Elsevier

Medical Hypotheses

Volume 85, Issue 6, December 2015, Pages 965-968
Medical Hypotheses

Could a first-trimester blood phosphatidylethanol concentration ⩾4 nM be useful to identify women with moderate-to-heavy prenatal alcohol exposure who are at high risk of adverse pregnancy outcomes?

https://doi.org/10.1016/j.mehy.2015.08.026Get rights and content

Abstract

It is accepted that blood phosphatidylethanol (PEth) concentrations are reliable biomarkers of ethanol (alcohol) exposure. We therefore conducted a preliminary study to test the hypothesis that elevated blood PEth concentrations can help to identifying women with prenatal alcohol exposure who are at higher risk of adverse pregnancy outcomes. The study included 35 first-trimester pregnant women who self-reported alcohol ingestion and had PEth blood concentration ⩾4 nM at recruitment. As a control group, 233 first-trimester pregnant women who self-reported as being either abstainers or light alcohol drinkers and had blood PEth concentrations <4 nM, were also included. All participants were followed up until completion of their pregnancies. Women with prenatal alcohol exposure and PEth concentrations ⩾4 nM had a risk ratio of spontaneous abortions of 3.21 (95%CI 0.93–11.06; P = 0.074). Because of the potential implications in the prenatal care of women reporting risky alcohol exposure, the preliminary results from the present study indicate the need for testing the hypothesis in a more definitive approach.

Introduction

Neither ingestion of light amounts of alcohol during pregnancy nor exposure limited to the first trimester of pregnancy has been found to be associated with an increased risk of adverse pregnancy outcomes such as spontaneous abortions or babies born small for gestational age [1], [2]. However, as the level and length of prenatal alcohol exposure increase, the risk of adverse pregnancy outcomes also increases. For example, ingestion of 2–4 drinks/week during pregnancy is associated with an increased risk of low birth weight and neonatal asphyxia [3]. Spontaneous abortions occurred in approximately 9% of pregnant women ingesting ⩾5 drinks/week [4].

Surprisingly, this dose–response effect between prenatal alcohol exposure and adverse pregnancy outcomes is far from being established in a definitive way. For example, a Danish cohort study found that even low amounts of alcohol consumption during early pregnancy increased the risk of spontaneous abortion substantially [5]. On the other side of the spectrum, two large European cohort studies and a systematic review of epidemiological studies failed to confirm any increased risk of adverse pregnancy outcomes among women who reported a daily ingestion of 1–1.5 drinks of alcohol [6], [7], even among women who were disadvantaged in terms of low education, high levels of distress, or smoking during pregnancy [6].

Although these contradictory results could be partially explained by a variety of methodological differences across studies, problems associated with the reliability of alcohol ingestion self-reported by participants could be a major factor explaining such differences. This problem could easily be overcome if epidemiological studies could incorporate a robust and inexpensive indicator of prenatal alcohol ingestion. Unfortunately, despite efforts to identify such biomarker conducted by several groups of investigators, independently, there is not yet one that could be considered as the gold standard.

Section snippets

The hypotheses

The short half-life of ethanol itself, as well as of that of its major oxidative metabolite acetaldehyde, limit their use as biomarkers of prenatal alcohol exposure in the clinical setting. Indirect biomarkers of prenatal alcohol exposure such as gamma glutamyltranspeptidase and mean corpuscular volume have shown poor sensitivity in pregnant women [8], [9]. However, non-oxidative metabolites of ethanol, such as phosphatidylethanol (PEth), have generated interest for their theoretically high

Participants

The study, conducted in compliance of the World Medical Association Declaration of Helsinki regarding ethical conduct of research involving human subjects, was based on a prospective follow-up of 284 participants who previously participated in the characterization of blood PEth concentration as a biomarker of prenatal alcohol exposure [11]. Briefly, after receiving approval by the institutional review board at the Cheil General Hospital and Women’s Healthcare Center, Seoul, Republic of Korea,

Consequences of the hypothesis and discussion

Extensive efforts have been made to identify biomarkers of prenatal alcohol exposure which, in turn, can help to identify those babies at risk of ethanol-related postnatal developmental alterations. In this context, the present study provides preliminary evidence to consider PEth as a promising biomarker to study the link between prenatal alcohol exposure and high risk of adverse pregnancy outcomes. A further, more detailed confirmation of these findings would have several important

Conflict of interest

The authors stated that there are no conflicts of interest regarding the publication of this article. No support was received, in any form, from the manufacturers or distributors of the reagents or equipment cited in the document.

Statement of author contributions

J.Y. Yang, J.Y. Han, and Y.J. Oh participated in the conception and design of the study. H.S. Kwak implemented the analytical methods and conducted all the laboratory analysis. Y. Han, J.S. Choi, and H.-K. Ahn recruited the participants and collected the blood samples. J.Y. Yang, J.Y. Han, Y.J. Oh, E.Y. Velázquez-Armenta, and A.A. Nava-Ocampo conducted the statistical analysis and drafted the interpretation of the results. All authors participated in the preparation of the manuscript and the

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