Jacobson Joseph L, Akkaya-Hocagil Tugba, Jacobson Sandra W, Coles Claire D, Richardson Gale A, Olson Heather Carmichael, Day Nancy L, Carter R Colin, Dodge Neil C, Dang Khue-Dung, Cook Richard J, Ryan Louise M
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.
Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada.
Alcohol Clin Exp Res (Hoboken). 2024 Apr;48(4):623-639. doi: 10.1111/acer.15283. Epub 2024 Mar 30.
Most studies of the effects of prenatal alcohol exposure (PAE) on cognitive function have assumed that the dose-response curve is linear. However, data from a few animal and human studies suggest that there may be an inflection point in the dose-response curve above which PAE effects are markedly stronger and that there may be differences associated with pattern of exposure, assessed in terms of alcohol dose per drinking occasion and drinking frequency.
We performed second-order confirmatory factor analysis on data obtained at school age, adolescence, and early adulthood from 2227 participants in six US longitudinal cohorts to derive a composite measure of cognitive function. Regression models were constructed to examine effects of PAE on cognitive function, adjusted for propensity scores. Analyses based on a single predictor (absolute alcohol (AA)/day) were compared with analyses based on two predictors (dose/occasion and drinking frequency), using (1) linear models and (2) nonparametric general additive models (GAM) that allow for both linear and nonlinear effects.
The single-predictor GAM model showed virtually no nonlinearity in the effect of AA/day on cognitive function. However, the two-predictor GAM model revealed differential effects of maternal drinking pattern. Among offspring of infrequent drinkers, PAE effects on cognitive function were markedly stronger in those whose mothers drank more than ~3 drinks/occasion, and the effect of dose/occasion was strongest among the very frequent drinkers. Frequency of drinking did not appear to alter the PAE effect on cognitive function among participants born to mothers who limited their drinking to ~1 drink/occasion or less.
These findings suggest that linear models based on total AA/day are appropriate for assessing whether PAE affects a given cognitive outcome. However, examination of alcohol dose/occasion and drinking frequency is needed to fully characterize the impact of different levels of alcohol intake on cognitive impairment.
大多数关于产前酒精暴露（PAE）对认知功能影响的研究都假定剂量反应曲线是线性的。然而，一些动物和人体研究的数据表明，剂量反应曲线可能存在一个拐点，超过该拐点后，PAE的影响会明显增强，并且可能存在与暴露模式相关的差异，这种差异可以根据每次饮酒场合的酒精剂量和饮酒频率来评估。
我们对来自美国六个纵向队列的2227名参与者在学龄期、青春期和成年早期获得的数据进行了二阶验证性因素分析，以得出认知功能的综合测量指标。构建回归模型来检验PAE对认知功能的影响，并根据倾向得分进行调整。将基于单一预测因子（每日绝对酒精摄入量（AA））的分析与基于两个预测因子（每次饮酒剂量和饮酒频率）的分析进行比较，使用（1）线性模型和（2）允许线性和非线性效应的非参数广义相加模型（GAM）。
单预测因子GAM模型显示，每日AA对认知功能的影响几乎没有非线性。然而，双预测因子GAM模型揭示了母亲饮酒模式的不同影响。在不常饮酒者的后代中，母亲每次饮酒超过约3杯的后代，PAE对认知功能的影响明显更强，且每次饮酒剂量的影响在饮酒非常频繁者中最为显著。对于母亲每次饮酒限制在约1杯或更少的参与者，饮酒频率似乎并未改变PAE对认知功能的影响。
这些发现表明，基于每日总AA的线性模型适用于评估PAE是否会影响特定的认知结果。然而，需要检查每次饮酒剂量和饮酒频率，以全面描述不同酒精摄入量水平对认知障碍的影响。
