Neonatal Abstinence Syndrome

Introduction

Neonatal abstinence syndrome (NAS) is a spectrum of neonatal behavioral dysregulation most closely associated with withdrawal from in utero exposure to:

  • Opioids
  • Alcohol
  • Benzodiazepines
  • Nicotine
  • Antipsychotics

 

Epidemiology

  • Opioid use in 5.6/1,000 births: most commonly heroin and methadone, but prescription drug abuse is rising fastest.

  • NAS in 3.39/1,000 hospital births

  •  Risk factors for opioid use and NAS:

  • Late or missed prenatal care, obstetric complications
  • Other children not living with mother, other children with neurological/behavioral issues
  • Partner or family members with substance abuse
  • Overall highest risk: young, unmarried, lower education levels

Symptoms

  • Irritability with high-pitched cry
  • Motor and tone: hypertonic, hyperactive primitive reflexes, tremors
  • GI: feeding difficulties, vomiting, diarrhea, and failure to thrive
  • Other autonomic dysfunction: sweating, sneezing, fever, nasal stuffiness, yawning
  • Abnormal EEG in over 30% and seizures in 2-11%
  • Small for gestational age

Of note, NAS is less likely to be seen in the more premature the infant is. Hypotheses for this include:  

  • Immature neurological development has blunted response to withdrawal
  •   Atypical presentation is underdiagnosed
  •  Less total in utero exposure

Diagnosis

Diagnosis is made with known (or highly suspected) maternal exposure and neonatal clinical signs

Universal prenatal screening for opioid exposure is recommended by history taking alone. Urine toxicology is indicated only if there is a known history of substance abuse, suspicious obstetric complication, or unexplained fetal death.

When a neonate presents with symptoms of NAS, it is important to rule out other etiologies: hypocalcemia, hypoglycemia, hypoxic-ischemic encephalopathy, sepsis, and hypothyroid.

Care of the infant

1. Identify the drug, timing, and amount of last maternal use in order to predict timing and likelihood of NAS. 

  • Decreased likelihood of NAS if last use occured greater than 1 week ago      
  •  Heroin has the shortest half-life; withdrawal typically within 24 hours
  • Methadone half-life is 24-72hrs
  • Delayed presentation may occur as late as up to 4wks

2. Observe for a minimum four days if known opioid exposure in order to monitor for NAS symptoms, and assess for IUGR, inaccurate gestational age, and congenital infection, (due to increased risk). 

3. Supportive Care

  •  Swaddle tightly and minimize sensory stimuli, including light, noise, touch, and even eye contact
  • Small, frequent feedings with high caloric formula for increased metabolic needs
  • Special dermatologic attention for excoriations and dermatitis secondary to diarrhea

4. Pharmacologic management must be initiated, titrated, and weaned based on abstinence scoring methods, such as Finnegan or the neonatal withdrawal inventory. 

There is no evidence that one abstinence scoring method is best, but nurseries should standardize and administer every 3-4 hours, including the mother in evaluations in order to gauge her perception of infant behaviors. 

Pharmacologic management should be initiated after two scores of eight.

  • First line: opiate agents lower risk of seizure and reduce time to regain birthweight

     Morphine and methadone are the best options (AAP)

     Tincture of opium works well, but its high concentration raises the risk of dosage error

     Buprenorphine and paregoric are not recommended because of the high alcohol vehicle and toxic compounds

  • Second line:

     Phenobarbital reduces hospital stay and symptom duration as adjunct medication

     Clonidine is preferred due to lower overall risk of adverse effects

5. Discharge is permissible 24 hours after weaning medications or after 4-5 days of observation with no symptoms of NAS.

Any discharge following NAS requires major social support, as well as intensive education around maternal mental health and substance use, home safety, domestic violence, SIDS, and recognition of late withdrawal symptoms.

These infants should have very early follow up with an outpatient pediatrician.

Outcomes

  • Care for mother and infant should be multidisciplinary, including social workers, drug counselors, obstetricians, and pediatricians. Involvement of these professionals before and after birth reduces hospital stay, use of ventilators, and entry into foster care.

  • Data on long-term outcomes of opiate use and NAS are severely confounded by:

        Poly-substance abuse, drug dose/purity

       Nutrition, poverty

       Scant prenatal care, risky behaviors, infections

References

Bio LL, Siu A, Poon CY. Update on the pharmacologic management of neonatal abstinence syndrome. J Perinatol 2011; 31:692.

Finnegan LP, Connaughton JF Jr, Kron RE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975; 2:141.

Herzlinger RA, Kandall SR, Vaughan HG Jr. Neonatal seizures associated with narcotic withdrawal. J Pediatr 1977; 91:638.

Hudak ML, Tan RC, COMMITTEE ON DRUGS, et al. Neonatal drug withdrawal. Pediatrics 2012; 129:e540.

Kandall SR, Gartner LM. Late presentation of drug withdrawal symptoms in newborns. Am J Dis Child 1974; 127:58.

Kocherlakota P.  State-of-the-Art Review Article: Neonatal Abstinence Syndrome. Pediatrics Vol. 134 No. 2 August 1, 2014.
Manchikanti L, Helm S 2nd, Fellows B, et al. Opioid epidemic in the United States. Pain Physician 2012; 15:ES9.

Patrick SW, Dudley J, Martin PR, et al. Prescription opioid epidemic and infant outcomes. Pediatrics 2015; 135:842.

Patrick SW, Schumacher RE, Benneyworth BD, et al. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. JAMA 2012; 307:1934.

Velez M, Jansson LM. The Opioid dependent mother and newborn dyad: non-pharmacologic care. J Addict Med 2008; 2:113.

Wiles JR, Isemann B, Ward LP, et al. Current management of neonatal abstinence syndrome secondary to intrauterine opioid exposure. J Pediatr 2014; 165:440.

Zahorodny W, Rom C, Whitney W, et al. The neonatal withdrawal inventory: a simplified score of newborn withdrawal. J Dev Behav Pediatr 1998; 19:89.