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Published on: February 28, 2025
Associations of Prenatal Cannabis Exposure and Neonatal Brain Development in the HBCD Cohort
Insights
Prenatal cannabis exposure is linked to brain development differences in newborns. The timing and frequency of exposure during pregnancy significantly impact neonatal brain structure and white matter microstructure.
Area of Science:
- Neuroscience
- Developmental Biology
- Public Health
Background:
- Prenatal cannabis exposure (PCE) is rising, but its effects on neonatal brain development are not fully understood.
- Understanding the impact of PCE timing and frequency is crucial for early risk identification and perinatal care.
Purpose of the Study:
- To investigate associations between maternal PCE patterns and neonatal brain structure and microstructure.
- To analyze how exposure presence, gestational timing, and frequency relate to brain development in the first month of life.
Main Methods:
- A cohort study of 1,782 mother-infant dyads from the HEALthy Brain and Child Development Study.
- Maternal PCE assessed via Timeline Follow-back; neonatal brain imaging (structural and diffusion MRI) performed within the first month.
- Analysis of regional brain volumes and white matter microstructure in relation to PCE presence, timing, and frequency.
Main Results:
- PCE associated with differences in cerebellar and subcortical limbic brain volumes (e.g., amygdala, thalamus, caudate).
- First-trimester exposure linked to smaller volumes; third-trimester exposure linked to larger volumes and white matter alterations.
- Higher frequency of PCE correlated with larger cerebral white matter volumes and microstructural differences.
Conclusions:
- Maternal PCE influences neonatal brain development in a timing- and frequency-dependent manner.
- Findings highlight the importance of considering PCE details beyond mere presence for prenatal counseling and infant monitoring.
- PCE is associated with significant alterations in brain development within the first month of life.
Importance:
Prenatal cannabis exposure is increasing in prevalence, yet its associations with early brain development-particularly how the timing and frequency of exposure relate to neonatal brain structure-remain insufficiently understood. Clarifying these associations is essential for informing early risk identification and guiding perinatal care.
Objective:
To examine associations between patterns of maternal prenatal cannabis exposure, including exposure presence, gestational timing, and frequency, and neonatal brain structure and microstructure during the first month of life.
Design Setting And Participants:
This cohort study included 1,782 mother-infant dyads (221 with PCE) from the HEALthy Brain and Child Development Study. Maternal cannabis use was assessed using the validated Timeline Follow-back method. Infants underwent natural-sleep magnetic resonance imaging, including T2-weighted structural imaging and diffusion imaging, within the first month of life.
Main Outcomes And Measures:
Associations between prenatal cannabis exposure and regional T2-weighted volumes and diffusion white matter microstructure metrics were examined as a function of (1) exposure presence, (2) gestational timing of exposure, and (3) frequency of exposure within exposed infants.
Results:
Prenatal cannabis exposure was associated with small but statistically significant differences in neonatal brain structure. Exposure was linked to volumetric variation in cerebellar and subcortical limbic regions, including smaller amygdala, thalamic, and cerebellar vermis volumes and larger caudate, hippocampal, and cerebellar cortex volumes. Timing-specific analyses revealed distinct patterns: first-trimester exposure was primarily associated with white matter microstructural alterations, particularly in cerebellar and association tracts, whereas sustained exposure throughout pregnancy was associated with volumetric differences across cerebellar and subcortical regions. Among exposed infants, higher exposure frequency was associated with larger cerebral white matter volume and lower fractional anisotropy in select regions. Effect sizes were modest, and regional findings varied in directionality.
Conclusions And Relevance:
Prenatal cannabis exposure was associated with timing-and frequency-dependent differences in neonatal brain structure within the first month of life. These differences likely reflect variation in early neurodevelopmental processes rather than uniformly adverse effects and may evolve with ongoing brain maturation and postnatal influences. Consideration of exposure timing and frequency, alongside broader clinical context and competing risks, may support more individualized, nonjudgmental counseling and longitudinal developmental monitoring.
Key Points:
Question: Is prenatal cannabis exposure associated with brain development in the first month of life?Findings: In a cohort of 1,782 mother-infant dyads, prenatal cannabis exposure was associated with region-specific differences in neonatal brain volumes. Brain volume and diffusion white matter microstructure associations differed between exposure limited to the first trimester versus exposure that continued into the third trimester. Greater frequency of exposure across gestation was also associated with volumetric and microstructural differences.Meaning: The timing and frequency of prenatal cannabis exposure is associated with alterations in neonatal brain development, underscoring the importance of addressing cannabis use in pregnancy.

