Neonatal Opioid Withdrawal Syndrome

(Full update January 2024)

Neonatal opioid withdrawal syndrome (NOWS), a specific type of neonatal abstinence syndrome (NAS), occurs when a baby withdraws from opiates the mother took or used chronically during pregnancy.2,13 The chart below answers common questions about NOWS.


Answer/Pertinent Information

What are the signs and symptoms of neonatal opioid withdrawal syndrome?

  • Symptoms typically occur within 24 to 72 hours of delivery.1
    • Symptoms may be delayed until up to seven days or longer after delivery with exposure to longer-acting meds (e.g., buprenorphine, methadone).1,2,13
    • Common symptoms include:2,13
      • central nervous system (e.g., high-pitched crying, sleep disturbances, tremors)
      • gastrointestinal (e.g., diarrhea, poor feeding, regurgitation)
      • autonomic (e.g., nasal flaring or stuffiness, sneezing, yawning, tachypnea [rapid breathing], sweating)
    • Symptoms can progress to dehydration, weight loss, seizures, or death.1,2

How should newborns be screened for neonatal opioid withdrawal syndrome?

  • Take a thorough history about maternal drug use, including prescription and non-prescription products.1
    • Use non-judgmental, open-ended questions to encourage honest responses regarding substance use.7
  • Urine (collected within hours of delivery) or meconium (newborn’s first stool) can be tested for opiates.2,13
    • Natural opiates show up on opiate screening (e.g., codeine, heroin, morphine).2
    • Synthetic opiates may not be detected on opiate screenings and need to be tested for separately (e.g., methadone, oxycodone).2
  • Several screening tools are available to assess the baby’s symptoms. Use a screening tool to assist with facility NOWS treatment, titration, and weaning protocol parameters. Examples include:2

How is the Modified Finnegan Scoring System used?

What supportive measures are recommended?

  • The “eat, sleep, console” or ESC method is a strategy used in the management of NOWS. The ESC method involves assessing if babies can eat well, sleep undisturbed, or be consoled within ten minutes before using medications.29 In addition, facilities may encourage the use of prn medications instead of using scheduled doses.30 Using ESC instead of traditional scoring methods may reduce length of stay and need for opioid treatment [Evidence level B-1].18
  • The nonpharmacologic suggestions below are included as part of ESC, but also encouraged even if other scoring methods are used instead of the ESC method at your facility.6,10,13,18
    • Encourage breastfeeding unless contraindicated (e.g., active substance abuse, HIV).10,13,24,29 Breastfeeding:
      • delays onset, and decreases severity, length of stay, and need for medication treatment of NOWS.10,24,27
      • promotes mother-infant bonding and provides optimal nutrition24,26
      • is compatible with buprenorphine and methadone.24
        • only about 3% of maternal methadone dose reaches milk.24
        • monitor infant for sedation and respiratory depression if methadone is being titrated, especially if the dose is >100 mg24
    • Utilize supportive measures, such as:
      • comforting techniques (e.g., holding skin to skin, swaying, rocking, swaddling, offering a pacifier)10,18,28
      • frequent, small volume, high-calorie feedings10
      • minimizing environmental stimuli (e.g., limit exposure to light or noise)10,18
      • clustered care18
    • Encourage infants “rooming-in” with mothers.10,13,28,29
      • May reduce length of stay and need for medication treatment of NOWS.29

When are medications appropriate?

  • Follow facility protocols for pharmacologic interventions. Using a protocol may be more impactful than the choice of medication used for weaning.7
    • Protocol-based therapy reduces opioid treatment duration and length of stay.6,7
  • Indications to initiate medications may include:
    • 24 Rule: either three consecutive Modified Finnegan scores ≥8 or two scores >12.5
    • withdrawal-associated seizures (phenobarbital)17
    • if using ESC, when non-pharmacologic methods are maximized and newborn is still unable to eat adequately, sleep for one hour undisturbed, and be consoled within ten minutes.5

Which medications should be used to treat neonatal opioid withdrawal syndrome?

  • Start with opioid replacement. Methadone or morphine are first-line.12
    • Oral morphine is most commonly used.8 It has a short half-life for ease of titration.7
    • Oral methadone may provide more consistent levels with less frequent adjustments than morphine.7
      • Methadone may reduce length of stay but pose a higher risk of oversedation (with a weight-based loading/taper protocol) than morphine [Evidence level B-1].12
    • There is less evidence with buprenorphine (sublingual), but it may be associated with a shorter length of stay than morphine or methadone [Evidence level B-3].9,12
    • Use of methadone and buprenorphine may be limited by ethanol content (~8% to 15% [methadone solution]; ~30% [compounded buprenorphine solution]).13,15
  • Adjunctive medications most often include clonidine or phenobarbital.16
    • Oral clonidine
      • Not typically used as monotherapy.8 Usually added to opiate therapy (e.g., morphine).8 Consider adding when total daily morphine doses is >1 mg/kg.5
      • Helps with autonomic symptoms.21
      • Clonidine may reduce the number of NOWS treatment days and the total dose of opioids used to treat NOWS over that period [Evidence Level B-2].19
      • Preferred over phenobarbital due to phenobarbital-associated neurotoxicity in animal studies and use being associated with adverse developmental outcomes.13
      • Monitor blood pressure and heart rate with use.2
    • Oral phenobarbital
      • Not typically used as monotherapy.8 Consider adding when: total daily morphine dose is >1 mg/kg; for neurologic symptoms such as insomnia or tremors; to facilitate a difficult morphine taper in conjunction with optimized nonpharmacologic interventions; for polydrug use (especially benzodiazepines or barbiturates).5,20,28
      • Not effective for gastrointestinal symptoms of NOWS.23
      • Causes central nervous system depression and impairs sucking reflex.23
      • Clonidine generally preferred over phenobarbital (see above).

How should morphinea be dosed for neonatal opioid withdrawal syndrome?

  • Initial oral dose: ~0.05 mg/kg/dose every three to four hours prn or scheduled.5,30
    • Increase dose by 10% to 20% about every 12 hours until symptoms are controlled.5
  • Max dose: 0.2 mg/kg/dose every four hours.30
  • Add additional therapy (e.g., clonidine) when total daily morphine doses are >1 mg/kg/day.5
  • Consider weaning once symptoms are controlled and stable for ~24 hours.5 Reduce dose by 10% up to two or three times every 24 hours.5
  • May discontinue once stable on a dose of 0.12 to 0.16 mg/kg/day (0.02 mg/kg/dose every four hours) for at least 12 hours.5
  • Once morphine is discontinued, continue monitoring every three to four hours for at least 48 hours.5 If Modified Finnegan score >8, recheck in two hours, and give a dose of morphine if score is still >8.5 Morphine may need to be resumed if more than a few doses are needed.5
  • May discharge home 48 hours after discontinuation, as long as all Modified Finnegan scores remain <8 off therapy.7

How should methadonea be dosed for neonatal opioid withdrawal syndrome?

  • In general, oral methadone can be dosed in a couple of different ways:
    • It can be started at a low dose (e.g., 0.05 mg/kg/dose every 12 hours), then increased (e.g., by 0.05 mg/kg/dose every 12 hours) until stabilization, then tapered (e.g., by 10% to 20% per week over four to six weeks).3
    • A different method (a weight-based loading/taper protocol) starts with a higher dose (e.g., 0.25 mg [if <3 kg] every six hours or 0.35 mg [if ≥3 kg] every six hours for four doses). Each day, the dose is either decreased per protocol, maintained, or an extra dose is given, based on the average modified Finnegan score over the past 24 hours.14

How should buprenorphinea be dosed for neonatal opioid withdrawal syndrome?

  • Initial sublingual dose: 4 to 6 mcg/kg/dose every eight hours.11,15
    • Buprenorphine dose can be increased by about 25% if the sum of the previous three Modified Finnegan scores is higher than 24 or after one score ≥12.11,22
  • Max dose: 60 mcg/kg/day.11
  • Consider weaning newborns off of buprenorphine by reducing the dose by about 10% per day if the total of the previous three Modified Finnegan scores is less than 18. Buprenorphine can be discontinued once the dose has been reduced to 10% of the initial dose.11,22
  • Monitor newborns for at least 48 hours after discontinuation prior to discharge.11

How should clonidinea be dosed for neonatal opioid withdrawal syndrome?

  • Initial oral dose: 0.5 to 1 mcg/kg/dose every four to six hours.5,21,23 Check blood pressure before administration.5
    • Increase by 0.5 mcg/kg/dose every six hours.5
  • Max dose: 6 mcg/kg/day.21,23 Higher doses (e.g., 24 mcg/kg/day) could be used if tolerating (e.g., no hypotension, bradycardia, sedation).5,20,23
  • Weaning may be attempted once the newborn is stable off opioid for 24 hours.20 Taper over three to four days (e.g., reduce dose by 25% per day by increasing the dosing interval).21,23
  • Monitor blood pressure for at least 48 hours after discontinuation of clonidine before discharging home.20,21

How should phenobarbitala be dosed for neonatal opioid withdrawal syndrome?

  • Initial oral dose: 16 to 20 mg/kg loading dose (as a single dose or divided as two doses of 8 to 10 mg/kg given three hours apart).5,20 After 24 hours, start 3 to 4 mg/kg/dose once daily, or 1.5 to 2 mg/kg/dose every 12 hours.5
  • Once morphine has been weaned to 0.3 mg/kg/day, phenobarbital may be stopped.5 Continue morphine wean as above.5 (Some centers send neonate home on phenobarbital.20)
  1. Facility protocol may vary from these doses. These are general, conservative dosing examples summarized from NOWS protocols and clinical trial data.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.



Study Quality


Good-quality patient-oriented evidence.*

  1. High-quality randomized controlled trial (RCT)
  2. Systematic review (SR)/Meta-analysis of RCTs with consistent findings
  3. All-or-none study


Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study


Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56.]


  1. Hudak ML, Tan RC, COMMITTEE ON DRUGS, et al. Neonatal drug withdrawal. Pediatrics. 2012 Feb;129(2):e540-60. Erratum in: Pediatrics. 2014 May;133(5):937.
  2. Holmes AP. NICU primer for pharmacists. Chapter 5: neonatal abstinence syndrome. 2016. (Accessed December 8, 2023).
  3. University of Iowa Children’s Hospital. Identifying Neonatal Abstinence Syndrome (NAS) and Treatment Guidelines. November 2014. (Accessed December 12. 2023).
  4. University of Texas Kids. University Health System: modified Finnegan’s neonatal abstinence scoring tool. June 2015. (Accessed December 18, 2023).
  5. Children’s Hospital of Philadelphia. Inpatient pathway for the evaluation/treatment of infants with neonatal abstinence syndrome. Revised September 2021. (Accessed December 9, 2023).
  6. Joint Commission. QuickSafety. Managing neonatal abstinence syndrome. April 2022. (Accessed December 9, 2023).
  7. McQueen K, Murphy-Oikonen J. Neonatal Abstinence Syndrome. N Engl J Med. 2016 Dec 22;375(25):2468-2479.
  8. Byerley EM, Mohamed MW, Grindeland CJ, et al. Neonatal Abstinence Syndrome Practices in the United States. J Pediatr Pharmacol Ther. 2021;26(6):577-583.
  9. Hall ES, Rice WR, Folger AT, Wexelblatt SL. Comparison of Neonatal Abstinence Syndrome Treatment with Sublingual Buprenorphine versus Conventional Opioids. Am J Perinatol. 2018 Mar;35(4):405-412 [abstract].
  10. Dow K, Ordean A, Murphy-Oikonen J, et al. Neonatal Abstinence Syndrome Work Group. Neonatal abstinence syndrome clinical practice guidelines for Ontario. J Popul Ther Clin Pharmacol. 2012;19(3):e488-506.
  11. Kraft WK, Adeniyi-Jones SC, Chervoneva I, et al. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. N Engl J Med. 2017 Jun 15;376(24):2341-2348.
  12. Sutter MB, Watson H, Yonke N, et al. Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study. BMC Pediatr. 2022 Jun 15;22(1):345.
  13. Patrick SW, Barfield WD, Poindexter BB; COMMITTEE ON FETUS AND NEWBORN, COMMITTEE ON SUBSTANCE USE AND PREVENTION. Neonatal Opioid Withdrawal Syndrome. Pediatrics. 2020 Nov;146(5):e2020029074.
  14. Celestin G, Balding M, Para JL, et al. Preliminary Assessment of the Effects of Pharmacist-Driven Methadone Stewardship for the Treatment of Neonatal Abstinence Syndrome at a Tertiary Children's Hospital. J Pediatr Pharmacol Ther. 2022;27(8):720-724.
  15. Lee JJ, Chen J, Eisler L, et al. Comparative effectiveness of opioid replacement agents for neonatal opioid withdrawal syndrome: a systematic review and meta-analysis. J Perinatol. 2019 Nov;39(11):1535-1545.
  16. Jansson LM, Patrick SW. Neonatal Abstinence Syndrome. Pediatr Clin North Am. 2019 Apr;66(2):353-367.
  17. Kushnir A, Garretson C, Mariappan M, Stahl G. Use of Phenobarbital to Treat Neonatal Abstinence Syndrome From Exposure to Single vs. Multiple Substances. Front Pediatr. 2022 Jan 31;9:752854.
  18. Young LW, Ounpraseuth ST, Merhar SL, et al. Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal. N Engl J Med. 2023 Jun 22;388(25):2326-2337.
  19. D'Abaco E. Does the addition of clonidine to opioid therapy improve outcomes in infants with Neonatal Abstinence Syndrome? J Paediatr Child Health. 2021 Jan;57(1):155-159.
  20. Nationwide Children’s Hospital. Neonatal abstinence syndrome management. October 2021. (Accessed December 13, 2023).
  21. Golisano Children’s Hospital of Southwest Florida- NICU. Management of the infant with neonatal abstinence syndrome. (Accessed December 13, 2023).
  22. Kraft WK, van den Anker JN. Pharmacologic management of the opioid neonatal abstinence syndrome. Pediatr Clin North Am. 2012 Oct;59(5):1147-65.
  23. Siu A, Robinson CA. Neonatal abstinence syndrome: essentials for the practitioner. J Pediatr Pharmacol Ther. 2014 Jul;19(3):147-55.
  24. Harris M, Schiff DM, Saia K, et al. Academy of Breastfeeding Medicine Clinical Protocol #21: Breastfeeding in the Setting of Substance Use and Substance Use Disorder (Revised 2023). Breastfeed Med. 2023 Oct;18(10):715-733.
  25. Allen A. Multi-site statewide collaboration for standardization of care for opioid exposed newborns. August 11, 2020. (Accessed December 9, 2023).
  26. Chantry CJ, Eglash A, Labbok M. ABM Position on Breastfeeding-Revised 2015. Breastfeed Med. 2015 Nov;10(9):407-11.
  27. Yen E, Davis JM. The immediate and long-term effects of prenatal opioid exposure. Front Pediatr. 2022 Nov 7;10:1039055.
  28. Anbalagan S, Mendez MD. Neonatal Abstinence Syndrome. [Updated 2023 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:
  29. Gomez Pomar E. A mini review of what matters in the management of NAS, is ESC the best care? Front Pediatr. 2023 Jul 14;11:1239107.
  30. UNC School of Medicine. Treatment Guidelines for Neonatal Abstinence Syndrome.. (Accessed December 9, 2023).

Cite this document as follows: Clinical Resource, Neonatal Opioid Withdrawal Syndrome. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. January 2024. [400163]

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