668 - Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome (NOWS) is Associated with Smaller Neonatal Brain Volumes

Publication Number: 668.6151

Stephanie L. Merhar, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Yao Wu, Children's National Hospital, Washington, DC, United States; Carla Bann, RTI International, Apex, NC, United States; Jamie E. Newman, RTI International, Carrboro, NC, United States; Josepheen De Asis-Cruz, Children's National Health System, Washington DC, DC, United States; Kushal Kapse, Children's National Health System, Washington, DC, United States; Jonathan Davis, Tufts Medical Center, Boston, MA, United States; Sara B.. DeMauro, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Scott A. Lorch, The Children's Hospital of Philadelphia, Philadelphia, PA, United States; Deanne Wilson-Costello, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Namasivayam Ambalavanan, University of Alabama School of Medicine, Birmingham, AL, United States; Brenda Poindexter, Children's Healthcare of Atlanta, Atlanta, GA, United States; Myriam Peralta-Carcelen, University of Alabama at Birmingham, School of Medicine, Birmingham, AL, United States; Catherine Limperopoulos, Children's National Health System, Washington DC, DC, United States

Background: Our previous work has shown that newborns with antenatal opioid exposure have smaller regional brain volumes than unexposed newborns. Newborns receiving pharmacotherapy for NOWS are considered to have a more severe form of withdrawal. Little is known about the differences in brain development between newborns who do/do not receive pharmacotherapy for NOWS.

Objective: To examine the association between pharmacotherapy for NOWS and brain volumes using quantitative 3-D volumetric MRI performed after pharmacologic treatment

Design/Methods: Newborns ≥37 weeks gestation with antenatal opioid exposure had brain MRI performed at < 6 weeks postnatal age at one of 4 centers participating in the NICHD-funded Outcomes of Babies with Opioid Exposure study. Receipt of and duration of pharmacotherapy were determined by review of the medical record. T2-weighted 3D MRI was acquired on Siemens and Philips 3T MRI scanners with protocols harmonized across sites. Brains were segmented into cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and left/right amygdala and hippocampus using DrawEM and a 3D U-Net based pipeline and manual corrections. ANCOVA compared brain volumes between opioid-exposed neonates receiving pharmacotherapy with those who were untreated. Linear regression models evaluated associations between brain volumes and days of pharmacotherapy.

Results: Neonates who received pharmacotherapy (n=47) were more likely to be born by C-section, had their MRI at a later postmenstrual age, and had more antenatal selective serotonin reuptake inhibitor (SSRI) exposure compared to those who did not receive pharmacotherapy (n=124) (Table 1). After controlling for variables which differed between groups, neonates who received pharmacotherapy had smaller volumes of the deep gray matter and right amygdala (Table 2). A longer duration of pharmacotherapy was significantly associated with smaller total and regional cortical gray matter, white matter, deep gray matter, and left hippocampal volumes (Table 3).

Conclusion(s): The need for and duration of pharmacotherapy for NOWS are associated with smaller brain volumes in opioid-exposed neonates. It is unclear whether this need for pharmacotherapy reflects more severe NOWS and an enhanced susceptibility to neonatal brain injury or whether the pharmacotherapy itself directly contributes to smaller brain volumes. Follow-up is underway to assess associations between newborn brain volumes and later neurodevelopmental outcomes

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