Maternal vagal tone change in response to methadone is associated with neonatal abstinence syndrome severity in exposed neonates

J Matern Fetal Neonatal Med. 2007 Sep;20(9):677-85. doi: 10.1080/14767050701490327.


Objective: Though methadone pharmacotherapy is the treatment of choice for opiate-dependence during pregnancy in the USA, most methadone-exposed neonates develop neonatal abstinence syndrome (NAS). NAS expression is widely variable among methadone-exposed neonates and only a subset requires pharmacotherapy. This study explores the potential predictors of NAS severity, including aspects of maternal substance use and methadone maintenance histories, concomitant exposure to other licit substances, and individual differences in intrinsic maternal or infant factors that may affect the infant's vulnerability to NAS expression.

Methods: Fifty methadone-maintained pregnant women attending a comprehensive substance abuse treatment facility, received electrocardiogram monitoring at 36 weeks of gestation at the times of trough and peak maternal methadone levels. Vagal tone, an estimate of the magnitude of an individual's respiratory sinus arrhythmia and an indicator of autonomic control, was derived.

Results: NAS expression was unrelated to maternal substance abuse history, methadone maintenance history, or psychotropic medication exposure. Male infants displayed more profound NAS symptoms and received more pharmacotherapy to treat NAS (all p < 0.05). NAS expression was related to maternal vagal reactivity; both suppression and activation of maternal vagal tone in response to methadone administration were positively and significantly associated with NAS symptomatology (F (2,44) = 4.15, p < 0.05) and treatment (F (2,44) = 3.39, p < 0.05). Infants of vagal non-responder mothers showed substantially lower NAS expression.

Conclusions: NAS severity is associated with maternal vagal tone change in response to methadone administration.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Apgar Score
  • Arrhythmia, Sinus / diagnosis
  • Electrocardiography*
  • Female
  • Heart / drug effects*
  • Heart / physiopathology*
  • Humans
  • Infant, Newborn
  • Male
  • Methadone / adverse effects*
  • Methadone / therapeutic use
  • Mothers*
  • Neonatal Abstinence Syndrome / diagnosis*
  • Opioid-Related Disorders / complications
  • Opioid-Related Disorders / physiopathology*
  • Opioid-Related Disorders / rehabilitation
  • Pregnancy
  • Prenatal Exposure Delayed Effects / diagnosis*
  • Severity of Illness Index
  • Sex Characteristics
  • Treatment Outcome
  • Vagus Nerve Diseases / chemically induced*
  • Vagus Nerve Diseases / complications*


  • Methadone