Pharmacogenetics of Neonatal Opioid Toxicity Following Maternal Use of Codeine During Breastfeeding: A Case–Control Study

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. Clinical Pharmacology & Therapeutics (2008); 85 , 1, 31–35 doi: 10.1038/clpt.2008.157