CHAPTER 3 1. Discuss the direct and indirect effects of drugs of abuse on the fetus. 2. Describe the maternal conditions that are contraindications for breastfeeding. 3. Describe the maternal and neonatal characteristics associated with drug use in pregnancy. 4. Describe the physical characteristics of an infant with a neonatal narcotic abstinence syndrome. 5. List four nonpharmacologic nursing interventions appropriate for managing withdrawal. 6. Discuss the pharmacologic management of neonatal abstinence syndrome. Substance abuse has been an issue for society since ancient times. Over the past several decades, attention has been directed toward the use of legal and illegal substances by pregnant women. Almost all drugs are known to cross the placenta and have effects on the fetus. The effects on the human fetus of prenatal smoking, alcohol use, and opiate use have been identified and studied over the past decades (Behnke and Smith, 2013; Hudak and Tan, 2012). Of more recent concern is the abuse of prescription drugs. In 2010, over 1.9 million people in the United States were addicted to prescription opioid pain relievers (National Institute of Drug Abuse [NIDA], 2012). The mean hospital cost for a neonatal abstinence syndrome (NAS) admission in 2009 was $53,400. The need to decrease resource utilization and the costs of treatment as well as improve psychosocial and developmental outcomes in infants exposed to substances in utero is paramount. Methods must be developed to decrease the risk of adverse neonatal outcomes such as low birth weight (< 2500 g) and mortality (Patrick et al., 2012). Future work on NAS should involve novel approaches designed to minimize and manage opiate exposure before pregnancy, such as opioid vaccines and pharmacogenomics (McLemore et al., 2013). Treatment of mothers during pregnancy must be evidence based. Multiple individual, family, and environmental factors such as nutritional status, extent of prenatal care, neglect or abuse, and socioeconomic conditions must also be addressed (NIDA, 2011a). A. Prevalence (Substance Abuse and Mental Health Services Administration [SAMHSA], 2013; Patrick et al., 2012). 2. Between 2000 and 2009, the rate of newborns diagnosed with NAS increased from 1.20 to 3.39 per 1000 births. 3. Compared with all other hospital births, newborns with NAS were significantly more likely to have respiratory diagnoses, low birth weight, feeding difficulties, and seizures. 4. Newborns with NAS were more likely to be covered by Medicaid and reside in zip codes within the lowest income quartile. 5. Prenatal exposure to alcohol, tobacco, and illicit drugs has the potential to cause a wide spectrum of physical, emotional, and developmental problems for these infants. The harm caused to the child can be significant and long-lasting, especially if the exposure is not detected and the effects are not treated as soon as possible. 6. While most pregnant women do not abuse illicit drugs, combined 2008 and 2009 data from the National Survey on Drug Use and Health found that, among pregnant women ages 15 to 44 years, the youngest ones generally reported the greatest substance use, as shown in Figure 3-1 (NIDA, 2011a). 7. Addiction to opioids (e.g., heroin, morphine, prescription pain relievers) is a serious global problem that affects the health, social, and economic welfare of all societies. An estimated 12 to 21 million people worldwide abuse opioids (NIDA, 2011b). B. Prescription drug abuse. 2. The increased use of prescription opiates in pregnant women to treat acute or chronic pain has been noted (Hudak and Tan, 2012). 3. In a recent report, chronic use of narcotic prescriptions (use for ≥ 1 intrapartum month) among pregnant women cared for at a single clinic increased five-fold from 1998 to 2008, and 5.6% of infants delivered to these women manifested signs of neonatal withdrawal (Kellogg et al., 2011). 4. Of great concern is that, in women between 15 and 17 years of age, the rate of prescription drug abuse is 23% in pregnant versus 13% in nonpregnant women (Johnston et al., 2008). C. Alcohol (National Institute on Alcohol Abuse and Alcoholism [NIAAA], 2010; SAMSHA, 2012; SAMHSA, 2012). 2. Alcohol can disrupt fetal development at any stage during a pregnancy. Research shows that binge drinking, which means consuming four or more drinks per occasion, and regular heavy drinking put a fetus at the greatest risk for severe problems. 3. Based on data averaged over 2009 and 2010, of pregnant women ages 15 to 44 years, an estimated 10.8% reported current alcohol use, 3.7% reported binge drinking, and 1% reported heavy drinking. 4. These rates were significantly lower than the rates for nonpregnant women in the same age group (54.7%, 24.6%, and 5.4%, respectively). Binge drinking during the first trimester of pregnancy was reported by 10.1% of pregnant women ages 15 to 44 years. D. Tobacco (SAMHSA, 2012). 2. However, among those ages 15 to 17 years, the rate of cigarette smoking was higher for pregnant women than nonpregnant women, 22.7% vs. 13.4%. B. Preconception women who smoke cigarettes or use any other form of tobacco product should be identified and encouraged and supported in an effort to quit. Importantly, tobacco cessation at any point during pregnancy yields substantial health benefits for the expectant mother and newborn. C. Smoking during pregnancy and sudden infant death syndrome (SIDS) have a strong association. Children born to mothers who smoke during pregnancy are at increased risk of asthma, infantile colic, and childhood obesity. Cessation of smoking is recommended before pregnancy. D. Other important behavioral issues to address prenatally include alcohol use and misuse and the abuse of prescription and nonprescription recreational drugs. All women should be asked about the quantity and frequency of their alcohol use. Women who are trying to become pregnant should be counseled to completely refrain from all alcohol use. E. Referral relationships with appropriate resources should be established and used as needed to assist women with these issues. Women who are counseled concerning their alcohol or drug use should be followed up to assess adherence to recommendations. Table 3-1 details the major drugs of abuse (Hudak and Tan, 2012). TABLE 3-1 Major Drugs of Abuse Adapted from Hudak, M.L., Tan, R.C., Committee on Drugs, and Committee on Fetus and Newborn, American Academy of Pediatrics: Neonatal drug withdrawal. Pediatrics, 129(2):e540-e560, 2012. Epub January 30, 2012. Retrieved from http://pediatrics.aappublications.org/content/129/2/e540. DET, Diethyltryptamine; DMT, dimethyltryptamine; LSD, lysergic acid diethylamide; MDA, methylenedioxyamphetamine; MDEA, 3,4-methylenedioxyethamphetamine; MDMA, 3,4-methylenedioxymethamphetamine (ecstasy); MMDA, 3-methoxy-4,5-methylenedioxyamphetamine. 1. Research shows that some medications that are effective in drug-abusing populations can also be beneficial for pregnant women and their babies. Methadone maintenance in opioid-dependent pregnant women has been used for the past 35 years, and is associated with improved birth weight and improvements in multiple areas (Kraft and van den Anker, 2012). 2. Methadone maintenance combined with prenatal care and a comprehensive drug treatment program can improve many of the detrimental maternal and neonatal outcomes associated with untreated heroin abuse (Kraft and van den Anker, 2012). 3. Another medication for treating opioid dependence, buprenorphine, has recently been shown to produce fewer neonatal abstinence symptoms in babies than methadone, resulting in shorter infant hospital stays (Kraft and van den Anker, 2012). B. Behavioral treatments. 2. Compared to a standard treatment condition, motivational incentive approaches appear to increase treatment retention and prolong abstinence in pregnant women with cocaine, opiate, and nicotine dependence. In general, it is important to closely monitor women who are trying to quit drug use during pregnancy and to adjust treatment as needed. C. Comorbidity associated with mental disorders. 2. More treatment research on co-occurring psychiatric and substance use problems in pregnant women, including an examination of mood-focused smoking cessation interventions, is needed. Drugs can affect the fetus in multiple ways, through either direct or indirect effects. B. Indirect effects. 2. Maternal factors such as decreased access to/compliance with health care, increased exposure to violence, and increased risk of mental illness and infection may place the fetus at risk. C. Ethanol. 2. Ethanol has direct teratogenic effects during the embryonic and fetal stage of development as well as altered neurotransmitter levels in the brain, altered brain morphology, altered neuronal development, and hypoxia. D. Tobacco. 2. Although the exact mechanisms by which nicotine produces adverse fetal effects are unknown, it is likely that hypoxia, undernourishment of the fetus, and direct vasoconstrictor effects on the placental and umbilical vessels all play a role. E. Marijuana. 2. Marijuana can remain in the body for up to 30 days, thus prolonging fetal exposure. Smoking marijuana produces as much as 5 times the amount of carbon monoxide, which may alter fetal oxygenation, as does cigarette smoking. F. Opiates. G. Cocaine. 2. It appears that the development of areas of the brain that regulate attention and executive functioning are particularly vulnerable to cocaine. Functions such as arousal, attention, and memory may be adversely affected by prenatal cocaine exposure. H. Methamphetamine. A. Characteristics associated with drug use (AAP and ACOG, 2012). 2. Maternal characteristics. b. Women who use illicit substances are at risk of human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), herpesvirus infection, hepatitis, and syphilis, each of which can have significant adverse effects on the fetus and newborn. 3. Infant characteristics. B. Identification of drug users (Behnke and Smith, 2013; Hudak and Tan, 2012). 1. Two basic methods are used to identify drug users: self-report or biological specimens. Although no single approach can accurately determine the presence or amount of drug used during pregnancy, it is more likely that fetal exposure will be identified if a biological specimen is collected at the time of a structured interview (Eyler et al., 2005). 2. Self-reported history. b. However, self-report suffers from problems with the veracity of the informant and recall accuracy (AAP and ACOG, 2012). 3. Biological specimens. b. The three most commonly used specimens to establish drug exposure during the prenatal and perinatal period are urine, meconium, and hair; however, none is accepted as a “gold standard.” Other specimens such as umbilical cord, cord blood, human milk, and amniotic fluid may also be tested. c. Breast milk. (1) A minimum of 10 mL of breast milk is required for testing (United States Drug Testing Laboratories, Inc. [USDTL], 2012b). Collection instructions can be found at http://www.usdtl.com/lactostat.html. d. Urine. (2) Marijuana metabolites can be excreted for as long as 10 days in the urine of regular users and up to 30 days in chronic, heavy users. Urine is a good medium as well for the detection of nicotine, opiate, cocaine, and amphetamine exposure. e. Meconium. (2) It is hypothesized that drugs accumulate in meconium throughout pregnancy, and this is thought to reflect exposure during the second and third trimesters of pregnancy when meconium forms. Meconium has been used for the detection of nicotine, alcohol, marijuana, opiate, cocaine, and amphetamine exposure. (3) Because meconium is heterogeneous and drugs do not appear to diffuse throughout the entire meconium mass, the pooling of multiple meconium stools is highly encouraged until the milk stool appears. For maximum sensitivity, 2 to 3 g (1 teaspoon) of meconium are necessary for testing (USDTL, 2012c). Collection instructions can be found at http://www.usdtl.com/mecstat.html. f. Hair. (1) Hair is easy to collect, although some parents may decline this sampling method. (2) Drugs become trapped within the hair and can reflect drug use over a long period of time. Hair is useful for the detection of nicotine, opiate, cocaine, and amphetamine exposure. g. Umbilical cord. (2) The cord may have a more rapid return of information to the clinician since meconium may not be passed for several days (Montgomery et al., 2006; USDTL, 2012a). (3) A 6-inch segment of the umbilical cord is required for testing (USDTL, 2012a). Collection instructions can be found at http://www.usdtl.com/cordstat.html. 4. Additional screenings. a. Additional assessment of infants of drug-abusing mothers should include possible screening for hepatitis B, hepatitis C, HIV, and other sexually transmitted infections (AAP and ACOG, 2012). C. Legal implications of drug screening. 1. The legal implications of testing and the need for consent from the mother may vary among the states; therefore, health care providers should be aware of local laws and legislative changes that may influence regional practice (AAP and ACOG, 2012). 2. Each hospital should consider adopting a policy for maternal and newborn screening to avoid discriminatory practices and to comply with local laws (AAP and ACOG, 2012; Hudak and Tan, 2012). A. Fetal growth (Behnke and Smith, 2013). 2. There is a vast literature on the teratogenic effects of prenatal alcohol exposure after the first description of fetal alcohol syndrome (FAS) in 1973. Growth restriction is a hallmark of FAS. More information is available from the American Academy of Pediatrics (www.aap.org) and on the National Institute on Alcohol Abuse and Alcoholism website (NIAAA, 2013). 3. Marijuana has not been associated with fetal growth restriction, particularly after controlling for other prenatal drug exposures. 4. Studies have reported lower birth weight in opiate-exposed newborn infants born at ≥ 33 weeks of gestation, independent of use of other drugs, prenatal care, or other medical risk factors. 5. Pregnant women who abuse methamphetamine are at increased risk of preterm birth, placental abruption, fetal distress, and intrauterine growth restriction at rates similar to those for pregnant women who use cocaine (Hudak and Tan, 2012). B. Neurobehavioral abnormalities (Behnke and Smith, 2013). 2. Prenatal alcohol exposure may cause poor habituation and low levels of arousal along with motor abnormalities. 3. Prenatal marijuana exposure is associated with increased startles and tremors in the newborn. 4. Abnormal neurobehavior in opiate-exposed newborn infants is related to neonatal abstinence. 5. Prenatal cocaine exposure may cause irritability and lability of state, decreased behavioral and autonomic regulation, and poor alertness and orientation. 6. Prenatal methamphetamine exposure has been documented to cause abnormal neurobehavioral patterns in exposed newborn infants consisting of poor movement quality, decreased arousal, and increased stress. There are reports of long-term adverse neurotoxic effects of in-utero methamphetamine exposure on behavior, cognitive skills, and physical dexterity (Hudak and Tan, 2012). A. For all drug classes except opioids, the symptoms of NAS are usually self-limited and do not require pharmacologic treatment (Patrick et al., 2012). B. Neonatal withdrawal most commonly results from intrauterine opioid exposure. Signs and symptoms of withdrawal worsen as drug levels decrease. In addition to prenatal exposure, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk of manifesting signs of withdrawal (AAP and ACOG, 2012; Behnke and Smith, 2013; Hudak and Tan, 2012). C. Other drugs cause signs in infants because of acute toxicity. Signs and symptoms of acute toxicity abate with drug elimination (AAP and ACOG, 2012). A. An opiate withdrawal syndrome was first described by Finnegan and colleagues (Finnegan et al., 1975a, 1975b). B. Neonatal withdrawal most commonly results from intrauterine opioid exposure. Infants with NAS often require prolonged hospitalization and treatment with medication (Hudak and Tan, 2012). C. The constellation of clinical findings associated with opioid withdrawal has been termed neonatal narcotic abstinence syndrome. This syndrome includes a combination of physiologic and neurobehavioral signs such as sweating, irritability, increased muscle tone and activity, feeding problems, diarrhea, and seizures (Behnke and Smith, 2013; Hudak and Tan, 2012). D. Withdrawal signs will develop in 55% to 94% of infants exposed to opioids in utero. Neonatal withdrawal signs also have been described in infants exposed antenatally to benzodiazepines, barbiturates, and alcohol (Behnke and Smith, 2013). E. Because fetal drug exposure often is unrecognized in the immediate newborn period, affected infants may be discharged to homes where they are at increased risk of a variety of medical and social problems, including abuse and neglect (AAP and ACOG, 2012; Hudak and Tan, 2012). F. The specific effect of drug exposure on the fetus and newborn varies widely with the substance ingested, the amount received, and individual susceptibility. B. Neurobehavioral abnormalities may occur in neonates with intrauterine cocaine exposure, most frequently on the second or third postnatal days. C. These abnormalities may include irritability, hyperactivity, tremors, high-pitched cry, and excessive sucking. Because cocaine or its metabolites may be detected in neonatal urine for as long as 7 days after delivery, observed abnormalities in exposed infants may reflect drug effect rather than withdrawal. B. Maintenance programs with methadone can sustain opioid concentrations in the mother and fetus to minimize opioid craving and prevent fetal stress. Disadvantages of methadone include the extremely unlikely achievement of successful detoxification after delivery and a more severe and prolonged course of NAS. C. The synthetic opioid buprenorphine is approved for the treatment of opioid dependence. Buprenorphine, either alone (Subutex) or in combination with naloxone (Suboxone), has been used both as a first-line treatment of heroin addiction and as a replacement drug for methadone. D. Buprenorphine has some advantages over methadone as a treatment of opioid addiction in pregnant women. Infants born to mothers treated with buprenorphine had shorter hospital stays (10 vs. 17.5 days), had shorter treatment durations for NAS (4.1 vs. 9.9 days), and required a lower cumulative dose of morphine (1.1 vs. 10.4 mg) compared with infants born to mothers on methadone maintenance (Jones et al., 2010b). B. Onset of signs attributable to neonatal withdrawal from heroin often begins within 24 hours of birth, whereas withdrawal from methadone usually commences around 24 to 72 hours of age. Infants exposed to buprenorphine may have an onset of withdrawal that peaks at 40 hours, and signs are most severe at 70 hours of age. C. Withdrawal from ethanol begins early during the first 3 to 12 hours after delivery. D. Barbiturate withdrawal has a median onset of 4 to 7 days, but a wide range of 1 to 14 days. Other sedative-hypnotics have exhibited even later onset, including as late as day 12 for diazepam and day 21 for chlordiazepoxide. E. Clinical features of NAS fall into two major categories: neurologic excitability (e.g., high-pitched cry, tremors, increased wakefulness) and gastrointestinal dysfunction (e.g., vomiting, fever, sweating) (see Fig. 3-1). B. The apparent decreased severity of signs in preterm infants may relate to developmental immaturity of the CNS, differences in total drug exposure, or lower fat depots of drug. C. The clinical evaluation of the severity of abstinence may be more difficult in preterm infants because scoring tools to describe withdrawal were largely developed in term or late preterm infants. A. Several tools are available for quantifying the severity of withdrawal symptoms. B. Each nursery should adopt a protocol for the evaluation and management of neonatal withdrawal, and staff should be trained in the correct use of an abstinence assessment tool. C. The Finnegan instrument was created to assess severity of disease in those with known opioid exposure. On day 2 of life, a score of 7 corresponds with the 95th percentile for nonexposed infants, meaning any score of 8 or greater is highly suggestive of in-utero opioid exposure even in infants of those women denying opioid use during pregnancy (Finnegan et al., 1975a, 1975b; Kraft and van den Anker, 2012). D. The modified Finnegan’s Neonatal Abstinence Scoring System is the predominant tool used in the United States (Fig. 3-2). This instrument assigns a cumulative score based on the interval observation of 21 items relating to signs of neonatal withdrawal.
Perinatal Substance Abuse
OVERVIEW
PRECONCEPTION COUNSELING AND INTERVENTIONS (AMERICAN ACADEMY OF PEDIATRICS [AAP] AND THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS [ACOG], 2012)
Opioids
CNS Stimulants
CNS Depressants
Hallucinogens
Agonists
Amphetamines
Alcohol
Indolealkylamines (LSD, psilocin, psilocybin, DMT, DET)
Morphine
Dextroamphetamine (Dexedrine)
Barbiturates
Phenylethylamines (mescaline, peyote)
Codeine
Methamphetamine
Benzodiazepines
Phenylisopropylamines (MDA, MMDA, MDMA, MDEA)
Methadone
Amphetamine sulfate
Other sedative-hypnotics
Inhalants
Meperidine (Demerol)
Amphetamine congeners
Methaqualone (Quaalude)
Solvents and aerosols (glues, gasoline, paint thinner, cleaning solutions, nail polish remover, Freon)
Oxycodone (Percodan, OxyIR, Percolone, Roxicodone, Percocet, OxyContin)
Benzphetamine (Didrex)
Glutethimide (Doriden)
Nitrites
Diethylpropion (Tenuate)
Chloral hydrate
Nitrous oxide
Fenfluramine
Cannabinoids
Propoxyphene (Darvon)
Phendimetrazine (Adipost, Bontril, Prelu-2)
Marijuana
Hydromorphone (Dilaudid)
Phentermine (Adipex-P, Zantryl)
Hashish
Hydrocodone (Lortab, Vicodin)
Cocaine
Fentanyl (Sublimaze)
Methylphenidate (Ritalin, Concerta)
Tramadol (Ultram, Ultracet)
Pemoline (Cylert)
Heroin
Phenylpropanolamine
Antagonists
Phencyclidines
Naloxone (Narcan)
Nicotine
Naltrexone (ReVia)
Mixed Agonist-Antagonists
Pentazocine (Talwin)
Buprenorphine (Buprenex)
TREATMENT APPROACHES FOR PREGNANT WOMEN (AAP AND ACOG, 2012)
MECHANISMS OF ACTION OF DRUGS ON THE FETUS (BEHNKE AND SMITH, 2013)
IDENTIFICATION OF PRENATAL EXPOSURE
MEDICAL ISSUES IN THE FETAL AND NEWBORN PERIOD
NEONATAL DRUG WITHDRAWAL AND ACUTE TOXICITY
NEONATAL NARCOTIC ABSTINENCE SYNDROME
COCAINE AND OTHER STIMULANTS (HUDAK AND TAN, 2012)
OPIOIDS (HUDAK AND TAN, 2012)
CLINICAL PRESENTATION OF OPIOID WITHDRAWAL (HUDAK AND TAN, 2012)
PRETERM INFANTS AND DRUG WITHDRAWAL (HUDAK AND TAN, 2012)
ASSESSMENT OF WITHDRAWAL
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3: Perinatal Substance Abuse
FIGURE 3-1 ■ Current substance use among pregnant women, 2008-2009 combined. (From National Institute of Drug Abuse: Topics in brief: Prenatal exposure to drugs of abuse. 2011. Retrieved from http://www.drugabuse.gov/publications/topics-in-brief/prenatal-exposure-to-drugs-abuse.)
FIGURE 3-2 ■ Modified Finnegan’s Neonatal Abstinence Scoring System. (Developed by L. Finnegan.)
