Neonatal Opioid Withdrawal Syndrome (NOWS): A Transgenerational Echo of the Opioid Crisis

Cold Spring Harb Perspect Med. 2021 Mar 1;11(3):a039669. doi: 10.1101/cshperspect.a039669.


The incidence of neonatal opioid withdrawal syndrome (NOWS) has increased substantially in the setting of the opioid epidemic, a major public health problem in the United States. At present, NOWS has commonly used assessment and treatment protocols, but new protocols have questioned old practices. However, because of limited access to opioid use disorder (OUD) treatment and socioeconomic factors, many pregnant (and postpartum) women with OUD do not receive treatment. The pathophysiology of NOWS is not completely understood, although limited research studies have been conducted in humans and animals to better understand its etiology. Moreover, there is evidence that epigenetic and genetic factors play a role in the development of NOWS, but further study is needed. Animal models have suggested that there are deleterious effects of in utero opioid exposure later in life. Clinical research has revealed the harmful long-term sequelae of NOWS, with respect to cognitive function and childhood development. Many psychiatric disorders begin during adolescence, so as infants born with NOWS approach adolescence, additional clinical and molecular studies are warranted to identify biologic and psychosocial risk factors and long-term effects of NOWS. Additionally, access to specialized OUD treatment for pregnant women must be more readily available in the United States, especially in rural areas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Female
  • Humans
  • Infant, Newborn
  • Models, Animal
  • Neonatal Abstinence Syndrome / epidemiology
  • Neonatal Abstinence Syndrome / etiology*
  • Opiate Substitution Treatment / methods
  • Opioid Epidemic
  • Opioid-Related Disorders / epidemiology
  • Opioid-Related Disorders / etiology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology*


  • Analgesics, Opioid