Critique 050: Multiple maternal risk factors for fetal alcohol disorders – 7 August 2011

May PA, Gossage JP.  Maternal risk factors for fetal alcohol spectrum disorders.  Not as simple as it might seem.  Alcohol Research & Health 2011;34:15-26.

Authors’ Abstract

Gathering information about drinking during pregnancy is one of the most difficult aspects of studying fetal alcohol spectrum disorders (FASD).  This information is critical to linking specific risk factors to any particular diagnosis within the FASD continuum.  This article reviews highlights from the literature on maternal risk factors for FASD and illustrates that maternal risk is multidimensional, including factors related to quantity, frequency, and timing of alcohol exposure; maternal age; number of pregnancies; number of times the mother has given birth; the mother’s body size; nutrition; socioeconomic status; metabolism; religion; spirituality; depression; other drug use; and social relationships.  More research is needed to more clearly define what type of individual behavioral, physical, and genetic factors are most likely to lead to having children with FASD.

Forum Comments

Background:  There is no question that heavy alcohol consumption among pregnant women, especially binge drinking associated with high BAC levels, can cause severe developmental defects in the fetus (fetal alcohol spectrum disorders , FASD), with the full-blown Fetal Alcohol Syndrome being the most severe.  Most policy statements and guidelines regarding drinking during pregnancy are based exclusively on maternal alcohol use, and often contain statements that “no level of alcohol consumption during pregnancy is safe.”  Certain scientists have argued that such an approach is an over-simplification of the topic, in that there is little evidence for abnormalities among infants born of mothers reporting only light or occasional alcohol use during pregnancy.^1,2

Further, Colin Gavaghan, an ethicist from the School of Law, Glasgow, Scotland, has pointed out potential dangers of over-strict recommendations for women during pregnancy.³ He argues that “the total abstinence policy advocated by the UK’s Department of Health . . . sits uneasily with recent data and is far from ethically unproblematic.  The ‘precautionary’ approach advocated . . . displays both scant regard for the autonomy of pregnant and prospectively pregnant women and a confused grasp of the principles of beneficence and non-maleficence.”³

Research over the past decades has begun to show that women who deliver infants with fetal alcohol syndromes are different in many ways from control women, and heavy alcohol use is only one factor that is different.  This review article by May and Gossage clearly points out a variety of genetic and environmental factors that relate to various types of fetal injury that are classified as “alcohol” disorders.  The article strongly emphasizes that in seeking the causes of FASD, researchers should collect considerable data related to the host (the individual pregnant woman), detailed information on the exposure to alcohol, and data on other environmental factors that may relate to these disorders.  The table below, modified from the current paper, summarizes some of the important maternal risk factors described.  (The reader is advised to go to the original paper for the complete list.)

Specific comments on the paper:  Forum members considered this to be an extremely well researched and written review.  It covers many factors (host, agent exposure, and environment) that have been found to relate to the occurrence of FASD.  The large majority of subjects included in the analyses reported in this paper are from South Africa, especially from areas where heavy binge drinking is common.  Only a small number are from Italy and from selected communities in the United States.  The frequency of such syndromes in most industrialized developed countries is low, making it difficult to have accurate estimates of the risk that apply to the general population.

Comments on alcohol use during pregnancy: There have been a very large number of studies describing the developmental abnormalities associated with alcohol use during pregnancy.  In addition, there are experimental studies in rats showing that high levels of alcohol immediately after birth (equivalent to the third trimester in humans) affect parts of the brain that relate to later physical and intellectual effects.  As stated by Kelly et al,⁴ “Whereas structures critically involved in social behaviors, such as the hypothalalmus, amygdale, septal region, and hippocampus, have been shown to be altered by exposure to alcohol during development,^5-7 strong causal links between specific behavioral alterations and neural changes have yet to be drawn.”⁴ It should be pointed out that most of the effects demonstrated in experimental animals involve very high levels of alcohol administration.

In Australia, approximately two-thirds of pregnant women report that they drink alcohol at least at some stage during their pregnancy but the vast majority drink only light to moderate amounts.  The incidence reported for FAS and FASD in Australia is relatively small, but higher in indigenous communities where there are generally more observed confounders.  The literature suggests that this concentration of risk among groups with high levels of alcohol abuse, low SES, and polysubstance use is similar for the USA and Canada.  Polydrug use appears to be a strong factor adding to the risk.

Drinking guidelines:  The Australian guidelines of 2001 included a statement to the effect that if pregnant women drink, then they should never become intoxicated, as advice to simply not drink provides little guidance for women who chose to continue to drink while pregnant.  Earlier guidelines in Denmark recommended limiting the consumption to less than 3 drinks per week and “never more than 1 drink per day and always with meals.”

The latest version of the Dietary Guidelines for Americans 2010 (DGA 2010)⁸ states “The consumption of alcohol can have beneficial or harmful effects, depending on the amount consumed, age, and other characteristics of the person consuming the alcohol.”  Referring to people who should not consume alcohol, the DGA 2010 includes women who are pregnant or who may be pregnant.  The guidelines state: “Drinking during pregnancy, especially in the first few months of pregnancy, may result in negative behavioral or neurological consequences in the offspring.  No safe level of alcohol consumption during pregnancy has been established.”⁸

Some Forum members tended to agree with the closing comments of the authors of the present paper, that it is better for women not to drink during pregnancy, although scientific data do not support an increase in risk from occasional or light drinking.  One Forum member comments: “There may be enough data to reassure the otherwise not-at-risk pregnant woman that a single drink now and then, or even daily, is harmless to her child.”  The Forum member adds: “This is such an emotionally charged subject, one that is truly important, that great caution is warranted in giving advice to pregnant women.”

References:

1.  O’Leary CM, Nassar N, Kurinczuk JJ, de Klerk N, Geelhoed E, Elliott EJ, Bower C.  Prenatal Alcohol Exposure and Risk of Birth Defects  Pediatrics 2010;126;e843-e850; DOI: 10.1542/peds.2010-0256

2.  Kelly YJ, Sacker A, Gray R, Kelly J, Wolke D, Head J, Quigley MA.  Light drinking during pregnancy: still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age?  J Epidemiol Community Health 2010; doi:10.1136/jech.2009.103002

3.  Gavaghan C.  ‘‘You can’t handle the truth’’; medical paternalism and prenatal alcohol use.   J Med Ethics 2009;35:300–303.

4.  Kelly SJ, Day N, Streissguth AP.  Effects of prenatal alcohol exposure on social behavior in humans and other species.   Neurotoxicol Terato 2000;22:143–149.

5.  Kelly SJ. Alcohol exposure during development alters hypothalamic neurotransmitter content. J Neural Transm 1996;103:55–67.

6.  Kelly SJ. Effects of alcohol exposure and artificial rearing during development on septal and hippocampal neurotransmitters in adult rats. Alcohol Clin Exp Res 1996;20:670–676.

7.  Kelly SJ, Dillingham RJ. Social behavior and the amygdala region are altered by perinatal alcohol exposure. Neurotoxicol Teratol 1994;16:377–384.

8.  Dietary Guidelines for Americans 2010; United States Department of Agriculture, Center for Nutrition Policy and Promotion.  Available through http://www.cnpp.usda.gov/DGAs2010-PolicyDocument.htm

Forum Summary

An extremely well researched and written review on the relation of maternal drinking during pregnancy to adverse fetal outcomes has been published by scientists from the University of New Mexico Center on Alcoholism, Substance Abuse, and Addictions.  It covers many factors (host, agent exposure, and environment) that have been found to relate to the occurrence of fetal alcohol spectrum disorders (FASD).  As stated by the authors, these factors are related to quantity, frequency, and timing of alcohol exposure; maternal age; number of pregnancies; number of times the mother has given birth; the mother’s body size; nutrition; socioeconomic status; metabolism; religion; spirituality; depression; other drug use; and social relationships.  The risk of fetal abnormalities is clearly increased with frequent consumption of large amounts of alcohol, and is greater among women who are alcoholics; however, these other factors modify the risk associated with alcohol consumption during pregnancy.  While current data do not show that light or occasional alcohol consumption during pregnancy increases the risk of FASD, Forum members do not believe that pregnant women should be encouraged to drink.

Forum members agree with the authors that “More research is needed to more clearly define what type of individual behavioral, physical, and genetic factors are most likely to lead to having children with FASD.”  Evaluating these multidimensional factors should help identify women at particular risk for having a child with FASD and lead to interventions to prevent such fetal abnormalities.

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Contributions to this critique by the International Scientific Forum on Alcohol Research were made by the following members:

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA.

Lynn Gretkowski, MD, Obstetrics/Gynecology, Mountainview, CA, Stanford University, Stanford, CA, USA

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.

Creina Stockley, clinical pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia.

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway.

Pierre-Louis Teissedre, PhD, Faculty of Oenology – ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France.

Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia.