Jansson Lauren M, Velez Martha, McConnell Krystle, Spencer Nancy, Tuten Michelle, Jones Hendree E, King Van L, Gandotra Neeraj, Milio Lorraine A, Voegtline Kristin, DiPietro Janet A
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Am J Obstet Gynecol. 2017 May;216(5):529.e1-529.e8. doi: 10.1016/j.ajog.2017.01.040. Epub 2017 Feb 7.
Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders.
The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development.
Forty-nine buprenorphine-maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement-fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling.
Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough.
Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication-assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.
在美国,孕期阿片类药物的使用/滥用情况正在升级;然而,对于用于治疗母亲阿片类药物使用障碍的药物对胎儿的影响,人们了解甚少。
本研究的目的是确定母亲使用丁丙诺啡对胎儿纵向神经行为发育的影响。
49名使用丁丙诺啡维持治疗的女性,她们在一家物质使用障碍治疗机构就诊,孕期一般无并发症,在母亲丁丙诺啡血药浓度处于谷值和峰值时,对胎儿进行了60分钟的监测。在妊娠24、28、32和36周时收集数据。通过心动描记仪收集胎儿神经行为指标(即心率、运动活动及其整合[胎动-胎心率耦合]),并进行数字化和量化。纵向数据分析依赖于分层线性模型。
与母亲丁丙诺啡血药浓度谷值相比,峰值时胎儿心率、心率变异性和心率加速显著降低。这些影响在妊娠28周时或之后显著,且随着孕周增加有加剧趋势。在妊娠36周时,胎儿运动活动和胎动-胎心率耦合从峰值到谷值均受到抑制。多物质暴露对胎儿神经行为参数没有显著影响,唯一例外是在妊娠36周时,吸烟较多的孕妇所怀胎儿的活动明显少于吸烟较少者。到妊娠末期,母亲丁丙诺啡剂量较高与谷值时胎儿心脏基线指标的抑制有关。
母亲使用丁丙诺啡对胎儿心率和运动有急性抑制作用,且随着孕周进展,这些作用的程度会增加。较高剂量(≥13毫克)似乎对胎儿心率和变异性指标有更大的抑制作用。这些发现应与孕期美沙酮的影响、丁丙诺啡暴露婴儿相对良好的结局以及认识到药物辅助治疗对患有阿片类药物使用障碍的孕妇在优化妊娠结局方面的益处进行权衡。