Effects of medications for opioid use disorder (MOUD) on fetal brain and cranial measurements.

Background: The use and misuse of opioids, as well as opioid use disorder (OUD) have increased remarkably among reproductive-aged and pregnant women. As many as 25% of pregnant women who report non-medical opioid use in the past month also report concurrent alcohol use. While teratogenic effects of alcohol are well established, there are limited studies evaluating fetal intracranial effects associated with medications for OUD (MOUD) and concurrent use of MOUD and alcohol during pregnancy. The objective of this study was to determine the effect of MOUD, with and without concomitant alcohol use, on fetal intracranial measurements. The type of maternal MOUD therapy (methadone vs. buprenorphine) was also examined.

Methods: This study was a secondary analysis of a prospective cohort study among participants (n = 196) assigned into three groups (MOUD [n = 94], MOUD+Alcohol [n = 47], and unexposed controls [n = 55]). Co-exposure with either methamphetamines or cocaine were exclusionary criteria; other co-exposures were carefully characterized with prospective repeated self-report measures and biomarkers. Fetal ultrasound measurements at 18-22 weeks (2nd trimester) and 28-32 weeks (early 3rd trimester) were compared among study groups. In addition to standard morphometrics, we performed specialized intracranial measurements of caval-calvarial distance (CCD), frontal lobe width (FLW), frontal lobe length (FLL), and fronto-thalamic distance (FTD).

Results: Brain and cranial measurements between MOUD, with or without alcohol co-exposure, and unexposed controls were generally not significantly different in multivariable analyses. Subjects in the MOUD groups had earlier gestational age at delivery and lower birth weight and birth weight percentile compared to unexposed controls with differences driven primarily by the methadone subgroup. Significant differences in standard and specialized intracranial indices at both second and third trimester as well as differences in the change of HC percentile over time were observed in the methadone subgroup compared to controls, while no differences between buprenorphine subgroup and controls were observed for any measures.

Conclusion: Patients receiving methadone therapy might require closer monitoring during pregnancy; however, detailed imaging of the fetal brain other than the standard measurements might not be warranted.