Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study

Clin Pharmacol Ther. 2009 Jan;85(1):31-5. doi: 10.1038/clpt.2008.157. Epub 2008 Aug 20.


A large number of women receive codeine for obstetric pain while breastfeeding. Following a case of fatal opioid poisoning in a breastfed neonate whose codeine prescribed mother was a CYP2D6 ultrarapid metabolizer (UM), we examined characteristics of mothers and infants with or without signs of central nervous system (CNS) depression following codeine exposure while breastfeeding in a case-control study. Mothers of symptomatic infants (n = 17) consumed a mean 59% higher codeine dose than mothers of asymptomatic infants (n = 55) (1.62 (0.79) mg/kg/day vs. 1.02 (0.54) mg/kg/day; P = 0.004). There was 71% concordance between maternal and neonatal CNS depression. Two mothers whose infants exhibited severe neonatal toxicity were CYP2D6 UMs and of the UGT2B7*2/*2 genotype. There may be a dose-response relationship between maternal codeine use and neonatal toxicity, and strong concordance between maternal-infant CNS depressive symptoms. Breastfed infants of mothers who are CYP2D6 UMs combined with the UGT2B7*2/*2 are at increased risk of potentially life-threatening CNS depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / metabolism*
  • Analgesics, Opioid / therapeutic use
  • Apnea / chemically induced
  • Breast Feeding / adverse effects*
  • Case-Control Studies
  • Codeine / adverse effects*
  • Codeine / metabolism*
  • Codeine / therapeutic use
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Milk, Human / chemistry*
  • Opioid-Related Disorders / etiology*
  • Opioid-Related Disorders / genetics*
  • Opioid-Related Disorders / physiopathology
  • Pain / drug therapy
  • Pharmacogenetics


  • Analgesics, Opioid
  • Cytochrome P-450 CYP2D6
  • Codeine