Neonatal withdrawal

Neonatal withdrawal or neonatal abstinence syndrome (NAS) is a withdrawal syndrome of infants after birth caused by in utero exposure to drugs of dependence.[1] Common signs and symptoms include tremors, irritability, vomiting, diarrhea, and fever.[2][3][4] NAS is primarily diagnosed with a detailed medication history and scoring systems.[5] First-line treatment should begin with non-medication interventions to support neonate growth, though medication interventions may be used in certain situations.[6]

Neonatal withdrawal
Other namesNeonatal abstinence syndrome
Nina wcześniak.jpg
Prematurity can accompany withdrawal
SpecialtyPediatrics Edit this on Wikidata

In 2009, approximately 6 per 1,000 newborns in the United States were born to pregnant persons with opioid use.[7] 55-94% of newborns who are exposed to drugs of dependence will show neurological symptoms at birth, ranging from mild to severe, depending on the quantity and type of substance exposure.[8]

The two types of NAS are prenatal and postnatal. Prenatal NAS is caused at birth by discontinuation of drugs taken by the pregnant person.[9] Postnatal NAS is caused by discontinuation of drugs that were given directly to the infant.[10]

Signs and symptomsEdit

Drug and alcohol use during pregnancy can lead to many health problems in the fetus and infants, including NAS. The onset of clinical presentation typically appears within 48 to 72 hours of birth, but may take up to 8 days.[8][11] The signs and symptoms of NAS may be different depending on which substance the pregnant person used.[12]

Common signs and symptoms in infants with NAS may include:[2][3][4]

  • Signs due to hyperactivity of the central nervous system:
    • Tremors (trembling)
    • Irritability (excessive mood crying)
    • Sleep problems
    • High-pitched crying
    • Muscle tightness
    • Hyperactive reflexes
    • Seizures (2% to 11%)
  • Signs due to hyperactivity of stomach and intestines:
    • Poor feeding and sucking reflex
    • Vomiting
    • Diarrhea
  • Signs due to hyperactivity of autonomous nervous system:
    • Fever
    • Sweating
    • Yawning, stuffy nose, and sneezing
    • Fast breathing

CausesEdit

The drugs involved can include opioids, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitor (SNRIs), tricyclic antidepressants (TCAs), ethanol, and benzodiazepines.[1][12][13] Opioids may be more likely to cause NAS than other substances due to an increase in its usage.[14] Exposure to heroin and methadone claimed to be correlated with a 60 to 80% occurrence of neonatal withdrawal, whereas buprenorphine has been associated with a lower risk.[15] Neonatal abstinence syndrome does not happen in prenatal cocaine exposure. Prematurity and exposure to other drugs may instead be the cause of symptoms.[16]

The main mechanistic pathway of prescribed and illicit substance-induced NAS is the hyperactivity of the central and autonomic nervous system and gastrointestinal tract[17] There are several potential mechanisms and pathways that have been proposed, which includes the interaction between the neurotransmitters and lack of adequate expression of opioid receptors.[14] However, the main pathophysiology of this syndrome remains unknown.[14] Most of the opioid induced NAS are due to opioid exposure during pregnancy for pain relief, misuse, or abuse of prescribed opioids or other medication-assisted treatment of opioid use disorder.[11]

DiagnosisEdit

The presence of withdrawal in the neonate can be confirmed by taking a detailed medical history from the birthing person. The medical history should include physical and mental health problems, prescription and non-prescription medication use, nutritional supplement use, history of alcohol and substance use, childhood adversities, cultural and social beliefs, past traumatic experiences, and infectious diseases such as HIV.[18] Since the medical history of the birth giver may not be available immediately after delivery, some testing needs to be done in the infant to confirm possible exposure. Infant's urine, meconium, umbilical cord tissue or hair can be used for testing.[14][18] The timing of urine sample collection is critical because some drugs may become undetectable after they are metabolized and eliminated from the body. Also, urine test results can only confirm if the fetus was exposed to drugs a few days before birth.[14] Meconium testing can be used to confirm drug exposure in earlier stage of pregnancy, but the collecting process is more difficult.[18] Umbilical cord tissue testing is a relatively new testing method but its accuracy is still controversial.[18] The birthing person's blood and urine sample should also be collected for drug screening.[19] Chest X-rays can confirm or infirm the presence of heart defects.[20][1]

AssessmentEdit

Depending on what hospital setting the infant is in, different scoring systems are used for assessing the severity and the need for medication treatment in neonatal withdrawal syndrome.[5] One challenge with existing clinical predication tools is that they were designed to assess opiate withdrawal only. The Finnegan Neonatal Abstinence Scoring System (FNASS), or its modified version is the most widely used prediction tool currently in the United States.[17] The FNASS tool focuses on 21 signs of neonatal opioid withdrawal, and a score from 0 to 5 is assigned based on the severity of the symptom. The measurement needs to be repeated every two to four hours.[21][22] The cutoff for initiation, escalation or de-escalation of medication treatment may be varied. A 2019 review shows that "most institutions using the FNASS have protocols that call for starting or increasing pharmacologic treatment after an infant has received three FNASS scores ≥8 or two scores ≥12."[22] However, there are limitations to the FNASS tool. The repeated measurements may delay treatment and result in increased treatment need. In order to assess some of the signs in the measurement process, infants will be stimulated as opposed to minimizing stimulation recommended in non-medication treatment.[22] A study also indicates that the FNASS tool "has not been validated to show utility in improving outcomes for infants with NAS".[17]

PreventionEdit

Neonatal withdrawal is prevented by the pregnant person abstaining from illicit or prescribed substances. In some cases, a prescribed medication may need to be discontinued during the pregnancy to prevent addiction by the infant. Early prenatal care can identify addictive behaviors in the pregnant person and family system.[23] Referrals to treatment centers is appropriate.[20] Some prescribed medicines should not be stopped without medical supervision, or harm may result. Suddenly stopping a medication can result in a premature birth, fetal complications, and miscarriage.[7] It is recommended that pregnant individuals discuss medication, alcohol, and tobacco use with their health-care provider and to seek assistance to abstain when appropriate. A pregnant person may need medical attention if they are using drugs non-medically, using drugs not prescribed to them, or using alcohol or tobacco.[1]

There are several strategies to prevent the incidence of NAS, those include:[11]

  • Primary Preventions [11]
    • Follow guidance of 2016 CDC Guideline for Prescribing Opioids for Chronic Pain, which addresses the effectiveness of opioid dosing and treatment, the benefits and risks, and strategies to avoid opioid misuse[24]
    • Utilize prescription drug monitoring programs (PDMPs) to avoid overuse of opioids[25]
  • Provision of treatment for opioid use disorder among pregnant persons[26]
  • Non-medicine strategies via minimizing environmental stimuli[13]

However, there are some barriers to prevention which includes lack of consensus to screening tools to identify substance use while pregnant, stigma, provider bias, and legal consequences.[11]

TreatmentEdit

Treatment depends on the drug involved, the infant's overall health, abstinence scores (FNASS scoring system), and whether the infant was born full-term or premature. It is recommended to observe and provide supportive measure to infants who are at risk of neonatal abstinence syndrome in the hospital.[27] Infants with severe symptoms may require both supportive measures and medicines.[28] Treatment for NAS may require the infant to stay in the hospital for weeks or months after birth.

The goal of treatment is to minimize negative outcomes and promote normal development.[29] Infants may be prescribed a drug similar to the one the pregnant person used during pregnancy, and slowly decrease the dose over time.[30] This helps wean the infant off the drug and relieves some withdrawal symptoms.

Non-Medication TreatmentEdit

First-line treatment should begin with non-medication interventions to support maturation of the neonate.

Common non-medication approaches include:

Adjusting physical environmentsEdit

Infants with NAS symptoms may have hypersensitivity to light and sounds. Techniques such as darkening the room and eliminating surrounding sounds work to lessen the neonate's visual and auditory stimuli.[14]

SwaddlingEdit

Swaddling (wrapping an infant firmly in a blanket) can help improve sleep, develop nerves and muscles, decrease stress, and improve motor skills.[31]

BreastfeedingEdit

Infants with NAS may have problems with feeding or slow growth, which require higher-calorie feedings that provide greater nutrition.[31] It is beneficial to give smaller portions more often throughout the day.[1] Breastfeeding promotes infant attachment and bonding, and is associated with a decreased need for medication, may lessen the severity of NAS, and lead to shorter hospital stays.[32] A 2020 Cochrane Review investigating the different non-medication therapies and their effects on NAS was inconclusive on whether one non-medication therapy was better than another.[33]

Most pregnant people who are taking buprenorphine or methadone can safely breastfeed their infant. Both buprenorphine and methadone remain in the human milk at low concentrations, which will reduce signs and symptoms of NAS and likely decrease the treatment time. However, there are exclusions in which it is not safe to breastfeed, such as an HIV-positive pregnant person and a pregnant person with history of street drug use or multiple illicit drug use.[18][12]

Medication TreatmentEdit

Although non-medication intervention remains first-line treatment, pharmacological intervention, when appropriate and indicated, can improve signs of neonatal withdrawal.[6]

Common medication approaches:

OpioidsEdit

Opioids have shown to improve symptoms to a clinically safe level but may not affect length of hospital stay.[34] Its common to slowly taper down to wean the infant off.[13]

SedativesEdit

Sedatives such as phenobarbital or diazepam are less effective at symptom control compared to opioids but can reduce length of hospital stay.[34]

ClonidineEdit

When compared to opioids, clonidine was just as effective at improving clinical symptoms.[34]

Additional medication is used to relieve fever, seizures, and weight loss or dehydration.[29] A 2021 systematic review found low-certainty evidence that phenobarbital lengthened hospital stays but resulted in a return to birth-weight more rapidly. Low-certainty evidence also showed phenobarbital reduced treatment failure rates compared to diazepam and chlorpromazine. There was also low-certainty evidence of increased hospitalization days with clonidine and opioid compared to phenobarbital and opioid.[35]

OutcomesEdit

A 2018 Meta-analysis reported that newborns diagnosed with NAS are likely to recover with non-medication intervention when roomed with family during their hospital stay compared to newborns diagnosed with NAS that are treated in newborn intensive care unit.[36]

Data is limited and more research needs to be conducted to properly evaluate long-term outcomes in children with a prior diagnosis of NAS.[37] However, long-term monitoring into adolescence may be necessary as a 2019 meta-analysis gave evidence of some longterm cognitive and physical side effects associated with prenatal opioid exposure.[38]

EpidemiologyEdit

United StatesEdit

A 2012 study analyzed information on 7.4 million discharges from 4,121 hospitals in 44 states, to measure trends and costs associated with NAS over the past decade. The study indicated that between 2000 and 2009, the number of pregnant people using opiates increased from 1.19 to 5.63 per 1,000 hospital births per year.[39]

In 2017 the Centers for Disease Control(CDC) reported an increase of diagnosis of NAS to 7 cases every 1,000 births with indiscrimination to state or demographic group. Additionally, the CDC reported in 2019 that 7% of pregnant individuals self-reported use of opioids at some point in their pregnancy.[40]

A 2018 Review of NAS reports that the epidemiology of NAS continues to change and evolve. Though opioids are still the most common drug reported in diagnosis of NAS, there are instances where opioids are not the only class of drug the infant is exposed to during pregnancy. Diagnosis of NAS continues and is substantially greater in rural areas compared to urban areas. As the epidemiology continues to change and evolve calls for the need for more research and standardization of treatment.[17]

OtherEdit

A 2020 literature review published by the Saskatchewan Prevention Institute reports that NAS has significantly increased in England, Western Australia, and Canada within the last decade, noting that current statistics may be underestimated as reluctance to report can be attributed to stigma associated with diagnosis or differing protocols amongst institutions. From 2016 to 2017 Canada overall reported 1,850 diagnosis of NAS.[41]

See alsoEdit

ReferencesEdit

  1. ^ a b c d e "Neonatal abstinence Syndrome". MedlinePlus. US Library of Medicine. 2017. Retrieved 27 July 2017.  This article incorporates text from this source, which is in the public domain.
  2. ^ a b Kocherlakota P (2014). "Neonatal abstinence syndrome". Pediatrics. 134 (2): e547-61. doi:10.1542/peds.2013-3524. PMID 25070299. S2CID 18722347.
  3. ^ a b "Neonatal abstinence syndrome: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2020-07-27.
  4. ^ a b Patrick SW, Barfield WD, Poindexter BB (2020). "Neonatal Opioid Withdrawal Syndrome". Pediatrics. 146 (5): e2020029074. doi:10.1542/peds.2020-029074. PMID 33106341. S2CID 225083661.
  5. ^ a b Sanlorenzo LA, Stark AR, Patrick SW (2018). "Neonatal abstinence syndrome: an update". Current Opinion in Pediatrics. 30 (2): 182–186. doi:10.1097/MOP.0000000000000589. PMC 5843557. PMID 29346142.
  6. ^ a b Anbalagan S, Mendez MD (2021). "Neonatal Abstinence Syndrome". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 31855342. Retrieved 2021-07-27.
  7. ^ a b "A Collaborative Approach to the Treatment of Pregnant Women with Opioid Use Disorders". Substance Abuse and Mental Health Administration (SAMHSA). U.S. Department Health & Human Services. Retrieved 2021-07-27.
  8. ^ a b Ghazanfarpour M, Najafi MN, Roozbeh N, Mashhadi ME, Keramat-Roudi A, Mégarbane B, et al. (2019). "Therapeutic approaches for neonatal abstinence syndrome: a systematic review of randomized clinical trials". Daru. 27 (1): 423–431. doi:10.1007/s40199-019-00266-3. PMC 6593026. PMID 31093953.
  9. ^ "Neonatal abstinence syndrome (NAS)". www.marchofdimes.org. Retrieved 2021-08-04.
  10. ^ Hall RW, Boyle E, Young T (2007). "Do ventilated neonates require pain management?". Seminars in Perinatology. 31 (5): 289–97. doi:10.1053/j.semperi.2007.07.002. PMID 17905183.
  11. ^ a b c d e Ko JY, Wolicki S, Barfield WD, Patrick SW, Broussard CS, Yonkers KA, Naimon R, Iskander J (2017). "CDC Grand Rounds: Public Health Strategies to Prevent Neonatal Abstinence Syndrome". MMWR. Morbidity and Mortality Weekly Report. 66 (9): 242–245. doi:10.15585/mmwr.mm6609a2. PMC 5687191. PMID 28278146.
  12. ^ a b c Kocherlakota P (2014). "Neonatal abstinence syndrome". Pediatrics. 134 (2): e547-61. doi:10.1542/peds.2013-3524. PMID 25070299. S2CID 18722347.
  13. ^ a b c Hudak ML, Tan RC (2012). "Neonatal drug withdrawal". Pediatrics. 129 (2): e540-60. doi:10.1542/peds.2011-3212. PMID 22291123. S2CID 2257683.
  14. ^ a b c d e f Anbalagan S, Mendez MD (2021). "Neonatal Abstinence Syndrome". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 31855342. Retrieved 2021-07-27.
  15. ^ Siu A, Robinson CA (2014). "Neonatal abstinence syndrome: essentials for the practitioner". The Journal of Pediatric Pharmacology and Therapeutics. 19 (3): 147–55. doi:10.5863/1551-6776-19.3.147. PMC 4187528. PMID 25309144.
  16. ^ 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.
  17. ^ a b c d Sanlorenzo LA, Stark AR, Patrick SW (2018). "Neonatal abstinence syndrome: an update". Current Opinion in Pediatrics. 30 (2): 182–186. doi:10.1097/MOP.0000000000000589. PMC 5843557. PMID 29346142.
  18. ^ a b c d e Patrick SW, Barfield WD, Poindexter BB (2020). "Neonatal Opioid Withdrawal Syndrome". Pediatrics. 146 (5): e2020029074. doi:10.1542/peds.2020-029074. PMID 33106341. S2CID 225083661.
  19. ^ Jansson LM, Patrick SW (2019). "Neonatal Abstinence Syndrome". Pediatric Clinics of North America. 66 (2): 353–367. doi:10.1016/j.pcl.2018.12.006. PMC 7605356. PMID 30819342.
  20. ^ a b Henry NJ, McMichael M, Johnson J, DiStasi A, Roland P, Wilford KL, Barlow MS (2016). RN Maternal Newborn Nursing (10th ed.). Stilwell, KS: Assessment Technologies Institute. p. 184. ISBN 978-1-56533-569-1.
  21. ^ Jansson LM, Velez M, Harrow C (2009). "The opioid-exposed newborn: assessment and pharmacologic management". Journal of Opioid Management. 5 (1): 47–55. doi:10.5055/jom.2009.0006. PMC 2729086. PMID 19344048.
  22. ^ a b c Schiff DM, Grossman MR (2019). "Beyond the Finnegan scoring system: Novel assessment and diagnostic techniques for the opioid-exposed infant". Seminars in Fetal & Neonatal Medicine. 24 (2): 115–120. doi:10.1016/j.siny.2019.01.003. PMC 6451877. PMID 30738754.
  23. ^ Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. (1998). "Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults: The Adverse Childhood Experiences (ACE) Study". American Journal of Preventive Medicine. 14 (4): 245–258. doi:10.1016/S0749-3797(98)00017-8. ISSN 0749-3797. PMID 9635069.
  24. ^ Dowell D, Haegerich TM, Chou R (2016). "CDC Guideline for Prescribing Opioids for Chronic Pain - United States". MMWR. Recommendations and Reports. 65 (1): 1–49. doi:10.15585/mmwr.rr6501e1. PMID 26987082.
  25. ^ Patrick SW, Fry CE, Jones TF, Buntin MB (2016). "Implementation Of Prescription Drug Monitoring Programs Associated With Reductions In Opioid-Related Death Rates". Health Affairs. 35 (7): 1324–32. doi:10.1377/hlthaff.2015.1496. PMC 5155336. PMID 27335101.
  26. ^ ACOG Committee on Health Care for Underserved Women; American Society of Addiction Medicine (2012). "ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy". Obstetrics and Gynecology. 119 (5): 1070–6. doi:10.1097/AOG.0b013e318256496e. PMID 22525931.
  27. ^ Wachman EM, Houghton M, Melvin P, Isley BC, Murzycki J, Singh R, et al. (2020). "A quality improvement initiative to implement the eat, sleep, console neonatal opioid withdrawal syndrome care tool in Massachusetts' PNQIN collaborative". Journal of Perinatology. 40 (10): 1560–1569. doi:10.1038/s41372-020-0733-y. PMID 32678314. S2CID 220576891.
  28. ^ Disher T, Gullickson C, Singh B, Cameron C, Boulos L, Beaubien L, Campbell-Yeo M (2019). "Pharmacological Treatments for Neonatal Abstinence Syndrome: A Systematic Review and Network Meta-analysis". JAMA Pediatrics. 173 (3): 234–243. doi:10.1001/jamapediatrics.2018.5044. PMC 6439896. PMID 30667476.
  29. ^ a b McQueen K, Murphy-Oikonen J (2016). "Neonatal Abstinence Syndrome". The New England Journal of Medicine. 375 (25): 2468–2479. doi:10.1056/NEJMra1600879. PMID 28002715.
  30. ^ Kraft WK, Stover MW, Davis JM (2016). "Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant". Seminars in Perinatology. 40 (3): 203–12. doi:10.1053/j.semperi.2015.12.007. PMC 4808371. PMID 26791055.
  31. ^ a b Mangat AK, Schmölzer GM, Kraft WK (2019). "Pharmacological and non-pharmacological treatments for the Neonatal Abstinence Syndrome (NAS)". Seminars in Fetal & Neonatal Medicine. 24 (2): 133–141. doi:10.1016/j.siny.2019.01.009. PMC 6451887. PMID 30745219.
  32. ^ Pritham UA, Paul JA, Hayes MJ (March 2012). "Opioid dependency in pregnancy and length of stay for neonatal abstinence syndrome". Journal of Obstetric, Gynecologic, and Neonatal Nursing. 41 (2): 180–190. doi:10.1111/j.1552-6909.2011.01330.x. PMC 3407283. PMID 22375882.
  33. ^ Pahl A, Young L, Buus-Frank ME, Marcellus L, Soll R, et al. (Cochrane Neonatal Group) (December 2020). "Non-pharmacological care for opioid withdrawal in newborns". The Cochrane Database of Systematic Reviews. 12: CD013217. doi:10.1002/14651858.CD013217.pub2. PMC 8130993. PMID 33348423.
  34. ^ a b c Zankl A, Martin J, Davey JG, Osborn DA, et al. (Cochrane Neonatal Group) (2021). "Opioid treatment for opioid withdrawal in newborn infants". The Cochrane Database of Systematic Reviews. 2021 (7): CD002059. doi:10.1002/14651858.CD002059.pub4. PMC 8261830. PMID 34231914.
  35. ^ Zankl A, Martin J, Davey JG, Osborn DA (2021). "Sedatives for opioid withdrawal in newborn infants". The Cochrane Database of Systematic Reviews. 2021 (5): CD002053. doi:10.1002/14651858.CD002053.pub4. PMC 8129634. PMID 34002380.
  36. ^ MacMillan KD, Rendon CP, Verma K, Riblet N, Washer DB, Volpe Holmes A (2018). "Association of Rooming-in With Outcomes for Neonatal Abstinence Syndrome: A Systematic Review and Meta-analysis". JAMA Pediatrics. 172 (4): 345–351. doi:10.1001/jamapediatrics.2017.5195. PMC 5875350. PMID 29404599.
  37. ^ Reddy UM, Davis JM, Ren Z, Greene MF (2017). "Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes: Executive Summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists, American Academy of Pediatrics, Society for Maternal-Fetal Medicine, Centers for Disease Control and Prevention, and the March of Dimes Foundation". Obstetrics and Gynecology. 130 (1): 10–28. doi:10.1097/AOG.0000000000002054. PMC 5486414. PMID 28594753.
  38. ^ Yeoh SL, Eastwood J, Wright IM, Morton R, Melhuish E, Ward M, Oei JL (2019). "Cognitive and Motor Outcomes of Children With Prenatal Opioid Exposure: A Systematic Review and Meta-analysis". JAMA Network Open. 2 (7): e197025. doi:10.1001/jamanetworkopen.2019.7025. PMC 6628595. PMID 31298718.
  39. ^ Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM (2012). "Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009". JAMA. 307 (18): 1934–40. doi:10.1001/jama.2012.3951. PMID 22546608.
  40. ^ CDC (2021). "Data and Statistics About Opioid Use During Pregnancy | CDC". Centers for Disease Control and Prevention. Retrieved 2021-07-29.
  41. ^ Williamson L (2020). "Neonatal Abstinence Syndrome Literature Review". Saskatchewan Prevention Institute. Retrieved 2021-07-29.

External linksEdit

Classification
External resources