Document Type : original article


Department of Pediatrics, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.


Background: Since there is insufficient data to compare the relative efficacy of commonly prescribed opioids (morphine and buprenorphine), the present study aimed to compare the effect of morphine and buprenorphine on term and near-term neonates with neonatal abstinence syndrome.
Methods: This double-blind randomized clinical trial was performed on 60 neonates whose mothers were addicted to drugs (opium and its derivatives) and the neonate had symptoms of withdrawal syndrome. They were all. Admitted to Valiasr Hospital in Birjand. Neonatal assessment was based on Finnegan score. The neonates were randomly assigned in two groups of buprenorphine (n = 30) and morphine (n = 30). The Chi square test, Fisher exact test, student t test and Mann-Whitney U test were used for comparing the background characteristics and treatment outcomes between the two groups.
Results: In the present study, a total of 53.3% of the patients in both groups were boys and the rest were girls. The mean lengths of hospital stay in the buprenorphine and morphine groups were 5.97 ± 3.38 and 7.53 ± 4.83 days, respectively (p=0.15). Also, apnea was observed in 33.3% of the total neonates in the buprenorphine group and 43.3% of the neonates in the morphine group (p=0.43). The two groups were homogenous in regards to apnea complications, oral intolerance, hypotension and blood culture result (p>0.05)
Conclusion: The results of the present study showed no significant difference in the outcomes of treatment and reduction of treatment complications between the buprenorphine and morphine-treated neonates.


  1. Pacurucu-Castillo SF, Ordóñez-Mancheno JM, Hernández-Cruz A, Alarcón RD. World opioid and substance use epidemic: a Latin American perspective. Psychiatric Research and Clinical Practice. 2019; 1(1):32-8.
  2. Brownstein MJ. A brief history of opiates, opioid peptides, and opioid receptors. Proc Natl Acad Sci U S A (1993) 90(12):5391–3.
  3. Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. New England Journal of Medicine. 2007; 356(26):2684-92.
  4. Rodriguez JJ, Smith VC, editors. Epidemiology of perinatal substance use: Exploring trends in maternal substance use. Seminars in Fetal and Neonatal Medicine; 2019: Elsevier.
  5. Banafsheh H, Mesdaghinia A, Ghoreishi FS, Gilasi H, Kashani Z, Gholami M, Ghaderi A. The survey of patterns of abuse and causes of addiction tendency among women undergoing methadone maintenance treatment in Kashan city during 2017-2018. Feyz Journal of Kashan University of Medical Sciences. 2018; 22(5):532-8. (Persian).
  6. Torshizi M, Saadatjoo S, Farabi M. Prevalence of narcotic substance abuse and the maternal and fetal outcomes in pregnant women. Journal of Jahrom University of Medical Sciences. 2011; 9 (3): 14-18. (Persian).
  7. Ko JY, Patrick SW, Tong VT, Patel R, Lind JN, Barfield WD. Incidence of neonatal abstinence syndrome-28 states, 1999–2013. Morbidity and Mortality Weekly Report. 2016; 65(31):799-802.
  8. Utah V. Incidence of Neonatal Abstinence Syndrome-28 States, 1999–2013. Cardiovascular Health Status by Occupational Group—21 States, 2013.799.
  9. Kraft WK. Buprenorphine in neonatal abstinence syndrome. Clinical Pharmacology & Therapeutics. 2018; 103(1):112-9.
  10. Winkelman TN, Villapiano N, Kozhimannil KB, Davis MM, Patrick SW. Incidence and costs of neonatal abstinence syndrome among infants with Medicaid: 2004–2014. Pediatrics. 2018; 141(4):e20173520.
  11. MacMillan KDL. Neonatal Abstinence Syndrome: Review of Epidemiology, Care Models, and Current Understanding of Outcomes. Clinics in perinatology. 2019; 46(4):817-32.
  12. Taleghani AA, Isemann BT, Rice WR, Ward LP, Wedig KE, Akinbi HT. Buprenorphine pharmacotherapy for the management of neonatal abstinence syndrome in methadone‐exposed neonates. Pediatric and Neonatal Pain. 2019; 1(2): 33-38.
  13. Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics. 2012; 129(2):e540-e60.
  14. Oei J, Lui K. Management of the newborn infant affected by maternal opiates and other drugs of dependence. Journal of pediatrics and child health. 2007; 43(1‐2):9-18.
  15. Sanz EJ, De-las-Cuevas C, Kiuru A, Bate A., Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. The Lancet. 2005; 365(9458):482-7.
  16. Greig E, Ash A, Douiri A. Maternal and neonatal outcomes following methadone substitution during pregnancy. Archives of gynecology and obstetrics. 2012; 286(4):843-51.
  17. Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB, Clark RH, Spitzer AR. Increasing incidence of the neonatal abstinence syndrome in US neonatal ICUs. New England Journal of Medicine. 2015; 372(22):2118-26.
  18. Wiles JR, Isemann B, Ward LP, Vinks AA, Akinbi H. Current management of neonatal abstinence syndrome secondary to intrauterine opioid exposure. The Journal of pediatrics. 2014; 165(3):440-6.
  19. Hall ES, Rice WR, Folger AT, Wexelblatt SL. Comparison of neonatal abstinence syndrome treatment with sublingual buprenorphine versus conventional opioids. American journal of perinatology. 2018; 35(04):405-12.
  20. Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, Li Y, Leggas M, Breheny P. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics. 2015; 135(2):e383-e91.
  21. Afrakhteh M, Saadvandian S, Kazemian M. Start breastfeeding in the first hour of life: An educational guide for health care workers. Andisheh Mandegar Publications. 2015 (Persian).
  22. Nayeri F, Sheikh M, Kalani M, Niknafs P, Shariat M, Dalili H, Dehpour AR. Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial. BMC pediatrics. 2015; 15(1):57.
  23. Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR, Fischer G. Neonatal abstinence syndrome after methadone or buprenorphine exposure. New England Journal of Medicine. 2010; 363(24):2320-31.
  24. Kraft WK, Adeniyi-Jones SC, Chervoneva I, Greenspan JS, Abatemarco D, Kaltenbach K, Ehrlich ME. Buprenorphine for the treatment of the neonatal abstinence syndrome. New England Journal of Medicine. 2017; 376(24):2341-8.
  25. Hall ES, Wexelblatt SL, Crowley M, Grow JL, Jasin LR, Klebanoff MA, McClead RE, Meinzen-Derr J, Mohan VK, Stein H, Walsh MC, Consortium O. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics. 2014; 134(2):e527-e34.
  26. Kraft WK, Dysart K, Greenspan JS, Gibson E, Kaltenbach K, Ehrlich ME. Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome. Addiction. 2011; 106(3):574-80.
  27. Hamunen K, Olkkola K, Maunuksela EL. Comparison of the ventilatory effects of morphine and buprenorphine in children. Acta anaesthesiologica scandinavica. 1993; 37(5):449-53.
  28. Enders J, Gebauer C, Pulzer F, Robel‐Tillig E, Knüpfer M. Morphine‐related apnoea in CPAP‐treated preterm neonates. Acta Pædiatrica. 2006; 95(9):1087-92.