Jansson Lauren M, Dipietro Janet A, Velez Martha, Elko Andrea, Knauer Heather, Kivlighan Katie T
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Matern Fetal Neonatal Med. 2009 Jan;22(1):29-35. doi: 10.1080/14767050802452291.
Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviours. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehaviour than single-dose administration.
Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36- and 37-weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens.
All fetal neurobehavioural parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single versus split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing versus single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition.
Split-dosed fetuses displayed less neurobehavioural suppression from trough to peak maternal methadone levels as compared with single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women.
每日美沙酮维持治疗是孕期阿片类药物依赖的标准治疗方法。先前的研究表明,单次给予母体美沙酮会显著抑制胎儿神经行为。本研究的目的是确定分次给药对胎儿神经行为的影响是否小于单次给药。
40名接受美沙酮维持治疗的女性在单次给药和分次给药方案下,于母体美沙酮血药浓度峰值和谷值时接受评估。在一项平衡研究设计中,于妊娠36周和37周进行监测。胎儿测量指标包括心率、变异性、加速、运动活动以及胎儿运动-心率耦合(FM-FHR)。母体测量指标包括心动周期、变异性、皮肤电导、呼吸和迷走神经张力。采用重复测量方差分析来评估分次给药和单次给药方案之间的受试者内变化。
无论给药方案如何,母体美沙酮给药均会抑制所有胎儿神经行为参数。与分次给药相比,单次美沙酮给药时峰值处的胎儿参数显著更低。与单次给药相比,分次给药时从谷值到峰值FM-FHR耦合受抑制程度更小。母体生理参数一般不受给药条件影响。
与单次给药的胎儿相比,分次给药的胎儿在母体美沙酮血药浓度从谷值到峰值时神经行为受抑制程度更小。分次给药可能对接受美沙酮维持治疗的孕妇有益。