Are male neonates more vulnerable to neonatal abstinence syndrome than female neonates?

Gend Med. 2011 Dec;8(6):355-64. doi: 10.1016/j.genm.2011.10.001. Epub 2011 Nov 15.


Background: Prior studies have shown an increased vulnerability among males to adverse outcomes during the postnatal period. Most children exposed to opioids and other medications in utero develop neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood.

Objective: This investigation examined the role of neonatal sex in the postnatal period for neonates exposed to standardized opioid maintenance treatment in utero with a focus on NAS regarding severity, medication requirements, and duration.

Methods: This was a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy, multicenter trial (MOTHER study) that examined the comparative safety and efficacy of methadone and buprenorphine during pregnancy. A total of 131 neonates born to opioid-dependent women randomized at 6 US sites (n = 74) and 1 European site (n = 37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed.

Results: Males had a significantly higher birth weight (P = 0.027) and head circumference (P = 0.017) compared with females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, or duration, or medication administered, and there were no significant differences in concomitant drug consumption during pregnancy (P = 0.959).

Conclusions: This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS. identifier: NCT 00271219.

Trial registration: NCT00271219.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Birth Weight / drug effects*
  • Buprenorphine / adverse effects*
  • Double-Blind Method
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Methadone / adverse effects*
  • Neonatal Abstinence Syndrome / epidemiology*
  • Opioid-Related Disorders / epidemiology*
  • Pregnancy
  • Pregnancy Complications / chemically induced
  • Pregnancy Outcome
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Sex Distribution
  • Sex Factors


  • Buprenorphine
  • Methadone

Associated data