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Abstinence Syndromes


Neonatal Abstinence (Withdrawal)

Scott L. Wexelblatt

Keywords

  • benzodiazepine

  • buprenorphine

  • cocaine

  • MAT

  • medication-assisted treatment

  • methadone

  • methamphetamine

  • NAS

  • neonatal abstinence syndrome

  • opioid

  • phenobarbital

Neonatal abstinence syndrome (NAS) is the clinical diagnosis given to infants who experience withdrawal signs after in utero exposure to opioids. Withdrawal signs develop in 55–94% of opioid-exposed infants, 30–65% of whom need pharmacologic treatment for severe withdrawal. The incidence of NAS has been increasing yearly since 2004 and was 5 times more prevalent in 2013 than 2004. This increase in NAS is caused by increased use of prescription medication by pregnant women, an increase in medication-assisted treatment (MAT) for opioid addiction, an increase in illicit use of prescription medications, and increased use of heroin. In 2011, 1.1% of pregnant women in the United States abused pain relievers and heroin, and up to 12.9–28% of women were prescribed an opioid at some point during their pregnancy. Many factors affect the severity and duration of withdrawal, including tobacco use during pregnancy, breastfeeding after delivery, rooming-in and parental involvement, genetic makeup, and polysubstance use.

The clinical signs of NAS result from central nervous system (CNS) hyperexcitability and autonomic instability ( Fig. 126.1 ). NAS signs can begin within 24 hr of birth after heroin exposure, within 48 hr after short-acting opioids, and 72-96 hr after exposure to long-acting opioids such as methadone and buprenorphine. Tremors, poor feeding, excessive crying, poor sleeping, and hyperirritability are the most prominent signs of NAS. Other signs include sneezing, yawning, hiccups, myoclonic jerks, skin breakdown and abrasions, vomiting, loose stools, nasal stuffiness, and seizures in the most severe cases.

Fig. 126.1, Neonatal abstinence score used for the assessment of infants displaying neonatal abstinence syndrome.

Identifying which infants are at risk for NAS before discharge is important because of the late onset of signs. Universal maternal screening for drug use is recommended by the American College of Obstetricians and Gynecologists (ACOG), and maternal consent should be obtained if drug testing is indicated. Universal maternal drug testing has been shown to improve identification of infants at risk for NAS but is more expensive and may not be helpful in states with punitive legislation. Maternal testing is preferred over infant testing because results are available promptly, typically by the time the infant is delivered. Testing mothers on admission to the hospital can also exclude iatrogenic exposure. Infant urine, meconium and umbilical cord testing are also used to help identify infants at risk for withdrawal and identify more distant use by the mother. Timing of these results and special collection methods makes routine use of these tests more difficult. Detectability in the neonatal urine specimen is typically 2-3 days for methadone (up to 6 days for methadone metabolites) and buprenorphine and 1-2 days for heroin.

MAT has been shown to be useful for pregnant women with an opioid substance use disorder. Mothers receiving MAT have a decreased mortality, reduced illicit drug use, reduced seroconversion of HIV, and decreased criminal activity. The most common medications in MAT are methadone or buprenorphine. Methadone is a full µ-opioid agonist with a half-life of 24-36 hr, given once daily in methadone clinics because of the potential for overdose. Buprenorphine is a partial µ-opioid agonist with a half-life of 36-48 hr, prescribed monthly as home therapy because a ceiling effect protects against overdosages.

Treatment

The first line of treatment for all opioid-exposed infants is nonpharmacologic support , which includes swaddling, placing the infant in a dark and quiet environment (e.g., dimmed lights, muted televisions), holding and Kangaroo care, reducing stimulation, and breastfeeding. Illicit (if continued) drug use is a contraindication to breastfeeding infants with NAS. Maternal methadone or buprenorphine use and hepatitis C are not contraindications to breastfeeding. Standardization of nonpharmacologic care with increased emphasis on clinical assessment(i.e., is the infant feeding well, sleeping well, and easily consoled?) over formal scoring tools, which typically require disturbing the infant, was associated with significantly less opioid use among infants with in utero methadone exposure.

The decision for pharmacologic treatment has been traditionally based on the nursing scoring assessment tool. The most widely used tools are the Finnegan and Modified Finnegan ( Fig. 126.1 ). Other scoring tools include the Lipsitz, Neonatal Narcotic Withdrawal Index, Neonatal Withdrawal Inventory, and MOTHER NAS Scale. The main objectives when initiating pharmacologic treatment are to improve signs and comfort of the infant and to prevent worsening withdrawal that could lead to seizures.

Pharmacologic treatment for NAS, when necessary, is typically morphine or methadone ( Table 126.1 ). Morphine is a short-acting opioid given every 3-4 hr as a weight-based or symptom-based regimen. Methadone is long-acting opioid that can be given twice a day after loading doses, and a pharmacokinetic weight-based weaning protocol is available. Sublingual buprenorphine has been proposed as an alternate treatment. Buprenorphine and some methadone formulations contain high ethanol levels, which may be deleterious to the infant. Following a stringent NAS protocol with guidelines on initiation and weaning has been shown to decrease both length of stay and number of opioid treatment days and may be as important as which primary opioid is used for first-line treatment.

Table 126.1
Medications Used in Pharmacologic Treatment of Neonatal Abstinence Syndrome (NAS)
DRUG INITIAL DOSING DOSING INCREASES WEANING SCHEDULE ADD ADJUVANT THERAPY
Morphine 0.05 mg/kg/dose q3h Increase dose 10–20% 10% of stabilizing dose q24h >1 mg/kg/day of morphine
Unable to wean for 2 days
Methadone 0.1 mg/kg/dose q6h for 4 doses Increase to q4h if unable to capture 0.7 mg/kg/dose q12h × 2 doses, then 0.05 mg/kg/dose q12h × 2;
0.04 mg/kg/dose q12h × 2;
0.03 mg/kg/dose q12h × 2;
0.02 mg/kg/dose q12h × 2;
0.01 mg/kg/dose q12h × 2;
0.01 mg/kg/dose q24h × 1		 Unable to wean for 2 days
Buprenorphine 4 µg/kg q8h 2 µg/kg until maximum of 15 µg/kg 3 µg/kg/dose q8h × 3 doses;
2 µg/kg/dose q8h × 3;
2 µg/kg/dose q8h × 2;
2 µg/kg/dose q24h × 1		 Unable to wean for 2 days
Phenobarbital 20 mg/kg — 5 mg/kg daily N/A
Clonidine 1.5 µg/kg/dose q3h 25% dose escalation q24hr 10% every day N/A
N/A, Not available; q24h, every 24 hours.

Adjuvant therapy is initiated when the primary opioid is not effective in controlling the signs of NAS. The 2 most common medications used as adjuvant therapy are phenobarbital and clonidine . Infants with NAS may also expend additional energy. Therefore, the infant should be weighted regularly and strategies to increase caloric intake implemented if weight loss beyond that expected in the 1st week of life occurs.

The long-term prognosis for infants with NAS is multifactorial and not fully known. Close follow-up needs to be initiated to monitor growth and development, visual disturbances, and behavioral/learning problems.

Phenobarbital and benzodiazepine withdrawal may occur in infants of mothers addicted to these drugs, but signs are self-limiting and do not require pharmacologic treatment. Signs may be late onset and begin at a median age of 7 days (range: 2-14 days). Infants may have a brief acute stage consisting of irritability, constant crying, sleeplessness, hiccups, and mouthing movements, followed by a prolonged stage consisting of increased appetite, frequent spit-ups and gagging, irritability, sweating, and a disturbed sleep pattern, all of which may last for weeks.

Cocaine and methamphetamine abuse in pregnant women is less common than opioid abuse, and acute withdrawal in these infants is unusual. However, labor complications can be severe with both drugs and may include preterm labor, placental abruption, intrauterine growth restriction, and fetal asphyxia. Detection in neonatal urine is 6-8 hr for cocaine and 1-2 days for methamphetamine. Early on, exposed infants may have abnormal sleep patterns, poor feeding, tremors, and hypertonia. Long-term outcomes include impaired auditory information processing, developmental delay, and learning disabilities. At age 4 yr, children exposed prenatally to cocaine demonstrate cognitive impairments and are less likely to have an IQ above the normative mean.

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Maternal Selective Serotonin Reuptake Inhibitors and Neonatal Behavioral Syndromes

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