The Validity of Phosphatidylethanol in Dried Blood Spots of Newborns for the Identification of Prenatal Alcohol Exposure

Abstract

Background Accurate identification of prenatal alcohol exposure (PAE) in the newborn period offers an opportunity for early identification of children at risk for future neurocognitive problems and the implementation of interventional approaches earlier in life. PAE newborn screening by measuring phosphatidylethanol in dried blood spot (PEth-DBS) cards is feasible, logistically easier, and more cost-efficient compared to other biomarkers. However, the sensitivity and specificity of this method have yet to be established. Methods This prospective cohort study examined validity of PEth-DBS among 28 infants with PAE and 32 controls relative to maternal self-report and other biomarkers. Pregnant women were recruited from a University of New Mexico clinic and followed to early postpartum period. The composite index, which was based on self-reported measures of alcohol use and allowed to classify subjects into PAE and control groups, was the criterion measure used to estimate sensitivity and specificity of PEth-DBS. Results The study included large proportions of patients representing ethnic minorities (7.4% American Indian, 81.7% Hispanic/Latina), low education (54.2% <high school), and unplanned pregnancy (90.0%). No differences in socio-demographic characteristics, smoking, or illicit drug use were observed among the study groups. The sensitivity of maternal biomarkers (GGT, %CDT, UEtG, UEtS) was low (<15%) reflecting a moderate chronic or intermittent binge pattern of drinking in this cohort. PEth-DBS demonstrated 100% specificity and the highest sensitivity (32.1%) compared to other biomarkers. A battery consisting of maternal direct ethanol metabolites (UEtG, UEtS, PEth) and newborn PEth-DBS increased sensitivity to 50% without a substantial drop in specificity (93.8%). Conclusions Newborn PEth-DBS is a highly specific biomarker and can facilitate accurate detection of PAE in conjunction with other biomarkers. Minimal invasiveness, ease of storage and transportation of DBS cards, absence of post-collection synthesis, cost savings, and potential integration with routine newborn screening are all unique advantages of this method.

Quantification of phosphatidylethanol 16:0/18:1, 18:1/18:1, and 16:0/16:0 in venous blood and venous and capillary dried blood spots from patients in alcohol withdrawal and control volunteers

“…To improve the stability of compounds in whole blood and to facilitate the storage and transportation of samples [21], DBS methods have been developed. Numerous DBS-based methods have been published for a wide variety of applications, including therapeutic drug monitoring and toxicology [22].…”

“…Also alcohol markers such as ethyl glucuronide, ethyl sulphate and PEths have been determined, starting from DBS ( [15,18,21,[23][24][25]; reviewed by Sadones et al, 2014 [26]). Since 2011, two publications have reported on the quantification of PEth 16:0/18:1 [15,18] and PEth 18:1/18:1 [15] in V-DBS samples, while only one [21] reported on the analysis of C-DBS samples (detection of PEth 16:0/18:1 in newborns to detect prenatal alcohol exposure). V-DBS are prepared by spotting a fixed volume of venous blood onto a filter paper, whereas C-DBS are generated by direct collection of blood drops appearing after a finger or heel prick onto a filter paper.…”

Retrospective assessment of prenatal alcohol exposure by detection of phosphatidylethanol in stored dried blood spot cards: An objective method for determining prevalence rates of alcohol consumption during pregnancy

“…Our laboratory previously developed and validated a highly sensitive liquid chromatography-tandem mass spectrometry system for the extraction and detection of PEth from DBS samples to facilitate detection of PAE (Jones, 2011). Bakhireva et al (2014) recently published results from a prospective cohort of 60 pregnant women and newborn pairs that reported detection of newborn PEth in DBS demonstrated 100% specificity and newborn PEth screening could accurately detect PAE with a higher sensitivity than other currently used direct and indirect alcohol metabolites. Their previous analysis of PEth in newborn DBS samples has also demonstrated the feasibility of collecting an additional DBS card during routine newborn screening for measurement of PEth as an indicator of PAE, a practice that also provides overall cost savings compared to either meconium fatty acid ethyl esters (FAEE) analysis or analysis of PEth from blood specimens obtained by phlebotomy (Bakhireva et al, 2013).…”

Ghent Symposium on Alternative Sampling Strategies in Toxicology and Therapeutic Drug Monitoring

“…Significant correlation between results from DBS and sera and CE and HPLC analysis were shown [17][18][19].…”