Opiate withdrawal in utero increases neonatal morbidity in the rat

Long-term oral administration of the long-acting opiate 1-α-acetylmethadol (LAAM) to female rats beginning on the day of conception interfered with the dams' ability to carry litters to term. When treatment was initiated 3 weeks prior to mating this effect was not observed. Daily administration of the opiate antagonist naloxone from day 14 of gestation through term, to precipitate withdrawal in utero, resulted in increased stillbirths, decreased pup weight and size, and weight loss 24 hours after birth. These data question the validity of animal experiments which purport to be models for methadone maintenance programs but in which treatment is started immediately prior to or soon after conception. They also suggest that withdrawal in utero may be responsible for many of the adverse effects of opiates on human and animal development.