USDTL Assisted Research
Phosphatidylethanol and Alcohol Consumption in Reproductive Age Women
Scott H. Stewart MD, Tameeka L. Law MD, Patrick K. Randall Ph.D., and Roger Newman MD
First Published: 07 December 2009 DIO: 10.1111/j.1530-0277.2009.01113.x
Fetal alcohol disorders are preventable, but self-reported alcohol consumption can be misleading and impede effective treatment. Biomarkers represent an alternative method for assessing alcohol use, and this study evaluated the relationship between blood phosphatidyl ethanol (PEth) and alcohol use in a sample of reproductive-age women.
Alcohol use was estimated by validated self-report methods in 80 non-pregnant women ages 18 to 35. PEth was measured by a contracted laboratory using a liquid chromatography-tandem mass spectrometry assay. Regression methods appropriate for the distribution of PEth were used to define its relationship to alcohol consumption during the prior 2 weeks and explore the effects of drinking patterns on this association. Receiver operating characteristic analysis was used to estimate the sensitivity of PEth for various drinking levels at 95% specific cutoffs.
PEth had a positive linear association with grams of alcohol consumed (p<0.001) and was detectable in 93% of subjects consuming an average of 2 or more drinks per day. The relationship between total alcohol consumption and PEth may be stronger in women with recent heavy drinking days. The relationship between drinking and PEth varied considerably between individuals, and sensitivity for a certain amount of drinking was low at a highly specific cutoff concentration.
PEth is a highly sensitive indicator of moderate and heavy alcohol consumption in reproductive-age women and may complement the use of self-report alcohol screens when additional objective markers of alcohol use are desirable. However, choosing a highly valid cutoff concentration for PEth to differentiate various levels of alcohol consumption may not be feasible.
Fetal alcohol spectrum disorders (FASD) are preventable birth defects in approximately 1 in 1,000 live births in the US. Fetal alcohol syndrome is a severe form of FASD related to chronic heavy drinking during pregnancy and is characterized by facial dysmorphology, diminished growth, and mental retardation. Other alcohol-related birth defects, including heart, kidney, and auditory deficits, can also occur. The alcohol-related neurodevelopmental disorder can be a subtler condition that may also be associated with heavy and perhaps even moderate drinking during pregnancy and is expressed as learning deficits and behavioral problems that may only become apparent as the child matures.
Strengths of this study included the detailed assessment of alcohol use and its association with a novel alcohol biomarker in a population of particular importance and the inclusion of a full range of recent alcohol exposures. This inclusion of a broad range of recent drinking activity explains why no cutoff concentration for PEth was highly sensitive and specific for a certain level of consumption. The main limitation was reliance on self-reported drinking as a reference standard, which provides a reasonable estimate but is certainly not error-free. Any non-random misclassification based on this standard would bias the estimated sensitivity and specificity of PEth for specific drinking categories. The study also evaluated non-pregnant women, and the prospect of pregnancy makes reproductive-age women of particular relevance for validating alcohol consumption biomarkers. A similar study during pregnancy would be ideal, but ensuring accurate self-report and recruitment of women with a range of alcohol involvement during pregnancy would be difficult. An additional limitation was the sample size, which was not large enough for reliably estimating the effects of drinking patterns (e.g., binging vs. regular moderate drinking) on the relationship between PEth and total consumption. Controlled drinking experiments over a period of several weeks could address these issues but would be expensive to conduct. Alternatively, additional epidemiologic studies such as this one may provide additional confidence if the results are similar. Finally, the PEth assay evaluated in this study is not routine, is currently only available in specialized laboratories, and would be expensive for clinical use. However, a monoclonal antibody to PEth has been developed, and less expensive immunoassays that can be utilized in most clinical laboratories may be on the horizon.
Identification of alcohol use in pregnant women and women trying to conceive is an important goal in preventing FASD, and validated self-report instruments are available for this purpose. This study suggests that PEth measured by mass spectrometry can be used as a very sensitive indicator of drinking over approximately 2 drinks per day in circumstances where there is a desire to obtain additional objective indicators of alcohol use, with diminished sensitivity for lower levels of drinking. PEth may also be useful in clinical research protocols for this same purpose. Future studies would be useful for identifying sources of variability in PEth concentration among women drinking at similar levels, verifying a similar relationship between PEth and drinking during pregnancy, and confirming the relationship between the amount of alcohol consumed and PEth concentration.