Gestational buprenorphine-naloxone exposure and fetal neurobehavior

IF 2.6 3区 医学 Q3 NEUROSCIENCES Neurotoxicology and teratology Pub Date : 2024-07-01 DOI:10.1016/j.ntt.2024.107368
Lauren M. Jansson , Krystle McConnell , Martha L. Velez , Nancy Spencer , Lorraine Milio , Jeannie Leoutsakos , Janet A. DiPietro
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Abstract

Background

Buprenorphine-naloxone treatment may confer substantial benefits for the treatment of opioid use disorder (OUD) during pregnancy including lower risk for overdose/death, less diversion potential and reduced use of other substances. Treatment may also result in less severe Neonatal Abstinence Syndrome (NAS), but little is known about the effects of this medication on fetal neurodevelopment.

Methods

The purpose of the current study is to evaluate neurobehaviors among fetuses exposed to buprenorphine-naloxone at four time points over the second and third trimesters of gestation in pregnant women with OUD on buprenorphine-naloxone therapy. Sixty minutes of continuous fetal monitoring via fetal actocardiograph with a single wide array abdominal transducer took place at times of peak and trough buprenorphine-naloxone levels in 24 pregnant women. Data collection, which included measures of fetal heart rate and motor activity, was conducted between 24 and 36 weeks gestation, with the majority (84.6%) monitored at two or more gestational ages. Medication dose and other substance use was monitored throughout the study and infant NAS severity was assessed.

Results

Fetal heart rate (FHR), FHR variability, accelerations in FHR, and motor activity were suppressed when buprenorphine-naloxone levels were at pharmacologic peak as compared to trough concentrations at 36 weeks, but not earlier in gestation. Maternal medication dose was unrelated to infant NAS severity.

Conclusions

Conclusions: There were evident subclinical fetal neurophysiological responses at times of peak maternal buprenorphine/naloxone levels in later gestation, similar to those previously described for buprenorphine only. Further studies evaluating the effects of these changes in fetal neurobehaviors on the longer-term infant development are needed.

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妊娠期丁丙诺啡-纳洛酮暴露与胎儿神经行为。
背景:丁丙诺啡-纳洛酮治疗可为孕期阿片类药物使用障碍(OUD)的治疗带来巨大益处,包括降低用药过量/死亡的风险、减少药物转用的可能性以及减少其他药物的使用。治疗还可能减轻新生儿窒息综合征(NAS)的严重程度,但人们对这种药物对胎儿神经发育的影响知之甚少:本研究的目的是评估接受丁丙诺啡-纳洛酮治疗的 OUD 孕妇在妊娠期第二和第三季度四个时间点暴露于丁丙诺啡-纳洛酮的胎儿的神经行为。在 24 名孕妇的丁丙诺啡-纳洛酮水平达到峰值和谷值时,使用单个宽阵列腹部传感器通过胎儿心动图对胎儿进行了 60 分钟的连续监测。数据收集包括胎儿心率和运动活动的测量,在妊娠 24 至 36 周期间进行,大多数孕妇(84.6%)在两个或两个以上的妊娠期接受监测。在整个研究过程中对药物剂量和其他药物使用情况进行监测,并对婴儿NAS的严重程度进行评估:结果:当丁丙诺啡-纳洛酮的药理浓度在36周达到峰值时,胎儿心率(FHR)、FHR变异性、FHR加速度和运动活动受到抑制,而在妊娠早期则没有抑制。产妇用药剂量与婴儿NAS的严重程度无关:结论在妊娠后期母体丁丙诺啡/纳洛酮水平达到峰值时,胎儿会出现明显的亚临床神经生理学反应,这与之前描述的仅丁丙诺啡的反应类似。需要进一步研究评估胎儿神经行为的这些变化对婴儿长期发育的影响。
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来源期刊
CiteScore
5.60
自引率
10.30%
发文量
48
审稿时长
58 days
期刊介绍: Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.
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