Medical Hypotheses xxx (2011) xxxxxx

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

Does light alcohol consumption during pregnancy improve offsprings cognitive development?
Wenbin Liang , Tanya Chikritzhs
National Drug Research Institute, Curtin University, Perth, Western Australia, Australia

a r t i c l e

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a b s t r a c t
We posit that: (i) light alcohol consumption during pregnancy does not improve the cognitive development of human offspring and (ii) observational study outcomes indicating apparent protective effects arise from residual confounding due to socioeconomic status. Our hypotheses counter emerging hypotheses apparent in the epidemiological literature that light alcohol consumption during pregnancy improves offsprings cognitive development. Determining the plausibility of this proposition is important given its potential to inuence womens alcohol consumption behavior during pregnancy. However, given ethical concerns, it is unlikely that a randomized control trial will be conducted to test this hypothesis. The veracity of alcohols purported positive effect on cognitive development is therefore explored here by comparing research evidence on light alcohol consumption to the evidence for folate and DHA supplementation intake during pregnancy. An alternative approach for further testing this hypothesis in observational studies is also suggested. 2011 Elsevier Ltd. All rights reserved.

Article history: Received 23 February 2011 Accepted 20 September 2011 Available online xxxx

Introduction In recent years, great efforts have been made to identify dietary elements that can optimize the outcome of pregnancy including improving the cognitive development of human offspring through dietary modication during pregnancy. Docosahexaenoic acid (DHA) and folate, for example, have received particular attention [1,2]. Biologically plausible mechanisms by which DHA and folic acid may inuence cognitive development in the fetus have been identied: DHA is an essential element of cell membranes in the brain and retina [3] and folic acid is important for amino acid metabolism and essential for DNA synthesis [4]. It is of particular interest therefore, that the association between light alcohol consumption during pregnancy, or, in other words, alcohol supplementation, and the cognitive development of offspring has been the focus of several recently published observational studies [58]. The hypothesis that light alcohol consumption during pregnancy improves offsprings cognitive development is emerging in the literature. However, the results from observational studies to date [58] have produced inconsistent outcomes. These outcomes are particularly puzzling given the absence of a priori evidence supporting physiological mechanisms which can explain physical effects of light drinking by pregnant mothers on fetal development.
Corresponding author. Address: National Drug Research Institute, Curtin University, GPO Box U1987, Perth, WA 6845, Australia. Tel.: +61 8 9266 1617; fax: +61 8 9266 1611. E-mail address: w.liang@curtin.edu.au (W. Liang).
0306-9877/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2011.09.043

We posit the following alternative hypotheses: (i) light alcohol consumption during pregnancy does not improve the cognitive development of human offspring and (ii) observational study outcomes indicating apparent protective effects arise from residual confounding due to socioeconomic status. Approach to testing the hypothesis The hypothesis that light alcohol consumption during pregnancy improves the cognitive development of human offspring is very unlikely to be tested in randomized control trials due to ethical concerns. Light alcohol consumption is dened here as not more than 10 g of alcohol per day on average, although denition can vary among studies. In order to gain further understanding of the validity of observed associations between light alcohol intake during pregnancy and the cognitive development of offspring, we compared the quality of current evidence on light alcohol intake and supplementation of DHA and folic acid (Table 1). Discussion It has been established that both folic acid and DHA are essential for health and development of the fetus, including stages of neurodevelopment [34]. Conversely, there is no evidence to suggest that ethanol is essential for healthy fetal development. The evidence from observational studies for both light alcohol consumption and folic acid supplementation is inconsistent. On the other hand, ndings from observational studies for DHA have

Please cite this article in press as: Liang W, Chikritzhs T. Does light alcohol consumption during pregnancy improve offsprings cognitive development? Med Hypotheses (2011), doi:10.1016/j.mehy.2011.09.043

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Table 1 Comparison of evidence for supplementation effects of light alcohol consumption, folic acid and DHA on the cognitive development of offspring. Light alcohol consumption Relation to health and role in fetal neurodevelopment There is no solid data supporting any benecial effects of light alcohol consumption during pregnancy on fetal neurodevelopment Inconsistent ndings [58] Folic acid supplementation Folate is important for amino acid metabolism; it is essential for DNA synthesis, and thus cell division and fetal growth, including nervous system development. Adequate folate intake is crucial to prevent of neural tube defects Inconsistent ndings Docosahexaenoic acid (DHA) supplementation DHA is a critical component of cell membranes, especially in the brain and retina [3]

Association between intake during pregnancy and cognitive development from observational studies Results from clinical trials

Higher sh/seafood intake during pregnancy is associated with better cognitive development among young Children [2,10]

No data available

A randomized, double-blind, controlled trial [1] found no effect of folate supplementation during pregnancy on cognitive development of offspring

Inconsistent ndings. Small clinical trials and clinical trials with methodological issues reported signicant effects of DHA supplements during pregnancy on cognitive development of offspring at young age [11]. A recent large scale double-blind randomized controlled trial did not nd any effect of DHA supplementation during pregnancy on cognitive development of offspring at 18 months [9]

consistently suggested benecial effects. Evidences from randomized, double-blind, controlled trials are available for folic acid supplementation and DHA supplementation. Despite, the strong evidence from observational studies, these trials indicated no effect for folic acid supplementation on offsprings cognitive development. Until recently, the effects of DHA appeared to be consistent and positive, but a new study with a large sample size and more conservative analytical approach suggested there was no effect [9] (Table 1). It should be obvious to most that due to their critical role in fetal neurodevelopment, both DHA and folic acid supplementation would have a much greater likelihood of showing benecial effects in randomized control trials than light alcohol consumption, a known neurotoxin. Based on the simple qualitative comparison described here, it would seem highly improbable that low level supplementation of alcohol during pregnancy would, a priori, be expected to provide a benecial effect on the cognitive development offspring. It is far more likely that the positive associations observed in the three epidemiological studies published to date [5,6,8] are due to residual confounding effects from clusters of factors related to socioeconomic status, which has also been found to be associated with light alcohol consumption during pregnancy in all three studies [57]. An alternative observational study design An alternative means of testing whether light drinking during pregnancy has any positive effects on the cognitive development of the fetus would be to investigate the association between alcohol consumption of fathers during pregnancy (controlling for maternal alcohol consumption) and mental development among their infants and young children in longitudinal studies. In such a study, a physiological mechanism via consumption during pregnancy (of the mother) could not possibly explain any association which may appear to exist between paternal alcohol use and positive effects on the cognitive development of their offspring. Conclusion The hypothesis that light alcohol consumption during pregnancy improves the cognitive development of offspring has been the focus of several recently published observational studies. How-

ever, given ethical concerns, it is unlikely that a randomized control trial will be conducted to test this hypothesis. Based on a comparison of research evidence for folate and DHA supplementation intake during pregnancy, the effects of which on fetal cognitive development are well established, it is unlikely that low level alcohol dosing during pregnancy will benet cognitive development in children. Conicts of Interest None. Reference
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Please cite this article in press as: Liang W, Chikritzhs T. Does light alcohol consumption during pregnancy improve offsprings cognitive development? Med Hypotheses (2011), doi:10.1016/j.mehy.2011.09.043