Baby boy blue – why is this newborn lethargic?

Abstract

Aone-week-old boy was seen in the emergency department with a two-day history of poor feeding and increasing lethargy. He was born at term after an uneventful pregnancy by repeat caesarean section. His birth weight was 3.2 kg. The patient’s Apgar scores were 8 and 9, and he was discharged home on day 3 with exclusive breastfeeding. He has two older siblings: a five-year-old sister born in the mother’s homeland of Sri Lanka, and a three-year-old brother born in Canada by caesarean section because of failure to progress. Both siblings and the parents are in good health, and there was no significant family history. On examination, the baby was a term male infant, afebrile with a blood pressure of 75/45 mmHg, heart rate of 120 beats/ min and shallow respirations with a rate of 16 breaths/min. He did not respond well to stimuli and had a poor suck. His physical examination was otherwise unremarkable. A full septic workup was performed, with unremarkable results. During the process of the workup, a urine drug screen was sent, which was positive for opiates. More specific analysis revealed a serum morphine concentration of 55 µg/mL – a potentially toxic concentration. A 0.01 mg/kg dose of naloxone was administered, with good clinical improvement. Further questioning revealed that the mother was given an acetaminophen-codeine product for analgesia postcaesarean section. She had been having increasing pain after discharge because she was caring for her newborn plus two busy older siblings. She reported taking one or two pain tablets three or four times a day, and noted excellent pain relief but also drowsiness and constipation. Genetic testing was performed to investigate the maternal and infant pathways of codeine and morphine metabolism. The mother was shown to have a gene duplication for cytochrome P450 2D6 (CYP2D6), which classified her as an ultrarapid metabolizer. The mother was also found to be homozygous for the UGT 2B7*2 allele, a polymorphism in the glucuronidation of morphine associated with increased production of morphine 6-glucuronide, the active metabolite of morphine. This ‘two-hit’ genetic variation would expose her newborn to very high concentrations of morphine and the active metabolite of morphine via breast milk.