Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Maternal-Fetal Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Am J Obstet Gynecol. 2019 Dec;221(6):602-608. doi: 10.1016/j.ajog.2019.07.022. Epub 2019 Jul 16.
Medication-assisted treatment is recommended for individuals with an opioid use disorder, including pregnant women. Medication-assisted treatment during pregnancy provides benefits to the mother and fetus, including better pregnancy outcomes, reduced illicit drug use, and improved prenatal care. An alternative approach, medically supervised withdrawal (detoxification), has, in recent reports, demonstrated a low risk of fetal death and low rates of relapse and neonatal abstinence syndrome. The rates of relapse and neonatal abstinence syndrome are questioned by many who view medically supervised withdrawal as unacceptable based on the concern for the potential adverse consequences of relapse to mother and baby. The impact of opioids on the fetal brain have not been integrated into this debate. Studies in animals and human brain tissues demonstrate opioid receptors in neurons, astroglia, and oligodendrocytes. Age-specific normative data from infants, children, and adults have facilitated investigation of the impact of opioids on the human brain in vivo. Collectively, these studies in animals, human neural tissue, adult brains, and the brains of children and newborns demonstrate that opioids adversely affect the human brain, primarily the developing oligodendrocyte and the processes of myelinization (white matter microstructure), connectivity between parts of the brain, and the size of multiple brain regions, including the basal ganglia, thalamus, and cerebellar white matter. These in vivo studies across the human lifespan suggest vulnerability of specific fronto-temporal-limbic and frontal-subcortical (basal ganglia and cerebellum) pathways that are also likely vulnerable in the human fetal brain. The long-term impact of these reproducible changes in the fetal brain in vivo is unclear, but the possibility of lasting injury has been suggested. In light of the recent data on medically supervised withdrawal and the emerging evidence suggesting adverse effects of opioids on the developing fetal brain, a new paradigm of care is needed that includes the preferred option of medication-assisted treatment but also the option of medically supervised opioid withdrawal for a select group of women. Both these treatment options should offer mental health and social services support throughout pregnancy. More research on both opioid exposure on the developing human brain and the impact of medically supervised withdrawal is required to identify appropriate candidates, optimal dose reduction regimens, and gestational age timing for initiating medically supervised withdrawal.
药物辅助治疗被推荐用于治疗阿片类药物使用障碍患者，包括孕妇。孕妇在怀孕期间进行药物辅助治疗可以使母亲和胎儿受益，包括更好的妊娠结局、减少非法药物使用以及改善产前保健。最近的报告表明，另一种替代方法，即医学监督下的戒断（解毒），具有较低的胎儿死亡风险和较低的复发率以及新生儿戒断综合征率。许多人对医学监督下的戒断表示质疑，认为它不能接受，因为担心复发会对母婴产生潜在的不良后果。但是，复发率和新生儿戒断综合征率受到质疑。许多人对医学监督下的戒断表示质疑，认为它不能接受，因为担心复发会对母婴产生潜在的不良后果。复发率和新生儿戒断综合征率受到质疑。许多人对医学监督下的戒断表示质疑，认为它不能接受，因为担心复发会对母婴产生潜在的不良后果。但是，复发率和新生儿戒断综合征率受到质疑。许多人对医学监督下的戒断表示质疑，认为它不能接受，因为担心复发会对母婴产生潜在的不良后果。但是，复发率和新生儿戒断综合征率受到质疑。许多人对医学监督下的戒断表示质疑，认为它不能接受，因为担心复发会对母婴产生潜在的不良后果。但是，复发率和新生儿戒断综合征率受到质疑。许多人对医学监督下的戒断表示质疑，认为它不能接受，因为担心复发会对母婴产生潜在的不良后果。但是，复发率和新生儿戒断综合征率受到质疑。
阿片类药物对胎儿大脑的影响尚未纳入这一辩论。在动物和人类脑组织中进行的研究表明，神经元、星形胶质细胞和少突胶质细胞中存在阿片受体。来自婴儿、儿童和成年人的特定年龄的正常数据促进了在体内研究阿片类药物对人类大脑的影响。这些研究表明，阿片类药物对人类大脑具有不良影响，主要是发育中的少突胶质细胞和髓鞘化（白质微观结构）过程、大脑各部分之间的连接以及包括基底神经节、丘脑和小脑白质在内的多个脑区的大小。这些跨人类生命范围的体内研究表明，特定的额颞叶边缘和额皮质下（基底神经节和小脑）通路存在脆弱性，这些通路在人类胎儿大脑中也可能存在脆弱性。在体内，这些可重复的胎儿大脑变化的长期影响尚不清楚，但有研究提示可能存在持久的伤害。鉴于最近关于医学监督下戒断的研究数据和阿片类药物对发育中胎儿大脑的不良影响的新证据，需要一种新的护理模式，包括首选药物辅助治疗，以及为特定的女性群体提供医学监督下的阿片类药物戒断的选择。这两种治疗选择都应在整个孕期提供心理健康和社会服务支持。需要更多关于阿片类药物暴露对发育中的人类大脑的影响以及医学监督下戒断的影响的研究，以确定合适的候选者、最佳剂量减少方案以及开始医学监督下戒断的最佳胎龄时机。
