678 - Brain-Growth Connection: Impact of Maternal Opioid Use on Neonatal Hypothalamic Changes and Anthropometric Measurements

Publication Number: 2661.678

Ana Leonard, Tufts University School of Medicine, Jamaica Plain, MA, United States; Marissa Chow, Floating Hospital for Children at Tufts Medical Center, Boston, MA, United States; Jerod Rasmussen, University of California, Irvine, School of Medicine, Long Beach, CA, United States; Neel Madan, Floating Hospital for Children at Tufts Medical Center, Boston, MA, United States; Kajeen Salih, Tufts Childrens Hospital, Wakefield, MA, United States; Kushal Kapse, Developing Brain Institute, Washington, DC, United States; Catherine Limperopoulos, Children's National Health System, Washington DC, DC, United States; Jonathan M. Davis, Tufts University School of Medicine, Boston, MA, United States; Josepheen De Asis-Cruz, Children's National Health System, Bethesda, MD, United States; Elizabeth Yen, Tufts Medicine Pediatrics-Boston Children's, Boston, MA, United States

Background: Neonates with in-utero opioid exposure often experience nutritional and growth challenges due to unclear mechanisms. The hypothalamus (HTH) is important for many homeostatic functions, yet its role in regulating growth in opioid-exposed neonates has not been studied. An inherent challenge in analyzing the neonatal HTH on magnetic resonance imaging (MRI) is its very small size of ~300 mm³. Further, much of the analysis has adopted segmentation tools developed for the adult brain.

Objective: Using a neonatal-specific segmentation tool, the impact of maternal opioid use on neonatal HTH volume and anthropometrics at birth was examined.

Design/Methods: Brain T1-weighted MRI obtained from opioid-exposed and non-exposed neonates ≥34 weeks gestation age (GA) within the first 48 hours of life were segmented into total and regional HTH subunits (anterior-thermoregulation, circadian rhythms; tubular-feeding behavior, energy balance; posterior-memory, emotional responses). Demographic data included race/ethnicity, delivery method, Apgar scores, GA, sex, and anthropometric measurements (birth weight/BW, head circumference/HC, length/L, and percentiles). Continuous data were analyzed using a Student's t-test and categorical data using a Fisher's exact test. Correlation was done using Pearson's analysis. Significance was set at p< 0.05.

Results: Opioid-exposed neonates had lower anthropometric measurements. more exposure to hepatitis C and tobacco use, and longer stay (p < 0.05, Table 1). Volumetric analyses showed smaller total (p < 0.01), anterior (p=0.11), tubular (p=0.09), and posterior (p < 0.001) HTH in the opioid-exposed cohort. After adjustment for HC and multivariate regression, significant differences remained for the total (p=0.04) and posterior hypothalamus (p < 0.001, Figure). Anthropometrics correlated with HTH measurements in opioid-exposed neonates, but not in non-exposed neonates (Table 2). Interaction between exposure and HTH (total and posterior) significantly affects anthropometrics.

Conclusion(s): In-utero opioid exposure is associated with reduced hypothalamic size affecting anthropometric measurements at birth. Non-significant differences in the anterior and tubular regions may be due to the small sample size. Our study is limited by the lack of longitudinal growth data. Given the roles of global/regional hypothalamus in many endocrine functions, our findings highlight the need to follow these neonates carefully over time. Future studies will include a larger sample size and clinical data related to the functions of these hypothalamic regions.

Table 1. Demographic and Clinical Data
BW=birth weight, HC=head circumference, L=length, SGA=small gestational, NSVD=normal spontaneous vaginal delivery, GBS=group B streptococcus. Data are presented as mean ± standard deviation or median (interquartile ranges) for continuous measures, and N (%) for categorical measures. Bold indicates significance.

Table 2. Anthropometric Measurements Related to Total and Regional Hypothalamic Volumes in Opioid-exposed Neonates
Data are presented as R (95% CI range); HTH: hypothalamus, BW: birth weight, HC: head circumference, L: length, %: percentile. Bolded p values indicate significance.

Figure. Smaller Hypothalamus in Opioid-exposed Neonates
Maternal opioid use is associated with significantly smaller total and posterior hypothalamus following multivariate regression adjustment. *p < 0.05, ***p < 0.001. HTH: hypothalamus, HC: head circumference, PMA: post-menstrual age, GA: gestational age, Hep: hepatitis.