Neonatal Abstinence Syndrome
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Published:
Sep 12, 2017
Keywords:
Neonatal abstinence;, drugs;, abuse
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Abstract
Introduction Substance abuse is a growing problematic in the global population, being a major risk factor for the appearance of neonatal abstinence syndrome (NAS), a disease that represents great challenges in clinical practice.
Objective To identify key aspects in the literature on neonatal abstinence syndrome in order to reinforce the knowledge about the topic and thus lay sound foundations for the clinical practice of neonatologists, pediatricians, and health personnel in general.
Materials and methods For this review, a systematic research of the literature (published between 1975 and 2016) about neonatal abstinence syndrome, its epidemiology, clinical manifestations, diagnosis, and treatment was done, as well as of complementary information, gathered from texts published by the United Nations Office on Drugs and Crimes (UNODC), the Pan American Health Organization (PAHO), the Colombian Health and Justice ministries and the Drug Observatory of Colombia (ODC). The databases used for the research of clinical studies, review and opinion articles, and case reports, both in English and Spanish, were: The National Library of Medicine of the United States (Pubmed/Medline), SciELO, Lilacs, ClinicalKey, and UpToDate.
Conclusions The neonatal abstinence syndrome is a currently frequent complication among the children of mothers who abuse substances and requires an integral treatment.
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Zapata Diaz, J. P., Rendón Fonnegra, J., & Berrouet, M. C. (2017). Neonatal Abstinence Syndrome. Pediatría, 50(2). https://doi.org/10.14295/pediatr.v50i2.60
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References
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8. Hall ES, Wexelblatt SL, Crowley M, Grow JL, Jasin LR, Klebanoff MA, et al. Implementation of a Neonatal Abstinence Syndrome Weaning Protocol: A Multicenter Cohort Study. PEDIATRICS. 1 de octubre de 2015;136(4):e803-10.
9. Hayes MJ, Brown MS. Epidemic of Prescription Opiate Abuse and Neonatal Abstinence. JAMA. 9 de mayo de 2012;307(18):1974-5.
10. Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB, et al. Increasing Incidence of the Neonatal Abstinence Syndrome in U.S. Neonatal ICUs. N Engl J Med. 28 de mayo de 2015;372(22):2118-26.
11. Kocherlakota P. Neonatal Abstinence Syndrome. PEDIATRICS. 1 de agosto de 2014;134(2):e547-61.
12. Nishimura M, Yaguti H, Yoshitsugu H, Naito S, Satoh T. Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. Mayo de 2003;123(5):369-75.
13. Šlamberová R. Drugs in pregnancy: the effects on mother and her progeny. Physiol Res. 2012;61 Suppl 1:S123-135.
14. Sivasubramaniam SD, Finch CC, Billett MA, Baker PN, Billett EE. Monoamine Oxidase Expression and Activity in Human Placentae from Pre-eclamptic and Normotensive Pregnancies. Placenta. 1 de febrero de 2002;23(2):163-71.
15. Bosque J del, Fuentes Mairena A, Bruno Díaz D, Espínola M, González García N, Loredo Abdalá A, et al. La cocaína: consumo y consecuencias. Salud Ment. Octubre de 2014;37(5):381-9.
16. Carrasco G, Cruz MA, Gallardo V, Miguel P, Dominguez A, González C. Transport and Metabolism of Serotonin in the Human Placenta from Normal and Severely Pre-Eclamptic Pregnancies. Gynecol Obstet Invest. 5 de abril de 2000;49(3):150-5.
17. Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet. 2004;43(8):487-514.
18. Prouillac C, Lecoeur S. The role of the placenta in fetal exposure to xenobiotics: importance of membrane transporters and human models for transfer studies. Drug Metab Dispos Biol Fate Chem. Octubre de 2010;38(10):1623-35.
19. Myllynen P, Pasanen M, Vähäkangas K. The fate and effects of xenobiotics in human placenta. Expert Opin Drug Metab Toxicol. Junio de 2007;3(3):331-46.
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21. Fujita W, Gomes I, Devi LA. Heteromers of μ-δ opioid receptors: new pharmacology and novel therapeutic possibilities. Br J Pharmacol. Enero de 2015;172(2):375-87.
22. Lindsay MK, Burnett E. The use of narcotics and street drugs during pregnancy. Clin Obstet Gynecol. 2013;56(1):133–141.
23. Lorenzo Fernández P. Drogodependencias: farmacología, patología, psicología, legislación. Buenos Aires; Madrid: Panamericana, 2009.
24. Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O’MALLEY K, Young JK. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr. 2004;25(4):228–238.
25. Behnke M, Smith VC, COMMITTEE ON SUBSTANCE ABUSE, COMMITTEE ON FETUS AND NEWBORN. Prenatal Substance Abuse: Short- and Long-term Effects on the Exposed Fetus. PEDIATRICS. 1 de marzo de 2013;131(3):e1009-24.
26. Solís Sánchez G, Sánchez S, L J, Díaz González T. Exposición prenatal a drogas y efectos en el neonato. Trastor Adict. :256-62.
27. Igarashi M. Floppy infant syndrome. J Clin Neuromuscul Dis. Diciembre de 2004;6(2):69-90.
28. Wikner BN, Stiller C-O, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. Noviembre de 2007;16(11):1203-10.
29. Jarosz M, Wierzejska R, Siuba M. Maternal caffeine intake and its effect on pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol. febrero de 2012;160(2):156-60.
30. Montes Bentura D, La Orden Izquierdo E, Álvarez Fernández B, Garín Fernández N, Ortiz Movilla R, Muro Brussi M. Síndrome de abstinencia neonatal debido a consumo materno excesivo de cafeína. An Pediatría. 1 de marzo de 2009;70(3):300-1.
31. Martín I, López-Vílchez MA, Mur A, García-Algar O, Rossi S, Marchei E, et al. Neonatal withdrawal syndrome after chronic maternal drinking of mate. Ther Drug Monit. Febrero de 2007;29(1):127-9.
32. Samet JM. Los riesgos del tabaquismo activo y pasivo. Salud Pública México. 2002;44:s144–s160.
33. Mund M, Louwen F, Klingelhoefer D, Gerber A. Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn. Int J Environ Res Public Health. Diciembre de 2013;10(12):6485-99.
34. Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol. Junio de 1997;29(7):1422-31.
35. Bustamante JFM, Mejía MCB. Cocaína y estado convulsivo. Rev CES Med. 2012;26(2):215–221.
36. Minnes S, Min MO, Singer LT, Edguer M, Wu M, Thi P. Cocaine use during pregnancy and health outcome after 10 years. Drug Alcohol Depend. 1 de noviembre de 2012;126(1-2):71-9.
37. Toledo E, Eugenia I, Mejía B, Claire M, Ramírez G, Mauricio D. Molecular Mechanism of Addiction to Marihuana. Rev Colomb Psiquiatr. Marzo de 2009;38(1):126-42.
38. Brown HL, Graves CR. Smoking and marijuana use in pregnancy. Clin Obstet Gynecol. marzo de 2013;56(1):107-13.
39. Bolea-Alamanac BM, Green A, Verma G, Maxwell P, Davies SJC. Methylphenidate use in pregnancy and lactation: a systematic review of evidence. Br J Clin Pharmacol. Enero de 2014;77(1):96-101.
40. Lazic-Mitrovic T, Mikovic Z, Mandic V, Hajnal-Avramovic L, Cecez D, Stanimirovic A, et al. Neonatal abstinence syndrome: Diagnostic dilemmas in the maternity ward. Srp Arh Celok Lek. 2015;143(9-10):573-7.
41. Barrero Virguetti MH, Escalera Solis C. Síndrome de abstinencia neonatal. Rev Médica Cochabamba. 2008;19:54.
42. Moro M, Almenar A, Tapia MC, Roldán M. Protocolos diagnósticos y terapeuticos de Neonatología en pediatría. [Internet]. España; 2002 [citado 27 de noviembre de 2016]. 340 p. Disponible en: http://ceince.edu.bo/descargas/neonatologia-completo.pdf#page=74
43. W Zahorodny CR. The Neonatal Withdrawal Inventory: A Simplified Score of Newborn Withdrawal. J Dev Behav Pediatr JDBP. 1998;19(2):89-93.
44. Jansson LM, Velez M, Harrow C. The Opioid Exposed Newborn: Assessment and Pharmacologic Management. J Opioid Manag. 2009;5(1):47-55.
45. Siu A, Robinson CA. Neonatal abstinence syndrome: essentials for the practitioner. J Pediatr Pharmacol Ther. 2014;19(3):147–155.
46. McCance-Katz EF, Sullivan LE, Nallani S. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review. Am J Addict. Febrero de 2010;19(1):4-16.
47. Brown MS, Hayes MJ, Thornton LM. Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. J Perinatol Off J Calif Perinat Assoc. Abril de 2015; 35(4):278-83.
48. Young ME, Hager SJ, Spurlock D. Retrospective chart review comparing morphine and methadone in neonates treated for neonatal abstinence syndrome. Am J Health-Syst Pharm AJHP Off J Am Soc Health-Syst Pharm. 1 de diciembre de 2015;72(23 Suppl 3):S162-167.
49. 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. 1 de agosto de 2014;134(2):e527-34.
50. Streetz VN, Gildon BL, Thompson DF. The Role of Clonidine in Neonatal Abstinence Syndrome A Systematic Review. Ann Pharmacother. 18 de enero de 2016;1060028015626438.
51. Rayner SG, Weinert CR, Peng H, Jepsen S, Broccard AF, Study Institution. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 23 de mayo de 2012;2(1):12.
52. Whalen LD, Di Gennaro JL, Irby GA, Yanay O, Zimmerman JJ. Long-Term Dexmedetomidine Use and Safety Profile Among Critically Ill Children and Neonates*: Pediatr Crit Care Med. octubre de 2014;15(8):706-14.
2. World Drug Report 2015. United Nations Office on Drugs and Crime. https://www.unodc.org/documents/wdr2015/World_Drug_Report_2015.pdf (Fecha de consulta: 18 de septiembre de 2017).
3. Drug use epidemiology in Latin America and the Caribbean: a public health approach. Washington, D.C.: Pan American Health Organization, 2009.
4. Ministerio de Justicia y del Derecho, Observatorio de Drogas de Colombia. Reporte de Drogas de Colombia. http://www.odc.gov.co/Portals/1/publicaciones/pdf/odc-libro-blanco/OD0100311215_reporte_de_drogas_de_colombia.pdf (Fecha de consulta: 18 de septiembre de 2017).
5. Observatorio de Drogas de Colombia, Ministerio de Justicia y del Derecho, Ministerio de Salud y Protección Social. Estudio Nacional de consumo de sustancias psicoactivas en Colombia 2013. https://www.unodc.org/documents/colombia/2014/Julio/Estudio_de_Consumo_UNODC.pdf (Fecha de consulta: 18 de septiembre de 2017).
6. Torres de Galvis Y, Posada Villa J. Primer estudio poblacional de salud mental Medellín, 2011-2012 (The World Mental Health Survey Consortium). Medellín: Universidad CES; Secretaría de Salud de Medellín, 2012.
7. Wendell AD. Overview and epidemiology of substance abuse in pregnancy. Clin Obstet Gynecol. 2013;56(1):91–96.
8. Hall ES, Wexelblatt SL, Crowley M, Grow JL, Jasin LR, Klebanoff MA, et al. Implementation of a Neonatal Abstinence Syndrome Weaning Protocol: A Multicenter Cohort Study. PEDIATRICS. 1 de octubre de 2015;136(4):e803-10.
9. Hayes MJ, Brown MS. Epidemic of Prescription Opiate Abuse and Neonatal Abstinence. JAMA. 9 de mayo de 2012;307(18):1974-5.
10. Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB, et al. Increasing Incidence of the Neonatal Abstinence Syndrome in U.S. Neonatal ICUs. N Engl J Med. 28 de mayo de 2015;372(22):2118-26.
11. Kocherlakota P. Neonatal Abstinence Syndrome. PEDIATRICS. 1 de agosto de 2014;134(2):e547-61.
12. Nishimura M, Yaguti H, Yoshitsugu H, Naito S, Satoh T. Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. Mayo de 2003;123(5):369-75.
13. Šlamberová R. Drugs in pregnancy: the effects on mother and her progeny. Physiol Res. 2012;61 Suppl 1:S123-135.
14. Sivasubramaniam SD, Finch CC, Billett MA, Baker PN, Billett EE. Monoamine Oxidase Expression and Activity in Human Placentae from Pre-eclamptic and Normotensive Pregnancies. Placenta. 1 de febrero de 2002;23(2):163-71.
15. Bosque J del, Fuentes Mairena A, Bruno Díaz D, Espínola M, González García N, Loredo Abdalá A, et al. La cocaína: consumo y consecuencias. Salud Ment. Octubre de 2014;37(5):381-9.
16. Carrasco G, Cruz MA, Gallardo V, Miguel P, Dominguez A, González C. Transport and Metabolism of Serotonin in the Human Placenta from Normal and Severely Pre-Eclamptic Pregnancies. Gynecol Obstet Invest. 5 de abril de 2000;49(3):150-5.
17. Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet. 2004;43(8):487-514.
18. Prouillac C, Lecoeur S. The role of the placenta in fetal exposure to xenobiotics: importance of membrane transporters and human models for transfer studies. Drug Metab Dispos Biol Fate Chem. Octubre de 2010;38(10):1623-35.
19. Myllynen P, Pasanen M, Vähäkangas K. The fate and effects of xenobiotics in human placenta. Expert Opin Drug Metab Toxicol. Junio de 2007;3(3):331-46.
20. Berrouet Mejia MC. Intoxicación por Opioides. En: El Paciente Urgente. Medellín, Colombia. CIB. p. 619-31.
21. Fujita W, Gomes I, Devi LA. Heteromers of μ-δ opioid receptors: new pharmacology and novel therapeutic possibilities. Br J Pharmacol. Enero de 2015;172(2):375-87.
22. Lindsay MK, Burnett E. The use of narcotics and street drugs during pregnancy. Clin Obstet Gynecol. 2013;56(1):133–141.
23. Lorenzo Fernández P. Drogodependencias: farmacología, patología, psicología, legislación. Buenos Aires; Madrid: Panamericana, 2009.
24. Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O’MALLEY K, Young JK. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr. 2004;25(4):228–238.
25. Behnke M, Smith VC, COMMITTEE ON SUBSTANCE ABUSE, COMMITTEE ON FETUS AND NEWBORN. Prenatal Substance Abuse: Short- and Long-term Effects on the Exposed Fetus. PEDIATRICS. 1 de marzo de 2013;131(3):e1009-24.
26. Solís Sánchez G, Sánchez S, L J, Díaz González T. Exposición prenatal a drogas y efectos en el neonato. Trastor Adict. :256-62.
27. Igarashi M. Floppy infant syndrome. J Clin Neuromuscul Dis. Diciembre de 2004;6(2):69-90.
28. Wikner BN, Stiller C-O, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. Noviembre de 2007;16(11):1203-10.
29. Jarosz M, Wierzejska R, Siuba M. Maternal caffeine intake and its effect on pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol. febrero de 2012;160(2):156-60.
30. Montes Bentura D, La Orden Izquierdo E, Álvarez Fernández B, Garín Fernández N, Ortiz Movilla R, Muro Brussi M. Síndrome de abstinencia neonatal debido a consumo materno excesivo de cafeína. An Pediatría. 1 de marzo de 2009;70(3):300-1.
31. Martín I, López-Vílchez MA, Mur A, García-Algar O, Rossi S, Marchei E, et al. Neonatal withdrawal syndrome after chronic maternal drinking of mate. Ther Drug Monit. Febrero de 2007;29(1):127-9.
32. Samet JM. Los riesgos del tabaquismo activo y pasivo. Salud Pública México. 2002;44:s144–s160.
33. Mund M, Louwen F, Klingelhoefer D, Gerber A. Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn. Int J Environ Res Public Health. Diciembre de 2013;10(12):6485-99.
34. Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol. Junio de 1997;29(7):1422-31.
35. Bustamante JFM, Mejía MCB. Cocaína y estado convulsivo. Rev CES Med. 2012;26(2):215–221.
36. Minnes S, Min MO, Singer LT, Edguer M, Wu M, Thi P. Cocaine use during pregnancy and health outcome after 10 years. Drug Alcohol Depend. 1 de noviembre de 2012;126(1-2):71-9.
37. Toledo E, Eugenia I, Mejía B, Claire M, Ramírez G, Mauricio D. Molecular Mechanism of Addiction to Marihuana. Rev Colomb Psiquiatr. Marzo de 2009;38(1):126-42.
38. Brown HL, Graves CR. Smoking and marijuana use in pregnancy. Clin Obstet Gynecol. marzo de 2013;56(1):107-13.
39. Bolea-Alamanac BM, Green A, Verma G, Maxwell P, Davies SJC. Methylphenidate use in pregnancy and lactation: a systematic review of evidence. Br J Clin Pharmacol. Enero de 2014;77(1):96-101.
40. Lazic-Mitrovic T, Mikovic Z, Mandic V, Hajnal-Avramovic L, Cecez D, Stanimirovic A, et al. Neonatal abstinence syndrome: Diagnostic dilemmas in the maternity ward. Srp Arh Celok Lek. 2015;143(9-10):573-7.
41. Barrero Virguetti MH, Escalera Solis C. Síndrome de abstinencia neonatal. Rev Médica Cochabamba. 2008;19:54.
42. Moro M, Almenar A, Tapia MC, Roldán M. Protocolos diagnósticos y terapeuticos de Neonatología en pediatría. [Internet]. España; 2002 [citado 27 de noviembre de 2016]. 340 p. Disponible en: http://ceince.edu.bo/descargas/neonatologia-completo.pdf#page=74
43. W Zahorodny CR. The Neonatal Withdrawal Inventory: A Simplified Score of Newborn Withdrawal. J Dev Behav Pediatr JDBP. 1998;19(2):89-93.
44. Jansson LM, Velez M, Harrow C. The Opioid Exposed Newborn: Assessment and Pharmacologic Management. J Opioid Manag. 2009;5(1):47-55.
45. Siu A, Robinson CA. Neonatal abstinence syndrome: essentials for the practitioner. J Pediatr Pharmacol Ther. 2014;19(3):147–155.
46. McCance-Katz EF, Sullivan LE, Nallani S. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review. Am J Addict. Febrero de 2010;19(1):4-16.
47. Brown MS, Hayes MJ, Thornton LM. Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. J Perinatol Off J Calif Perinat Assoc. Abril de 2015; 35(4):278-83.
48. Young ME, Hager SJ, Spurlock D. Retrospective chart review comparing morphine and methadone in neonates treated for neonatal abstinence syndrome. Am J Health-Syst Pharm AJHP Off J Am Soc Health-Syst Pharm. 1 de diciembre de 2015;72(23 Suppl 3):S162-167.
49. 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. 1 de agosto de 2014;134(2):e527-34.
50. Streetz VN, Gildon BL, Thompson DF. The Role of Clonidine in Neonatal Abstinence Syndrome A Systematic Review. Ann Pharmacother. 18 de enero de 2016;1060028015626438.
51. Rayner SG, Weinert CR, Peng H, Jepsen S, Broccard AF, Study Institution. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 23 de mayo de 2012;2(1):12.
52. Whalen LD, Di Gennaro JL, Irby GA, Yanay O, Zimmerman JJ. Long-Term Dexmedetomidine Use and Safety Profile Among Critically Ill Children and Neonates*: Pediatr Crit Care Med. octubre de 2014;15(8):706-14.