Prenatal exposure to buprenorphine or methadone: effects on physical growth, neurological development and temperament in early childhood.

Abstract

Pharmaceutical maintenance with methadone is the current gold standard for pregnant women with opioid-dependence. While there are many benefits of methadone, its use during pregnancy is associated with high rates of neonatal abstinence syndrome, and long term developmental and behavioural deficits in exposed infants and children. Buprenorphine is increasingly being prescribed as pharmaceutical treatment for opioid dependence due to its milder withdrawal effects, longer duration of action, and improved safety profile, compared with methadone. Although there is a growing body of research supporting the safety and efficacy of buprenorphine during pregnancy and the early neonatal period, studies of the longer term development of children exposed to buprenorphine are scarce. This is the first study to provide comprehensive, longitudinal information about the physical growth, neurological and psychological development of Australian children prenatally exposed to buprenorphine or methadone. Participants were 30 women maintained on buprenorphine, 24 women maintained on methadone, and 33 women who were not opioid-dependent, and their children. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study, and children were assessed at four, 12 and 24 months post partum. Physical development was monitored in terms of weight, length and head circumference (HC) at each follow-up assessment. Neurological development was assessed by measuring latency of Visual Evoked Potentials (VEP) at four months of age and the Bayley Scales of Infant Development (2nd ed.) at 12 and 24 months. Care-giver ratings of child temperament were used as a measure of psychological development, and were collected at each follow-up assessment. Assessment of social, environmental and family risk factors was also undertaken. Results showed that children prenatally exposed to buprenorphine did not differ from a nonexposed control group in their physical growth, neurological development, or temperament over the first two years of life. However, results indicated that prenatal exposure to methadone may have a pervasive influence on weight in early childhood, with children prenatally exposed to methadone continuing to have significantly lower weight, compared with non-exposed children, until two years of age. Additionally, it appears that prenatal exposure to methadone may result in significant delays to visual maturation in infancy. At four months of age, VEP latencies of infants prenatally exposed to methadone were found to be prolonged compared with those of both infants prenatally exposed to buprenorphine, and those of non-exposed infants. Scores on the Bayley Scales at 12 and 24 months of age, and caregiver-rated infant temperament at 4-, 12- and 24-months, did not differ between children prenatally exposed to methadone, buprenorphine, or non-exposed controls. Finally, regardless of substance-exposure, the quality of a child’s caregiving environment was shown to have a strong influence over infant cognitive, motor and behavioural development, while maternal-infant attachment was found to be an important predictor of child temperament. Overall, the findings of this study suggest that maternal use of buprenorphine in pregnancy appears to be as safe as methadone in terms of early child developmental outcomes. The benefits of buprenorphine, in terms of early neurodevelopment and healthy weight gain, suggest that it should be considered as a first line treatment for opioid dependence in pregnant women. More-over, results from this study highlight the importance of a child’s care-giving environment, and of early maternal mental health, over and above prenatal substance exposure, in shaping future developmental outcomes.