Associations of maternal prenatal drug abuse with measures of newborn brain structure, tissue organization, and metabolite concentrations

Abstract

Importance: Increasing rates of illicit drug use during pregnancy may be associated with risk for long-term health problems in prenatally exposed children. Objective: To identify the associations of prenatal exposure to illicit drugs with organization of the newborn brain. Design, Setting, and Participants: For this cohort study, a volunteer sample of 210 illicit drug-using and nonusing mothers and their newborns was enrolled from prenatal clinics and drug abuse treatment programs in New York, New York. Enrollment, scanning, and long-term follow-up occurred from September 2004 through February 2012, and image processing and statistical analyses continued through fall 2018. In addition to 26 participants with incomplete data, a total of 64 mothers were lost to follow-up during pregnancy, and 13 newborns were lost to follow-up at birth because of perinatal complications. Exposures: Newborns were assigned to 1 of 4 primary exposure groups based on the history of most frequent maternal drug use: marijuana, cocaine, methadone maintenance, and/or heroin. Unexposed newborns were controls. Main Outcomes and Measures: Unsedated magnetic resonance imaging (MRI) of newborn brains was performed shortly after birth. Infant neurodevelopmental outcomes were assessed at age 12 months. MRI modalities included anatomical imaging, diffusion tensor imaging, T2 relaxometry, and magnetic resonance spectroscopic imaging. Infant neurodevelopmental outcomes included Bayley scales of infant development-III and Vineland Adaptive Behavior Scales. Statistical analyses were performed with results represented on the brain images. Results: Of 118 mothers, 42 (35%) were in the control group (mean [SD] age, 25.9 [6.1] years), 29 (25%) were in the cocaine group (mean [SD] age, 29.0 [6.1] years), 29 (25%) were in the marijuana group (mean [SD] age, 24.3 [5.5] years), and 18 (15%) were in the methadone and/or heroin group (mean [SD] age, 30.9 [5.7] years). Not all newborns could be scanned successfully; therefore, usable MRIs were acquired for 118 newborns from predominantly minority groups and with economically disadvantaged mothers. Anatomic abnormalities were detected in similar locations across all 3 drug exposures and included smaller volumes in the dorsal, medial, and ventral surfaces of the frontal lobe and dose-related increases in volumes in the lateral temporal lobe, dorsal parietal lobe, and superior frontal gyrus. Dose-related increases in diffusion tensor measures of tissue organization, decreases in T2 relaxometry times, and increases in spectroscopy metabolite concentrations were similar across exposures. These associations of exposures with brain measures were similar to the associations of newborn age with brain measures. The anatomic and diffusion tensor imaging measures suppressively mediated the associations of prenatal exposure with poorer 12-month infant outcomes. Conclusions and Relevance: The findings suggest that prenatal drug exposure is associated with measures of newborn brain tissue in patterns that may indicate that exposures accelerated normal fetal brain maturation, which in turn mediated the associations with poorer 12-month infant outcomes..