Fetal Alcohol Syndrome, Anthocyanins and FAEE in Meconium as Biomarker
October 16, 2009© Copyright A.CaleekalCitation Information : First Publication (2009) in www. Digitalism.ca . Citation should read:
Fetal Alcohol Syndrome, Anthocyanins and FAEE in Meconium as Biomarker
by Anuppa Caleekal B.A., M.Sc. © Copyright A.Caleekal, www.digitalism.ca October 16,2009
This article aims to integrate findings from research which may help in the screening, detection and prevention of fetal alcohol syndrome and its spectrum of disorders. Dietary interventions of antioxidants such as anthocyanins with their possible benefits on the liver, brain and eye, its neuroprotective factor, ability to penetrate beyond the blood-brain barrier and treating ethanol neurotoxicity are discussed in the context of fetal alcohol syndrome. Fatty acid ethyl esters(FAEE) meconium analysis as a biomarker of prenatal exposure to alcohol in conjunction with anthocyanin dietary intervention is proposed as a possible area of research to be explored in the future. Legal implications of fetal rights, achieving zero tolerance to an established minimum elevated FAEE cut off limit to prenatal alcohol exposure are questions posed in the light of Fetal Alcohol Syndrome being preventable.
The offspring of mothers who drink alcohol heavily during pregnancy are commonly known to have Fetal Alcohol Syndrome (FAS). The fetal alcohol syndrome spectrum of disorders (FASD) ranges from a variety of cognitive, neurological and behavioural impairments where the magnitude of these effects as well as the alcohol drinking patterns of the pregnant mothers vary. There is no amount of alcohol to be taken by a pregnant mother which is deemed as a safe prescribed amount.(FAS) lies at the extreme end of the continuum of alcohol effects on the fetus with heavy persistent maternal alcohol consumption during pregnancy contributing most significantly to the full blown syndrome. Clinically, three areas are affected: (1) prenatal and/or postnatal growth retardation (e.g. infants shorter in length and less in weight); (2) Central Nervous System (CNS) damage such as permanent and irreversible brain damage, learning and behavioral disorders, deficits in memory and attention, hyperactivity, speech and language delays, poor coordination; (3) head and facial abnormalities (e.g. small head circumference and abnormally small eyes).
There is a high occurence of visual impairments as well as various ocular abnormalities common among FAS children. There is such a high frequency in ocular pathology in FASD that an early eye examination can help in verifying early diagnosis. The earlier the detection, the better the prospects are for the management of the disorder. Strömland and Pinazo-Durán outline the many eye conditions apparent by maternal alcohol misuse on the developing eye of the fetus both externally and internally within the eye.The eye being very sensitive to environmental variables, is thus physiologically highly susceptible to the misuse of maternal misuse of alcohol for the fetus in utero and as the baby develops into adulthood.
(Sources:Strömland and Pinazo-Durán. “Ophthalmic Involvement In The Fetal Alcohol Syndrome: Clinical And Animal Model Studies” Alcohol and Alcoholism Vol. 37, No. 1, pp. 2-8, 2002
Störmland,”Visual impairment and ocular abnormalities in children with fetal alcohol syndrome” Addiction Biology, Vol.9, Issue 2, pp 153 – 157, June 2004 )
The external ocular signs include short palpebral fissures, telecanthus, epicanthus, blepharoptosis, microphthalmos and strabismus. Within the eyes, the signs and symptoms most commonly detected are optic nerve hypoplasia, increased tortuosity of the retinal vessels and impaired vision caused by abnormal development of the optic nerve.Problems include the ability to see detail, far and near sightedness and permanent reduction of vision. Clouding of the lens, involuntary eye movements and malformations of the cornea and iris are other possible problems among FAS children.
A canadian study indicates the possible benefits to the function of brain and eyes with anthocyanins as a dietary intervention.Laboratory experiments were conducted on pigs and since pigs have a comparative model of digestive absorption to humans,they were used to study the pattern of anthocyanins being deposited in tissues of the liver, eye and brain.Blueberries contain anthocyanins and the variety of Blueberries ( Vaccinium corymbosum L. ‘Jersey’) were given to the pigs for a month.
Results indicated that anthocyanins were apparent in intact concentrations in the liver, eye, cortex and cerebellum and not in the plasma or urine of the animals. Unlike other types of flavonoids, anthocyanins have been shown to be deposited in tissues including those beyond the blood-brain barrier.
(Source:Kalt W, Blumberg JB, McDonald JE, Vinqvist-Tymchuk MR, Fillmore SA, Graf BA, O’Leary JM, Milbury PE.”Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs” J Agric Food Chem.56(3),pp.705-12,Feb 13 2008)
The question whether anthocyanins can play a positive role in treating ethanol neurotoxicity in the context of fetal alcohol syndrome has been posed in studies by Gang Chen1 and Jia Luo. The studies postulates that based on the general thought that oxidative stress is significant in understanding the underlying cellular/molecular mechanism of ethanol’s neurotoxicity, there is the possibility of neuroprotective agents such as anthocyanins found in many berries which may be beneficial in improving the condition of neurotoxicity caused by teratogens such as ethanol. The researchers found that Cyanidin-3-glucoside (C3G)played a significant role both in enhancing neurite outgrowth as well as reversing ethanol mediated activation of Glycogen synthase kinase 3ß (GSK3ß) and inhibition of neurite outgrowth.This study is significant in that there lies the potential of preventing or making better the teratogenic effects of alcohol damage on the developing central nervaous system which is characteristic of Fetal Alcohol Syndrome.
(Source: Gang Chen, Kimberly A. Bower, Mei Xu1, Min Ding, Xianglin Shi, Zun-Ji Ke and Jia Luo.”Cyanidin-3-Glucoside Reverses Ethanol-Induced Inhibition of Neurite Outgrowth: Role of Glycogen Synthase Kinase 3 Beta “Neurotoxicity Research
Volume 15:No4, May 2009.
Gang Chen and Jia Luo.”Anthocyanins: Are They Beneficial in Treating Ethanol Neurotoxicity?”Journal Neurotoxicity Research, July, 2009)
Part of the problem in determining prenatal exposure to alcohol from a preventive perspective is reliability problems in maternal self reporting.Under-reporting and non reporting of alcohol intake by mothers makes it particularly difficult in predicting fetal exposures to high levels of alcohol.Research in traceability of alcohol exposure from mother to fetus has been of interest for laboratories developing fatty acid ethyl esters(FAEE) meconium analysis,which is a test formulated to measure prenatal alcohol exposure.FAEE is a relatively new biomarker and is capable of detecting high levels of prenatal alcohol exposure. Meconium which is the first stool is known to be produced in the fetus between 12-13 weeks of gestation.Measuring fetal exposures to alcohol by means of meconium analysis in the second and third trimester becomes a significant traceability tool for analysis in determining the reliability and validity of drinking patterns reported by pregnant mothers. Also this analysis assists in monitoring the critical time-dosage period of fetal alcohol syndrome.
(Source:
Joey Gareri,”Fatty Acid Ethyl Esters In Meconium: An Emerging Biomarker For In Utero Alcohol Exposure”, Department of Pharmacology, University of Toronto,JFAS Int 2003
©The Hospital for Sick Children 2003
Janine Hutson,” Meconium Fatty Acid Ethyl Esters and Prediction of Fetal Alcohol Effects”JFAS Int 2006
© The Hospital for Sick Children 2006)
It would be beneficial to track fetal exposure to alcohol in utero and to enable the pregnant mother to take immediate steps through the introduction of diet to possibly minimize or prevent fetal alcohol sydrome and/or effects.Researchers are well aquainted with the problem of under reporting or non reporting of women who drink while pregnant.Intervention with anthocyanins into the diet of alcoholic pregnant mothers and pregnant mothers who drink alcohol on a regular or binge drinking frequency patterns,may proove to be neuroprotective and beneficial in treating ethanol neurotoxicity as well as detrimental effects alcohol plays to the structural function of the fetal liver, eye and brain. Intervention of anthocyanins could also be beneficial to postnatal development of FAS and FAE children.
By monitoring the FAEE in meconium to study ethanol metabolism and neurotoxicity in pre and postnatal development, it may demonstrate possible positive outcomes worth investigating in future research.FAEE as a biomarker of prenatal alcohol exposure can be used as a clinical tool to detect or screen children with prenatal alcohol exposure. Elevated FAEEs in meconium analysis have been shown to to be associated with poorer mental and psychomotor skills during the first two years of life in a study done by Peterson’s et.al study(2007). It would be a useful tool to study if anthocyanin introduction in the diet of the mother or FAS child has any effect in FAEE meconium levels. Early detection and screening by using FAEE analysis would benefit in preventing secondary symptoms of FASD.
(Source:
Janine Hutson,” Meconium Fatty Acid Ethyl Esters and Prediction of Fetal Alcohol Effects”JFAS Int 2006
© The Hospital for Sick Children 2006)
Jennifer Peterson, MD, H. Lester Kirchner, PhD, Wei Xue, MS, Sonia Minnes, PhD, Lynn T. Singer, PhD, and Cynthia F. Bearer, MD, PhD.”Fatty Acid Ethyl Esters in Meconium are Associated with Poorer Neurodevelopmental Outcomes to Two Years of Age” The Journal of Pediatrics, DOI 10.1016/j.jpeds.2007.11.009, published by Elsevier.)
With the ability of FAEE’s to act as biomarker of prenatal alcohol exposure it also raises many legal and moral issues.Should there be fetal legal rights when a mother chooses to drink while pregnant? With the FAEE as a biomarker,should it be mandatory that these tests be done for the first two years of life in the pursuit of prevention of fetal alcohol syndrome and minimizing fetal alcohol effects. Will cultural, economic, and health norms move in the direction similar to some other preventive programs such as adopting a zero tolerance to driving while intoxicated? FAS is preventable and eventhough we know that in utero alcohol exposure does not always lead to adverse effects of alcohol, we do know that there is no safe established amount of alcohol that can be ingested by the mother while pregnant. With this being the case and we now have a clinical tool for screening and detection, is there not a moral obligation to correct the situation? Should there be a standardization of a minimal cut off limit of elevated FAEE levels? Research in diet interventions with antioxidants such as anthocyanins need to be further investigated as this might have a potential corrective factor to alcohol insult that is already in place and detected in a fetus or offspring.
Fetal Alcohol Syndrome, Anthocyanins and FAEE in Meconium as Biomarker
October 16, 2009© Copyright A.Caleekal
Citation Information : First Publication (2009) in www. Digitalism.ca . Citation should read:
Fetal Alcohol Syndrome, Anthocyanins and FAEE in Meconium as Biomarker
by Anuppa Caleekal B.A., M.Sc. © Copyright A.Caleekal, www.digitalism.ca October 16,2009
Copyright © Anuppa Caleekal
No image, text, or part of, may be duplicated without written permission. Read above for citation.