Shaken not stirred: how soon should I share a drink with my baby?
Abstract: Alcohol is a powerful teratogen. Consumption of alcohol during pregnancy has the potential to cause a range of birth defects, with the greatest impact on the central nervous system. Damage to the central nervous system is likely to be due to the interaction of a number of mechanisms. Figures for alcohol related birth defects in Australia are between 0.68 and 1.87 per 1000 live births, with the indigenous population most at risk. Practitioners of herbal medicine can assist in reducing the prevalence of these diseases through researching and understanding how alcohol can impact on the unborn child, and then educating their patients about the risks of consuming alcohol prior to and during pregnancy.
Subject: Fetal alcohol syndrome (Risk factors)
Fetal alcohol syndrome (Research)
Drinking in pregnancy (Health aspects)
Drinking in pregnancy (Research)
Birth defects (Risk factors)
Birth defects (Research)
Teratogenic agents (Health aspects)
Teratogenic agents (Research)
Fetus (Effect of alcohol on)
Fetus (Risk factors)
Fetus (Research)
Fetus (Growth)
Author: Carter, Jocelyn
Pub Date: 03/22/2010
Publication: Name: Australian Journal of Medical Herbalism Publisher: National Herbalists Association of Australia Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 National Herbalists Association of Australia ISSN: 1033-8330
Issue: Date: Spring, 2010 Source Volume: 22 Source Issue: 1
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: Australia Geographic Code: 8AUST Australia
Accession Number: 223823988
Full Text: Background

For over 30 years research has shown that alcohol is a teratogen that is capable of effecting the growth and development of the fetus from pre-embryonic and embryonic development through to and including fetal growth. Teratogens differ from mutagens in that they generally do not damage genes or chromosomes (Jones 2006). However a teratogen can potentially lead to miscarriage, stillbirth or varying degrees of birth defects should the fetus survive to be born.

Consumption of alcohol while pregnant can lead to a range of birth defects that typically lead to dysfunction within the central nervous system (CNS) (Astley 2000a), plus a range of dysmorphic facial features (Kvigne 2004). Children born to mothers who consume alcohol while pregnant may potentially develop abnormalities associated with other body systems such as sight, hearing, the renal system and/or the cardiac system. Many of these children display a range of cognitive and behavioural disorders (Welch-Carre 2005), which has led to alcohol being regarded as a behavioural teratogen and a leading cause of mental retardation in the Western world (Dunty 2001).

Alcohol in the maternal body

When a pregnant woman consumes alcohol it diffuses readily through the walls of her stomach and small intestine. From here it is carried via the hepatic portal system to her liver where it is metabolised. The liver is able to metabolise around one standard drink per hour (Whitney 2007). Alcohol that is not broken down by the liver remains in the maternal blood stream and is circulated via the placenta to the fetal blood stream (Rosett 1984). This leads to alcohol in the maternal and fetal blood supply to be almost equal in concentration (O'Leary 2002).

An interesting point worth noting at this stage is that there is evidence to indicate that there is a genetic link that may indicate that some women are better able to metabolise alcohol, therefore reducing alcohol distributed to the unborn child. Research has indicated that women coded with the ADH2*2 or the ADH2*3 alleles are able to metabolise alcohol faster (Riley 2003). These alleles code for more of the enzyme that breaks down alcohol, alcohol dehydrogenase, to be produced. However unmetabolised alcohol will still circulate to their unborn child. How much will depend on factors such as genetic makeup, body size and composition, age, gender, nutrition and metabolism as these influence how much alcohol is metabolised by the maternal liver and how much passes to the fetus (National Health and Medical Research Council 2009).

Role of the placenta

The placenta provides respiration, nutrition and excretion for the developing fetus. It also provides protection to the fetus from larger molecules such as maternal protein hormones and most bacteria. However small molecules, for example alcohol, can readily cross the placenta and enter the fetal blood supply (Jones 2006, Whitney 2007). Neither the pre-embryo, embryo nor fetus can metabolise alcohol, which means fetal blood alcohol concentrations remain high until the alcohol diffuses back into the maternal blood circulation and is metabolised by the maternal liver (Rosett 1984). Once in the fetal blood supply, alcohol may have weak to strong teratogenic effects on the embryo and fetus (Welch-Carre 2005).

The result of this early exposure to alcohol may lead to a range of negative outcomes referred to as either fetal alcohol syndrome (FAS), fetal alcohol spectrum disorder (FASD), alcohol related neurodevelopmental disorder (ARND), or alcohol related birth defects (ARBD) (Goodlett 2005, Kvigne 2004, Welch-Carre 2005). These disorders exhibit a range of cognitive and behavioural disorders, and physiological malformations.

Australia is not exempt from the blight of FAS, FASD, ARND and ARBD. Rates are estimated at between 0.68 and 1.87 per 1000 live births in the general population, and 1.7 to 4.7 per 1000 live births in the Indigenous population (Elliott 2004). However these figures are likely to be underestimated as those children with ARND and ARBD are unlikely to have been included in statistical analysis of children affected by maternal alcohol consumption (Harris 2003).

Alcohol and the central nervous system

While alcohol can impact negatively on the embryo and fetus to produce a range of physical and behavioural defects, perhaps the most significant effect is on brain development. The embryonic and fetal brain develops rapidly and continues to grow and develop throughout pregnancy (Rosett 1984). The CNS is most vulnerable to major morphological abnormalities from 2 to 6 weeks after conception, and vulnerable to minor morphological abnormalities and physiological defects for the rest of the pregnancy (Jones 2006).

The CNS and the skull form from the ectoderm and mesoderm, with development of the cerebellum beginning as early as gastrulation i.e. around 12 days after conception (Martini 2001). The neural tube develops at around 21 to 28 days following conception, further developing into the brain and spinal cord. By around 12 weeks of development the cerebral hemispheres, diencephalon, mesencephalon, cerebellum, pons, medulla oblongata and spinal cord have formed (Martini 2004).

Research has provided some possible reasons for CNS impairment, however it is likely that a number of mechanisms interact to contribute to alcohol related birth defects to the CNS. These include:

* oxidative stress

* disruption to the way cells process glucose and synthesise DNA and proteins

* alterations to cellular mitosis and development

* changes to the regulation of gene expression

* changes to cell to cell interactions

* disturbance to growth factors

* cell apoptosis

* secondary damage such as a dysfunctional placenta, hypoxia or ischemia (Goodlett 2005).

Research by Sowell et al (2008) has indicated that embryonic and fetal exposure to alcohol may lead to reduced or delayed myelin deposition which possibly leads to greater grey matter thickness. The reduced level of white matter in the brain may be what is responsible for impaired cognitive function and behavioural problems in children who have FAS, FASD, ARBD or ARND.

Another possibility is that alcohol interferes with the synthesis of retinoic acid, a major regulator of embryonic neural development. Retinoic acid is synthesised from retinol which requires alcohol dehydrogenase. Alcohol in the fetal blood stream competes with alcohol dehydrogenase and may suppress, or interfere with, the synthesis of retinoic acid (Goodlett 2005).

Research has also shown that alcohol increases oxidative stress on cells which may ultimately lead to cell apoptosis. Under normal circumstances cells are able to prevent oxidative stress through utilisation of antioxidant and free radical scavengers to counteract reactive oxygen species. Alcohol may increase oxidative stress to the point where there are inadequate antioxidants and free radical scavengers to mop up the excess reactive oxygen species. This may be sufficient to lead to permanent cell damage and cell death (Goodlett 2005).

Apoptosis may also be tied in with other mechanisms such as a cell's inherent programming to die. Research has indicated that alcohol has the ability to upregulate cell suicide receptors leading to early cell death. This cell death is not limited to those areas where cell death is occurring naturally, it is seen in discrete cell populations, particularly cells in the developing CNS (Dunty 2001).

Alcohol also disturbs the normal growth cycle of cells through disruption of growth factor at several stages of cell proliferation. Cell growth cycles are partly regulated by cyclins and cyclin dependent kinases (CDKs). While alcohol has been shown to inhibit cyclins and CDKs, the actual changes in genetic expression that lead to the teratogenic effects of alcohol are not yet known (Goodlett 2005). It is known that alcohol causes an increase in cell cycle events dependent on growth factor and a decrease in cell proliferation (Goodlett 2005). Therefore while the actual mechanism of damage to cell growth is unclear, it can be posited that alcohol's negative effects on cell growth may be, in part, responsible for alcohol related birth defects.

FAS, and to some extent FASD, also typically include facial dysmorphology and eyesight and hearing impairment. Animal studies have indicated that embryonic cells associated with the development of the branchial arch, mandible, frontonasal and maxillary prominences, and ocular and auditory structures are particularly vulnerable to exposure to alcohol (Dunty 2001).

Bones which make up the skull and mandible begin forming at around 8 weeks following conception, with ossification well progressed by 12 weeks (Martini 2004). Prior to this development neural crest cells, which are particularly vulnerable to the effects of alcohol, may already have been reduced due to alcohol induced apoptosis. This places the teratogenic effects of alcohol earlier than visible development of skull and facial bones (Dunty 2001).

Neural crest cells also give rise to ocular and auditory structures. Loss of neural crest, ganglion and glial cells as a result of alcohol consumption are thought to be responsible for eyesight abnormalities in children with FAS. Hearing defects in children with FAS are thought to be due to alcohol damage to the neural crest, and later the vestibulocochlear nerve (Dunty 2001).

Alcohol and the neuroendocrine system

Alcohol may impact on the hypothalamic adrenal pituitary (HPA) axis. The HPA axis is the mediator for the stress response and the release of glucocorticoids. Secretion of glucocorticoids is controlled by a negative feedback mechanism (Welberg 2001). The main glucocorticoid in humans is cortisol, and its main role is in the stress response and its action as an anti-inflammatory (Martini 2001). As a part of the CNS, the HPA axis is particularly vulnerable to the effects of prenatal exposure to alcohol, causing it to be reprogrammed, increasing HPA tone throughout life. It is this very early reprogramming that may contribute to alcohol related problems with immune function, memory, learning, cognition and behaviour. Given that the HPA axis controls the secretion of a number of hormones, including growth hormone, gonadal hormones, corticosteroids and thyroid hormones, it is reasonable to expect that prenatal programming of the HPA may have significant effects on the a number of body systems (Zhang 2005).

Increasing the tone of the HPA axis may make it more responsive to stress, causing increased release of glucocorticoids, particularly cortisone, which is known to suppress the immune response (Martini 2001). Studies have indicated that children with FAS, FASD, ARBD and ARND have a higher incidence of bacterial infections such as urinary and upper respiratory tract infections, pneumonia, ear infections and gastric infections. Along with increased bacterial infections, these children show lower counts of immune cells such as lymphocytes, eosinophils and neutrophils. Immune function may also be affected through fetal exposure to alcohol at the time the thymus is developing. Alcohol at this time may disrupt thymus development leading to impairments with T-cell immunity, which may reduce immune function (Zhang 2005).

How much alcohol is too much?

While it is accepted that there is a link between alcohol and a range of birth defects, there are still questions about how much alcohol needs to be consumed before there is irreversible damage to the unborn embryo and fetus. There is no easy answer to this question.

The NHMRC (2009) advise that it is not possible to set a safe or no risk limit for alcohol consumption by pregnant women, therefore the safest course of action is not to consume alcohol while pregnant. However it is known that women who are classed as alcoholic are at greatest risk of giving birth to an infant with alcohol related birth defects. Women who drink heavily and/or frequently during pregnancy, but are not alcoholics, are also at a high risk but the effects may be less severe. Further down the scale, a pregnant woman who has a single episode of binge drinking, i.e. more than five standard drinks on one occasion (Kvigne 2003), at a point where embryonic or fetal development is particularly vulnerable to teratogens, may also be at risk of giving birth to an alcohol effected child.

At this point it is worth noting that the NHMRC (2009) does not define what is light and what is heavy drinking. Instead it provides clear guidelines that recommend limiting alcohol consumption to 'no more than 2 standard drinks on any day' in order to reduce the risk of harm.

In addition to alcohol consumption there are other factors that need to be taken into consideration. Maternal and fetal sensitivity to alcohol may reduce or increase the risk. Women who drink heavily, but consume large amounts of food while doing so may have a reduced risk (Jacobson 1998). Those women who are genetically coded to form more alcohol dehydrogenase may also have a reduced risk (Riley 2003). As it is not possible to determine even the approximate amount of alcohol needed to permanently damage the unborn child, it is probably better to suggest total abstinence from alcohol when planning to become pregnant, and post conception (NHMRC 2009). This includes those women who have a genetic link allowing them to better metabolise alcohol.

Prevention

FAS, FASD, ARND and ARBD are considered to be easily prevented through non consumption of alcohol during pregnancy or not becoming pregnant while consuming alcohol (Astley 2000b). Where this may seem to be an easy solution, FAS, FASD, ARND and ARBD are the end result of a range of factors which interact to produce excessive alcohol consumption by pregnant women and women of child bearing age.

Factors such as lack of contraception, poor education, housing and nutrition, social acceptance of alcohol use and low socioeconomic status all contribute to the development of alcohol related birth defects (Elliott 2004). Studies across the world have indicated that women at the lower end of the socioeconomic scale who do not have access to contraception, who are poorly educated etc, are those most likely to give birth to alcohol effected children (Astley 2000a, 2000b, Goodlett 2005, Jacobson 1998, Kvigne 2003, 2004). There is also some evidence to suggest that mothers of children with FAS are more likely to be abused, have mental health problems, and are more likely to need care for injuries relating to alcohol (Kvigne 2003).

Preventing alcohol related birth defects involves intervention at a number of levels. There is no ' quick fix' solution. Health care professionals (including herbalists and naturopaths), the government and the public need to make a co-ordinated effort if FAS, FASD, ARND and ARBD are to be prevented, or at least reduced, in this particularly vulnerable population (Harris 2003), and those populations identified as being less vulnerable to these diseases.

Prevention of FAS, FASD, ARND and ARBD involves publication of warnings about the risks of consuming alcohol when pregnant; linking these diseases to specific types of alcohol consumption, for example binge drinking or moderate to heavy alcohol consumption while pregnant; assisting women who do consume alcohol to gain access to contraception; and educating the public, particularly women of child bearing age, about the risks of consuming alcohol while pregnant (Riley 2003).

Alcohol consumption is entrenched in Australian culture. While alcohol remains such an intrinsic part of Australian society, and women are not educated about the potential damaging effects of alcohol to their unborn child, reducing FAS, FASD, ARBD and ARND will remain a challenge.

Conclusion

Research indicates that consuming alcohol from conception onwards has the potential to cause a range of birth defects with varying degrees of severity. Mothers who consume alcohol may be condemning their child to a lifetime of ongoing problems such as behavioural and cognitive disorders, learning disability, facial dysmorphology, and long term effects to the their immune system.

There is no safe limit, although a small amount of alcohol on isolated occasions is less likely to lead to giving birth to an alcohol effected child. However alcohol consumed at a critical time of embryonic or fetal development has the potential to cause ARBD of some degree. Women of child bearing age who consume alcohol and are planning to become pregnant need to ask themselves whether the risk is worth it.

Prevention involves a multi faceted approach by health care professionals, the public and the government (Harris 2003). It is important to note that funding for prevention programs will have to compete against funding for other public health issues, and is best adapted to individual high risk populations (Riley 2003).

Practitioners of herbal medicine can assist in preventing these diseases through educating their patients as to the damage alcohol may do to their unborn child. Ideally all women of child bearing age need to be educated about the teratogenic effects of alcohol as teratogenic damage can occur from the pre embryonic stage of development through the embryonic and fetal stages.

References

Astley SJ, Bailey D, Talbot C, Clarren SK. 2000a. Fetal alcohol syndrome (FAS) primary prevention through FAS diagnosis I. Identification of high risk birth mothers through the diagnosis of their children. Alcohol & Alcoholism 35;5:499-508.

Astley SJ, Bailey D, Talbot C, Clarren SK. 2000b. Fetal alcohol syndrome (FAS) primary prevention through FAS diagnosis II. A comprehensive profile of 80 birth mothers of children with FAS. Alcohol & Alcoholism 35;5:509-19.

Dunty WC, Chen S, Zucker RM, Dehart DB, Sulik KK. 2001. Selective vulnerability of embryonic cell populations to ethanol-induced apoptosis: implications for alcohol-related birth defects and neurodevelopmental disorder. Alcoholism: Clin & ExperRes 25;10:1523-35.

Elliott EJ, Bower C. 2004. FAS in Australia: fact or fiction? J Paediatric Child Health 40;8-10.

Goodlett CR, Horn KH, Zhou FC. 2005. Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Exper Biol 230;394406.

Harris KR, Bucens IK. 2003. Prevalence of fetal alcohol syndrome in the Top End NT. J Paediatric Child Health 39;528-33.

Jacobson JL, Jacobson SW, Sokol RJ, Ager JW. 1998. Relation of maternal age and pattern of pregnancy drinking to functionally significant cognitive deficit in infancy. Alcoholism: Clin & Exper Res 22;2:345-51.

Jones RE, Lopez KH. 2006. Human Reproductive Biology 3rd edn. China: Elsevier Academic Press.

Kvigne VL, Leonardson GR, Borzelleca J, Brock E, Neff-Smith M, Welty TK. 2003. Characteristics of mothers who have children with fetal alcohol syndrome or some characteristics of fetal alcohol syndrome. J Am Board Fam Med 16;4:296-303.

Kvigne VL, Leonardson GR, Neff-Smith M, Brock E, Borzelleca J, Welty TK. 2004. Characteristics of children who have full or incomplete fetal alcohol syndrome. J Paediatrics Nov;635-40.

Martini FH. 2001. Fundamentals of Anatomy and Physiology 6th edn. USA: Prentice Hall Inc.

Martini FH. 2004. Martini's Atlas of the Human Body. USA: Benjamin Cummings.

National Health and Medical Research Council. 2009. Aust Guidelines to Reduce Health Risks from Drinking Alcohol.

O'Leary C. 2002. Fetal alcohol syndrome: a literature review. Prepared for the National Expert Committee on Alcohol.

Riley EP, Guerri C, Calhoun F, Charness ME, Foroud TM, Li T et al. 2003. Prenatal alcohol exposure: advancing knowledge through international collaborations. Alcoholism: Clin & Exper Res 27;1: 118-35.

Rosett HL, Wiener L. 1984. Alcohol and the fetus. New York: Oxford University Press.

Sowell ER, Johnson A, Kan E, Lu LH, Van Horn JD, Toga AW et al. 2008. Mapping white matter integrity and neurobehavioural correlates in children with fetal alcohol spectrum disorders. JNeurosci 28;3:1313-19.

Welberg LAM, Seckl JR. 2001. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendo 13; 113-28.

Welch-Carre E. 2005. The neurodevelopmental consequences of prenatal alcohol exposure. Adv Neonat Care 5;4:217-29.

Whitney E, Rolfes SR. 2007. Understanding nutrition 11th edn. Belmont CA USA: Thomson Wadsworth.

Zhang X, Sliwowska JH, Weinberg J. 2005. Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function. Exper Biol & Med 230;376-88.

Jocelyn Carter BHSc(CompMed) AdvDipWHM MNHAA

jecarter@yless4u.com.au

Jocelyn Carter is a medicinal herbalist and practitioner of aromatic medicine. She has a Bachelor of Health Science (Complementary Medicine) from Charles Sturt University. This article was originally an assignment as part of her final studies. Jocelyn has an Advanced Diploma in Western Herbal Medicine, and a certificate in massage and aromatherapy. She has been working in the field of natural medicine since 1999. Her aim is to provide an integrative approach to health care through educating patients about the benefits of natural medicine.

Disclaimer

Jocelyn Carter has no pecuniary interest in companies which produce herbal extracts and tinctures. Nor has she formed an opinion on the relative merits and risks of the inclusion or exclusion of alcohol in liquid herbs dispensed to patients.
Gale Copyright: Copyright 2010 Gale, Cengage Learning. All rights reserved.