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Neonatal withdrawal

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Neonatal withdrawal
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Neonatal withdrawal or neonatal abstinence syndrome (NAS) is a withdrawal syndrome of infants, caused by the cessation of the administration of licit or illicit drugs. Tolerance, dependence, and withdrawal may occur as a result of repeated administration of drugs or even after short-term high-dose use—for example, during mechanical ventilation in intensive care units. There are two types of NAS: prenatal and postnatal. Prenatal NAS is caused by discontinuation of drugs taken by the pregnant mother, while postnatal NAS is caused by discontinuation of drugs directly to the infant.[1][2]

Signs and Symptoms

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NAS signs and symptoms vary depending on the drugs used by the birthing parent, how long the drugs were used, and the amount of drug used that made it to the child.[3]

Causes

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The drugs involved can include opioids, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) ethanol, benzodiazepines, anticonvulsants, and muscle relaxants to name a few.[4][5][1][6] Opioids have become the most associated with NAS due to the growing opioid crisis leading to increased opioid use among pregnant people. Although NAS generally includes opioid and nonopioid exposures, studies have shown that such cases have primarily resulted from in utero opioid exposure; thus, resulting in the use of Neonatal Opioid Withdrawal Syndrome (NOWS) as a subset of NAS.[7][8][9] Neonatal abstinence syndrome does not happen in prenatal cocaine exposure (with babies exposed to cocaine in utero) in the sense that such symptoms are difficult to separate in the context of other factors such as prematurity or prenatal exposure to other drugs.[10]

Although the main pathophysiology of NAS is still not fully understood, there are several potential mechanisms and pathways that are being investigated that may be related to the development of NAS caused by abnormal levels of neurotransmitters and inadequate expression of opioid receptors.[4] Due to the differing substances that can lead to NAS, each substance can result in a different cause leading to the symptoms of NAS. [9] Examples of such differences include: opioid withdrawal resulting in decreases in serotonin and dopamine with an increase in corticotrophin, norepinephrine, and acetylcholine; TCA withdrawal resulting in a cholinergic rebound phenomenon; benzodiazepine withdrawal resulting in an increased release of g-aminobutyric acid (GABA); and methamphetamine withdrawal resulting in a decrease in dopamine, serotonin, and other monoamines. [9]

Risk Factors

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Several studies have shown that multiple risk factors, ranging from social aspects to genetics, can contribute to the severity of NAS and the recovery process. [4][9] Mutations in the genes for opioid receptor expression (mu-opioid receptors OPRM1, delta-OPRD1, and kappa-OPRK1 genes) and the dopamine metabolism pathway (COMT gene) have been associated with quicker recovery resulting in shorter duration of treatment. [11][4][9] Environmental influences that can affect expression of the aforementioned genes, like DNA methylation that results in decreased OPRM1 gene expression, have also been associated with increased severity of NAS. [4] Some non-genetic risk factors include smoking and methadone use of the birthing person during pregnancy that can result in increased severity of NAS. [9]

Management

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Objectives of management are to minimize negative outcomes and promote normal development.[12] Supportive care is the first step in management, but this is typically not enough and is complemented with medication.

Supportive

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Non-medication based approaches to treat neonatal symptoms include swaddling the infant in a blanket, minimizing environmental stimuli, and monitoring sleeping and feeding patterns.[13] Breastfeeding promotes infant attachment and bonding and is associated with a decreased need for medication. These approaches may lessen the severity of NAS and lead to shorter hospital stays.[14]

Medication

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Medication is used to relieve fever, seizures, and weight loss or dehydration.[12] When medication is use for opiate withdrawal in newborn babies is deemed necessary, opiates are the treatment of choice; they are slowly tapered down to wean the baby off opiates.[15] Phenobarbital is sometimes used as an alternative but is less effective in suppressing seizures; however, phenobarbital is superior to diazepam for neonatal opiate withdrawal symptoms. In the case of sedative-hypnotic neonatal withdrawal, phenobarbital is the treatment of choice.[16][17] Clonidine is an emerging add-on therapy.[18] Buprenorphine is under development as an alternative to morphine or methadone as initial therapy.[19]

Opioids such as neonatal morphine solution and methadone are commonly used to treat clinical symptoms of opiate withdrawal, but may prolong neonatal drug exposure and duration of hospitalization.[20] A study demonstrated a shorter wean duration in infants treated with methadone compared to those treated with diluted tincture of opium. When compared to morphine, methadone has a longer half-life in children, which allows for less frequent dosing intervals and steady serum concentrations to prevent neonatal withdrawal symptoms.[21]

Epidemiology

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NAS rates correlate with rates of opioid use disorder among pregnant individuals in the population. The misuse of opioids, along with other illicit substances by this group has increased since the early 2000s, all this while cases and this problem are likely being underreported. [22]

A 2013 study examined the incidence of neonatal abstinence syndrome in 28 states. The researchers found that this rate increased by about 300% (from 1.5 cases to 6.0 cases per 1,000 hospital births) during 1999 to 2013.[23]

[24][25]

Geography

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Neonatal abstinence syndrome is a growing health issue amongst the country. While Ontario claims the highest rate of narcotic use in the country and one of the highest rates of prescription narcotic use in the world (Dow et al., 2012),[26] Northern cities such as North bay are influential contributors. The number of neonates born with addiction or experiencing withdrawal symptoms are increasing at an undesirable rate in North Bay from 22 babies in 2012-2013 to 48 babies born with NAS in 2014-2015 (Leslie, 2015).[27] Furthermore, North Bay Regional Health Centre was home to 10 NAS babies in January 2016 alone (Sheikh, 2016).[28] The dramatic growth in numbers of neonates born with drug addiction will continue to grow if not confronted and managed in a way that is specific and appropriate for the city of North Bay. 

References

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  1. ^ a b Neonatal Abstinence Syndrome on eMedicine
  2. ^ Hall, RW.; Boyle, E.; Young, T. (Oct 2007). "Do ventilated neonates require pain management?". Semin Perinatol. 31 (5): 289–97. doi:10.1053/j.semperi.2007.07.002. PMID 17905183.
  3. ^ "Neonatal abstinence syndrome: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2024-07-26.
  4. ^ a b c d e Kocherlakota, Prabhakar (2014) [March 7, 2014]. "Neonatal Abstinence Syndrome". Pediatrics. 134 (2): e547–e561. doi:10.1542/peds.2013-3524. PMID 25070299.
  5. ^ Convertino, Irma; Sansone, Alice Capogrosso; Marino, Alessandra; Galiulo, Maria T.; Mantarro, Stefania; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado; Tuccori, Marco (2016-10-01). "Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects". Drug Safety. 39 (10): 903–924. doi:10.1007/s40264-016-0435-8. ISSN 1179-1942.
  6. ^ Iqbal MM, Sobhan T, Ryals T (January 2002). "Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant". Psychiatric Services. 53 (1): 39–49. doi:10.1176/appi.ps.53.1.39. PMID 11773648.
  7. ^ Patrick, Stephen; Barfield, Wanda; Poindexter, Brenda; COMMITTEE ON FETUS AND NEWBORN; COMMITTEE ON SUBSTANCE USE AND PREVENTION (November 2020). "Neonatal Opioid Withdrawal Syndrome". Pediatrics. 146 (5): e2020029074. doi:10.1542/peds.2020-029074. PMID 33106341.
  8. ^ Piccotti, Lucia; Voigtman, Barbara; Vongsa, Rebecca; Nellhaus, Emma M.; Rodriguez, Karien J.; Davies, Todd H.; Quirk, Stephen (2019-05-01). "Neonatal Opioid Withdrawal Syndrome: A Developmental Care Approach". Neonatal Network: NN. 38 (3): 160–169. doi:10.1891/0730-0832.38.3.160. ISSN 1539-2880. PMID 31470383.
  9. ^ a b c d e f Anbalagan, Saminathan; Falkowitz, Daria M.; Mendez, Magda D. (2024), "Neonatal Abstinence Syndrome", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31855342, retrieved 2024-07-25
  10. ^ Mercer, J (2009). "Claim 9: "Crack babies" can't be cured and will always have serious problems". Child Development: Myths and Misunderstandings. Thousand Oaks, Calif: Sage Publications, Inc. pp. 62–64. ISBN 978-1-4129-5646-8.
  11. ^ Wachman, Elisha M.; Hayes, Marie J.; Brown, Mark S.; Paul, Jonathan; Harvey-Wilkes, Karen; Terrin, Norma; Huggins, Gordon S.; Aranda, Jacob V.; Davis, Jonathan M. (2013-05-01). "Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome". JAMA. 309 (17): 1821–1827. doi:10.1001/jama.2013.3411. ISSN 1538-3598. PMC 4432911. PMID 23632726.
  12. ^ a b Longo, Dan L.; McQueen, Karen; Murphy-Oikonen, Jodie (22 December 2016). "Neonatal Abstinence Syndrome". New England Journal of Medicine. 375 (25): 2468–2479. doi:10.1056/NEJMra1600879. PMID 28002715.
  13. ^ Lee, Kimberly G. "Neonatal abstinence Syndrome". MedlinePlus. A.D.A.M., Inc. Retrieved 2 November 2014.
  14. ^ Pritham, Ursula A.; Paul, Jonathan A.; Hayes, Marie J. (March 2012). "Opioid Dependency in Pregnancy and Length of Stay for Neonatal Abstinence Syndrome". Journal of Obstetric, Gynecologic, & Neonatal Nursing. 41 (2): 180–190. doi:10.1111/j.1552-6909.2011.01330.x. PMC 3407283. PMID 22375882.
  15. ^ Hudak, ML; Tan, R. C. (30 January 2012). "Neonatal Drug Withdrawal". Pediatrics. 129 (2): e540–e560. doi:10.1542/peds.2011-3212. PMID 22291123.
  16. ^ Osborn, DA; Jeffery, HE; Cole, M (2010). Osborn, David A (ed.). "Opiate treatment for opiate withdrawal in newborn infants". Cochrane Database Syst Rev (3): CD002059. doi:10.1002/14651858.CD002059.pub3. PMID 20927730.
  17. ^ Osborn, DA; Jeffery, HE; Cole, MJ (2010). Osborn, David A (ed.). "Sedatives for opiate withdrawal in newborn infants". Cochrane Database Syst Rev (3): CD002053. doi:10.1002/14651858.CD002053.pub3. PMID 20927729.
  18. ^ Kraft, WK; van den Anker, JN (Oct 2012). "Pharmacologic management of the opioid neonatal abstinence syndrome". Pediatric Clinics of North America. 59 (5): 1147–65. doi:10.1016/j.pcl.2012.07.006. PMC 4709246. PMID 23036249.
  19. ^ Kraft, WK; Dysart, K; Greenspan, JS; Gibson, E; Kaltenbach, K; Ehrlich, ME (Mar 2011). "Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome". Addiction (Abingdon, England). 106 (3): 574–80. doi:10.1111/j.1360-0443.2010.03170.x. PMC 3022999. PMID 20925688.
  20. ^ Logan, Beth A.; Brown, Mark S.; Hayes, Marie J. (March 2013). "Neonatal Abstinence Syndrome: Treatment and Pediatric Outcomes". Clinical Obstetrics and Gynecology. 56 (1): 186–192. doi:10.1097/GRF.0b013e31827feea4. PMC 3589586. PMID 23314720.
  21. ^ Johnson, Melissa R.; Nash, David R.; Martinez, Michael A. (July 2014). "Development and Implementation of a Pharmacist-Managed, Neonatal and Pediatric, Opioid-Weaning Protocol". The Journal of Pediatric Pharmacology and Therapeutics. 19 (3): 165–173. doi:10.5863/1551-6776-19.3.165. PMC 4187529. PMID 25309146.
  22. ^ Hudak, Mark L.; Tan, Rosemarie C.; THE COMMITTEE ON DRUGS; THE COMMITTEE ON FETUS AND NEWBORN; Frattarelli, Daniel A. C.; Galinkin, Jeffrey L.; Green, Thomas P.; Neville, Kathleen A.; Paul, Ian M.; Van Den Anker, John N.; Papile, Lu-Ann; Baley, Jill E.; Bhutani, Vinod K.; Carlo, Waldemar A.; Cummings, James (2012-02-01). "Neonatal Drug Withdrawal". Pediatrics. 129 (2): e540–e560. doi:10.1542/peds.2011-3212. ISSN 0031-4005.
  23. ^ "Hudak ML, Tan RC, The Committee on Drugs and the Committee on Fetus and Newborn. Neonatal Drug Withdrawal. Pediatrics. 2012;129;e540". Pediatrics. 133 (5): 937–938. 2014-05-01. doi:10.1542/peds.2014-0557. ISSN 0031-4005.
  24. ^ "Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009". JournalistsResource.org, retrieved May 15, 2012
  25. ^ Patrick, SW; Schumacher, RE; Benneyworth, BD; Krans, EE; McAllister, JM; Davis, MM (May 9, 2012). "Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009". JAMA: The Journal of the American Medical Association. 307 (18): 1934–40. doi:10.1001/jama.2012.3951. PMID 22546608.
  26. ^ Dow, Ordean (2012). "Neonatal Abstinence syndrome clinical practice guidelines for Ontatio" (PDF). Journal of Population Therapeutics and Clinical Pharmacology. 19: 488–506.
  27. ^ Leslie, K (2015). "Officials can't explain increase in North Bay babies born to addicted moms". CTV News.
  28. ^ Sheikh, I. "North Bay's struggle with opioid-dependent babies". TVO.
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