks down into active metabolites (e.g., benzoylecgonine, benzoylnorecgonine) of similar or yet more powerful pharmacological activity. Many of these substances are independently neurotoxic and may be responsible for perceived cocaine effects.^4,5

Cocaine and its metabolites readily pass the placenta, achieving variable levels in the fetus.⁶ The mechanism by which cocaine affects the fetus is not fully known, but is postulated to result from either a direct effect to the fetus or an indirect effect mediated through the maternal autonomic and cardiovascular system, especially at the level of the uterus.⁷

1.3 ADDICTION

A discussion of the biological and psychological basis of cocaine addiction is warranted to gain a better understanding of the behavioral correlates associated with cocaine use. In adults, cocaine use produces a state of euphoria characterized by increased energy and enhanced alertness. According to classical and operational conditioning theory, the degree of euphoria is a prominent positive reinforcer. The level of euphoria in turn is predicated on the speed of delivery and cerebral concentrations attained by cocaine. Because crack/cocaine is smoked, this preparation delivers the highest levels of cocaine to the brain in the most expedient fashion,⁸ thus producing a more intense euphoria than other methods of delivery, i.e., snorting or injecting. This intense sensation, described by addicts as a “rush” of pleasure, gradually gives way to dysphoria, an equally intense but opposite sensation that is described as a “crash” from cocaine. Dysphoria is characterized by a strong craving for the drug, a depressed state, and hypersomnia; it acts as a powerful negative reinforcer.

Converging lines of evidence support a dopaminergic hypothesis of cocaine addiction related to a mesocortical limbic reward system. Experimentally different animal species will self-administer cocaine, dopamine (DA), and D2 receptor agonists such as apomorphine, but not Dl receptor, serotonin, or noradrenergic agonists.⁹.¹° This response is mitigated by co-administration of D2 receptor blockers. Ablation studies of the medial prefrontal region with 6-hydroxydopamine, which selectively decreases dopamine levels, results in a decrease in the cocaine maintained response, which can...