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  • Updated 07.28.2023
  • Released 10.10.2002
  • Expires For CME 07.28.2026

Neonatal opioid withdrawal syndrome



Neonatal abstinence syndrome, including neonatal opioid withdrawal syndrome, is a clinical diagnosis that describes the constellation of symptoms that result from the abrupt discontinuation of chronic fetal exposure to, most commonly, opioid use in pregnancy. Neonatal abstinence syndrome describes newborns at risk for polysubstance exposure, including opioids, whereas neonatal opioid withdrawal syndrome describes opioid-only withdrawal symptoms (87). In this article, the term “neonatal abstinence syndrome” is used for both opioid-only and polysubstance exposure. The authors provide a brief historical background and information on the pathophysiology, clinical spectrum, and management of neonatal abstinence syndrome. The clinical or consulting neurologist will find this information useful in formulating a differential diagnosis when faced with a newborn with signs and symptoms pertaining to central nervous system/autonomic dysfunction.

Key points

• From 2010 to 2017, the estimated rate of neonatal abstinence syndrome significantly increased by 3.3 per 1000 birth hospitalizations (from 4.0 to 7.3) (39).

• Management of neonatal abstinence syndrome involves appropriately identifying infants at risk for withdrawal, assessing symptoms with objective assessment tools, and managing symptoms with supportive measures and pharmacologic therapy where appropriate.

• Standardization of care, which includes standardization of scoring, use of nonpharmacologic and pharmacologic therapy, and strict adherence to treatment protocols, have all been shown to decrease the duration of pharmacologic therapy and length of hospital stay.

Historical note and terminology

Medical use of opium dates to Mesopotamian and Egyptian cultures. However, morphine, named after Morpheus, the Greek god of dreams, was only isolated from opium in 1806, followed by the isolation of codeine. Congenital morphinism was first described in Germany in 1875 in a newborn with signs of opioid withdrawal at birth. The first report of successful treatment in an infant was in 1903 (76).

Opioids can be divided into natural, semisynthetic, and synthetic opioids. Opium, morphine, and codeine are examples of natural opiates. Semisynthetic opioids are derived from opium, and examples include heroin, hydromorphone, oxycodone, and buprenorphine. Examples of synthetic substances with morphine-like activities include meperidine, fentanyl, methadone, and propoxyphene (40). Methadone has become the most commonly used opiate during pregnancy associated with neonatal abstinence syndrome (31%) (88).

Other substances such as alcohol, tobacco, benzodiazepine, and selective serotonin-reuptake inhibitors (SSRIs) can provoke neurobehavioral dysregulation symptoms similar to those occurring in neonatal abstinence syndrome (98).

Neonatal opioid withdrawal syndrome describes the clinical withdrawal syndrome seen in infants born to mothers who have used opioids only during pregnancy. As polysubstance use is common, it is not always possible to attribute the cause of neonatal abstinence syndrome to exposure to opioids alone (64). Thus, this article focuses on neonatal abstinence syndrome as a postnatal withdrawal syndrome that occurs among opioid-exposed infants with or without polysubstance exposure. An expert consensus panel proposed a standardized definition that requires a known history of in-utero opioid exposure (by history, not necessarily by toxicology) and the presence of at least two of the five most common clinical signs characteristic of withdrawal (excessive/continuous crying, fragmented sleep, tremors, increased muscle tone, gastrointestinal dysfunction) (46).

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