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Special Issue on Fetal Alcohol Spectrum Disorders

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Inhibition of cholinergic muscarinic signaling by ethanol: Potential mechanism of developmental neurotoxicity and biological plausibility for the beneficial effects of choline supplementation

Lucio G Costa, Gennaro Giordano, Marina Guizzetti


Central nervous system dysfunctions are among the most significant effects of in utero exposure to ethanol. Ethanol has been shown to affect neurons and glial cells, causing cell loss and impaired cell migration and maturation. Multiple mechanisms have been suggested to underlie the effects of ethanol, including interference with growth factors, cytokines, cell adhesion molecules and neurotransmitters. Here we propose that a relevant mechanism of ethanol’s developmental neurotoxicity may be represented by its ability to inhibit the actions of acetylcholine in the developing nervous system mediated by activation of cholinergic muscarinic receptors. Acetylcholine has been shown to induce proliferation of astrocytes, to protect neurons against apoptotic cell death, and to foster astrocyte-neuronal interactions thereby increasing neuritogenesis. By interfering with muscarinic receptor signal transduction pathways (mostly at the level of phospholipase D), ethanol inhibits all these effects of acetylcholine in the developing brain. Such action of ethanol may be responsible, at least in part, for some manifestations of developmental neurotoxicity, such as microencephaly, neuronal cell death and impaired neuronal differentiation. Among potential therapeutic interventions for Fetal Alcohol Spectrum Disorders, choline supplementation appears to be one of the most promising. The cholinergic hypothesis of ethanol’s developmental neurotoxicity provides biological plausibility for the beneficial effects of choline. Indeed, by “potentiating” the cholinergic system during development (through increased synthesis of acetylcholine and phosphatidylcholine, and increased phospholipase D activity), choline would antagonize at least some of the deleterious effects of ethanol.

Case management is efficacious in reducing major risks for fetal alcohol spectrum disorders among high risk women during pregnancy

Philip A May, Anna-Susan Marais, J. Phillip Gossage, Ronel Barnard, Belinda Joubert, Marise Cloete, Natalie Hendricks, Sumien Roux, Annalien Blom, Jeanetta Steenekamp, Theresa Alexander, Romena Andreas, Suzanne Human, Cudore Snell, Soraya Seedat, Charles D Parry, Wendy O Kalberg, David Buckley, Jason Blankenship


Aim: Evaluate the efficacy of case management (CM) for women at high risk of bearing a child with fetal alcohol spectrum disorders (FASD).

Design: Women were recruited from antenatal clinics and engaged in 18 months of CM.

Setting: A South African community with a subculture of heavy, regular, weekend, recreational, social drinking and the highest documented rates of FASD in the world.

Participants: Forty-one women who had previously borne, or were high risk for having, a child with FASD.

Measures: Statistical analysis of trends in drinking and other risk factors.

Findings: At intake: 87.8% were pregnant, most had borne a previous child with an FASD, most/all of their friends drink alcohol (67.5%), and 50.0% had stressful lives.  CM was particularly efficacious for pregnant women entering CM, as significant reductions in alcohol risk were registered for them in vitally important variables: total drinks on weekends after six months of CM (p = .026) and estimated peak blood alcohol concentration (BAC) at six (p < .001) and 18 months (p < .001). For all participants completing 18 months of CM, AUDIT scores improved significantly by 6-month follow-up (from 19.8 to 9.7, p = .000), and even though rising at 12 and 18 months, AUDIT scores and problematic drinking remained lower than baseline throughout CM.

Conclusions: An enduring change in drinking behavior is difficult in this social setting.  Yet, CM when provided by skilled and empathic case managers, reduced maternal drinking at critical times and therefore alcohol exposure levels to the fetus.

Alcohol knowledge among the public and professionals and its relationship to the risk of drinking during pregnancy in the UK

Raja A S Mukherjee, Elizabeth Wray, Leopold Curfs, Sheila Hollins



Research has shown different results regarding safe consumption levels of alcohol in pregnancy. We argued in 2005 that an individual’s inability to accurately predict their alcohol consumption may be one factor influencing risk. In order to re-evaluate within the UK, this study sought to assess how much both the general public and health professionals know about the strength by volume of alcohol and how this knowledge impacted on their behaviour. 


Both alcohol knowledge questionnaires and pouring tasks were conducted. Recruitment was by self selection via advertisements for both the health professionals and general public. Standard ethical committee-approved methods were used to assess both the knowledge of volume and strength, as well as the use of pouring tasks at different sites across the UK. 


In total 1265 questionnaires were completed (688 public and 577 professionals). 140 people completed the pouring task. In general, people’s ability to calculate accurately from strength and volume was within 20% of the accurate figure for units, although with a wide range. The range of their predictions was most affected by the size of the glass into which the fluid was being poured. 


These findings support the hypothesis that when asked to pour their own drinks, individuals are poor at estimating the alcohol content of that same drink. This has implications for public health strategies. Glass size and the strength of alcohol concentration have different implications in different countries. For those drinking in pregnancy however, the message that no exposure is no risk remains true.