MRC Centre for Reproductive Health, University of Edinburgh, UK.
Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Neuroimage Clin. 2017 Dec 24;18:9-14. doi: 10.1016/j.nicl.2017.12.033. eCollection 2018.
Methadone is used for medication-assisted treatment of heroin addiction during pregnancy. The neurodevelopmental outcome of children with prenatal methadone exposure can be sub-optimal. We tested the hypothesis that brain development is altered among newborn infants whose mothers were prescribed methadone. 20 methadone-exposed neonates born after 37 weeks' postmenstrual age (PMA) and 20 non-exposed controls underwent diffusion MRI at mean PMA of 39 and 41 weeks, respectively. An age-optimized Tract-based Spatial Statistics (TBSS) pipeline was used to perform voxel-wise statistical comparison of fractional anisotropy (FA) data between exposed and non-exposed neonates. Methadone-exposed neonates had decreased FA within the centrum semiovale, inferior longitudinal fasciculi (ILF) and the internal and external capsules after adjustment for GA at MRI (p < 0.05, TFCE corrected). Median FA across the white matter skeleton was 12% lower among methadone-exposed infants. Mean head circumference (HC) z-scores were lower in the methadone-exposed group (- 0.52 (0.99) 1.15 (0.84), p < 0.001); after adjustment for HC z-scores, differences in FA remained in the anterior and posterior limbs of the internal capsule and the ILF. Polydrug use among cases was common. Prenatal methadone exposure is associated with microstructural alteration in major white matter tracts, which is present at birth and is independent of head growth. Although the findings cannot be attributed to methadone , the data indicate that further research to determine optimal management of opioid use disorder during pregnancy is required. Future studies should evaluate childhood outcomes including infant brain development and long-term neurocognitive function.
美沙酮用于妊娠期间海洛因成瘾的药物辅助治疗。接受产前美沙酮治疗的儿童的神经发育结果可能不理想。我们检验了一个假设，即母亲接受美沙酮治疗的新生儿的大脑发育会发生改变。20 名在妊娠 37 周后出生的美沙酮暴露新生儿和 20 名未暴露对照者分别在平均妊娠 39 周和 41 周时接受弥散 MRI 检查。使用年龄优化的基于束的空间统计学（TBSS）管道对暴露组和未暴露组新生儿的各向异性分数（FA）数据进行了体素-wise 统计比较。在 MRI 时调整 GA 后，美沙酮暴露的新生儿的半卵圆中心、下纵束（ILF）以及内、外囊的 FA 值降低（p<0.05，TFCE 校正）。美沙酮暴露婴儿的整个白质骨架的 FA 中位数低 12%。美沙酮暴露组的平均头围（HC）z 评分较低（-0.52（0.99）1.15（0.84），p<0.001）；在调整 HC z 评分后，内囊前肢和后肢以及 ILF 的 FA 差异仍然存在。病例中多药使用很常见。产前美沙酮暴露与主要白质束的微观结构改变有关，这些改变在出生时就存在，并且与头围生长无关。虽然这些发现不能归因于美沙酮，但数据表明，需要进一步研究确定妊娠期间阿片类药物使用障碍的最佳管理方法。未来的研究应评估包括婴儿大脑发育和长期神经认知功能在内的儿童结局。
