Which symptoms would the RN observe in the newborn exhibiting symptoms of neonatal abstinence syndrome?

Practice Essentials

Neonatal abstinence syndrome (NAS) is a group of problems that occur in a newborn who was exposed to addictive illegal or prescription drugs while in the mother’s womb. Two major types of NAS are recognized: NAS due to prenatal or maternal use of substances that result in withdrawal symptoms in the newborn and postnatal NAS secondary to discontinuation of medications such as fentanyl or morphine used for pain therapy in the newborn.

Signs and symptoms

Symptoms of NAS depend on various factors including the type of drug the mother used, how much of the drug she used, how long she used the drug, and how the mother’s body breaks down the drug.

Symptoms may include the following:

• High-pitched cry

• Jitteriness

• Tremors

• Generalized convulsions

• Sweating

• Fever

• Mottling

• Excessive sucking or rooting

• Poor feeding

• Vomiting

• Diarrhea

See Clinical Presentation for more detail.

Diagnosis

The following studies may be necessary to diagnose cases of NAS:

• Radioimmunoassay and enzyme immunoassay

• Blood tests

• Urine toxicology assays

• Meconium analysis

• Umbilical cord drug testing

• Hair analysis

See Workup for more detail.

Management

The optimal treatment for NAS has not been established. Primary treatment of neonatal symptoms related to prenatal substance exposure should be supportive because pharmacologic therapy can prolong hospitalization and exposes the infant to additional agents that are often not necessary. However, pharmacotherapy for infants with more severe expression of NAS is necessary to allow them to feed, sleep, gain weight, and interact with caregivers. Opioids are currently considered the first-line therapy. Second-line therapy has been phenobarbital. Phenobarbital has been effective for the treatment of opioid withdrawal seizures and polydrug exposure.

See Treatment and Medication for more detail.

Background

Neonatal withdrawal syndrome, generically termed neonatal abstinence syndrome (NAS), is a complex disorder. It is defined as a constellation of behavioral and physiological signs and symptoms in newborns that are remarkably similar despite marked differences in the properties of the causative agent. [1] Two major types of NAS are recognized: NAS due to prenatal or maternal use of substances that result in withdrawal symptoms in the newborn and postnatal NAS secondary to discontinuation of medications such as fentanyl or morphine used for pain therapy in newborns admitted to the neonatal intensive care unit (NICU). [2]  Chronic opioid exposure in the most common source of NAS. [1]

Postnatal NAS results when an abrupt discontinuation of opioid analgesia occurs, usually after prolonged drug exposure. Fentanyl is the most commonly used analgesic drug in the neonatal intensive care unit (NICU). It is a potent, rapid-acting, synthetic opioid with a relative lack of hemodynamic side effects. Clinical studies have found that continuous infusions of fentanyl and morphine produce a high rate of opioid withdrawal when administered to critically ill infants. Tolerance and physical dependence are thought to develop more rapidly with shorter acting drugs and after continuous infusions rather than with intermittent administration. Tolerance and withdrawal symptoms may occur after 5 or more days of continuous infusion of fentanyl. This occurs more often with fentanyl than morphine. [3, 4] This article focuses on prenatal or maternal use of licit or illicit drugs, although symptoms and therapy for postnatal NAS are similar.

Maternal substance abuse, the cause of prenatal NAS, is a leading preventable cause of mental, physical, and psychological problems in infants and children. Substance use by pregnant women has both medical and developmental consequences for the newborn, in addition to the legal, health, and economic consequences for the mother.

Drug abuse in pregnancy and neonatal psychomotor behavior consistent with withdrawal from opiate and polydrug withdrawal is currently a significant clinical and social problem. An estimated average of 5.4% of pregnant women aged 15-44 years used illicit drugs in 2012-2013, with the highest rate seen in those aged 15-17 years (14.6%), followed by women aged 18-25 years (8.6%), and those aged 26-44 years (3.2%). [5] From 2000-2009, the annual rate of NAS diagnosis among newborns in the United States increased almost 3-fold. [6]

Drugs frequently associated with neonatal problems are listed below.

Opiates and narcotics include the following:

• Codeine

• Fentanyl

• Heroin

• Methadone

• Meperidine (Demerol)

• Oxycodone

• Morphine

• Hydromorphone (Dilaudid)

• Butorphanol (Stadol)

• Pentazocine

• Propoxyphene (Darvon)

• Chlordiazepoxide

• Buprenorphine [7]

Other drugs include the following:

• Barbiturates

• Caffeine

• Cocaine

• Selective serotonin reuptake inhibitors (SSRIs)

• Antihistaminics (Diphenhydramine, Hydroxyzine)

• Ethanol

• Marijuana

• Nicotine

• Phencyclidine

• Meprobamate

• Glutethimide

• Ethchlorvynol

• Diazepam and lorazepam

Pathophysiology

Most illicit drugs cause an addiction in the mother and dependence in the infant. Dependence or tolerance in the latter is due to passage of the drugs across the placental barrier; this occurs in varying degrees, depending on the pharmacokinetic properties of the individual drugs. Substances that act on the central nervous system (CNS) are usually highly lipophilic and have relatively low molecular weight. These characteristics facilitate crossing from maternal to fetal circulation, with rapid equilibration of free drug between mother and fetus. Once drugs cross the placenta, they tend to accumulate in the fetus because of the immaturity of the renal function and the enzymes used for metabolism. Disruption of the transplacental passage of drugs at birth results in the development of a withdrawal syndrome.

Neonatal abstinence syndrome (NAS) is often a multisystem disorder that frequently involves the CNS, gastrointestinal (GI) system, autonomic system, and respiratory system. Manifestations of NAS depend on various factors, including the drug used, its dose, frequency of use, and the infant's own metabolism and excretion of the active compound or compounds. In addition, prenatal NAS depends on the infant's last intrauterine drug exposure and the mother's drug metabolism and excretion. Withdrawal is generally a function of the drug's half-life; the longer the half-life, the later the onset of withdrawal. A longer half-life is also associated with a decreased likelihood of NAS in the infant.

It has been suggested that brain-derived neurotrophic factor (BDNF) may have a neuromodulatory role during withdrawal after in utero opiate exposure. A study of 67 infants with NAS (n = 34) and without NAS (n = 33) noted significantly elevated levels of plasma BDNF in infants with NAS during the first 48 hours of birth compared to those without NAS. [8]

The specific effects of illicit substances are complex and depend on the type of substance, the frequency and duration of use, the dose, the route of substance intake, and the timing of substance exposure with respect to gestational period.

Opiates produce the most dramatic effects on both the mother and fetus. Aside from the withdrawal symptoms, common findings in infants exposed to opiates include low birth weight, prematurity, and intrauterine growth retardation (IUGR). Because of its short half-life, heroin withdrawal may start as early as 24 hours after birth and usually peaks within 48-72 hours in 50-80% of infants born to mothers who are dependent on heroin. Some delayed withdrawal may occur as long as 6 days after birth. Sedative-hypnotics such as benzodiazepines and barbiturates have an even longer half-life, and withdrawal may not start until after the infant has been discharged from hospital (age 2 wk).

Methadone maintenance has been an acceptable form of therapy for opiate-dependent pregnant women since the late 1960s. This is currently the recommended treatment for opioid-dependent pregnant women; when properly used, methadone is considered relatively safe for the fetus. Methadone has been shown to decrease illicit behaviors, improve prenatal care and obstetric outcomes, and prevent acute maternal withdrawal that is associated with fetal death. [9] However, maternal methadone use is also associated with NAS, and its effects on the fetus are similar to the effects of heroin. Methadone's half-life is longer than 24 hours, and acute withdrawal may occur within the first 48 hours after birth and as long as 7-14 days later. The withdrawal may even be delayed for as long as 4 weeks after birth, with subacute signs developing as late as 6 months after birth. Neonates face an increased risk of fetal distress and demise, impaired fetal growth, and an increased risk of sudden infant death syndrome (SIDS). Thrombocytosis may occur in the second week of life and may continue until age 4 months.

The relationship between maternal methadone dosage and NAS is controversial, and the available data are conflicting. Several studies have showed that higher maternal doses are associated with an increase in the risk of preterm birth, the risk of symmetrically smaller infants, and longer hospital stays; the need for treatment for NAS indicates more significant withdrawal symptoms. [9, 10, 11] However, a more recent study showed that the incidence and duration of the NAS is not associated with maternal methadone dose. [12]

Buprenorphine, a semi-synthetic opioid, is a more recently approved medication for treating opioid addiction and dependence. The Suboxone and Subutex preparations were approved for this indication by the United States Food and Drug Administration (FDA) in October 2002. A review suggested that buprenorphine and methadone have comparable maternal efficacy. Although methadone seems superior in terms of retaining patients in treatment, infants who had prenatal exposure to buprenorphine required significantly less morphine for the treatment of NAS, a significantly shorter period of NAS treatment, and a significantly shorter hospital stay than did infants with prenatal exposure to methadone. [13, 14]

The relationship between maternal buprenorphine dose and either NAS incidence or severity has been inconsistent. Secondary analysis study of data from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study failed to support any relationship between maternal buprenorphine dose at delivery and NAS severity, total amount of morphine needed to treat NAS, duration of treatment, or duration of hospital stay. [15]  A more recent study indicated that polysubstance exposure was the most potent predictor of NAS severity in a group of buprenorphine-exposed neonates; there was a positive association between maternal buprenorphine dose and lower infant birth weight and length. [16] In another study, preliminary findings suggest that although marijuana exposure in the third trimester does not appear to complicate the pregnancy or the delivery process, such exposure may impact the severity of NAS, particularly the likelihood of needing pharmacologic therapy for NAS and the duration of hospital stay. [17]

Cocaine and amphetamines are stimulants with potent vasoconstrictor effects that stimulate the release and block the reuptake of the neurotransmitters dopamine, epinephrine, norepinephrine, and serotonin.

Cocaine, a potent CNS stimulant, alters the major neurotransmitters and rapidly crosses the placenta. Neurobehavioral abnormalities frequently occur in neonates with intrauterine cocaine exposure, most frequently on day 2-3 postnatally. Because cocaine or its metabolites may be detected in neonatal urine up to 7 days after delivery, [18] observed abnormalities in exposed infants may reflect drug effect rather than withdrawal. Early studies suggested neonates exposed to cocaine exhibited a hyperactive Moro reflex, jitteriness, and excessive sucking. More recent studies do not support that neonates exposed to cocaine differ behaviorally from unexposed infants. The unresolved question is whether cocaine acts to limit head growth or disrupt brain development. A synergistic effect between cocaine and other CNS toxins is still possible.

Methylxanthine accumulates in the blood of breastfed infants whose mothers regularly consume caffeine substances. Nicotine is transferred through the placenta and may reach concentrations 15% higher than maternal levels. In utero exposure impairs neonatal habituation, orientation, autonomic regulation, and orientation to sound. Exposure also affects the infant's ability to be comforted and is associated with exaggerated startle reflex and tremor.

No evidence suggests neonatal withdrawal problems associated with maternal use of marijuana during pregnancy. Fetal exposure to marijuana has been associated with hypoglycemia, hypocalcemia, sepsis, hypoxic encephalopathy, intracranial hemorrhage, and jitteriness. Effects on the fetus depend on the dose, with evidence of intrauterine growth retardation (IUGR) noted in cases of heavier usage.

Neonates exposed to marijuana while in utero may also exhibit signs of nicotine toxicity, such as tachycardia, poor perfusion, irritability, and poor feeding. Growth inhibition is pronounced at birth and affects weight, length, and head circumference. Catch-up growth occurs within the first year in each growth category. Cognitive effects may persist to school age. However, withdrawal symptoms are generally not noted in infants in the newborn period. Extended follow-up does not show any effect in children aged 5-6 years.

Several studies have demonstrated that maternal cigarette smoking during pregnancy increases the risk of having a low birth weight infant. [19] Neonates born to mothers who smoke during pregnancy weigh an average of 150-250 g less at birth than neonates born to mothers who do not smoke during pregnancy. Research findings also suggest that infants of mothers who smoke during pregnancy may develop nicotine withdrawal in a pattern that is related to the magnitude of in utero exposure. Infants who have been exposed to tobacco have been found to be more excitable and hypertonic and demonstrate more stress and abstinence signs.

Neonates exposed to antidepressant medications during gestation are at increased risk of NAS. Selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine, paroxetine, sertraline, citalopram, escitalopram, and fluvoxamine) are now the most frequently used drugs to treat depression both in the general population and in pregnant women, and they are also used to treat a wide spectrum of other mood and behavioral disorders. Infants exposed to SSRIs during the last trimester of pregnancy may exhibit neonatal adaptation syndrome. This is primarily manifested as CNS signs (eg, irritability, seizure), motor signs (eg, agitation, tremors, hypertonia), respiratory (eg, increased respiratory rate, nasal congestion), and GI signs (eg, emesis, diarrhea, feeding difficulty), fever, and hypoglycemia. [20] The onset of these signs ranges from several hours to several days after birth, and they are self-limiting, usually disappear by age 2 weeks. Symptoms are more commonly reported with fluoxetine and paroxetine exposure.

A prospective study showed no statistically significant differences between tricyclic antidepressants and SSRIs. It also revealed that women using antidepressants often use other medications as well during pregnancy, making the interpretation of antidepressant withdrawal symptoms difficult. A decrease in maternal SSRI and tricyclic antidepressant use during the third trimester may lower the neonatal risk of developing withdrawal syndrome; however, this needs to be balanced against the harmful effects of depression during pregnancy.

A case has been reported in which maternal tianeptine (atypical antidepressant) dependence during pregnancy appeared to induce a type of NAS that mimics opiate NAS. [21]

Etiology

The current resurgence in heroin use is associated with the introduction of a cheap, smokeable form that is comparable to crack cocaine, only more potent. Cocaine's current popularity is related to increased availability and the presence of newer, cheaper forms.

Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal abstinence syndrome.

Epidemiology

United States data

Neonatal drug withdrawal is a common problem in populations in which drugs taken for therapeutic, recreational, or addiction purposes are readily available to pregnant women. However, the incidence is difficult to determine because it is not uniformly tracked, [1] because of unreliable histories of maternal drug abuse, and because of limited health provider skills in eliciting drug histories and diagnosing nonopiate drug exposure in the newborn period. In addition, maternal use of more than one drug makes ascribing a given effect on the neonate to a specific drug difficult. One reported estimate was 3.39 per 1,000 hospital births (13,500 newborns). [1]

In the United States, substance use among pregnant and postpartum women is a public health issue. An estimated one third of childbearing women take prescription opioids. [22]  A pooled analysis of data from the 2009-2013 National Survey on Drug Use and Health (NSDUH) revealed 0.9% of pregnant women met criteria for opioid analgesics, and 0.2% met the criteria for heroin. [1]

Between 2004 and 2013, neonatal abstinence syndrome (NAS) quadrupled and hospital length of stay increased from 13 days to 19 days, resulting in 7-fold increases neonatal intensive care unit stays for NAS. [22]

In 2011-2012, the NSDUH in the United States found that 5.9% of pregnant women aged 15-44 years reported using illicit drugs, compared with 10.7% of nonpregnant women in this age group. [23] The rate of illicit drug use among pregnant women aged 15-17 years was 18.3%, 9% among pregnant women aged 18-25 years, and 3.4% among pregnant women aged 26-44 years. [23]

In the 2013 report, among pregnant women aged 15-44 years, an estimated 8.5% reported current alcohol use, 2.7% reported binge drinking, and 0.3% reported heavy drinking. These rates were lower than the rates for nonpregnant women in the same age group (55.5, 24.7, and 5.2%, respectively). [23] In the same report, first trimester consumption was 17.9%, compared with significantly lower reporting during the second (4.2%) and third (3.7%) trimesters.

According to data from the Treatment Episode Data Set (TEDS), the proportion of female substance abuse treatment admissions aged 15 to 44 who were pregnant at treatment entry remained relatively stable between 2000 and 2010 (4.4 and 4.8 percent). However, there were shifts in the types of substances reported by these treatment admissions. The percentage of pregnant admissions reporting alcohol abuse (with or without drug abuse) decreased from 46.6 percent in 2000 to 34.8 percent in 2010, and the percentage reporting drug abuse but not alcohol abuse increased from 51.1 percent in 2000 to 63.8 percent in 2010. [24]

About 1 in 6 pregnant women aged 15-44 years had smoked cigarettes in the past month, based on combined data for 2011 and 2012. The rate of past-month cigarette use was lower among those who were pregnant (15.9%) than it was among those who were not pregnant (24.6%). This pattern was also evident among women aged 18-25 years (20.9 vs. 28.2 for pregnant and nonpregnant women, respectively) and among women aged 26-44 years (12.5 vs. 25.2, respectively). However, among those aged 15-17 years, the rate of cigarette smoking was higher for pregnant women than nonpregnant women (22.7% vs 13.4%). [23]

Data from the 2009 NSDUH report provide indirect evidence of dramatic increases in the prevalence of substance use following childbirth. Marijuana use was higher for recent mothers with children younger than 3 months in the household (3.8%) than for women in the third trimester of pregnancy (1.4%), suggesting resumption of use among mothers in the first 3 months after childbirth. [25]

Overall the incidence of drug-exposed newborns is reportedly 3-50%, depending on the specific patient population, with urban centers usually reporting higher rates. An estimated 10–11% of the 4.1 million live births (in 2005) involved prenatal exposure to alcohol or illegal drugs. When tobacco data are included more than one million children are affected by prenatal exposure. Among offspring exposed to opioids or heroin in utero, withdrawal signs develop in 55-94%.

Patrick et al reported that from 2000-2009, the rate of newborns diagnosed with NAS increased from 1.20 (95% CI, 1.04-1.37) to 3.39 (95% CI, 3.12-3.67) per 1000 hospital births per year. During the same period, total hospital charges for NAS are estimated to have increased from $190 million (95% CI, $160-$230 million) to $720 million (95% CI, $640-$800 million), adjusted for inflation. In 2009, the estimated number of newborns with NAS was 13,539 (95% CI, 12 441-14 635) or approximately 1 infant born per hour in the United States with signs of drug withdrawal. [6]

International data

No accurate data are available concerning worldwide incidence. Data from the UK Advisory Council on the Misuse of Drugs suggests 6,000 babies are born to mothers who abuse drugs each year (1% of all UK deliveries). [26, 27] In the past, heroin was the most commonly abused drug. Women are now more likely to use cocaine, methadone, or more than one illicit drug.

In Europe, each year as many as 30,000 pregnant women use opioids, and the number of pregnant women using drugs other than opioids may be equally as high. [28]

In Canada, 3 of every 1,000 babies born from 2009–2010 had NAS. [29]

In Australia, the incidence of NAS as a discharge diagnosis decreased from 5.07 per 1000 live births in 2002, to 3.18 in 2011. [30]

Race- and age-related demographics

Pregnant white women and Hispanic women had lower rates of illicit drug use (4.4% and 3%, respectively) than black women (8%). [31] Among women aged 15-44 years, the rate of cigarette use is higher among pregnant white women than among pregnant black or pregnant Hispanic women. [31]

Rates of substance use among pregnant women vary by age group, with past-month illicit drug and alcohol use highest among teenagers. The rate of illicit drug use among pregnant women aged 15-17 years was 16.2%, was 7.4% among pregnant women aged 18-25 years, and was 1.9% among pregnant women aged 26-44 years. [23]

Prognosis

Infants born to mothers who are chemically dependent face not only the experience of sudden withdrawal from poly intoxicants but also other medical and social challenges. Prognosis widely varies and depends on the family, socioeconomic variables, and whether either or both parents continue to use illicit drugs. A home environment with an addicted mother is a compromising variable.

Irner et al showed that children of mothers ceasing or decreasing their use of substances up to time of the birth delivered healthier babies than the mothers who continued to use substances. In addition, their results indicated that early intervention, including treatment of addiction during pregnancy, prenatal care, and psychosocial support, can help to prevent some developmental defects of newborn children of substance-using mothers. [32]

Long-term problems of children exposed to illicit drugs in utero include adverse neurodevelopmental outcomes. Lower intelligence quotient scores have been reported in children with in utero exposure to cocaine or methadone. Speech, perceptual, and cognitive disturbances have been reported in toddlers who were exposed to opiates. Difficulties with expressive language articulation have been reported in children of mothers who abused cocaine. Behavioral problems are also reported in children of mothers who have taken illicit substances in pregnancy. These include lower levels of learning and adapting to new situations; higher sensitivity to their environment resulting in irritability, agitation, aggression, poor social skills; and a lack of imitative play and late emergence of symbolic play.

In utero opioid exposure may have the potential to also affect gastrointestinal tract and the gut biome, which, in turn, may impair immunity and protection against pathogens, thereby affecting health over the long term. [33]

Prenatal exposure to marijuana has been associated with increased levels of depression during childhood. [34] Another study showed increased hyperactivity, impulsivity, inattention symptoms, and delinquency has been associated with prenatal marijuana use. [35]

The severity of withdrawal signs, including seizures, has not been proven to be associated with differences in long-term outcome after intrauterine drug exposure. Furthermore, treatment of drug withdrawal may not alter the long-term outcome.

Morbidity/mortality

Death is rarely associated with withdrawal alone but occurs as a consequence of prematurity, infection, and severe perinatal asphyxia.

Long-term mortality rate is likely to be extremely low, although the risk for SIDS is significantly higher among infants who are exposed to opiates. Infants exposed to methadone have a 3.7-fold higher risk of SIDS compared with controls. Infants exposed to cocaine have a 2.3-fold higher risk for SIDS compared with infants with no exposure. This increased risk is related to a complex interplay of factors; the compromised home environment associated with a mother who is drug addicted is an important variable.

Prenatal opioid exposures may cause birth defects, altered brain development and neonatal abstinence syndrome. [2, 22]

Complications

Narcotics may have a direct effect on the development of the respiratory center in the brain stem, but an adverse effect of opiates on long-term postnatal growth is not evident. In longitudinal studies, developmental sequelae have not been proven. Problems with habituation, visual and auditory responsiveness, and interactive patterns have been observed in the first months of life.

1. National Association of State Alcohol and Drug Abuse Directors, Inc (NASADAD). Neonatal abstinence syndrome. June 2015. Available at http://nasadad.wpengine.com/wp-content/uploads/2015/06/NAS-Fact-Sheet-Final.pdf.

2. Stover MW, Davis JM. Opioids in pregnancy and neonatal abstinence syndrome. Semin Perinatol. 2015 Nov. 39(7):561-5. [QxMD MEDLINE Link].

3. Chana S, Anand K. Can we use methadone for analgesia in neonates?. Arch Dis Child Fetal Neonatal Ed. 2001. 85:79-81. [QxMD MEDLINE Link]. [Full Text].

4. Franck LS, Vilardi J, Durand D, Powers R. Opioid withdrawal in neonates after continuous infusions of morphine or fentanyl during extracorporeal membrane oxygenation. Am J Crit Care. 1998 Sep. 7(5):364-9. [QxMD MEDLINE Link].

5. Substance Abuse and Mental Health Services Administration (SAMHSA). Results from the 2013 National Survey on Drug Use & Health: summary of national findings. HHS publication no 14-4863. US Department of Health and Human Services. September 2014. Available at https://www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.pdf.

6. Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. JAMA. 2012 May 9. 307(18):1934-40. [QxMD MEDLINE Link].

7. Hytinantti T, Kahila H, Renlund M, Jarvenpaa AL, Halmesmaki E, Kivitie-Kallio S. Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero. Acta Paediatr. 2008 Aug. 97(8):1040-4. [QxMD MEDLINE Link].

8. Subedi L, Huang H, Pant A, et al. Plasma brain-derived neurotrophic factor levels in newborn infants with neonatal abstinence syndrome. Front Pediatr. 2017. 5:238. [QxMD MEDLINE Link].

9. Lim S, Prasad MR, Samuels P, Gardner DK, Cordero L. High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome. Am J Obstet Gynecol. 2009 Jan. 200(1):70.e1-5. [QxMD MEDLINE Link].

10. Dryden C, Young D, Hepburn M, Mactier H. Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources. BJOG. 2009 Apr. 116(5):665-71. [QxMD MEDLINE Link].

11. Wouldes TA, Woodward LJ. Maternal methadone dose during pregnancy and infant clinical outcome. Neurotoxicol Teratol. 2010 May-Jun. 32(3):406-13. [QxMD MEDLINE Link].

12. Cleary BJ, Eogan M, O'Connell MP, et al. Methadone and perinatal outcomes: a prospective cohort study. Addiction. 2012 Aug. 107(8):1482-92. [QxMD MEDLINE Link].

13. Minozzi S, Amato L, Bellisario C, Ferri M, Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst Rev. 2013. 12:CD006318. [QxMD MEDLINE Link].

14. National Institutes of Health. Buprenorphine treatment in pregnancy: less distress to babies. December 9, 2010. Available at http://www.nih.gov/news/health/dec2010/nida-09.htm.

15. Jones HE, Dengler E, Garrison A, et al. Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy. Drug Alcohol Depend. 2014 Jan 1. 134:414-7. [QxMD MEDLINE Link].

16. Jansson LM, Velez ML, McConnell K, et al. Maternal buprenorphine treatment and infant outcome. Drug Alcohol Depend. 2017 Nov 1. 180:56-61. [QxMD MEDLINE Link].

17. O'Connor AB, Kelly BK, O'Brien LM. Maternal and infant outcomes following third trimester exposure to marijuana in opioid dependent pregnant women maintained on buprenorphine. Drug Alcohol Depend. 2017 Nov 1. 180:200-3. [QxMD MEDLINE Link].

18. Kandall SR. Treatment strategies for drug-exposed neonates. Clin Perinatol. 1999 Mar. 26(1):231-43. [QxMD MEDLINE Link].

19. Law KL, Stroud LR, LaGasse LL, et al. Smoking during pregnancy and newborn neurobehavior. Pediatrics. 2003 Jun. 111(6 Pt 1):1318-23. [QxMD MEDLINE Link]. [Full Text].

20. Haddad PM, Pal BR, Clarke P, Wieck A, Sridhiran S. Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome?. J Psychopharmacol. 2005 Sep. 19(5):554-7. [QxMD MEDLINE Link].

21. Bence C, Bonord A, Rebillard C, et al. Neonatal abstinence syndrome following tianeptine dependence during pregnancy. Pediatrics. 2016 Jan. 137(1):[QxMD MEDLINE Link].

22. Anand KJ, Campbell-Yeo M. Consequences of prenatal opioid use for newborns. Acta Paediatr. 2015 Nov. 104 (11):1066-9. [QxMD MEDLINE Link].

23. Substance Abuse and Mental Health Services Administration. Results from the 2012 National Survey on Drug Use and Health: summary of national findings. HHS publication no 13-4795. US Department of Health and Human Services. September 2013. Available at http://www.samhsa.gov/data/NSDUH/2012SummNatFindDetTables/NationalFindings/NSDUHresults2012.htm#ch2.6.

24. Trends in Substances of Abuse among Pregnant Women and Women of Childbearing Age in Treatment. July 2013. Available at http://www.samhsa.gov/data/spotlight/spot110-trends-pregnant-women-2013.pdf.

25. Substance Abuse and Mental Health Services Administration (SAMHSA). National Survey on Drug Use and Health: the NSDUH report. Substance use among women during pregnancy and following childbirth. May 21, 2009. Available at http://archive.samhsa.gov/data/2k9/135/PregWoSubUse.htm.

26. Cairns PA. Drug misuse: Conception into childhood. Current Paediatrics. 2001 December. 11(6):475-9.

27. Prentice S. Substance misuse in pregnancy. Obstetrics, Gynaecology & Reproductive Med. 2007 September. 17:272-7.

28. Gyarmathy VA, Giraudon I, Hedrich D, Montanari L, Guarita B, Wiessing L. Drug use and pregnancy - challenges for public health. Euro Surveill. 2009 Mar 5. 14(9):33-6. [QxMD MEDLINE Link]. [Full Text].

29. Finnegan L. Licit and illicit drug use during pregnancy: maternal, neonatal and early childhood consequences. Substance Abuse in Canada. 2013. Available at http://www.ccsa.ca/Resource%20Library/CCSA-Drug-Use-during-Pregnancy-Report-2013-en.pdf.

30. Uebel H, Wright IM, Burns L, Hilder L, Bajuk B, Breen C, et al. Epidemiological Evidence for a Decreasing Incidence of Neonatal Abstinence Syndrome, 2000–11. Paediatr. Perinat. Epidemiol. February 2016. 30:267–273.

31. Substance Abuse and Mental Health Services Administration (SAMHSA). National Survey on Drug Use and Health: the NSDUH report. Substance use during pregnancy: 2002 and 2003 update. June 2, 2005. Available at http://archive.samhsa.gov/data/2k5/pregnancy/pregnancy.pdf.

32. Irner TB, Teasdale TW, Nielsen T, Vedal S, Olofsson M. Substance use during pregnancy and postnatal outcomes. J Addict Dis. 2012 Jan. 31(1):19-28. [QxMD MEDLINE Link].

33. Maguire D, Groer M. Neonatal abstinence syndrome and the gastrointestinal tract. Med Hypotheses. 2016 Dec. 97:11-15. [QxMD MEDLINE Link].

34. Gray KA, Day NL, Leech S, Richardson GA. Prenatal marijuana exposure: effect on child depressive symptoms at ten years of age. Neurotoxicol Teratol. 2005 May-Jun. 27(3):439-48. [QxMD MEDLINE Link].

35. Goldschmidt L, Day NL, Richardson GA. Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol. 2000 May-Jun. 22(3):325-36. [QxMD MEDLINE Link].

36. Lester BM, ElSohly M, Wright LL, et al. The Maternal Lifestyle Study: drug use by meconium toxicology and maternal self-report. Pediatrics. 2001 Feb. 107(2):309-17. [QxMD MEDLINE Link].

37. [Guideline] American Academy of Pediatrics Committee on Substance Abuse. Drug-exposed infants. Pediatr. 1995 Aug. 96(2 Pt 1):364-7. [QxMD MEDLINE Link].

38. Doberczak TM, Kandall SR, Wilets I. Neonatal opiate abstinence syndrome in term and preterm infants. J Pediatr. 1991 Jun. 118(6):933-7. [QxMD MEDLINE Link].

39. Liu AJ, Jones MP, Murray H, Cook CM, Nanan R. Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy. Aust N Z J Obstet Gynaecol. 2010 Jun. 50(3):253-8. [QxMD MEDLINE Link].

40. [Guideline] Hudak ML, Tan RC; Committee on Drugs; Committee on Fetus and Newborn; American Academy of Pediatrics. Neonatal drug withdrawal. Pediatrics. 2012 Feb. 129(2):e540-60. [QxMD MEDLINE Link]. [Full Text].

41. Finnegan LP. Neonatal abstinence syndrome: assessment and pharmacolotherapy. Neonatal therapy: An update. New York, NY: Excerpta Medica; 1986. 122-46.

42. Ostrea EM, Ostrea AR, Simpson PM. Mortality within the first 2 years in infants exposed to cocaine, opiate, or cannabinoid during gestation. Pediatrics. 1997 Jul. 100(1):79-83. [QxMD MEDLINE Link]. [Full Text].

43. Lester BM, Tronick EZ. History and description of the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Pediatrics. 2004 Mar. 113(3 Pt 2):634-40. [QxMD MEDLINE Link].

44. Timpson W, Killoran C, Maranda L, Picarillo A, Bloch-Salisbury E. A quality improvement initiative to increase scoring consistency and accuracy of the Finnegan tool: challenges in obtaining reliable assessments of drug withdrawal in neonatal abstinence syndrome. Adv Neonatal Care. 2017 Oct 17. [QxMD MEDLINE Link].

45. US Department of Health and Human Services. The Child Abuse Prevention and Treatment Act: including adoption opportunities & the Abandoned Infants Assistance Act. As amended by the Keeping Children and Families Safe Act of 2003. June 25, 2003. Available at https://www.acf.hhs.gov/sites/default/files/cb/capta2003.pdf.

46. Jaudes PK, Ekwo E, Van Voorhis J. Association of drug abuse and child abuse. Child Abuse Negl. 1995 Sep. 19(9):1065-75. [QxMD MEDLINE Link].

47. Smith DK, Johnson AB, Pears KC, Fisher PA, DeGarmo DS. Child maltreatment and foster care: unpacking the effects of prenatal and postnatal parental substance use. Child Maltreat. 2007 May. 12(2):150-60. [QxMD MEDLINE Link].

48. Chasnoff IJ. Prenatal substance abuse. Neoreviews. 2003. 4(9):e228-e235.

49. Colby JM. Comparison of umbilical cord tissue and meconium for the confirmation of in utero drug exposure. Clin Biochem. 2017 Sep. 50 (13-14):784-790. [QxMD MEDLINE Link].

50. Montgomery DP, Plate CA, Jones M, et al. Using umbilical cord tissue to detect fetal exposure to illicit drugs: a multicentered study in Utah and New Jersey. J Perinatol. 2008 Nov. 28 (11):750-3. [QxMD MEDLINE Link].

51. Kassima Z, Greenough A. Neonatal abstinence syndrome: identification and management. Curr Paediatrics. 2006 June. 16:172-5.

52. Jones JT, Jones M, Jones B, Sulaiman K, Plate C, Lewis D. Detection of codeine, morphine, 6-monoacetylmorphine, and meconin in human umbilical cord tissue: method validation and evidence of in utero heroin exposure. Ther Drug Monit. 2015 Feb. 37(1):45-52. [QxMD MEDLINE Link].

53. Palmer KL, Wood KE, Krasowski MD. Evaluating a switch from meconium to umbilical cord tissue for newborn drug testing: A retrospective study at an academic medical center. Clin Biochem. 2017 Apr. 50 (6):255-261. [QxMD MEDLINE Link].

54. Gray T, Huestis M. Bioanalytical procedures for monitoring in utero drug exposure. Anal Bioanal Chem. 2007 Aug. 388(7):1455-65. [QxMD MEDLINE Link].

55. Frank DA, McCarten KM, Robson CD, Mirochnick M, Cabral H, Park H, et al. Level of in utero cocaine exposure and neonatal ultrasound findings. Pediatrics. 1999 Nov. 104 (5 Pt 1):1101-5. [QxMD MEDLINE Link].

56. van Huis M, van Kempen AA, Peelen M, et al. Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy. Pediatr Radiol. 2009 Mar. 39(3):232-8. [QxMD MEDLINE Link].

57. Rivkin MJ, Davis PE, Lemaster JL, Cabral HJ, Warfield SK, Mulkern RV, et al. Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco, and marijuana. Pediatrics. 2008 Apr. 121 (4):741-50. [QxMD MEDLINE Link].

58. Gibson KS, Stark S, Kumar D, Bailit JL. The relationship between gestational age and the severity of neonatal abstinence syndrome. Addiction. 2017 Apr. 112(4):711-16. [QxMD MEDLINE Link].

59. [Guideline] Jansson LM, Choo R, Velez ML, et al. Methadone maintenance and breastfeeding in the neonatal period. Pediatrics. 2008 Jan. 121(1):106-14. [QxMD MEDLINE Link].

60. [Guideline] American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. [published erratum appears in Pediatrics 1998 Sep;102(3 Pt 1):660]. Pediatrics. 1998 Jun. 101(6):1079-88. [QxMD MEDLINE Link].

61. [Guideline] American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Sep. 108(3):776-89. [QxMD MEDLINE Link].

62. ACOG Committee on Health Care for Underserved Women., American Society of Addiction Medicine. ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy. Obstet Gynecol. 2012 May. 119(5):1070-6. [QxMD MEDLINE Link]. [Full Text].

63. Anthony BE, Bryan BL. Neonatal abstinence syndrome. NeoReviews. 2009. 10(5):e222.

64. Hale TW. Pharmacology review: drug therapy and breastfeeding: antidepressants, antipsychotics, antimanics, and sedatives. NeoReviews. May 2004. e451-e456.

65. Lainwala S, Brown ER, Weinschenk NP, Blackwell MT, Hagadorn JI. A retrospective study of length of hospital stay in infants treated for neonatal abstinence syndrome with methadone versus oral morphine preparations. Adv Neonatal Care. 2005 Oct. 5(5):265-72. [QxMD MEDLINE Link].

66. McKnight S, Coo H, Davies G, Holmes B, Newman A, Newton L, et al. Rooming-in for Infants at Risk of Neonatal Abstinence Syndrome. Am J Perinatol. 2016 Apr. 33 (5):495-501. [QxMD MEDLINE Link].

67. Holmes AV, Atwood EC, Whalen B, et al. Rooming-in to treat neonatal abstinence syndrome: improved family-centered care at lower cost. Pediatrics. 2016 Jun. 137 (6):[QxMD MEDLINE Link].

68. McQueen K, Murphy-Oikonen J. Neonatal Abstinence Syndrome. N Engl J Med. 2016 Dec 22. 375 (25):2468-2479. [QxMD MEDLINE Link].

69. Young ME, Hager SJ, Spurlock D Jr. Retrospective chart review comparing morphine and methadone in neonates treated for neonatal abstinence syndrome. Am J Health Syst Pharm. 2015 Dec 1. 72 (23 suppl 3):S162-7. [QxMD MEDLINE Link].

70. Brown MS, Hayes MJ, Thornton LM. Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. J Perinatol. 2015 Apr. 35 (4):278-83. [QxMD MEDLINE Link].

71. Hall ES, Isemann BT, Wexelblatt SL, et al. A cohort comparison of buprenorphine versus methadone treatment for neonatal abstinence syndrome. J Pediatr. 2016 Mar. 170:39-44.e1. [QxMD MEDLINE Link].

72. Mucke S, Nagel M, Siedentopf J, Buhrer C, Huseman D. Neonatal abstinence syndrome: twelve years of experience at a regional referral center. Klin Padiatr. 2017 Jan. 229(1):32-9. [QxMD MEDLINE Link].

73. Tolia VN, Murthy K, Bennett MM, et al. Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome. J Perinatol. 2017 Oct 19. [QxMD MEDLINE Link].

74. Kraft WK, Adeniyi-Jones SC, Chervoneva I, Greenspan JS, Abatemarco D, Kaltenbach K, et al. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. N Engl J Med. 2017 Jun 15. 376 (24):2341-2348. [QxMD MEDLINE Link].

75. Wachman EM, Hayes MJ, Sherva R, et al. Variations in opioid receptor genes in neonatal abstinence syndrome. Drug Alcohol Depend. 2015 Oct 1. 155:253-9. [QxMD MEDLINE Link].

76. Wachman EM, Hayes MJ, Brown MS, et al. Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA. 2013 May 1. 309(17):1821-7. [QxMD MEDLINE Link].

77. Ryan G, Bimaadiziwin A, Dooley J, Finn LG, Kelly L. Nonpharmacological management of neonatal abstinence syndrome: A review of the literature. J Matern Fetal Neonatal Med. 2017 Dec 5. 1-121. [QxMD MEDLINE Link].

78. Hall ES, Wexelblatt SL, Crowley M, et al. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics. 2014 Aug. 134(2):e527-34. [QxMD MEDLINE Link].

79. Saiki T, Lee S, Hannam S, Greenough A. Neonatal abstinence syndrome--postnatal ward versus neonatal unit management. Eur J Pediatr. 2010 Jan. 169(1):95-8. [QxMD MEDLINE Link].

80. Backes CH, Backes CR, Gardner D, Nankervis CA, Giannone PJ, Cordero L. Neonatal abstinence syndrome: transitioning methadone-treated infants from an inpatient to an outpatient setting. J Perinatol. 2012 Jun. 32(6):425-30. [QxMD MEDLINE Link].

81. Jansson LM. ABM clinical protocol #21: Guidelines for breastfeeding and the drug-dependent woman. Breastfeed Med. 2009 Dec. 4(4):225-8. [QxMD MEDLINE Link]. [Full Text].

82. Grim K, Harrison TE, Wilder RT. Management of neonatal abstinence syndrome from opioids. Clin Perinatol. 2013 Sep. 40(3):509-24. [QxMD MEDLINE Link].

83. Agthe AG, Kim GR, Mathias KB, et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics. 2009 May. 123(5):e849-56. [QxMD MEDLINE Link]. [Full Text].

84. Sarkar S, Donn SM. Management of neonatal abstinence syndrome in neonatal intensive care units: a national survey. J Perinatol. 2006 Jan 1. 26(1):15-7. [QxMD MEDLINE Link].

85. Mazurier E, Cambonie G, Barbotte E, Grare A, Pinzani V, Picaud JC. Comparison of chlorpromazine versus morphine hydrochloride for treatment of neonatal abstinence syndrome. Acta Paediatr. 2008 Oct. 97(10):1358-61. [QxMD MEDLINE Link].

86. HR2634 - Drug Addiction Treatment Act of 2000 (DATA 2000). Congress.gov. Available at https://www.congress.gov/bill/106th-congress/house-bill/2634. July 27, 2000; Accessed: December 20, 2017.

87. Kraft WK, Gibson E, Dysart K, et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. 2008 Sep. 122(3):e601-7. [QxMD MEDLINE Link]. [Full Text].

88. Kraft WK, Adeniyi-Jones SC, Chervoneva I, Greenspan JS, Abatemarco D, Kaltenbach K, et al. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. N Engl J Med. 2017 Jun 15. 376 (24):2341-2348. [QxMD MEDLINE Link].

89. Kraft WK, Gibson E, Dysart K, et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. 2008 Sep. 122(3):e601-7. [QxMD MEDLINE Link]. [Full Text].

90. American Academy of Pediatrics. Pickering LK, Baker CJ, Long SS, McMillan JA, eds. The Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove, Illinois: American Academy of Pediatrics; 2006. [Full Text].

91. [Guideline] American Academy of Pediatrics Committee on Fetus and Newborn. The initiation or withdrawal of treatment for high-risk newborns. Pediatrics. 1995 Aug. 96(2 Pt 1):362-3. [QxMD MEDLINE Link].

92. Bahwere P, Haumont D, Delange F. Congenital hypothyroidism and neonatal withdrawal syndrome. Eur J Pediatr. 1996 Nov. 155(11):937-8. [QxMD MEDLINE Link].

93. Bauer CR. Perinatal effects of prenatal drug exposure. Neonatal aspects. Clin Perinatol. 1999 Mar. 26(1):87-106. [QxMD MEDLINE Link].

94. Boukydis CF, Lester BM. The NICU Network Neurobehavioral Scale. Clinical use with drug exposed infants and their mothers. Clin Perinatol. 1999 Mar. 26(1):213-30. [QxMD MEDLINE Link].

95. Buchi KF. The drug-exposed infant in the well-baby nursery. Clin Perinatol. 1998 Jun. 25(2):335-50. [QxMD MEDLINE Link].

96. Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr. 1986 Mar. 108(3):456-9. [QxMD MEDLINE Link].

97. Connolly WB Jr, Marshall AB. Drug addiction, pregnancy, and childbirth: legal issues for the medical and social services communities. Clin Perinatol. 1991 Mar. 18(1):147-86. [QxMD MEDLINE Link].

98. Franck L, Vilardi J. Assessment and management of opioid withdrawal in ill neonates. Neonatal Netw. 1995 Mar. 14(2):39-48. [QxMD MEDLINE Link].

99. Heier LA, Carpanzano CR, Mast J, Brill PW, Winchester P, Deck MD. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol. 1991 Sep-Oct. 12(5):951-6. [QxMD MEDLINE Link].

100. Johnson K, Gerada C, Greenough A. Treatment of neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed. 2003 Jan. 88(1):F2-5. [QxMD MEDLINE Link].

101. Jones HE, Heil SH, Baewert A, et al. Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review. Addiction. 2012 Nov. 107 Suppl 1:5-27. [QxMD MEDLINE Link].

102. Kallen B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med. 2004 Apr. 158(4):312-6. [QxMD MEDLINE Link]. [Full Text].

103. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy. Effects and management. Obstet Gynecol Clin North Am. 1998 Mar. 25(1):139-51. [QxMD MEDLINE Link].

104. Hagemeier NE, Click IA, Flippin H, et al. Pharmacists' and prescribers' neonatal abstinence syndrome (NAS) prevention behaviors: a preliminary analysis. Int J Clin Pharm. 2017 Dec 5. [QxMD MEDLINE Link].

105. Kuschel C. Managing drug withdrawal in the newborn infant. Semin Fetal Neonatal Med. 2007 Apr. 12(2):127-33. [QxMD MEDLINE Link].

106. McKim EM. Caffeine and its effects on pregnancy and the neonate. J Nurse Midwifery. 1991 Jul-Aug. 36(4):226-31. [QxMD MEDLINE Link].

107. Moses-Kolko EL, Bogen D, Perel J, et al. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA. 2005 May 18. 293(19):2372-83. [QxMD MEDLINE Link].

108. Oei J, Lui K. Management of the newborn infant affected by maternal opiates and other drugs of dependency. J Paediatr Child Health. 2007 Jan-Feb. 43(1-2):9-18. [QxMD MEDLINE Link].

109. Pierog S, Chandavasu O, Wexler I. Withdrawal symptoms in infants with the fetal alcohol syndrome. J Pediatr. 1977 Apr. 90(4):630-3. [QxMD MEDLINE Link].

110. Pritham UA. Breastfeeding promotion for management of neonatal abstinence syndrome. J Obstet Gynecol Neonatal Nurs. 2013 Sep-Oct. 42(5):517-26. [QxMD MEDLINE Link].

111. Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. 2005 Feb 5-11. 365(9458):482-7. [QxMD MEDLINE Link].

112. Ter Horst PG, Jansman FG, van Lingen RA, Smit JP, de Jong-van den Berg LT, Brouwers JR. Pharmacological aspects of neonatal antidepressant withdrawal. Obstet Gynecol Surv. 2008 Apr. 63(4):267-79. [QxMD MEDLINE Link].

113. Theis JG, Selby P, Ikizler Y, Koren G. Current management of the neonatal abstinence syndrome: a critical analysis of the evidence. Biol Neonate. 1997. 71(6):345-56. [QxMD MEDLINE Link].

114. Umans JG, Szeto HH. Precipitated opiate abstinence in utero. Am J Obstet Gynecol. 1985 Feb 15. 151(4):441-4. [QxMD MEDLINE Link].

115. Vance JC, Chant DC, Tudehope DI, et al. Infants born to narcotic dependent mothers: physical growth patterns in the first 12 months of life. J Paediatr Child Health. 1997 Dec. 33(6):504-8. [QxMD MEDLINE Link].

116. Wagner CL, Katikaneni LD, Cox TH, Ryan RM. The impact of prenatal drug exposure on the neonate. Obstet Gynecol Clin North Am. 1998 Mar. 25(1):169-94. [QxMD MEDLINE Link].

117. Young TE, Mangum B. CNS Drugs. Thomson Reuters clinical editorial staff. Neofax: A manual of drugs used in neonatal care. 22nd ed. Montvale, New Jersey: Thomson Reuters healthcare; 2009. 187-214.

118. Zeskind PS, Stephens LE. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics. 2004 Feb. 113(2):368-75. [QxMD MEDLINE Link].

119. Mbah AK, Alio AP, Fombo DW, Bruder K, Dagne G, Salihu HM. Association between cocaine abuse in pregnancy and placenta-associated syndromes using propensity score matching approach. Early Hum Dev. 2012 Jun. 88(6):333-7. [QxMD MEDLINE Link].

120. Holmes AV, Atwood EC, Whalen B, et al. Rooming-in to treat neonatal abstinence syndrome: improved family-centered care at lower cost. Pediatrics. 2016 Jun. 137(6):[QxMD MEDLINE Link].

121. Boucher AM. Nonopioid management of neonatal abstinence syndrome. Adv Neonatal Care. 2017 Apr. 17(2):84-90. [QxMD MEDLINE Link].

122. Reece-Stremtan S, Marinelli KA. ABM clinical protocol #21: guidelines for breastfeeding and substance use or substance use disorder, revised 2015. Breastfeed Med. 2015 Apr. 10(3):135-41. [QxMD MEDLINE Link].

123. Willford JA, Chandler LS, Goldschmidt L, Day NL. Effects of prenatal tobacco, alcohol and marijuana exposure on processing speed, visual-motor coordination, and interhemispheric transfer. Neurotoxicol Teratol. 2010 Nov-Dec. 32(6):580-8. [QxMD MEDLINE Link].

124. Lemon LS, Caritis SN, Venkataramanan R, Platt RW, Bodnar LM. Methadone versus buprenorphine for opioid use dependence and risk of neonatal abstinence syndrome. Epidemiology. 2017 Nov 6. [QxMD MEDLINE Link].

125. Devlin LA, Lau T, Radmacher PG. Decreasing total medication exposure and length of stay while completing withdrawal for neonatal abstinence syndrome during the neonatal hospital stay. Front Pediatr. 2017. 5:216. [QxMD MEDLINE Link]. [Full Text].

Author

Ashraf H Hamdan, MD, MBBCh, MSc, MRCP, FAAP Adjunct Associate Clinical Professor of Pediatrics, Vanderbilt University Medical Center; Neonatologist, Pediatrix Medical Group of Nashville

Ashraf H Hamdan, MD, MBBCh, MSc, MRCP, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Brian S Carter, MD, FAAP Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Attending Physician, Division of Neonatology, Children's Mercy Hospital and Clinics; Faculty, Children's Mercy Bioethics Center

Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Pediatric Society, American Society for Bioethics and Humanities, American Society of Law, Medicine & Ethics, Society for Pediatric Research, National Hospice and Palliative Care Organization

Disclosure: Nothing to disclose.

Chief Editor

Additional Contributors

Scott S MacGilvray, MD Clinical Professor, Department of Pediatrics, Division of Neonatology, The Brody School of Medicine at East Carolina University

Scott S MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Drugs & Diseases, gratefully acknowledge the contributions of previous authors Jaques Belik, MD, and Judy Hawes, RN, MN, to the writing and development of this article.

What are symptoms of neonatal abstinence syndrome?

What is the abstinence syndrome?

What is the 1st line of treatment indicated in infants presenting with neonatal abstinence syndrome?

What is one of the first signs of withdrawal?