Introduction

Neonatal abstinence syndrome (NAS) is recognized as the effect of intrauterine exposure to substances that can cause physical dependence.¹ In other words, it is withdrawal of the neonate from substances that the mother ingested during pregnancy. Addiction is a behavior-related problem, which is different from physical dependence. It is important to distinguish between addiction and physical dependence. Babies are born physically dependent on substances (particularly opiates) and can become seriously ill due to abrupt discontinuation of them. However, babies are NOT born addicted to drugs. Opiate withdrawal is the most common and most studied withdrawal syndrome. For purposes of this chapter, NAS will refer to opiate withdrawal.

The incidence of NAS following in utero exposure is reported between 55 and 94%.² From 2000 to 2009, a three-fold increase in the incidence was reported.³ This correlates to the reported five-fold increase in opiate use during pregnancy over the last 10 years.⁴ One study found that although infants born to substance-abusing mothers accounted for 2.9% of hospital births, they accounted for 18.2% of neonatal intensive care bed days demonstrating the economic burden this problem can create.⁵ Furthermore, long hospital stays can disrupt family life and affect an infant’s attachment to his or her parents.⁶

NAS is associated with chronic use at or near the time of delivery. If more than 2 weeks have passed since the last exposure, then withdrawal in the newborn is unlikely. Onset of withdrawal can range from 3 to 14 days and varies depending on several factors, including half-life of the substance and time of last exposure. The American Academy of Pediatrics (AAP) Policy Statement on NAS recommends that infants exposed to short-actingopiates (e.g., hydrocodone, oxycodone) be monitored for 3 to 5 days for signs and symptoms of NAS and those exposed to longer acting opiates (e.g., methadone) be monitored for 7 days prior to discharge from the hospital.⁷ If a baby requires treatment, lengths of stay vary greatly. Most infants are treated in an inpatient setting until pharmacologic treatment is complete, but some are discharged to home to complete their treatment.

Substances of Abuse

There are multiple substances of abuse, and many users will abuse more than one substance leading to multiple exposures in the infant. Marijuana may be one of the most frequently abused substances, but its use is not associated with withdrawal in infants. Because cocaine causes a psychological addiction but does not result in a physical dependence, it is not associated with withdrawal in infants. When cocaine is used in conjunction with opiates, symptoms associated with the opiate withdrawal may be worsened. Maternal opiate and benzodiazepine use are both associated with withdrawal in the neonate.

Serotonin reuptake inhibitors (SSRIs) are not associated with NAS. The irritability that results from maternal SSRI use is referred to by some as serotonin discontinuation syndrome.⁷ This self-limiting condition occurs early after birth with symptoms mimicking NAS and usually resolves in 48 to 72 hours of life. Rather than withdrawal, this syndrome is thought to be associated with the drug’s direct effect and symptom resolution correlates with drug excretion.

It is important to note that not all NAS is a result of illicit or recreational drug use. As women delay having children to a later stage of life, more women are getting pregnant while dealing with chronic medical conditions. Infants born to women who are taking prescribed opiates for chronic pain conditions may develop NAS and, therefore, need to be observed.

Opiate maintenance therapy (particularly methadone) is associated with more frequent and more severe withdrawal in the neonate than active drug abuse or illicit drug use.⁸ Maintenance therapy is preferred in pregnant women because it stabilizes the mother’s lifestyle, reduces risk-taking behavior, and decreases the incidence of preterm birth and intrauterine growth restriction. Buprenorphine use for opiate addiction management in pregnancy has been associated with less severe NAS and decreased overall treatment dose in the infant than methadone but may not be an acceptable alternative for all substance abusers.^8–11 Women in opiate maintenance therapy should not attempt to wean from their medication during pregnancy.¹² Contrarily, they often require dose increases as their pregnancy progresses.

Screening and Scoring

Different tools can be used for screening for maternal substance abuse. Testing of the newborn’s urine is of use only when collected in the early post-delivery hours. Meconium, the first stool passed by a newborn, is a good source for screening and gives a broader picture of exposure throughout the later stages of pregnancy. Hair and umbilical cord can also be used for screening. One should pay close attention to what is screened for at the institution as these tests have different panels associated with them. Be aware that opiate screens look only for natural opiates such as morphine, codeine, and heroin. Exposure to methadone, a synthetic opiate, can lead to a negative opiate screen. Methadone and other synthetic opiates (e.g., oxycodone) must be tested for specifically in order to capture them.

Symptoms of NAS can be categorized as respiratory, gastrointestinal (GI), or central nervous system (CNS) symptoms.^4,6,7 Respiratory symptoms include tachypnea, sneezing, nasal flaring, and nasal stuffiness. GI symptoms include excessive sucking, poor feeding, regurgitation, and watery diarrhea. CNS symptoms include excessive high-pitched cry, sleep disturbance, tremors, increased tone, and convulsions. Following treatment and/or hospital discharge, subclinical symptoms may persist for weeks or months.

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