1. ¹Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada
2. ²The Ivey Chair in Molecular Toxicology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
3. ³Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
4. ⁴Pharmaceutical Outcomes and Policy Innovations Program, University of British Columbia, Vancouver, British Columbia, Canada
5. ⁵Section of Developmental Pharmacology and Therapeutics, Children's Mercy Hospital, Kansas City, Missouri, USA
6. ⁶Motherisk Program, Hospital for Sick Children, Toronto, Ontario, Canada

Correspondence: G Koren, (gkoren@sickkids.ca) or (gkoren@uwo.ca)

Received 28 May 2008; Accepted 26 June 2008; Published online 20 August 2008.

Abstract

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.