666 - Characteristics of Maternal Opioid Use and Early Brain Changes in Offspring

Publication Number: 666.4139

Elizabeth Yen, Tufts University School of Medicine, Boston, MA, United States; Ana Leonard, Tufts University School of Medicine, Jamaica Plain, MA, United States; Marissa Chow, Tufts Medical Center, Boston, MA, United States; Kushal Kapse, Children's National Health System, Washington, DC, United States; Kajeen Salih, Tufts Childrens Hospital, Wakefield, MA, United States; Kiran Singh, Tufts Medical Center, Boston, MA, United States; Jonathan Davis, Tufts Medical Center, Boston, MA, United States; Catherine Limperopoulos, Children's National Health System, Washington DC, DC, United States; Josepheen De Asis-Cruz, Children's National Health System, Washington DC, DC, United States

Background: Reductions in regional brain volumes in opioid-exposed infants and older children have been widely reported. However, the effects of antenatal opioid exposure within the immediate postnatal period are understudied. It is also unclear if changes in brain volumes are affected by the specific type of maternal opioid.

Objective: To examine the impact of maternal opioid use disorder (OUD) on early brain changes and to explore associations between volumetric changes and the characteristics of drug exposure (types of opioids, polysubstance use).

Design/Methods: Brain MRIs were acquired within 48 hours of birth from neonates with and without prenatal opioid exposure born between 34 and 42 weeks of gestation. Within the exposed cohort, MRIs were obtained prior to the initiation of pharmacotherapy. High-resolution T2-weighted images were semi-automatically segmented into eight tissue labels: external cerebral spinal fluid, cortical gray matter, white matter, lateral ventricles, cerebellum, deep gray matter, brainstem, and amygdala/hippocampus. Student’s t-tests were used for continuous data and Chi-squared for categorical data. Significance was set at p< 0.05.

Results: A total of 39 brain MRIs were acquired from 24 opioid-exposed and 15 non-exposed neonates. Opioid-exposed neonates were significantly smaller at birth (Table) and had significantly reduced white matter volume than their non-exposed peers. Compared to no opioid use, maternal buprenorphine significantly reduced white matter, and maternal methadone significantly reduced both cortical gray matter and white matter volumes (Figure). A trend of smaller brain volumes was seen with maternal methadone compared to buprenorphine use, and with maternal polysubstance than monosubstance use.

Conclusion(s): Antenatal opioid exposure is associated with early brain changes in neonates, evidenced by reduced brain volumes within the immediate postnatal period. The trend of worse effects with methadone and polysubstance use in our pilot study highlights the importance of studying maternal drug characteristics to understand the impact of OUD on offspring brain development. We will validate our results using a larger sample size and perform neurodevelopmental tests to understand the clinical relevance of these brain changes.

Table. Demographic Data
GA: gestational age, BW: birth weight, L: length; HC: head circumference, NAS: neonatal abstinence syndrome, GBS: group B streptococcus, NA: not available. Data are presented as mean (standard deviation) for normally distributed continuous measures, median (interquartile ranges) for non-normally distributed continuous measures, and N (%) for categorical measures. Bolded p values represent significance.

Figure. The Effects of Maternal Opioid Use on Offspring Brain Volumes.
Opioid-exposed neonates have significantly smaller white matter than non-exposed neonates. Maternal buprenorphine reduces white matter volume, while methadone reduces both cortical gray and white matter volumes. eCSF=external cerebral spinal fluid, cGM=cortical gray matter, WM=white matter, LV=lateral ventricles, CRB=cerebellum, dGM=deep gray matter, BS=brainstem, AH=amygdala and hippocampus. *p < 0.05; ***p < 0.001, ****p < 0.0001.

Table. Demographic Data
GA: gestational age, BW: birth weight, L: length; HC: head circumference, NAS: neonatal abstinence syndrome, GBS: group B streptococcus, NA: not available. Data are presented as mean (standard deviation) for normally distributed continuous measures, median (interquartile ranges) for non-normally distributed continuous measures, and N (%) for categorical measures. Bolded p values represent significance.

Figure. The Effects of Maternal Opioid Use on Offspring Brain Volumes.
Opioid-exposed neonates have significantly smaller white matter than non-exposed neonates. Maternal buprenorphine reduces white matter volume, while methadone reduces both cortical gray and white matter volumes. eCSF=external cerebral spinal fluid, cGM=cortical gray matter, WM=white matter, LV=lateral ventricles, CRB=cerebellum, dGM=deep gray matter, BS=brainstem, AH=amygdala and hippocampus. *p < 0.05; ***p < 0.001, ****p < 0.0001.