Could Buprenorphine Replace Morphine for the Treatment of Neonatal Abstinence Syndrome?

Reem Gebrekidan, Mercer University College of Pharmacy

Maternal use and abuse of opioids, benzodiazepines, alcohol, and tobacco could lead to signs and symptoms of withdrawal, also known as neonatal abstinence syndrome (NAS). The symptoms and severity of withdrawal are considered to be different based on the specific drug the neonate is exposed to. Common symptoms may include: hyperactivity, tremor, irritability, feeding difficulty, sleep disturbance and gastrointestinal symptoms such as diarrhea and vomiting. [1]

Guidelines suggest the use of pharmacologic treatment in neonates who have moderate to severe signs of neonatal abstinence syndrome (NAS) and who do not respond to nonpharmacological treatments. The drug of choice was recommended to match the type of agent causing withdrawal. [1]

Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome (BBORN) trial [2]
Design Single-site, randomized, double-blind study; N= 63
Objective To evaluate the efficacy of buprenorphine compared to morphine for treatment of NAS
Study Groups Buprenorphine (n= 33); morphine (n= 30)
Methods Included were full term infants (≥37 weeks of gestation) with prenatal exposure to opioids and Finnegan scoring of 24 for the sum of three scores or a single score of 12. Infants were excluded if they had major congenital malformation, < 2.2 kg birth weight, a serious medical or neurologic illness, seizures, hypoglycemia requiring intravenous glucose, a bilirubin level of > 20 mg/dL, or prenatal exposure to benzodiazepine 30 days before birth.

Infants received sublingual buprenorphine or oral morphine based on maternal exposure of methadone or buprenorphine and the maternal intention to breast-feed or bottle-feed. Clinical success was determined by any reduction of duration of treatment  from the first dose of a trial drug compared to morphine

Duration Recruitment from 2011-2016
Primary Outcome Measure Clinical success based on duration of treatment
Secondary outcome measure Length of hospital stay, addition of phenobarbital
Baseline Characteristics  

Buprenorphine Morphine
Median gestational age, wks (range) 38.5 (37.0–42.0) 39 (37.0–41.0)
Median age at treatment initiation, days (range) 2 (1–9) 2 (1–14)

 

Median birth weight, kg (range) 3.04 (2.27–4.38) 3.004 (2.197–3.85)
Male, n (%) 17 (52) 18 (60)
Breast-feeding subgroup, n (%) 12 (36) 9 (30)
Apgar score, (range)
1 8 (3–9) 8 (5–10)
2 9 (7–9) 9 (7–10)

 

Results  

Buprenorphine Morphine p-value
Median duration of  treatment, days (range) 15 (3-67) 28 (13-67) <0.001
Median length of stay, days (range) 21(7-71) 33 (18-70) <0.001
Use of supplemental phenobarbital, n (%) 5 (15%) 7 (23%) 0.36

 

Adverse Events Common Adverse Events (buprenorphine vs morphine, n): any (13 vs. 10), skin condition (5 vs. 3), gastrointestinal condition (3 vs. 3),  respiratory infection (0 vs. 2).
Serious Adverse Events (buprenorphine vs morphine, n): inguinal hernia repair, (1 vs 0); supraglottoplasty (1 vs 0)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Sublingually administered buprenorphine was more effective than oral morphine in reducing the duration of treatment for  NAS.

The wide therapeutic index and longer half-life of buprenorphine decreases the risk of respiratory depression and indicates the potential for treatment for NAS. Both agents demonstrated similar safety profiles which is important for such a fragile patient population. While these mothers may be likely to birth pre-term and take benzodiazepines, utility of buprenorphine in that situation cannot be extrapolated from this study. Also, no information comparing the severity of withdrawal symptoms before treatment was given between the groups which may restrict its implication for NAS.

References

[1] Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics. 2012;129(2):e540-60.

[2] Kraft WK, Adeniyi-jones SC, Chervoneva I, et al. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. N Engl J Med. 2017.

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