Jacobson B, Nyberg K, Grönbladh L, Eklund G, Bygdeman M, Rydberg U
Karolinska Institute, Stockholm, Sweden.
BMJ. 1990 Nov 10;301(6760):1067-70. doi: 10.1136/bmj.301.6760.1067.
To test the hypothesis that opiate addiction in adults might stem partly from an imprinting process during birth when certain drugs are given to the mother.
Retrospective study by logistic regression of opiate addicts with siblings as controls.
Stockholm, Sweden.
200 Opiate addicts born in Stockholm during 1945-66, comprising 41 identified during interviews of probands for an earlier study; 75 patients whose death from opiate addiction had been confirmed during 1978-88; and 84 accepted for the methadone programme. 262 Siblings (controls) born in Stockholm during the same period, 24 of whom were excluded for drug addiction or being brought up outside the family. Birth records were unavailable for eight, leaving 230 siblings and 139 corresponding probands.
Administration of opiates, barbiturates, and nitrous oxide (for greater than 1 h) to mothers of all subjects during labour within 10 hours before birth as a risk factor for adult opiate addiction.
In subjects who had subsequently become addicts a significant proportion of mothers had received opiates or barbiturates, or both, compared with unmatched siblings (25% v 16%, chi 2 = 5.83, df = 1, p = 0.02), and these mothers had received nitrous oxide for longer and more often. After controlling for hospital of birth, order of birth, duration of labour, presentation other than vertex, surgical intervention, asphyxia, meconium stained amniotic fluid, and birth weight the relative risk for offspring subsequently becoming an adult opiate addict increased with the number of administrations of any of the three drugs. When the addicts were matched with their own siblings the estimated relative risk was 4.7 (95% confidence interval 1.8 to 12.4, p for trend = 0.002) for three administrations compared with when no drug was given.
The results are compatible with the imprinting hypothesis. Therefore, for obstetric pain relief methods are preferable that do not permit substantial passage of drugs through the placenta.
验证成年阿片类药物成瘾可能部分源于出生时母亲使用某些药物所导致的印记过程这一假说。
以同胞作为对照，通过逻辑回归进行回顾性研究。
瑞典斯德哥尔摩。
1945年至1966年在斯德哥尔摩出生的200名阿片类药物成瘾者，其中包括在一项早期研究中对先证者进行访谈时确定的41人；1978年至1988年期间因阿片类药物成瘾死亡得到确认的75名患者；以及84名接受美沙酮治疗项目的患者。262名同期在斯德哥尔摩出生的同胞（对照），其中24人因药物成瘾或在家庭外抚养而被排除。8人没有出生记录，剩余230名同胞和139名相应的先证者。
在出生前10小时内分娩过程中，所有研究对象的母亲使用阿片类药物、巴比妥类药物和一氧化二氮（使用时间超过1小时）作为成年后阿片类药物成瘾的危险因素。
在后来成瘾的研究对象中，与不匹配的同胞相比，有相当比例的母亲使用过阿片类药物或巴比妥类药物，或两者都使用过（25%对16%，卡方 = 5.83，自由度 = 1，p = 0.02），而且这些母亲使用一氧化二氮的时间更长、频率更高。在控制了出生医院、出生顺序、产程时长、非头位产、手术干预、窒息、羊水胎粪污染和出生体重后，后代随后成为成年阿片类药物成瘾者的相对风险随着这三种药物中任何一种的使用次数增加而增加。当成瘾者与他们自己的同胞匹配时，与未使用药物相比，三种药物使用的估计相对风险为4.7（95%置信区间1.8至12.4，趋势p = 0.002）。
结果与印记假说相符。因此，对于产科疼痛缓解，更可取的方法是不允许药物大量通过胎盘。
