Prenatal alcohol exposure can be determined from baby teeth: Proof of concept

Abstract

Background: Prenatal alcohol exposure (PAE), leading to fetal alcohol spectrum disorders (FASD), is a serious public health issue in the United States and globally. Diagnosis of FASD is crucial in obtaining appropriate care, but it is not always possible when PAE cannot be documented.

Methods: Deciduous teeth from a child with known PAE and a child with known absence of PAE were analyzed using liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) in a multiple-reaction monitoring mode for direct markers and LC-high resolution MS in positive and negative mode with hydrophilic interaction liquid chromatography and reverse-phase chromatography, respectively, for indirect markers.

Results: Direct markers of PAE (ethyl glucuronide and ethyl sulfate) were detected in prenatal and postnatal dentine from a case tooth but not from a control tooth. Indirect biomarker analysis indicated a dysregulation of amino acids and an increase in cholesterol sulfate in the case compared to the control tooth.

Conclusions: This proof-of-concept study demonstrates for the first time that direct biomarkers of PAE are detectable and measurable in deciduous teeth which begin forming in utero and are typically naturally shed between 5 and 12 years of age. Further examination of these novel biomarkers may allow diagnosis of FASD where documentation of PAE is otherwise unavailable. Furthermore, because teeth grow incrementally, defined growth zones can be sampled allowing for identification of gestational timing of PAE to help better understand mechanisms underlying alcohol's disruption of perinatal development.

Keywords: alcohol; biomarkers; fetal alcohol spectrum disorder; prenatal.

Figure 1.. Key aspects of tooth development.

Tooth mineralization begins early in the second trimester, with completion of the enamel covered crown occurring 3–12 months after birth, depending on the tooth type. The neonatal line, a histological landmark visible in teeth, can be used to determine the timing of growth layers throughout the crown (Nina Sabel et al., 2008). Reprinted with permission (Morishita & Arora, 2017).

Figure 2.. Chromatograms of Direct Biomarkers EtG and EtS in tooth powder.

Extracted ion chromatograms from LC-IDMS/MS analysis of (A) EtG and EtS standard (0.1 ng/mL), (B) reagent blank, (C) extract fraction from prenatal dentine collected from case tooth, and (D) extract fraction from prenatal dentine from control tooth.