Substance abuse during pregnancy is more prevalent than commonly realized, with up to 25% of gravidas using illicit drugs.¹ In fact, substance abuse is more common among women of reproductive age than among the general population.² The average pregnant woman will take four or five drugs during her pregnancy, with 82% of pregnant women taking prescribed substances and 65% using nonprescription substances, including illicit drugs.¹ Substance abuse during pregnancy is difficult to detect because the signs and symptoms of this behavior are often subtle, self-reports of substance use may be misleading or infrequently elicited, physicians may fail to routinely screen for use, and substance abusing pregnant women may seek little or no prenatal care. Once detected, substance abuse during pregnancy confronts the physician with issues regarding treatment, management, and maternal and fetal complications. Because pregnant women with substance use problems are more likely than nonpregnant females to seek assistance from a health care provider and to be motivated for substance abuse treatment, pregnancy offers the physician a unique opportunity for both detecting and treating substance abuse. Some would describe pregnancy as a “treatable moment” for mothers who use and abuse substances. In this chapter, we address the epidemiology, basic definitions describing substance use behaviors, biology and etiology, detection and differential diagnosis, prognosis, maternal and fetal complications, use of specific substances, screening, management, and treatment of substance abuse during pregnancy.

Approximately 26 million Americans will suffer with a substance abuse problem during their lifetime.³ The incidence of substance abuse among women of reproductive age continues to increase, thus contributing to the growing problem of substance abuse during pregnancy. The highest rates of alcohol and drug use are among women in their childbearing years, with 6 million women experiencing alcohol problems, and more than 5 million currently using illicit substances.³ Greater than 50% of women aged 18 to 35 years responding to the National Institute on Drug Abuse Household Survey reported that they had used alcohol in the past month, and 5% reporting illicit drug use in the same interval, with marijuana the most frequently used substance.⁴ The incidence of substance abuse during pregnancy ranges from 0.5% to 25% depending on the type of screening method utilized, such as urine drug screens versus self-reports of substance use, and the intensity of the screening program, with inherent biases in those screening only certain subpopulations of pregnant women. The largest population-based survey of 29,000 urine samples at delivery estimated the prevalence of substance abuse during pregnancy as 5.2% and alcohol use as 6.7%.⁴ Of the 4 million women who become pregnant each year, at least 20% smoke cigarettes, 19% drink alcohol, 20% use legal drugs, and 10% use illicit drugs during their pregnancy.³ Thus, substance use is highly prevalent in pregnant women.

The four general categories of substances abused by pregnant women are central nervous system depressants, including alcohol, sedatives, anxiolytics, and hypnotics; stimulants, including cocaine and amphetamines; opiates; and hallucinogens/psychotomimetics, including lysergic acid diethylamide (LSD) and phencyclidine (PCP). With the exception of caffeine and nicotine, these substances are associated with both abuse and dependence disorders.³

Intoxication and withdrawal represent the most common substance-related disorders. Intoxication, defined as the development of a reversible substance-specific syndrome during or after substance use, becomes a clinical problem when significant maladaptive patterns of behavior lead to distress and impairment. Withdrawal, another substance-specific syndrome, occurs when the chronic intake of a substance is abruptly discontinued. Tolerance is defined as the need to use an increasing amount of the drug to attain the desired effects or the decreased intensity in effects experienced with the continued use of the same amount of the substance. The term addiction combines the qualities of both tolerance and withdrawal. Drug addiction, a primary disease with the potential to be progressive and life-threatening, presents as a preoccupation with and inability to control substance use.

Substance dependence includes tolerance, withdrawal, taking the drug in larger amounts over longer periods than originally intended, the desire or ineffective attempts to reduce or cease drug use, extensive amounts of time involved with substance use, and persistent use despite problems attributed to the substance. Substance abuse is a maladaptive pattern of use that results in clinically significant functional impairment without satisfying the criteria for substance dependence. Abuse is indicated by any one of the following: failure to fulfill reasonable obligations, drug use in dangerous situations, and continued use despite recurrent legal, social, and psychological problems associated with the substance.³

Depending on the class of agent ingested, drug use appears to activate or deactivate the limbic system, with dopamine serving as the major neurotransmitter in the reinforcement of substance use.³ Although the etiology of substance abuse remains unclear at the present time, studies have revealed a significant genetic basis for alcoholism, with a penetrance of 50% to 60%.⁴ Other factors that may be involved in increasing one’s susceptibility to substance abuse problems include life stressors with poor coping skills, limited social support systems, easy access to alcohol and illicit substances, previous traumatic crises, and identity/self-esteem problems. Those individuals with mental health disorders, reproductive problems, and eating disorders appear more likely to develop substance abuse problems. In fact, the prevalence of all psychiatric diagnoses is higher among female alcoholics than nonalcoholics. The Epidemiologic Catchment Area sample discovered that 37% of women with alcohol problems have comorbid mental illness, with major depression the most frequently diagnosed.⁴

Before discussing characteristics more frequently observed among substance abusers, we must remind the reader that most women with substance abuse problems do not manifest any of the following conditions. Indicators suggesting substance abuse during pregnancy include self-reported use, avoidance of prenatal care, premature labor and delivery, placental abruption, and fetal death. Advanced-stage substance abusers commonly live chaotic lifestyles, characterized by frequent changes in residence/employment, long-standing substance abuse, and domestic violence.⁵ Risk factors for frequent drinking during the periconceptional period include being unmarried, a smoker, Caucasian, 25 years or older, and a college graduate.⁶ A detailed history and physical examination followed by pertinent laboratory studies assist the physician in detecting those pregnant women with substance abuse problems.

When performing a substance use history, the physician should ask the patient about the type, amount, and frequency of substance use in a nonjudgmental manner, with emphasis on forming a patient-physician alliance. It is important to obtain information regarding the exact amount of alcohol and/or drugs being used at the time the patient discovered she was pregnant, searching for signs of poly-substance abuse. By incorporating questions regarding substance use into one’s general history-taking template, one can diminish their novelty and put the patient at ease. One may begin the substance use history with questions regarding drug use prior to conception to lessen the shame that many women feel regarding current use. Then the consequences of substance use should be explored, with emphasis on physical symptoms, relationship and employment problems, and emotional/psychological issues. Input from partners, close family members, and friends may help better define the magnitude of the patient’s substance abuse problem, especially for those patients in denial.

The CAGE (cut down, annoyed by criticism, guilty about drinking, eye-opener drinks) and TACE (tolerance, annoyed by criticism, cut down, eye-opener drinks) questionnaires, MAST (Michigan Alcoholism Screening Test), DAST (Drug Abuse Screening Test), and ASI (Addiction Severity Index) are frequently used, relatively effective methods for detecting substance use. The CAGE screening tool, composed of four questions to identify those with alcohol problems, will accurately identify 80% to 90% of male alcoholics, yet its applicability to pregnant women is unclear.² TACE, designed to identify those women drinking heavily enough to cause potential damage to the fetus, can correctly identify 70% of women with alcohol problems during pregnancy.⁷ The TACE questions include the following:

1. Tolerance—How many drinks does it take for you to feel high?
   
2. Annoyed—Have people annoyed you by criticizing your drinking?
   
3. Cut down—Have you felt the need to cut down on your drinking?
   
4. Eye-opener—Do you need to have an eye-opener to get started in the morning?
   

MAST and DAST, self-report questionnaires that contain weighted items, are prone to false-positive results and should be administered concomitantly to detect poly-substance abuse. ASI, a multifactorial diagnostic procedure, provides a way to assess the impact of substance use on the patient’s life.⁵ Although these questionnaires are useful, Colmorgen and associates have shown that self-report alone is an incomplete method for identifying maternal drug abuse.⁷

When contemplating the diagnosis of substance abuse, other conditions should be considered, including depression, anxiety, personality disorders, and posttraumatic stress disorder. Symptoms of anxiety and depression may be side effects of substance use; thus the diagnosis of a psychiatric illness is difficult to make until the patient has been abstinent for several weeks.

The prognosis is relatively good yet varies from individual to individual. The longer the substance abuse problem, the more difficult it is to eradicate. The more barriers the patient has to treatment, the less likely she is to remain abstinent. Common barriers to treatment include a partner who also uses alcohol or drugs, a chaotic lifestyle, a poor social support system, and lack of safe and affordable child care services. Those women who have been in multiple treatment programs yet subsequently relapse may be recalcitrant to general treatment methods.

The effects of substance abuse during pregnancy may be classified into three categories: effects on the mother, effects on the course of pregnancy and delivery, and effects on the fetus, newborn, and developing child.⁸

Maternal complications may be respiratory, such as bacterial infections; cardiovascular, including hypertension and endocarditis; neurologic, with seizures, cerebrovascular accidents, and psychoses; infectious, such as sexually transmitted diseases and human immunodeficiency virus; renal and gastrointestinal, including acute tubular necrosis and hepatitis; and/or metabolic, such as malnutrition and vitamin deficiencies.⁸ However, other than sexually transmitted diseases and psychiatric comorbidity, major medical complications are rare in pregnant women with substance abuse problems and few will experience end-organ damage secondary to substance use.

Obstetric and fetal complications associated with maternal substance abuse include placenta previa, abruptio placentae, premature rupture of membranes, spontaneous abortion, intrauterine growth retardation, premature delivery, birth defects, and neonatal and long-term developmental effects.⁸ Whether these obstetric and fetal problems are caused by substance abuse or just associated with use remains an active area of discussion and investigation. Neonatal effects of substance abuse depend on the particular substance being abused and are discussed individually in later sections yet generally include congenital anomalies, neonatal medical complications, and neurobehavioral changes.⁹ Specific neonatal medical complications of maternal substance abuse include sudden infant death syndrome (SIDS), neonatal abstinence syndrome (NAS), and respiratory distress syndrome.

Chronic alcohol use during pregnancy, defined as the ingestion of two or more drinks per day, is associated with increased rates of spontaneous abortion, higher rates of low-birth-weight infants, placental abruption, increased perinatal mortality, amnionitis, and a threefold increase in preterm deliveries.⁴ Some evidence suggests that alcohol impairs the placental transfer of essential amino acids and zinc, thus increasing the risk for intrauterine growth retardation by inhibiting protein synthesis.¹⁰ Fetal alcohol syndrome (FAS), the only cause of mental retardation that in theory is entirely preventable, effects 1 to 3 of every 1000 newborns, with another 3 to 5 per 1000 exhibiting less severe fetal alcohol effects.³ FAS is characterized by varying degrees of craniofacial dysmorphism, impaired prenatal and postnatal growth, central nervous system abnormalities, and cardiac defects. Fetal alcohol effects include congenital malformations, genitourinary defects, and learning disabilities.⁴ Day and coworkers performed a prospective study of 650 women and their newborns that showed that low birth weight, decreased head circumference and length, and an increased rate of fetal alcohol effects were correlated with exposure to alcohol during the first 2 months of pregnancy. They found that 30% to 40% of the offspring of women who abuse alcohol exhibit FAS, which was associated with both chronic, heavy drinking and binge drinking.¹¹ In a recent study utilizing magnetic resonance imaging to examine the effects of alcohol exposure on the fetal brain, findings revealed that severe prenatal alcohol exposure produces a specific pattern of brain hypoplasia.¹²

Alcohol withdrawal in pregnant women, which may be treated with benzodiazepines or phenobarbital, is rare, and withdrawal in affected infants is even rarer. When neonatal withdrawal does occur, it is characterized by agitation and hyperactivity, with marked tremors lasting for 72 hours, followed by 48 hours of lethargy, before recovery.¹⁰

Cocaine use during pregnancy, affecting 1% to 5% of neonates, is associated with decreased uterine blood flow leading to poor fetal oxygenation and increased fetal blood pressure and heart rate. Cocaine use during early gestation is associated with an increased risk of spontaneous abortion, whereas later use is associated with premature labor and delivery, placental abruption, low birth weight, SIDS, intrauterine growth retardation, low Apgar scores, meconium staining, fetal death, microcephaly, neurodevelopmental delay, and structural/congenital anomalies, especially involving the gastrointestinal and renal systems.⁸ The increased risk for meconium staining and nonreassuring fetal heart tracings associated with maternal cocaine use may be due to the fact that the normal catecholamine surge in the newborn that occurs during labor may overwhelm the myocardium in the cocaine-exposed infant. Studies on cocaine abuse indicate that maternal cocaine use during pregnancy is associated with an increased incidence of high maternal gravidity, poor prenatal care, and preterm birth.¹³

With regard to the long-term neurodevelopmental effects that maternal cocaine use may have on the fetus, a recent systematic review concluded that among children aged 6 years or younger, there is no convincing evidence that prenatal cocaine exposure has effects significantly different from those attributed to other prenatal exposures, including maternal tobacco and alcohol use.¹⁴ However, this remains an area in need of more research with well-designed studies.

Although maternal cocaine use rarely requires specific treatment regimens, psychotic symptoms may occur and should be treated with antipsychotics.

Marijuana is a commonly abused substance, with greater than 25% of women in their reproductive years admitting to past or current marijuana use. Although marijuana use during pregnancy has been associated with few short-term or long-term effects on the exposed neonate, its risks are dose-dependent, with an increased incidence of intrauterine growth retardation and SIDS seen in the infants born to heavy users.^11,15,16 The use of marijuana may be most beneficial as an indicator of poly-substance abuse and lower socioeconomic status that may influence both prenatal care and the home environment.¹⁷

Maternal use of sedatives/hypnotics leads to physical dependency in the fetus characterized by the neonatal abstinence/withdrawal syndrome. Drugs that are associated with neonatal withdrawal include heroin/methadone, caffeine, cocaine, ethanol, marijuana, PCP, and nicotine. The NAS includes behavioral and autonomic nervous system dysfunction plus gastrointestinal, respiratory, and central nervous system abnormalities.¹¹ Women using sedatives/hypnotics during pregnancy may need to be hospitalized during detoxification because the risk for seizures and other central nervous system effects is relatively high.

Narcotic abuse during pregnancy is associated with a higher-than-normal incidence of premature labor, chorioamnionitis, SIDS, premature rupture of the membranes, meconium staining, preeclampsia, and placental abruption.⁸ According to Ostrea and Chavez, infants exposed to heroin are at higher risk for congenital abnormalities.

Heroin abuse during pregnancy is associated with a 50% incidence of low-birth-weight infants, with up to 50% of these infants being small for gestational age, many of whom experience respiratory depression and low Apgar scores.^8,10 The majority of infants born to heroin-dependent mothers exhibit some signs of addiction, with up to 75% showing clinical signs of withdrawal within the first 48 hours after birth. NAS is characterized by a conglomeration of central nervous system, gastrointestinal, metabolic, respiratory, and vasomotor involvement. Common symptoms include tremors, hyperirritability, fever, poor feeding, diarrhea, respiratory compromise, and weight loss.¹⁸ Treatment for symptomatic infants may include one of the following: 0.2 mL paregoric every 4 hours, 0.1 to 0.5 mg/kg/day of methadone, 8 mg/kg/day of phenobarbital, or 1 to 2 mg/kg of diazepam every 8 hours.¹⁹

Methadone, along with producing fetal dependence and withdrawal in the majority of exposed infants, is associated with higher rates of neonatal morbidity and mortality, yet the average birth weight for methadone-addicted neonates is higher than that for heroin-dependent infants. Neonatal withdrawal from methadone may be treated with 1 to 2 mg of methadone given twice daily.⁸ Conversely, nursing mothers who continue on methadone maintenance in the puerperium may prevent newborn withdrawal by transferring narcotic metabolites via their breastmilk.

Researchers have concluded that the increased relative risk of neonatal mortality seen for those women abusing heroin and/or methadone during pregnancy, compared with those on methadone maintenance therapy, may be more associated with the chaotic, high-risk lifestyle seen in narcotic abusers than with drug exposure.²⁰ Others have found that, although methadone maintenance alone is associated with an improved neonatal outcome, those women who continue to use heroin while receiving methadone maintenance therapy may counteract the birth weight advantages seen with the use of methadone alone. Thus, methadone maintenance may be reserved for those women who refrain from heroin use during pregnancy.²¹

After comparing the sensitivity and specificity of maternal interview, maternal hair analysis, and meconium analysis in detecting perinatal exposure to opiates, cocaine, and marijuana, a study concluded that both meconium and hair analyses yielded the highest sensitivities for detecting perinatal use of opiates and cocaine. Maternal hair analysis, although a good screening test for detecting maternal drug use during the previous 3 months with drug metabolites persisting for up to 3 months in the infant’s hair after birth, is falsely positive in those women exposed passively to second-hand smoke from crack cocaine and marijuana.¹¹ Although theoretically useful, hair analysis is unavailable to most clinicians on a routine basis. They concluded that meconium analysis, which is easily performed, gives a picture of the drug use pattern during the latter half of pregnancy and may be the ideal screening test for maternal drug use.²² Because meconium can be attained only at delivery, it is not useful for antepartum screening. In clinical practice, urine toxicology assays are more frequently ordered. Although these assays can detect maternal drug use within the past 48 to 72 hours, they may miss the infrequent users and cannot quantify the frequency or amount of drug used.²³ Some physicians rely more heavily on the substance abuse history, often combining it with the urine drug screen. Frank and colleagues found that relying solely on the substance abuse history results in the failure to detect over 25% of women abusing cocaine during pregnancy. Surveys may miss many abusers because the women often feel guilty or deny their substance use, fearing loss of custody.²³ These researchers also found that when urine drug screens are used alone, up to 50% of the patients are missed; thus, urine drug screens and substance abuse histories should be used concomitantly to detect women using substances during pregnancy.⁹ Biologic screening for substance abuse should be performed only with informed consent from the mother and for the purpose of treating the substance abuse disorder once identified.

Abstinence should be the ultimate goal of the management and treatment of substance abuse during pregnancy. Researchers have found that participating in prenatal care alone can improve the outcome of the substance abuse pregnancy and that ceasing substance use during the pregnancy can further decrease perinatal morbidity. Most infants exposed to substances still have good outcomes, and early neonatal interventions can prevent or lessen future neurodevelopmental problems.⁹ Common obstacles to treatment include poor social support systems, failure to identify substance abusers during pregnancy, inadequate financial resources, and fear of custody loss with admission to problems of substance abuse.⁴ To attract enrollment, treatment should include multidisciplinary health care, family therapy, child care, vocational/parenting skills training, and psychiatric services.⁴

There is still a shortage of treatment programs for pregnant women. In 1989, of 78 drug treatment facilities in New York City, 54% refused to treat pregnant women, 67% denied treatment to women on Medicaid, and 87% denied treatment to pregnant women addicted to crack cocaine.⁴ Finkelstein has documented the shortage of substance abuse treatment services available to women, specifically mothers and pregnant women.²³ More recently, Breibart and associates conducted a study to assess availability of substance abuse treatment programs for pregnant women in five U.S. cities, finding that only 80% of the programs surveyed accepted pregnant women; thus, barriers to treatment still remain.²³

According to Schrager and coworkers, a residential treatment program combined with consistent outpatient follow-up is the best way to prevent or decrease maternal substance use.²³ Other treatment options include formal counseling programs, self-help groups, women’s shelters, and halfway houses. Involuntary treatment should be considered when the substance abuser refuses to enter a treatment program and when her behavior creates significant problems for herself and the fetus.

The pregnant drug abuser should be seen frequently, ideally at 2-week intervals until 32 to 34 weeks, then weekly, with urine drug screens obtained at each visit.¹ Rehabilitation services include educational sessions, group and individual counseling, and 12-step groups.⁵ Reed suggests that services individually address the woman’s unique treatment needs, reduce barriers to intervention and recovery, express goals compatible with the patient’s lifestyle, and consider the special issues associated with pregnancy.⁵

As the incidence of substance use among women of reproductive age continues to increase, substance abuse during pregnancy is a growing health issue because it affects the future generations of our country. Because substance abuse during pregnancy is often difficult to detect, the physician should include a detailed substance abuse history in every new patient encounter, with follow-up questions performed during subsequent visits. Once detected, substance abuse during pregnancy confronts the physician with issues regarding management, treatment, and potential maternal, fetal, and pregnancy-related complications, yet also provides the physician with a unique opportunity for intervention at a time when the woman may be most amenable to change. Many management and treatment options exist with the ultimate goal of abstinence and should be designed to meet the needs and address the concerns of the individual. By increasing the awareness of substance abuse during pregnancy among the medical community, physicians may better recognize and address this problem, thus improving the overall health of this population.

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