Response to article - alternative interpretation of "there is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome".
Response to article - alternative interpretation of "there is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome".
复制标题
对文章的回应 - “严重新生儿阿片类药物戒断综合征中胎盘芳香酶免疫组织化学染色减少”的另一种解释。
DOI：
10.1080/14767058.2023.2183469
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Brents,LisaK
中科院分区：
文献类型：
--
作者：
Tobacyk,Julia;Brents,LisaK
我们最近在《母胎和新生儿医学杂志》上读到一篇非常有趣和重要的研究，题为：“严重新生儿阿片类药物戒断综合征[1]中胎盘芳香化酶免疫组化染色减少。”在这项研究中，作者调查了怀孕期间阿片类药物暴露对胎盘芳香化酶（即CYP19A1）免疫染色强度的影响。此外，作者将新生儿阿片类药物戒断综合征（NOWS）的严重程度与接受美沙酮或丁丙诺啡药物辅助治疗阿片类药物使用障碍的阿片类药物暴露孕妇胎盘中芳香化酶的免疫染色强度联系起来。芳香化酶在美沙酮[2]和丁丙诺啡[3]的胎盘代谢中起主要作用。这项研究很重要，因为了解这些阿片类药物和胎盘芳香化酶之间的相互作用将更好地告诉我们胎儿阿片类药物暴露和美沙酮和丁丙诺啡引起的NOWS的决定因素。作者报道，与未暴露的对照组相比，阿片类药物暴露的胎盘中芳香化酶免疫染色减少。我们对他们的其他发现特别感兴趣，即严重NOWS婴儿的胎盘芳香酶免疫染色低于非严重NOWS婴儿。基于这一发现，作者假设“芳香化酶免疫染色减少导致胎盘内芳香化酶功能改变，导致循环活性阿片样物质从胎盘转移到胎室”，并提出这种现象可能导致更高的严重NOWS发生率。然而，NOWS的增加更可能是由于在发生严重NOWS的组中，美沙酮治疗比丁丙诺啡治疗更有代表性。美沙酮诱导的NOWS比丁丙诺啡更严重，这种影响被认为是由于美沙酮比丁丙诺啡更有效地激活mu阿片受体。我们承认美沙酮抑制或下调胎盘芳香化酶的程度可能比丁丙诺啡更大，这反过来可能允许更多的美沙酮分布到胎儿，导致美沙酮治疗后观察到的NOWS更严重。然而，我们认为这是不可能的，因为丁丙诺啡抑制芳香酶的Ki比美沙酮低大约10倍
We recently read a very interesting and important study in the Journal of Maternal-Fetal & Neonatal Medicine entitled:“There is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome [1].” In this study, the authors investigated the effects of opioid exposure during pregnancy on placental immunostaining intensity of aromatase (ie CYP19A1). Additionally, the authors related severity of neonatal opioid withdrawal syndrome (NOWS) to immunostaining intensity of aromatase in placentas from opioid-exposed pregnancies of women undergoing medication-assisted treatment for opioid use disorder with either methadone or buprenorphine. Aromatase plays a major role in placental metabolism of methadone [2] and buprenorphine [3]. This investigation is important because understanding the interplay between these opioids and placental aromatase will better inform us on the determinants of fetal opioid exposure and NOWS caused by methadone and buprenorphine.The authors reported a reduction in aromatase immunostaining in opioid-exposed placenta compared to unexposed controls. We were particularly interested in their additional finding that babies with severe NOWS had lower placental aromatase immunostaining than babies with non-severe NOWS. Based on this finding, the authors hypothesized that “reduced aromatase immunostaining results in altered aromatase function within the placenta, leading to higher circulating active opioid transferring from the placenta to the fetal compartment,” and offered that this phenomenon may cause higher rates of severe NOWS. However, the increased NOWS is more likely explained by a greater representation of treatment with methadone than buprenorphine in the group that developed severe NOWS. Methadone induces more severe NOWS than buprenorphine [4], and this effect is thought to be mediated by the higher efficacy of methadone than buprenorphine to activate the mu opioid receptor. We acknowledge the possibility that methadone inhibits or downregulates placental aromatase to a greater degree than buprenorphine, which in turn may permit greater methadone distribution to the fetus, contributing to the greater severity of NOWS observed following methadone treatment. However, we think this is unlikely because buprenorphine has an approximately 10-fold lower Ki than methadone to inhibit aromatase