Singer L T, Garber R, Kliegman R
Department of Pediatrics, Case Western Reserve University, School of Medicine, Cleveland, Ohio.
J Pediatr. 1991 Oct;119(4):667-72. doi: 10.1016/s0022-3476(05)82426-6.
The number of infants born to cocaine-using mothers has continued to rise during the past 5 years. Maternal cocaine use during pregnancy is associated with medical and life-style characteristics detrimental to fetal and infant development. Cocaine exposure has been independently linked to growth retardation and impaired fetal oxygenation even when polydrug use and other confounding factors are considered. Neurologic and neurobehavioral abnormalities noted in the immediate neonatal period have also been associated with fetal cocaine exposure. The direct and indirect toxic effects of cocaine, per se, have not yet been independently linked to specific behavioral outcomes because of small sample sizes, confounding factors, and lack of long-term follow-up. The impoverished environments and increased risk for out-of-family placement of cocaine-exposed infants are known independent correlates of negative developmental outcomes. Poor maternal nutrition, lack of prenatal care, and other health and life-style factors related to maternal cocaine use during pregnancy also appear to be factors mediating the developmental problems of cocaine-exposed infants. The cocaine-using mother often uses other drugs, particularly alcohol, independently known to be linked to growth and behavioral impairments similar to those proposed for cocaine-exposed infants. Accounting for these multiple confounding variables in studies of the specific effects of cocaine on neurobehavioral outcome may be scientifically appropriate, but in clinical practice these factors cannot be "isolated," and their statistical consideration in studies does not diminish clinical risk. Finally, currently available studies of behavioral outcome have restricted their samples to term infants. It is possible that preterm infants may be less affected by prenatal cocaine exposure because of decreased exposure. However, because epidemiologic studies suggest that prematurity is a sequelae of maternal cocaine use, restriction of samples to term or appropriately sized infants may underestimate the spectrum of morbidity associated with cocaine exposure. We believe that maternal cocaine use during pregnancy is a "marker" variable for early impairments in infant growth and behavioral functioning that have long-term implications for later developmental outcome, especially for learning disabilities and behavioral disorders. Critically assessing the independent contribution of cocaine to negative developmental outcome and determining whether early neonatal abnormalities are permanent or modifiable may allow clinical intervention and improved social policy. Assessing the independent effects of cocaine on child developmental outcome will require carefully designed, long-term, longitudinal, population-based studies with samples large enough to allow multivariate data analyses and statistical control of confounding medical and social variables.
在过去5年中，可卡因成瘾母亲所生婴儿的数量持续上升。孕期母亲使用可卡因与对胎儿和婴儿发育有害的医学及生活方式特征相关。即使考虑到多药滥用和其他混杂因素，可卡因暴露也已被独立地与生长发育迟缓及胎儿氧合受损联系起来。在新生儿期即刻出现的神经和神经行为异常也与胎儿可卡因暴露有关。由于样本量小、混杂因素以及缺乏长期随访，可卡因本身的直接和间接毒性作用尚未被独立地与特定行为结果联系起来。可卡因暴露婴儿所处的贫困环境以及被安置到家庭外的风险增加是已知的与不良发育结果相关的独立因素。孕期母亲使用可卡因相关的不良母体营养、缺乏产前护理以及其他健康和生活方式因素似乎也是介导可卡因暴露婴儿发育问题的因素。使用可卡因的母亲通常还会使用其他药物，尤其是酒精，已知其与类似于可卡因暴露婴儿所出现的生长和行为损害有关。在研究可卡因对神经行为结果的特定影响时考虑这些多个混杂变量在科学上可能是合适的，但在临床实践中这些因素无法“分离”，而且在研究中对它们进行统计考量并不会降低临床风险。最后，目前关于行为结果的研究将样本限制在了足月儿。由于暴露减少，如果早产婴儿可能受产前可卡因暴露的影响较小。然而，因为流行病学研究表明早产是母亲使用可卡因的后遗症，将样本限制在足月儿或大小合适的婴儿可能会低估与可卡因暴露相关的发病范围。我们认为孕期母亲使用可卡因是婴儿生长和行为功能早期受损的一个“标志”变量，这些损害对后期发育结果有长期影响，尤其是对学习障碍和行为障碍。批判性地评估可卡因对不良发育结果的独立作用，并确定新生儿早期异常是永久性的还是可改变的，可能会带来临床干预和更好的社会政策。评估可卡因对儿童发育结果的独立影响将需要精心设计的、长期的、纵向的、基于人群的研究，其样本量要足够大，以便进行多变量数据分析并对混杂的医学和社会变量进行统计控制。
