PROJECT SUMMARY/ABSTRACT The increasing prevalence of opioid dependence among pregnant women is a major public health concern, partially because prenatal opioid exposure is associated with a range of adverse neurodevelopmental and medical outcomes for infants. Prenatal opioid exposure has been associated with atypical autonomic nervous system (ANS) functioning in the first days of life, but there have been few investigations later in development. Further, although prenatal opioid exposure is frequently accompanied by exposure to other substances, few studies account for polysubstance exposure. Thus, the unique effects of prenatal opioid exposure on autonomic functioning are not well understood. [In addition, although the postnatal caregiving environment may moderate the effect of opioid exposure on infant functioning, parenting quality as a moderator of prenatal opioid exposure has received relatively little attention.] Autonomic dysregulation has important implications for physical and mental health, so determining the degree to which prenatal opioid exposure affects infant ANS functioning, and identifying modifiable moderators of this effect, are critical steps to inform treatment. Consistent with NIH’s programmatic interests (i.e., the HEAL Initiative), the proposed study will assess the effect of prenatal opioid exposure on infant ANS regulation at six months of age [and will examine parenting quality as a modifiable moderator of this effect.] As part of a larger randomized controlled trial, the proposed study will [examine the effect of opioid exposure within a group of women receiving medication-assisted treatment for opioid dependence (e.g., methadone).] Substance exposure information will be collected with a validated interview (the Timeline Followback) with mothers during pregnancy and when infants are six months old. [Parenting quality will be assessed via observational coding of a video-recorded free play activity when infants are six months old.] Two indicators of infant ANS functioning will also be collected at six months: respiratory sinus arrhythmia (RSA) and cardiac pre-ejection period (PEP). Infant RSA and PEP will be measured at rest and in response to a social stressor (the still-face paradigm). The proposed study will determine the degree to which prenatal opioid exposure is related to infant autonomic activity at six months of age, [and will examine parenting quality as a moderator of this effect.] Because receiving medication-assisted treatment (MAT) during pregnancy is the current standard of care for opioid-dependent pregnant women, understanding the impact of prenatal opioid exposure, and identifying malleable moderators of this effect, are critical steps to identify treatment targets and inform treatment planning for women and their infants. The proposed plan includes advanced training for the applicant in ANS, prenatal substance exposure, parenting, and community-based research.