Antenatal Opioid Exposure tied to smaller brain volumes in Newborn: JAMA

The prospective cohort study was performed between August 2020 and December 2023 at four U.S. sites and involved a total of 269 term newborns: 173 with antenatal opioid exposure and 96 unexposed controls. MRI scans were performed prior to the infants' age of 8 weeks, with a mean postmenstrual age of 42.84 weeks at imaging. 3D volumetric MRI was used without sedation, with harmonized protocols on Siemens and Philips 3T scanners. Automated segmentation with DrawEM and 3D U-Net pipelines was followed by manual corrections for accuracy.

Statistical analysis was performed using analysis of covariance (ANCOVA), controlling for important covariates such as postmenstrual age at MRI, sex, birth weight, maternal education, and pregnancy smoking.

Key Findings

The research found that opioid-exposed infants had significantly reduced brain volumes in almost all brain regions compared with unexposed controls.

Total brain volume:

• Exposed: 387.51 cm³

• Controls: 407.06 cm³

• Difference: 19.55 cm³ (95% CI, 8.75–30.35)

Cortical volume:

• Exposed: 167.07 cm³

• Controls: 176.35 cm³

• Difference: 9.28 cm³ (95% CI, 3.86–14.70)

Deep gray matter volume:

• Exposed: 27.22 cm³

• Controls: 28.76 cm³

• Difference: 1.54 cm³ (95% CI, 0.66–2.43)

White matter volume:

• Exposed: 159.90 cm³

• Controls: 166.65 cm³

• Difference: 6.76 cm³ (95% CI, 1.71–11.81)

Cerebellar volume:

• Exposed: 23.47 cm³

• Controls: 24.99 cm³

• Difference: 1.52 cm³ (95% CI, 0.67–2.36)

Brainstem volume:

• Exposed: 6.80 cm³

• Controls: 7.18 cm³

• Difference: 0.38 cm³ (95% CI, 0.19–0.57)

Amygdala volume:

• Left: 0.48 cm³ vs 0.51 cm³ (difference: 0.03 cm³)

• Right: 0.51 cm³ vs 0.55 cm³ (difference: 0.04 cm³)

Subgroup analysis demonstrated that:

• Methadone-exposed infants had significantly reduced white matter volumes compared to controls.

• Buprenorphine-exposed infants had a reduced right amygdala compared to controls.

• Infants exposed to opioids alone and polysubstance-exposed infants had significant volume decreases in the cortex, deep gray matter, cerebellum, brainstem, right amygdala, and total brain.

• Polysubstance-exposed newborns also had reduced white matter and left amygdala volumes compared to controls.

The study authors concluded that antenatal opioid exposure was found to be associated with lower global and regional brain volumes in neonates, as well as lower cortical, white matter, deep gray matter, cerebellar, and amygdala volumes. These observations highlight the susceptibility of the developing brain to in-utero opioid exposure and support proactive measures to counteract long-term neurodevelopmental effects.

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