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Prenatal alcohol exposure can be determined from baby teeth: Proof of concept
Annika C Montag1, Christina D Chambers1,2, Kenneth Lyons Jones1
1Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
Insights
Direct biomarkers for prenatal alcohol exposure (PAE) are detectable in deciduous teeth, offering a new diagnostic tool for fetal alcohol spectrum disorders (FASD) when exposure history is unknown. This method may also pinpoint the timing of exposure during pregnancy.
Area of Science:
- Biomarker discovery
- Analytical chemistry
- Developmental toxicology
Background:
- Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorders (FASD), a significant global health concern.
- Accurate diagnosis of FASD is vital for patient care but challenging without documented PAE.
- Deciduous teeth offer a potential biological matrix for retrospective PAE assessment.
Purpose of the Study:
- To investigate the presence of direct and indirect biomarkers of PAE in deciduous teeth.
- To establish a novel method for diagnosing FASD in cases with undocumented PAE.
- To explore the potential for determining the gestational timing of PAE using incremental tooth growth.
Main Methods:
- Analysis of deciduous teeth from children with and without known PAE.
- Utilized liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) for direct biomarkers (ethyl glucuronide, ethyl sulfate).
- Employed LC-high resolution MS for indirect biomarkers, including amino acids and cholesterol sulfate.
Main Results:
- Direct PAE biomarkers were detected in prenatal and postnatal dentine of a case tooth, but not in the control.
- Indirect biomarker analysis revealed amino acid dysregulation and increased cholesterol sulfate in the case tooth.
- This study provides proof-of-concept for biomarker detection in deciduous teeth.
Conclusions:
- Direct biomarkers of PAE are measurable in deciduous teeth, which form during gestation.
- This finding may enable FASD diagnosis when PAE documentation is lacking.
- Incremental analysis of tooth growth zones could reveal the timing of PAE, aiding research into alcohol's developmental effects.
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.
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