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Early white matter tract changes in neonates with prenatal opioid exposure: a pilot study

Journal of Perinatology volume 43, pages 390–391 (2023)Cite this article

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The impact of prenatal opioids on the developing brain is not well studied, specifically on white matter tract development shortly after birth [1,2,3]. Our pilot study aims to evaluate and compare white matter changes in opioid- and non-exposed neonates in the immediate postnatal period.

Brain MRI was acquired within 48 h of birth using a ‘feed-and-swaddle’ method in 10 opioid-exposed neonates born at ≥34 weeks’ gestational age (GA), prior to the start of pharmacotherapy, and 11 healthy sex- and age-matched non-exposed controls. Exclusion criteria were <34 weeks’ GA, those already on pharmacotherapy at the time of recruitment, and those with congenital or chromosomal anomalies. Due to the GA matching and fixed timing of the brain MRI, neonates in both cohorts were equivalent in postmenstrual age at MRI acquisition. Diffusion tensor imaging (DTI) was acquired for each patient with a baseline image (b = 0 s/mm2) and 15 different diffusion orientations (b = 1 000 s/mm2). The pediatric radiologist was blinded to the clinical status of the neonates. Single-subject and group-level DTI analyses were carried out using FMRIB’s Software Library (www.fmrib.ox.ac.uk/fsl), including corrections for eddy current-induced distortions and gross subject movement. Slices with signal loss caused by subject movement coinciding with the diffusion encoding were detected and replaced by predictions made by a Gaussian Process. To determine differences in white matter between the two groups, voxel-wise whole tract analysis of the fractional anisotropy (FA) data was performed with Tract Based Spatial Statistics using a pipeline optimized for neonatal DTI data (thresholded at FA > 0.19), with sex and GA at birth listed as covariates [4]. Continuous data were analyzed using a t-test, and categorical data using Chi-square. Significance was set at p ≤ 0.05. All FA data were further subjected to permutation (10,000) testing and family-wise error correction for multiple comparisons following threshold-free cluster enhancement (TFCE) to obtain a corrected t-statistical map, representing areas in the white matter tracts with relative FA reduction across the exposed and non-exposed cohorts.

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References

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Acknowledgements

We would like to thank all the families for their participation in this study and the entire staff at the Tufts Shields MRI for their assistance in organizing and acquiring the images. Authors would also like to acknowledge the following groups for their support: (A) K12 Building Interdisciplinary Research for Careers in Women’s Health; (B) Tufts Tiny Feet Funds.

Funding

This study received funding from K12 Building Interdisciplinary Research for Careers in Women’s Health (BIRCWH) Grant #5K12HD092535-05 (EY) and Tufts Tiny Feet Funds (EY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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Authors and Affiliations

  1. Tufts University School of Medicine, Boston, MA, USA

    Pooja Sikka

  2. Department of Radiology, Tufts Medical Center, Boston, MA, USA

    Neel Madan

  3. Department of Pediatrics, Tufts Medical Center, Boston, MA, USA

    Elizabeth Yen

  4. Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA

    Elizabeth Yen

Authors
  1. Pooja Sikka
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  2. Neel Madan
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  3. Elizabeth Yen
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Contributions

PS critically analyzed the DTI data, performed statistical analysis, interpreted the data, and drafted, reviewed, and finalized the paper. NM designed the study, protocolized, acquired, and read the structural brain MRI images, reviewed the DTI analyses, reviewed and revised the paper. EY conceptualized and designed the study, obtained IRB approval, consented and enrolled patients, performed statistical analysis, interpreted the data, reviewed and revised the paper. All authors approved the final paper as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Elizabeth Yen.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study protocol was approved by the Tufts Institutional Review Board (IRB). Consent from each participant was obtained prior to study enrollment. This study was performed in accordance with the Declaration of Helsinki.

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Sikka, P., Madan, N. & Yen, E. Early white matter tract changes in neonates with prenatal opioid exposure: a pilot study. J Perinatol 43, 390–391 (2023). https://doi.org/10.1038/s41372-022-01427-0

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  • DOI: https://doi.org/10.1038/s41372-022-01427-0

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