Drug Withdrawal in the Neonate*

11. Drug Withdrawal in the Neonate*


Susan M. Weiner and Loretta P. Finnegan



The epidemic of maternal substance abuse over the past 35 years has continued to escalate at an alarming rate. The extent of drug use during pregnancy is often underestimated, as are the effects on the fetus and neonate. According to the National Survey on Drug Use and Health (Substance Abuse and Mental Health Services Administration [SAMHSA]), 80,86 an estimated 4% of pregnant women (ages 15 to 44 years) reported using illicit drugs in any given month. An estimated 11.8% of pregnant women reported current alcohol use with 2.9% reporting binge drinking and 0.7% reporting heavy drinking. Cigarette use was reported as 16.5% in pregnant women of the same age. 66 Using prevalence data from SAMHSA’s National Survey on Drug Use and Health combined with live birth data from National Vital Statistics, out of the 4.1 million births in 2004, 160,370 pregnancies involved illicit drugs. 66 Data also showed that 8% of black pregnant women reported using an illicit drug in the past month, compared with 4.4% of white women and 3% of Hispanic women. 66

The National Institute of Drug Abuse (NIDA)–funded 2007 Monitoring the Future study showed that 0.8% of 8th graders, 0.8% of 10th graders, and 0.9% of 12th graders had abused heroin at least once in the year before being surveyed. 58 As health care providers, we must recognize these data as a snapshot of affected young people who are future parents. The sequelae of both licit and illicit substance abuse by the mother during pregnancy must be recognized and addressed to provide optimal medical care of the neonate. Stereotypic biases should not interfere with the diagnosis or treatment. Drug dependence in pregnancy crosses all socioeconomic and racial barriers. Therefore health care providers should not rule out drug exposure in any neonate who is exhibiting symptoms at birth related to withdrawal from or exposure to illicit or prescribed drugs.

Opioid addiction in the mother during pregnancy has been studied in detail for decades in terms of its effects on the woman, the fetus, and the developing child. * An opioid is defined as any natural or synthetic drug that has pharmacologic properties similar to those of opium. 25 An opiate is derived from opium or contains opium. Because time, circumstances, and knowledge have changed, other factors now should be considered in treating neonates. Diagnostic data can no longer be gathered on the assumption that one drug or substance was used. Polydrug use (the concurrent use of three or more drugs) is now the norm and not the exception.35 Polydrug use also can be the combination of illicit substances with those that are legal or found over the counter. The impact on the fetus and neonate is not necessarily minimized by the legality of the substance. Patterns of abuse, purity of the illicit drug, and sometimes potent or poisonous additions to them also may cause catastrophic sequelae in newborns.


Iatrogenic physical dependence has been documented in infants given intravenous fentanyl or morphine to maintain continuous analgesia and/or sedation during extracorporeal membrane oxygenation (ECMO) and mechanical ventilation.83 Among the first to document this was Franck and Vilardi29 in 1995 when neonatal abstinence syndrome (NAS) or neonatal opiate abstinence syndrome (NOAS) 66 was observed after abrupt withdrawal of sedation. The signs of withdrawal are much like those reported in infants born to opioid-dependent mothers. Fifty to 84% of neonates removed from fentanyl within a 24-hour period exhibited withdrawal symptoms, and 48% exhibited signs and symptoms with morphine withdrawal. 83 Regardless of the agent(s) used for sedation, once the decision is made to start weaning the medication, careful observation of the infant is crucial to monitor for signs and symptoms of withdrawal.83 A review of the literature points out the importance of initiatives for adequate analgesia in neonates, to the development of formal policies concerning intensive care sedation, and to treatment of the withdrawal2,4,82,83 (see Chapter 12).

Osborn et al in a Cochrane Database Review of opiate treatment for newborn withdrawal discuss the use of the Lipsitz Tool (1975), the Finnegan Scoring System (1975), and the Neonatal Withdrawal Inventory by Zahorodny (1998) for the documentation of manifestations of withdrawal by various institutions. 59,62 The literature cites various pharmacologic agents that have been used to alleviate the symptoms of opioid withdrawal with methadone, buprenorphine, and oral morphine sulfate. 19,52,56,59,62 Advances in neonatology have continued to broaden the period of viability as many more premature infants are being kept alive. What appears to be decreased severity of abstinence in preterm infants may be related to developmental immaturity of the central nervous system (CNS) or to differences in total drug exposure. This proves to be a problem in evaluating the severity of abstinence signs in a preterm infant, because scoring tools were developed largely for use with term or near-term infants. 3,57

This chapter presents current information about treatment issues surrounding drug-exposed neonates, with the main focus on opioid withdrawal. The effects of other substances such as stimulants, hallucinogens, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, non-opioid CNS depressants, tobacco, methamphetamines, and alcohol are addressed when symptoms deviate from those of NAS.


PHYSIOLOGY


Because of their low molecular weight and lipid solubility, all drugs of abuse reach the fetal circulation by crossing the placenta, causing direct toxic effects on the fetus. * Although certain drugs may produce specific effects, many abused drugs produce similar manifestations of fetal and neonatal disease. In addition, the effects of legal drugs such as tobacco, caffeine, and alcohol may confound simple drug-effect relationships. 3 A hostile intrauterine environment also may be caused by adverse effects of the mother’s drug addiction and must be considered when diagnosing the neonate’s problems. Examples of factors that could have an impact on neonatal outcome include lifestyle, homelessness, physical or sexual abuse, prostitution, poverty, poor or no prenatal care, polydrug abuse, intravenous drug abuse, binge and withdrawal cycles, anorexia, poor maternal nutrition, pica, dehydration, alcoholism, sexually transmitted diseases, dental abscesses, preexisting medical conditions requiring pharmacologic therapy, human immunodeficiency virus (HIV)–positive status or acquired immunodeficiency syndrome (AIDS), and hepatitis B and hepatitis C.†




Opioid Substances


When drugs such as heroin, methadone, morphine, buprenorphine, and meperidine cross the placenta, the fetus may become passively dependent. Morphine, the major metabolite of heroin, methadone, as well as buprenorphine and its metabolite have been identified and measured in amniotic fluid, cord blood, breast milk, 1,30,33,51 neonatal urine, and meconium. 17,43,49,51,63 Non-opioid CNS depressants (e.g., benzodiazepines, barbiturates) and the other opiates/opioids (e.g., codeine, hydrocodone, oxycodone, hydromorphone, pentazocine, propoxyphene) all have been identified in neonatal urine and meconium. 19,47,92 Ethanol and its primary metabolite, acetaldehyde, have been identified in placental tissue and amniotic fluid. 10,11,73,77.78. and 79.

Human and animal studies have shown that use of opioids during pregnancy directly affects fetal growth. Heroin is associated with intrauterine growth restriction (IUGR), with only a slight reduction in gestational length, although the mechanism by which heroin inhibits growth is not known. 18 Although early speculation that maternal opiate (heroin) use during pregnancy was reported to accelerate fetal lung maturity, this has not been borne out when formally studied and no plausible mechanism by which heroin exposure resulted in this was elucidated—even the associated growth restriction and chronic stress. 36 Older studies comparing methadone-exposed with non-exposed infants have found that methadone-exposed infants had lower birth weights. However, infants born to methadone-maintained women have been reported to have higher birth weights than those born to women using heroin. Decreased head circumference has been an inconsistent finding with these babies. Shempf conducted a meta-analysis looking at illicit drug use and neonatal outcomes and found birth weights of newborns born to mothers using heroin were lower than those of newborns whose mothers used methadone alone and those of newborns whose mothers used both heroin and methadone during their pregnancy. 69 A mean reduction of 483 g in birth weight and a relative risk for low birth weight were associated with any opiate use during pregnancy. 69 Neither heroin nor methadone has been associated with congenital malformations or any specific dysmorphic syndrome in offspring.

Methadone maintenance has been an accepted treatment strategy for opioid dependence for the past 40 years. Recently, several multi-site research studies have been studying buprenorphine instead of methadone, which was approved by the FDA for general use but not for the opiate-addicted pregnant woman. 57 The preliminary results of these studies have been inconclusive, although buprenorphine may offer some advantages for treatment of opiate dependence during pregnancy as seen in European studies. 27,28,44 It seems clear that patient preferences for methadone or buprenorphine seem to exist, so choices of medication should be considered now for non-pregnant women and perhaps in the future for pregnant women in the United States.

Neonatal withdrawal from psychoactive substances that the fetus is exposed to occurs in varying degrees. Because most opiates/opioids are short acting and not stored by the fetus in appreciable amounts, neonatal abstinence is usually apparent within the first 24 to 72 hours of life.26The onset of clinical NAS symptoms depends on which opiates/opioids the pregnant women used.16,26 For example, with heroin, NAS may occur in the first 24 hours, whereas with methadone, it may not develop until after 48 hours. 16Symptoms of NAS in heroin-exposed infants occur earlier than in infants of methadone-maintained mothers because of heroin’s shorter half-life.25 When compared with methadone, a lower incidence of NAS has been reported in buprenorphine-exposed neonates and it has been suggested that it is because of the limited placental transfer of this drug, thereby limiting fetal exposure and development of dependency. 37,40,42,44 A study by Ebner et al showed that a significant portion of neonates of buprenorphine-maintained mothers did not require pharmacologic treatment of their withdrawal. 16


Non-opioid Substances



COCAINE


Although still controversial, the neonatal impact of maternal cocaine use, especially on fetal growth, is more consistently observed. 69 Researchers hypothesize that cocaine reduces fetal growth through maternal vasoconstriction, reduced uteroplacental transfer, and direct effect on fetal metabolism interfering with fat deposition. 69 Cocaine crosses the placenta by simple diffusion. This occurs because of its high lipid solubility, low molecular weight, and low ionization at physiologic pH. In addition, the low level of plasma esterases in the fetus and the relatively low pH of fetal blood (cocaine is a weak base) enhance the accumulation of cocaine in fetal compartments. 23 Taking advantage of the fact that cocaine and its metabolite benzoylecgonine (BE) accumulate and can be detected months after exposure in maternal and neonatal hair, an analytic test for cocaine and BE was developed by Garcia-Bournissen. These investigators looked at the characteristics of maternal and neonatal hair cocaine as biomarkers of fetal exposure. 32 They found that cocaine in hair and BE concentrations were not normally distributed, and they did not observe a correlation between maternal hair cocaine concentration and the baby-to-mother cocaine ratio, which ruled out a dose-dependent mechanism. However, the positive correlation between cocaine concentrations in maternal and neonates’ hair corroborates previous reports showing transplacental transfer of cocaine. 32 Cocaine has a significant vasoconstrictive property, which decreases blood flow to the placenta and fetus, contributing to fetal growth restriction and hypoxia. 5,32

Although direct teratogenic effects of cocaine have been dismissed by many authors and researchers on the basis of epidemiologic studies, available data appear to confirm an association between cocaine use and low birth weight, prematurity, placental abruption, and behavioral abnormalities. 32,37 In a recent review by Helmbrecht and Thiagarajah, it was posited that the mechanism by which cocaine induces placental abruption is via intense transient hypertension and vasoconstriction produced by the drug. 37 Several studies have shown that the placenta itself is a direct target for cocaine toxicity, which may play an important role in the pathogenesis of cocaine-induced complications in pregnancy. 32,37 Aside from generalized sympathetic effects, cocaine may more specifically impair fetal/neonatal cardiac function caused by apoptosis (programmed cell death) in fetal heart muscle. 1 This effect is attributed to the formation of oxygen free radicals. 5 The literature has suggested that these infants have an increased risk for prematurity, perinatal cerebral infarctions, abnormal electroencephalograms (EEGs) at birth, non-duodenal intestinal and anal atresias, necrotizing enterocolitis, terminal limb defects, cardiovascular effects, genitourinary anomalies, reduced head circumference, and, rarely, a pattern of congenital malformations termed fetal vascular disruption. 39 Maternal cocaine abuse also has been shown to produce neuromotor deficits, which include impaired muscle tone leading to abnormal movement patterns and tremors. 5,37,69 The most important central action of cocaine is its stimulation of the central nervous system by inhibiting the reuptake of norepinephrine, serotonin, and dopamine. In the neonatal period, cocaine, unlike opiates, does not produce an abstinence syndrome but, rather, causes a direct neurotoxicity. 23,32,37 Initial signs of irritability and tremulousness are transient, usually lasting only a few days. This period of CNS irritability is followed by a more extended period of hyporeactivity, lethargy, and poor interaction with caregivers. 23

As part of the Maternal Lifestyle Study, Bada et al used multivariate regression models with over 11,000 mother-infant dyads to try to estimate the effects of cocaine exposure on intrauterine growth and to investigate when fetal growth deviation would manifest itself in the woman’s gestation. 6 After controlling for confounders, at 40 weeks’ gestation, cocaine exposure was estimated to be associated with decreases of 151 g in birth weight, 0.71 cm in length, and 0.43 cm in head circumference. Investigators concluded that in utero cocaine exposure was associated with growth deceleration that becomes more pronounced as gestation advances. 6

Lester et al compared auditory brain response (ABR) in 1-month-old infants exposed to cocaine and/or opiates and in those who were not exposed. Three previous published studies were conducted more than 20 years ago, before sophistication of research methodology and toxicology. 51 Their results both confirmed and expanded upon the earlier findings that perinatal cocaine or opiate exposure does affect neural transmission, which suggests delayed brainstem maturation in these infants. 51,91


ALCOHOL


Alcohol has been shown to cause diminished deoxyribonucleic acid (DNA) synthesis, disruption of protein synthesis, and impaired cellular growth, differentiation, and migration. These cellular effects can be seen with both ethanol and acetaldehyde and are instrumental in inducing fetal malformations. It is unclear whether ethanol exerts its effects by interacting with neuronal membrane lipids or by interfering with membrane receptors and intracellular signaling systems. 23 The literature discusses altered embryonic cell organization, with IUGR and chronic fetal hypoxia as the result. 78,81

The most serious effect to the infant of maternal alcohol use during pregnancy is fetal alcohol spectrum disorders (FASD). FASD is an umbrella term describing the range of effects that can occur in an individual who was prenatally exposed to alcohol. These effects may include physical, mental, behavioral, and/or learning disabilities with lifelong implications. FASD is not a diagnostic term. It refers to specific conditions such as fetal alcohol syndrome (FAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). 75,79 Recent research documenting deleterious outcomes for children prenatally exposed to small amounts of alcohol (0.5 drink per day) has led to a realization that a threshold has not been adequately identified; therefore the woman should be counseled by her health care professional to not drink any alcohol while pregnant. 75,76

When women consume cocaine and alcohol together, they compound the danger. Researchers have found that the human liver combines cocaine and alcohol to produce a unique metabolite, cocaethylene, which intensifies cocaine’s euphoric effects. Cocaethylene is associated with a greater risk for sudden death than cocaine alone. 60 Discussions in the 1990s surrounding the use of cocaine and alcohol together suggested that cocaethylene was reported to be 10 times more potent than cocaine alone and more toxic to the growing fetus. This has not been discussed in more current literature; however, Vidaeff and Mastrobattista state that the expression of fetal cocaine effects or nonspecific anomalies could be expected to increase when the pregnant woman is combining cocaine with the teratogen ethanol, because the toxicity is augmented. 88


AMPHETAMINES


Amphetamines and methamphetamines known as crystal, ice, or crank are abused by pregnant women in many geographic areas in the United States with the same frequency as cocaine. Like cocaine and “crack,” the amphetamines are potent stimulants and effects on the fetus and neonate are similar; and like cocaine, the preponderance of available data would suggest little or no effect of amphetamine on organogenesis. 23,37 Early research has shown how in utero amphetamine exposure can lead to congenital brain lesions, including hemorrhage, infarction, or cavitary lesions. Investigators also described the sites of these lesions as frontal lobes, basal ganglia, posterior fossa, or generalized atrophy; the effects of the lesions are not exhibited until the child is older. In the neonatal period, neurologic abnormalities including decreased arousal, poor state control, difficulty with habituation, tremors, hyperactive neonatal reflexes, abnormal cry, increased stress, drowsiness, poor feeding, and seizures have been reported. 23,74 Outcome effects of prenatal exposure to amphetamines have yet to be isolated from the effects of alcohol and nicotine, the two drugs most often used with the methamphetamines. 60

A review of the most recent literature documents lack of prenatal care as the hallmark of maternal cocaine and amphetamine use with an increase in maternal morbidity and mortality as its consequence. 3,70,77,78The use of these stimulants is reported to be toxic to the fetal brain, and there may be an increase in sudden infant death syndrome (SIDS).3Stimulants (amphetamines and cocaine) have been found in breast milk in extremely high levels and may produce an acute neurotoxic syndrome with hypertonia, tremors, apnea, and seizures.*



MARIJUANA


Marijuana, one of the most popular illicit drugs, has also been studied for many years. 31 de Moraes et al, in a prospective cross-sectional study that included full-term infants born to adolescent mothers who used marijuana, found that marijuana exposure was detected in both the mother’s and the infant’s hair and that the exposure during pregnancy altered the neurobehavioral performance of the term newborns when assessed with the neonatal intensive care unit (NICU) Network Neurobehavioral Scale (NNNS). 14 Other recent studies have highlighted the long-term impact of marijuana use in pregnancy on the neonate and child. These studies showed that prenatal marijuana use was “significantly related to increased hyperactivity, impulsivity, inattention symptoms, and delinquency” as the child grew older. 60


INHALANTS


No well-controlled, prospective studies have been done on maternal inhalant use—often substances of abuse in poor and underprivileged communities and groups because they are widely available, legal, and relatively inexpensive. 89 Organic solvents are chemical compounds used to dissolve substances, and although their chemical structures widely differ, they share some common features: low molecular weight, lipophilia, and volatility at room temperature. 54,71 Inhalants are classified into four different groups: volatile solvents, aerosols, gases, and nitrites. 54,55,71

Inhalants may produce a variety of rapid neuropsychiatric effects with euphoria or drowsiness coming on within seconds to minutes. Case reports and follow-up studies of children of inhalant/solvent–abusing mothers are available. Inhalant/solvent–abusing mothers give birth to babies who are small for gestational age (SGA) and who have developmental delays, craniofacial deformities, and an alcohol-like withdrawal syndrome. 41


ANTIDEPRESSANT USE IN PREGNANT WOMEN AND NAS OCCURRENCE


Another area of concern is the psychopharmacology employed in the complex care needs of pregnant women with coexisting mental health diagnoses. 34 It has been estimated that up to 70% of pregnant women experience some symptoms of depression, with 10% to 16% of pregnant women meeting diagnostic criteria for a major depressive disorder. 84 The typical or atypical antipsychotic drugs and lithium all pass the blood-placenta barrier, with significant difference among compounds. 67Continuing treatment throughout the pregnancy may be necessary to prevent relapse, and the pharmacologic treatment for depressive disorders may be either the tricyclic antidepressants (TCAs) or the SSRIs. A prospective study done by Kallen showed that both maternal TCA and SSRI use significantly increased the risk for neonatal respiratory distress, hypoglycemia, neonatal convulsions, and the occurrence of NAS. 45,46Table 11-1 gives the signs and symptoms of withdrawal from TCAs and SSRIs.



















































































TABLE 11-1 Neonatal Ssri and Tca Withdrawal Symptoms
Modified from ter Horst PG, Jansman FG, van Lingen RA, et al: Pharmacological aspects of neonatal antidepressant withdrawal, Obstet Gynecol Surv 63(4):267, 2008.
B/P, Blood pressure; CNS, central nervous system; GI, gastrointestinal; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

CNS, Sleep, Energy Gi System Motor Somatic Respiratory/Cardio

SSRI TCA SSRI TCA SSRI TCA SSRI TCA SSRI TCA
Somnolence X X






Irritability X X
Convulsions X X
Abnormal cry patterns X
Aberrant stool X
Poor suck/may need tube feedings X X
Agitation X X
Tremors, jitteriness, shivering X X
Decreased tone X X
Increased tone, rigidity, apathy X X
Temperature instability X X
Hypoglycemia X
Tachypnea X X
Dyspnea, respiratory distress X X
Dysrhythmias, unstable B/P, cyanosis X X


Lithium


Lithium, often used for bipolar disorders, should be avoided during the first trimester of pregnancy. The placenta provides no protection to the developing fetus, and neonatal lithium toxicity is exhibited as hypotonia, cyanosis, lethargy, jaundice, hypothermia, poor sucking, poor respiratory effort, poor Moro reflex, reversible inhibition of thyroid function, and diabetes insipidus. 61


ETIOLOGY OF NEONATAL ABSTINENCE SYNDROME


NAS is occurring in two ways: (1) by the passive exposure to opiates/opioids in utero as a consequence of maternal addiction to heroin, methadone, and other narcotic analgesics or to treatment of opiate/opioid addiction with methadone or buprenorphine; and (2) iatrogenically, by the administration of opiates/opioids such as fentanyl, morphine, and methadone to the neonate for analgesia and sedation. 29 Infants exposed in utero and born to heroin-, methadone-, or buprenorphine-dependent mothers have a high incidence of NAS (60% to 90%). 20 Less potent opioids or opioid-like agents have also been implicated in the development of NAS. (Box 11-1 gives a complete list.) Neonatal abstinence is described as a generalized disorder characterized by CNS hyperirritability, gastrointestinal dysfunction, respiratory distress, and autonomic dysfunction manifesting as vague symptoms such as yawning, hiccups, sneezing, mottled skin color, and fever.16,22,48,50 When narcotics cross the placenta, equilibrium is established between maternal and fetal circulations. Before birth, the drug is cleared from the infant’s circulation primarily by the mother’s excretory and metabolic mechanisms. 25

BOX 11-1
Drugs Associated With Neonatal Abstinence Syndrome




Opioids






• Heroin


• Fentanyl


• Methadone/buprenorphine


• Morphine


• Meperidine (Demerol)


Less Potent Opioids and Opioid-like Agents






• Propoxyphene hydrochloride


• Codeine


• Pentazocine (Talwin)


Non-opioid Central Nervous System Depressants






• Tranquilizers and sedatives


• Bromides


• Chlordiazepoxide (Librium)


• Desipramine (Pertofrane, Norpramin)


• Diazepam (Valium)


• Ethchlorvynol (Placidyl)


• Glutethimide (Doriden)


• Hydroxyzine HCl (Atarax)


• Oxazepam (Serax)


• Alcohol


• Inhalant solvent abuse


BOX 11-2
Factors Influencing the Onset of Passively Acquired Neonatal Abstinence Syndrome







• Drugs used by the mother


• Both the timing and the dose of the drugs before delivery


• Character of labor


• Type of analgesia and/or anesthesia given during labor


• Maturity, nutritional status, and the presence of intrinsic disease in the neonate

BOX 11-3
Factors Influencing the Onset of Iatrogenic Neonatal Abstinence Syndrome







• Prolonged opiate sedation for mechanical ventilation


• Duration of opioid analgesia use during extracorporeal membrane oxygenation


• Type of opiate used


• Maturity and presence of intrinsic disease in the neonate



Buprenorphine


Buprenorphine, an opioid agonist/antagonist, has a wide safety profile (e.g., less respiratory depression, less risk for overdose), few autonomic symptoms with abrupt cessation, an occurrence of NAS at 20% to 60%, and a shorter duration of NAS and fewer symptoms, as evidenced by a decreased length of stay when compared with methadone-exposed neonates. 20,27,28,42

Both methadone and buprenorphine are found in breast milk. Methadone appears in very low levels so that the mean daily methadone ingestion for an infant is 0.05 mg/day. 20 Buprenorphine’s plasma-to–breast milk ratio approximates 1, and its poor oral bioavailability enables an infant to be exposed to one fifth to one tenth of the total available amount—the lowest amount of any opiate. 20 If a mother is compliant with methadone maintenance and is HIV negative, breast feeding is safely recommended (see Chapter 18). Further research and comparisons of the use of methadone and buprenorphine, especially in large randomized controlled trials such as the MOTHER study, are needed. 20,42

Withdrawal may be mild, transient, and delayed in onset, or it may increase stepwise in severity. Symptoms may be present intermittently or follow a biphasic course characterized by acute NAS signs, followed by improvement and then the onset of a subacute withdrawal reaction.18,21,23,49,90 Withdrawal seems to be more severe in infants whose mothers have taken large amounts of drugs for an extended period. In general, the closer to delivery a mother takes the drug, the more severe the symptoms and the greater the delay in onset.

Usually the origin of NAS lies in the abnormal intrauterine environment. A series of steps appear to be necessary for the onset of NAS and thus the recovery of the infant. The growth and ongoing survival of the fetus are threatened by the continuing or episodic transfer of addictive substances from the maternal to the fetal circulation. During this time, the fetus goes through a biochemical adaptation to the abnormal element. At delivery, abrupt removal of the drug is the catalyst needed to start the onset of symptoms. The newborn continues to metabolize and excrete the substance, so that withdrawal signs occur when critically low tissue levels have been reached. Recovery from NAS is gradual and occurs as the infant’s metabolism is reorganized to adjust to the absence of the offending drug. 22,23

Studies of the relationship between maternal dose of methadone and severity of NAS have yielded inconsistent results: 50% of the studies find a relationship, whereas 50% find no relationship. 8,13,20,72 Use of adequate maternal methadone for therapeutic effect may decrease concomitant drug use and fetal risk; there is no compelling evidence to reduce maternal dosing to avoid NAS. 20Box 11-4 outlines the impact of maternal methadone maintenance on mother and newborn.



PREVENTION


Neonatal drug withdrawal is preventable if women do not use dependence-producing substances, licit or illicit, during pregnancy. Through intense educational efforts, the desirability and availability of drugs may be thwarted. Unfortunately, the psychosocial and socioeconomic milieu of modern society continues to propagate dysfunctional families, victimization of women, and an intergenerational cycle of substance abuse.

Therefore our goals must be to provide prenatal care for the pregnant drug-dependent woman and her fetus to diminish or eliminate the sequelae of passive addiction. The medical community is challenged to become more astute in its assessment and intervention for the problems of drug-dependent parturients. More treatment is necessary for these women and their neonates through inpatient residential care and outpatient interdisciplinary clinics that focus on the elimination, as well as the consequences, of addiction.

Franck and Vilardi, in addressing iatrogenic NAS, stated that guidelines for effective weaning of neonates from opiate analgesics and sedatives are becoming more established. 29Investigators encourage dose reductions of 10% to 20% per day. For the prevention of iatrogenic NAS, discussions in recent literature include limiting total doses of fentanyl during ECMO therapy by administering morphine boluses or using continuous morphine infusions to replace fentanyl, substituting enteral methadone for morphine, or using sublingual buprenorphine. 48,56

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Jun 18, 2016 | Posted by in PEDIATRICS | Comments Off on Drug Withdrawal in the Neonate*

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