The Effects of Prenatal Exposure to Methadone on Clinical and Neurobehavioural Outcomes of Infants Measured at Term

Abstract

This study examined the effects of prenatal exposure to methadone on clinical and neurobehavioural outcomes of infants between 40 and 42 weeks gestation. The aims of this study were: (a) to describe clinical and neurobehavioural outcomes of infants exposed to methadone during pregnancy, (b) to examine the effects of maternal methadone dose during pregnancy on infant clinical and neurobehavioural measures, and (c) to examine the extent to which associations between exposure to methadone during pregnancy and infant outcomes persisted after statistical control for a range of confounding variables. Two groups of study infants were recruited. These consisted of 51 consecutively recruited infants born to mothers maintained on methadone during their pregnancy and 42 randomly identified non-methadone exposed comparison infants. Prior to her child's birth, each pregnant woman completed a comprehensive maternal interview. At birth and during the infant's hospital stay a broad perinatal data-base was collected. At 42 weeks gestation infants underwent a neurobehavioural assessment including the NICU Network Neurobehavioural Scale (NNNS; Lester & Tronick, 2004) and infant cry analysis. Study results showed significant differences across several clinical and neurobehavioural measures. Infants exposed to methadone in utero were found to be significantly lighter, have smaller head circumferences, and spend longer in hospital. Neurobehaviourally, they were significantly less well regulated, less attentive, more easily aroused, more excitable, and more hypertonic. In addition, they exhibited less motor maturity, displayed more stress abstinence symptomatology, and required more support from the assessor in order to remain in an appropriate state. Concurrent analysis of infant cry characteristics revealed no significant differences between the fundamental frequencies or the melody contours of the two groups. However, infants prenatally exposed to methadone did display higher levels of frequency perturbation in their cries, as evidenced by analysis of their jitter factor and percentage of directional jitter. Analysis of the effects of maternal dose during pregnancy suggested that maternal dose levels above 60mg/day were general indicative of poorer infant outcomes than those below 60mg/day, with significant linear trends occurring across a number of measures. The extent to which associations between methadone exposure during pregnancy and infant outcomes reflected either a) the direct effects of methadone exposure and/or b) the effects of confounding factors correlated with maternal methadone use was examined using regression analysis. The results of this analysis for infant clinical outcomes showed confounding variables attenuated the effects of methadone exposure on infant birth length and, to some degree, infant head circumference. In contrast, associations between methadone exposure during pregnancy and most neurobehavioural outcomes remained significant, suggesting that maternal methadone use during pregnancy is an important, independent predictor of infant neurobehavioural functioning. These findings support the view that prenatal exposure to methadone has at least short term impacts on the infant's central nervous system (CNS) development. Important implications of possible vulnerabilities faced by these infants and their families are discussed.