Neonatal abstinence syndrome

Background

• Incidence has quadrupled since 1999 from 1.5 per 1000 hospital births to 6.0 per 1000 in 2013
• Condition caused by neonatal withdrawal from substance exposure in utero
  • Withdrawal within first 24-48 hrs → fetal alcohol syndrome
  • Withdrawal within 48-72 hrs → heroin
  • Withdrawal at 7-14 days → methadone
• Polysubstance withdrawal must also be considered

Clinical Features

• Agitated - high-pitched cry, restlessness, tremors, hypertonia, convulsions
• Vasomotor - sweating, fever
• Respiratory - nasal congestion, persistent sneezing, RR > 60/min, nasal flaring
• Metabolic - poor feeding, vomiting, loose stools

Differential Diagnosis

• Neonatal sepsis
• Hyperthyroidism/hypothyroidism
• Hypocalcemia
• Hypoglycemia
• Vertically transmitted diseases (HepB, HepC, HIV, etc.)
• Other withdrawal (caffeine, cocaine, nicotine, amphetamines, SSRIs)

Evaluation

• Pharmacologic treatment when 3 consecutive ≥ 8 on NAS(Finnegan scale
• Enzyme immunoassay, urine toxicology, meconium analysis
• Consider cranial ultrasound for cocaine-exposed neonates with abnormal neurologic signs

Management

• Supportive - swaddling to decrease sensory stimulation, frequent small feedings of 24 cal/oz formula
• Opiates when supportive measures fail
• Morphine is 1st line for infants exposed to both opioids and benzos
• Longer acting buprenorphine may significantly reduce hospital admission and treatment duration as compared to morphine
  • Morphine q4 hours vs. buprenorphine q8 hours if NAS scale > 12
  • Buprenorphine dosed initially at 5 mcg/kg q8 hrs to max dose of 20 mcg/kg q8 hrs
  • Neonatal morphine 0.4mg/ml PO sln
    • Watch for side effect limiting dose (urinary retention)
    • Withdrawal symptoms need to be stabilized for 3-5 days before taper
    • Mother's methadone < 50mg (or other opiate)
      • Start morphine PO sln 0.1mg/kg q3hrs with feeds
      • Increase by 0.1mg/kg hourly if NAS score ≥ 8, max 1mg/kg
    • Mother's methadone > 50mg
      • Start 0.2mg/kg q3hrs
      • Increase by 0.2mg/kg hourly if NAS score ≥ 8, max 1mg/kg
  • If NPO, use preservative free morphine at 50 mcg/ml
    • Load 30 mcg/kg over 1hr, then infusion at 2 mcg/kg/hr
    • Increase by 1 mcg/kg/hr hourly until NAS < 8, max 6 mcg/kg/hr
• Benzo withdrawal treatment
  • Midazolam 0.1mg/kg IV q3hrs or 0.3mg/kg PO q3hrs
  • OR phenobarbital 3mg/kg IV or PO q24hrs
• Phenobarbital for seizures OR side effect limiting morphine effects OR max morphine dose reached
  • 16mg/kg load divided into two consecutive feedings for day 1
  • 24 hrs later, use 2-8mg/kg/day maintenance dose

Disposition

• Admit

See Also

• Opioid withdrawal

References

• Hudak ML, Tan RC. Neonatal Drug Withdrawal. Pediatrics. January 2012. 129(2):e540-560.
• 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.
• Hall ES, Wexelblatt SL, Crowley M, Grow JL, Jasin LR, Klebanoff MA, et al. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics. 2014 Aug. 134(2):e527-34.
• Pullen L. Neonatal Abstinence Syndrome: Stringent Weaning Protocol Best. Available at http://www.medscape.com/viewarticle/829115. Accessed: August 12, 2016.