Meconium Fatty Acid Ethyl Esters as Biomarkers of Late Gestational Ethanol Exposure and Indicator of Ethanol-Induced Multi-Organ Injury in Fetal Sheep

Zelner, Irene; Kenna, Kelly R.; Brien, James F.; Bocking, Alan D.; Harding, Richard; Walker, David; Koren, Gideon

doi:10.1371/journal.pone.0059168

Cited by 19 publications

(13 citation statements)

References 38 publications

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“…Multiple animal models suggest that in utero alcohol also alters the development of the lung, 5, 6, 34–37 but no clinical data have been reported regarding pulmonary outcomes of alcohol-exposed newborns, particularly those born prematurely. In the current study population, we did not find a significance effect of alcohol exposure on the individual outcomes of BPD or neonatal Death.…”

Section: Discussionmentioning

confidence: 99%

Maternal Alcohol Use During Pregnancy and Associated Morbidities in Very Low Birth Weight Newborns

Gauthier

Guidot

Kelleman

et al. 2016

The American Journal of the Medical Sciences

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Background We hypothesized that maternal alcohol use occurs in pregnancies that end prematurely and that in utero alcohol exposure is associated with an increased risk of morbidities of premature newborns. Methods In an observational study of mothers who delivered very low birth weight newborns ≤ 1500 grams (VLBW), maternal alcohol use was determined via a standardized administered questionnaire. We compared the effect of maternal drinking on the odds of developing late onset sepsis, bronchopulmonary dysplasia (BPD), Death, BPD or death (BPD/Death), days on oxygen or Any Morbidity (either late onset sepsis, BPD or Death). The effect of drinking amounts (light versus heavy) was also evaluated. Results One hundred twenty nine subjects who delivered 143 VLBW newborns were enrolled. Approximately one in three (34%) subjects reported drinking alcohol during the 1st Trimester (‘Exposed’). Within the Exposed group, 15% reported drinking ≥ 7 drinks/week (‘heavy’) and 85% of the subjects reported drinking < 7 drinks/week (‘light’). When controlling for maternal age, drug/tobacco use during pregnancy and neonatal gestational age, any drinking increased the odds of BPD/Death and Any Morbidity. Furthermore, light or heavy drinking increased the odds of BPD/Death and Any Morbidity, while heavy drinking increased the odds of late onset sepsis. Conclusions In utero alcohol exposure during the first trimester occurred in 34% of VLBW newborns. Maternal drinking in the first trimester was associated with significantly increased odds of neonatal morbidity. Further studies are warranted to determine the full effect of in utero alcohol exposure on adverse outcomes of VLBW premature newborns.

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Section: Discussionmentioning

confidence: 99%

Maternal Alcohol Use During Pregnancy and Associated Morbidities in Very Low Birth Weight Newborns

Gauthier

Guidot

Kelleman

et al. 2016

The American Journal of the Medical Sciences

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“…Animal models may also be useful for the development of novel testing procedures for PAE. 49,114,115 However, translation from animal studies to human populations is complicated by differences in alcohol exposure methods, gestation, and alcohol metabolism. In summary, validation will rely on an ongoing body of research that produces convergent evidence to suggest that objective measures are meaningfully associated with PAE.…”

Section: Discussionmentioning

confidence: 99%

Objective Measures of Prenatal Alcohol Exposure: A Systematic Review

McQuire¹,

Paranjothy²,

Hurt³

et al. 2016

Pediatrics

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CONTEXT: Objective measurement of prenatal alcohol exposure (PAE) is essential for identifying children at risk for adverse outcomes, including fetal alcohol spectrum disorders. Biomarkers have been advocated for use in universal screening programs, but their validity has not been comprehensively evaluated. OBJECTIVE:To systematically review the validity of objective measures of PAE. DATA SOURCES:Thirteen electronic databases and supplementary sources were searched for studies published between January 1990 and October 2015.STUDY SELECTION: Eligible studies were those that evaluated the diagnostic accuracy of objective measures of PAE.DATA EXTRACTION: Three reviewers independently verified study inclusion, quality assessments, and extracted data. RESULTS:Twelve studies met inclusion criteria. Test performance varied widely across studies of maternal blood (4 studies; sensitivity 0%-100%, specificity 79%-100%), maternal hair (2 studies; sensitivity 19%-87%, specificity 56%-86%) maternal urine (2 studies; sensitivity 5%-15%, specificity 97%-100%), and biomarker test batteries (3 studies; sensitivity 22%-50%, specificity 56%-97%). Tests of the total concentration of 4 fatty acid ethyl esters (in meconium: 2 studies; in placenta: 1 study) demonstrated high sensitivity (82%-100%); however, specificity was variable (13%-98%).LIMITATIONS: Risk of bias was high due to self-report reference standards and selective outcome reporting.CONCLUSIONS: Current evidence is insufficient to support the use of objective measures of prenatal alcohol exposure in practice. Biomarkers in meconium and placenta tissue may be the most promising candidates for further large-scale population-based research. a Division of Population Medicine and b Specialist Unit for Review Evidence, Cardiff University, Cardiff, United KingdomMs McQuire developed the draft protocol and search strategy, data extraction sheet, and quality coding criteria; carried out study selection, data extraction, quality assessment, and evidence synthesis; and prepared the initial manuscript and subsequent revisions; Dr Paranjothy developed the initial concept for the study, contributed to development of the protocol, extracted data, verifi ed study inclusion decisions and quality assessments, and reviewed and revised the manuscript; Dr Hurt contributed to development of the protocol, extracted data, verifi ed study inclusion decisions and quality assessments, and reviewed and revised the manuscript; Ms Mann contributed to the design of the search strategy and reviewed and revised the manuscript; Dr Farewell provided statistical advice and reviewed and revised the manuscript; Dr Kemp contributed to development of the protocol and reviewed and revised the manuscript; and all authors approved the fi nal manuscript as submitted.This review has been registered at the PROSPERO international prospective register of systematic reviews (www. crd. york. ac. uk) (identifi er CRD42014015420).

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“…30 Furthermore, early administration of alcohol to pregnant mice caused significant DNA damage in the foetal mouse lung. 31 Reductions in surfactant protein-B (SP-B) and altered surfactant phospholipid composition have been reported in multiple models including rat 32 and sheep, 33,34 suggesting direct effects on the epithelial cells of the developing lung. Finally, in these models, increased collagen type III alpha1 gene 32 and increased collagen deposition 34 were also demonstrated in exposed pup lungs, suggesting fibroblast alterations with alcohol exposure.…”

Section: Alcohol-induced Cellular Injury To the Developing Lungmentioning

confidence: 99%

“…31 Reductions in surfactant protein-B (SP-B) and altered surfactant phospholipid composition have been reported in multiple models including rat 32 and sheep, 33,34 suggesting direct effects on the epithelial cells of the developing lung. Finally, in these models, increased collagen type III alpha1 gene 32 and increased collagen deposition 34 were also demonstrated in exposed pup lungs, suggesting fibroblast alterations with alcohol exposure. These data, taken together, suggest that in utero alcohol exposure alters multiple cell types in the developing lung and could potentially increase the risk of respiratory distress in the newborn.…”

Section: Alcohol-induced Cellular Injury To the Developing Lungmentioning

confidence: 99%

“…35 In sheep models, foetal alcohol exposure resulted in reduction of the collectins SP-A 33,34 and SP-D 36 and alters baseline pro-inflammatory cytokine mRNA expression in the exposed neonatal lung. 33,37 We have demonstrated in multiple animal models that in utero alcohol suppresses the maturation and function of the resident alveolar macrophage (AM), increasing the risk of bacterial infection.…”

Section: In Utero Alcohol and Altered Immune Defensesmentioning

confidence: 99%

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In utero alcohol effects on foetal, neonatal and childhood lung disease

Gauthier

Brown

2017

Paediatric Respiratory Reviews

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Summary Maternal alcohol use during pregnancy exposes both premature and term newborns to the toxicity of alcohol and its metabolites. Foetal alcohol exposure adversely effects the lung. In contrast to the adult “alcoholic lung” phenotype, an inability to identify the newborn exposed to alcohol in utero has limited our understanding of its effect on adverse pulmonary outcomes. This chapter will review advances in biomarker development of in utero alcohol exposure. We will highlight the current understanding of in utero alcohol’s toxicity to the developing lung and immune defense. Finally, we will present recent clinical evidence describing foetal alcohol’s association with adverse pulmonary outcomes including bronchopulmonary dysplasia, viral infections such as respiratory syncytial virus and allergic asthma/atopy. With research to define alcohol’s effect on the lung and translational studies accurately identifying the exposed offspring, the full extent of alcohol’s effects on clinical respiratory outcomes of the newborn or child can be determined.

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Meconium Fatty Acid Ethyl Esters as Biomarkers of Late Gestational Ethanol Exposure and Indicator of Ethanol-Induced Multi-Organ Injury in Fetal Sheep

Cited by 19 publications

References 38 publications

Maternal Alcohol Use During Pregnancy and Associated Morbidities in Very Low Birth Weight Newborns

Maternal Alcohol Use During Pregnancy and Associated Morbidities in Very Low Birth Weight Newborns

Objective Measures of Prenatal Alcohol Exposure: A Systematic Review

In utero alcohol effects on foetal, neonatal and childhood lung disease

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