Phosphatidylethanol as a screening tool for alcohol consumption during pregnancy

Background

No safe level of alcohol consumption during pregnancy exists. Screening of alcohol consumption in antenatal healthcare in Finland is based on self-reporting, and there is a need for an objective screening method. Phosphatidylethanol (PEth) is a sensitive and specific biomarker revealing alcohol intake up to a few weeks after alcohol consumption. So far, PEth has been a tool for detecting moderate and heavy consumption of alcohol. 

Our aim was to develop a more sensitive PEth method to assess whether PEth could also reveal minor alcohol consumption during pregnancy. With this sensitive PEth analysis we estimated the prevalence of alcohol consumption during pregnancy in southern Finland.

Methods

We improved the PEth method to reach a lower limit of quantification to also reveal minor alcohol intake during pregnancy, while preserving the specificity of the method. Currently, a detection limit of 35 ng/ml is available in Finland, but our limit for a positive PEth result was 2 ng/ml.

We developed a new sensitive analysis method for UPLC-MS/MS (Ultra High-Pressure Liquid Chromatography Tandem Mass Spectrometry) equipment using liquid-liquid extraction of PEth from whole blood. The extraction and analysis method was validated according to FINAS SFS-EN ISO/IEC 17025:2017 guidelines.

We performed the PEth analysis on 3000 anonymous antenatal blood samples collected from Helsinki University Hospital Diagnostic Center between June and September 2023. The samples were originally collected for blood group typing and antibody screening by the Finnish Red Cross Blood Service, as part of the routine antenatal blood screening programme in the Finnish antenatal services.

Results

We detected a positive PEth result in 156/3000 of the antenatal blood samples. Of these, 4.2% were 2–19 ng/ml, 0.9% were 20–199 ng/ml, and 0.1% were above 200 ng/ml. The sensitive PEth test enabled an objective way to measure even mild alcohol use. With the present Finnish PEth detection limit of 35 ng/ml, the proportion of PEth positive cases would have been only 0.6%. The detection time of PEth at low concentrations can be several weeks, especially after heavy alcohol consumption, and it remained unknown whether the positive PEth test resulted from deliberate alcohol consumption during pregnancy or from consumption that occurred before a positive pregnancy test.

Conclusions

Although all alcohol use is discouraged in Finnish antenatal healthcare, 5.2% of the unselected pregnant population had an elevated PEth concentration during pregnancy and, therefore, the foetuses also presumably had alcohol exposure. A sensitive PEth method could be a promising, objective screening tool for even mild alcohol consumption in antenatal healthcare.