Maternal Substance Abuse and the Developing Nervous System

Ian S. Zagon, Theodore A. Slotkin, Ian S. Zagon, Theodore A. Slotkin

• Publisher: Academic Press
• Year: 2012
• ISBN:
  9780080926674
• Topic: Psychologie
• Subtopic: Sucht in der Psychologie

The purpose of this book is to review the basic science and clinical findings concerning maternal substance abuse and the developing nervous system of unborn children. The short-term but vitally significant repercussions of such exposure on biological development, with particular reference to the nervous system, are discussed. The book also discusses the profound influence of maternal substance abuse on behavior in adulthood, which is caused by subtle changes in the chemistry or structure of the developing nervous system. The subject will not only be of interest to clinical and basic science researchers and teachers in the field of maternal substance abuse, but also to individuals in psychology, social work, cellular and molecular biolgoy, embryology, neuroscience, pharmacology, and in clinical professions such as pediatrics, neonatology, and obstetrics. The breadth of topics covered includes alcohol, cocaine, opiates, nicotine, benzodiazepines, marijuana, and the role of stress and hormones. Emphasis is placed on the relationship of the effects of substance abuse on neurotrophic factors and receptors.

• Shows how abused substances act directly or indirectly to mimic or influence the action of neurotrophic factors
• Explains that the transient expression of peptides, neurotransmitters, and receptors can be markedly disturbed by drugs
• Demonstrates that animal and tissue culture studies are consistent with clinical observations and important in understanding and ameliorating adverse actions of drugs in early life

1

Introduction

Duane Alexander    National Institute of Child Health and Human Development, Bethesda, Maryland 20892

Picture for a moment, if you will, the profile of the woman with the maximum chance of having an adverse pregnancy outcome. First, she is likely to be in her middle or late teens and probably has not finished high school. Her pregnancy is probably unplanned and unwanted, and the father may be unknown. She is likely to be unemployed, in the lowest socioeconomic group, and may be homeless. She is probably from a minority group, is poorly nourished, and is likely to have received little or no prenatal care. She is likely to have one or more sexually transmitted diseases. In addition to this scenario, she may smoke tobacco and abuse alcohol. And in recent years, added to this profile has been drug abuse—opioids, marijuana, and most recently, cocaine.

All these factors individually portend problems for the infant, but among all of them, the one that correlates highest with immediate adverse outcome is cocaine abuse, with a fourfold higher risk of low birth weight and its attendant problems. Longer-term adverse effects have been more difficult to determine and associate with drug abuse or any one of these factors, because the most common profile seen in the substance-abusing pregnant woman combines many of the above, making correlation of adverse outcome with one factor alone virtually impossible. Further, this profile is increasing in frequency and, in the inner city, is threatening to overwhelm maternity and infant health care systems; the attendant social crisis has already begun to reverse the downward trend in infant mortality.

Indicating the extent to which the problem of drug abuse is being added to already problematic pregnancies, surveys in major cities reveal that in some hospitals 40 to 50% of women deliveting test positive for drugs, usually cocaine. But the problem is not confined there—surveys in general obstetric practices have indicated that approximately 10% of pregnant women are using some illicit drug, again, usually cocaine. Based on these surveys, an estimated 375,000 infants of the nearly 4,000,000 births each year in the United States have been exposed to illicit drugs prenatally.

The concerns about opioids and cocaine come in addition to relatively recent discoveries about the adverse effects of tobacco and alcohol on the fetus during pregnancy. Tobacco clearly reduces birth weight in a dose-related manner, to such an extent that of all the things we know that will lower the incidence of low birth weight, stopping smoking in pregnancy would have the greatest impact. Less is known about the long-term effect of nicotine on brain development, but the immediate adverse effect on pregnancy outcome is sufficient to have induced legislative requirements for warning labels on cigarette packs.

By contrast, alcohol use during pregnancy seems to have little effect on immediate pregnancy outcome, but has devastating consequences for the physical and mental development of the fetus. The physical anomalies and mental retardation composing the fetal alcohol syndrome and the milder fetal alcohol effect have been known since the 1970s and, as its extent has become clearer, it has become evident that fetal alcohol syndrome is currently the leading known preventable cause of mental retardation, with an incidence of more than 1% in some population groups. Still being determined is the extent of alcohol-induced adverse central nervous system effects short of mental retardation and the timing and dose of alcohol required to produce these effects. Nonetheless, as with tobacco, legislatively mandated warnings about adverse effects of alcohol use during pregnancy now appear on alcoholic beverage containers.

The cocaine epidemic has brought a double threat in pregnancy. Like tobacco, but even stronger, cocaine clearly has an immediate adverse effect by reducing birth weight and triggering premature labor. And like alcohol, but weaker, it seems to have adverse long-term effects on brain function, and may produce some physical anomalies, although evidence of anomalies is inconsistent and so far unsubstantiated. These effects are still being determined and evaluated, in part because enough time has not elapsed to assess longer-term subtle effects, and in part because the subtle effects occur amid a constellation of adverse social circumstances that make it difficult to distinguish the possible effects of the environment in which the child is raised from the effects of prenatal cocaine exposure. Conducting these studies is further complicated by the fact that drug use, unlike alcohol or tobacco use, is illegal, and obtaining information on which of many drugs is used at what time and in what amount during pregnancy is extremely difficult. The barriers to conducting definitive studies of drug use during pregnancy, and possible ways to resolve the attendant problems, have been well described in a recent report to Congress from the National Institute of Child Health and Human Development (NICHD, 1991).

The studies presented in the book describe our current state of knowledge of the effects of maternal substance abuse during pregnancy on the developing nervous system of the fetus. From both animal and human studies, they document what is known and what remains to be learned. Clearly we already know enough to justify even stronger efforts to curtail the use of tobacco, alcohol, and illicit drugs during pregnancy. It is equally clear that we have no effective means of inducing the necessary behavioral changes. It is important that we continue to expand our knowledge in this area, and that studies of the effects of maternal substance abuse on the developing central nervous system continue to receive support from federal agencies, such as the National Institute on Drug Abuse and the National Institute of Child Health and Human Development, as well as from nonfederal sources.

REFERENCE

National Institute of Child Health and Human Development. Effects of Drug Exposure In Utero. In: Report to Congress. Bethesda, MD; 1991.

2

Fetal Alcohol Syndrome and Fetal Alcohol Effects: A Clinical Perspective of Later Developmental Consequences

Ann Pytkowicz Streissguth Fetal Alcohol and Drug Uni, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington

INTRODUCTION

Alcohol is now well recognized as a teratogenic drug: prenatal exposure can cause death to the embryo and fetus, growth deficiency, malformations, and central nervous system aberrations that can last a lifetime. Whereas definitive documentation of the etiology and mechanisms comes from the experimental animal literature (see Goodlett and West, Chapter 4), the clinical literature is important in understanding the significant impact of this most widely used teratogen on our children. The epidemiologic literature is relevant for establishing public policy and guiding programs of prevention for this most preventable cause of mental retardation and developmental disability, and understanding the clinical phenomena of fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE) is essential for developing appropriate treatment and intervention programs for affected children so that they can lead as productive and fulfilling lives as possible. There has been a shocking paucity of such research in the United States in the past 18 years since FAS was identified.

Fetal alcohol syndrome is generally recognized as the leading known cause of mental retardation (Abel and Sokol, 1987), surpassing Down’s syndrome and spina bifida. (Most mental retardation cannot be attributed to a specific etiology.) Precise figures on FAS are difficult to obtain, however, and it seems likely that most attempts at estimating prevalence [including those most recently proposed by Abel and Sokol (1991)] are underestimates owing to difficulties with ascertainment and identification, confusion over diagnostic criteria, and problems in making interpretations based on literature surveys, including studies of variable validity. FAS is a clinical diagnosis (see below). The term FAS does not include all individuals affected by alcohol in utero, but rather it represents one specific and identifiable end of the continuum of disabilities caused by maternal alcohol use during pregnancy.

The clinical features of FAS were independently identified in France (Lemoine et al., 1968) and the United States (Jones et al., 1973; Jones and Smith, 1973). Most of the patients described have been infants or young children, but increasingly maladaptive behaviors among adolescents with FAS (Streissguth et al., 1991) make this an important topic for further study. A systematic examination of all school-age children with only mild mental retardation (IQ 55 to 70), born in Sweden during a 2-year period, indicated that 8% were afflicted with alcohol-related disabilities (Hagberg et al., 1981a,b). A recent report involving ophthalmology examinations of this same cohort raised the proportion with suspected FAS to 10% [a larger proportion than was identified by all known genetic disorders (Hagberg et al., 1981a,b; Stromland, 1990)]. Enough is currently known to indicate that FAS is a major health problem. The fact that precise figures are not available should not dissuade us from recognizing the urgency of the need for research on the characteristics and special needs of this underserved population of disabled persons.

FETAL ALCOHOL SYNDROME AND FETAL ALCOHOL EFFECTS: DIAGNOSTIC ISSUES AND TERMINOLOGY

Fetal alcohol syndrome is diagnosed when patients have a positive history of maternal alcohol abuse during pregnancy and (1) growth deficiency of prenatal origin (height and/or weight); (2) a pattern of specific minor anomalies that includes a characteristic facies (generally defined by short palpebral fissures, midface hypoplasia, smooth and/or long philtrum, and thin upper lip); and (3) central nervous system manifestations (including microcephaly or history of delayed development, hyperactivity, attention deficits, learning disabilities, intellectual deficits, or seizures) (Clarren and Smith, 1978; Smith, 1982). Patients exposed to alcohol in utero with some partial FAS phenotype, and/or central nervous system dysfunction, but without sufficient features for a firm diagnosis of FAS or strong consideration of any alternative diagnosis, are identified as possible FAE (Clarren and Smith, 1978).

Fetal alcohol syndrome is a specific medical diagnosis usually given by a dysmorphologist, a geneticist, or a pediatrician with special training in birth defects or dysmorphology. It is not appropriately diagnosed by checklists or without a full clinical examination by a specially trained person. Unfortunately, most physicians have not received special training in syndrome identification, and as dysmorphology is a rather new field, many persons with FAS go unrecognized. This is a particular problem with regard to persons who have not been identified before puberty, as the facial features are less distinctive in adolescence and adulthood. The optimal age for making the diagnosis is between 8 months and 8 years, although the most severely affected children can be identified at birth by a skilled diagnostician. Diagnosis in the adolescent and adult is facilitated by photographs from infancy and childhood.

Fetal alcohol effects is a term used in two different ways. In the clinical sense, possible or probable FAE refers to individual children given a clinical examination who were known to be born to an alcohol-abusing mother and who have some, but not all, of the characteristics necessary for a diagnosis of the full FAS. Partial syndrome expression is not uncommon in syndromology. The words possible or probable precede the term FAE as an expression of uncertainty that the observed characteristics (in the absence of the full syndrome) are all attributable to alcohol. From the standpoint of understanding the patient’s needs, the distinction may be irrelevant. Clearly for research purposes and for making prognostications for the individual patient, the criteria used for making the diagnosis are extremely important.

Fetal alcohol effects is also a generic term used for all the “effects” or outcomes known from epidemiologic studies ...