Ventilatory response to carbon dioxide of infants following chronic prenatal methadone exposure

Nine infants chronically exposed to methadone in utero were studied from birth to 7 weeks of age (66 studies). The maternal dose of methadone/HCl during the third trimester ranged from 14 to 70 mg orally once a day. The mean (range) of serum methadone t 1/2 in the neonates was 53 hours (22 to 113). In the first four days of life the methadone-exposed infants had a significantly (P less than 0.005) decreased sensitivity to carbon dioxide compared to control infants as measured by the slope of the ventilatory response curve. The mean slope +/- SD for the methadone-exposed infants, 10.4 +/- 7.7 ml/minute/kg mm Hg, was one third that of the control group (30.0 +/- 9.9 ml/minute/kg/mm Hg). Total ventilation, respiratory frequency, oxygen consumption, and end-tidal PCO2 were not significantly different in the two groups. The depressed ventilatory response to carbon dioxide persisted for an average of 15 days and lasted as long as 31 days in one infant. The time required to achieve a normal slope was not related to the size of the maternal methadone dose, to neonatal serum methadone t 1/2, or to the severity of and therapy for methadone withdrawal. If this abnormality in sensitivity to carbon dioxide persists beyond the neonatal period in some infants, it may contribute to the increased incidence of the sudden infant death syndrome among infants exposed to methadone in utero. Measurement of the ventilatory response to carbon dioxide may be clinically useful to determine which of these infants are at risk for SIDS.